Search

Objective: Previous studies have reported that vitamin D deficiency increased the risk of Alzheimer's disease (AD) dementia in older adults. However, little is known about how vitamin D is involved in the pathophysiology of AD. Thus, this study aimed to examine the association and interaction of serum vitamin D levels with in vivo AD pathologies including cerebral beta-amyloid (Aβ) deposition and neurodegeneration in nondemented older adults., Methods: 428 Nondemented older adults were recruited from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease, a prospective cohort that began in 2014. All participants underwent comprehensive clinical assessments, measurement of serum 25-hydroxyvitamin D (25[OH]D), and multimodal brain imaging including Pittsburgh compound B (PiB) positron emission tomography and magnetic resonance imaging. Global PiB deposition was measured for the Aβ biomarker. Intracranial volume-adjusted hippocampal volume (HVa) was used as a neurodegeneration biomarker., Results: Overall, serum 25(OH)D level was not associated with either Aβ deposition or HVa after controlling for age, sex, apolipoprotein E ε4 positivity, and vascular risk factors. However, serum 25(OH)D level had a significant moderating effect on the association between Aβ and neurodegeneration, with lower serum 25(OH)D level significantly exacerbating cerebral Aβ-associated hippocampal volume loss (B = 34.612, p = 0.008)., Conclusion: Our findings indicate that lower serum vitamin D levels may contribute to AD by exacerbating Aβ-associated neurodegeneration in nondemented older adults. Further studies to explore the potential therapeutic effect of vitamin D supplementation on the progression of AD pathology will be necessary.

Objective: We intended to investigate the relationships between visual sensory impairment (VSI) or auditory sensory impairment (ASI) and brain pathological changes associated with cognitive decline in older adults., Methods: We primarily tried to examine whether each sensory impairment is related to Alzheimer's disease (AD) pathology, specifically beta-amyloid (Aβ) deposition, through both cross-sectional and longitudinal approaches in cognitively unimpaired older adults. Self-report questionnaires on vision and hearing status were administered at the baseline. Neuroimaging scans including brain [ 11 C] Pittsburgh Compound B PET and MRI, as well as clinical assessments, were performed at baseline and 2-year follow-up., Results: Cross-sectional analyses showed that the VSI-positive group had significantly higher Aβ deposition than the VSI-negative group, whereas there was no significant association between ASI positivity and Aβ deposition. Longitudinal analyses revealed that VSI positivity at baseline was significantly associated with increased Aβ deposition over 2 years (β = 0.153, p = 0.025), although ASI positivity was not (β = 0.045, p = 0.518). VSI positivity at baseline was also significantly associated with greater atrophic changes in AD-related brain regions over the 2-year follow-up period (β = -0.207, p = 0.005), whereas ASI positivity was not (β = 0.024, p = 0.753). Neither VSI nor ASI positivity was related to cerebrovascular injury, as measured based on the white matter hyperintensity volume., Conclusion: The findings suggest that VSI is probably related to AD-specific pathological changes, which possibly mediate the reported relationship between VSI and cognitive decline. In contrast, ASI appears not associated with AD pathologies but may contribute to cognitive decline via other mechanisms.

Purpose: Microfocused ultrasound with real-time visualization (MFU-V) is often used for noninvasive skin lifting, by precisely targeting dermal and subcutaneous tissues to create thermal coagulation points (TCPs). These TCPs denature collagen and initiate a transient inflammatory response, ultimately attracting dermal fibroblasts and inducing efficient neocollagenesis and extracellular matrix (ECM) remodeling, yielding to MFU-V's desired skin-lifting effects. The current study investigates MFU-V's underlying mode of action based on the histological progression of TCPs in the skin, providing new insight into the technology's regenerative effect., Methods: Following standard triple-depth MFU-V treatment, in vivo skin samples were assessed using histology and immunohistochemistry to evaluate TCPs, heat shock protein (HSP47), and elastin expression in fibroblasts., Results: MFU-V treatment induced elongated, flame-like TCPs with denatured collagen at focal depths of 1.5, 3.0, and 4.5 mm within the skin-each corresponding to its respective transducer depth. Time-dependent progression of TCPs showed significantly increased scores of fibroblasts and mature collagen along with recruitment of HSP47-positive fibroblasts to TCP areas on Day 90. Collagen formation and later maturation were visualized. Newly synthesized elastin significantly increased in the TCP area on Day 90 compared to Day 14., Conclusion: This work provides histological evidence of stimulation and regeneration of newly synthesized elastin fibers after TCP induction. MFU-V-generated TCPs triggered the body's own healing cascade of collagen denaturation, transient inflammation, proliferation, and tissue remodeling, resulting in attraction of HSP47-positive fibroblasts to the TCP sites, and new collagen and elastin fiber regeneration by fibroblasts. Besides the well-described neocollagenesis, this study demonstrates that MFU-V treatment induces elastin neogenesis that may result not only in skin lifting but also in improved skin elasticity, providing an overall regenerative effect., (© 2024 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Background/aims: : The relationship between genetic polymorphisms and gastric inflammation remains unclear. This study aimed to evaluate the impact of genetic polymorphisms on Helicobacter pylori (HP)-associated gastritis according to sex., Methods: : Two hundred thirty-two male and 404 female subjects with current HP infection were prospectively enrolled. The genotyping of IL-1B-511 C/T, IL-1RN variable number of tandem repeats, IL-6-572 G/C, IL-8-251 A/T, IL-8-781 C/T, IL-10-1082 G/A, IL-10-592 C/A, TNF-A-308 G/A, and transforming growth factor ( TGF )- B-509 C/T, was determined by polymerase chain reaction-restriction fragment length polymorphism. The degree of monocyte or neutrophil infiltration, atrophic gastritis, and intestinal metaplasia was evaluated using the updated Sydney system., Results: : Among the male subjects, moderate/severe atrophic gastritis of the corpus was higher in IL-1B-511 CC carriers than in CT and TT carriers independent of age, alcohol consumption, and HP virulence factors (26.9% vs 10.4%; adjusted hazard ratio [HR], 4.377; 95% confidence interval, 1.387 to 13.814). In females, IL-8-251 AA carriers were independently and significantly associated with moderate/severe atrophic gastritis of the corpus compared with that in AT and TT carriers (21.4% vs 6.0%, adjusted HR=3.799). In males, the IL-8-251 TT genotype was associated with moderate/severe intestinal metaplasia of the corpus compared with the AT and AA genotypes (13.4% vs 5.6%, adjusted HR=3.128), while the IL-10-592 CA and CC genotypes were associated with moderate/severe monocyte infiltration of the antrum compared with AA genotype (83.6% vs 71.8%, adjusted HR=2.227)., Conclusions: : Genetic polymorphisms in cytokines play different roles in HP-associated gastritis according to sex.

Early and accurate detection of colorectal cancer (CRC) is critical for improving patient outcomes. Existing diagnostic techniques are often invasive and carry risks of complications. Herein, we introduce a plasmonic gold nanopolyhedron (AuNH)-coated needle-based surface-enhanced Raman scattering (SERS) sensor, integrated with endoscopy, for direct mucus sampling and label-free detection of CRC. The thin and flexible stainless-steel needle is coated with polymerized dopamine, which serves as an adhesive layer and simultaneously initiates the nucleation of gold nanoparticle (AuNP) seeds on the needle surface. The AuNP seeds are further grown through a surface-directed reduction using Au ions-hydroxylamine hydrochloride solution, resulting in the formation of dense AuNHs. The formation mechanism of AuNHs and the layered structure of the plasmonic needle-based SERS (PNS) sensor are thoroughly analyzed. Furthermore, a strong field enhancement of the PNS sensor is observed, amplified around the edges of the polyhedral shapes and at nanogap sites between AuNHs. The feasibility of the PNS sensor combined with endoscopy system is further investigated using mouse models for direct colonic mucus sampling and verifying noninvasive label-free classification of CRC from normal controls. A logistic regression-based machine learning method is employed and successfully differentiates CRC and normal mice, achieving 100% sensitivity, 93.33% specificity, and 96.67% accuracy. Moreover, Raman profiling of metabolites and their correlations with Raman signals of mucus samples are analyzed using the Pearson correlation coefficient, offering insights for identifying potential cancer biomarkers. The developed PNS-assisted endoscopy technology is expected to advance the early screening and diagnosis approach of CRC in the future., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background/aims: : Accurately diagnosing diffuse gastric wall thickening is challenging. Hypertrophic gastritis (HG), while benign, mimics the morphology of Borrmann type 4 advanced gastric cancer (AGC B-4). We compared the features of endoscopy and endoscopic ultrasonography (EUS) between them., Methods: : We retrospectively reviewed patients who underwent EUS for gastric wall thickening between 2000 and 2021, selecting HG and pathologically confirmed advanced gastric cancer cases. Ulceration and antral wall thickening were determined via endoscopy, while EUS assessed the 5-layered gastric wall structure, measuring the proper muscle (PM) layer and total wall thickness., Results: : Male dominance was observed in AGC B-4, and the hemoglobin and albumin levels were significantly lower. The rate of antral wall thickening and presence of ulceration were significantly higher in AGC B-4 cases. Destruction of the PM layers was observed only in AGC B-4 cases, and the PM was significantly thicker in AGC B-4 cases. Forceps biopsy had an excellent success rate in ulcer-present AGC B-4 cases, but only a 42.6% success rate was observed for cases without ulcers, necessitating additional diagnostic modalities. A PM thickness of 2.39 mm distinguished between AGC B-4 and HG effectively. The multivariable analysis showed that a thickened PM layer and the presence of ulceration were significant risk factors for the diagnosis of AGC B-4., Conclusions: : Endoscopic findings of a thickened gastric wall, including antral involvement, and presence of ulcer were significant risk factors for the diagnosis of AGC B-4. EUS findings of destroyed wall layers and a thickened PM of >2.39 mm were the key points of differentiation between HG and AGC B-4.

Perceived temperature (PT), which encompasses meteorological factors such as wind speed, cloud cover, and humidity, reflects the actual effect of temperature on the human body. However, limited data exist on the health implications of prolonged exposure to low temperatures during winter in individuals with chronic kidney disease (CKD). We investigated the association between winter PT and long-term outcomes among CKD patients. A total of 32,870 CKD patients from three tertiary hospitals in Seoul were enrolled in this retrospective study (2001-2018). PT was calculated using Staiger's equation, integrating temperature data from 29 automated weather stations across Seoul, along with dew point temperature, wind velocity, and cloud cover data. Kriging interpolation was utilized to estimate PT values at the patients' locations. Overall mortality and major adverse cardiovascular events (MACEs) were assessed using a time-varying Cox proportional hazards model. Additionally, the Cox regression model evaluated PT corresponding to temperature thresholds for cold surge watches or warnings. Over a median follow-up of 6.14 ± 3.96 years, 6147 deaths (18.7%) were recorded. We found that as the average or minimum PT and Ta decreased by 1 °C, the risk of overall mortality significantly increased. In multivariable analyses, the hazard ratio (HR) for the average PT was 1.049 (95% confidence interval [CI] 1.028-1.071), and that for the minimum PT was 1.038 (CI 1.027-1.052). Furthermore, a cold surge warning at a PT of -25.63 °C indicated an HR of 1.837 (CI 1.764-1.914) and a C-index of 0.792. The increased risk of mortality was more pronounced in patients with low or middle socioeconomic statuses. For MACEs, lower average and minimum PT and Ta were associated with an increased risk, following a similar trend to overall mortality, although not all results reached statistical significance. These findings emphasize the importance of targeted public health policies to mitigate risks among vulnerable CKD patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Atherosclerosis is a major contributor to cardiovascular disease, characterized by inflammation and lipid accumulation in arterial walls, leading to plaque formation. Elevated low-density lipoprotein cholesterol is a primary risk factor for atherosclerosis. All-trans retinoic acid (ATRA), a metabolite of vitamin A, has demonstrated anti-inflammatory effects and potential in regulating vascular injury. 9-cisretinoic acid (9cRA) is an active metabolite of vitamin A and activates the retinoid X receptor. This study investigates whether potassium retinoate (PA9RA), a synthetic combination of ATRA and 9cRA, offers superior efficacy in treating atherosclerosis compared to established treatments such as clopidogrel and atorvastatin. Male ApoE -/- mice were fed a Western-type diet and treated with PA9RA, clopidogrel, or atorvastatin for 10 weeks. The body weight, organ weight, serum biochemistry, and histopathology, including atherosclerotic lesion area and liver steatosis were assessed. PA9RA treatment led to a significant reduction in body weight and inguinal fat, with the 45 mg/kg/day dose showing marked efficacy in decreasing atherosclerotic lesion size and ameliorating liver steatosis. Histopathological evaluation revealed decreased foam cell formation and improved liver histology in PA9RA-treated groups compared to controls. Notable side effects included epidermal hyperplasia and gastric hyperplasia at high doses of PA9RA. PA9RA exhibits superior efficacy over clopidogrel and atorvastatin in ameliorating atherosclerosis and fatty liver in ApoE -/- mice. This study highlights PA9RA's potential as a promising therapeutic agent for atherosclerosis. Further research is needed to elucidate its mechanisms of action and assess long-term safety and efficacy.

RIPK1/RIPK3-MLKL signaling molecules are fundamental in initiating necroptotic cell death, but their roles in the development of colon cancer are unclear. This study reports that RIPK3 interacted with SPOP, a component of the E3 ligase within the Cul3 complex. This interaction leads to K48-linked ubiquitination and subsequent proteasomal degradation of RIPK3. Two distinct degron motifs, PETST and SPTST, were identified within the linker domain of RIPK3 for SPOP. RIPK3 phosphorylations at Thr403 by PIM2 and at Thr412/Ser413 by ERK2 are essential to facilitate its interaction with SPOP. Computational docking studies and immunoprecipitation analyses showed that these PIM2 and ERK2 phosphorylations bolster the stability of the RIPK3-SPOP interaction. In particular, mutations of RIPK3 at the degron motifs extended the half-life of RIPK3 by preventing its phosphorylation and subsequent ubiquitination. The deletion of SPOP, which led to increased stability of the RIPK3 protein, intensified LPS/sMAC/zVAD-induced necroptotic cell death in colon cancer cells. These findings underscore the critical role of the SPOP-mediated RIPK3 stability regulation pathway in controlling necroptotic cell death., Competing Interests: Declarations Consent for publication All authors read and approved the submission and final publication. Conflict of interest The authors have no relevant financial or non-financial interests to disclose., (© 2024. The Author(s).)

Autophagy is a crucial intracellular degradation process that provides energy and supports nutrient deprivation adaptation. However, the mechanisms by which these cells detect lipid scarcity and regulate autophagy are poorly understood. In this study, we demonstrate that protein kinase A (PKA)-dependent lipolysis delays autophagy initiation during short-term nutrient deprivation by inhibiting AMP-activated protein kinase (AMPK). Using coherent anti-Stokes Raman spectroscopy, we visualized free fatty acids (FFAs) in vivo and observed that lipolysis-derived FFAs were used before the onset of autophagy. Our data suggest that autophagy is triggered when the supply of FFAs is insufficient to meet energy demands. Furthermore, PKA activation promotes lipolysis and suppresses AMPK-driven autophagy during early fasting. Disruption of this regulatory axis impairs motility and reduces the lifespan of Caenorhabditis elegans during fasting. These findings establish PKA as a critical regulator of catabolic pathways, prioritizing lipolysis over autophagy by modulating AMPK activity to prevent premature autophagic degradation during transient nutrient deprivation., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Coronavirus disease-2019 (COVID-19), attributed to the severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2), has posed global health challenges since it first emerged in 2019, and its impact continues to persist. The neurotropic nature of SARS-CoV-2 remains undisclosed, though researchers are proposing hypotheses on how the virus is transmitted to the central nervous system. One of the prevailing hypotheses is that SARS-CoV-2 travels through the olfactory nerve system via the olfactory epithelium (OE). Using a K18-human angiotensin converting-enzyme 2 (hACE2) transgenic mouse model with impaired olfactory sensory neurons (OSNs) induced by zinc sulfate, we examined the role of the olfactory nerve in the brain invasion by SARS-CoV-2. Mice lacking OSNs exhibited reduced levels of viral transmission to the brain, leading to significantly improved outcomes following SARS-CoV-2 infection. Moreover, a positive correlation was observed between viral persistence in the OE and brain infection. These results indicate that early inhibition of the olfactory nerve pathway effectively prevents viral invasion of the brain in K18-hACE2 mice. Our study underscores the significance of the olfactory nerve pathway in the transmission of SARS-CoV-2 to the brain., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Metastasis is the leading cause of cancer-related mortality. Paneth cells provide stem cell niche factors in homeostatic conditions, but the underlying mechanisms of cancer stem cell niche development are unclear. Here, we report that Dickkopf-2 (DKK2) is essential for the generation of cancer cells with Paneth cell properties during colon cancer metastasis. Splenic injection of Dkk2 knockout (KO) cancer organoids into C57BL/6 mice resulted in a significant reduction of liver metastases. Transcriptome analysis showed reduction of Paneth cell markers such as lysozymes in KO organoids. Single-cell RNA sequencing analyses of murine metastasized colon cancer cells and patient samples identified the presence of lysozyme positive cells with Paneth cell properties including enhanced glycolysis. Further analyses of transcriptome and chromatin accessibility suggested hepatocyte nuclear factor 4 alpha (HNF4A) as a downstream target of DKK2. Chromatin immunoprecipitation followed by sequencing analysis revealed that HNF4A binds to the promoter region of Sox9 , a well-known transcription factor for Paneth cell differentiation. In the liver metastatic foci, DKK2 knockout rescued HNF4A protein levels followed by reduction of lysozyme positive cancer cells. Taken together, DKK2-mediated reduction of HNF4A protein promotes the generation of lysozyme positive cancer cells with Paneth cell properties in the metastasized colon cancers., Competing Interests: JS, JP, JL, JJ, RD, SM, JK, SP, JH, JW, AB No competing interests declared, JC Reviewing editor, eLife, (© 2024, Shin, Park et al.)

Background: COVID-19 is known to cause psychological problems. Psychological rehabilitation can be performed to reduce anxiety, depression, and insomnia. Facing patients with infectious diseases can be difficult for medical staff. Therefore, this study compared the effects of psychiatric tele-rehabilitation (TR) and conventional psychiatric rehabilitation (CR) in isolated patients with COVID-19., Methods: This randomized controlled study, conducted at a single community-based hospital, included 40 patients (24 in the psychiatric tele-rehabilitation group [TRG] and 16 in the conventional psychiatric rehabilitation group [CRG]) with COVID-19 were recruited from November 18, 2021, to April 7, 2022. Psychiatric rehabilitation is an occupation-based intervention in which patients perform meaningful activities and tasks. Patients in the TRG selected activities, received counseling, and underwent monitoring over the phone, while those in the CRG participated in face-to-face sessions. The interventions were conducted for 50 min each day during an isolation period of 7 days in both groups, and all participants received the interventions individually. The primary outcome was anxiety assessed using the Visual Analog Scale (VAS) and the Zung Self-Rating Anxiety Scale (SAS). Secondary outcomes include the Visual Analog Scale (VAS) and the Patient Health Questionnaire-9 (PHQ-9) to evaluate depression, the Multidimensional State Boredom Scale-8 (MSBS-8) to assess boredom. The Korean version of the Insomnia Severity Index (ISI-K) was used to assess the quality of sleep, and the World Health Organization Quality of Life Assessment Instrument-BRIEF (WHOQOL-BREF) was used to evaluate quality of life. Questionnaires were administered at admission, discharge, and at the 6-month follow-up., Results: In the time × group analysis, the SAS total score (p = .033) and the VAS score for depression (p = .012) in the CRG were significantly lower than those in the TRG at the time of discharge. The VAS score for anxiety (p = .007), total SAS score (p = .050), and VAS score for depression (p = .003) in the CRG were also significantly lower than those in the TRG at the 6-month follow-up. The PHQ-9, MSBS-8, ISI-K, and WHOQOL-BREF scores showed no significant interactions in the time × group analysis., Conclusions: TR was effective in reducing anxiety and improving quality of life during hospitalization, but had no remained effects after discharge. Otherwise, CR was more effective than TR for anxiety and depression during hospitalization and had remained effects at 6-month follow-up. However, considering the characteristics of infectious conditions that involve risk in contact, TR will still play an important role, and efforts will be needed to improve the effect that remained., Trial Registration: The trial was registered with the Korea Clinical Trials Registry (KCT0006714, Date of registration 08/11/2021)., Competing Interests: Declarations Ethics approval and consent to participate The study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board of Seoul National University Bundang Hospital (B-2111-719-302). The requirement for obtaining written informed consent was waived by the Institutional Review Board of Seoul National University Bundang Hospital (B-2111-719-302). Consent for publication Not applicable. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

This study proposes a synthetic data generation model to create a classification framework for cerebellar ataxia patients using trajectory data from the visuomotor adaptation task. The classification objectives include patients with cerebellar ataxia, age-matched normal individuals, and young healthy subjects. Synthetic data for the three classes is generated based on class conditions and random noise by leveraging a combination of conditional adversarial generative neural networks and reconstruction networks. This synthetic data, alongside real data, is utilized as training data for the patient classification model to enhance classification accuracy. The fidelity of the synthetic data is assessed visually to measure the validity and diversity of the generated data qualitatively while quantitatively evaluating distribution similarity to real data. Furthermore, the clinical efficacy of the patient classification model employing synthetic data is demonstrated by showcasing improved classification accuracy through a comparative analysis between results obtained using solely real data and those obtained when both real and synthetic data are utilized. This methodological approach holds promise in addressing data insufficiency in the digital healthcare domain, employing deep learning methodologies, and developing early disease diagnosis tools., Competing Interests: Declarations Ethics approval and consent to participate All experimental procedures, including recruitment, were conducted in accordance with ethical guidelines and procedures approved by the Institutional Review Board of Seoul Metropolitan Government Seoul National University Boramae Medical Center (IRB no. 30-2019-88). All participants gave their written informed consent prior to participation. Consent for publication N/a. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Stem cell transplantation offers a promising therapy that can be administered days, weeks, or months after a stroke. We recognize 2 major mitigating factors that remain unresolved in cell therapy for stroke, notably: (1) well-defined donor stem cells and (2) mechanism of action. To this end, we advance the use of ProtheraCytes, a population of non-adherent CD34+ cells derived from human peripheral blood and umbilical cord blood, which have been processed under good manufacturing practice, with testing completed in a phase 2 clinical trial in post-acute myocardial infarction (NCT02669810). We also reveal a novel mechanism whereby ProtheraCytes secrete growth factors and extracellular vesicles (EVs) that are associated with angiogenesis and vasculogenesis. Our recent data revealed that intranasal transplantation of ProtheraCytes at 3 days after experimentally induced stroke in adult rats reduced stroke-induced behavioral deficits and histological damage up to 28 days post-stroke. Moreover, we detected upregulation of human CD63+ EVs in the ischemic brains of stroke animals that were transplanted with ProtheraCytes, which correlated with increased levels of DCX-labeled neurogenesis and VEGFR1-associated angiogenesis and vasculogenesis, as well as reduced Iba1-marked inflammation. Altogether, these findings overcome key laboratory-to-clinic translational hurdles, namely the identification of well-characterized, clinical grade ProtheraCytes and the elucidation of a potential CD63+ EV-mediated regenerative mechanism of action. We envision that additional translational studies will guide the development of clinical trials for intranasal ProtheraCytes allografts in stroke patients, with CD63 serving as a critical biomarker., (© The Author(s) 2024. Published by Oxford University Press.)

Background: Renal replacement therapy (RRT) is an important treatment option for sepsis-associated acute kidney injury (AKI); however, the optimal timing for its initiation remains controversial. Herein, we investigated the clinical outcomes of early continuous kidney replacement therapy (CKRT), defined as CKRT initiation within 6 hours of sepsis-associated AKI onset, which was earlier than the initiation time defined in previous studies., Methods: We used clinical data sourced from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. This study included patients aged ≥ 18 years who met the sepsis diagnostic criteria and received CKRT because of stage 2 or 3 AKI. Early and late CKRTs were defined as CKRT initiation within 6 hours and after 6 hours of the development of sepsis-associated AKI, respectively., Results: Of the 33,236 patients diagnosed with sepsis, 553 underwent CKRT for sepsis-associated AKI. After excluding cases of early mortality and patients with a dialysis history, 45 and 334 patients were included in the early and late CKRT groups, respectively. After propensity score matching, the 28-day mortality rate was significantly lower in the early CKRT group than in the late CKRT group (26.7% vs. 43.9%, P = 0.035). The early CKRT group also had a significantly greater number of days free of mechanical ventilation (median, 19; interquartile range [IQR], 3-25) and vasopressor administration (median, 21; IQR, 5-26) than the late CKRT group did (median, 10.5; IQR, 0-23; P = 0.037 and median, 13.5; IQR, 0-25; P = 0.028, respectively). The Kaplan-Meier curve also showed that early CKRT initiation was associated with an improved 28-day mortality rate (log-rank test, P = 0.040). In contrast, there was no significant difference in the 28-day mortality between patients who started CKRT within 12 hours and those who did not (log-rank test, P = 0.237)., Conclusion: Early CKRT initiation improved the survival of patients with sepsis-associated AKI. Initiation of CKRT should be considered as early as possible after sepsis-associated AKI onset, preferably within 6 hours., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Background: This study aimed to compare the outcomes and complications of active young adults undergoing open reduction and plate fixation (ORPF) and intramedullary nailing (IMN) for displaced midshaft clavicle fractures (MCFs)., Methods: A retrospective review was performed on all patients undergoing ORPF and IMN of complete MCFs at a single center between 2018 and 2022. Patients who were younger than 60 years with radiographic follow-up until union were included in the study. The mean age of the patients was 33.1 years. Outcome measures were achievement of union, time to healing, residual deformity, complications, and need for additional procedures., Results: Of 39 patients, 29 underwent ORPF and 10 underwent IMN. Plate fixation provided faster functional recovery in the first 6 months, but no difference was observed after 1 year. All fractures in the IMN group healed (100%), compared to 90% in the ORPF group (P=0.08). Mean time to union was 21±8.9 weeks and was significantly different between the two groups (P<0.01), with the ORPF group averaging 23.1 weeks and the IMN group 20.8 weeks. Nonunion rates were higher in the ORPF group (10.3%) than in the IMN group (0.0%), but the difference was not significant (P=0.10)., Conclusions: Both methods restored patients to their pre-injury functional levels. However, IMN, with its higher healing rate, fewer required revision surgeries, and lower incisional numbness, appears to be the preferred method for treating MSFs without comminution in young adults. Level of evidence: III.

Background: The quantification of mRNA expression in urinary sediments is a reliable biomarker for various diseases. However, few studies have investigated the clinical relevance of urinary mRNA levels in IgA nephropathy (IgAN). Thus, we investigated the expression of urinary mRNAs and their clinical significance in IgAN., Methods: Overall, 200 patients with biopsy-proven IgAN, 48 disease controls, and 76 healthy controls were enrolled. We identified the differential expression of mRNAs in renal tissue between patients with IgAN and normal subjects using the Gene Expression Omnibus dataset and selected candidate mRNAs. mRNA expression in the urinary sediment was measured using quantitative real-time polymerase chain reaction. Associations between urinary mRNA levels and clinicopathological parameters were analyzed and the predictive value of mRNAs for disease progression was evaluated., Results: The urinary expression of CCL2, CD14, DNMT1, FKBP5, Nephrin, and IL-6 was significantly upregulated in patients with IgAN compared with healthy controls. C3, FLOT1, and Podocin levels were significantly correlated with renal function, where C3, FLOT1, and TfR levels were significantly correlated with urinary protein excretion. During follow-up, 26 (13.0%) patients with IgAN experienced disease progression, defined as a greater than 50% reduction in the estimated glomerular filtration rate or progression to end-stage renal disease. Urinary mRNA levels of FLOT1 (HR 3.706, 95% CI 1.373-10.005, P = 0.010) were independently associated with an increased risk of disease progression., Conclusions: Our results suggest that urinary sediment mRNAs are a useful biomarker in IgAN patients. Further studies with larger sample sizes and longer follow-up durations are required., (© 2024. The Author(s).)

Introduction: Despite the recognized importance of including ethnic diversity in Alzheimer's disease (AD) research, substantial knowledge gaps remain, particularly in Asian populations., Methods: RNA sequencing was performed on blood samples from the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease (KBASE) to perform differential gene expression (DGE), gene co-expression network, gene-set enrichment, and machine learning analyses for amyloid beta (Aβ) deposition on positron emission tomography., Results: DGE analysis identified 265 dysregulated genes associated with Aβ deposition and replicated three AD-associated genes in an independent Korean cohort. Network analysis identified two modules related to pathways including a natural killer (NK) cell-mediated immunity. Machine learning analysis showed the classification of Aβ positivity improved with the inclusion of gene expression data., Discussion: Our results in a Korean population suggest Aβ deposition-associated genes are enriched in NK cell-mediated immunity, providing a better understanding of AD molecular mechanisms and yielding potential diagnostic and therapeutic strategies., Highlights: Dysregulated genes were associated with amyloid beta (Aβ) deposition on positron emission tomography in a Korean cohort. Dysregulated genes in Alzheimer's disease were replicated in an independent Korean cohort. Gene network modules were associated with Aβ deposition. Natural killer (NK) cell proportion in blood was associated with Aβ deposition. Dysregulated genes were related to a NK cell-mediated immunity., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Confinement of reactants within nanoscale spaces of low-dimensional materials has been shown to provide reorientation of strained reactants or stabilization of unstable reactants for synthesis of molecules and tuning of chemical reactivity. While few studies have reported chemistry within zero-dimensional pores and one-dimensional nanotubes, organic reactions in confined spaces between two-dimensional materials have yet to be explored. Here, we demonstrate that reactants confined between atomically thin sheets of graphene or hexagonal boron nitride experience pressures as high as 7 gigapascal, which allows the propagation of solvent-free organic reactions that ordinarily do not occur under standard conditions. Specifically, we show that cyclodehydrogenation of hexaphenylbenzene without catalysts as a proof of concept and oxidative polymerization of dopamine into sheet-like crystalline structure are enabled by the effective high pressure experienced by the reactants between the graphene layers. Our results demonstrate a facile, general approach for performing high-pressure chemistry based on confinement of reactants within two-dimensional materials.

Background: Limited research has explored the effect of cardiovascular risk and amyloid interplay on cognitive decline in East Asians., Methods: Vascular burden was quantified using Framingham's General Cardiovascular Risk Score (FRS) in 526 Korean Brain Aging Study (KBASE) participants. Cognitive differences in groups stratified by FRS and amyloid positivity were assessed at baseline and longitudinally., Results: Baseline analyses revealed that amyloid-negative (Aβ-) cognitively normal (CN) individuals with high FRS had lower cognition compared to Aβ- CN individuals with low FRS (p < 0.0001). Longitudinally, amyloid pathology predominantly drove cognitive decline, while FRS alone had negligible effects on cognition in CN and mild cognitive impairment (MCI) groups., Conclusion: Our findings indicate that managing vascular risk may be crucial in preserving cognition in Aβ- individuals early on and before the clinical manifestation of dementia. Within the CN and MCI groups, irrespective of FRS status, amyloid-positive individuals had worse cognitive performance than Aβ- individuals., Highlights: Vascular risk significantly affects cognition in amyloid-negative older Koreans. Amyloid-negative CN older adults with high vascular risk had lower baseline cognition. Amyloid pathology drives cognitive decline in CN and MCI, regardless of vascular risk. The study underscores the impact of vascular health on the AD disease spectrum., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Background: Diabetic nephropathy (DN) is a progressive complication among patients with diabetes and the most common cause of end-stage kidney disease. Neutrophil extracellular traps (NETs) are known to play a role in kidney disease, thus this study aimed to determine their role in the development of diabetic kidney disease using diabetic murine models., Results: Protein and histological analyses revealed that db/db mice and streptozotocin DN models expressed no significant NET-related proteins, myeloperoxidase, citrullinated histone H3 (citH3), neutrophil elastase, and lymphocyte antigen 6 complex locus G6D (Ly6G). However, the inflamed individuals in the DN model showed that citH3 and Ly6G were highly deposited in the renal system based on immunohistochemistry images. In vitro, NET treatment did not induce apoptosis in glomerular endothelial and renal tubular epithelial cells. NET inhibition by DNase administration demonstrated no significant changes in cell apoptosis., Conclusions: NET-related proteins were only expressed in the DN model with tubulointerstitial inflammation. Our study revealed that NETs are only induced in mice with hyperglycemia-induced inflammation., (© 2024. The Author(s).)

We studied the hydroboration of the C 70 fullerene using both B3LYP-D3(BJ)/6-311G(d,p) and M06-2X-D3/6-311G(d,p) levels of theory, incorporating the empirical dispersion interaction, and Fukui index calculations. Potential energy surfaces (PESs) and Gibbs free energy surfaces (GFESs) were calculated for the pathways from four BH 3 adducts (located at the AB , CC , D , and E sites) on the C 70 to eight products formed by the 1,2-addition of BH 3 across the four [6,6]-ring fused bonds ( AB , CC , DE , and EE ) and across the two [5,6]-ring fused bonds ( AA and DD ). These pathways are two-step consecutive reactions. We denoted the positions on the fullerene cage as A through E , from the pole to the equator, based on the D 5h symmetry of the C 70 fullerene. In the first step reaction, the product ratios for the four adduct intermediates should be as the primary intermediate BH 3 ( D ), the secondary intermediate BH 3 ( AB ), the tertiary intermediate BH 3 ( CC ), and the minor intermediate BH 3 ( E ), based on the Fukui indices. In addition, in the second step reaction, transition states (TSs) from four adduct intermediates to eight product isomers, namely, BH 2 ( A )H ( B ) to BH 2 ( E )H ( E ), were obtained using the QST2 method. The calculated reaction coordinates showed exothermic reactions for all bonds except the EE bond. We also confirmed the transition states by frequency calculations and intrinsic reaction coordinate (IRC) analyses. The PESs and GFESs suggest spontaneous processes for the four isomers, of which the primary products are BH 2 ( A )H ( B ) and its isomer BH 2 ( B )H ( A ), the secondary product is BH 2 ( C )H ( C ), and the tertiary product is BH 2 ( D )H ( D ), all formed through adduct intermediates. Therefore, through the hydroboration reaction of C 70 , we could predict and design the site selectivity of C 70 by controlling the energy barrier of the transition state in the second step of the reaction. This implies that we could selectively synthesize mainly BH 2 ( B )H ( A ) isomers across the AB-[6,6]-ring fused bond and also design BH 2 ( D )H( D ) isomers across the DD-[5,6]-ring fused bond. Also, the calculations of formation rate constants can well simulate the experimental ratio of two C 70 H 2 isomers by the hydrolysis of BH 2 ( A )H( B ), BH 2 ( B )H( A ), and BH 2 ( C )H( C ) products at room temperature.

The ability to learn novel motor skills is essential for patients with Parkinson's disease (PD) to regain activities of daily living. However, the underlying mechanisms of motor learning in PD remain unclear. To identify motor features that are distinctively manifested in PD during motor learning, we quantified a rich set of variables reflecting various aspects of the learning process in a virtual throwing task. While the performance outcome improved similarly over 3 days of practice for both PD patients and age-matched controls, further analysis revealed distinct learning processes between the two groups. PD patients initially performed with a slow release velocity and gradually increased it as practice progressed, whereas the control group began with an unnecessarily rapid release velocity, which they later stabilized at a lower value. Performance characteristics related to the timing of ball release and the inter-release interval did not show significant group differences, although they were modulated across practice in both groups. After one week, both groups retained the performance outcomes and underlying kinematics developed over practice. This study underscores the importance of analyzing the multi-faceted learning process to characterize motor skill learning in PD. The findings may provide insights into PD pathophysiology and inform rehabilitation strategies., (© 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).)

Neural underpinnings of Parkinson's disease psychosis remain unclear to this day with relatively few studies and reviews available. Using a systematic review approach, here, we aimed to qualitatively synthesize evidence from studies investigating Parkinson's psychosis-specific alterations in brain structure, function or chemistry using different neuroimaging modalities. PubMed, Web of Science and Embase databases were searched for functional MRI (task-based and resting state), diffusion tensor imaging, PET and single-photon emission computed tomography studies comparing Parkinson's disease psychosis patients with Parkinson's patients without psychosis. We report findings from 29 studies (514 Parkinson's psychosis patients, mean age ± SD = 67.92 ± 4.37 years; 51.36% males; 853 Parkinson's patients, mean age ± SD = 66.75 ± 4.19 years; 55.81% males). Qualitative synthesis revealed widespread patterns of altered brain function across task-based and resting-state functional MRI studies in Parkinson's psychosis patients compared with Parkinson's patients without psychosis. Similarly, white matter abnormalities were reported in parietal, temporal and occipital regions. Hypo-metabolism and reduced dopamine transporter binding were also reported whole brain and in sub-cortical areas. This suggests extensive alterations affecting regions involved in high-order visual processing and attentional networks., Competing Interests: The authors report no competing interests., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Guarantors of Brain.)

Background: There is no conclusive evidence regarding the survival benefits of automated peritoneal dialysis (APD) or the use of icodextrin. This study aimed to evaluate patient and technique survival among four groups divided based on peritoneal dialysis modality and icodextrin use over 1 year., Methods: We specifically included patients who underwent a single peritoneal dialysis modality for at least 1 year during that period (n = 148). The participants were categorized into four groups for comparison: continuous ambulatory peritoneal dialysis (CAPD) without icodextrin (CAPD-ET, n = 39); CAPD with icodextrin (CAPD+ET, n = 35); APD without icodextrin (APD-ET, n = 40); and APD with icodextrin (APD+ET, n = 34)., Results: The CAPD+ET group had a higher patient survival rate than that of the APD-ET group and also had a higher technique survival trend than that of the APD-ET group, despite no statistical significance. In patients without diabetes mellitus (DM), the APD-ET group had a poorer patient survival trend than those of the APD+ET or CAPD+ET groups. In patients without DM, the APD+ET group had a higher technique survival than the APD-ET group. In addition, the APD+ET group showed a higher technique survival trend than did the CAPD-ET group, despite non-statistical significance. The edema index after 1 year of follow-up was higher in the APD-ET group than in the other groups., Conclusion: The present study demonstrated that patients undergoing APD without icodextrin had poor patient and technique survival trends, which may be caused by poor volume control.

Background: Microfocused ultrasound with visualization (MFU-V) is widely used in aesthetic medicine for skin tightening and rejuvenation. However, its role in regenerative aesthetics and its precise mechanism of action are not fully understood., Objective: This narrative review aims to contextualize and articulate the mechanism of action of MFU-V, evaluate its role in regenerative aesthetics, and assess its effectiveness based on existing clinical, histological, and skin-mechanical studies., Methods: A comprehensive literature search was performed to collect and analyze studies on MFU's biological mechanisms, clinical outcomes, and impact on extracellular matrix (ECM) regeneration. The review integrates findings from clinical trials, histological analyses, and biomechanical assessments to provide a cohesive understanding of MFU-V's role in aesthetic medicine., Results: MFU-V emits focused ultrasound energy that penetrates multiple skin layers and the superficial musculoaponeurotic system, creating localized thermal coagulation points. These points initiate biological responses that recruit fibroblasts and stimulate the production of new collagen and elastin fibers. Enhanced ECM protein synthesis leads to significant improvements in skin biomechanics and quality, reducing skin laxity and enhancing appearance. Clinical studies support these findings, showing improvements in skin firmness and texture following MFU-V treatment., Conclusion: Through analyzing the underlying biological mechanisms and the observable clinical outcomes, this narrative review sets the stage for a comprehensive understanding of the mechanism of action and role of MFU-V in regenerative aesthetics., (© 2024 The Author(s). Journal of Cosmetic Dermatology published by Wiley Periodicals LLC.)

Objectives: Cutibacterium acnes is a Gram-positive bacterium commonly found on human skin, particularly in sebaceous areas. While it is typically considered a commensal, specific strain types based on single locus sequence typing (SLST) have been associated with pathogenic conditions or healthy skin. Recently, SLST D1 strains, part of phylotype IA1, have received attention for their potential benefits related to skin health. However, their genetic characteristics remain underexplored. Therefore, the whole genome of C. acnes CN6, an SLST D1 strain isolated from the facial skin of a healthy individual, was sequenced to expand the understanding of SLST D1 strains and identify genomic features that may support skin health., Data Description: The whole genome sequencing of C. acnes CN6 was conducted using MinION reads based on de novo assembly, revealing a single circular complete chromosome. With the length of 2,550,458 bp and G + C content of 60.04%, the genome contains 2,492 genes, including 2,433 CDSs, 9 rRNAs, 46 tRNAs, 4 ncRNAs, and 134 pseudo genes. Previously predicted virulence proteins of C. ances were detected in the genome. Genome comparation with 200 C. acnes strains isolated from healthy facial skin revealed SLST D1 strain-specific genes and a unique variant of the znuC gene in D1 strains., (© 2024. The Author(s).)

Background: Helicobacter pylori changes from spiral to coccoid depending on the host state, environmental factors, and surrounding microbial communities. The coccoid form of H. pylori still maintains its complete cellular structure, retains virulence genes, and thus plays a role in pathogenicity. To understand the coccoid form, it is crucial to establish the in vitro generation of the coccoid H. pylori. Although some conditions have been studied for the generation of the coccoid form, few studies have compared these conditions for coccoid generation. Here, we generated coccoid forms via three methods and compared the differences in morphology, viability, culturability, and protein expression., Results: The coccoid H. pylori was generated in vitro via three methods: a starvation method, a method using amoxicillin, and a method using the culture supernatant of Streptococcus mitis. The morphology and viability of the cells were examined by fluorescence microscopy after staining with SYTO9 and propidium iodide. The culturability of H. pylori was examined by counting colony-forming units on chocolate agar plates. In the starvation group, no colonies formed after 7 days, but viable coccoids were continuously observed. In the amoxicillin-treated group, the culturability decreased rapidly after 12 h, and showed a viable but non culturable (VBNC) state after the third day. Most cells treated with S. mitis supernatant changed to coccoid forms after 7 days, but colonies were continuously formed, probably due to living spiral forms. We performed proteomics to analyse the differences in protein profiles between the spiral and coccoid forms and protein profiles among the coccoid forms generated by the three methods., Conclusion: Amoxicillin treatment changed H. pylori to VBNC cells faster than starvation. Treatment with the S. mitis supernatant prolonged the culturability of H. pylori, suggesting that the S. mitis supernatant may contain substances that support spiral form maintenance. Proteomic analysis revealed that the expression of proteins differed between the spiral form and coccoid form of H. pylori, and this variation was observed among the coccoid forms produced via three different methods. The proteins in the coccoid forms produced by the three methods differed from each other, but common proteins were also observed among them., (© 2024. The Author(s).)

Background: TP53 mutations are associated with poor prognosis in myelodysplastic neoplasm (MDS) and AML. The updated 5th WHO classification and International Consensus Classification (ICC) categorize TP53 -mutated MDS and AML as unique entities. We conducted a multicenter study in Korea to investigate the characteristics of TP53 -mutated MDS and AML, focusing on diagnostic aspects based on updated classifications., Methods: This study included patients aged ≥ 18 yrs who were diagnosed as having MDS (N=1,244) or AML (N=2,115) at six institutions. The results of bone marrow examination, cytogenetic studies, and targeted next-generation sequencing, including TP53 , were collected and analyzed., Results: TP53 mutations were detected in 9.3% and 9.2% of patients with MDS and AML, respectively. Missense mutation was the most common, with hotspot codons R248/R273/G245/Y220/R175/C238 accounting for 25.4% of TP53 mutations. Ten percent of patients had multiple TP53 mutations, and 78.4% had a complex karyotype. The median variant allele frequency (VAF) of TP53 mutations was 41.5%, with a notable difference according to the presence of a complex karyotype. According to the 5th WHO classification and ICC, the multi-hit TP53 mutation criteria were met in 58.6% and 75% of MDS patients, respectively, and the primary determinants were a TP53 VAF >50% for the 5th WHO classification and the presence of a complex karyotype for the ICC., Conclusions: Collectively, we elucidated the molecular genetic characteristics of patients with TP53 -mutated MDS and AML, highlighting key factors in applying TP53 mutation-related criteria in updated classifications, which will aid in establishing diagnostic strategies.

Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne infectious disease caused by the SFTS virus (SFTSV). CP-COV03 is a novel antiviral candidate that significantly enhanced the bioavailability of niclosamide through inorganic-based drug delivery technology. The active pharmaceutical ingredient of CP-COV03, niclosamide, has been previously shown to possess broad-spectrum antiviral activity against over 30 different viruses in the in vitro tests. The aim of this study is to confirm the antiviral activity of CP-COV03 against the SFTSV in an in vitro model. Vero cells and SFTS viral stock NCCP43270, a 2015 Gangwon Province isolate, were used to obtain the 50% tissue culture infective dose of the virus. Vero cells seeded in 96-well plates were infected with SFTSV for 1 h. SFTSV-infected cells were treated with CP-COV03 at various concentrations of 0.1-100 μM and incubated for 7 days. On the seventh day of the culture, the cytopathic effect (CPE) of SFTSV was checked by microscopy and the cell viability was checked by using Cell Counting Kit-8 assay. The CPE reduced as the CP-COV03 concentration increased. The 50% inhibitory concentration (IC 50 ) range of CP-COV03 was below 0.125 µM, as determined from the viral titers of culture supernatants collected on the third day posttreatment of CP-COV03. The plaque reduction assay showed that the IC 50 of CP-COV03 was 1.893 µM, as determined from the percentage reduction of plaque counts for each drug concentration on the second day posttreatment with CP-COV03. This study suggests that CP-COV03 could be used as a potential antiviral agent for SFTS.IMPORTANCEWe demonstrated a concentration-dependent response and identified low a IC 50 of CP-COV03. This result is comparable to other antiviral drugs used against viruses like severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We believe that our study makes a significant contribution to the literature as our findings suggest that CP-COV03 may serve as a potential treatment for SFTS, highlighting its importance in the field of antiviral research., Competing Interests: The authors declare no conflict of interest.

Background: A rapid decline in forced expiratory volume in 1 second (FEV1) is considered an important phenotype of the development of chronic obstructive pulmonary disease (COPD). However, the associations between specific genetic variants (single-nucleotide polymorphisms; SNPs) and this phenotype remain uncertain., Methods: We enrolled 6,516 individuals from the Korean Genome and Epidemiology Study (KoGES). A rapid decline in FEV1 was defined as an annual decrease of FEV1 ≥ 60 mL/year. A multivariable logistic regression model was used to assess the associations between SNP variants and the rapid decline in FEV1. Considering the significant impact of smoking on lung function, a subgroup analysis based on smoking history was also conducted., Results: A genome-wide association analysis of the rapid decline in FEV1 identified 15 association signals ( P < 5.0 × 10 -8 ). Among the 15 nucleotide variants, rs9833533 and rs1496255 have been previously reported to be associated with lung function development. In the subgroup analysis, rs16951883 (adjusted odds ratio [aOR], 3.24; P = 5.87 × 10 -8 ) was the most significant SNP associated with rapid decline in FEV1 among never smokers, followed by rs41476549, rs16840064, and rs1350110. Conversely, among ever smokers, rs10959478 (aOR, 4.74; P = 8.27 × 10 -7 ) showed the highest significance, followed by rs6805861, rs9833533, and rs16906215., Conclusion: We identified 15 nucleotide variants linked to a rapid decline in FEV1, including two SNPs previously reported to be associated with lung function development. Additional SNPs, which were associated with COPD, may be found using novel phenotypes., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

This study employs machine learning models to predict the adsorption characteristics of biochar-activated carbon derived from waste wood. Activated carbon is a high-performance adsorbent utilized in various fields such as air purification, water treatment, energy production, and storage. However, its characteristics vary depending on the activation conditions or raw materials, making explaining or predicting them challenging using physicochemical or mathematical methods. Therefore, using machine learning techniques to determine the adsorption characteristics of activated carbon in advance will provide economic and time benefits for activated carbon production. Datasets, consisting of 108 points, were used to predict the adsorption characteristics of biochar-activated carbon derived from waste wood. The input variables were the activation conditions, and the iodine number of activated carbon was used as the output variable. The datasets were randomly split into 75% for training and 25% for model validation and normalized by the min-max function. Four models, including artificial neural networks, random forests, extreme gradient boosting, and support vector machines, were used to predict the adsorption properties of biochar-activated carbon. After optimization, the artificial neural network model was identified as the best model, with the highest coefficient determination (0.96) and the lowest mean squared error (0.004017). As a result of the SHAP analysis, activation time was the most crucial variable influencing the adsorption properties. The machine learning model precisely predicts the adsorption characteristics of biochar-activated carbon and can optimize the activated carbon production process.

The rich set of mechanoreceptors found in human skin 1,2 offers a versatile engineering interface for transmitting information and eliciting perceptions 3,4 , potentially serving a broad range of applications in patient care 5 and other important industries 6,7 . Targeted multisensory engagement of these afferent units, however, faces persistent challenges, especially for wearable, programmable systems that need to operate adaptively across the body 8-11 . Here we present a miniaturized electromechanical structure that, when combined with skin as an elastic, energy-storing element, supports bistable, self-sensing modes of deformation. Targeting specific classes of mechanoreceptors as the basis for distinct, programmed sensory responses, this haptic unit can deliver both dynamic and static stimuli, directed as either normal or shear forces. Systematic experimental and theoretical studies establish foundational principles and practical criteria for low-energy operation across natural anatomical variations in the mechanical properties of human skin. A wireless, skin-conformable haptic interface, integrating an array of these bistable transducers, serves as a high-density channel capable of rendering input from smartphone-based 3D scanning and inertial sensors. Demonstrations of this system include sensory substitution designed to improve the quality of life for patients with visual and proprioceptive impairments., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background and Purpose: An intracranial vertebral artery dissecting aneurysm (iVADA) increases the risk of future subarachnoid hemorrhage, which is a severe complication with high rebleeding rates and poor outcomes. Identifying potential risk factors associated with iVADA growth is crucial for their effective management., Methods: This observational study was carried out at a single center and included patients who had been diagnosed with iVADA based on neuroimaging findings. We divided the patients into two groups: with and without iVADA growth. Growth was defined as any enlargement of a dilated region or a morphological change in follow-up imaging. We measured the vertebral artery tortuosity index (VTI) in the contralateral vertebral artery (VA), defined as its actual length divided by its straight length. We investigated the factors associated with iVADA growth., Results: This study included 124 patients. The median follow-up period was 7 months. We observed iVADA growth in 54 patients (43.5%), who were more likely to be current smokers (33.3% vs. 14.3%, p =0.012) and have a higher VTI (1.14±0.11 [mean±standard deviation] vs. 1.06±0.12, p =0.035) compared with those without iVADA growth. A multivariate analysis revealed that the VTI (adjusted odds ratio=28.490, 95% confidence interval=1.025-792.046, p =0.048) was independently associated with iVADA growth., Conclusions: This study has identified an independent association between VA tortuosity and iVADA growth., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2024 Korean Neurological Association.)

Aim: This study aimed to adapt and validate the Korean version of the Caregiver Burden Questionnaire for Family Caregivers of Hemodialysis Patients, originally developed by Hejazi et al. in 2022, to ensure its applicability and validity in Korea., Methods: Using both online and offline approaches, this study included 230 family caregivers. Data analysis was performed with SPSS AMOS version 29.0 using the Korean version of the Caregiver Burden Questionnaire for Family Caregivers of Hemodialysis Patients and the Korean version of the Zarit Burden Interview as the primary instruments., Results: The findings confirmed the high content validity of the questionnaire (scale-level content validity index = .99), and confirmatory factor analysis established its construct validity. Convergent validity was confirmed with average variance extracted values ranging from .43 to .87, and composite reliability scores ranging from .80 to .91. A significant positive correlation with the Korean version of the Zarit Burden Interview (r = .81) demonstrated concurrent validity. The tool consists of 21 items across four factors on a 5-point Likert scale, exhibiting excellent internal consistency (Cronbach's α = .91) and good test-retest reliability (intraclass correlation coefficient = .79)., Conclusions: This study validated a reliable instrument for assessing caregiver burden in families of hemodialysis patients in Korea. This tool accurately measures caregiver challenges and has the potential to enhance societal health and welfare., (Copyright © 2024. Published by Elsevier B.V.)

Background: Air pollution, notably particulate matter (PM), significantly impacts chronic respiratory disease such chronic obstructive pulmonary disease (COPD). Although asthma-COPD overlap (ACO), considered one of the COPD etiotype, is associated with greater severity in both symptoms and outcomes, effects of PM exposure remain unclear. Thus, this study aimed to evaluate impact of PM on chronic airway disease animal models., Methods: We established two distinct COPD etiotypes, cigarette smoking-related COPD (COPD-C) and COPD with asthma (COPD-A), using porcine pancreatic elastase (PPE) for COPD-C and a combination of PPE with ovalbumin for COPD-A. To reflect smoking influence, cigarette smoking extract was administered to both disease models. To assess impact of PM exposure, bronchoalveolar lavage fluid (BALF), proinflammatory cytokines, lung histology, and cellular damage mechanisms were analyzed., Results: In the COPD-A model, cell counts and type 2 cytokines were elevated in BALF independent of PM exposure. All models exhibited increased lung inflammation and emphysema due to PM exposure. Expression levels of apoptosis-related protein B-cell lymphoma protein 2 (Bcl-2) associated X (Bax) showed an inclination to increase with PM exposure. In the COPD-A model, decreased expression of basal nuclear factor erythroid-derived 2-like 2 (Nrf-2) and increased production of reactive oxygen species (ROS) due to PM exposure were noted., Conclusion: We developed two distinct models for the etiotypes of COPD and found increased vulnerability to cell damage in COPD-A after PM exposure. Moreover, the control group displayed escalated airway inflammation and emphysema due to PM exposure, substantiating the risk of respiratory diseases., (© 2024. The Author(s).)

Myh1 is a mouse deafness gene with an unknown function in the auditory system. Hearing loss in Myh1-knockout mice is characterized by an elevated threshold for the auditory brainstem response and the absence of a threshold for distortion product otoacoustic emission. Here, we investigated the role of MYH1 in outer hair cells (OHCs), crucial structures in the organ of Corti responsible for regulating cochlear amplification. Direct whole-cell voltage-clamp recordings of OHCs revealed that prestin activity was lower in Myh1-knockout mice than in wild-type mice, indicating abnormal OHC electromotility. We analyzed whole-exome sequencing data from 437 patients with hearing loss of unknown genetic causes and identified biallelic missense variants of MYH1 in five unrelated families. Hearing loss in individuals harboring biallelic MYH1 variants was non-progressive, with an onset ranging from congenital to childhood. Three of five individuals with MYH1 variants displayed osteopenia. Structural prediction by AlphaFold2 followed by molecular dynamic simulations revealed that the identified variants presented structural abnormalities compared with wild-type MYH1. In a heterogeneous overexpression system, MYH1 variants, particularly those in the head domain, abolished MYH1 functions, such as by increasing prestin activity and modulating the membrane traction force. Overall, our findings suggest an essential function of MYH1 in OHCs, as observed in Myh1-deficient mice, and provide genetic evidence linking biallelic MYH1 variants to autosomal recessive hearing loss in humans., (© 2024. The Author(s).)

This study explores the separation and optimization of molybdenum (Mo) from mixed mineral acids derived from semiconductor industry waste streams with tributyl phosphate (TBP) by implementing machine learning (ML) models. Considerable experimental tests were performed to evaluate the impact of various operational variables on the effectiveness of Mo extraction and stripping. The support vector regression (SVR) paired with harmony search algorithm (HSA), genetic algorithm (GA), and shuffled frog leaping algorithm (SFLA) were employed for enhancement in the separation process and structural optimization. The SVR-SFLA model yielded the most meticulous predictions, identifying optimal extraction conditions with a TBP concentration, mixing time, temperature, and O/A ratio of 50%, 30 min, 25 °C, and 1, respectively, achieving 77.8% efficiency. The derived results from the SVR-SFLA model, in tandem with the McCabe-Theil diagram, indicated a four-stage counter-current extraction process required to achieve a yield exceeding 99%. For the stripping process, the hybrid model indicated optimal conditions with 3 M NH 4 OH and an A/O ratio of 0.5 at 50 °C for 20 min, requiring two counter-current stages for nearly complete stripping. Feature importance analysis using a random forest algorithm (RFA) highlighted the NH 4 OH concentration and phase ratio as the most significant factors, contributing 40.3% and 29.1%, respectively, to the stripping from the loaded TBP phase. The final product, obtained after crystallization and thermal decomposition of the strip solutions, was characterized by X-ray diffraction (XRD), thermogravimetric analysis (TGA), scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy (EDS), revealing 99.74% purity for molybdenum trioxide., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

We conducted a self-controlled case series study to investigate the association between COVID-19 vaccination and facial palsy (FP) in South Korea. We used a large immunization registry linked with the national health information database. We included 44,564,345 patients >18 years of age who received >1 dose of COVID-19 vaccine (BNT162b2, mRNA-1273, ChAdOx1 nCoV-19, or Ad.26.COV2.S) and had an FP diagnosis and corticosteroid prescription within 240 days postvaccination. We compared FP incidence in a risk window (days 1-28) with a control window (the remainder of the 240-day observation period, excluding any risk windows). We found 5,211 patients experienced FP within the risk window and 10,531 experienced FP within the control window. FP risk increased within 28 days postvaccination, primarily after first and second doses and was observed for both mRNA and viral vaccines. Clinicians should carefully assess the FP risk-benefit profile associated with the COVID-19 vaccines and monitor neurologic signs after vaccination.

Saxidomus purpurata extract (SPE) is a highly consumable seafood worldwide with known health-related benefits. However, there are no reports of its' anti-obesity effect. This study explores the potential of SPE for anti-obesity effects by modulating adipogenesis and lipolysis. SPE reduced intracellular lipid and triglyceride accumulation while increasing free glycerol release in adipocytes. SPE inhibited lipogenesis protein expressions and increased the phosphorylation of hormone-sensitive lipase and Adenosine monophosphate-activated protein kinase (AMPK) to promote lipolysis. In addition, SPE suppressed adipogenesis by downregulating protein expression of key adipogenic markers, peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer-binding protein α (C/EBPα), and sterol regulatory element-binding protein 1 (SREBP1) via Wnt/β-catenin signaling. SPE augmented the heme oxygenase-1 (HO-1) expression. Thus, pharmacological intervention with Zinc protoporphyrin (ZnPP-HO-1 antagonist) was employed to validate the HO-1 role. The presence of ZnPP increased the lipid accumulation and reduced the free glycerol release. At the molecular level, adipogenic transcription factors (PPARγ, C/EBPα, and SREBP1) expressions were restored in the presence of ZnPP. GC-MS analysis revealed that SPE was comprised of several fatty acids, contributing to its anti-obesity activity. SPE is an effective nutraceutical that can be used to reduce the progression of obesity. HO-1 expression during adipogenesis might be the mechanism of action for the anti-obesity effect of SPE.

Background: Coexistent sarcopenia and frailty is more strongly associated with adverse health outcomes than each condition alone. As the importance of coexistent sarcopenia and frailty increases, exploring their underlying mechanisms is warranted. Recently, noncoding ribonucleic acids (RNAs) have been suggested as potential biomarkers of sarcopenia and frailty. This systematic review aimed to summarize noncoding RNAs commonly expressed in sarcopenia and frailty, and to search the predicted target genes and biological pathways of them., Methods: We systematically searched the literatures on PubMed, Embase, Cochrane Library, Web of Science, and Scopus for literature published till November 15, 2023. A total of 7,202 literatures were initially retrieved. After de-duplication, 34 studies (26 sarcopenia-related and 8 frailty-related) were full-text reviewed, and 15 studies (11 sarcopenia-related and 4 frailty-related) were finally included., Results: miR-29a-3p, miR-29b-3p, and miR-328 were identified as commonly expressed in same direction in sarcopenia and frailty. These microRNAs (miRNAs), identified in the literature search using PubMed, modulate transforming growth factor-β signaling via extracellular matrix components and calcineurin/nuclear factor of activated T cells 3 signaling via sarcoplasmic/endoplasmic reticulum Ca 2+ ATPase 2a, which are involved in regulating skeletal muscle fibrosis and the growth of slow-twitch muscle fibers, respectively. miR-155-5p, miR-486, and miR-23a-3p were also commonly expressed in two conditions, although in different or conflicting directions., Conclusion: In this systematic review, we highlight the potential of shared miRNAs that exhibit consistent expression patterns as biomarkers for the early diagnosis and progression assessment of both sarcopenia and frailty., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Multiple myeloma (MM) is an incurable hematologic cancer that originates from plasma cells and occurs primarily in patients over 60. The prognosis of MM has improved after the introduction of new treatments, such as thalidomide, bortezomib, and lenalidomide. However, in recurrent and refractory MM patients, factors such as age and drug toxicity are important when choosing treatment options. Because of this, the demand for novel, low-toxicity drugs is increasing. This study demonstrated that KBB-N1, an ultra-low molecular weight ginsenoside compound K, effectively treated MM by increasing the expression of phosphorylated p53. Given its minimal toxicity to hematopoietic stem cells and major organs, KBB-N1 is a promising new drug for treating MM in older patients., Competing Interests: Declaration of Competing Interest Myung Geun Shin is the founder and CEO of KBlueBio Inc. This study did not receive financial or non-financial support from KBlueBio Inc. and was conducted purely as a research and development study., (Copyright © 2024. Published by Elsevier Masson SAS.)

Objective: Intracerebral hemorrhage (ICH) accompanies higher mortality rates than other type of stroke. This study aimed to investigate the association between hospital volume and mortality for cases of ICH., Methods: We used nationwide data from 2013 to 2018 to compare high-volume hospitals (≥32 admissions/year) and low-volume hospitals (<32 admissions/year). We tracked patients' survival at 3-month, 1-year, 2-year, and 4-year endpoints. The survival of ICH patients was analyzed at 3-month, 1-year, 2-year, and 4-year endpoints using Kaplan-Meier survival analysis. Multivariable logistic regression analysis and Cox regression analysis were performed to determine predictive factors of poor outcomes at discharge and death., Results: Among 9086 ICH patients who admitted to hospital during 18-month period, 6756 (74.4%) and 2330 (25.6%) patients were admitted to high-volume and low-volume hospitals. The mortality of total ICH patients was 18.25%, 23.87%, 27.88%, and 35.74% at the 3-month, 1-year, 2-year, and 4-year, respectively. In multivariate logistic analysis, high-volume hospitals had lower poor functional outcome at discharge than low-volume hospitals (odds ratio, 0.80; 95% confidence interval, 0.72-0.91; p<0.001). In the Cox analysis, high-volume hospitals had significantly lower 3-month, 1-year, 2-year, and 4-year mortality than low-volume hospitals (p<0.05)., Conclusion: The poor outcome at discharge, short- and long-term mortality in ICH patients differed according to hospital volume. High-volume hospitals showed lower rates of mortality for ICH patients, particularly those with severe clinical status.

Introduction: Preparing appropriate red blood cells (RBCs) before surgery is crucial for improving both the efficacy of perioperative workflow and patient safety. In particular, thoracic surgery (TS) is a procedure that requires massive transfusion with high variability for each patient. Hence, the precise prediction of RBC requirements for individual patients is becoming increasingly important. This study aimed to 1) develop and validate a machine learning algorithm for personalized RBC predictions for TS patients and 2) assess the usability of a clinical decision support system (CDSS) integrating this artificial intelligence model., Methods: Adult patients who underwent TS between January 2016 and October 2021 were included in this study. Multiple models were developed by employing both traditional statistical- and machine-learning approaches. The primary outcome evaluated the model's performance in predicting RBC requirements through root mean square error and adjusted R 2 . Surgeons and informaticians determined the precision MSBOS-Thoracic Surgery (pMSBOS-TS) algorithm through a consensus process. The usability of the pMSBOS-TS was assessed using the System Usability Scale (SUS) survey with 60 clinicians., Results: We identified 7,843 cases (6,200 for training and 1,643 for test sets) of TSs. Among the models with variable performance indices, the extreme gradient boosting model was selected as the pMSBOS-TS algorithm. The pMSBOS-TS model showed statistically significant lower root mean square error (mean: 3.203 and 95% confidence interval [CI]: 3.186-3.220) compared to the calculated Maximum Surgical Blood Ordering Schedule (MSBOS) and a higher adjusted R 2 (mean: 0.399 and 95% CI: 0.395-0.403) compared to the calculated MSBOS, while requiring approximately 200 fewer packs for RBC preparation compared to the calculated MSBOS. The SUS score of the pMSBOS-TS CDSS was 72.5 points, indicating good acceptability., Conclusions: We successfully developed the pMSBOS-TS capable of predicting personalized RBC transfusion requirements for perioperative patients undergoing TS., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [Financial support for this study was provided entirely by a grant from the Ministry of Health & Welfare, Republic of Korea. The funding agreement ensured the authors’ independence in designing the study, interpreting the data, writing, and publishing the report.]., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: To investigate the highest opportunity skin puncture point and needle orientation according to facial asymmetry and classification., Methods: Computed tomography of 136 patients was analyzed. Horizontal and vertical angles and distances from the canthal-tragal line were investigated to determine the puncture point and needle's angle., Result: All patients' average points were 7.39 (±2.85) mm anterior to the tragus and 3.44 (±4.18) mm below the canthal-tragal line with an angle of 8.53 (±6.90)° anteriorly and 32.26 (±7.23)° superiorly. Regarding asymmetry, there was a statistical difference in horizontal angle, depth, and canthal-tragal distance between the deviated and non-deviated sides. Especially, vertical distances were 4.44 (±4.66) mm and 2.59 (±4.11) mm in the deviated and non-deviated sides, respectively ( p < 0.001)., Conclusion: In closed-mouth, the puncture point was closer to the tragus and lower than the conventional point. The point in the deviated side should be considered lower than the non-deviated side.

Background: The primary aim of this proof-of-concept study was to investigate whether the Cardiac Power Index (CPI) could be a novel alternative method to assess fluid responsiveness in the prone position., Methods: Patients undergoing scheduled elective lumbar spine surgery in the prone position under general anesthesia were enrolled in the criteria of patients aged 19-75 years with American Society of Anesthesiologists (ASA) physical status I-II. The hemodynamic variables were evaluated before and after changes in posture after administering a colloid bolus (5 mL.kg -1 ) in the prone position. Fluid responsiveness was defined as an increase in the Stroke Volume Index (SVI) ≥ 10%., Results: A total of 28 patients were enrolled. In responders, the CPI (median [1/4Q-3/4Q]) decreased to 0.34 [0.28-0.39] W.m -2 (p = 0.035) after the prone position. After following fluid loading, CPI increased to 0.48 [0.37-0.52] W.m -2 (p < 0.008), and decreased SVI (median [1/4Q-3/4Q]) after prone increased from 26.0 [24.5-28.0] mL.m -2 to 33.0 [31.0-37.5] mL.m -2 (p = 0.014). Among non-responders, CPI decreased to 0.43 [0.28-0.53] W.m -2 (p = 0.011), and SVI decreased to 29.0 [23.5-34.8] mL.m -2 (p < 0.009). CPI exhibited predictive capabilities for fluid responsiveness as a receiver operating characteristic curve of 0.78 [95% Confidence Interval, 0.60-0.95; p = 0.025]., Conclusion: This study suggests the potential of CPI as an alternative method to existing preload indices in assessing fluid responsiveness in clinical scenarios, offering potential benefits for responders and non-responders., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 Sociedade Brasileira de Anestesiologia. Published by Elsevier España S.L.U. All rights reserved.)

Background: Critical limb ischemia (CLI) is a condition characterized by insufficient blood flow to the lower limbs, resulting in severe ischemia and potentially leading to amputation. This study aims to identify novel vasculogenic precursor cells (VPCs) in human bone marrow and evaluate their efficacy in combination with bone marrow-derived mesenchymal stem cells (BM-MSCs) for the treatment of CLI., Methods: Ex vivo cultured VPCs and BM-MSCs from bone marrow were characterized and their effects on neovascularization and long-term tissue regeneration were tested in a mouse CLI model., Results: VPCs, expressing high levels of hepatocyte growth factor and c-MET, were identified from human bone marrow aspirates. These cells exhibited strong vasculogenic capacity in vitro but possessed a cellular phenotype distinct from those of previously reported endothelial precursor cells in circulation or cord blood. They also expressed most surface markers of BM-MSCs and demonstrated multipotent differentiation ability. Screening of 376 surface markers revealed that VPCs uniquely display CD141 (thrombomodulin). CD141 + VPCs are present in BM aspirates as a rare population and can be expanded ex vivo with a population doubling time of approximately 20 h, generating an elaborate vascular network even under angiogenic factor-deficient conditions and recruiting BM-MSCs to the network as pericyte-like cells. Intramuscular transplantation of a combination of human CD141 + VPCs and BM-MSCs at a ratio of 2:1 resulted in limb salvage, blood flow recovery, and regeneration of large vessels in the femoral artery-removed CLI model, with an efficacy superior to that of singular transplantation. Importantly, large arteries and arterioles in dual cell transplantation expressed human CD31 in the intima and human α-smooth muscle actin in media layer at 4 and 12 weeks, likely indicating their lineage commitment to endothelial cells and vascular smooth muscle, respectively, in vivo., Conclusion: Dual-cell therapy using BM-derived CD141 + VPCs and BM-MSCs holds potential for further development in clinical trials to treat peripheral artery disease and diabetic ulcers., (© 2024. The Author(s).)