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Inhye Kim,1,* Young Ho Song,2,* Nem Singh,2 Yong Joon Jeong,3 Jung Eun Kwon,3 Hyunuk Kim,4 Young Mi Cho,3 Se Chan Kang,3 Ki-Whan Chi2 1Laboratory of Bio-Resources, Yongin-si, Gyeonggi-Do, 2Department of Chemistry, University of Ulsan, Ulsan, 3Department of Life Science, Gachon University, Seongnam, 4Energy Materials Lab, Korea Institute of Energy Research, Daejeon, Republic of Korea *These authors contributed equally to this work Abstract: Nano-sized multinuclear ruthenium complexes have rapidly emerged as promising therapeutic candidates with unique anticancer activities. Here, we describe the coordination-driven self-assembly and anticancer activities of a set of three organometallic tetranuclear Ru(II) molecular bowls. [2+2] Coordination-driven self-assembly of 3,6-bis(pyridin-3-ylethynyl)phenanthrene (bpep) (1) and one of the three dinuclear arene ruthenium clips, [(ƞ6-p-iPrC6H4Me)2Ru2-(OO\OO)][OTf]2 (OO\OO =2,5-dioxido-1,4-benzoquinonato, OTf = triflate) (2), 5,8-dioxido-1,4-naphthoquinonato (3), or 6,11-dioxido-5,12-naphthacenediona (4), resulted in three molecular bowls 5–7 of general formula [{(ƞ6-p-iPrC6H4Me)2Ru2-(OO\OO)}2(bpep)2][OTf]4. All molecular bowls were obtained as triflate salts in very good yields (>90%) and were fully characterized using multinuclear nuclear magnetic resonance (NMR), electrospray ionization–mass spectrometry (ESI-MS), and elemental analysis. The structure of the representative molecular bowl 5 was confirmed by single-crystal X-ray diffraction analysis. The anticancer activities of molecular bowls 5–7 were determined by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide, autophagy, and Western blot analysis. Bowl 6 showed the strongest cytotoxicity in AGS human gastric carcinoma cells and was more cytotoxic than doxorubicin. In addition, autophagic activity and the ratio of apoptotic cell death increased in AGS cells by treatment with bowl 6. Bowl 6 also induced autophagosome formation via upregulation of p62 and promotion of the conversion of LC3-I to LC3-II. Moreover, bowl 6 promoted apoptotic cell death through downregulation of Akt/mTOR activation, followed by increased caspase-3 activity. These results suggest that bowl 6 induces gastric cancer cell death via modulation of autophagy and apoptosis. Bowl 6 is a potent anticancer agent and a potential treatment for human gastric cancer that merits further study. Keywords: phenanthrene, ruthenium, coordination self-assembly, gastric cancer, Akt/mTOR

This study evaluated the efficacy of Web-based diabetes self-management education for newly diagnosed patients with type II diabetes as an alternative to group lectures. Using a non-equivalent control group, pretest-post-test design, the participants in the Web group (n = 15) took part in a Web-based diabetes self-management program, while those in the lecture group (n = 16) attended 3 h of group lectures provided by health-care professionals specializing in diabetes care. The outcome variables were measured at the baseline (T0), and 6 weeks (T1) and 3 months (T2) after the interventions. The glycosylated hemoglobin (HbA1c) percentage and diabetes care knowledge in the Web group improved significantly from T0 to T1, while the diabetes care behavior improved significantly from T0 to T1 and from T1 to T2. The diabetes care knowledge and diabetes care behavior in the lecture group improved significantly from T0 to T1, but the HbA1c percentage did not change significantly between any times. These results show the potential of the Web-based program as an alternative to group lectures for diabetes self-management education. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this study was to determine the frequency of recurrent gestational diabetes mellitus (GDM) and to find risk factors that can predict the recurrence of GDM in Korean women with previous GDM.Research Design and Methods: We evaluated women who had GDM in an index pregnancy (1993-2001) and a subsequent pregnancy by 2003. An oral glucose tolerance test (OGTT) was performed during the index pregnancy and 2 months postpartum. The recurrence rate of GDM was assessed among 111 women who had a subsequent pregnancy. Multivariate logistic regression analysis was used to identify independent predictors of recurrent GDM.Results: The frequency of recurrent GDM in subsequent pregnancies was 45.0% (95% CI 35.6-54.4%). Women with impaired fasting glucose and/or impaired glucose tolerance 2 months postpartum were at increased risk for recurrent GDM (relative risk 2.31, 95% CI 1.24-4.30). Higher BMI before the subsequent pregnancy (P = 0.024), higher fasting glucose concentration (P = 0.007) 2 months postpartum, and lower 1-h insulin concentration (P = 0.004) of the diagnostic OGTT in the index pregnancy were independent risk factors for recurrence of GDM in subsequent pregnancies.Conclusions: GDM recurred in nearly half of subsequent pregnancies in Korean women. Fasting glucose 2 months postpartum might be a clinically valuable predictor of recurrent GDM risk. [ABSTRACT FROM AUTHOR]

AIMS: We examined whether the common polymorphisms of the peroxisome proliferator-activated receptor-gamma (PPARgamma) gene are associated with Type 2 diabetes or obesity in the Korean population. METHODS: We genotyped two common PPARgamma polymorphisms (Pro12Ala and 161C > T) and examined their association with the clinical phenotypes found in 684 patients with Type 2 diabetes mellitus and 291 non-diabetic control subjects. RESULTS: The 12Ala allele was less frequent in the Type 2 diabetic patients than in the non-diabetic control subjects (0.036 vs. 0.053, P = 0.024). The allele frequencies of the 161C > T polymorphism did not differ between the control and Type 2 diabetic group (0.158 vs. 0.173). In the non-diabetic controls, those with the T allele had lower BMI and fasting serum triglyceride (TG) concentrations than those with the C/C homozygote (22.7 +/- 2.9 vs. 23.8 +/- 3.2 kg/m2, P = 0.002; 1.45 +/- 0.81 vs. 1.65 +/- 0.83 mmol/l, P = 0.03, respectively). The 12Ala-161T haplotype was associated with a decreased risk for Type 2 diabetes (OR = 0.47, P = 0.009), whereas the 12Pro-161T haplotype was associated with lower BMI and lower fasting serum TG (22.5 +/- 2.8 vs. 23.7 +/- 3.2 kg/m2, P = 0.004; 1.41 +/- 0.87 vs. 1.64 +/- 0.79 mmol/l, P = 0.02, respectively). CONCLUSIONS: The PPARgamma 12Ala allele was associated with a reduced risk of Type 2 diabetes, whereas the PPARgamma 161T allele was associated with lower BMI and fasting serum TG concentrations in the Korean subjects. The subjects with 12Ala-161T haplotypes had a reduced risk of Type 2 diabetes. [ABSTRACT FROM AUTHOR]

Many studies show poor agreement between fasting plasma glucose (FPG)-based and 2-h postchallenge glucose (2-h PG)-based criteria to assess glucose metabolism. We examined the rate of agreement between FPG- and 2-h PG-based criteria in the diagnosis of intermediate hyperglycemia in four representative cohort studies in South Korea and compared the clinical characteristics and biochemical parameters in subjects with impaired fasting glucose (IFG) according to their FPG values. Of 6234 subjects from four population-based studies performed from 1993 to 2000, 4610 individuals with data from a 75g oral glucose tolerance test (OGTT) and no previous history of diabetes were selected. We examined the concordance rate between the FPG and 2-h PG-based criteria. We also investigated the differences in the clinical characteristics and biochemical parameters between individuals with IFG according to their FPG values. The fasting and 2-h PG criteria had large discordance rates in the diagnosis of diabetes and impaired glucose tolerance (IGT) in Korean adults. When individuals with IFG were classified into stage 1 [5.6-6.1mmol/L (100-109mg/dL)] and stage 2 [6.1-7.0mmol/L (110-125mg/dL)] IFG, individuals with stage 2 IFG are more obese and had higher blood pressure and total cholesterol and triglycerides concentrations compared with those with stage 1 IFG. In addition, more individuals with stage 2 IFG were with diabetes as determined by a 2-h PG>or=11.1mmol/L (14.1% vs. 1.9%) (P<0.05). Considering the poorer metabolic profile and higher percentage of people with diabetes by OGTT, these data indicate that, in the Korean population, individuals with stage 2 IFG should be treated differently from those with stage 1 IFG. To detect more cases of diabetes, the OGTT is recommended for all individuals with stage 2 IFG and cases with stage 1 IFG with some additional risk factors for diabetes. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the impact of the revised papillary renal cell carcinoma (PRCC) classification and evaluate its validity with regard to oncological outcome stratification., Patients and Methods: Identifying 527 patients with PRCC who underwent surgical resection from 1995 to 2022, a tissue microarray was constructed for immunohistochemical and molecular characterisation. Re-classification according to the World Health Organization (WHO) 2022 criteria and nuclear grading according to the WHO/International Society of Urological Pathologists criteria were done. In addition to the revised subtype, alleged clinicopathological prognosticators were analysed with respect to progression-free (PFS) and cancer-specific survival (CSS)., Results: Initially, 247 (46.9%) cases were Type 1, 234 (44.4%) were Type 2, and 46 (8.7%) were papillary not-otherwise-specified. According to the revised criteria, 29.9% of Type 1 and 57.7% of Type 2 PRCC cases were re-classified. Re-classified from Type 1 included more indolent tumours while from Type 2 PRCC many molecularly defined tumours were newly identified. After re-classification, still 373 tumours remained with distinct histomorphological features of Type 1 (254 [70%]) and Type 2 (119 [42.2%]) PRCC. Furthermore, significant differences in survival outcomes were obtained when the revised criteria was used particularly for tumours of ≤4 cm. For a median (interquartile range) follow-up of 79 (38.2-132.8) months, the 5-year PFS was 97% for Type 1, 80% for Type 2, 75% for transcription factor for immunoglobulin heavy-chain enhancer 3 (TFE3)-rearranged, and 43.5% for fumarate hydratase-deficient RCC. No disease progression was observed in patients with papillary renal neoplasm with reverse polarity., Conclusion: The revised WHO 2022 classification enhanced prognostic accuracy for PRCC particularly for small tumours. Retaining previous subtypes may confer further clinical as well as prognostic value., (© 2024 BJU International.)

This study compares biomarker levels among environmentally vulnerable residents in Korea, the general Korean population, and Asians in the United States. We selected 953 exposed residents and 204 controls from the Forensic Research via Omics Markers in Environmental Health Vulnerable Areas (FROM) study (2021-2023), 4,239 participants from the fourth Korean National Environmental Health Survey (2018-2020), and 996 Asians from the US National Health and Nutrition Examination Survey (2017-March 2020). The analyzed biomarkers included blood and urinary metals, urinary metabolites of polycyclic aromatic hydrocarbons (PAHs), nicotine, volatile organic compounds (VOCs), and serum perfluorocarbon metabolites. The highest median biomarker levels varied by pollution source among older adults. In refineries, blood lead and cadmium (Cd), as well as urinary Cd and 2-hydroxyfluorene (2-OHFlu), were highest. Abandoned metal mines exhibited the highest blood and urinary mercury (Hg), urinary Cd, total arsenic (As), 2-naphthol, and cotinine levels. Coal-fired power plants showed the highest urinary 1-PHEN levels, while cement factories had the highest urinary As3+ levels. Sprawls demonstrated the highest urinary monomethylarsonic acid, 1-hydroxypyrene, and phenylglyoxylic acid levels, and industrial areas recorded the highest levels of trans, trans-muconic acid, benzylmercapturic acid, and 2-MHA. In general, biomarker levels were higher among exposed residents in the FROM study than in the general population; however, urinary 2-hydroxyfluorene and As5+ levels did not differ significantly. Exposure to pollution sources in environmentally vulnerable areas may elevate biomarker levels in residents.

Objective: We aimed to examine how different types of adrenal hormone excess influence body composition., Design: A retrospective, cross-sectional, single-centre study., Methods: We retrospectively enrolled 2971 consecutive adults with adrenal tumours and age-, sex-, and body mass index-matched controls at a 1:3 ratio. The area and attenuation of skeletal muscle and fat at the L3 vertebrae were measured using computed tomography-based analysis software. Prevalence ratios of cardiometabolic outcomes were calculated using the Poisson regression., Results: Patients with non-functioning adenoma (n = 1354) and mild autonomous cortisol secretion (MACS; n = 786) showed similar body compositions. Patients with overt Cushing's syndrome (CS) had the highest visceral fat (VF) area to skeletal muscle area ratio (1.14), while pheochromocytoma (PHEO) patients had the lowest (0.52). Muscle attenuation was lowest in CS and highest in PHEO (32.6 vs 41.5 Hounsfield units, P < .001). Mild autonomous cortisol secretion patients had higher risks of hypertension and dyslipidaemia than non-functioning adenoma patients. Non-functioning adenoma and MACS patients had higher VF area and lower muscle/fat attenuation compared with controls, while primary aldosteronism patients had body compositions similar to controls, except for higher fat attenuation., Conclusions: Adrenal tumours are associated with altered body composition. Even patients with non-functioning adenoma and MACS had increased VF area and lower muscle and fat attenuation compared with controls, indicating potential cardiometabolic risks., Competing Interests: Conflict of interest: S.J.P. is the founder of MEDICALIP. Other authors have no conflict of interest relevant to this article., (© The Author(s) 2025. Published by Oxford University Press on behalf of European Society of Endocrinology. 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.)

Several ongoing trials are evaluating incretin-based therapies, including GLP-1 receptor agonists, for their effects on CKD and MASLD. These studies will offer insights into their potential for metabolic diseases in people with type 2 diabetes and obesity., (© 2024 The Author(s). Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Aim/introduction: We assess the efficacy of artificial intelligence (AI)-based, fully automated, volumetric body composition metrics in predicting the risk of diabetes., Materials and Methods: This was a cross-sectional and 10-year retrospective longitudinal study. The cross-sectional analysis included health check-up data of 15,330 subjects with abdominal computed tomography (CT) images between January 1, 2011, and September 30, 2012. Of these, 10,570 subjects with available follow-up data were included in the longitudinal analyses. The volume of each body segment included in the abdominal CT images was measured using AI-based image analysis software., Results: Visceral fat (VF) proportion and VF/subcutaneous fat (SF) ratio increased with age, and both strongly predicted the presence and risk of developing diabetes. Optimal cut-offs for VF proportion were 24% for men and 16% for women, while VF/SF ratio values were 1.2 for men and 0.5 for women. The subjects with higher VF/SF ratio and VF proportion were associated with a greater risk of having diabetes (adjusted OR 2.0 [95% CI 1.7-2.4] in men; 2.9 [2.2-3.9] in women). In subjects with normal glucose tolerance, higher VF proportion and VF/SF ratio were associated with higher risk of developing prediabetes or diabetes (adjusted HR 1.3 [95% CI 1.1-1.4] in men; 1.4 [1.2-1.7] in women). These trends were consistently observed across each specified cut-off value., Conclusions: AI-based volumetric analysis of abdominal CT images can be useful in obtaining body composition data and predicting the risk of diabetes., (© 2024 The Author(s). Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Objective: To examine the hepatic effectiveness of sodium-glucose cotransporter-2 inhibitors (SGLT-2i) through a head-to-head comparison with glucagon-like peptide-1 receptor agonists (GLP-1RA) or thiazolidinediones (TZD) in patients with metabolic dysfunction-associated steatotic liver disease (MASLD)., Design: This population-based cohort study was conducted using a nationwide healthcare claims database (2014-2022) of Korea. We included individuals with MASLD (aged ≥40 years) who initiated SGLT-2i or comparator drugs (GLP-1RA or TZD). Primary outcome was a composite of hepatic decompensation events, including ascites, oesophageal varices with bleeding, hepatic failure or liver transplant. Liver-cause death and all-cause death were also assessed as secondary outcomes. Cox proportional hazards models were used to estimated HRs with 95% CIs., Results: After 1:1 propensity score matching, we included 22 550 patients who initiated SGLT-2i and GLP-1RA (median age=57 years, 60% male), and 191 628 patients who initiated SGLT-2i and TZD (median age=57 years, 72% male). Compared with GLP-1RA, SGLT-2i showed a similar risk of hepatic decompensation events (HR 0.93, 95% CI 0.76 to 1.14). Compared with TZD, SGLT-2i demonstrated a reduced risk of hepatic decompensation events (HR 0.77, 95% CI 0.72 to 0.82). As compared with TZD, the results of secondary analyses showed significantly lower hepatic decompensation event risks with SGLT-2i when stratified by sex (male: HR 0.87 (95% CI 0.80-0.94); female: HR 0.62 (95% CI 0.55-0.69))., Conclusions: In this nationwide cohort study, SGLT-2i was associated with a lower risk of hepatic decompensation events in patients with MASLD compared with TZD, while demonstrating similar effectiveness to GLP-1RA., Competing Interests: Competing interests: J-YS received grants from the Ministry of Food and Drug Safety, the Ministry of Health and Welfare, the National Research Foundation of Korea, and pharmaceutical companies, including LG Chem, UCB, SK bioscience and Pfizer, outside the submitted work., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Despite increasing heavy metal pollution, traditional epidemiology often fails to link exposure to health outcomes. This study used multi-omics to investigate associations between heavy metal exposure and health. Blood and urine samples from 294 participants in heavy metal-exposed and control areas were analyzed, revealing key biomarkers. Meta P analysis revealed consistent trends in apolipoprotein C3 (APOC3) expression, and mediation analysis showed significant effects of APOC3 and zinc-alpha-2-glycoprotein (ZA2G) on metabolites: the mediating effect of APOC3 from blood cadmium to serotonin was 0.023 (P < 0.001) and that to 3-phosphoglyceric acid (3PG) was 0.0125 (P = 0.002). Mendelian randomization confirmed the positive impact of APOC3 and Complement Factor I (CFAI) and the negative effect of ZA2G on metabolites, with apolipoprotein H (APOH) methylation significantly altering APOC3 (β = -0.22, P = 0.017), CFAI (β = 0.176, P = 0.035), and ZA2G (β = 0.139, P = 0.048) protein levels. Liver function variables, including albumin, total protein, calcium, and lactate dehydrogenase, correlated with 3PG and serotonin levels in the exposed areas. Sex-specific analysis showed that men exhibited stronger compensatory mechanisms via CFAI and myo-inositol, while women's greater vulnerability to heavy metal exposure highlighted the need for targeted interventions. These findings suggest APOH methylation affects APOC3, CFAI, and ZA2G levels, elevating 3PG, inosine monophosphate, and serotonin levels and harming liver function via lipolysis, supporting the use of these markers in health monitoring, therapies, and policies to limit heavy metal risks., 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 B.V.)

Objectives: This study measured cooking fumes to which workers in school cafeterias may be exposed., Methods: The measurement items were respirable dust, formaldehyde, and carbon monoxide. A total of 111 samples were obtained from 55 schools. Data on variables such as school size and daily cooking oil usage were collected. Correlation and association analysis were performed., Results: The median of concentrations of respirable dust was 38.37 µg/m3 (min-max: 20.73-49.71 µg/m3). The concentrations of formaldehyde and carbon monoxide also showed levels that did not exceed 20% for occupational exposure limits. The increase in school size was significantly correlated with the increase in daily cooking oil usage and had a significant correlation with respirable dust concentration (Spearman's correlation coefficient, 0.36; P <0.05). The linear regression test results adjusting for other variables were also similar., Conclusions: Cooking food by frying at high heat using cooking oil can increase the exposure of kitchen workers to respirable dust., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Occupational Hygiene 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.)

Background: Chronic musculoskeletal pain (CMP) affects around 1.7 billion people globally, causing significant physical, psychological, and economic burdens. Current treatments often involve medications with risks, creating an urgent need for accessible alternatives. Interventionist-administered Auricular Point Acupressure (APA) has shown effectiveness in reducing pain. To explore whether this low-risk, non-invasive, non-pharmacologic, and non-opioid pain relief method can be expanded digitally, this study developed a self-managed APA program using mobile health technology and coaching videos, allowing individuals to self-administer APA and evaluate its impact and sustainability., Methods: A 3-group pilot randomized controlled trial was conducted among 37 participants with CMP. The participants were randomly assigned to in-person APA (n=14) with face-to-face APA instruction, self-guided APA (n=12) with remote APA coaching, or control (n=11). All received conventional healthcare, with the APA groups also receiving adjuvant APA intervention for a 4-weeks supplemented with mobile app coaching videos, followed by monthly monitoring for three months. Data on pain intensity, physical disability, physical function, anxiety, depression, fatigue, sleep disturbance, fear avoidance of work, and satisfaction were collected at baseline, immediately following the 4-week APA intervention, and during the 2-month and 3-month follow-ups post-intervention., Results: Both the in-person and self-guided APA groups experienced a 47% reduction in pain intensity. Over 50% of participants achieved at least a 30% reduction in pain, and more than 17% had a 30% reduction in physical disability. Improvements included an 18% boost in physical function, decreased fatigue, improved sleep disturbance, and less depression (with increases noted in the control group), a 50% reduction in fear-avoidance of work, and only 3.8% reported not being satisfied with the APA at the 3-month follow-up. No adverse effects related to APA were reported., Conclusion: APA improved physical and mental health in participants with CMP, enhanced readiness to return to work, and demonstrated sustainability for at least three months. Coaching videos delivered via a mobile app proved to be a feasible approach for teaching APA, increasing the accessibility of the intervention. This study highlights the impact of APA and recommends further research into its mechanisms and long-term benefits to support integration into standard practice., Competing Interests: Competing interests The authors declare that they have no competing interests.

Diagnosing post-gastrectomy hypoglycemia is challenging, often relying on medical history with documented low plasma glucose levels. Here, we present three cases of patients who presented a high probability of post-gastrectomy hypoglycemia diagnosed and managed successfully using "theragnostic" continuous glucose monitoring and alpha-glucosidase inhibitors. In the first week, patients maintained their current lifestyle without medical intervention; in the second week, voglibose 0.2 mg before meals was prescribed. Continuous glucose monitoring data from the first week confirmed the diagnosis with multiple hypoglycemic events after postprandial peaks, whereas data from the second week showed reduced hypoglycemic events and lower glycemic variability, demonstrating voglibose's therapeutic effect. This report highlights the effective management of post-gastrectomy hypoglycemia using voglibose and theragnostic continuous glucose monitoring, showing its potential benefits and safety for similar cases., (© 2024 The Author(s). Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)

Background: Papillary renal cell carcinoma (pRCC) is the second most common histological subtype of renal cell carcinoma and is considered a morphologically and molecularly heterogeneous tumor. Accurate classification and assessment of the immunohistochemical features of possible therapeutic targets are needed for precise patient care. We aimed to evaluate immunohistochemical features and possible therapeutic targets of papillary renal neoplasms., Methods: We collected 140 papillary renal neoplasms from three different hospitals and conducted immunohistochemical studies on tissue microarray slides. We performed succinate dehydrogenase B, fumarate hydratase, and transcription factor E3 immunohistochemical studies for differential diagnosis and re-classified five cases (3.6%) of papillary renal neoplasms. In addition, we conducted c-MET, p16, c-Myc, Ki-67, p53, and stimulator of interferon genes (STING) immunohistochemical studies to evaluate their pathogenesis and value for therapeutic targets., Results: We found that c-MET expression was more common in pRCC (classic) (p = .021) among papillary renal neoplasms and Ki-67 proliferation index was higher in pRCC (not otherwise specified, NOS) compared to that of pRCC (classic) and papillary neoplasm with reverse polarity (marginal significance, p = .080). Small subsets of cases with p16 block positivity (4.5%) (pRCC [NOS] only) and c-Myc expression (7.1%) (pRCC [classic] only) were found. Also, there were some cases showing STING expression and those cases were associated with increased Ki-67 proliferation index (marginal significance, p = .063)., Conclusions: Our findings suggested that there are subsets of pRCC with c-MET, p16, c-MYC, and STING expression and those cases could be potential candidates for targeted therapy.

Activated carbon (AC) sediment amendment is an in-situ remediation technology in which the applied AC immobilizes organic contaminant flux from sediments, thereby reducing contaminant bioavailability and associated risks. While various studies have demonstrated the feasibility of in-situ AC treatment, hesitation to apply this technology exists due to limited experience under field-specific scour conditions and hydrodynamic forces. To address this concern, we conducted a feasibility study for an AC-blended cover at the Lauritzen Channel of the United Heckathorn Superfund Site in Richmond, California, United States, which was contaminated with dichlorodiphenyltrichloroethane and its metabolites (DDx) as well as dieldrin. Vessel activities causing sediment disturbance were identified as key factors for remedy selection. A blended cover with AC and coarse materials was designed to withstand varied hydrodynamic conditions and AC stability was tested in a current flume. The cover comprised medium-size gravel (D 50  = 15 mm, D 90  = 19 mm) with 4 % granular AC by weight. Flume erosion studies showed minimal AC loss (1-2 % of total AC) under shear forces of 9-31 Pa, which was equivalent to or exceeded the estimated worst-case erosional conditions in the channel induced by a hypothetical, stationary tugboat propelling at high power thrust. The treatability performance of the engineered blended cover design was evaluated through mesocosm studies using site sediment and various cover options. Post-treatment assessments on days 5 and 145 showed rapid reductions in freely dissolved (C free ) DDx and dieldrin in the blended cover layers and surface water. For example, by day 145, C free DDx was reduced by over 98 %, meeting US EPA remedial goals for the site. It is concluded that the combination of both stability and performance testing demonstrates that an engineered blended cover-AC design would be a feasible remedial option at the site, and that this testing approach can be applied to evaluate in-situ treatment in other sediment cleanup activities., 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 B.V. All rights reserved.)

Aim: To evaluate whether the use of sodium-glucose cotransporter-2 (SGLT2) inhibitors which have shown potential neuroprotective effects, is associated with lower risk of dementia in patients with type 2 diabetes (T2D) and comorbid mental disorders, who are considerably more susceptible to dementia., Methods: Using the nationwide healthcare data of South Korea between 2010 and 2022, we conducted a retrospective cohort study among patients with T2D and comorbid mental disorders initiating SGLT2 inhibitors versus active comparator (Dipeptidyl Peptidase IV (DPP4) inhibitors). Hazard ratios (HRs) and rate differences (RDs) per 1000 person-years of incident dementia were estimated after weighting by propensity score fine stratification method., Results: Over a 4.8-year median follow-up, SGLT2 inhibitors were associated with a 12 % lower risk of dementia compared with DPP4 inhibitors (11.31 vs. 12.86 events per 1000 person years; HR 0.88, 95 % CI 0.84 to 0.92; RD -1.55, -2.13 to -0.97). The results were consistent when stratified by age, sex, individual component, severe mental disorders, presence of insulin, history of cardiovascular disease, or history of hypertension., Conclusions: SGLT2 inhibitors versus DPP4 inhibitors were associated with a lower risk of incident dementia in patients with T2D and comorbid mental disorders. Further randomized controlled trials are required to confirm our findings., Competing Interests: Declaration of competing interest All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: this study was funded by the Ministry of Food and Drug Safety, South Korea. JYS received grants from the Ministry of Food and Drug Safety, Ministry of Health and Welfare, National Research Foundation of Korea, and Government-wide R&D Fund for Infectious Disease Research and Pharmaceutical Companies, including Pfizer, LG Chemical, and Union Chimique Belge. BH was supported by China Scholarship Council (Grant no. #202,308,260,057). YMC received research grants from Daewoong Pharmaceuticals and Sanofi, and consultation fees from Hanmi and LG Chemical. The other authors report no financial relationships with any organizations that might have an interest in the submitted work in the previous three years, and no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Background: The increased incidence of breast cancer implies the appearance of frequent symptoms associated with disease and treatments, such as pain. For the management of this issue, auricular therapy has been used in a complementary manner, especially for its safety and analgesic action., Objective: This systematic review aims to summarize available evidence on the effects of auricular therapy on pain in women undergoing breast cancer treatment., Methods: This is a systematic review that includes randomized controlled trials that evaluated the effects of auricular therapy on pain in women with breast cancer, as compared with other interventions (sham or placebo auricular therapy, other nonpharmacological interventions, and routine pain treatments) during the treatment of the disease. Pain, whether induced or not by cancer treatments, is the main outcome to be evaluated. The search for the studies was performed in the following databases: MEDLINE through PubMed, CINAHL, CENTRAL, Embase, Web of Science, Scopus, VHL, TCIM Americas Network, CNKI, and Wanfang Data. The reviewers have independently evaluated the full texts, and in the near future, they will extract the data and assess the risk of bias in the included studies. The certainty of the evidence will be assessed using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE), and a meta-analysis will be carried out to evaluate the intervention, considering the homogeneity of the results, using the Cochran Q test and quantified by the Higgins inconsistency index. The guidelines of the PRISMA-P (Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols) have been respected in the elaboration of this protocol., Results: The records screening stage has been completed, and the synthesis and meta-analysis were conducted in February 2024. We hope to have finished the preparation of the paper for publication by September 2024. Review reporting will follow standard guidelines for reporting systematic reviews. The results will be published in peer-reviewed scientific journals., Conclusions: This review will compile the strength of evidence for the use of auricular therapy in the management of pain in women with breast cancer during the treatment of the disease, identifying gaps in the available evidence as well as assisting health professionals in indicating the intervention for clinical practice., Trial Registration: PROSPERO CRD42022382433; https://www.crd.york.ac.uk/prospero/display&#95;record.php?RecordID=382433., International Registered Report Identifier (irrid): DERR1-10.2196/55792., (©Ludmila Oliveira Ruela, Caroline de Castro Moura, Bianca Shieu, Yu-Min Cho, Chao Hsing Yeh, Franklin Fernandes Pimentel, Juliana Stefanello. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 15.10.2024.)

This study investigated neurodevelopment and risk factors in children surgically treated for congenital gastrointestinal anomalies (CGIA), excluding those with known high-risk factors such as low birth weight or chromosomal anomalies. Data of children born between 2008 and 2015 who underwent surgical treatment for CGIA were retrieved from the Korean National Health Insurance Database. CGIA included esophageal atresia, duodenal atresia, jejunoileal atresia, anorectal malformations, and congenital megacolon. Neurodevelopmental impairment (NDI) was defined as Korean Ages and Stages Questionnaire scores below the determined cut-off or Korean Developmental Screening Test scores < 2 standard deviations at 3 years of age. Children with CGIA had a significantly higher risk of NDI than controls (6.2% vs. 2.7%, p < 0.001). Growth failure was correlated with NDI. Longer durations of oxygen support (adjusted odds ratio [aOR], 1.037; 95% confidence interval [CI], 1.013-1.063), mechanical ventilation (aOR, 1.053; 95% CI, 1.018-1.089), and number of surgeries (aOR, 1.137; 95% CI, 1.016-1.273) were significantly associated with NDI. These findings emphasize that cautious yet proactive neurodevelopmental monitoring is crucial in affected children, ensuring timely intervention and that excessive concern among families is unnecessary., (© 2024. The Author(s).)

Background: Both sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1 RAs) may have neuroprotective effects in patients with type 2 diabetes (T2D). However, their comparative effectiveness in preventing dementia remains uncertain., Objective: To compare the risk for dementia between SGLT2 inhibitors and dulaglutide (a GLP-1 RA)., Design: Target trial emulation study., Setting: Nationwide health care data of South Korea obtained from the National Health Insurance Service between 2010 and 2022., Patients: Patients aged 60 years or older who have T2D and are initiating treatment with SGLT2 inhibitors or dulaglutide., Measurements: The primary outcome was the presumed clinical onset of dementia. The date of onset was defined as the year before the date of dementia diagnosis, assuming that the time between the onset of dementia and diagnosis was 1 year. The 5-year risk ratios and risk differences comparing SGLT2 inhibitors with dulaglutide were estimated in a 1:2 propensity score-matched cohort adjusted for confounders., Results: Overall, 12 489 patients initiating SGLT2 inhibitor treatment (51.9% dapagliflozin and 48.1% empagliflozin) and 1075 patients initiating dulaglutide treatment were included. In the matched cohort, over a median follow-up of 4.4 years, the primary outcome event occurred in 69 participants in the SGLT2 inhibitor group and 43 in the dulaglutide group. The estimated risk difference was -0.91 percentage point (95% CI, -2.45 to 0.63 percentage point), and the estimated risk ratio was 0.81 (CI, 0.56 to 1.16)., Limitation: Residual confounding is possible; there was no adjustment for hemoglobin A 1c levels or duration of diabetes; the study is not representative of newer drugs, including more effective GLP-1 RAs; and the onset of dementia was not measured directly., Conclusion: Under conventional statistical criteria, a risk for dementia between 2.5 percentage points lower and 0.6 percentage point greater for SGLT2 inhibitors than for dulaglutide was estimated to be highly compatible with the data from this study. However, whether these findings generalize to newer GLP-1 RAs is uncertain. Thus, further studies incorporating newer drugs within these drug classes and better addressing residual confounding are required., Primary Funding Source: Ministry of Food and Drug Safety of South Korea., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M23-3220.

Objective: Chemotherapy-induced neuropathy (CIN) significantly impacts cancer patients, leading to functional disability, diminished quality of life, and increased healthcare costs amid the ongoing opioid crisis. Auricular point acupressure (APA), a non-invasive and non-pharmacological alternative, has shown potential for alleviating the pain, numbness, and tingling associated with CIN. This study aims to assess the efficacy of APA for CIN symptoms and physical function and to examine the mechanisms underlying APA's effects on CIN., Methods: This is a three-arm randomized controlled clinical trial protocol. Patients aged 18 and older who are experiencing CIN are randomly assigned to one of the three groups: an APA group (in-person APA; mAPA), a sham control group (virtual APA; vAPA), and a wait-list usual care control group (UC). During the four-week program, participants in the mAPA receive an in-person APA treatment and training; the sham control participants (vAPA) receive a self-guided smartphone APA application with APA demonstration videos; and the UC participants will continue with the usual care and be re-randomized into one of the APA groups. The primary outcomes are changes in CIN symptoms and physical function. Secondary outcomes include evaluating pain sensory thresholds, motor and cognitive functioning, inflammatory signaling, brain connectivity, opioid use, and quality of life. The outcomes are measured at baseline, program completion (4 weeks), and at monthly follow-up for 3 months post-intervention., Discussion: This study will provide evidence supporting the potential viability of APA as an intervention for CIN., Trial Registration: ClinicalTrials.gov, ID NCT04920097 registered on 3 June 2021., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Lukkahatai 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.)

Purpose: A pressure of approximately 15-25 mmHg is used for effective compression therapy to prevent and treat hypertrophic scar formation in patients with burns. However, conventional facial compression garments present challenges owing to inadequate pressure distribution in curved areas such as the cheeks, around the mouth, and the slope of the nose. This study aimed to evaluate the utility of a custom-made 3D compression mask equipped with pressure sensors to treat facial burn scars., Methods: This single-blinded, prospective randomized controlled trial was conducted between May and October 2023, involving 48 burn scars in 12 inpatients with facial burns. We created the custom-made 3D compression mask equipped with pressure sensors, inner lined with biocompatible silicon, and a harness system using 3D printing technology, which can continuously monitor whether an appropriate pressure of 15-25 mmHg maintains. The biological scar properties, Vancouver Scar Scale (VSS), and Patient and Observer Scar Assessment Scale (POSAS) scores in patients with facial burns were assessed before applying the compression mask and garment and at 4 and 12 weeks after application., Results: Pre-application assessment of biological scar properties, VSS, and POSAS revealed no statistically significant differences between the 3D mask and control groups (p > 0.05 for all). Throughout the 12-week application, skin hydration and scar thickness significantly increased (p < 0.001) and reduced (p = 0.010), respectively, in the 3D mask group compared to the control group. Additionally, significant improvements in scar pliability (p = 0.004) and height (p = 0.009) of VSS, itching (p = 0.047), scar stiffness (p = 0.001), thickness (p = 0.011), and irregularity (p < 0.001) of POSAS-patient component, and scar thickness (p = 0.001), pliability (p = 0.012), and surface area (p = 0.027) of the POSAS-observer component were observed in 3D mask group throughout the 12-week application compared to the control group., Conclusion: The customized 3D compression mask equipped with pressure sensors significantly improved scar thickness, skin hydration, and various assessment scale parameters throughout the 12-week application., Competing Interests: Declaration of Competing Interest None. The funder played no role in the design of the study, collection, analyses, or interpretation of data, writing of the manuscript, or the decision to publish the results., (Copyright © 2024 Elsevier Ltd and International Society of Burns Injuries. All rights reserved.)

Background: Bladder cancer is characterized by frequent mutations, which provide potential therapeutic targets for most patients. The effectiveness of emerging personalized therapies depends on an accurate molecular diagnosis, for which the accurate estimation of the neoplastic cell percentage (NCP) is a crucial initial step. However, the established method for determining the NCP, manual counting by a pathologist, is time-consuming and not easily executable., Methods: To address this, artificial intelligence (AI) models were developed to estimate the NCP using nine convolutional neural networks and the scanned images of 39 cases of urinary tract cancer. The performance of the AI models was compared to that of six pathologists for 119 cases in the validation cohort. The ground truth value was obtained through multiplexed immunofluorescence. The AI model was then applied to 41 cases in the application cohort that underwent next-generation sequencing testing, and its impact on the copy number variation (CNV) was analyzed., Results: Each AI model demonstrated high reliability, with intraclass correlation coefficients (ICCs) ranging from 0.82 to 0.88. These values were comparable or better to those of pathologists, whose ICCs ranged from 0.78 to 0.91 in urothelial carcinoma cases, both with and without divergent differentiation/ subtypes. After applying AI-driven NCP, 190 CNV (24.2%) were reclassified with 66 (8.4%) and 78 (9.9%) moved to amplification and loss, respectively, from neutral/minor CNV. The neutral/minor CNV proportion decreased by 6%., Conclusions: These results suggest that AI models could assist human pathologists in repetitive and cumbersome NCP calculations.

We examined whether quarantined individuals complied with rules to prevent transmission at home and whether the government provided appropriate support to individuals in quarantine. Between November 2020 and August 2021, we surveyed 198 individuals who had been or were quarantined at home without infection. The online survey results show that respondents experienced difficulties living in close quarters with their cohabitants and had low compliance with in-house hygiene rules. The government needed to provide adequate employment protection, living expense, or care support. Such failures of the system were mainly due to a lack of legal grounds for the government to operate. To improve compliance, the government can amend laws to permit active communication of public health messages with those quarantined at home and provide the necessary support., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

A resurgence of Mycoplasma pneumoniae (MP)-the leading cause of community-acquired bacterial pneumonia, particularly in children-occurred following the COVID-19 pandemic. We aimed to investigate the clinical manifestations, macrolide resistance patterns, and therapeutic approaches related to the MP pneumonia epidemic. Children and adolescents diagnosed with MP pneumonia in September-December 2023 were screened. Clinical data were retrospectively collected from 13 major hospitals using concordant microbiological criteria, including either a positive PCR result or four-fold increase in serological markers. Demographic characteristics, treatment modalities, and clinical outcomes were analyzed. Of the 474 screened patients, 374 (median age: 7.7 [IQR, 5.4-9.6] years; hospitalization rate: 88.6%) met the microbiological confirmation criteria. Most patients experienced fever (98.9%), and lobular/lobar consolidation (59.1%) was the dominant radiological finding. The macrolide resistance rate remained high at 87.0%; corticosteroids were widely used (55.6%) alongside macrolides, despite resistance. Patients with consolidation had prolonged fever (median 8 vs. 7 days, p = 0.020) and higher hospitalization rates (92.3% vs. 83.0%, p = 0.008). Macrolide resistance did not significantly influence radiological outcomes. This study highlights the ongoing challenge of macrolide resistance in MP pneumonia and need for tailored therapeutic approaches. Despite high resistance, macrolides remain commonly prescribed, often concurrently with corticosteroids.

We report on a search for magnetic monopoles (MMs) produced in ultraperipheral Pb-Pb collisions during Run 1 of the LHC. The beam pipe surrounding the interaction region of the CMS experiment was exposed to 184.07  μb^{-1} of Pb-Pb collisions at 2.76 TeV center-of-mass energy per collision in December 2011, before being removed in 2013. It was scanned by the MoEDAL experiment using a SQUID magnetometer to search for trapped MMs. No MM signal was observed. The two distinctive features of this search are the use of a trapping volume very close to the collision point and ultrahigh magnetic fields generated during the heavy-ion run that could produce MMs via the Schwinger effect. These two advantages allowed setting the first reliable, world-leading mass limits on MMs with high magnetic charge. In particular, the established limits are the strongest available in the range between 2 and 45 Dirac units, excluding MMs with masses of up to 80 GeV at a 95% confidence level.

We investigated the potential association between ketonuria during treatment with sodium-glucose cotransporter-2 (SGLT2) inhibitors and its renoprotective effect in patients with type 2 diabetes. We included 192 patients who had received SGLT2 inhibitors for more than 6 months. After propensity score matching, 52 patients each were allocated into groups with or without ketonuria, respectively. The estimated glomerular filtration rate exhibited a significant improvement only in subjects with ketonuria (without ketonuria: mean difference, -0.02 mL/min/1.73 m2 [95% confidence interval (CI), -3.87 to 3.83 mL/min/1.73 m2] vs. with ketonuria: mean difference, 6.81 mL/min/1.73 m2 [95% CI, 3.16 to 10.46 mL/min/1.73 m2]; P<0.001). Improvement in estimated glomerular filtration rate at 6 months was associated with female sex and lower baseline body weight, blood pressure, and triglyceride levels in patients with ketonuria. In conclusion, the presence of ketonuria was associated with the renoprotective effect of SGLT2 inhibitors, and female sex and the absence of metabolic syndrome components may serve as additional indicators of these medications' substantial renoprotective effects in individuals with ketonuria.