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We investigated plasma phosphorylated tau217 (p-tau217) and p-tau181 efficacy in predicting positive amyloid positron emission tomography (PET) results and cognitive stage transitions. Plasma p-tau217 and p-tau181 were measured in participants who were cognitively unimpaired (CU, n = 121), had mild cognitive impairment (n = 102), or dementia (n = 75) from two independent cohorts (Cohort 1: KBASE-V and Cohort 2: Asan) who underwent amyloid PET. In Cohort 1, plasma p-tau217 (area under the curve [AUC] = 0.938, P < 0.001) outperformed p-tau181 (AUC = 0.857, P < 0.001) in predicting amyloid PET positivity (P difference  < 0.001). In Cohort 2, p-tau217 (AUC = 0.893, P < 0.001) and p-tau181 (AUC = 0.856, P < 0.001) showed comparably good discrimination for predicting amyloid PET positivity (P = 0.377). P-tau217 (AUC = 0.852, P < 0.001) and p-tau181 (AUC = 0.828, P < 0.001) demonstrated similarly good discriminations for predicting cognitive stage transition (P difference  = 0.093). Plasma p-tau217 and p-tau181 predicted amyloid PET positivity and cognitive stage transitions well. Plasma p-tau217 might perform better, especially in the early stages., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Consent for publication: Not applicable. Consent statement: This study was performed in accordance with the Good Clinical Practice guidelines and the Declaration of Helsinki and was approved by the Institutional Review Boards of the Asan Medical Center (Approval #2018-0614), Inha University Hospital (INHAUH 2015-03-021), and each participating center. All participants or their proxies provided written informed consent., (© 2025. The Author(s).)

We aimed to compare amyloid-β (Aβ) accumulation rates between different tracers and investigate whether the relationship between changes in Aβ uptake and cognitive decline varies depending on tracer type. Two cohorts were analyzed: (1) a head-to-head longitudinal cohort using 18 F-Florbetaben (FBB) and 18 F-Flutemetamol (FMM) tracers (n = 13), and (2) separate longitudinal cohorts for each tracer (n = 174 for both FMM and FBB), matched by propensity score. Aβ uptake was measured using regional direct comparison of Centiloid (rdcCL) values. In the head-to-head cohort, subtracting changes in FMM rdcCL from FBB rdcCL yielded median values above zero in all regions except the cingulate. In the individual tracer cohorts, FBB rdcCL showed faster accumulation than FMM rdcCL in all cortical regions except the striatum (β [SE] =  - 2.49 to - 1.56 [0.47-0.54], p < 0.001). Mini-Mental State Examination changes were associated with annualized FMM rdcCL changes in the temporal cortex (p = 0.02) and striatum (p = 0.01); however, no such differences were found in the FBB cohort. Our findings suggest that longitudinal Aβ positron emission tomography studies should consider the specific characteristics of tracers depending on the context of use., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Pre-transplantation red blood cell transfusion (RBCT) is a well-recognized cause of allosensitization. However, the effects of RBCT after kidney transplantation remain controversial. This study evaluates the impacts of RBCT within the first 30 days post-transplantation (early RBCT) with regard to long-term patient and graft outcomes. We retrospectively analyzed 785 patients who underwent HLA- and ABO-compatible kidney transplantation between 2014 and 2020. Patients were categorized based on whether they received early RBCT. Overall, 18.9% of patients received early RBCT. On multivariable analysis, early RBCT was independently associated with increased risks of all-cause mortality (hazard ratio, 2.264; 95% CI 1.186-4.324; P = 0.013) and death-censored graft loss (hazard ratio, 1.995; 95% CI 1.045-3.810; P = 0.036). Cumulative incidence of antibody-mediated rejection was significantly higher in the early RBCT group (P = 0.024). In the sensitivity analysis, the early RBCT significantly increased the risk of patient mortality (P = 0.017), death-censored graft loss (P = 0.018) and antibody-mediated rejection (P = 0.05), regardless of the donor profile. Early post-transplantation RBCT was associated with increased risks of all-cause mortality, graft loss, and antibody-mediated rejection, highlighting the need for reconsideration of transfusion practices following kidney transplantation., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Idiopathic pulmonary fibrosis (IPF) is characterised by progressive worsening of lung function. In some cases, IPF is accompanied by air-trapping and emphysema. This study aimed to evaluate air trapping quantified with RV/TLC in patients with IPF. This retrospective study included 122 patients diagnosed with IPF in South Korea between January 2011 and December 2020. Air trapping was defined as RV/TLC ≥ 0.40. Increased RV/TLC was found in 34.4% of all patients. The RV/TLC negatively correlated with lung function (forced expiratory volume in 1 s and functional vital capacity [FVC]) and showed consistent results after 1 year of follow-up. After propensity score matching, FVC and diffusion capacity between the groups showed no statistical difference. No difference in lung function decline was found between the increased and not increased RV/TLC groups. Regarding univariable analysis, the patients in the increased RV/TLC group had a lower risk of all-cause mortality (hazard ratio 1.753, P = 0.034). Using multivariable analysis, age, pirfenidone treatment, and FVC were significant factors for survival but not increased RV/TLC. Increased RV/TLC was related to emphysema and demonstrated a negative relationship with lung function. Although increased RV/TLC might relate to poor clinical outcome, it was not independent prognostic factor for IPF., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethics approval: The study protocol was reviewed and approved by the Institutional Review Board of the Keimyung University College of Medicine (approval no. 2023-07-087-001). The study conformed to the tenets of Declaration of Helsinki (revised edition 2013). The requirement for informed consent was waived by IRB of Keimyung University College of Medicine because of the retrospective nature of the study., (© 2025. The Author(s).)

Individual differences in sleep duration have been reported, and genetic components of sleep duration have been identified showing various heritability. To identify genetic variants that contribute to sleep duration, we conducted a human genome-wide identification on sleep duration and performed confirmatory experiments using a Drosophila model. Genome-wide association study in human was analyzed to determine the association of the genetic variants with self-aware sleep duration from two community-based cohort, Ansan (cohort 1, n = 4635) and Ansung (cohort 2, n = 4205), recruited from the Korean Genome and Epidemiology Study. Individual single nucleotide variants (rs16948804 and rs4887991) in the WW domain containing oxidoreductase (WWOX) gene were associated with self-aware sleep duration in human (p-values, 1.11 × 10 - 7 and 2.05 × 10 - 7 , retrospectively). To examine the functional relevance of the WWOX gene identified in the genome-wide association study, we analyzed the sleep duration of Drosophila loss-of-function mutants. The deletion of Wwox in flies reduced sleep duration and quality with average bout length during daytime and increased night-time sleep duration (all of p-values < 0.01). Our findings suggested that WWOX expression is associated with sleep duration in both humans and Drosophila and genetic factors play a role in inter-individual variability in sleep characteristics., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Lysine-specific histone demethylase (KDM) 5 inhibition by KDM5-C70 induces astrocytogenesis and highlights the importance of modulation of histone methylation in cell fate specification. This study investigated the role of the histone demethylase inhibitor KDM5-C70 in modulating the metabolic and lipidomic landscape during astrocyte differentiation of rat neural stem cells (NSCs). Using chemical derivatisation combined with gas chromatography-mass spectrometry, 42 metabolites were detected, indicating potential regulation of phospholipid metabolism. Subsequent lipidomic analysis, employing reverse-phase liquid chromatography with high-resolution quadrupole time-of-flight mass spectrometry, identified 180 lipid species and 9 lipid subclasses. Integrative analysis revealed that KDM5-C70 promoted astrocytogenesis through epigenetic changes linked to the attenuation of phosphatidylethanolamine (PE) biosynthesis pathways. The reduced expression of transcripts related to PE highlighted the significance of the PE pathway in influencing cell fate decisions. These quantitative metabolomic and lipidomic analyses not only advance our understanding of NSC differentiation but also lay the groundwork for potential therapeutic strategies targeting metabolic pathways in neurodegenerative diseases and neural injuries., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Global evidence on the association between vaccines and renal adverse events (AEs) is inconclusive. This pharmacovigilance study analyzed a total of 120,715,116 reports from VigiBase collected between 1967 and 2022. We evaluated the global reporting of acute kidney injury (AKI), glomerulonephritis (GN), and tubulointerstitial nephritis (TIN) and assessed disproportionate signals between vaccines and renal AEs using reporting odds ratios (ROR) and the lower limit of the 95% confidence interval of the information component (IC 025 ) in comparison with the entire database. The number and proportion of reports on AKI, GN, and TIN gradually increased, with a substantial increase after 2020. Disproportionate reporting of AKI was significant for COVID-19 mRNA vaccines (ROR, 2.38; IC 025 , 1.09). Fourteen vaccines were significantly disproportionate for higher GN reporting, and the highest disproportionality for GN reporting was observed for COVID-19 mRNA (ROR, 13.41; IC 025 , 2.90) and hepatitis B vaccines (ROR, 11.35; IC 025 , 3.18). Disproportionate TIN reporting was significant for COVID-19 mRNA (ROR, 2.43; IC 025 , 0.99) and human papillomavirus (ROR, 1.75; IC 025 , 0.19) vaccines. Significant disproportionality in the reporting of AKI, GN, and TIN was observed in patients exposed to multiple vaccines, including COVID-19 mRNA vaccines, alongside increasing global reports of vaccine-associated renal AEs., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

This cross-sectional study investigated the association between sarcopenia components and depressed mood in community-dwelling adults aged 70-84 years from the Korean Frailty and Aging Cohort Study. Depressed mood was assessed using the Geriatric Depression Scale short form. Logistic regression was used to examine sex-specific associations between sarcopenia components and depressed mood. Among 1,913 participants (mean age: 75.9 years, 49.0% women), 12.2% and 23.6% had depressed mood and sarcopenia, respectively. Sarcopenia prevalence increased among individuals with depressed mood in both sexes (men: P < 0.001; women: P = 0.016). Severe sarcopenia (men: OR, 3.620; 95% CI, 1.634-8.022; women OR, 3.332; 95% CI, 1.689-6.574) and concurrent low muscle strength and physical performance (men: OR, 3.660; 95% CI, 1.541-8.691; women: OR, 2.333; 95% CI, 1.294-4.206) correlated with depressed mood across sexes. The co-occurrence of low muscle mass and muscle strength (OR, 2.451; 95% CI, 1.007-5.964) was associated with depressed mood in men, whereas low physical performance (OR, 2.007; 95% CI, 1.275-3.160) and the coexistence of low muscle mass and physical performance (OR, 1.804; 95% CI, 1.003-3.248) correlated with depressed mood in women. Sarcopenia and depressed mood were significantly associated among older adults, underscoring the need to account for sex-specific differences in sarcopenia components when evaluating mental health outcomes to tailor interventions targeting sarcopenia and improve the mental well-being of aging populations., Competing Interests: Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Subcortical vascular cognitive impairment (SVCI) is caused by white matter degeneration. Multiple lacunar infarction due to deep small vascular disease around the subcortical structure and incomplete infarction of white matter owing to decreased perfusion are some of the causes of vascular cognitive impairment. Damage to subcortical structures and prefrontal-cortical circuits can affect motor skills along with cognitive abilities. In this study, we identified the indicators, such as pen pressure, speed, and deviation (degree of deviation from the target line), which can be observed in drawing performance in patients with SVCI. A total of 24 patients with SVCI and 26 healthy adults (HC) were subjected to digitized drawing along straight lines and spiral drawing (drawing along spiral lines, free spiral drawing). In the drawing along straight lines, the SVCI group showed a greater deviation than the HC group. In the drawing along spiral lines, the SVCI group showed greater pen pressure and deviation than the HC group. In the free spiral drawing tasks, the SVCI group showed greater pen pressure and deviation than the HC group. In the free spiral drawing task, the deviation of the SVCI group increased as the wheels of the spiral increased in the clockwise and counterclockwise directions. The SVCI group showed greater pressure to hold and press pencils during drawing compared to HC due to damage to cognitive and motor skills; Further, it deviated from the provided target line. These results may be due to complex cognitive-motor deficits, motor patterns, or impaired motor termination and conversion following damage to the frontal-subcortical circuit. This study provides essential clinical basic data that can be utilized to precisely determine the diminished kinematic behavior within the SVCI group., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

This paper reports the proton response function for solution-grown trans-stilbene scintillator from 1 to 25 MeVee and its application for unfolding neutron spectra of Cf-252 and AmBe sources. Low energy proton response was measured by the Time-of-Flight technique at the Korea Research Institute of Standards and Science. In contrast, high energy response was investigated using a 45 MeV proton beam at the Korea Institute of Radiological & Medical Sciences. The photomultiplier tube nonlinearity effect was studied and corrected for high-energy measurement. Several energy calibration functions were examined to minimize the effects of the light yield nonlinearity of the scintillator, which was observed as nonnegligible in the measurement. A new approach was applied to obtain 1.3 ns full width at half maximum timing resolution in the Time-of-Flight experiment when using a 500 Mega samples per second analog to digital converter. The unfolding was performed using the iterative Bayesian method without any constraints, smoothness, or assumption of prior knowledge of original spectra. For the first time, we achieved one of the best unfolding results for both Cf-252 and AmBe spectra. Results from this study are promising for fast neutron spectroscopy., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

To validate the clinical feasibility of deep learning-driven magnetic resonance angiography (DL-driven MRA) collateral map in acute ischemic stroke. We employed a 3D multitask regression and ordinal regression deep neural network, called as 3D-MROD-Net, to generate DL-driven MRA collateral maps. Two raters graded the collateral perfusion scores of both conventional and DL-driven MRA collateral maps and measured the grading time. They also qualitatively assessed the image quality of both collateral maps. Interrater and inter-method agreements for collateral perfusion grading between the two collateral maps were analyzed, along with a comparison of grading time and image quality. In the analysis of the 296 acute ischemic stroke patients, the inter-method agreement for collateral perfusion grading was almost perfect (κ = 0.96, 95% CI: 0.95-0.98). Compared to conventional MRA collateral maps, the time taken for collateral perfusion grading on DL-driven MRA collateral maps was shorter (P < 0.001 for rater 1 and P = 0.003 for rater 2), and the image quality of the DL-driven MRA collateral maps was superior (P < 0.001 for rater 1 and P = 0.002 for rater 2). The DL-driven MRA collateral map demonstrates clinical feasibility for collateral perfusion grading in acute ischemic stroke, with the added benefits of reduced generation and interpretation time, along with improved image quality of the MRA collateral map., Competing Interests: Declarations. Competing interests: Ye Jin Jeon, Sumin Jung, Hyun Yang, Hee Jong Ki, Jeong Jin Park, Take-Jun Lee, Na Il Shin, and Ji Sung Lee have no financial interests. Hong Gee Roh, Jin Tae Kwak, and Hyun Jeong Kim are founders of DeepClue Inc., (© 2025. The Author(s).)

Adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) is a rare white matter disease characterized by axonal and glial injury. Although its clinical characteristics have been described in case reports, the prevalence of CSF1R mutations in clinically suspected ALSP cases remains unclear. Herein, we analysed the frequency of CSF1R mutations in patients with probable or possible ALSP and describe the genetic, clinical, radiological, and pathological findings of ALSP cases in individuals of Korean ancestry. Twenty-eight patients with probable or possible ALSP diagnosed at Samsung Medical Center, Seoul, between January 2014 and August 2020, were retrospectively reviewed. All participants underwent brain magnetic resonance imaging (MRI) and CSF1R genetic testing. Overall, 9 of the 28 patients (32.1%) [5/6 (83.3%) of probable ALSP and 4/22 (18.2%) of possible ALSP] were confirmed to have pathogenic or likely pathogenic variants in CSF1R gene. Additionally, one patient without CSF1R mutation exhibited histopathological findings consistent with ALSP on brain biopsy. All patients with CSF1R mutation presented with cognitive impairment and/or psychiatric symptoms. Brain MRI revealed bilateral white matter hyperintensities in all patients, and 5/8 (62.5%) showed diffusion-restricted lesions. Notably, patients with CSF1R mutation had younger age at onset, rapidly progressive course, and diffuse hyperintensity in the splenium compared to patients without CSF1R mutation. Our findings suggest that for definite diagnosis, CSF1R genetic testing is recommended in patients who meet the diagnostic criteria for possible or probable ALSP. Our findings provide insights into the genetic, clinical, radiological, and pathological dimensions of ALSP in individuals of Korean ancestry., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Colon cancer is a significant health concern, and obesity is a well-established risk factor. However, previous studies have mainly focused on assessing body weight as a risk factor for colon cancer at a specific time point. This nationwide cohort study investigated the association between body weight changes, which can fluctuate throughout an individual's lifespan, and the incidence of colon cancer using the South Korean population database provided by the National Health Insurance Service (NHIS). Participants who underwent biennial health screenings between 2004 and 2006, and had follow-up health check-ups between 2014 and 2016, were included in this study. Body weight changes were categorized as follows: < 5%, decrease 5-20%, decrease > 20%, increase 5-20%, or > 20%. The primary outcome was the incidence of newly diagnosed colon cancer. Statistical analysis was used to examine the relationship between body weight changes and the incidence of colon cancer stratified according to age and sex. The Kaplan-Meier method estimated the cumulative incidence of colon cancer, and Cox proportional hazards models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI), adjusting for confounding factors. The analysis included data from 10,332,397 individuals, with a mean (± SD) age of 45.5 ± 13.1 years, and 54.9% were male. In males with a body mass index (BMI) range of 18-30 kg/m 2 , both a weight gain of 5-20% (HR 1.07, P > z 0.01 [95% CI 1.02-1.13]) and weight gain > 20% (HR 1.27, P > z 0.03 [95% CI 1.03-1.56]) were associated with an increased risk for colon cancer. In addition, males < 40 years of age exhibited a higher risk for colon cancer with > 20% weight gain (HR 1.65, P > z < 0.001 [95% CI 1.18-2.30]). Whereas, females within the BMI range of 18-30 kg/m 2 who exhibited > 20% weight loss demonstrated a reduced risk (HR 0.77, P > z 0.04 [95% CI 0.60-0.98]). Moreover, females ≥ 40 years of age, who experienced weight loss > 20%, exhibited a decreased risk for colon cancer (HR 0.76; P > 0.02 [95% CI 0.60-0.96]). This nationwide cohort study demonstrated a relationship between body weight changes and the incidence of colon cancer, with differences based on sex and age. In particular, avoiding weight gain is crucial for males < 40 years of age, whereas weight loss could be beneficial for females > 40 years of age in reducing the risk of colon cancer., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Given the increasing trend of cholecystectomy, it is imperative to reassess surgical and surveillance strategies in consideration of the potential long-term risks for digestive tract cancers. The objective of this study was to assess the risk of gastrointestinal (GI) and hepato-biliary-pancreatic (HBP) cancer incidence after cholecystectomy. The data for this cohort study was obtained from the National Health Insurance Service database in Korea. 715,872 patients who underwent cholecystectomy between 2004 and 2020 were compared to 1,431,728 individuals who did not underwent cholecystectomy after age, sex, and year of cholecystectomy was matched. The overall incidence rate ratio (IRR) for all GI and HBP cancers was 1.08 (95% C.I., 1.06-1.10). Specifically, the risk of diagnosis of extrahepatic bile duct cancer (IRR 1.92), intrahepatic bile duct cancer (1.78), hepatocellular carcinoma (1.22), and pancreatic cancer (1.13) was significantly increased in the cholecystectomy group. The highest IRR was observed within the 1-3 years following cholecystectomy. Subsequently, the risk of diagnosis gradually decreased and returned to a level comparable to that of the matched control group after 5 to 10 years. In conclusion, hepato-biliary-pancreatic cancer are frequently diagnosed subsequent to cholecystectomy. Too short period of post-cholecystectomy follow-up may hinder monitoring of hepato-biliary-pancreatic cancer occurrence., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

In breast-conserving surgery (BCS), clear resection margins are crucial to prevent recurrence. Accurate imaging is vital for precise BCS, with MRI being the most accurate. However, MRI has limitations in identifying the exact extent of breast cancer in patients who have undergone neoadjuvant chemotherapy (NACT). A 3D-Printed Breast Surgical Guide (3DP-BSG) can address this issue by effectively pinpointing cancer extent in NACT patients, thus enhancing surgical accuracy. This retrospective single-institution cohort study focused on female patients diagnosed with invasive breast cancer who underwent NACT. Between November 2015 and October 2021, patients received BCS with the aid of a 3DP-BSG. Personalized 3DP-BSG targeted tumors by tracking changes in breast and tumor anatomy on MRI before and after NACT. 203 patients with invasive breast cancer were enrolled in the study. According to exclusion criteria, 197 patients were analyzed. The median follow-up period was 35.3 months (range: 2.2-96.8 months). 3 patients (1.5%) had positive resection margins. During the follow-up period, 17 patients (8.6%) experienced recurrence, with one patient (0.5%) confirmed local recurrences. The application of MRI-based 3DP-BSG is effective in achieving low positive margins and local recurrence in patients undergoing BCS after NACT, offering a promising approach for improving surgical outcomes., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

We investigated the safety and performance of the Da Vinci SP single-port robot (SP robot) in nipple-sparing mastectomy (NSM) with immediate reconstruction. Medical records of 60 women aged ≥ 19 years who had undergone SP robot-assisted unilateral or bilateral NSM with immediate reconstruction between October 2020 and August 2021 were retrospectively analyzed. Stage I (31, 47.1%) was the most common pathological tumor-node-metastasis stage, followed by stages II (22, 33.3%), 0 (7, 10.6%), and III (4, 6.0%). The median total duration of NSM performed by a breast surgeon and reconstruction performed by a plastic surgeon was 154.0 min (interquartile range [IQR], 130.5-206.0 min) and 133.0 min (IQR, 80.0-255.0 min), respectively. The median length of hospitalization was 5.5 days (IQR, 3.0-9.0 days). Conversion to robotic multiport or open surgery was not required in any case. The median duration to drain removal was 5.0 days (IQR, 4.0-6.0 days). Recurrence of cancer within 6 months was not observed in any patient. SP robot-assisted NSM with immediate reconstruction was performed successfully in all patients without conversion to open surgery or the incidence of significant perioperative complications, indicating its precision and ability to minimize the size of the surgical incision., Competing Interests: Declarations. Competing interests: The authors declare no competing interests. Ethical approval: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent: Informed consent was waived because the study was based on retrospective clinical data., (© 2024. The Author(s).)

This study characterizes the influence of self-assembly conditions on the aggregation pathway and resulting photophysical properties of one-dimensional aggregates of the simple imide-substituted perylene diimide, N, N'-didodecyl-3,4,9,10-perylenedicarboximide (ddPDI). We show that ddPDI, which has symmetric alkyl chains at the imide positions, assembles into fibers with distinct morphology, emission spectra, and temperature-dependent behavior as a function of preparation conditions. In all conditions explored, aggregates are one-dimensional; however, assembly conditions can bias formation to either J-like or H-like aggregates. Specifically, a solvent phase interfacial (SPI) method yields two types of aggregates with distinct morphology and photophysical properties while a surface and solvent vapor assisted method (SSVA) generates more uniform aggregates with H-dominant behavior. A combined SPI and SSVA approach facilitates the simultaneous generation and in situ characterization of distinct ddPDI assemblies, some of which assemble via seeded growth. Microscopic and spectroscopic imaging unveil the heterogeneity among ddPDI aggregates, each with unique photophysical properties including H-dominant aggregates with a very high degree of molecular alignment and uniformity in intermolecular organization. Overall, this study highlights the pathway complexity in self-assembly of even the simplest PDI molecules, paving the way for utilization of simple PDI aggregates in applications that demand diverse photophysical behavior., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Chronic kidney disease is defined as a progressive loss of kidney function associated with impaired recovery after acute kidney injury. Renal ischemia-reperfusion (IR) induces oxidative stress and inflammatory responses leading to severe tissue damage, where incomplete or maladaptive repair accelerates renal fibrosis and aging. To investigate the role of the purinergic P2Y2 receptor (P2Y2R) in these processes, we used P2Y2R knockout (KO) mice subjected to IR. KO mice showed severe kidney dysfunction and structural damage compared to WT mice. KO mice showed higher senescence-associated β-galactosidase expression and shorter telomere length than WT mice. Consistently, interstitial collagen accumulation and fibrogenic mediators were significantly upregulated in KO mice. Renal apoptosis and inflammation were highly elevated in KO mice. Interestingly, cell proliferation as shown by Ki-67 and PCNA expression, was increased for 3 days after IR in WT mice, whereas it maintained increased for 14 days in KO mice. Cell cycle inhibitors, p16 and p21, and regulators JunB and cyclin E were significantly increased after IR in KO mice, suggesting that cell cycle progression was impaired during recovery after IR. Proximal tubular cells treated with JunB siRNA showed a reduced expression of fibrogenic mediators and proinflammatory cytokines, consistent with the mice treated with MRS2768, a P2Y2 agonist that downregulated JunB levels. In conclusion, P2Y2R reduces kidney tissue damage after IR and repairs the tissue properly by regulating JunB-mediated signaling during the recovery process., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Airway compromise due to prevertebral soft tissue swelling is a potentially devastating complication following anterior cervical discectomy and fusion (ACDF). However, there are no studies on the postoperative patient posture for enhancing airway patency after ACDF. This study aimed to analyze the effect of neck and mouth postures on airway patency following ACDF and to suggest the beneficial postoperative patient posture for improving airway patency. A retrospective review of 39 patients who underwent ACDF in C3 or C4 level was conducted. Airway diameter and prevertebral soft tissue thickness were measured in six different neck-mouth postures using lateral radiographs. The diameters of the airway and prevertebral soft tissues showed significant changes in relation to the neck postures and mouth openings after ACDF (P < 0.001). Regarding postures, neck extension with closed mouth posture showed significant wider airway diameter than that of the other postures (P < 0.001). Moreover, this posture showed the thinnest prevertebral soft tissues; however, it showed no significant difference compared to the neutral-closed and extension-open postures (P = 1.00 and P = 0.053). In conclusion, neck extension with a closed mouth significantly widened the airway diameter and reduced prevertebral soft tissue swelling, making it the best posture to maintain airway patency after ACDF., Competing Interests: Competing interests: The authors declare no competing interests. Ethical approval: The study was reviewed and approved by the institutional review board of Seoul National University Bundang Hospital (Approval Number: B-1707-409-106). The informed consent was waived due to the retrospective nature of the study by the institutional review board of Seoul National University Bundang Hospital. All methods were carried out by relevant guidelines and regulations., (© 2024. The Author(s).)

Corneal endothelial cells, situated on the innermost layer of the cornea, are vital for maintaining its clarity and thickness by regulating fluid. In this study, we investigated the differences in the transcriptome between young and old corneal endothelial cells using next-generation sequencing (NGS). Cultured endothelial cells from both young and elderly donors were subjected to NGS to unravel the transcriptomic landscape. Subsequent analyses, facilitated by Metascape, allowed for the dissection of gene expression variances, unearthing pivotal biological pathways. A total of 568 genes showed differences, and were related to Endomembrane system organization, nuclear receptors meta pathway, efferocytosis, etc. Notably, a reduction in the expression of 260 genes was observed in the aged cells form old donors, and in the related analysis, eukaryotic translation initiation, integrator complex, and Hippo YAP signaling were significant. Conversely, 308 genes exhibited elevated expression levels in the elderly, correlating with processes including transition metal ion transport and glycoprotein biosynthesis. In conclusion, our investigation has revealed critical genes involved in the aging process of corneal endothelial cells and elucidated their underlying biological pathways. These insights are instrumental in selecting targets for therapeutic intervention, thereby facilitating the advancement of novel therapeutic approaches for the restoration and preservation of corneal endothelial cell function., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Conventional methods for assessing tongue bacterial biofilms have low inter-examiner reliability due to visualization challenges. This study aimed to develop and assess a novel Tongue Biofilm Fluorescence Index (TBFI) for the accurate detection and objective evaluation of the quantitative and qualitative characteristics of tongue biofilms at the chairside. Data were collected from 81 elderly individuals (n = 162 images). Qraycam captured white-light and fluorescence images of the dorsal tongue, and two examiners assessed tongue coating (TC) using the TBFI. The TBFI was calculated based on biofilm intensity and coverage (0-2 scale). Inter-examiner agreement (Kappa) was compared with the Winkel's Tongue Coating Index (WTCI) and the Oho Index. Validity was evaluated through correlations with hydrogen sulfide (H₂S) and methyl mercaptan (CH₃SH) levels. TBFI demonstrated the highest inter-examiner reliability (TBFI, κ = 0.752; WTCI, κ = 0.317; Oho Index, κ = 0.496), particularly for thickness rating (agreement rate: TBFI, 96.3%; WTCI, 76.5%; Oho Index, 79.6%). H₂S and CH₃SH concentrations showed significant positive correlations with all three indices, with the highest correlation observed between H₂S and TBFI (TBFI, r = 0.369; WTCI, r = 0.304; Oho Index, r = 0.308; p < 0.01). Furthermore, H₂S levels increased significantly with higher TBFI scores (p < 0.0001). TBFI shows enhanced reliability and validity, supporting its clinical potential., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Real-time PCR assays are valuable tools for the rapid and accurate diagnosis of infectious diseases by identifying the nucleic acid sequences of pathogens. Here, we aimed to develop a recombinant plasmid-based standard for validating the sensitivity of different molecular diagnostic methods adopting the Jonstrup assay (J assay). Chimeric plasmid DNA (cpDNA) harboring various pathogen genes and the target site of the J assay was constructed. Our findings revealed that the J assay could detect a single copy of the target gene similar to digital droplet PCR. The detection sensitivity of each established real-time PCR method for various disease diagnoses was evaluated using the cpDNA. Although most methods showed high sensitivity, similar to that of the J assay, the VHS Garver and SARS-CoV-2 diagnostic methods exhibited detection sensitivities tenfold lower than that of the J assay. To ensure accuracy of results and avoid genetic contamination from positive controls, we introduced an additional probe attachment site emitting distinct fluorescent signals within the cpDNA. Target genes and exogenous sequences within the plasmid DNA were simultaneously detected in a single assay using this unique method. Our approach will help improve the sensitivity of diagnostic methods and develop novel diagnostic methods based on molecular techniques., (© 2024. The Author(s).)

Metabolic syndrome is a significant risk factor for poor graft outcomes in kidney transplant (KT) patients. However, the effects of variability in metabolic parameters on graft outcomes in KT patients have not been completely elucidated. A total of 852 KT patients were included from the Korean Organ Transplantation Registry. The study exposure was variability in body mass index (BMI) or other metabolic parameters measured at 6 months, 1 year, and 2 years after KT. Patients were classified into tertiles according to the degree of variability. The primary outcome was a composite of adverse kidney outcomes, such as death-censored graft loss or ≥ 30% decline in estimated glomerular filtration rate. The adverse kidney outcomes occurred in 73 (8.6%) participants. The high-BMI variability group had a higher risk for adverse kidney outcomes compared to the low-variability group. High variabilities in triglyceride, fasting blood glucose, and systolic blood pressure were also associated with adverse kidney outcomes. Furthermore, high variability in metabolic syndrome-related composite indices, such as the triglyceride and glucose index and metabolic variability scores, showed a higher risk for adverse kidney outcomes. In conclusion, high variability in metabolic parameters could be associated with an increased risk of adverse kidney outcome in KT patients., (© 2024. The Author(s).)

Osteoarthritis (OA) is a degenerative disease of the joints, prevalent worldwide. Polydeoxyribonucleotide (PDRN) is used for treating knee OA. However, the role of PDRN in IL-1β-induced inflammatory responses in human bone marrow-derived mesenchymal stem cells (hBMSCs) remains unknown. Here, we investigated the role of PDRN in IL-1β-induced impairment of chondrogenic differentiation in hBMSCs. hBMSCs treated with PDRN showed a large micromass, enhanced safranin O and alcian blue staining intensity, and increased expression of chondrogenic genes in IL-1β-induced inflammatory responses, in addition to regulation of catabolic and anabolic genes. In addition, PDRN treatment suppressed the expression of inflammatory cytokines and mitigated IL-1β-induced apoptosis in hBMSCs. Mechanistically, PDRN treatment increased the formation of cyclic adenosine monophosphate (cAMP) and upregulated the phosphorylation of cAMP-dependent protein kinase A (PKA)/cAMP response element binding protein (CREB) through the adenosine A2A receptor in hBMSCs and thus blocked the nuclear factor kappa-light-chain-enhancer of activated B cell (NF-κB) signaling pathway. Thus, IL-1β-induced expression of inflammatory cytokines in hBMSCs was directly reduced by adenosine A2A receptor activation. Based on our results, we suggest that PDRN may be a promising MSC-based therapeutic agent for OA., (© 2024. The Author(s).)

While obesity, rapid weight loss, and sedentary lifestyles contribute to gallstones, the impacts of long-term weight patterns and physical activity on gallstone risk have not been extensively studied at the population level. Using Korea's population-based health database, we created a cohort of 5,062,154 subjects who received over five consecutive biannual health check-ups from 2002 to 2018. Gallstone risk was calculated using hazard ratios (HRs) based on weight patterns (gain, loss, and cycling) and physical activity. Adjustments were made for covariates, such as body mass index (BMI), waist circumference, diabetes, and life style factors. Subgroup analysis was performed by sex and age groups (< 45 and ≥ 45 years). All groups with weight changes showed increased HRs 1.32 (95% CI 1.07-1.65) for > 20% weight loss, 1.13 (0.96-1.33) for > 20% weight gain, 1.04 (1.02-1.06) for weight cycling, 1.03 (1.01-1.05) for 5-20% weight gain, and 1.02 (1.00-1.04) for 5-20% weight loss. Risk increased with weight loss or gain in underweight or overweight BMI categories, respectively, and in any weight change for normal BMI. Males and older individuals had higher risks with weight loss, while females and younger individuals had higher risks with weight gain. Weight cycling increased risk for both sexes. Regular physical activity reduced gallstone risk in weight changers to levels similar to weight maintainers, with the highest reduction in those with > 20% weight gain (61%) and the lowest in weight cycling (1%). The risks of gallstones associated with weight gain, loss, or cycling can be mitigated by regular physical activity. The risks vary by sex and age., (© 2024. The Author(s).)

Oyster aquaculture is one of the fastest-growing food production industries worldwide; however, it faces a significant challenge from the protist Perkinsus marinus, particularly in the USA. Although several quantitative molecular diagnostic methodologies are available for identifying diseases caused by P. marinus, the primer pairs used therein led to non-specific identification of other Perkinsus spp. Hence, a quantitative real-time PCR (Pm-qPCR) assay specific for P. marinus was developed using a TaqMan-based probe with the internal quencher in this study. A primer pair and probe specific to P. marinus were designed from a hypothetical protein of P. marinus collected from the whole-genome shotgun sequence database of the National Center for Biotechnology Information (NCBI). In silico analysis using homologous sequences of P. olseni and P. chesapeaki confirmed the high specificity of primers designed in this study. The Pm-qPCR assay was performed using seven different strains of P. marinus, P. olseni, and P. chesapeaki, revealing high specificity and sensitivity for detecting only P. marinus strains. In conclusion, it was demonstrated that Pm-qPCR can effectively and accurately diagnose P. marinus with high specificity and sensitivity. This assay is promising for monitoring oyster health and disease management in ecosystems and aquaculture., (© 2024. The Author(s).)

Despite the significant impact of the COVID-19 pandemic on various factors related to adolescent mental health problems such as stress, sadness, suicidal ideation, and suicide attempts, research on this topic has been insufficient to date. This study is based on the Korean Youth Risk Behavior Web-based Survey from 2006 to 2022. We analyzed the mental health problems of adolescents based on questionnaires with medical interviews, within five income groups and compared them with several risk factors. A total of 1,138,804 participants were included in this study, with a mean age (SD) of 15.01 (0.75) years. Of these, 587,256 were male (51.57%). In 2022, the recent period from the study, the weighted prevalence of stress in highest income group was 40.07% (95% CI, 38.67-41.48), sadness was 28.15% (26.82-29.48), suicidal ideation was 13.92% (12.87-14.97), and suicide attempts was 3.42% (2.90-3.93) while the weighted prevalence of stress in lowest income group was 62.77% (59.42-66.13), sadness was 46.83% (43.32-50.34), suicidal ideation was 31.70% (28.44-34.96), and suicide attempts was 10.45% (8.46-12.45). Lower income groups showed a higher proportion with several risk factors. Overall proportion had decreased until the onset of the pandemic. However, a significant increase has been found during the COVID-19 pandemic. Our study showed an association between household income level and the prevalence of mental illness in adolescents. Furthermore, the COVID-19 pandemic has exacerbated mental illness among adolescents from low household income level, underscoring the necessity for heightened public attention and measures targeted at this demographic., (© 2024. The Author(s).)

Preeclampsia is a hypertensive disorder of pregnancy that can lead to stillbirth and preterm birth if not treated promptly. Currently, the diagnosis of preeclampsia relies on clinical symptoms such as hypertension and proteinuria, along with invasive blood tests. Here, we investigate the role of soluble proteins and exosomes in noninvasive diagnosing preeclampsia non-invasively using maternal urine and urine-derived exosomes. We quantified the levels of particles and the presence of TSG101 and CD63 in urine and urinary exosomes via the biologically intact exosome separation technology (BEST) platform. Then, we obtained higher levels of soluble proteins such as fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) from urine as it was than urinary exosomes. Compared to commercial blood tests, the sensitivity of the sFlt-1/PlGF ratio was found to be 4.0 times higher in urine tests and 1.5 times higher in tests utilizing urine-derived exosomes. Our findings offer promising possibilities for the early and non-invasive identification of high-risk individuals at risk of preeclampsia, allowing for comprehensive preventive management., (© 2024. The Author(s).)

We aimed to assess the association of tramadol use with the risk of dementia. This population-based retrospective cohort study using the Korean National Health Insurance Service database included a total of 1,865,827 older adult patients aged 60 years or older with common musculoskeletal pain between January 1, 2003, and December 31, 2007. Individuals who were newly dispensed tramadol (N = 41,963) were identified and propensity score-matched with those who were not (N = 41,963). Over a maximum of 14-year follow-up, the incidence rates (events per 1000 person-years) of all-cause dementia were 6.1 for nonusers, 6.2 for those with cumulative tramadol use of 1-14 days, 7.7 for those with 15-90 days of use, and 8.0 for those with > 90 days of use. Longer cumulative duration of tramadol use was associated with an increased risk of all-cause dementia compared with nonuse (1 to 14 days: aHR 1.06, 95% CI 0.96-1.17; 15 to 90 days: aHR 1.14, 95% CI 1.10-1.35; and more than 90 days: aHR 1.18, 95% CI 1.00-1.39; test for trend: P < 0.001). The results showed a similar pattern for Alzheimer's disease and were robust across subgroup and sensitivity analyses, but not for vascular dementia. This study found that exposure to tramadol was associated with an increased risk of dementia. Taking this potential risk into consideration, clinicians should carefully weigh potential benefits and risks when prescribing tramadol to older adults with musculoskeletal pain., (© 2024. The Author(s).)

Endothelial cell dysfunction can lead to various vascular diseases. Blood flow disorder is a common symptom of vascular diseases. Regenerative angiogenesis, which involves transplanting vascular cells or stem cells into the body to shape new vasculature, can be a good therapeutic strategy. However, there are several limitations to using autologous cells from the patients themselves. We sought to investigate the new vascular cells that can play a role in the formation of angiogenesis in vivo using stem cells from alternative animals suitable for cellular therapy. Porcine is an optimal animal model for xenotransplantation owing to its physiological similarity to humans. We used differentiated porcine endothelial cells (pECs) as a therapeutic strategy to restore vessel function. Differentiated pECs formed vessel-like structures in mice, distinguishing them from stem cells. MMPs activity and migration assays indicated that differentiated pECs possessed angiogenic potential. Tube formation and 3D spheroid sprouting assays further confirmed the angiogenic phenotype of the differentiated pECs. Immunofluorescence and immunoprecipitation analyses revealed claudin-mediated tight junctions and connexin 43-mediated gap junctions between human ECs and differentiated pECs. Additionally, the movement of small RNA from human ECs to differentiated pECs was observed under co-culture conditions. Our findings demonstrated the in vivo viability and angiogenetic potential of differentiated pECs and highlighted the potential for intercellular communication between human and porcine ECs. These results suggest that transplanted cells in vascular regeneration completed after cell therapy have the potential to achieve intercellular communication within the body., (© 2024. The Author(s).)

This study evaluates the diagnostic efficacy of automated machine learning (AutoGluon) with automated feature engineering and selection (autofeat), focusing on clinical manifestations, and a model integrating both clinical manifestations and CT findings in adult patients with ambiguous computed tomography (CT) results for acute appendicitis (AA). This evaluation was compared with conventional single machine learning models such as logistic regression(LR) and established scoring systems such as the Adult Appendicitis Score(AAS) to address the gap in diagnostic approaches for uncertain AA cases. In this retrospective analysis of 303 adult patients with indeterminate CT findings, the cohort was divided into appendicitis (n = 115) and non-appendicitis (n = 188) groups. AutoGluon and autofeat were used for AA prediction. The AutoGluon-clinical model relied solely on clinical data, whereas the AutoGluon-clinical-CT model included both clinical and CT data. The area under the receiver operating characteristic curve (AUROC) and other metrics for the test dataset, namely accuracy, sensitivity, specificity, PPV, NPV, and F1 score, were used to compare AutoGluon models with single machine learning models and the AAS. The single ML models in this study were LR, LASSO regression, ridge regression, support vector machine, decision tree, random forest, and extreme gradient boosting. Feature importance values were extracted using the "feature&#95;importance" attribute from AutoGluon. The AutoGluon-clinical model demonstrated an AUROC of 0.785 (95% CI 0.691-0.890), and the ridge regression model with only clinical data revealed an AUROC of 0.755 (95% CI 0.649-0.861). The AutoGluon-clinical-CT model (AUROC 0.886 with 95% CI 0.820-0.951) performed better than the ridge model using clinical and CT data (AUROC 0.852 with 95% CI 0.774-0.930, p = 0.029). A new feature, exp(-(duration from pain to CT) 3  + rebound tenderness), was identified (importance = 0.049, p = 0.001). AutoML (AutoGluon) and autoFE (autofeat) enhanced the diagnosis of uncertain AA cases, particularly when combining CT and clinical findings. This study suggests the potential of integrating AutoML and autoFE in clinical settings to improve diagnostic strategies and patient outcomes and make more efficient use of healthcare resources. Moreover, this research supports further exploration of machine learning in diagnostic processes., (© 2024. The Author(s).)

To establish normal reference ranges for fetal right ventricular modified myocardial performance index (RV Mod-MPI) using automatic synchronization of the RV inflow and outflow images (MPI +TM ). Additionally, we aimed to clinically apply RV Mod-MPI to investigate its changes in fetal right congenital diaphragmatic hernia (CDH) compared to normal fetuses. This prospective study included uncomplicated singleton pregnancies between 16 and 38 weeks of gestational age. Cases with any maternal or fetal complications that developed during the enrollment period were excluded. Two experienced operators measured the RV Mod-MPI using the automated and manual methods. The intraclass correlation coefficients (ICC) were calculated for intra- and inter-operator reproducibility. The mean differences between the manual and automated measurements were also compared. The RV Mod-MPI was then compared between the right CDH fetuses and normal fetuses. Seventy normal fetuses were analyzed for the feasibility of an automated system, and 364 examinations from 272 fetuses were analyzed for developing the normal references. The automated system showed significantly higher intra- and inter-operator reproducibility of Mod-MPI than those of manual measurements (ICC = 0.962 vs. 0.913 and 0.961 vs. 0.889, respectively). The mean difference in Mod-MPI between the manual and automated method was 0.0002 ± 0.0586 with a 95% confidence interval of -0.0095-0.0099. The Mod-MPI and isovolumetric relaxation time increased throughout the gestational weeks. The isovolumetric contraction time increased until 24 weeks of gestation and then slightly decreased afterwards, and the ejection time also increased until 31 weeks of gestation and then decreased. There was no significant difference in the Mod-MPI between right CDH and normal fetuses. The automated system showed high inter- and intra-operator reproducibility. Furthermore, the normal reference values of Mod-MPI for each gestational age were established. Our results suggest that the automated system might be clinically feasible for evaluating fetal cardiac function., (© 2024. The Author(s).)

Glioblastoma multiforme (GBM) is the most aggressive type of primary brain tumor, and the presence of glioma stem cells (GSCs) has been linked to its resistance to treatments and recurrence. Additionally, aberrant glycosylation has been implicated in the aggressiveness of cancers. However, the influence and underlying mechanism of N-glycosylation on the GSC phenotype and GBM malignancy remain elusive. Here, we performed an in-silico analysis approach on publicly available datasets to examine the function of N-glycosylation-related genes in GSCs and gliomas, accompanied by a qRT-PCR validation experiment. We found that high α-1,2-mannosidase MAN1C1 is associated with immunological functions and worse survival of glioma patients. Differential gene expression analysis and qRT-PCR validation revealed that MAN1C1 is highly expressed in GSCs. Furthermore, higher MAN1C1 expression predicts worse outcomes in glioma patients. Also, MAN1C1 expression is increased in the perinecrotic region of GBM and is associated with immunological and inflammatory functions, a hallmark of the GBM mesenchymal subtype. Further analysis confirmed that MAN1C1 expression is closely associated with infiltrating immune cells and disrupted immune response in the GBM microenvironment. These suggest that MAN1C1 is a potential biomarker for gliomas and may be important as an immunotherapeutic target for GBM., (© 2024. The Author(s).)

Patients with diabetes mellitus (DM) are at a higher risk of infectious diseases, and exercise is an important treatment modality for DM. Despite their susceptibility to infection in diabetic patients, the association between the amount of physical activity and the incidence of infective endocarditis (IE) is unclear. We attempted to demonstrate risk reduction by physical activity in diabetic patients with IE. From the National Health Insurance database, patients with DM were verified, and the incidence of IE was investigated. The level of physical activity was categorized into < 500, 500-999, 1,000-1,499, and ≥ 1,500 metabolic equivalent task (METs) minutes/week. Cox proportional hazard models were used to analyze the relationship between incident IE and physical activity. A total of 2,603,012 patients were included in this study. The incidence rate of IE was 10.06, 9.45, 7.78, and 8.84 in < 500, 500-999, 1,000-1,499, and ≥ 1,500 METs-minutes/week groups, respectively (100,000 person/year). A significant risk reduction of incident IE was observed in the 1,000-1499 and ≥ 1,500 METs-min/week groups compared to the < 500 METs-min/week group (Hazard ratio = 0.82, 95% confidence interval [0.690-0.976], HR = 0.831, 95% CI [0.704-0.981]). An analysis of a large national cohort database demonstrated that physical exercise reduced the risk of IE in patients with DM., (© 2024. The Author(s).)

The aim of this study was to evaluate the impact of COVID-19 on ocular diseases and changes in risk factors before and after the COVID-19 pandemic. This study was conducted using data from the Korea National Health and Nutrition Examination Survey (KNHANES) 2015-2021, a national cross-sectional health examination and survey. Associations between ocular diseases and risk factors were determined using the chi-squared test and logistic regression analysis. Bivariable adjusted logistic regression analysis was performed to examine the odds ratio (OR) and 95% confidence interval (CI) to evaluate of the impact of COVID-19 on ocular diseases. Individuals were divided into two age groups (< 60 and ≥ 60 years). A total of 50,158 people were diagnosed, of whom 7270 were diagnosed with cataract, 921 with glaucoma, and 439 with age-related macular degeneration (AMD). Risk factors for cataract were COVID-19 pandemic (OR 1.161), hypertension (OR 1.608), diabetes (OR 1.573), dyslipidemia (OR 1.167), stroke (OR 1.272), and depression (OR 1.567). Risk factors for AMD were COVID-19 pandemic (OR 1.600), dyslipidemia (OR 1.610), and depression (OR 1.466). Risk factors for glaucoma were hypertension (OR 1.234), dyslipidemia (OR 1.529), diabetes (OR 1.323), and depression (OR 1.830). The COVID-19 pandemic was a risk factor for cataracts and AMD, but not for glaucoma. Cataracts and AMD may be more influenced by the acquired health conditions or the environment., (© 2024. The Author(s).)

The prevalence and dynamics of circulating tumor DNA (ctDNA) in patients with breast cancer recurrence or de novo metastatic cancer were examined in a retrospective analysis of a prospective observational cohort. Twenty-three recurrent/metastatic breast cancer cases (8 locoregional, 15 distant metastasis) were enrolled, and sequential plasma samples were obtained. Anchor mutations were selected from the target sequencing of each patient's primary and/or metastatic tumor. An in-house developed assay (UHS assay) was employed for a tumor-informed ctDNA assay during treatment and follow-up. A median of three (range 1-5) anchor mutations per case were applied for ctDNA detection. ctDNA was detected in 14 (63.6%, 14/22) cases at the time of enrollment and 18 (78.5%, 18/23) cases during follow-up. More anchor mutations and higher tumor burden were significantly related to higher ctDNA positive rates (p-value 0.036, 0.043, respectively). The mean enriched variant allele frequency (eVAF) at each time point was significantly higher for stable or progressive disease responses (ANOVA test p-value < 0.001). Eight patients showed an increase in their ctDNA eVAF prior to clinical progression with a mean lead time of 6.2 months (range 1.5-11 months). ctDNA dynamics measured using personalized assay reflected the clinical course of breast cancer recurrence., (© 2024. The Author(s).)

Trastuzumab emtansine (T-DM1) is widely utilized as a second-line and subsequent treatment for metastatic HER2+ breast cancer and has shown promise in early breast cancer treatment, particularly in adjuvant settings for residual disease after neoadjuvant chemotherapy. However, concerns have arisen regarding long-term hepatic adverse drug reactions (ADRs) not identified in clinical trials. We investigated potential safety signals of T-DM1 in hepatobiliary disorders and the time-to-onset of ADRs using the FDA Adverse Event Reporting System (FAERS) database. Suspected ADRs were extracted and divided into two groups: T-DM1 (N = 3387) and other drugs (N = 11,833,701). Potential signal for T-DM1 in hepatobiliary disorder were identified (reporting odds ratio [ROR] = 5.66, 95% confidence interval [CI] = 5.11-6.27; information component [IC] = 2.35, 95% Credibility Interval [Crl] = 2.18-2.51). A breast cancer indicated subgroup analysis (2519 T-DM1; 172,329 other drugs) also identified a potential safety signal (ROR = 3.28, 95% CI = 2.92-3.68; IC = 1.53, 95%CrI = 1.35-1.71). The median time-to-onset for T-DM1-associated hepatobiliary disorders was 41 days. For prolonged and chronic hepatobiliary disorders, median times were 322.5 and 301.5 days, respectively. These findings highlight the need for further research to inform clinical decisions on optimal T-DM1 treatment duration, balancing benefits with potential adverse reactions., (© 2024. The Author(s).)

The vulnerability during pregnancy has raised concerns about the potential impact of COVID-19 on obstetric anesthesia, an essential aspect of maternal care during cesarean section procedures. To evaluate the influence of COVID-19 infection on obstetric anesthesia during cesarean section, we analyzed the data from Korean National Health Insurance System (NHIS). This retrospective study utilized data from Korean NHIS. We included patients admitted with operation codes specific to cesarean section between January 1, 2020, and December 31, 2021. We classified patients into a COVID (+) group with a diagnosis code (U071) 30 days around surgery and a COVID (-) group without the code in the same period. The primary outcome was 30-day mortality that was defined as death within 30 days of admission due to any causes. Secondary outcomes were pulmonary complications (pneumonia, acute respiratory distress syndrome [ARDS], pulmonary thromboembolism [PTE], or unexpected postoperative mechanical ventilation), ICU admission, cardiac arrest, myocardial infarction [MI], other thromboembolic events, surgical site infection, sepsis, acute renal failure [ARF], and hepatic failure. Among 75,268 patients who underwent cesarean section, 107 had a COVID-19 diagnosis code, while 75,161 did not. After 1:4 propensity score matching (PSM), 535 patients were included in each group. 30-day mortality showed no significant differences between the two groups both before and after PSM. The COVID (+) group demonstrated significantly elevated rates of pneumonia, ARDS, PTE, and surgical site infection both before and after PSM. Hospital length of stay and admission costs were also significantly longer and higher, respectively, in the COVID (+) group before and after PSM. In subgroup analysis, no differences were observed in mortality and postoperative complications based on the anesthesia method after matching. COVID-19 infection is associated with increased rates of postoperative complications, including pneumonia, ARDS, PTE, surgical site infection, longer hospital stays, and increased admission costs, in patients who underwent cesarean section., (© 2024. The Author(s).)

Despite the improved outcomes in patients with hematological malignancies, infections caused by multidrug-resistant organisms (MDROs) pose a new threat to these patients. We retrospectively reviewed the patients with hematological cancer and bacterial bloodstream infections (BSIs) at a tertiary hospital between 2003 and 2022 to assess the impact of MDROs on outcomes. Among 328 BSIs, 81 (24.7%) were caused by MDROs. MDRO rates increased from 10.3% (2003-2007) to 39.7% (2018-2022) (P < 0.001). The 30-day mortality rate was 25.0%, which was significantly higher in MDRO-infected patients than in non-MDRO-infected patients (48.1 vs. 17.4%; P < 0.001). The observed trend was more pronounced in patients with newly diagnosed diseases and relapsed/refractory disease but less prominent in patients in complete remission. Among MDROs, carbapenem-resistant Gram-negative bacteria exhibited the highest mortality, followed by vancomycin-resistant enterococci, methicillin-resistant Staphylococcus aureus, and extended-spectrum β-lactamase-producing Enterobacteriaceae. Multivariate analysis identified independent risk factors for 30-day mortality as age ≥ 65 years, newly diagnosed disease, relapsed/refractory disease, MDROs, polymicrobial infection, CRP ≥ 20 mg/L, and inappropriate initial antibiotic therapy. In conclusion, MDROs contribute to adverse outcomes in patients with hematological cancer and bacterial BSIs, with effects varying based on the underlying disease status and causative pathogens. Appropriate initial antibiotic therapy may improve patient outcomes., (© 2024. The Author(s).)

Low blood pressure (BP) is associated with poor outcomes in patients with heart failure (HF). We investigated the influence of initial BP on the prognosis of HF patients at admission, and prescribing patterns of HF medications, such as angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB), and beta-blockers (BB). Data were sourced from a multicentre cohort of patients admitted for acute HF. Patients were grouped into heart failure reduced ejection fraction (HFrEF) and HF mildly reduced/preserved ejection fraction (HFmrEF/HFpEF) groups. Initial systolic and diastolic BPs were categorized into specific ranges. Among 2778 patients, those with HFrEF were prescribed ACEi, ARB, or BB at discharge, regardless of their initial BP. However, medication use in HFmrEF/HFpEF patients tended to decrease as BP decreased. Lower initial BP in HFrEF patients correlated with an increased incidence of all-cause death and composite clinical events, including HF readmission or all-cause death. However, no significant differences in clinical outcomes were observed in HFmrEF/HFpEF patients according to BP. Initial systolic (< 120 mmHg) and diastolic (< 80 mmHg) BPs were independently associated with a 1.81-fold (odds ratio [OR] 1.81, 95% confidence interval [CI] 1.349-2.417, p < 0.001) and 2.24-fold (OR 2.24, 95% CI 1.645-3.053, p < 0.001) increased risk of long-term mortality in HFrEF patients, respectively. In conclusion, low initial BP in HFrEF patients correlated with adverse clinical outcomes, and BP < 120/80 mmHg independently increased mortality. However, this relationship was not observed in HFmrEF/HFpEF patients., (© 2024. The Author(s).)

Microplastic pollution, especially secondary microplastics (MPs), poses a significant threat to marine ecosystems. Despite its prevalence, the impact of natural-aged MPs on marine organisms, hindered by collection challenges, remains poorly understood. This study focused on 1-3 μm natural-aged MPs collected from Japan's coastal sea, investigating their effects on the rotifer Brachionus plicatilis sensu stricto and its reproductive mechanisms. Rotifers exposed to varying MP concentrations (0, 20, and 200 particles/mL) over 14-day batch cultures exhibited reduced population growth and fertilization rates. Down-regulation of reproductive genes and up-regulation of oxidative stress-related genes were observed, indicating MP-induced disruptions. Enhanced activities of superoxide dismutase and acetylcholinesterase and elevated malondialdehyde levels further emphasized oxidative stress. These findings underscore the detrimental impact of MPs on rotifer reproductivity, shedding light on the underlying mechanisms., (© 2024. The Author(s).)

Breast cancer is the most commonly diagnosed cancer among women worldwide. Breast cancer patients experience significant distress relating to their diagnosis and treatment. Managing this distress is critical for improving the lifespan and quality of life of breast cancer survivors. This study aimed to assess the level of distress in breast cancer survivors and analyze the variables that significantly affect distress using machine learning techniques. A survey was conducted with 641 adult breast cancer patients using the National Comprehensive Cancer Network Distress Thermometer tool. Participants identified various factors that caused distress. Five machine learning models were used to predict the classification of patients into mild and severe distress groups. The survey results indicated that 57.7% of the participants experienced severe distress. The top-three best-performing models indicated that depression, dealing with a partner, housing, work/school, and fatigue are the primary indicators. Among the emotional problems, depression, fear, worry, loss of interest in regular activities, and nervousness were determined as significant predictive factors. Therefore, machine learning models can be effectively applied to determine various factors influencing distress in breast cancer patients who have completed primary treatment, thereby identifying breast cancer patients who are vulnerable to distress in clinical settings., (© 2024. The Author(s).)

This split-mouth blinded randomized controlled study compared the efficacy of a desensitizing agent with oxalate/resin polymer and a universal adhesive containing mesoporous bioactive glass (MBG) for dentin hypersensitivity (DH) relief, using Schiff sensitivity score (SSS) and visual analog scale (VAS). Split quadrants containing teeth with DH were treated with either MS Coat ONE or Hi-Bond Universal with MBG as the functional additive. Assessments at baseline, immediately post-application, and at 1- and 2-week follow-ups used standardized stimulus protocols (air, cold, and acid). The SSS difference was the primary outcome, while the VAS difference was the secondary outcome. A mixed linear effect model performed statistical analysis. Immediate DH reduction occurred in response to air stimuli, with a significant decrease in Group HB than in Group MS (p = 0.0178). Cold stimulus reduction exhibited a gradual cumulative effect, with consistently greater reductions in Group HB than in Group MS (p ≤ 0.0377). Both groups effectively managed acidic stimuli, with no significant differences (p > 0.05). The VAS scores decreased gradually over the follow-up period (p < 0.0001). This study highlights the differential efficacy of treatments for various DH triggers and recommends specific approaches based on different stimulus types. The universal adhesive containing MBG demonstrated DH relief potential, promising efficacy identical to or superior to that of a dedicated desensitizing agent. Further research exploring the long-term efficacy and underlying mechanisms is warranted. The universal adhesive containing MBG can be adopted as an in-office desensitizing agent for DH relief. The desensitizing efficacy of universal adhesive matches or surpasses dedicated agents for air and cold stimuli., (© 2024. The Author(s).)

In this study, polyurethane (PU) foams were manufactured using kraft lignin and castor oil as bio-based polyols by replacing 5-20 wt% and 10-100 wt% of conventional polyol, respectively. To investigate the effects of unmodified bio-based polyols on PU foam production, reactivity and morphology within PU composites was analyzed as well as mechanical and thermal properties of the resulting foams. Bio-based PU foam production was carried out after characterizing the reagents used in the foaming process (including hydroxyl group content, molecular weight distribution, and viscosity). To compare the resulting bio-based PU foams, control foam were produced without any bio-based polyol under the same experimental conditions. For lignin-incorporated PU foams, two types, LPU and lpu, were manufactured with index ratio of 1.01 and 1.3, respectively. The compressive strength of LPU foams increased with lignin content from 5 wt% (LPU5: 147 kPa) to 20 wt% (LPU20: 207 kPa), although it remained lower than that of the control foam (PU0: 326 kPa). Similarly, the compressive strength of lpu foams was lower than that of the control foam (pu0: 441 kPa), with values of 164 kPa (lpu5), 163 kPa (lpu10), 167 kPa (lpu15), and 147 kPa (lpu20). At 10 wt% lignin content, both foams (LPU10 and lpu10) exhibited the smallest and most homogenous pore sizes and structures. For castor oil-incorporated PU foams with an index of 1.01, denoted as CPU, increasing castor oil content resulted in larger cell sizes and void fractions, transitioning to an open-cell structure and decreasing the compressive strength of the foams from 284 kPa (CPU10) to 23 kPa (CPU100). Fourier transform infrared (FT-IR) results indicated the formation of characteristic urethane linkages in PU foams and confirmed that bio-based polyols were less reactive with isocyanate compared to traditional polyol. Thermogravimetric analysis (TGA) showed that incorporating lignin and castor oil affected the thermal decomposition behavior. The thermal stability of lignin-incorporated PU foams improved as the lignin content increased with char yields increasing from 11.5 wt% (LPU5) to 15.8 wt% (LPU20) and from 12.4 wt% (lpu5) to 17.5 wt% (lpu20). Conversely, the addition of castor oil resulted in decreased thermal stability, with char yields decreasing from 10.6 wt% (CPU10) to 4.2 wt% (CPU100). This research provides a comprehensive understanding of PU foams incorporating unmodified biomass-derived polyols (lignin and castor oil), suggesting their potential for value-added utilization as bio-based products., (© 2024. The Author(s).)

Predicting outcomes in pulmonary tuberculosis is challenging despite effective treatments. This study aimed to identify factors influencing treatment success and culture conversion, focusing on artificial intelligence (AI)-based chest X-ray analysis and Xpert MTB/RIF assay cycle threshold (Ct) values. In this retrospective study across six South Korean referral centers (January 1 to December 31, 2019), we included adults with rifampicin-susceptible pulmonary tuberculosis confirmed by Xpert assay from sputum samples. We analyzed patient characteristics, AI-based tuberculosis extent scores from chest X-rays, and Xpert Ct values. Of 230 patients, 206 (89.6%) achieved treatment success. The median age was 61 years, predominantly male (76.1%). AI-based radiographic tuberculosis extent scores (median 7.5) significantly correlated with treatment success (odds ratio [OR] 0.938, 95% confidence interval [CI] 0.895-0.983) and culture conversion at 8 weeks (liquid medium: OR 0.911, 95% CI 0.853-0.973; solid medium: OR 0.910, 95% CI 0.850-0.973). Sputum smear positivity was 49.6%, with a median Ct of 26.2. However, Ct values did not significantly correlate with major treatment outcomes. AI-based radiographic scoring at diagnosis is a significant predictor of treatment success and culture conversion in pulmonary tuberculosis, underscoring its potential in personalized patient management., (© 2024. The Author(s).)

In this study, changes in bioactive compound contents and the in vitro biological activity of mixed grains, including oats, sorghum, finger millet, adzuki bean, and proso millet, with eight different blending ratios were investigated. The total phenolic compounds and flavonoid contents ranged from 14.43-16.53 mg gallic acid equivalent/g extract and 1.22-5.37 mg catechin equivalent/g extract, respectively, depending on the blending ratio. The DI-8 blend (30% oats, 30% sorghum, 15% finger millet, 15% adzuki bean, and 10% proso millet) exhibited relatively higher antioxidant and anti-diabetic effects than other blending samples. The levels of twelve amino acids and eight organic acids in the grain mixes were measured. Among the twenty metabolites, malonic acid, asparagine, oxalic acid, tartaric acid, and proline were identified as key metabolites across the blending samples. Moreover, the levels of lactic acid, oxalic acid, and malonic acid, which are positively correlated with α-glucosidase inhibition activity, were considerably higher in the DI-blending samples. The results of this study suggest that the DI-8 blend could be used as a functional ingredient as it has several bioactive compounds and biological activities, including anti-diabetic activity., (© 2024. The Author(s).)

Previous studies have examined the prevalence of allergic diseases in adolescents 1-2 years after the emergence of the COVID-19 pandemic. However, more data is needed to understand the long-term impact of COVID-19 on allergic diseases. Thus, we aimed to examine the trend of the atopic dermatitis prevalence in Korean adolescents before and during the COVID-19 pandemic across 14 years. Additionally, we analyze the risk factors of atopic dermatitis (AD) based on the results. The Korean Disease Control and Prevention Agency conducted the Korea Youth Risk Behavior Web-based Survey from 2009 to 2022, from which the data for this study were obtained. Prevalence trends were compared across subgroups, and the β difference (β diff ) was calculated. We computed odds ratios to examine changes in the disease prevalence before and during the pandemic. This study included a total of 917,461 participants from 2009 to 2022. The prevalence of atopic dermatitis increased from 6.79% (95% CI 6.66-6.91) in 2009-2011 to 6.89% (95% CI 6.72-7.05) in 2018-2019, then decreased slightly to 5.82% (95% CI 5.60-6.04) in 2022. Across the 14 years, middle school student status, low parent's highest education level, low household income, non-alcohol consumption, non-smoker smoking status, no suicidal thoughts, and no suicide attempts were associated with increased risk of atopic dermatitis, while female sex, rural residence, high BMI, low school performance, low household income, and no feelings of sadness and despair was associated with a small increase. This study examined the prevalence of atopic dermatitis across an 18-year, and found that the prevalence increased in the pre-pandemic then decreased during the start of the pandemic and remained constant throughout the pandemic. This trend could be explained mainly by the large scale social and political changes that occurred during the COVID-19 pandemic., (© 2024. The Author(s).)