Search

Research has documented that neighborhood disadvantage is associated with increased cardiovascular disease risk, but it is unclear which mechanistic pathways mediate this association across the life course. Leveraging a natural experiment in which refugees to Denmark were quasi-randomly assigned to neighborhoods across the country during 1986-1998, and using 30 years of follow-up data from population and health registers, we assessed whether and how individual-level poverty, unstable employment, and poor mental health mediate the relation between neighborhood disadvantage and the risk of hypertension, hyperlipidemia, and type 2 diabetes among Danish refugees (n = 40 811). Linear probability models using the discrete time-survival framework showed that neighborhood disadvantage was associated with increased risk of hypertension (0.05 percentage points [pp] per year [95% CI, -0.00 to 0.10]); hyperlipidemia (0.03 pp per year [95% CI, -0.01 to 0.07]), and diabetes (0.01 pp per year [95% CI, -0.02 to 0.03]). The Baron-Kenny product-of-coefficients method for counterfactual mediation analysis indicated that cumulative income mediated 6%-28% of the disadvantage effect on these outcomes. We find limited evidence of mediation by unstable employment and poor mental health. This study informs our theoretical understanding of the pathways linking neighborhood disadvantage with cardiovascular disease risk and identifies income security as a promising point of intervention to be studied in future research., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Various combination therapies have been investigated to overcome the limitations of using immune checkpoint inhibitors. However, determining the optimal combination therapy remains challenging. To overcome the therapeutic limitation, we conducted a translational research to elucidate the mechanisms by which AXL inhibition enhances antitumor effects when combined with anti-PD-1 antibody therapy. Herein, we demonstrated improved antitumor effects through combination treatment with denfivontinib and pembrolizumab which resulted in enhanced differentiation into effector CD4+ and CD8+ memory T cells, accompanied by an increase in IFN-γ expression in the YHIM-2004 xenograft model derived from patients with non-small cell lung cancer. Concurrently, a reduction in the number of immunosuppressive M2 macrophages and myeloid-derived suppressor cells was observed. Mechanistically, denfivontinib potentiated the NOD-like receptor pathway, thereby facilitating NLRP3 inflammasome formation. This leads to macrophage activation via NF-κB signaling pathway activation. We have confirmed that the positive interaction between macrophages and T cells arises from the enhanced antigen-presenting machinery of activated macrophages. Furthermore, the observed tumor effects in AXL knockout mice confirmed that AXL inhibition by denfivontinib enhances the antitumor effects, thus opening new avenues for therapeutic interventions aimed at overcoming limitations in immunotherapy. To demonstrate the extent to which our findings reflect clinical results, we analyzed bulk RNA sequencing data from 21 patients with non-small cell lung cancer undergoing anti-PD-1 immunotherapy. The NLRP3 inflammasome score influenced enhanced immune responses in patient data undergoing anti-PD-1 immunotherapy, suggesting a role for the NLRP3 inflammasome in activating immune responses during treatment., (©2024 The Authors; Published by the American Association for Cancer Research.)

Background/aim: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a serious global public health concern. Long non-coding RNAs (lncRNAs) have been identified as key contributors to MASLD pathogenesis. Zebrafish can be utilized to study the relationship between MASLD and lncRNAs because of their similarity to human genes. Oil Red O staining is a traditional method for confirming liver fatty changes; however, it has several limitations. This study aimed to evaluate the efficacy of boron-dipyrromethene (BODIPY) in detecting fatty changes in the liver., Materials and Methods: Liver tissues were collected from 30 zebrafish that were fed a BODIPY-containing high-cholesterol diet. Oil Red O and BODIPY staining were evaluated by two pathologists, and next-generation sequencing (NGS) was performed using liver tissues categorized into high fatty change (six liver tissues) and low fatty change (six liver tissues) groups., Results: BODIPY and Oil Red O staining of zebrafish liver sections correlated significantly ( p =0.009). NGS identified eight differentially expressed lncRNAs with over a 10-fold difference between the high- and low-fatty acid change groups. Of these, three showed lncRNA-mRNA interaction networks linked to human disorders., Conclusion: BODIPY staining is a reliable alternative to Oil Red O staining for assessing fatty changes in MASLD zebrafish models, particularly when examining frozen liver sections., (Copyright © 2025, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: To investigate the risk of genitourinary (GU) cancer in kidney transplant recipients (KTRs) compared to that in the general population, focusing on potential risk factors and clinical implications., Methods: Using a national cohort of approximately 360,000 individuals, including 31,542 KTRs, we conducted a retrospective analysis of the data from 2007 to 2018. Propensity score matching was used to compare KTRs with a healthy population, adjusting for age, sex, diabetes, hypertension, and hypercholesterolemia., Results: We identified a significantly increased risk of GU cancers, particularly bladder and kidney cancers, in KTRs. Multivariate analysis revealed a higher risk of GU cancer associated with kidney transplantation [hazard ratio (HR) 2.133, 95% confidence interval (CI) 1.641-2.772] and hypercholesterolemia (HR 1.725, 95% CI 1.227-2.425), with older age and male sex also being significant risk factors. Conversely, no significant increase in prostate cancer risk was observed in KTRs compared to the general population., Conclusion: This national cohort-based study indicated an increased risk of GU cancer in KTRs, underscoring the need for targeted cancer surveillance and pre- and post-transplant counseling. These findings provide valuable insights for the development of cancer surveillance programs for KTRs and highlight the necessity for further research in this field., Competing Interests: Declarations. Conflict of interest: The authors declare no competing interests. Ethics approval and consent to participate: Ethical clearance for this study was granted by the Institutional Review Board of The Catholic University of Korea (IRB No. PC19ZNSE0128). As the research involved the use of data from the National Health Database, where consent for the use of collected data for research purposes had already been obtained, individual informed consent from participants was not required. This study adhered to the ethical standards outlined in the Declaration of Helsinki and ensured the integrity and ethical compliance of the research., (© 2024. The Author(s).)

Maximizing the sorption capacity of gaseous Hg 0 by sulfur-functionalized biochar can lead to increased energy consumption and the production of secondary environmental pollutants such as greenhouse gases. This study evaluates the environmental impact of producing sulfurized biochar through a life cycle assessment (LCA), weighing these impacts against the benefits of enhanced Hg removal efficiencies. The biochar's Hg 0 adsorption capacity, which ranges between 3 and 22 μg-Hg 0 /g-biochar, is influenced by several factors: it increases with higher sulfur loading (0-15 %), higher O 2 levels (0-21 %), and longer pyrolysis times (1-5 h). However, it also decreases with increased pyrolysis temperature (100-500 °C). XPS and FT-IR analysis confirm that the sulfur in the biochar primarily exists as elemental sulfur, but each sulfurization condition also resulted in the formation of sulfate, organic sulfur, and sulfone. LCA results indicate that using biochar as a sorbent for Hg 0 is carbon-negative when the biochar is disposed of in landfills. Sensitivity analysis showed that increasing mercury adsorption capacity through excessive investment in energy and resources does not necessarily reduce the overall environmental impact. Consequently, when selecting an adsorbent for mercury removal, it is crucial to consider both sorption capacity and environmental impact., 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 © 2025 Elsevier Ltd. All rights reserved.)

Background: Patients with severe asthma are susceptible to lung function decline (LFD), but biomarkers that reliably predict an accelerated LFD have not been fully recognized., Objective: To identify variables associated with previous LFD occurrences in patients with severe asthma by exploring the computed tomography (CT) imaging features within predefined LFD groups., Methods: We obtained inspiratory and expiratory CT images of 102 patients with severe asthma and derived 2 airway structural parameters (wall thickness [WT] and hydraulic diameter) and 2 parenchymal variables (functional small airway disease and emphysema). We retrospectively calculated the annual changes in forced expiratory volume in 1 second and grouped participants by their values determined. The 4-imaging metrics, along with levels of several biomarkers, were compared among the LFD groups., Results: Patients with severe asthma with enhanced LFD exhibited significantly lower WT and smaller hydraulic diameter compared with those with minimal change or slight decline in lung function, after an adjustment of smoking status. Conversely, CT-based percentages of emphysema and functional small airway disease did not significantly differ according to LFD. Furthermore, fractional exhaled nitric oxide (FeNO) level and the blood matrix metalloproteinase-9/TIMP metallopeptidase inhibitor 1 ratio were significantly higher in patients with severe asthma with enhanced LFD compared with those in the others., Conclusion: Lower WT on CT scans with increased FeNO that may represent increased airway inflammation significantly correlated with enhanced LFD in patients with severe asthma. Consequently, active management plans may help to attenuate LFD for patients with severe asthma with lower WT and high FeNO., Competing Interests: Disclosures All authors declare that they have no conflicts of interest related to this article., (Copyright © 2024 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

The long-term complications of coronavirus disease 2019 (COVID-19) continue to cause global concern. This study aimed to estimate the incidence and risk of chronic urticaria, vitiligo, alopecia areata, and herpes zoster following COVID-19 infection. Only participants confirmed by real-time reverse transcription-polymerase chain reaction tests to have COVID-19 were enrolled in the COVID-19 group. The matched cohort without COVID-19 was enrolled randomly at a ratio of 1:1. The incidence and risk of chronic urticaria, vitiligo, alopecia areata, and herpes zoster were assessed in both groups using univariable and multivariable Cox proportional hazard analyses. A total of 4 976 589 COVID-19 patients (9.58% of the total population of South Korea) and an equivalent number of matched non-infected control subjects were analyzed. Chronic urticaria, vitiligo, alopecia areata, and herpes zoster manifested at higher rates within the COVID-19 cohort, even after multivariable adjustment for potential confounders. COVID-19 may increase the risk of developing chronic urticaria, vitiligo, alopecia areata, and herpes zoster., (© 2024 Japanese Dermatological Association.)

Purpose: There have been efforts to find alternative samples other than standard samples of tissue or plasma for mutational analyses for lung cancer patients. However, no other sample or technique has replaced the mutational analyses using standard samples. In this prospective study, we assessed a novel bronchoscopy method, named as targeted washing technique, for detecting the EGFR mutation., Materials and Methods: A 3.0-mm ultrathin bronchoscope was precisely navigated to the target lung lesion with the assistance of virtual bronchoscopic navigation and fluoroscopy. Once the bronchoscope is placed in front of target lung lesion, 0.9% normal saline was instilled for targeted washing. EGFR testing using targeted washing fluid (TWF) was compared to standard methods using plasma or tumor tissue., Results: In 41 TWF samples, the T790M mutation was detected in tissue, plasma, and TWF samples at rates of 22%, 10%, and 29%, respectively. The overall EGFR T790M detection rate using tissue, plasma, or TWF samples was 37%, with TWF samples increasing the T790M mutation detection rate by up to 10%. The accuracy of T790M mutation detection using TWF sample was 83% compared with standard samples. Four patients were found to have the EGFR T790M mutation solely through EGFR testing using TWF, which repeated rebiopsies using either plasma or tissue finally confirmed to have the T790M mutation., Conclusion: We demonstrated the clinical potential of targeted washing technique for molecular testing, which can be a good option to overcome spatial heterogeneity, low sensitivity of plasma sample or technical limitations in collecting tumor tissues.

Apart from conventional redox chemistries, exploring high-voltage anionic redox processes, such as pure oxygen or high-valent transition metal ion redox, poses challenges due to the instability of O nonbonding or O-dominant energy states. These states are associated with destructive behaviors in layered oxide cathodes, including local structural distortion, cationic disordering, and oxygen gas evolution. In this study, we suppress first-cycle voltage hysteresis and irreversible O 2 evolution in Li-rich oxide cathodes through covalency competition induced by the substitution of electropositive groups. We found that the nonequivalent electron distribution within an asymmetric M A -O-M B backbone (metal-to-metal charge transfer via oxygen ligands) increases electron density on electronegative transition metal ions, preventing them from reaching unstable oxidation states within an operating voltage range. This phenomenon is observed across diverse transition metal combinations, providing insights into controlling unnecessary oxygen redox activity. Our findings open new avenues for controlling intrinsic redox chemistry and enabling the rational design of high-energy density Li-rich oxide cathodes.

Context: Thyroid hormones are essential for energy metabolism related to thermogenesis and oxygen consumption., Objective: This study evaluated the potential association of thyroid function including thyroid peroxidase antibodies (TPOAb) with physical activity in nationally representative data., Design/setting/participants: This retrospective cohort study used data from the Korean National Health and Nutrition Examination Survey between 2013 and 2015. Physical activity (PA) was assessed using metabolic equivalents based on the validated Korean version of the International Physical Activity Questionnaire Short Form. PA level was categorized into 3 groups of high, moderate, and low. Participants with abnormal thyroid function test, restricted activity, or previous history of thyroid disease were excluded in the study., Results: A total of 5372 participants was finally selected. The free T4 level was lowest in the low PA group, while TSH was not significantly different among the groups. TPOAb titers increased in the following order: moderate PA, low PA, and high PA. After adjustment for confounding factors, moderate PA was associated with a high T4 level and a decrease in TSH and TPOAb with significance. However, there were no significant changes in free T4, TSH, or TPOAb titer in the high PA group. In a subanalysis, females with moderate PA showed a significant decrease in TSH and TPOAb. In both males and females, insulin sensitivity was increased with moderate PA. In obese participants, TSH negatively correlated with PA, and free T4 levels decreased in the low PA. The sensitivity to thyroid hormone did not differ in our study., Conclusion: The present study found an association between thyroid function and moderate PA. Therefore, moderate-intensity PA should be recommended to improve thyroid function., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Traditional intracranial pressure (ICP) monitoring methods, using intraventricular catheters, face significant limitations, including high invasiveness, discrete data, calibration complexities, and drift issues, which hinder long-term and stable monitoring. Here, a non-surgical, in-stent membrane bioelectronic system is presented for continuous and reliable ICP monitoring. This platform integrates a capacitive thin-film sensor with a stent, enabling precise real-time detection of pressure fluctuations directly within the dural venous sinus without requiring skull penetration or frequent recalibration. The sensor demonstrates a high sensitivity of 0.052%/mmHg and a broad, readable pressure range of 3-30 mmHg while maintaining calibration-free and drift-free performance. A series of in vivo studies highlight the system's superior sensitivity, rapid sampling rate, and long-term stability compared to conventional microcatheters. Statistical analyses reveal a strong agreement between the device and clinical reference, underscoring its potential to revolutionize ICP monitoring. These advancements pave the way for broader clinical applications, minimizing complications and improving patient outcomes in neurocritical care., (© 2025 The Author(s). Advanced Healthcare Materials published by Wiley‐VCH GmbH.)

Tumor-derived extracellular vesicle (tEV)-associated RNAs hold promise as diagnostic biomarkers, but their clinical use is hindered by the rarity of tEVs among nontumor EVs. Here, we present EV-CLIP, a highly sensitive droplet-based digital method for profiling EV RNA. EV-CLIP utilizes the fusion of EVs with charged liposomes (CLIPs) in a microfluidic chip. Optimized CLIP surface charge enables exceptional sensitivity and selectivity for EV-derived miRNAs and mRNAs. This approach streamlines detection with minimal plasma volume (20 μL) and eliminates the need for prior EV isolation or RNA preparation, preventing loss of EVs or RNA. In testing with 83 patient samples, EV-CLIP detected EGFR L858R and T790M mutations with high AUC values of 1.0000 and 0.9784, respectively. Its success in serial monitoring during chemotherapy highlights its potential for precise quantification of rare EV subpopulations, facilitating the exploration of single EV RNA content and enhancing understanding of diverse EV populations in various disease states.

Background: The increasing prevalence of atrial fibrillation (AF) requires efforts to understand racial differences in disease distribution and risk factors., Objective: We aimed to compare associations between risk factors and AF in White Europeans from the UK Biobank and Asians from the Korean National Health Insurance Service-Health Screening (NHIS-HEALS) study., Methods: This study included participants from the Korean NHIS-HEALS and UK Biobank. After matching for age and sex, 206,704 participants in the Korean NHIS-HEALS and 206,704 participants in the UK Biobank were enrolled in the study. The incidence of AF, its associations with biomarkers, prevalent cardiovascular disease, and population attributable risk by race were examined., Results: During a median follow-up of 7.1 years in the Korean NHIS-HEALS and 11.9 years in the UK Biobank, those in the UK Biobank showed a higher incidence and risk of AF (3.99 vs 3.41 per 1000 person-years; hazard ratio, 1.20; 95% confidence interval [CI], 1.15-1.25) compared with the population in the Korean NHIS-HEALS. Body mass index (BMI), systolic blood pressure, alcohol, heart failure, myocardial infarction, and stroke were associated with an increased risk of new-onset AF in both cohorts. Higher BMI and smoking were more strongly related to the increased risk of new-onset AF in the UK Biobank compared with the Korean NHIS-HEALS, with a relative risk ratio of 1.21 (95% CI, 1.17-1.25) and 1.12 (95% CI, 1.02-1.21), respectively., Conclusion: In this first large-scale comparison of White and Asian populations, the cumulative risk for development of AF was higher in the United Kingdom than in Korea. Higher BMI and smoking were associated with a higher risk of AF in the United Kingdom than in Korea., Competing Interests: Disclosures Boyoung Joung has served as a speaker for Bayer, BMS/Pfizer, Medtronic, and Daiichi-Sankyo and has received research funds from Medtronic and Abbott. No fees were received, either directly or personally. Gregory Lip has been a consultant and speaker for BMS/Pfizer, Boehringer Ingelheim, Daiichi-Sankyo, and Anthem. No personal fees were received. He is the co-principal investigator of the AFFIRMO project on multimorbidity in AF, which has received funding from the European Union’s Horizon 2020 research and innovation program under grant agreement No. 899871. The remaining authors have no conflicts of interest to disclose., (Copyright © 2025 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Eriobotrya japonica (Thunb.) Lindl., commonly known as loquat, is a plant belonging to the Rosaceae family. While its fruit is widely consumed as food and used in traditional medicine, research on other parts of the plant remains insufficient. Therefore, the chemical constituents and biological activities of its leaves were investigated. Phytochemical analysis of E. japonica leaves identified 30 compounds, including flavonoids, phenolics, and megastigmanes. The flavonoids isolated from the leaves include flavones, flavans, flavolignans, flavonoid glycosides, and coumaroyl flavonoid glycosides. Coumaroyl flavonoid rhamnosides were characteristically present in E. japonica leaves, and the configurations of coumaric acids, as well as the binding position to the rhamnose in each compound, were identified through detailed NMR analysis. Notably, three of them were isolated from this plant for the first time. Phenolic compounds were found to be present as conjugates with organic acids, such as quinic acid, shikimic acid, and glucose. Flavonoid and phenolic compounds demonstrated significant antioxidant and α-glucosidase inhibitory effects, whereas megastigmanes showed little activity. Notably, coumaroyl flavonoid rhamnosides, which consist of flavonoids combined with the phenolic acid, coumaric acid, exhibited excellent anti-diabetic effects. Further molecular docking analysis confirmed that these compounds effectively bind to the α-glucosidase enzyme. In conclusion, the present study identified flavonoid and phenolic components with various structures in E. japonica leaves and clarified their anti-diabetic and antioxidant effects. These findings support the beneficial potential of E. japonica leaves for the treatment and/or prevention of metabolic diseases.

We aimed to investigate which factors, including socioenvironmental factors and emotional regulation, were associated with pronounced delayed sleep patterns during the COVID-19 social restriction. We evaluated 744 adults aged 20-65 y using a web-based survey with a self-reported questionnaire in May 2022. Based on the survey, we estimated the mid-sleep time on free days corrected for oversleeping on free days (MSFsc) and social jet lag (SJL). We determined delayed sleep patterns using ΔMSFsc, which was defined as the difference between MSFsc during the pre- and mid-pandemic. The high-risk group for delayed sleep patterns (H-DSP) group was younger with evening person and had more severe insomnia, depression with rumination, and smartphone addiction ( p  < 0.05). Logistic regression revealed that stronger tendencies to express emotions and rumination were independent risk factors associated with a pronounced pattern of delayed sleep during the pandemic. In the H-DPS group, SJL increased even more during the pandemic. In socially restricted environments, emotion regulation significantly affects the severity of delayed sleep patterns, and people with H-DSP also had more disrupted circadian rhythms. Therefore, active education of sleep hygiene and emotional support with psychological interventions are needed in socially restricted environments.

Objective: To evaluate the association between various regimens and combinations of menopausal hormone therapy (MHT) and the risk of cardiovascular disease (CVD) in clinical practice., Design: This was a population-based cohort study., Methods: This population-based cohort study used data from the Health Insurance Review and Assessment Service. The data of women who reported entering menopause at ≥40 years of age with no history of CVD in the national health examination between 2011 and 2014 were extracted. A total of 134 298 pairs were included in the MHT and non-MHT groups after 1:1 propensity score matching. The participants were followed until December, 31, 2020., Results: During a median follow-up of 7.9 (IQR 6.9-8.9) years, the incidences of CVD were 146 per 100 000 person/year and 179 per 100 000 person/year for the non-MHT and MHT groups, respectively. After adjusting for covariates, MHT use was associated with an increased CVD risk (hazard ratio [HR], 1.22 [1.14-1.31]) compared with the non-MHT group; the risk was based on an increased risk of stroke and coronary artery revascularization. Tibolone (HR, 1.38, [1.27-1.50]) was associated with increased CVD, but estrogen alone or combined estrogen/progestogen was not. There was no difference in CVD risk, regardless of the type of estrogen agent used. For combined estrogen/progestogen therapy, dydrogesterone was associated with reduced CVD risk., Conclusions: There was an increased risk of CVD in MHT users. By regimen, tibolone use was associated with increased risk of CVD, whereas estrogen either alone or in combination with progestogen was not. There was no difference according to the type of estrogen. The type of progestogen seems to modify the results, since dydrogesterone was associated with reduced CVD risk., Competing Interests: Conflict of interest: All authors declare no conflict of interest., (© 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.)

Background: Although total intravenous anesthesia (TIVA) with propofol and remifentanil is frequently used to optimize intraoperative neurophysiological monitoring (IONM), the exact effect of remimazolam on IONM remains unknown. Here, we compared the effects of propofol and remimazolam along with remifentanil on IONM during TIVA., Methods: In this prospective, double-blind, randomized controlled trial, 64 patients requiring IONM during cervical spine surgery were administered either propofol (Group P) or remimazolam (Group R). The preoperative latencies of the somatosensory-evoked potentials (SEP; N20 for the median nerve and P37 for the tibial nerve) were measured. SEP latencies and amplitudes and motor-evoked potential (MEP) amplitudes were measured 30 min after anesthetic induction (T1), 30 min after surgical incision (T2), after laminectomy or discectomy (T3), immediately after plate insertion or pedicle screw fixation (T4), and before surgical wound closure (T5). The primary outcome was the between-group difference in the N20 latency changes measured at T1 and preoperatively., Results: The change in SEP latencies including N20 and P37 at T1 compared with preoperative time was not significantly different between Groups P and R. Except for the amplitude of the right abductor brevis, there was no significant group-by-time interaction effect for intraoperative MEP amplitudes or SEP latencies and amplitudes., Conclusions: TIVA with remimazolam and remifentanil for cervical spine surgery yielded stable IONM, comparable to those observed with conventional TIVA with propofol and remifentanil. Further clinical trials are needed in other surgical contexts and with more diverse patient populations to determine the effects of remimazolam on IONM.

Transgenic soybean (Glycine max) plants expressing mutant potyviral coat proteins that disrupt virion assembly exhibited non-strain-specific resistance against soybean mosaic virus., (© 2024 Institute of Botany, Chinese Academy of Sciences.)

Background: Disruption of cyclin D-dependent kinases (CDKs), particularly CDK4/6, drives cancer cell proliferation via abnormal protein phosphorylation. This open-label, single-arm, phase Ib/II trial evaluated the efficacy of the CDK4/6 inhibitor, abemaciclib, combined with paclitaxel against CDK4/6-activated tumors., Patients and Methods: Patients with locally advanced or metastatic solid tumors with CDK4/6 pathway aberrations were included. Based on phase Ib, the recommended phase II doses were determined as abemaciclib 100 mg twice daily and paclitaxel 70 mg/m 2 on days 1, 8, and 15, over 4-week-long cycles. The primary endpoint for phase II was the overall response rate (ORR). The secondary endpoints included the clinical benefit rate (CBR), progression-free survival (PFS), overall survival (OS), and safety. Tissue-based next-generation sequencing and exploratory circulating tumor DNA analyses were carried out., Results: Between February 2021 and April 2022, 30 patients received abemaciclib/paclitaxel (median follow-up: 15.7 months), and 27 were included in the efficacy analysis. CDK4/6 amplification (50%) and CCND1/3 amplification (20%) were common activating mutations. The ORR was 7.4%, with two partial responses, and the CBR was 66.7% (18/27 patients). The median OS and PFS were 9.9 months [95% confidence interval (CI) 5.7-14.0 months] and 3.5 months (95% CI 2.6-4.3 months), respectively. Grade 3 adverse events (50%, 21 events) were mainly hematologic. Genetic analysis revealed a 'poor genetic status' subgroup characterized by mutations in key signaling pathways (RAS, Wnt, PI3K, and NOTCH) and/or CCNE amplification, correlating with poorer PFS., Conclusion: Abemaciclib and paclitaxel showed moderate clinical benefits for CDK4/6-activated tumors. We identified a poor genetic group characterized by bypass signaling pathway activation and/or CCNE amplification, which negatively affected treatment response and survival. Future studies with homogeneous patient groups are required to validate these findings., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Recent evidence indicates that a dysregulated host metabolism influences treatment outcomes in patients with breast cancer. We investigated the association of computed tomography (CT)-derived body composition indices with therapeutic responses in patients with hormone receptor-positive, HER2-negative advanced breast cancer (ABC) on endocrine plus CDK4/6 inhibitor (CDK4/6i) treatment., Methods: The study involved a retrospective cohort of patients with ABC at the Yonsei Cancer Center who received CDK4/6i and aromatase inhibitors as first-line therapy between January 2017 and October 2020. Body composition parameters were estimated from the non-enhanced CT images of the third lumbar spine by commercialized deep learning software. Patients with low skeletal muscle radiodensity (SMD) were defined as patients with SMD of low tertile (≤ 28.7 Hounsfield Units). The primary outcome was progression-free survival (PFS)., Results: Among the 247 female participants (median age, 53 years; mean body mass index [BMI], 23.7 kg/m 2 ), 45.7% had disease progression or death during a median follow-up of 36.4 months. After adjusting for age and visceral metastasis, SMD was the only independent predictor among body composition parameters for worse PFS (adjusted hazard ratio [HR] = 1.20 per standard deviation decrement, 95% CI: 1.01-1.42, p = 0.041), whereas BMI, muscle area, and fat area were not. Participants with low SMD had a higher risk of progression than those without (PFS, 27.2 vs. 51.1 months, p = 0.009; adjusted HR 1.84, 95% CI: 1.22-2.76, p = 0.003). Strong associations between low SMD and poor PFS were observed in groups with pre-menopause status (HR, 3.04 vs. 1.19 in post-menopause; 95% CI: 1.54-5.99, p for interaction < 0.05) and without visceral metastases (HR, 2.95 vs. 1.19 in with visceral metastases; 95% CI: 1.59-5.49, p for interaction < 0.05)., Conclusions: CT-defined low SMD predicts poor treatment outcomes in patients with ABC undergoing first-line treatment with aromatase inhibitors and CDK4/6i., (© 2024 The Author(s). Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Tuberculosis, a disease of poverty, continues to disproportionately affect socioeconomically disadvantaged populations worldwide. This is particularly concerning given the recent resurgence of TB following the COVID-19 pandemic. In South Korea, despite substantial socioeconomic development, TB remains a prominent problem, ranking as the leading infectious killer in the country. The severe stigma associated with TB, coupled with the significant vulnerability of TB patients, has resulted in the voices of these patients being completely underrepresented in both policy and research. This article addresses this research gap by conducting a qualitative assessment of Korea's national TB control efforts through the lens of the UN's AAAQ (Availability, Accessibility, Acceptability, Quality) right to health framework. Through field observations and 20 in-depth interviews with TB patients, healthcare providers, policymakers, and advocates, we explore the lived experiences of socioeconomically disadvantaged TB patients in accessing care and support in Korea. Findings reveal that the failure to integrate the right to health into TB care and support, including inadequate availability, accessibility, acceptability, and quality of services tailored to the needs of this population, contributes significantly to Korea's TB burden. The findings have important implications for TB policy and practice in countries with high TB burdens or those experiencing a resurgence of TB. Prioritizing the right to health in TB care and support is crucial to effectively combat this disease., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: To assess the utility and challenges of using natural language processing (NLP) in electronic health records (EHRs) to ascertain health-related social needs (HRSNs) among older adults., Study Setting and Design: We extracted HRSN information using the NLP system Clinical Text Analysis and Knowledge Extraction System (cTAKES), combined with Concept Unique Identifiers and Systematized Nomenclature for Medicine codes. We validated cTAKES performance, via manual chart review, on two HRSNs: food insecurity, which was included in the healthcare system's HRSN screening tool, and housing insecurity, which was not., Data Sources and Analytic Sample: De-identified EHRs in a large California healthcare system (January 2013 through October 2022) from 119,127 patients aged 55+ in primary and emergency care settings (n = 1,385,259 clinical notes)., Principal Findings: Although cTAKES had a moderate positive predictive value (77.5%) for housing insecurity, housing challenges among older adults frequently did not align with the concepts the algorithm recognized. cTAKES performed poorly for food insecurity (positive predictive value: 18.5%) because this NLP system incorrectly flagged structured fields from the screening tool., Conclusion: Unstandardized terminology and poor integration of HRSN screeners in EHR remain important barriers to identifying older adults' food and housing insecurity using cTAKES., (© 2025 The Author(s). Health Services Research published by Wiley Periodicals LLC on behalf of Health Research and Educational Trust.)

Cd99 molecule-like 2 (Cd99l2) is a type I transmembrane protein that plays a role in the transmigration of leukocytes across vascular endothelial cells. Despite its high expression in the brain, the role of Cd99l2 remains elusive. We find that Cd99l2 is expressed primarily in neurons and positively regulates neurite outgrowth and the development of excitatory synapses. We demonstrate that Cd99l2 inversely regulates the expression of immediate-early genes (IEGs), including Arc, Egr1, and c-Fos, by inhibiting the activity of the transcription factors CREB and SRF. Neuronal inactivation increases the transport of Cd99l2 to the cell surface from recycling endosomes, thereby enhancing Cd99l2-mediated inhibitory signaling. Additionally, Cd99l2 knockout mice exhibit impaired excitatory synaptic transmission and plasticity in the hippocampus, along with deficits in spatial memory and contextual fear conditioning. Based on these findings, we propose that neuronal Cd99l2 functions as a synaptic cell adhesion molecule that inversely controls neuronal activation., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Protein tyrosine kinase 7 (PTK7), a catalytically defective receptor protein tyrosine kinase, is frequently upregulated in various cancers, including triple-negative breast cancer (TNBC), and is associated with poor clinical outcomes. Analysis of The Cancer Genome Atlas (TCGA) data confirmed that PTK7 mRNA expression is significantly higher in TNBC tumor tissues compared with adjacent normal tissues and non-TNBC breast cancer subtypes. Kaplan-Meier survival analysis demonstrated a strong correlation between high PTK7 expression and worse relapse-free survival in TNBC patients (HR = 1.46, p = 0.015). In vitro, anti-PTK7 monoclonal antibodies (mAbs) significantly reduced proliferation, wound healing, migration, and invasion in TNBC MDA-MB-231 cells. Ki-67 immunofluorescence assays revealed substantial decreases in cell proliferation following treatment with PTK7 mAbs (32-m, 43-m, 50-m, and 52-m). Moreover, actin polymerization, a critical process in cell migration and invasion, was markedly impaired upon PTK7 mAb treatment. In vivo, PTK7 mAbs significantly reduced tumor volume and weight in a TNBC xenograft mouse model compared with controls. Treated tumors exhibited decreased expression of Ki-67 and vimentin, indicating reduced proliferation and epithelial-to-mesenchymal transition. These findings highlight PTK7 as a promising therapeutic target in TNBC and demonstrate the potent anti-cancer effects of PTK7-neutralizing mAbs both in vitro and in vivo. Further exploration of PTK7-targeted therapies, including humanized mAbs and antibody-drug conjugates, is warranted to advance treatment strategies for PTK7-positive TNBC.

Introduction: We aimed to compare and analyze the cost-effectiveness of laparoscopic vs. open colorectal surgery (CRS) for colorectal cancer using health insurance claims data derived from multiple institutions in South Korea as well as the differences in hospital length of stay (LOS) and 30-day readmission rates related to postoperative complications., Methods: We retrospectively reviewed the clinical data of patients who underwent curative resection for colorectal cancer between January 1, 2020 and December 31, 2022 using national health insurance claims data in South Korea. We determined the surgical approach based on the presence or absence of treatment material codes specific to laparoscopic surgery, and divided the patients into the laparoscopic-CRS (lap-CRS) and open-CRS groups., Results: A total of 34,779 patients were included [open-CRS: 3,262 patients [9.4%]; lap-CRS: 31,517 patients [90.6%]]. The mean LOS was 14.11 and 11.27 days for the open- and lap-CRS groups, respectively ( p  < 0.001). The mean medical costs were 9,163 USD and 8,963 USD in the open- and lap-CRS groups, respectively ( p  < 0.001). A total of 1,192 (3.4%) patients were readmitted within 30 days of discharge, with a rate of 5.4% (176 cases) and 3.2% (1,016 cases) in the open- and lap-CRS groups, respectively ( p  < 0.001). Open surgery, male sex, and rectal surgery were identified as factors that increased medical cost., Discussion: According to this South Korean nationwide population-based study, laparoscopic surgery demonstrated a reduction in LOS, medical costs, and readmission rates compared with open surgery in patients with colorectal cancer., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2025 An, Hong, Kim and Kim.)

PHENIX presents a simultaneous measurement of the production of direct γ and π^{0} in d+Au collisions at sqrt[s&#95;{NN}]=200  GeV over a p&#95;{T} range of 7.5 to 18  GeV/c for different event samples selected by event activity, i.e., charged-particle multiplicity detected at forward rapidity. Direct-photon yields are used to empirically estimate the contribution of hard-scattering processes in the different event samples. Using this estimate, the average nuclear-modification factor, R&#95;{dAu,EXP}^{π^{0}}, is 0.925±0.023(stat)±0.15(scale), consistent with unity for minimum-bias (MB) d+Au collisions. For event classes with low and moderate event activity, R&#95;{dAu,EXP}^{π^{0}} is consistent with the MB value within 5% uncertainty. This result confirms that the previously observed enhancement of high-p&#95;{T} π^{0} production found in small-system collisions with low event activity is a result of a bias in interpreting event activity within the Glauber framework. In contrast, for the top 5% of events with the highest event activity, R&#95;{dAu,EXP}^{π^{0}} is suppressed by 20% relative to the MB value with a significance of 4.5σ, which may be due to final-state effects. This suppression corresponds to a p&#95;{T} shift of δp&#95;{T}=0.213±0.055  Gev/c at 9  Gev/c.

Objectives: The data were collected to obtain the complete genome sequence of Pseudarthrobacter sp. NIBRBAC000502770, isolated from the rhizosphere of Sasamorpha in a heavy metal-contaminated coal mine in Hongcheon, Republic of Korea. The objective was to explore the strain's genetic potential for plant growth promotion and heavy metal resistance, particularly arsenate and copper. The aim focused on identifying microbes that enhance plant growth in metal-tolerant environments and evaluating the strain's bioremediation and agricultural uses. This study sought key genes for bioremediation and agricultural applications in contaminated soils, aiding sustainable management and biotechnology., Data Description: We report the complete genome sequence of Pseudarthrobacter sp. NIBRBAC000502770, isolated from a coal mine in Hongcheon, Republic of Korea. The genome contains a chromosome (4,403,796 bp) and a plasmid (74,326 bp, named pMK-1) with 286-fold coverage. Genome annotation identified 4,209 genes, including 3,926 protein-coding genes, 51 tRNA genes, and 15 rRNA genes, with a G + C content of 66.1%. Functional analysis revealed genes related to plant growth promotion and heavy metal resistance, such as arsenate (arsR, arsC) and copper (copC, copD) resistance genes. Genes involved in auxin biosynthesis suggest potential agricultural applications. The genome and plasmid are available in GenBank (CP041198.1, CP014497.1), offering insights into bioremediation and plant growth in metal-contaminated environments., Competing Interests: Declarations. Ethics approval and consent to participate: The bacterial strain was obtained from a National Institute of Biological Resources (NIBR) with permission. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Study Objectives: Undiagnosed or untreated moderate to severe obstructive sleep apnea (OSA) increases cardiovascular risks and mortality. Early and efficient detection is critical, given its high prevalence. We aimed to develop a practical and efficient approach for obstructive sleep apnea screening, using simple facial photography and sleep questionnaires., Methods: We retrospectively included 748 participants who completed polysomnography, sleep questionnaires (STOP-BANG, SBQ), and facial photographs at a university hospital between 2012 and 2023. Owing to class imbalance, we randomly undersampled the participants, categorized into the moderate/severe or no/mild OSA group, based on an apnea-hypopnea index of 15 events/h. Using a validated convolutional neural network, we extracted the OSA probability scores from photographs, which were used as the input for the questionnaires. Four machine learning models were employed to classify the moderate/severe versus no/mild groups and evaluated in the test dataset., Results: We analyzed 426 participants (213 each in the moderate/severe and no/mild groups). The mean (standard deviation) age was 44.6 (14.7) years; 80.8% were men. Logistic regression achieved the highest performance: the area under the receiver operator curve was 97.2%, and accuracy was 91.9%. Adding OSA probability, retrieved from facial photographs, to the questionnaires improved performance, compared with using questionnaires or photographs alone (area under the receiver operator curve: 97.2%, 64% and 79.1% for threshold SBQ 3 and 4, and 85.7%, respectively)., Conclusions: Using simple facial photographs and sleep questionnaires, a two-stage approach (convolutional neural network + machine learning) accurately classified OSA into moderate/severe versus no/mild OSA groups. This method may facilitate optimal OSA treatment and avoid unnecessary costly evaluations., (© 2025 American Academy of Sleep Medicine.)