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Chai Young Lee,1,&ast; Sun Hye Shin,1,&ast; Hye Sook Choi,2 Yunjoo Im,1 Bo-Guen Kim,1 Ju Yeun Song,1 Daegeun Lee,1 Hye Yun Park,1 Jun Hyeok Lim3 1Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; 2Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Kyung Hee University Hospital, Seoul, Republic of Korea; 3Division of Pulmonology, Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon, Republic of Korea&ast;These authors contributed equally to this workCorrespondence: Hye Yun Park, Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea, Tel +82-2-3410-3429, Fax +82-2-3410-3849, Email hyeyunpark@skku.edu Jun Hyeok Lim, Division of Pulmonology, Department of Internal Medicine, Inha University Hospital, Inha University School of Medicine, Incheon, Republic of Korea, Tel +82-32-890-1038, Fax +82-32-890-3099, Email jhl@Inha.ac.krPurpose: Vitamin D insufficiency or deficiency is prevalent in patients with chronic obstructive pulmonary disease (COPD). However, the association between vitamin D levels and respiratory symptoms in patients with stable COPD has not been fully investigated. This study evaluated the association between vitamin D levels and respiratory symptoms in patients with stable COPD.Patients and Methods: Patients with COPD who had their serum 25-hydroxyvitamin D (25-OH vitamin D) level measured within 6 months of spirometry between January 2016 and April 2020 were retrospectively included. Respiratory symptoms were assessed using the modified Medical Research Council (mMRC) scale and COPD assessment test (CAT) score.Results: Of the 329 included patients, 193, 88, and 48 were categorized as having vitamin D deficiency (< 20 ng/mL), insufficiency (20– 29 ng/mL), and sufficiency (≥ 30 ng/mL), respectively. The mean serum 25-OH vitamin D level of each group was 13.45 ng/mL, 24.61 ng/mL, and 38.90 ng/mL, respectively. Patients with vitamin D insufficiency/deficiency showed higher CAT scores than those with vitamin D sufficiency (p = 0.004). In multivariable adjusted models, vitamin D insufficiency/deficiency was significantly associated with a CAT score of 10 or more (adjusted odds ratio [aOR] = 2.41, 95% confidence interval [CI] = 1.20– 4.82, p = 0.013) and mMRC ≥ 2 (aOR = 2.39, 95% CI = 1.08– 5.32, p = 0.032). Among CAT items, the amount of phlegm (p = 0.008), chest tightness (p = 0.030), breathlessness walking upstairs (p < 0.001), home activity limitations (p = 0.002), and lack of energy (p = 0.003) were significantly associated with vitamin D insufficiency/deficiency after adjustment for age, sex, body mass index, smoking history, Charlson comorbidity index, post-bronchodilator forced expiratory volume in 1 second, and season of blood draw.Conclusion: Vitamin D insufficiency/deficiency were associated with worse respiratory symptoms in patients with stable COPD.Keywords: chronic obstructive pulmonary disease, vitamin D, respiratory symptoms, COPD assessment test, modified Medical Research Council

Hyun-Il Gil,1,* Sungmin Zo,2,* Paul W Jones,3,4 Bo-Guen Kim,2 Noeul Kang,2 Yeonseok Choi,5 Hyun Kyu Cho,6 Danbee Kang,7 Juhee Cho,7 Hye Yun Park,2 Sun Hye Shin2 1Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; 2Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; 3Institute For Infection and Immunity, St George’s University of London, London, UK; 4Value Evidence and Outcomes, Global Medical R&D, GlaxoSmithKline, Uxbridge, UK; 5Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Kyung Hee University School of Medicine, Seoul, Republic of Korea; 6Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon, Republic of Korea; 7Samsung Advanced Institute for Health Sciences & Technology (SAIHST), Sungkyunkwan University, Seoul, Republic of Korea*These authors contributed equally to this workCorrespondence: Sun Hye Shin; Hye Yun ParkDivision of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of KoreaTel +82-2-3410-3429Fax +82-2-3410-3849Email freshsunhye@gmail.com; hyeyunpark@skku.eduPurpose: The chronic obstructive pulmonary disease (COPD) assessment test (CAT) is widely used to assess the impact of COPD symptoms on health status. Whilst the CAT consists of eight different items, details on the distribution of each item are limited. This study aimed to investigate the distribution and clinical implication of each CAT item, stratified by CAT severity group, in stable COPD patients.Patients and Methods: This was a cross-sectional study at a single referral hospital in South Korea. Spirometry confirmed COPD patients with CAT measured at the first clinical visit were retrospectively identified. Patients were categorized into three groups: low (0 ≤ CAT < 10), medium (10 ≤ CAT < 20), and high (20 ≤ CAT ≤ 40) impact group. For the purpose of this analysis, the first four items (cough, sputum, chest tightness, and dyspnea) and the remaining four items (activities, confidence, sleep and energy) were also grouped as “pulmonary” and “extra-pulmonary”, respectively.Results: A total of 815 patients were included, and mean (SD) forced expiratory volume in 1 s (FEV1) was 62.8 (17.4) % pred. Among them, 300 patients (36.8%) were in the high impact group and had a greater exacerbation history and lower lung function. The proportion of “extra-pulmonary” items score was greater in patients with higher total CAT scores, with the activity and confidence items showing higher scores.Conclusion: In our study, in addition to dyspnea, activity limitation is a particular problem in individual patients with higher CAT total scores, for which physicians need to pay more attention. Our study suggests that whilst CAT total score captures the overall impact of COPD, each item of the CAT contains potentially useful information in understanding the patient’s symptom burden.Keywords: COPD, COPD assessment test, patient reported outcome, symptom

We present a hybrid method for spectral reflectivity recovery, using 3D extrapolation as a supplemental method for 3D interpolation. The proposed 3D extrapolation is an extended version of 3D interpolation based on the barycentric algorithm. It is faster and more accurate than the conventional spectral-recovery techniques of principal-component analysis and nonnegative matrix transformation. Four different extrapolation techniques (based on nearest neighbors, circumcenters, in-centers, and centroids) are formulated and applied to recover spectral reflectivity. Under the standard conditions of a D65 illuminant and 1964 10° observer, all reflectivity data from 1269 Munsell color chips are successfully reconstructed. The superiority of the proposed method is demonstrated using statistical data to compare coefficients of correlation and determination. The proposed hybrid method can be applied for fast and accurate spectral reflectivity recovery in image processing.

Hwa-young Lee,1 Bong-Min Yang,1 Ji-min Hong,1 Tae-Jin Lee,1 Byoung-Gie Kim,2 Jae-Weon Kim,3 Young-Tae Kim,4 Yong-Man Kim,5 Sokbom Kang61Graduate School of Public Health, Seoul National University, Seoul, South Korea; 2Department of Obstetrics and Gynecology, Samsung Medical Center, Seoul, South Korea; 3Department of Obstetrics and Gynecology, Seoul National University, Seoul, South Korea; 4Department of Obstetrics and Gynecology, Yonsei University, Seoul, South Korea; 5Department of Obstetrics and Gynecology, University of Ulsan, Ulsan, South Korea; 6Department of Obstetrics and Gynecology, National Cancer Center, Kyeonggi-do, South KoreaObjective: We performed a cost–utility analysis to assess the cost-effectiveness of a chemotherapy sequence including a combination of polyethylene glycolated liposomal doxorubicin (PLD)/carboplatin versus paclitaxel/carboplatin as a second-line treatment in women with platinum-sensitive ovarian cancer.Methods: A Markov model was constructed with a 10-year time horizon. The treatment sequence consisted of first- to sixth-line chemotherapies and best supportive care (BSC) before death. Cycle length, a time interval for efficacy evaluation of chemotherapy, was 9 weeks. The model consisted of four health states: responsive, progressive, clinical remission, and death. At any given time, a patient may have remained on a current therapy or made a transition to the next therapy or death. Median time to progressions and overall survivals data were obtained through a systematic literature review and were pooled using a meta-analytical approach. If unavailable, this was elicited from an expert panel (eg, BSC). These outcomes were converted to transition probabilities using an appropriate formula. Direct costs included drug-acquisition costs for chemotherapies, premedication, adverse-event treatment and monitoring, efficacy evaluation, BSC, drug administration, and follow-up tests during remission. Indirect costs were transportation expenses. Utilities were also derived from the literature. Costs and utilities were discounted at an annual rate of 5% per cycle.Results: PLD/carboplatin combination as the second line in the sequence is more effective and costly than paclitaxel/carboplatin combination, showing an additional US$21,658 per quality-adjusted life years. This result was robust in a deterministic sensitivity analysis except when median time to progression of second-line therapies and administration cost of PLD/carboplatin per administration cycle were varied. The probability of cost-effectiveness for PLD/carboplatin combination was 49.4% at a willingness to pay $20,000.Conclusion: A PLD/carboplatin combination is an economically valuable option as second-line chemotherapy for the treatment of platinum-sensitive ovarian cancer in South Korea.Keywords: cost, utility, Markov modeling, ovarian cancer, chemotherapy

Thi Hoan Le1,2, Ellinor Ottosson3, Thi Kim Chuc Nguyen4, Bao Giang Kim5, Peter Allebeck11Department of Public Health Sciences, Karolinska Institute, Stockholm, Sweden; 2Department of Environmental Health, Hanoi Medical University, Hanoi, Vietnam; 3Department of Medicine, Gothenburg University, Gothenburg, Sweden; 4Department of Family Medicine, Hanoi Medical University, Hanoi, Vietnam; 5Department of Health Education, Hanoi Medical University, Hanoi, VietnamAims: To explore the knowledge, attitudes, and behaviors of parents in their use of drugs for respiratory illness or diarrhea among children under 5 years of age, and to understand factors influencing self-medication.Methods: A qualitative study was conducted, using in-depth interviews with two drug sellers and three health care providers, and four focus-group discussions with mothers of children under 5 years of age. Verbatim transcriptions were analyzed, and emerging themes and categories identified, using content analysis.Results: Use of a number of different drugs was reported, including broad-spectrum antibiotics and corticosteroids. There was poor awareness of side-effects, antibiotic resistance, and drug efficacy. Factors influencing self-medication were perceptions of the illness in the child, waiting time, and convenience, the attitudes of public health medical staff, insufficient drug supply in public health facilities, and poor control of prescribed drugs on the market.Conclusion: Misuse and misconceptions regarding drug use gave rise to considerable problems. Mothers' knowledge and attitudes to illness and health care services played an important role in determining the nature of self-medication. Financial barriers were not the only obstacle to adequate treatment. Health services should be more accessible and responsive to the needs of the population.Keywords: health services, parental attitudes, education

Background/aims: Although access to [18F]2-fluoro-2-deoxyglucose (18F-FDG) positron emission tomography and computed axial tomography (PET/CT) for patients with malignancy has increased, little information is available on the suitability of PET/CT for diagnosis of advanced colonic neoplasms in oncology patients and on the clinical significance of incidental 18F-FDG focal uptake confined to the left-sided colon.Methods: Patients who underwent 18F-FDG PET/CT followed, within 90 days, by colonoscopy were identified. Case-control analysis was undertaken to determine whether focal 18F-FDG uptake confined to the left-sided colon was associated with advanced neoplasms in the right-sided colon.Results: One hundred ninety-five patients with colonic 18F-FDG uptake and 561 without colonic (18)F-FDG uptake were identified. Of the 195 patients with focal colonic 18F-FDG activity, 103 patients (52.8%) had 145 advanced colonic neoplasms, including 58 colon cancers and 11 metastatic cancers. In the detection of advanced colonic neoplasms, the sensitivity, specificity, positive predictive value, and negative predictive value of PET/CT were 54.4, 82.4, 46.9, and 86.3%, respectively. Overall accuracy was 76.2%. Ten (8.0%) of the 125 patients with focal 18F-FDG uptake confined to the left-sided colon had three colon cancers and seven advanced adenomas in the right-sided colon. Case-control analysis revealed that focal 18F-FDG uptake confined to the left-sided colon was associated with an advanced neoplasms in the right-sided colon (OR, 3.02; 95% CI, 1.12-8.13; P = 0.023).Conclusions: Colonic focal (18)F-FDG uptake by oncology patients warrants endoscopic verification. Complete colon evaluation by colonoscopy is required, even for patients with focal 18F-FDG uptake confined to the left-sided colon. [ABSTRACT FROM AUTHOR]

STUDY DESIGN.: Both sequestrated nucleus pulposus (SNP) and the remaining nucleus pulposus (RNP) were studied from the discs of the same patient to evaluate apoptosis using immunohistochemical staining. OBJECTIVE.: To compare apoptosis of the SNP and the RNP in the disc of the same patient. SUMMARY OF BACKGROUND DATA.: Many studies have been conducted on the natural history and apoptosis of the herniated nucleus pulposus; however, apoptosis of the remaining nucleus cells, after removal of the sequestrated disc, in the same patient, has not been reported. MATERIALS AND METHODS.: Eight samples of SNP and RNP from the disc of the same patient were obtained. The TUNEL stain was performed to confirm the occurrence of apoptosis in disc cells. Immunohistochemistry staining and Western blot analysis were performed to determine the presence of proteins, including caspase-3,-8,-9, and Bid. RESULTS.: TUNEL-positive chondrocytes were identified in all of the SNP and RNP samples; the apoptotic index was 5.8 ± 1.9% and 5.9 ± 1.2%, respectively (P = 0.60). Caspase-3,-8,-9, and Bid were expressed in the SNP and the RNP of the cytoplasm and the nucleus by the immunohistochemical staining. The expression of active caspase-3,-8,-9, and Bid in the RNP of the disc and the SNP was different in each patient. CONCLUSION.: The frequency of chondrocyte apoptosis in the SNP and the RNP was not different in the disc. The pathways involved in chondrocyte apoptosis of the SNP and the RNP differed among individuals and included intrinsic and/or extrinsic pathways. [ABSTRACT FROM AUTHOR]

This study investigates changes in autonomic nervous function through Qi-training. The power spectrum of heart rate variability (HRV) was examined in 20 sedentary healthy subjects and 20 Qi-trainees. It was found that Qi-training in healthy young subjects during controlled respiration increases the high frequency (HF) power and decreases the low frequency/high frequency (LF/HF) power ratio of HRV. These results support the hypothesis that Qi-training increases cardiac parasympathetic tone. In addition, Qi-trainees were found to have higher parasympathetic heart modulation compared with their age-matched, sedentary counterparts. This augmented HRV in Qi-trainees provides further support for long-term Qi-training as a possible non-pharmacological cardio-protective maneuver. In conclusion, Qi-training may stabilize the autonomic nervous system by modulating the parasympathetic nervous system. [ABSTRACT FROM AUTHOR]

The prediction of response to treatment would be valuable for managing cervical carcinoma with neoadjuvant chemotherapy.~Background~Background~To this end, the expression of VEGF was analyzed by immunohistochemistry using paraffin-embedded pre-treatment cervical biopsy tissues. This study included 29 patients with bulky IB to IIA cervical squamous cell carcinoma treated with neoadjuvant chemotherapy.~Methods~Methods~Fifteen (51.7%) of 29 patients were scored as VEGF-positive. Response to chemotherapy (complete response or residual tumor with less than 3 mm stromal invasion) was observed in eight patients (27.6%), and it was negatively associated with VEGF expression (P = 0.009). With logistic regression analysis, VEGF positivity continued to be an independent predictor for poor response (P = 0.032). In addition, the progression-free survival rate was significantly lower in patients with VEGF-positive tumors (P = 0.033).~Results~Results~Pretreatment assessment of VEGF expression may provide additional information for identification of patients with cervical cancer who had a low likelihood of response to neoadjuvant chemotherapy and an unfavorable prognosis.~Conclusion~Conclusions [ABSTRACT FROM AUTHOR]

OBJECTIVE: To estimate and analyse the costs for providing the expanded programme on immunization (EPI) in a rural community in the north of Viet Nam in 2005. METHODS: An ingredient approach was used to collect cost data from the perspective of the service providers. FINDINGS: The total annual cost of EPI in Bavi district was US$58,460 [purchasing power parity (PPP) 282,076]. Vaccines and supplies were the largest cost category (33%), followed by personnel costs (30.2%). The largest share of the total cost was due to activities at commune level (38%). The average cost per fully vaccinated child (FVC) was US$4.81 (PPP 23.21), much lower than the figure of US$15 that is generally accepted as the cost-effective threshold for EPI in developing countries. CONCLUSION: This empirical study indicates that EPI has been implemented efficiently in rural Viet Nam, but that opportunities exist to make it even more efficient. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the incidence, clinical characteristics, and risk factors of pelvic insufficiency fracture (PIF) after pelvic radiotherapy (RT) in cervical cancer.Methods and Materials: Medical records and imaging studies, including bone scintigraphy, CT, and MRI of 557 patients with cervical cancer who received whole-pelvic RT between January 1998 and August 2005 were reviewed.Results: Eighty-three patients were diagnosed as having PIF after pelvic RT. The 5-year cumulative incidence of PIF was 19.7%. The most commonly involved site was the sacroiliac joint. Pelvic pain developed in 48 patients (57.8%) at diagnosis. Eleven patients (13.3%) needed admission or narcotics because of severe pain, and others had good relief of symptoms with conservative management. In univariate analysis, age>or=55 years (p<0.001), anteroposterior/posteroanterior parallel opposing technique (p=0.001), curative treatment (p<0.001), and radiation dose>or=50.4 Gy (p=0.005) were the predisposing factors for development of PIF. Concurrent chemotherapy (p=0.78) was not significant. Multivariate analysis showed that age>or=55 years (p<0.001), body weight<55 kg (p=0.02), curative treatment (p=0.03), and radiation dose>or=50.4 Gy (p=0.04) were significant predisposing factors for development of PIF.Conclusion: The development of PIF is not rare after pelvic RT. The use of multibeam arrangements to reduce the volume and dose of irradiated pelvic bone can be helpful to minimize the risk of fracture, especially in elderly women with low body weight. [ABSTRACT FROM AUTHOR]

The quality and safety of meat products are critical concerns in the food industry, and consumer demand for clean-label products is increasing. To meet these needs, this study aimed to develop a nitrite-free meat spread using an astaxanthin (0.04 wt%) and carvacrol (15 wt%) co-encapsulated emulsion (AE) and chitosan. Thermal stability and antimicrobial activity of prepared AE were evaluated. Nitrite-free meat spreads were formulated by adding astaxanthin and carvacrol-containing oil (AO), AE, and/or chitosan, and physicochemical, rheological, and antimicrobial properties were assessed. Adding AE, and/or 1 % chitosan improved the physicochemical and antimicrobial properties of the meat spreads. AE increased the unsaturated fatty acid content, improved redness, reduced cooking loss, and enhanced emulsion stability. Microsurface and rheological analyses revealed a more uniform fat/oil distribution and lower textural values in samples containing AE. AE and/or chitosan also enhanced microbiological stability. Correlation analysis suggested that AE and/or chitosan could effectively replace nitrite., 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.)

Purpose: This open-label, investigator-initiated, phase II study was conducted to evaluate the safety, survival and neoadjuvant outcomes of NAC combined with dual immune checkpoint inhibitors in advanced-stage EOC., Patients and Methods: Between June 2019 and July 2021, 45 patients with unresectable stage III-IV EOC were enrolled. The patients received three cycles of NAC combined with durvalumab and tremelimumab. All patients underwent interval debulking surgery and received three cycles of durvalumab and adjuvant chemotherapy, followed by 12 cycles of durvalumab as maintenance therapy. The primary endpoint was the 12-month progression-free survival (PFS) rate; the secondary endpoints were the objective response rate (ORR) after NAC, a chemotherapy response score (CRS), pathologic complete response (pCR), overall survival (OS), and safety. The pre-planned exploratory analyses assessed the lymphocyte infiltration, PD-L1 expression, and genomic profiles of pre-treatment tumors., Results: The 12-month PFS rate was 65.9% (95% CI, 52.8-NE), while the 24- and 30-month PFS rates were 38.6% (95% CI, 26.7-NE) and 36.4% (95% CI, 24.7-NE), respectively. After NAC, the ORR was 86.7%, while 14 patients (31.1%) had a CRS 3, and five (11.1%) achieved pCR. The 30-month OS rate was 87.7%. The most common grade ≥ 3 adverse events was neutropenia (26.7%). In an exploratory analysis, patients with pre-NAC tumors showing PD-L1 (CPS) ≥1, high Mutation Signature 3, and a high extracellular matrix signature demonstrated improved PFS outcomes., Conclusions: NAC combined with dual immune checkpoint inhibitors is feasible for advanced-stage EOC and shows promising activity with a durable clinical response.

Background: Previous studies have identified an increased risk of suicidal behaviors among individuals with asthma., Objective: To evaluate the long-term risk and factors related to suicide in the adult population with asthma., Methods: This study used the Korean National Health Insurance Service data. We investigated the risk of suicide concerning the presence or absence of asthma and potential risk factors for suicide among 3,914,041 adults aged 20 years or more., Results: During a median follow-up of 12.3 years (interquartile range, 12.1-12.6 years), 1383 (0.48%) individuals with asthma died by suicide. Individuals with asthma had an increased risk of suicide compared with controls (adjusted hazard ratio [aHR], 1.26; 95% CI, 1.19-1.33). Suicide risk was especially high in individuals with asthma phenotypes: hospitalization-prone (aHR, 1.61; 95% CI, 1.40-1.84), nonobese (aHR, 1.37; 95% CI, 1.27-1.64), and asthma-chronic obstructive pulmonary disease overlap (aHR, 1.47; 95% CI, 1.22-1.76). Coexisting underweight status (aHR, 2.54; 95% CI, 2.05-3.16), mental health disorders (schizophrenia [aHR, 3.38; 95% CI, 2.28-5.02], depression [aHR, 3.24; 95% CI, 2.85-3.68], and anxiety disorder [aHR, 2.47; 95% CI, 2.00-3.05]), and cancers (aHR, 2.22; 95% CI, 1.73-2.84) further increased the suicide risk., Conclusions: Asthma was associated with an increased risk of suicide, particularly in hospitalization-prone, nonobese, and asthma-chronic obstructive pulmonary disease overlap phenotypes. The risk was further increased when asthma coexisted with underweight status, mental health disorders, or cancers., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

Probiotic metabolites are gaining attention as potential antibiotic candidates against antibiotic-resistant bacteria. The disk diffusion test, by measuring bacterial aggregate responses, faces challenges in accurately evaluating antimicrobial efficacy when these responses to different probiotic strains are indistinguishable at a macroscopic level. Here, this study presents an analytical method for accurately evaluating antimicrobial activity by analyzing bacterial cell proliferation suppression at a microscopic level. This assay can be used in a coculture system, designed to continuously expose pathogenic bacteria growing on the bottom surface of the culture plate to probiotic metabolites, selectively released from porous capsules positioned above. Bacterial proliferation is optically monitored in real-time and tracked via a computer vision algorithm. Specifically, bacterial proliferation is quantified as their doubling time, calculated using a proposed stochastic kinetic model. This method identifies the most potent antimicrobial strains by determining which probiotic candidates most effectively extend the bacterial doubling time. In comparative experiments using the same strains, this proposed method demonstrated clear distinctions in the antimicrobial efficacy of each strain, unlike the disk diffusion test. Therefore, this approach provides a reliable solution for identifying superior probiotic strains, with potential for widespread use in discovering new antimicrobial agents.

The present study aimed to develop equations for estimating the dry matter (DM), nitrogen (N), and gross energy (GE) concentrations in pig urine using Brix values. A total of 96 urine samples were obtained from pigs of 6.0 to 62.2 kg initial body weight fed 12 diets in three experiments. The animals were fed a corn-soybean meal-based diet or a corn diet. The N concentrations in the urine samples ranged from 0.12 to 2.06% and the GE concentrations ranged from 2 to 187 kcal/kg. The urine Brix values were positively correlated with urinary DM, N, and GE concentrations (r = 0.94, 0.87, and 0.93, respectively; p<0.001). The models for estimating urinary DM, N, and GE concentrations were: urinary DM (%) = 0.590×Brix + 0.315 (r2 = 0.91; p<0.001); urinary N (%) = 0.0798×Brix + 0.148 (r2 = 0.84; p<0.001); urinary GE (kcal/kg) = 11.96×Brix + 2.33 (r2 = 0.87; p<0.001), where the Brix value of urine is expressed as %. Overall, the Brix values correlated positively with the DM, N, and GE concentrations in pig urine and can thus be used for estimating the concentrations of these urinary components.

Objectives: Pulmonary involvement is common in systemic lupus erythematosus (SLE), but the relative risk of pulmonary manifestations in SLE versus non-SLE subjects remains unclear. This study aimed to evaluate the risk of pulmonary manifestations in SLE subjects compared with matched controls., Methods: Using data from the Korean National Health Insurance Service (2009-2017), we identified 6074 individuals aged ≥20 years with newly diagnosed SLE and 60 740 matched controls by age and sex (1:10 ratio) who did not have prior pulmonary manifestations., Results: Over a mean follow-up of 9.3±2.7 years, the incidence of pulmonary manifestations was 15.2 per 1000 person-years in the SLE cohort and 4.5 per 1000 person-years in the matched cohort. The SLE cohort had a significantly higher risk of pulmonary manifestations (adjusted HR (aHR) 3.26; 95% CI 2.99 to 3.56). The highest risk was observed for pulmonary hypertension (aHR 14.66; 95% CI 9.43 to 22.80), followed by interstitial lung disease (aHR 9.58; 95% CI 7.99 to 11.49), pleural disorders (aHR 3.29; 95% CI 2.84 to 3.81), pulmonary embolism (aHR 2.66; 95% CI 2.06 to 3.43), tuberculosis (aHR 2.35; 95% CI 1.88 to 2.93), acute respiratory distress syndrome and haemorrhage (aHR 1.85; 95% CI 1.51 to 2.25) and lung cancer (aHR 1.41; 95% CI 1.02 to 1.95)., Conclusions: Subjects with SLE have an approximately 3.3-fold higher risk of pulmonary manifestations compared with matched controls. Notably, the risks of pulmonary hypertension and interstitial lung disease are particularly elevated., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.)

Poststroke inflammation critically influences functional outcomes following ischemic stroke. Arginase-1 (Arg1) is considered a marker for anti-inflammatory macrophages, associated with the resolution of inflammation and promotion of tissue repair in various pathological conditions. However, its specific role in poststroke recovery remains to be elucidated. This study investigates the functional impact of Arg1 expressed in macrophages on poststroke recovery and inflammatory milieu. We observed a time-dependent increase in Arg1 expression, peaking at 7 d after photothrombotic stroke in mice. Cellular mapping analysis revealed that Arg1 was predominantly expressed in LysM-positive infiltrating macrophages. Using a conditional knockout (cKO) mouse model, we examined the role of Arg1 expressed in infiltrating macrophages. Contrary to its presumed beneficial effects, Arg1 cKO in LysM-positive macrophages significantly improved skilled forelimb motor function recovery after stroke. Mechanistically, Arg1 cKO attenuated fibrotic scar formation, enhanced peri-infarct remyelination, and increased synaptic density while reducing microglial synaptic elimination in the peri-infarct cortex. Gene expression analysis of fluorescence-activated single cell sorting (FACS)-sorted CD45 low microglia revealed decreased transforming growth factor-β (TGF-β) signaling and proinflammatory cytokine activity in peri-infarct microglia from Arg1 cKO animals. In vitro coculture experiments demonstrated that Arg1 activity in macrophages modulates microglial synaptic phagocytosis, providing evidence for macrophage-microglia interaction. These findings present unique insights into the function of Arg1 in central nervous system injury and highlight an interaction between infiltrating macrophages and resident microglia in shaping the poststroke inflammatory milieu. Our study identifies Arg1 in macrophages as a potential therapeutic target for modulating poststroke inflammation and improving functional recovery., Competing Interests: Competing interests statement:The authors declare no competing interest.

Interstitial lung disease (ILD) leads to worse outcomes in subjects with rheumatoid arthritis (RA). Few large-scale longitudinal studies have provided comprehensive data on the incidence and risk of ILD in RA compared with non-RA populations. We compare the risk of incident ILD in subjects with RA and matched controls, while also evaluating the impact of RA serologic status. Using the Korean National Health Insurance Service Data between 2010 and 2017, we identified 52,325 individuals with RA and 261,625 without RA. During a median follow-up period of 4.4 years, 3.7% of the RA cohort and 0.5% of the matched cohort developed ILD, with incidence rates of 8.30 and 1.01 per 1,000 person-years. Compared to controls, the risk of incident ILD was significantly higher in the RA cohort (adjusted hazard ratio [aHR] 7.84 [7.29-8.44]), and seropositive and seronegative RA exhibited aHRs of 9.00 (8.34-9.72) and 4.81 (4.25-5.44). Although the risk of ILD was higher in seropositive RA than seronegative RA, the risk of developing ILD was also higher in subjects with seronegative RA than in matched controls, suggesting that close monitoring for ILD should be performed in this population., Competing Interests: Declarations. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)

Introduction: Relative fibular shortening compared to the tibia and syndesmotic widening are recognized contributors to the valgus tilt of the talus. This study aimed to assess: (1) the impact of fibular shortening relative to the tibia; and (2) the influence of syndesmotic widening, in correcting a large varus talar tilt (TT) associated with advanced ankle osteoarthritis through medial opening wedge valgization supramalleolar osteotomy (SMO)., Materials and Methods: We retrospectively reviewed the clinico-radiographic findings of 41 patients with a preoperative TT of 8 degrees or more who underwent SMO for varus ankle osteoarthritis, with a minimum follow-up of more than two years. We compared several clinico-radiographic parameters between the three groups based on postoperative TT changes (decreased TT by 2 degrees or more, no TT changes [TT change between - 2 and 2 degrees], and increased TT by 2 degrees or more)., Results: In total, 18, 16, and 7 patients were included in the groups with postoperative decreased TT, no TT changes, and postoperative increased TT, respectively. The postoperative talocrural angle was greater in the postoperative increased TT group than in the postoperative decreased TT group (P =.036). The postoperative tibiofibular clear space was greatest in the postoperative decreased TT group (P =.037), whereas the other two groups were not significantly different (P =.260). In the postoperative increased TT group, postoperative tibial plafond inclination was the lowest among the three groups (P =.048 and 0.023, respectively), indicating the greatest plafond valgus inclination to the ground. All postoperative clinical parameters were significantly lower in the postoperative increased TT group (P <.05)., Conclusion: When performing SMO for varus ankle osteoarthritis, TT correction might be associated with the relative length of the fibula to the tibia and the role of the syndesmosis, implying the need for fibular shortening/valgization and syndesmotic widening. Additionally, excessive correction during SMO that places the tibial plafond in a valgus position relative to the ground floor can paradoxically increase TT and exacerbate ankle osteoarthritis., Level of Evidence: Level III., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: To evaluate the association between various regimens and combinations of menopausal hormone therapy (MHT) and the risk of cardiovascular disease (CVD) in clinical practice., Design: This was a population-based cohort study., Methods: This population-based cohort study used data from the Health Insurance Review and Assessment Service. The data of women who reported entering menopause at ≥40 years of age with no history of CVD in the national health examination between 2011 and 2014 were extracted. A total of 134 298 pairs were included in the MHT and non-MHT groups after 1:1 propensity score matching. The participants were followed until December, 31, 2020., Results: During a median follow-up of 7.9 (IQR 6.9-8.9) years, the incidences of CVD were 146 per 100 000 person/year and 179 per 100 000 person/year for the non-MHT and MHT groups, respectively. After adjusting for covariates, MHT use was associated with an increased CVD risk (hazard ratio [HR], 1.22 [1.14-1.31]) compared with the non-MHT group; the risk was based on an increased risk of stroke and coronary artery revascularization. Tibolone (HR, 1.38, [1.27-1.50]) was associated with increased CVD, but estrogen alone or combined estrogen/progestogen was not. There was no difference in CVD risk, regardless of the type of estrogen agent used. For combined estrogen/progestogen therapy, dydrogesterone was associated with reduced CVD risk., Conclusions: There was an increased risk of CVD in MHT users. By regimen, tibolone use was associated with increased risk of CVD, whereas estrogen either alone or in combination with progestogen was not. There was no difference according to the type of estrogen. The type of progestogen seems to modify the results, since dydrogesterone was associated with reduced CVD risk., Competing Interests: Conflict of interest: All authors declare no conflict of interest., (© The Author(s) 2025. Published by Oxford University Press on behalf of European Society of Endocrinology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Abstract: Spinal cord injury results in permanent loss of neurological functions due to severance of neural networks. Transplantation of neural stem cells holds promise to repair disrupted connections. Yet, ensuring the survival and integration of neural stem cells into the host neural circuit remains a formidable challenge. Here, we investigated whether modifying the intrinsic properties of neural stem cells could enhance their integration post-transplantation. We focused on phosphatase and tensin homolog (PTEN), a well-characterized tumor suppressor known to critically regulate neuronal survival and axonal regeneration. By deleting Pten in mouse neural stem cells, we observed increased neurite outgrowth and enhanced resistance to neurotoxic environments in culture. Upon transplantation into injured spinal cords, Pten-deficient neural stem cells exhibited higher survival and more extensive rostrocaudal distribution. To examine the potential influence of partial PTEN suppression, rat neural stem cells were treated with short hairpin RNA targeting PTEN, and the PTEN knockdown resulted in significant improvements in neurite growth, survival, and neurosphere motility in vitro. Transplantation of shPTEN-treated neural stem cells into the injured spinal cord also led to an increase in graft survival and migration to an extent similar to that of complete deletion. Moreover, PTEN suppression facilitated neurite elongation from NSC-derived neurons migrating from the lesion epicenter. These findings suggest that modifying intrinsic signaling pathways, such as PTEN, within neural stem cells could bolster their therapeutic efficacy, offering potential avenues for future regenerative strategies for spinal cord injury., (Copyright © 2025 Neural Regeneration Research.)

The conventional carbonization process for synthesizing hard carbons (HCs) requires high-temperature furnace operations exceeding 1000 °C, leading to excessive energy consumption and lengthy processing times, which necessitates the exploration of more efficient synthesis methods. This study demonstrates the rapid preparation of HC anodes using intense pulsed light (IPL)-assisted photothermal carbonization without the prolonged and complex operations typical of traditional carbonization methods. A composite film of microcrystalline cellulose (MCC) and single-walled carbon nanotubes (SWCNTs) is carbonized at high temperatures in less than 1 min. The SWCNTs efficiently absorbed light energy, enabling ultrafast heating and eliminating the need for prolonged, high-energy furnace-based processes. The IPL-assisted HC anodes exhibited excellent electrochemical performance, with an initial desodiation capacity of 260.4 mAh g⁻¹ anode and 97.5% capacity retention after 200 cycles. These results are comparable to those achieved using traditional furnace-based carbonization processes, such as carbonizing HC anodes at 1200 °C, validating the effectiveness of IPL-assisted processes. Additionally, surface and structural analyses revealed the development of pseudo-graphitic domains, crucial for enhanced sodium-ion storage. This research highlights IPL-assisted photothermal carbonization as a viable, time-efficient, and energy-saving alternative to conventional methods, offering a sustainable pathway for the large-scale production of HC anodes for future sodium-ion battery technologies., (© 2025 Wiley‐VCH GmbH.)

Objective: This study was performed to investigate the prevalence of falls, mental health issues, and health behaviors among older adults, as well as to analyze the association between multiple falls and mental health status in this population., Methods: We utilized data from the 2017, 2019, and 2021 Korean Community Health Survey, a nationwide survey organized by region and conducted by the Korea Disease Control and Prevention Agency. Participants were categorized into no-fall, single-fall, and multiple-fall groups based on responses to an index question regarding fall experiences and the number of such incidents reported in the survey. The chi-square test was applied to understand the characteristics of the elderly population in the community. Subsequently, multinomial logistic regression analysis was conducted to clarify the association between falls and mental health., Results: Integrated data analysis revealed that 11.3% of participants experienced a single fall, while 5.7% reported multiple falls. Participants from low-education and low-income backgrounds exhibited relatively high rates of falls. Additionally, non-drinkers and non-smokers reported falls more frequently than their counterparts who consumed alcohol and smoked. Multinomial logistic regression revealed significant associations between multiple falls and mental health factors. In particular, the severity of depression was directly proportional to the likelihood of experiencing multiple falls, with an odds ratio of 2.953 (95% confidence interval, 2.493 to 3.497)., Conclusions: We identified associations between various mental health-related factors-including sleep duration, subjective stress, the presence of depression, and Patient Health Questionnaire-9 score-and the occurrence of multiple falls.

Introduction: In vitro , primary rat oligodendrocytes (OLs) are widely used for research on OL development, physiology, and pathophysiology in demyelinating diseases such as multiple sclerosis. Primary culture methods for OLs from rats have been developed and improved over time, but there are still multiple aspects in which efficiency can be boosted., Methods: To make use of excess oligodendrocyte progenitor cells (OPCs) from primary cultures, a cryopreservation process utilizing a commercially available serum-free cryopreservation medium was established to passage and freeze OPCs at -80°C for later use., Results: Cryopreserved OPCs stored for up to 6 months were viable, and retained their OL lineage purity of ~98%. While OPCs cryopreserved for 3-6 months showed a decrease in cell density after two days of proliferation, ~17% of cryopreserved OPCs maintained the potential for proliferation comparable to control OPCs that had not frozen. After induction of differentiation for four days, ~43% of both control and cryopreserved OPCs differentiated into mature OLs, and when differentiation was induced on aligned nanofibers mimicking axonal structure, myelin sheath-like structures indicative of in vitro myelination was observed in all experimental groups., Conclusion: The validation of cryopreserved primary OLs as a functionally robust in vitro model can help improve the efficiency of primary OL culture, expand its applications, and reduce the inevitable sacrifice of animals., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2025 Kim, Kim, Koh, Cho, Kim and Choi.)

Background: Recurrent gynecological clear cell carcinoma (rGCCC) has a low objective response rate (ORR) to chemotherapy. Previous preclinical and clinical data suggest a potential synergy between immune checkpoint inhibitors and bevacizumab in rGCCC. Dostarlimab, a humanized monoclonal antibody targeting programmed cell death protein 1 (PD-1), combined with the anti-angiogenic bevacizumab, presents a novel therapeutic approach. This study will investigate the efficacy of dostarlimab +/- bevacizumab in rGCCC., Methods: DOVE is a global, multicenter, international, open-label, randomized phase 2 study of dostarlimab +/- bevacizumab with standard chemotherapy in rGCCC. We will enroll 198 patients with rGCCC and assign them to one of three groups in a 1:1:1 ratio: arm A (dostarlimab monotherapy), B (dostarlimab + bevacizumab), and C (investigator's choice of chemotherapy [weekly paclitaxel, pegylated liposomal doxorubicin, doxorubicin, or gemcitabine]). Patients with disease progression in arm A or C will be allowed to cross over to arm B. Stratification factors include prior bevacizumab use, prior lines of therapy (1 vs. >1), and primary site (ovarian vs. non-ovarian). Key inclusion criteria are histologically proven recurrent or persistent clear cell carcinoma of the ovary, endometrium, cervix, vagina, or vulva; up to five prior lines of therapy; disease progression within 12 months after platinum-based chemotherapy; and measurable disease. Key exclusion criteria are prior treatment with an anti-PD-1, anti-programmed death-ligand 1, or anti-programmed death-ligand 2 agent. The primary endpoint is progression-free survival determined by investigators. Secondary endpoints are ORR, disease control rate, clinical benefit rate, progression-free survival 2, overall survival, and toxicity. Exploratory objectives include immune biomarkers., Trial Registration: ClinicalTrials.gov Identifier: NCT06023862., Competing Interests: Dr. KYT reports receiving research funding from AstraZeneca. Further, Dr. Tse also reports receiving payments or honoraria from AstraZeneca, Zai Lab, MSD, GlaxoSmithKline, and Eisai for lectures, presentations, speakers bureaus, manuscript writing, or educational events; and receiving support for attending meetings and/or travel from Zai Lab. She reports participation on a Data Safety Monitoring Board or Advisory Board for AstraZeneca, Eisai, MSD, and GlaxoSmithKline., (© 2025. Asian Society of Gynecologic Oncology, Korean Society of Gynecologic Oncology, and Japan Society of Gynecologic Oncology.)

Epidemiological evidence has shown that diabetes is associated with overt heart failure (HF) and worse clinical outcomes. However, the presence of a distinct primary diabetic cardiomyopathy (DCM) has not been easy to prove because the association between diabetes and HF is confounded by hypertension, obesity, microvascular dysfunction, and autonomic neuropathy. In addition, the molecular mechanisms underlying DCM are not yet fully understood, DCM usually remains asymptomatic in the early stage, and no specific biomarkers have been identified. Nonetheless, several mechanistic associations at the systemic, cardiac, and cellular/molecular levels explain different aspects of myocardial dysfunction, including impaired cardiac relaxation, compliance, and contractility. In this review, we focus on recent clinical and preclinical advances in our understanding of the molecular mechanisms of DCM and the role of anti-hyperglycemic agents in preventing DCM beyond their glucose lowering effect., Competing Interests: Conflict of Interest: The authors have no conflicts of interest to declare., (© 2025 The Korean Society of Lipid and Atherosclerosis.)