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Jeeyoung Kim,1 Bharathi Suresh,2 Myoung Nam Lim,1 Seok-Ho Hong,3 Kye-Seong Kim,2,4 Ha Eun Song,5 Hyo Yeong Lee,5 Hyun Ju Yoo,5 Woo Jin Kim1 1Department of Internal Medicine and Environmental Health Center, Kangwon National University Hospital, Kangwon National University School of Medicine, Chuncheon, Korea; 2Graduate School of Biomedical Science and Engineering, Hanyang University, Seoul, South Korea; 3Department of Internal Medicine, School of Medicine, Kangwon National University, Chuncheon, South Korea; 4College of Medicine, Hanyang University, Seoul, South Korea; 5Department of Convergence Medicine, Asan Medical Center, Asan Medical Institute of Convergence Science and Technology, University of Ulsan College of Medicine, Seoul, South KoreaCorrespondence: Hyun Ju Yoo, Department of Convergence Medicine, Asan Institute for Life Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul, 05505, Korea, Tel +82-2-3010-4029, Fax +82-2-3010-8566, Email yoohyunju@amc.seoul.kr Woo Jin Kim, Department of Internal Medicine, Kangwon National University School of Medicine, 1 Gangwondaehak-gil, Chuncheon, 24341, Korea, Tel +82-33-258-9364, Fax +82-33-258-2404, Email pulmo2@kangwon.ac.krPurpose: Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease presenting as multiple phenotypes, such as declining lung function, emphysema, or persistent airflow limitation caused by several risk factors, including cigarette smoking and air pollution. The inherent complexity of COPD phenotypes propounds difficulties for accurate diagnosis and prognosis. Although metabolomic profiles on COPD have been reported, the role of metabolism in COPD-related phenotypes is yet to be determined. In this study, we investigated the association between plasma sphingolipids and amino acids, and between COPD and COPD-related phenotypes in a Korean cohort.Patients and Methods: Blood samples were collected from 120 patients with COPD and 80 control participants who underwent spirometry and quantitative computed tomography. The plasma metabolic profiling was carried out using LC-MS/MS analysis.Results: Among the evaluated plasma sphingolipids, an increase in the metabolism of two specific sphingomyelins, SM (d18:1/24:0) and SM (d18:1/24:1) were significantly associated with COPD. There was no significant correlation between any of the SMs and the emphysema index, FVC and FEV1 in the COPD cohort. Meanwhile, Cer (d18:1/18:0) and Cer (d18:1/24:1) were significantly associated with reduced FEV1. Furthermore, the levels of several amino acids were altered in the COPD group compared to that in the non-COPD group; glutamate and alpha AAA were substantial associated with emphysema in COPD. Kynurenine was the only amino acid significantly associated with reduced FEV1 in COPD. In contrast, there was no correlation between FVC and the elevated metabolites.Conclusion: Our results provide dysregulated plasma metabolites impacting COPD phenotypes, although more studies are needed to explore the underlying mechanism related to COPD pathogenesis.Keywords: targeted sphingolipids, amino acids, sub-phenotypes, lung function

The purpose of the study was to evaluate theMR imaging features that differentiate between low-grade chondrosarcoma (LGCS) and high-grade chondrosarcoma (HGCS) and to determine the most reliable predictors for differentiation. MR images of 42 pathologically proven chondrosarcomas (28 LGCS and 14 HGCS) were retrospectively reviewed. There were 13 male and 29 female patients with an age range of 23–72 years (average age 51 years). On MR images, signal intensity, specific morphological characteristics including entrapped fat, internal lobular architecture, and outer lobular margin, soft tissue mass formation and contrast enhancement pattern were analysed. MR imaging features used to identify LGCS and HGCS were compared using univariate analysis and multivariate stepwise logistic regression analysis. On T1-weighted images, a central area of high signal intensity, which was not seen in LGCS, was frequently observed in HGCS (n = 5, 36%) (p<0.01). Entrapped fat within the tumour was commonly seen in LGCS (n = 26, 93%), but not in HGCS (n = 1, 4%) (p<0.01). LGCS more commonly (n = 24, 86%) preserved the characteristic internal lobular structures within the tumour than HGCSs (n = 4, 29%) (p<0.01). Soft tissue formation was more frequently observed in HGCS (n = 11, 79%) than in LGCS (n = 1, 4%) (p<0.01). On gadolinium-enhanced images, large central nonenhancing areas were exhibited in only two (7.1%) of LGCS, while HGCS frequently (n = 9, 64%) had a central nonenhancing portion (p<0.01). Results of multivariate stepwise logistic regression analysis showed that soft tissue formation and entrapped fat within the tumour were the variables that could be used to independently differentiate LGCS from HGCS. There were several MR imaging features of chondrosarcoma that could be helpful in distinguishing HGCS from LGCS.Among them, soft tissue mass formation favoured the diagnosis of HGCS, and entrapped fat within the tumour was highly indicative of LGCS. [ABSTRACT FROM AUTHOR]

Objective: Ectrodactyly is a rare malformation with various presentations. The current report describes a case of ectrodactyly detected using 2-dimensional (2D) and 3-dimensional (3D) ultrasonography at 16 weeks' gestation. Methods and Results: The 2D ultrasonographic findings were ectrodactyly in the right hand and monodactyly in the left hand, and these results were confirmed and further clarified using 3D imaging. The postmortem X-ray findings were consistent with the ultrasonography. Conclusion: We conclude that 3D ultrasonography can assist in clarifying 2D ultrasonography findings of hand malformations during the second trimester of pregnancy. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: Vascular malformations involving the mandible and maxilla are uncommon, and no uniform treatment of these lesions has been defined. The purpose of the study was to evaluate the effectiveness of treating vascular malformations with a multidisciplinary approach and emphasis on endovascular therapy.Study Design: Retrospective chart review of patients.Methods: The treatment of 31 patients (13 male and 18 female patients) with mandibular and/or maxillary vascular malformations presenting between 1979 to 2001 was reviewed.Results: Thirteen patients (42%) presented with mandibular vascular malformations, and an equal number of patients had maxillary vascular malformations. Five patients had involvement of both the mandible and maxilla. Twenty-six patients (84%) had adjacent soft tissue extension, whereas five patients had a vascular malformation isolated either to the mandible (four cases) or maxilla (one case). Twenty-six cases consisted of arterial vascular malformations, and five patients had venous and capillary types. Twenty-five patients (81%) were treated with embolization only, whereas six patients (19%) underwent combined embolization and surgical resection. "Cure" was defined as the complete eradication of disease or permanent resolution of symptoms with complete devascularization by embolization. The cure rates were 70% for mandibular malformations and 46% for maxillary lesions. None of the combined maxillary/mandibular lesions were cured, but all achieved improvement or stabilization of symptoms. The follow-up range was 1 to 22 years with an average follow-up of 6.7 years.Conclusion: The location and extent of vascular malformations dictate the treatment and resulting success. Endovascular therapy alone can effectively "cure" most mandibular and maxillary vascular malformations with limited soft tissue involvement. Extensive vascular malformations can be stabilized with control of symptoms, but eradication of the vascular malformation is unlikely even with combined surgery and embolization. [ABSTRACT FROM AUTHOR]

Objective: We examined prevalence of sarcopenia in Korean patients with type 2 diabetes and compared body compositional parameters between subjects with and without type 2 diabetes.Research Design and Methods: The Korean Sarcopenic Obesity Study (KSOS) included 810 subjects (414 patients with diabetes and 396 control subjects) who were examined using dual-energy X-ray absorptiometry. Prevalence of sarcopenia was defined using the skeletal muscle index (SMI).Results: Prevalence in patients with diabetes and in the control group was 15.7 and 6.9%, respectively. In both men and women, SMI values were significantly decreased in patients with diabetes compared with subjects without diabetes. Furthermore, multiple logistic regression analysis showed that type 2 diabetes was independently associated with sarcopenia.Conclusions: Type 2 diabetes was associated with increased risk of sarcopenia. These characteristics may contribute to physical disability and metabolic disorders in older adults with diabetes. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effectiveness of ovarian transposition procedures in preserving ovarian function in relation to the location of the transposed ovaries in patients who underwent surgery with or without pelvic radiotherapy. Design: Retrospective. Setting: Uterine cancer center. Patient(s): A total of 53 patients with cervical cancer who underwent ovarian transposition between November 2002 and November 2010. Intervention(s): Ovarian transposition to the paracolic gutters with or without radical hysterectomy and lymph node dissection. Main Outcome Measure(s): Preservation of ovarian function, which was assessed by patient's symptoms and serum FSH level. Result(s): Lateral ovarian transposition was performed in 53 patients. Based on receiver operator characteristic curve analysis, optimum cutoff value of location more than 1.5 cm above the iliac crest was significantly associated with preservation of ovarian function after treatment (area under receiver operator characteristic curve: 0.757, 95% confidence interval [CI]: 0.572-0.943). In univariate analysis, higher location of transposed ovary more than 1.5 cm from the iliac crest was the only independent factor for intact ovarian function (odds ratio 9.91, 95% CI: 1.75-56.3). Multivariate analysis confirmed that the location of transposed ovary (odds ratio 11.72, 95% CI 1.64-83.39) was the most important factor for intact ovarian function. Conclusion(s): Location of transposed ovary higher than 1.5 cm above the iliac crest is recommended to avoid ovarian failure after lateral ovarian transposition after primary or adjuvant pelvic radiotherapy in cervical cancer. [ABSTRACT FROM AUTHOR]

This study investigated the potential of 2'-Fucosyllactose (2'-FL) and galactooligosaccharides (GOS) combinations as a novel and cost-effective substitute for human milk oligosaccharides (HMOs) in promoting gut health and reducing inflammation. In vitro studies using Caco-2 cells showed that 2'-FL and GOS combinations (H1: GOS:2'-FL ratio of 1.8:1; H2: ratio of 3.6:1) reduced lipopolysaccharide-induced inflammation by decreasing pro-inflammatory markers, while individual treatments had no significant effects. In a mouse model of dextran sulfate sodium (DSS)-induced colitis, combined 2'-FL and GOS supplementation alleviated symptoms, improved gut permeability, and enhanced intestinal structure, with the GH1 group (H1 combo with DSS) being the most effective. 2'-FL and GOS combinations also enhanced short-chain fatty acid production in infant fecal batch fermentation and mouse fecal analysis, with GH1 showing the most promising results. GH1 supplementation altered gut microbiota in mice with DSS-induced colitis, promoting microbial diversity and a more balanced Firmicutes to Bacteroidota ratio. Infant formula products (IFPs) containing 2'-FL and GOS combinations (IFP2: 174 mg GOS and 95 mg 2'-FL per 14 g serving, 1.8:1 ratio; IFP3: 174 mg GOS and 48 mg 2'-FL per 14 g serving, 3.6:1 ratio) demonstrated gastrointestinal protective and anti-inflammatory properties in a coculture model of Caco-2 and THP-1 cells. These findings suggest that 2'-FL and GOS combinations have potential applications in advanced infant formulas and supplements to promote gut health and reduce inflammation., (© 2024, The Authors. Published by Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).)

Background: Sarcopenia is an age-related progressive loss of muscle mass and function. Sarcopenia is a multifactorial disorder, including metabolic disturbance; therefore, metabolites may be used as circulating biomarkers for sarcopenia. We aimed to investigate potential biomarkers of sarcopenia using metabolomics., Methods: After non-targeted metabolome profiling of plasma from mice of an aging mouse model of sarcopenia, sphingolipid metabolites and muscle cells from the animal model were evaluated using targeted metabolome profiling. The associations between sphingolipid metabolites identified from mouse and cell studies and sarcopenia status were assessed in men in an age-matched discovery (72 cases and 72 controls) and validation (36 cases and 128 controls) cohort; women with sarcopenia (36 cases and 36 controls) were also included as a discovery cohort., Results: Both non-targeted and targeted metabolome profiling in the experimental studies showed an association between sphingolipid metabolites, including ceramides (CERs) and sphingomyelins (SMs), and sarcopenia. Plasma SM (16:0), CER (24:1), and SM (24:1) levels in men with sarcopenia were significantly higher in the discovery cohort than in the controls (all P < 0.05). There were no significant differences in plasma sphingolipid levels for women with or without sarcopenia. In men in the discovery cohort, an area under the receiver-operating characteristic curve (AUROC) of SM (16:0) for low muscle strength and low muscle mass was 0.600 (95% confidence interval [CI]: 0.501-0.699) and 0.647 (95% CI: 0.557-0.737). The AUROC (95% CI) of CER (24:1) and SM (24:1) for low muscle mass in men was 0.669 (95% CI: 0.581-0.757) and 0.670 (95% CI: 0.582-0.759), respectively. Using a regression equation combining CER (24:1) and SM (16:0) levels, a sphingolipid (SphL) score was calculated; an AUROC of the SphL score for sarcopenia was 0.712 (95% CI: 0.626-0.798). The addition of the SphL score to HGS significantly improved the AUC from 0.646 (95% CI: 0.575-0.717; HGS only) to 0.751 (95% CI: 0.671-0.831, P = 0.002; HGS + SphL) in the discovery cohort. The predictive ability of the SphL score for sarcopenia was confirmed in the validation cohort (AUROC = 0.695, 95% CI: 0.591-0.799)., Conclusions: SM (16:0), reflecting low muscle strength, and CER (24:1) and SM (16:0), reflecting low muscle mass, are potential circulating biomarkers for sarcopenia in men. Further research on sphingolipid metabolites is required to confirm these results and provide additional insights into the metabolomic changes relevant to the pathogenesis and diagnosis of sarcopenia., (© 2024 The Author(s). Journal of Cachexia, Sarcopenia and Muscle published by Wiley Periodicals LLC.)

Background: Collaborative learning is an educational method widely used in nursing education that involves learners solving problems through teamwork. This study investigated the effects of using a metaverse virtual space for collaborative learning among nursing students., Method: A nonequivalent control group posttest design was used, and focus group interviews were conducted. This mixed-methods study included second-year nursing students ( n = 43) divided into two groups. The intervention group used metaverse methods for the group projects and the control group used traditional methods., Results: Satisfaction with collaborative learning and peer evaluation of team projects were significantly higher in the intervention group compared with the control group. Participants' learning experiences were categorized into "unwelcome changes in the learning environment," "discovering the potential of a learning environment that encourages participation," and "tips for building a metaverse learning environment.", Conclusion: Metaverse collaborative learning is a student-centered educational approach that fosters active interaction and addresses the shortcomings of traditional approaches. [ J Nurs Educ . 2024;63(9):585-593.] .

Aim: To evaluate the efficacy and safety of gemigliptin and dapagliflozin dual add-on therapy (GEMI + DAPA) to metformin in type 2 diabetes (T2D) patients who had inadequate glycaemic control on metformin alone, compared with a single add-on of either gemigliptin (GEMI) or dapagliflozin (DAPA) to metformin., Materials and Methods: In this randomized, double-blind, double-dummy, active-controlled, parallel-group, phase 3 study, 469 T2D patients treated with a stable dose of metformin for 8 weeks or longer were randomized to receive GEMI + DAPA (n = 157) and either GEMI (n = 156) or DAPA (n = 156). The primary endpoint was change in HbA1c levels from baseline at week 24., Results: Baseline characteristics including body mass index and T2D duration were similar among groups. At week 24, the least square mean changes in HbA1c from baseline were -1.34% with GEMI + DAPA, -0.90% with GEMI (difference between GEMI + DAPA vs. GEMI -0.44% [95% confidence interval {CI}: -0.58% to -0.31%], P < .01) and -0.78% with DAPA (difference between GEMI + DAPA vs. DAPA -0.56% [95% CI: -0.69% to -0.42%], P < .01). Both upper CIs were less than 0, demonstrating the superiority of GEMI + DAPA for lowering HbA1c. The rates of responders achieving HbA1c less than 7% and less than 6.5% were greater with GEMI + DAPA (84.9%, 56.6%) than with GEMI (55.3%, 32.2%) and DAPA (49.3%, 15.3%). The incidence rate of adverse events was similar across groups, with low incidence rates of hypoglycaemia, urinary tract infection and genital infection., Conclusions: These results suggest that the addition of GEMI + DAPA to metformin as triple combination therapy was effective, safe and well-tolerated, especially for T2D patients who experienced poor glycaemic control on metformin alone., (© 2024 John Wiley & Sons Ltd.)

Advanced glycation end products (AGEs) are important contributors to the progression of chronic kidney diseases (CKD), including renal fibrosis. Although the relationship between AGEs and renal fibrosis has been well studied, the mechanisms of individual AGE-induced renal injury remain poorly understood. This study investigated the adverse effect of methylglyoxal-derived hydroimidazolone-1 (MG-H1), a methylglyoxal (MG)-derived AGE generated by the glycation of MG and arginine residues, on kidney damage. We aimed to elucidate the molecular mechanisms of MG-H1-mediated renal injury and fibrosis, focusing on the receptor for AGEs (RAGE) signaling and its effects on the Wnt/β-catenin pathway, MAPK pathway, and inflammatory responses. Our results suggest that the MG-H1/RAGE axis plays a significant role in the pathogenesis of CKD and its downstream events involving MAPK kinase-related factors and inflammatory factors. MG-H1 treatment modulated the expression of inflammatory cytokines (TNF-α, IL-6, and IL-1β) and MAPK proteins (ERK1/2, JNK, and p38)., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kwang-Won Lee reports a relationship with Korea University that includes: employment. If there are other authors, they 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 B.V. All rights reserved.)

Background: Mounting evidence indicates the importance of the interplay between skeletal muscles and lipid metabolism. Remnant cholesterol (remnant-C) is considered one of the principal residual risk factors for cardiovascular disease and metabolic disorders; however, there are limited studies on the impact of remnant-C on sarcopenia., Methods: Data from the Korea National Health and Nutrition Examination Surveys (KNHANES) between 2008 and 2011 were used in this nationwide population-based study. In total, 17,408 participants were enrolled in this study. The subjects were categorized into four groups according to the quartile of remnant-C values. We conducted multivariable logistic regression analysis to evaluate the association between remnant-C and muscle mass measured using dual-energy X-ray absorptiometry., Results: A total of 1,791 participants (10.3%) presented low muscle mass, and there was a sequential increase in the percentage of low muscle mass across remnant-C quartiles (Q1, 5.2%; Q2, 8.7%; Q3, 11.5%; Q4, 15.7%). In the full adjusted model, those in the highest remnant-C quartile group showed significantly increased odds ratio (OR) for low muscle mass compared with those in the lowest remnant-C group after adjusting for various confounding factors (OR = 1.33, 95% confidence interval (CI) = 1.06-1.68, P < 0.05). A wide range of subgroups and sensitivity analyses showed consistent results, supporting the robustness of our findings., Conclusions: Increased remnant-C value was associated with a high risk of low muscle mass in the Korean population. Remnant-C may be a novel marker for the prediction and management of sarcopenia in aging societies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Jang, Hwang, Jang, Kim, Yu, Kim, Yoo, Kim, Baik and Choi.)

Our previous study suggested that the Mono-ADP ribosylhydrolase 2 ( MACROD2 ) rs6110695 A>G polymorphism is significantly associated with white blood cell (WBC) count in the Korean population. The present study aimed to evaluate the clinical relevance of the MACROD2 rs6110695 A>G polymorphism for predicting WBC count by utilizing plasma metabolites and a single-nucleotide polymorphism (SNP). Two groups were characterized by MACROD2 rs6110695 A>G SNP genotypes among 139 healthy subjects based on the genetic information provided in our previous work: rs6110695 AA genotype group ( n = 129) and rs6110695 AG genotype group ( n = 10). Plasma global metabolic profiling was performed using ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). To estimate the predictive abilities of WBC count models using the rs6110695 genotype and/or significant differential metabolites, multiple linear regression analysis and receiver operating characteristic (ROC) curve analysis were conducted. The AG genotype had greater WBC-to-apolipoprotein (apo) A-I ratios; counts of WBCs, lymphocytes, monocytes, and granulocytes; monocyte-to-lymphocyte ratio (MLR); and monocyte-to-platelet ratio (MPR) than the AA genotype. In terms of metabolic profile, indoleacetic acid, and butyrylcarnitine levels were considerably distinct between the two groups, and these metabolites were considered to be meaningful prognostic variables for the rs6110695 genotype. Finally, ROC curve analysis demonstrated that the model containing the rs6110695 genotype and the two main metabolites was reliable. The present study revealed that individuals carrying the rs6110695 AG genotype with high plasma indoleacrylic acid and butyrylcarnitine levels might have elevated WBC counts. The rs6110695 genotype and the concentrations of indoleacrylic acid and butyrylcarnitine could contribute to reducing the risk of chronic diseases in the future.

Background: Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined., Methods: This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months., Conclusion: This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.

Background: The surplus cytokines remaining after use in the early stages of the inflammatory response stimulate immune cells even after the response is over, causing a secondary inflammatory response and ultimately damaging the host, which is called a cytokine storm. Inhibiting heat shock protein 90 (Hsp90), which has recently been shown to play an important role in regulating inflammation in various cell types, may help control excessive inflammatory responses and cytokine storms., Methods: We discovered an anti-inflammatory compound by measuring the inhibitory effect of CD86 expression on spleen DCs (sDCs) using the chemical compounds library of Hsp90 inhibitors. Subsequently, to select the hit compound, the production of cytokines and expression of surface molecules were measured on the bone marrow-derived DCs (BMDCs) and peritoneal macrophages. Then, we analyzed the response of antigen-specific Th1 cells. Finally, we confirmed the effect of the compound using acute lung injury (ALI) and delayed-type hypersensitivity (DTH) models., Results: We identified Be01 as the hit compound, which reduced CD86 expression the most in sDCs. Treatment with Be01 decreased the production of pro-inflammatory cytokines (IL-6, TNF-α, and IL-1β) in BMDC and peritoneal macrophages stimulated by LPS. Under the DTH model, Be01 treatment reduced ear swelling and pro-inflammatory cytokines in the spleen. Similarly, Be01 treatment in the ALI model decreased neutrophil infiltration and lower levels of secreted cytokines (IL-6, TNF-α)., Conclusions: Reduction of CD80 and CD86 expression on DCs by Be01 indicates reduced secondary inflammatory response by Th1 cells, and reduced release of pro-inflammatory cytokines by peritoneal macrophages may initially control the cytokine storm., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: To prevent the infection from spreading, patients who were dying from COVID-19 were treated in isolation with restricted family access, which differed from existing end-of-life care procedures. This was a significant change that affected the care provided by nurses., Objectives: This study explored nurses' end-of-life care experiences in a limited family visitation setting during the COVID-19 pandemic., Methods: A descriptive qualitative study was conducted. Data were collected through individual, in-depth, semistructured interviews with ten critical care nurses who provided end-of-life care to patients with COVID-19 in South Korea. The data were analysed using thematic analysis. The Consolidated Criteria for Reporting Qualitative Research checklist was used to assess the study's rigour., Findings: Three themes were identified: 'Witnessing patients' and families' heartbreak over separation', 'The gaps between the ideals and realities of end-of-life care', and 'Efforts to provide patients with a comfortable final journey'. Nurses realise the importance of their central role in supporting interactions between patients and families during end-of-life care., Conclusions: Family participation, facilitated by nurses' interest and efforts as mediators connecting patients and families, is essential for achieving high-quality care for inpatients facing end of life. This study is significant as it emphasises that the direction of end-of-life care should be family centric, even in a pandemic situation with limited family participation. To improve interaction between patients and families, creating an environment based on family participation that builds trust and strengthens communication is essential. Additionally, hospital support, such as professional education and counselling, should be provided to strengthen nurses' end-of-life care competency., Competing Interests: Conflict of 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 manuscript., (Copyright © 2024 Australian College of Critical Care Nurses Ltd. Published by Elsevier Ltd. All rights reserved.)

Background: No standard treatment guidelines have been established for postpartum hemorrhage (PPH). We aimed to assess the differences in outcomes and prognoses between patients with PPH who underwent surgical and non-surgical treatment., Methods: This retrospective study included 230 patients diagnosed with PPH at two referral hospitals between August 2013 and October 2023. The patients were divided into non-surgical (group 1, n = 159) and surgical intervention groups (group 2, n = 71). A subgroup analysis was performed by dividing the surgical intervention group into immediate (n = 45) and delayed surgical intervention groups (n = 26)., Results: Initial lactic acid levels and shock index were significantly higher in group 2 (2.85 ± 1.37 vs. 4.54 ± 3.63 mmol/L, p = 0.001, and 0.83 ± 0.26 vs. 1.10 ± 0.51, p < 0.001, respectively). Conversely, initial heart rate and body temperature were significantly lower in group 2 (92.5 ± 21.0 vs. 109.0 ± 28.1 beat/min, p < 0.001, and 37.3 ± 0.8 °C vs. 37.0 ± 0.9 °C, p = 0.011, respectively). Logistic regression analysis identified low initial body temperature, high lactic acid level, and shock index as independent predictors of surgical intervention (p = 0.029, p = 0.027, and p = 0.049, respectively). Regarding the causes of PPH, tone was significantly more prevalent in group 1 (57.2% vs. 35.2%, p = 0.002), whereas trauma was significantly more prevalent in group 2 (24.5% vs. 39.4%, p = 0.030). Group 2 had worse overall outcomes and prognoses than group 1. The subgroup analysis showed significantly higher rates of uterine atony combined with other causes, hysterectomy, and disseminated intravascular coagulopathy in the delayed surgical intervention group than the immediate surgical intervention group (42.2% vs. 69.2%, p = 0.027; 51.1% vs. 73.1%, p = 0.049; and 17.8% vs. 46.2%, p = 0.018, respectively)., Conclusions: Patients with PPH presenting with increased lactic acid levels and shock index and decreased body temperature may be surgical candidates. Additionally, immediate surgical intervention in patients with uterine atony combined with other causes of PPH could improve prognosis and reduce postoperative complications., (© 2024. The Author(s).)

Aim: To assess basic data for developing appropriate interventions by examining the effects of patient-centered care (PCC) on the mental health of patients with heart failure in the intensive care unit (ICU)., Background: Patients with heart failure are frequently admitted to ICUs, and ICU stays are associated with prolonged mental health problems., Methods: We conducted a systematic review using the CINAHL, Cochrane Library, Embase, MEDLINE, PsycINFO, and gray literature databases. Inclusion criteria were studies with participants aged ≥18 years with heart failure in the ICU who received a PCC intervention, and studies that described the outcomes for mental health problems. Data were extracted from five selected studies published after 2020 and analyzed., Results: PCC is classified into three areas: comprehensive nursing, multidisciplinary disease management, and targeted motivational interviewing with conventional nursing. The two specific areas of focus for PCC regarding mental health were integrated mental healthcare and specific psychological nursing. Specific psychological nursing comprised relationship building, therapeutic communication, relaxation and motivational techniques, active therapeutic cooperation, psychological status evaluation, music therapy, and environmental management., Conclusions: This review provides a distinctive understanding of multidisciplinary and multicomponent PCC interventions for patients with heart failure in the ICU as an effective approach for improving their mental health. Future PCC intervention strategies aimed at patients with heart failure in the ICU should consider their preferences and family participation., Competing Interests: Declaration of competing interest None., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aims: To evaluate the long-term safety and efficacy of enavogliflozin monotherapy (0.3 mg/day) in individuals with type 2 diabetes mellitus (T2DM)., Materials and Methods: Following a 24-week randomized, double-blind treatment period with enavogliflozin 0.3 mg/day (n = 77) or placebo (n = 69), consenting participants received enavogliflozin 0.3 mg/day for an additional 28 weeks during an open-label extension (OLE) period. The safety and efficacy of enavogliflozin were assessed at Week 52., Results: A total of 37 participants continued enavogliflozin (maintenance group), and 26 participants switched from placebo to enavogliflozin (switch group). No additional adverse drug reactions related to enavogliflozin were observed during the OLE period. At Week 52, glycated haemoglobin (HbA1c) and fasting plasma glucose were significantly lower than at the baseline, by 0.9% and 24.9 mg/dL, respectively, in the maintenance group (p < 0.0001 for both), and by 0.7% and 18.0 mg/dL, respectively, in the switch group (p < 0.0001 and p = 0.002). The proportions of participants reaching HbA1c 7.0% (53 mmol/mol) at Week 52 were 69.4% in the maintenance group and 65.4% in the switch group. A significant increase in urine glucose-to-creatinine ratio was observed at Week 52, by 84.9 g/g and 67.1 g/g in the maintenance and switch groups, respectively (p < 0.0001 for both). Body weight in both groups decreased significantly (p < 0.0001) from baseline to Week 52, by 3.5 kg and 3.8 kg in the maintenance and switch groups, respectively., Conclusions: Enavogliflozin 0.3 mg monotherapy provides long-term glycaemic control in T2DM and is safe and well tolerated during a 52-week treatment period., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Background: The fatty infiltration and atrophy in the muscle after a rotator cuff (RC) tear are important in surgical decision-making and are linked to poor clinical outcomes after rotator cuff repair. An accurate and reliable quantitative method should be developed to assess the entire RC muscles., Purpose: To develop a fully automated approach based on a deep neural network to segment RC muscles from clinical magnetic resonance imaging (MRI) scans., Material and Methods: In total, 94 shoulder MRI scans (mean age = 62.3 years) were utilized for the training and internal validation datasets, while an additional 20 MRI scans (mean age = 62.6 years) were collected from another institution for external validation. An orthopedic surgeon and a radiologist manually segmented muscles and bones as reference masks. Segmentation performance was evaluated using the Dice score, sensitivities, precision, and percent difference in muscle volume (%). In addition, the segmentation performance was assessed based on sex, age, and the presence of a RC tendon tear., Results: The average Dice score, sensitivities, precision, and percentage difference in muscle volume of the developed algorithm were 0.920, 0.933, 0.912, and 4.58%, respectively, in external validation. There was no difference in the prediction of shoulder muscles, with the exception of teres minor, where significant prediction errors were observed (0.831, 0.854, 0.835, and 10.88%, respectively). The segmentation performance of the algorithm was generally unaffected by age, sex, and the presence of RC tears., Conclusion: We developed a fully automated deep neural network for RC muscle and bone segmentation with excellent performance from clinical MRI scans., Competing Interests: Declaration of conflicting interestsThe authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: SHY is the Chief Medical Officer of MEDICAL IP, Co. Ltd.; SJP is the CEO of MEDICAL IP, Co. Ltd.

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

Purpose: Despite the importance of self-monitoring blood glucose (SMBG) for management of diabetes mellitus (DM), frequent blood sampling is discouraged by bleeding risk due to dual-antiplatelet agent therapy (DAPT) or thrombocytopenia., Methods: We compared the bleeding time (BT) of sampling by using a laser-lancing-device (LMT-1000) and a conventional lancet in patients with DM and thrombocytopenia or patients undergoing DAPT. BT was measured using the Duke method, and pain and satisfaction scores were assessed using numeric rating scale (NRS) and visual analog scale (VAS). The consistency in the values of glucose and glycated-hemoglobin (HbA1c) sampled using the LMT-1000 or lancet were compared., Results: The BT of sampling with the LMT-1000 was shorter than that with the lancet in patients with thrombocytopenia (60s vs. 85s, P = 0.024). The NRS was lower and the VAS was higher in laser-applied-sampling than lancet-applied sampling in the DAPT-user group (NRS: 1 vs. 2, P = 0.010; VAS: 7 vs. 6, P = 0.003), whereas the group with thrombocytopenia only showed improvement in the VAS score (8 vs. 7, P = 0.049). Glucose and HbA1c sampled by the LMT-1000 and lancet were significantly correlated in both the DAPT-user and the thrombocytopenia groups., Conclusion: The LMT-1000 can promote SMBG by shortening BT in subject with thrombocytopenia and by increasing satisfaction score, as well as by showing reliable glucose and HbA1c value., (© 2024. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

X-linked adrenoleukodystrophy (ALD), an inherited neurometabolic disorder caused by mutations in ABCD1, which encodes the peroxisomal ABC transporter, mainly affects the brain, spinal cord, adrenal glands, and testes. In ALD patients, very-long-chain fatty acids (VLCFAs) fail to enter the peroxisome and undergo subsequent β-oxidation, resulting in their accumulation in the body. It has not been tested whether in vivo base editing or prime editing can be harnessed to ameliorate ALD. We developed a humanized mouse model of ALD by inserting a human cDNA containing the pathogenic variant into the mouse Abcd1 locus. The humanized ALD model showed increased levels of VLCFAs. To correct the mutation, we tested both base editing and prime editing and found that base editing using ABE8e(V106W) could correct the mutation in patient-derived fibroblasts at an efficiency of 7.4%. Adeno-associated virus (AAV)-mediated systemic delivery of NG-ABE8e(V106W) enabled robust correction of the pathogenic variant in the mouse brain (correction efficiency: ∼5.5%), spinal cord (∼5.1%), and adrenal gland (∼2%), leading to a significant reduction in the plasma levels of C26:0/C22:0. This established humanized mouse model and the successful correction of the pathogenic variant using a base editor serve as a significant step toward treating human ALD disease., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.)

Aim: Short tandem repeats (STRs) are repetitive DNA sequences and highly mutable in various human disorders. While the involvement of STRs in various genetic disorders has been extensively studied, their role in autism spectrum disorder (ASD) remains largely unexplored. In this study, we aimed to investigate genetic association of STR expansions with ASD using whole genome sequencing (WGS) and identify risk loci associated with ASD phenotypes., Methods: We analyzed WGS data of 634 ASD families and performed genome-wide evaluation for 12,929 STR loci. We found rare STR expansions that exceeded normal repeat lengths in autism cases compared to unaffected controls. By integrating single cell RNA and ATAC sequencing datasets of human postmortem brains, we prioritized STR loci in genes specifically expressed in cortical development stages. A deep learning method was used to predict functionality of ASD-associated STR loci., Results: In ASD cases, rare STR expansions predominantly occurred in early cortical layer-specific genes involved in neurodevelopment, highlighting the cellular specificity of STR-associated genes in ASD risk. Leveraging deep learning prediction models, we demonstrated that these STR expansions disrupted the regulatory activity of enhancers and promoters, suggesting a potential mechanism through which they contribute to ASD pathogenesis. We found that individuals with ASD-associated STR expansions exhibited more severe ASD phenotypes and diminished adaptability compared to non-carriers., Conclusion: Short tandem repeat expansions in cortical layer-specific genes are associated with ASD and could potentially be a risk genetic factor for ASD. Our study is the first to show evidence of STR expansion associated with ASD in an under-investigated population., (© 2024 The Authors. Psychiatry and Clinical Neurosciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Psychiatry and Neurology.)

Aim: To compare the image quality of virtual noncontrast (VNC) and true noncontrast (TNC) CT images and to evaluate the clinical feasibility of VNC CT images for assessing osteochondral lesions of the talus (OLTs)., Materials and Methods: Forty-five OLT patients who underwent ankle CT arthrography (CTA) using dual-layer spectral detector CT were enrolled. Reconstruction of VNC and three-dimensional volume rendering images was performed. Afterward, image noise, the signal-to-noise ratio (SNR), and the contrast-to-noise ratio (CNR) were measured. For the subjective evaluation, two board-certified musculoskeletal radiologists [R2-1] assessed spatial resolution, overall image quality, and lesion conspicuity. The accuracy rate for OLT grading was determined in 23 patients who underwent arthroscopic surgery., Results: While VNC images showed significantly less noise than TNC images, TNC images showed better SNRs and CNRs (p<.01). In the subjective analysis, TNC images showed better overall image quality (p<.001). For the 3D volume rendering images, VNC images scored significantly higher for lesion conspicuity (p<.001). The accuracy rates of CTA and CTA with VNC images for OLT grading were 79.2% and 83.3%, respectively. Regarding confidence level, when CTA and VNC images were evaluated together, the confidence level was significantly higher than that when only CTA images were evaluated (p<.001)., Conclusion: VNC imaging can provide better confidence level of OLT grading and evaluation of the integrity of the subchondral bone plate when combined with conventional CTA without additional radiation dose to the patient. In addition, VNC images-based 3D volume rendering reconstruction would be helpful for preoperative planning in OLT patients., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Menopause, a dramatical estrogen-deficient condition, is considered the most significant milestone in women's health., Purpose: To investigate the metabolite changes attributed to estrogen deficiency using random forest (RF)-based machine learning (ML) modeling strategy in ovariectomized (OVX) mice as well as determine the clinical relevance of selected metabolites in older women., Methods and Results: Untargeted and targeted metabolomic analyses revealed that metabolites related to TCA cycle, sphingolipids, phospholipids, fatty acids, and amino acids, were significantly changed in the plasma and/or muscle of OVX mice. Subsequent ML classifiers based on RF algorithm selected alpha-ketoglutarate (AKG), arginine, carnosine, ceramide C24, phosphatidylcholine (PC) aa C36:6, and PC ae C42:3 in plasma as well as PC aa 34:1, PC aa C34:3, PC aa C36:5, PC aa C32:1, PC aa C36:2, and sphingosine in muscle as top featured metabolites that differentiate the OVX mice from the sham-operated group. When circulating levels of AKG, arginine, and carnosine, which showed the most significant changes in OVX mice blood, were measured in postmenopausal women, higher plasma AKG levels were associated with lower bone mass, weak grip strength, poor physical performance, and increased frailty risk., Conclusions: Metabolomics- and ML-based methods identified the key metabolites of blood and muscle that were significantly changed after ovariectomy in mice, and the clinical implication of several metabolites was investigated by looking at their correlation with body composition and frailty-related parameters in postmenopausal women. These findings provide crucial context for understanding the diverse physiological alterations caused by estrogen deficiency in women., (© 2024. The Author(s), under exclusive licence to Italian Society of Endocrinology (SIE).)

With advances in artificial intelligence, machine learning (ML) has been widely applied to predict functional outcomes in clinical medicine. However, there has been no attempt to predict walking ability after spinal cord injury (SCI) based on ML. In this situation, the main purpose of this study was to predict gait recovery after SCI at discharge from an acute rehabilitation facility using various ML algorithms. In addition, we explored important variables that were related to the prognosis. Finally, we attempted to suggest an ML-based decision support system (DSS) for predicting gait recovery after SCI. Data were collected retrospectively from patients with SCI admitted to an acute rehabilitation facility between June 2008 to December 2021. Linear regression analysis and ML algorithms (random forest [RF], decision tree [DT], and support vector machine) were used to predict the functional ambulation category at the time of discharge (FAC&#95;DC) in patients with traumatic or non-traumatic SCI (n = 353). The independent variables were age, sex, duration of acute care and rehabilitation, comorbidities, neurological information entered into the International Standards for Neurological Classification of SCI worksheet, and somatosensory-evoked potentials at the time of admission to the acute rehabilitation facility. In addition, the importance of variables and DT-based DSS for FAC&#95;DC was analyzed. As a result, RF and DT accurately predicted the FAC&#95;DC measured by the root mean squared error. The root mean squared error of RF and the DT were 1.09 and 1.24 for all participants, 1.20 and 1.06 for those with trauma, and 1.12 and 1.03 for those with non-trauma, respectively. In the analysis of important variables, the initial FAC was found to be the most influential factor in all groups. In addition, we could provide a simple DSS based on strong predictors such as the initial FAC, American Spinal Injury Association Impairment Scale grades, and neurological level of injury. In conclusion, we provide that ML can accurately predict gait recovery after SCI for the first time. By focusing on important variables and DSS, we can guide early prognosis and establish personalized rehabilitation strategies in acute rehabilitation hospitals., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Posterior femoral condylar osteophytes were frequently observed in patients with the ultra-congruent (UC) deep-dish design prosthesis. Therefore, the purpose of the present study was to verify the clinical relevance of osteophyte formation in the UC design., Methods: From March 2014 to February 2018, a comparative study was conducted on 96 knees using the UC design. They were divided into 2 groups (group 1: osteophyte +, group 2: osteophyte -). Intraoperative findings, indirect femoral rollback assessment using 30° flexion and active full flexion lateral radiographs, serial change of the osteophyte, and outcomes were compared., Results: The mean follow-up period was 49.35 ± 3.47 months in group 1 and 47.52 ± 3.37 months in group 2. Posterior component coverage was significantly different between the groups: group 1 exhibited more underhang and group 2 exhibited more overhang ( p = 0.022). On the indirect assessment of the femoral rollback, there was a statistically significant difference in deep flexion and change in distance ( p < 0.001 and p < 0.001, respectively). There was no statistical difference between the 2 groups in the American Knee Society knee and function score, and group 2 showed significant improvement in pain compared to group 1 in Western Ontario and McMaster University Arthritis Index pain score ( p = 0.029)., Conclusions: Posterior condylar osteophyte formation was related to posterior impingement. It was more frequently observed in the underhang of the femoral component and insufficient femoral rollback. In addition, it changed with time and caused negative effects, including a gradual decrease in flexion and more pain., Competing Interests: CONFLICT OF INTEREST: No potential conflict of interest relevant to this article was reported., (Copyright © 2024 by The Korean Orthopaedic Association.)

Aim: To investigate the efficacy and safety of pioglitazone compared to placebo when added to metformin plus dapagliflozin, a sodium-glucose cotransporter-2 (SGLT2) inhibitor, for patients with type 2 diabetes mellitus (T2DM)., Materials and Methods: In a multicentre study, with a randomized, double-blind, placebo-controlled design, 249 Korean patients with T2DM suboptimally managed on metformin and dapagliflozin were assigned to receive either pioglitazone (15 mg daily) or placebo for 24 weeks, followed by a 24-week pioglitazone extension. Primary outcomes included changes in glycated haemoglobin (HbA1c), with secondary outcomes assessing insulin resistance, adiponectin levels, lipid profiles, liver enzymes, body weight and waist circumference., Results: Pioglitazone administration resulted in a significant reduction in HbA1c levels (from 7.80% ± 0.72% to 7.27% ± 0.82%) compared with placebo (from 7.79% ± 0.76% to 7.69% ± 0.86%, corrected mean difference: -0.42% ± 0.08%; p < 0.01) at 24 weeks. Additional benefits from pioglitazone treatment included enhanced insulin sensitivity, increased adiponectin levels, raised high-density lipoprotein cholesterol levels and reduced liver enzyme levels, resulting in improvement in nonalcoholic fatty liver disease liver fat score. Despite no serious adverse events in either group, pioglitazone therapy was modestly but significantly associated with weight gain and increased waist circumference., Conclusions: Adjunctive pioglitazone treatment in T2DM inadequately controlled with metformin and dapagliflozin demonstrates considerable glycaemic improvement, metabolic benefits, and a low risk of hypoglycaemia. These advantages must be weighed against the potential for weight gain and increased waist circumference., (© 2024 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Objectives: To identify nurses' caring behaviours toward patients with left ventricular assist devices and deepen their understanding of experiences in nursing care. Patients with left ventricular assist devices require care in many aspects, but there is limited in-depth research about caring behaviours and experiences from the perspective of nurses providing care., Research Methodology/design: Mixed methods study with a sequential explanatory design. Data were collected from clinical nurses with experience caring for patients using left ventricular assist devices in South Korea between May-August 2022., Main Outcome Measures: Quantitative data (n = 79) were collected through an online survey of the Caring Behaviours Inventory - 24 and analysed using descriptive statistics. For qualitative data (n = 15), nurses' caring experiences were collected through individual interviews and analysed using Colaizzi's phenomenological method., Results: The overall average of caring behaviours was 4.80 ± 0.85, specifically, 'knowledge and skill' (5.04 ± 0.78), 'assurance' (5.01 ± 0.79), 'respect' (4.85 ± 0.90), and 'connectedness' (4.04 ± 0.99), respectively. The experience of caring was trapped in the uncomfortable reality of left ventricular assist device nursing, causing device-focused care, and approaching the essence of nursing through care focused on the patient's wholeness., Conclusions: Caring for patients with a left ventricular assist devices was challenging for nurses. However, through the care process, they realised the meaning of patient-centred care, reflected in the essence of nursing, and sublimated it into an opportunity to grow., Implications for Clinical Practice: Nurses must focus on patient-centred care for left ventricular assist devices. To achieve this, it is essential to create a clinical environment and educational system for nurses to provide effective nursing care and enhance patient participation., 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.)