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Christopher Kitchen,1 Hsien-Yen Chang,1 Jonathan P Weiner,1 Hadi Kharrazi1,2 1Center for Population Health IT, Department of Health Policy and Management, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA; 2Division of Health Sciences Informatics, Johns Hopkins School of Medicine, Baltimore, MD, USACorrespondence: Christopher Kitchen, Center for Population Health IT, Department of Health Policy and Management, Johns Hopkins University, Bloomberg School of Public Health, 624 N Broadway, Room 500, Baltimore, MD, 21205, USA, Tel +1 410 614-7409, Email ckitche2@jhu.eduPurpose: Patient vital signs are related to specific health risks and outcomes but are underutilized in the prediction of health-care utilization and cost. To measure the added value of electronic health record (EHR) extracted Body Mass Index (BMI) and blood pressure (BP) values in improving healthcare risk and utilization predictions.Patients and Methods: A sample of 12,820 adult outpatients from the Johns Hopkins Health System (JHHS) were identified between 2016 and 2017, having high data quality and recorded values for BMI and BP. We evaluated the added value of BMI and BP in predicting health-care utilization and cost through a retrospective cohort design. BMI, mean arterial pressure (MAP), systolic and diastolic BPs were summarized as annual aggregated values. Concurrent annual BMI and MAP changes were quantified as the difference between maximum and minimum recorded values. Model performance estimates consisted of repeated 10-fold cross validation, compared to base model point estimates for demographic and diagnostic, coded events: (1) patient age and sex, (2) age, sex, and the Charlson weighted index, (3) age, sex and the Johns Hopkins ACG system’s DxPM risk score.Results: Both categorical BMI and BP were progressively indicative of disease comorbidity, but not uniformly related to health-care utilization or cost. Annual change in BMI and MAP improved predictions for most concurrent year outcomes when compared to base models.Conclusion: When a healthcare system lacks relevant diagnostic or risk assessment information for a patient, vital signs may be useful for a simple estimation of disease risk, cost and utilization.Keywords: health care costs, health care organizations and systems, information technology in health, technology assessment

Ya-Ting Yang,1,2 Han-Yun Chang,1 Chung-Yao Hsu,3 Jamie M Zeitzer2,4 1Institute of Education, National Cheng Kung University, Tainan City, Taiwan; 2Department of Psychiatry and Behavioral Sciences, Stanford University, Stanford, CA, USA; 3Department of Neurology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; 4Mental Illness Research Education and Clinical Center, VA Palo Alto Health Care System, Palo Alto, CA, USACorrespondence: Jamie M Zeitzer Email jzeitzer@stanford.eduPurpose: The Cleveland Adolescent Sleepiness Questionnaire was originally developed and published in English and has served as a valid and effective tool for the assessment of adolescents’ experiences with sleepiness in a variety of situations. To allow for comparisons between sleepiness in adolescents from different cultures, and with different linguistic backgrounds, reliable and valid measurement tools are necessary. The purpose of this study was to translate and validate a Chinese version of the Cleveland Adolescent Sleepiness Questionnaire (C-CASQ).Materials and Methods: Sensitivity, specificity, internal consistency, and criterion validity data for the C-CASQ were tested using 458 adolescents in Taiwan. Data from 191 participants were used to establish internal consistency reliability and conduct exploratory factor analysis (EFA), while data from 267 participants were used to establish criterion validity and conduct confirmatory factor analysis (CFA). Initial criterion validity was established through a comparison of the C-CASQ with scores from the Chinese version of the Morningness-Eveningness Scale for Children, a measure of chronotype.Results: EFA resulted in four factors, consistent with the original English version of the CASQ, while CFA established goodness of fit. The scale demonstrated acceptable to good internal consistency (α = 0.77∼ 0.86). Initial criterion validity was evident as the total score and each of the subscale scores on the C-CASQ was significantly higher (greater sleepiness) in evening-types.Conclusion: The C-CASQ appears to be a psychometrically sound measure to evaluate sleepiness in Chinese-speaking adolescents.Keywords: teens, sleep, alertness, chronotype

Hsing-Yi Chang,1,2 Hsin-Ling Fang,1 Te-Tien Ting,3 Jersey Liang,4 Shao-Yuan Chuang,1 Chih-Cheng Hsu,1 Chin-Yin Wu,5 Wen-Harn Pan1,2,6 1Institute of Population Health Sciences, National Health Research Institutes, Maoli, Taiwan; 2Institute of Public Health, National Yang-Ming University, Taipei, Taiwan; 3School of Big Data Management, Soochow University, Taipei, Taiwan; 4Department of Health Management and Policy, School of Public Health, University of Michigan, Ann Arbor, MI, USA; 5Institute of Sociology, Academia Sinica, Taipei, Taiwan; 6Institute of Biomedical Sciences, Academia Sinica, Taipei, TaiwanCorrespondence: Hsing-Yi ChangInstitute of Population Health Sciences, National Health Research Institutes, 35 Keyan Road, A3223, Zhunan Town, Maoli County, ROC 35053, TaiwanTel +886 37 246166Fax +886 37 586261Email hsingyi@nhri.org.twPurpose: The co-occurrence of frailty and depression in late life, the possibility for symptom reversal, their reciprocal relationship, and the effects on mortality have rarely been investigated. We aimed to examine the co-occurrence of frailty and depressive symptoms in late life, the possibility for symptom reversal, their reciprocal relationship, and the effects on mortality using all the information from a longitudinal study.Patients and methods: We used the Taiwan Longitudinal Study of Aging (TLSA) for this study. TLSA was initiated in 1989 and followed periodically. We included participants from 1989 to 2007, who had data on frailty and depressive symptoms. Frailty was assessed by accumulation of functional deficits in 6 dimensions including disease status, sensory dysfunction, balance, functional limitations, health risk behaviors, and life satisfaction. Depressive symptoms were measured with the Center for Epidemiologic Studies Depression Scale (CES-D). A multistate model with interval censoring was used to examine the transition between states of frailty with or without depressive symptoms, and finally to death. A mixed model was used to examine the relationships between frailty and depressive symptoms.Results: The coexistence of frailty and depressive symptoms was associated with higher mortality. Individuals with depressive symptom had a lower probability of reversal to a better state. Previous depression score predicted current frailty, but the coefficient was smaller than that of previous frailty. Previous frailty predicted current depression score, and the coefficient was stronger than that of previous depression.Conclusion: Depressive symptoms increased the mortality and decreased the probability of reversal in the frail older adults.Keywords: TLSA, cumulative functional deficits, depressive symptom, multistate model, mortality

Chia-Lin Li,1,2 Fiona F Stanaway,3 Jen-Der Lin,2 Hsing-Yi Chang4 1Department of Health Care Management, College of Management, Chang Gung University, Kwei-Shan, Tao-Yuan 333, Taiwan; 2Division of Endocrinology and Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Linkou, Tao-Yuan 333, Taiwan; 3Sydney School of Public Health, University of Sydney, Sydney 2006, NSW, Australia; 4Division of Preventive Medicine and Health Service Research, Institute of Population Health Sciences, National Health Research Institutes, Maoli 350, Taiwan Purpose: The aims of this study were to investigate the prevalence of frailty and its relationship with health care use among community-dwelling older adults with diabetes.Methods: We analyzed data from a nationally representative sample of people aged 65 years and above (n=3,203) participating in the 2013 National Health Interview Survey in Taiwan. A total of 719 participants had a history of self-reported physician-diagnosed diabetes. The presence of frailty was determined based on the Fatigue, Resistance, Ambulation, Illness, and Loss of weight (FRAIL) scale proposed by the International Association of Nutrition and Aging. FRAIL scores range from 0 to 5 and are categorized as frail (3–5), pre-frail (1–2), and robust (0). Participants were asked whether they had been hospitalized or had visited an emergency department in the past year.Results: Among community-dwelling older adults with diabetes, 9.4% of participants were frail and 35.3 % were pre-frail. After adjustment for other factors, being frail was significantly associated with hospitalization during the past year (OR =5.31, 95% CI =1.87–15.10), whereas being pre-frail was not associated with hospitalization. Both being pre-frail and frail were significantly associated with emergency department visits during the past year (OR =2.64, 95% CI =1.35–5.17 and OR =4.05, 95% CI =1.31–12.49, respectively) after adjustment for other factors.Conclusion: Our results highlight the high prevalence of frailty in community-dwelling older adults with diabetes. Furthermore, being frail is associated with a greater burden of hospitalizations and emergency department visits. Keywords: diabetes mellitus, elderly, frailty, health care use, Taiwan

Li Pan,1,2 Zhongwang Zhang,1,2 Jianliang Lv,1,2 Peng Zhou,1,2 Wenfa Hu,1,2 Yuzhen Fang,1,2 Haotai Chen,1,2 Xinsheng Liu,1,2 Junjun Shao,1,2 Furong Zhao,1,2 Yaozhong Ding,1,2 Tong Lin,1,2 Huiyun Chang,1,2 Jie Zhang,1,2 Yongguang Zhang,1,2 Yonglu Wang1,2 1State Key Laboratory of Veterinary Etiological Biology, National Foot-and-Mouth Disease Reference Laboratory, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences (CAAS), Lanzhou, Gansu, People’s Republic of China; 2Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, People’s Republic of China Abstract: The aim of this study was to enhance specific mucosal, systemic, and cell-mediated immunity and to induce earlier onset of protection against direct-contact challenge in cattle by intranasal delivery of a nanoparticle-based nasal vaccine against type A foot-and-mouth disease (FMD). In this study, two kinds of nanoparticle-based nasal vaccines against type A FMD were designed: (1) chitosan-coated poly(lactic-co-glycolic acid) (PLGA) loaded with plasmid DNA (Chi-PLGA-DNA) and (2) chitosan-trehalose and inactivated foot-and-mouth disease virus (FMDV) (Chi-Tre-Inactivated). Cattle were immunized by an intranasal route with nanoparticles and then challenged for 48 hours by direct contact with two infected donor cattle per pen. Donors were inoculated intradermally in the tongue 48 hours before challenge, with 0.2 mL cattle-passaged FMDV. Serological and mucosal antibody responses were evaluated, and virus excretion and the number of contact infections were quantified. FMDV-specific secretory immunoglobulin (Ig)A (sIgA) antibodies in nasal washes were initially detected at 4 days postvaccination (dpv) with two kinds of nanoparticles. The highest levels of sIgA expression were observed in nasal washes, at 10 dpv, from animals with Chi-PLGA-DNA nanoparticles, followed by animals immunized once by intranasal route with a double dose of Chi-Tre-Inactivated nanoparticles and animals immunized by intranasal route three times with Chi-Tre-Inactivated nanoparticles (P

Chun-Ming Chang,1,* Yen-Ching Chang,2,3 Hsiao-Yun Chang,4 Li-Wei Chou5,6,* 1Department of Applied Informatics and Multimedia, Asia University, Taichung, Taiwan; 2Department of Medical Informatics, Chung Shan Medical University, Taichung, Taiwan; 3Department of Medical Imaging, Chung Shan Medical University Hospital, Taichung, Taiwan; 4Department of Biotechnology, Asia University, Taichung, Taiwan; 5Department of Physical Medicine and Rehabilitation, China Medical University Hospital, Taichung, Taiwan; 6School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan*These authors contributed equally to this workBackground: Increases in the aging population and in the number of accidents have resulted in more people suffering from physical impairments or disabilities. Rehabilitation therapy thus attracts greater attention as a means of helping patients recover and return to a normal life. With the extremely long and tedious nature of traditional rehabilitation, patients are reluctant to continue the entire process, thus the expected effects of the therapy cannot be obtained. Games are well known to help patients improve their concentration and shift their attention away from the discomfort of their injuries during rehabilitation. Thus, incorporating game technology into a rehabilitation program may be a promising approach.Methods: In this study, a gaming system used for shoulder rehabilitation was developed. The mechanical parts and electric circuits were integrated to mimic the functionalities of a shoulder wheel. Several games were also designed to suit the rehabilitation needs of the patients based on the age and gender differences among the individual users, enabling individuals to undergo the rehabilitation process by playing games. Two surveys were conducted to evaluate the satisfaction of the participants regarding the gaming system.Results: The results of the online survey among a larger population coincide with the responses of the hands-on participants through a paper-and-pencil survey. Statistical results suggest that the participants are willing to accept this novel approach.Conclusion: This gaming system can distract a patient from the sensation of pain or anxiety, and increase their motivation to participate in the therapeutic program. Advantages in terms of low-cost and easy setup increase the attractiveness of this new equipment for various potential users.Keywords: virtual reality, virtual rehabilitation, shoulder wheel, game design

Purpose This study examined longitudinal changes in interstitial lung abnormalities (ILAs) and predictors of clinically significant interstitial lung diseases (ILDs) in a screening population with ILAs. Materials and Methods We retrieved 36891 low-dose chest CT records from screenings between January 2003 and May 2021. After identifying 101 patients with ILAs, the clinical findings, spirometry results, and initial and follow-up CT findings, including visual and artificial intelligence-based quantitative analyses, were compared between patients diagnosed with ILD (n = 23, 23%) and those who were not (n = 78, 77%). Logistic regression analysis was used to identify significant parameters for the clinical diagnosis of ILD. Results Twenty-three patients (n = 23, 23%) were subsequently diagnosed with clinically significant ILDs at follow-up (mean, 8.7 years). Subpleural fibrotic ILAs on initial CT and signs of progression on follow-up CT were common in the ILD group (both p < 0.05). Logistic regression analysis revealed that emerging respiratory symptoms (odds ratio [OR], 5.56; 95% confidence interval [CI], 1.28–24.21; p = 0.022) and progression of ILAs at follow-up chest CT (OR, 4.07; 95% CI, 1.00–16.54; p = 0.050) were significant parameters for clinical diagnosis of ILD. Conclusion Clinically significant ILD was subsequently diagnosed in approximately one-quarter of the screened population with ILAs. Emerging respiratory symptoms and progression of ILAs at followup chest CT can be predictors of clinically significant ILDs.

Abstract Background Numerous studies have been conducted to manage anemia in surgical patients through iron supplementation as an alternative to blood transfusion. However, patients with locally advanced rectal cancer have often been excluded from these studies, due to their standard treatment involving neoadjuvant chemoradiotherapy. This study aims to evaluate the impact of intravenous versus oral iron supplementation on iron deficiency anemia in patients with rectal cancer receiving preoperative chemoradiotherapy. Methods This open-label, single-center, parallel, superiority, randomized trial includes patients with primary rectal cancer who are candidates for preoperative chemoradiotherapy and have confirmed iron-deficiency anemia. A total of 94 patients will be randomly assigned in a 1:1 ratio to receive either intravenous or oral iron supplementation. Stratification factors include age (> 70 vs. ≤ 70 years) and baseline serum hemoglobin levels (7–10 g/dL vs. 10–13 g/dL). The primary endpoint is the percentage of patients achieving normalized hemoglobin levels from the start of treatment to the day of admission for surgery. Secondary endpoints include changes in serum hemoglobin from baseline to postoperatively, changes in iron assay parameters, time needed to hemoglobin normalization, volume of blood transfusions required, and incidence of postoperative complications. Discussion This study is the first randomized controlled trial investigating the effect of iron supplementation in iron-deficient patients with rectal cancer undergoing neoadjuvant chemoradiotherapy. This trial is expected to provide evidence for the benefits of administering iron supplementation in patients with rectal cancer undergoing neoadjuvant chemoradiotherapy. Trial registration Clinical Research Information Service (CRIS) of Republic of Korea, KCT0009260, Registered on March 21, 2024.

Abstract Objective White matter hyperintensities (WMH) on brain MRI images are the most common feature of cerebral small vessel disease (CSVD). Studies have yielded divergent findings on the modifiable risk factors for WMH and WMH’s impact on cognitive decline. Mounting evidence suggests sex differences in WMH burden and subsequent effects on cognition. Thus, we aimed to identify sex-specific modifiable risk factors for WMH. We then explored whether there were sex-specific associations of WMH to longitudinal clinical dementia outcomes. Methods Participants aged 49–89 years were recruited at memory clinics and underwent a T2-weighted fluid-attenuated inversion recovery (FLAIR) 3T MRI scan to measure WMH volume. Participants were then recruited for two additional follow-up visits, 1–2 years apart, where clinical dementia rating sum of boxes (CDR-SB) scores were measured. We first explored which known modifiable risk factors for WMH were significant when tested for a sex-interaction effect. We additionally tested which risk factors were significant when stratified by sex. We then tested to see whether WMH is longitudinally associated with clinical dementia that is sex-specific. Results The study utilized data from 713 participants (241 males, 472 females) with a mean age of 72.3 years and 72.8 years for males and females, respectively. 57.3% and 59.5% of participants were diagnosed with mild cognitive impairment (MCI) for males and females, respectively. 40.7% and 39.4% were diagnosed with dementia for males and females, respectively. Of the 713 participants, 181 participants had CDR-SB scores available for three longitudinal time points. Compared to males, females showed stronger association of age to WMH volume. Type 2 Diabetes was associated with greater WMH burden in females but not males. Finally, baseline WMH burden was associated with worse clinical dementia outcomes longitudinally in females but not in males. Discussion Older females have an accelerated increase in cerebrovascular burden as they age, and subsequently are more vulnerable to clinical dementia decline due to CSVD. Additionally, females are more susceptible to the cerebrovascular consequences of diabetes. These findings emphasize the importance of considering sex when examining the consequences of CSVD. Future research should explore the underlying mechanisms driving these sex differences and personalized prevention and treatment strategies. Clinical trial registration The BICWALZS is registered in the Korean National Clinical Trial Registry (Clinical Research Information Service; identifier, KCT0003391). Registration Date 2018/12/14.

Background: The inflation-deflation (ID) method has long been the standard for intraoperative margin assessment in segmentectomy. However, with advancements in vision technology, the use of near-infrared mapping with indocyanine green (ICG) has become increasingly common. This study was conducted to compare the perioperative outcomes and resection margins achieved using these methods. Methods: This retrospective study included patients who underwent direct segmentectomy for clinical stage I lung cancer between January 2018 and September 2022. We compared perioperative factors, including bronchial and parenchymal resection margins, according to the margin assessment method and the type of segmentectomy performed. Since the ICG approach was adopted in April 2021, we also examined a recent subgroup of patients treated from then onward. Results: A total of 319 segmentectomies were performed. ID and ICG were utilized for 261 (81.8%) and 58 (18.2%) patients, respectively. Following April 2021, 61 patients (51.3%) were treated with ID, while 58 (48.7%) received ICG. We observed no significant difference in resection margins between ID and ICG for bronchial (2.7 cm vs. 2.3 cm, p=0.07) or parenchymal (2.5 cm vs. 2.3 cm, p=0.46) margins. Additionally, the length of hospitalization and the complication rate were comparable between groups. Analysis of the recent subgroup confirmed these findings, showing no significant differences in resection margins (bronchial: 2.6 cm vs. 2.3 cm, p=0.25; parenchymal: 2.4 cm vs. 2.3 cm, p=0.75), length of hospitalization, or complication rate. Conclusion: The perioperative outcomes and resection margins achieved using ID and ICG were comparable, suggesting that both methods can safely guide segmentectomy procedures.

Background: The maintenance of antiplatelet therapy increases the risk of bleeding during lung cancer surgery. Conversely, the perioperative interruption of antiplatelet therapy may result in serious thrombotic complications. This study aimed to investigate the safety of continuing antiplatelet therapy in the context of lung cancer surgery. Methods: We retrospectively reviewed a cohort of 498 elderly patients who underwent surgery for lung cancer. These patients were categorized into 2 groups: group N, which did not receive antiplatelet therapy, and group A, which did. Group A was subsequently subdivided into group Am, where antiplatelet therapy was maintained, and group Ai, where antiplatelet therapy was interrupted. We compared the incidence of bleeding-related and thrombotic complications across the 3 groups. Results: There were 387 patients in group N and 101 patients in group A (Ai: 70, Am: 31). No significant differences were found in intraoperative blood loss, thoracotomy conversion rates, transfusion requirements, volume of chest tube drainage, or reoperation rates for bleeding control between groups N and A or between groups Am and Ai. The duration of hospital stay was longer for group A compared to group N (7 days vs. 6 days, p=0.005), but there was no significant difference between groups Ai and Am. The incidence of cardiovascular or cerebrovascular complications did not differ significantly between groups Ai and Am. However, group Ai included a severe case of in-hospital ST-elevation myocardial infarction. Conclusion: The maintenance of antiplatelet therapy was found to be safe in terms of perioperative bleeding and thrombotic complications in elderly lung cancer surgery patients.

Fetal lung interstitial tumor (FLIT), which is characterized by immature interstitial cells resembling the fetal lung parenchyma of 20 to 24 weeks of gestation, is a rare respiratory neoplasm. This study presents the first reported FLIT in Korea. It also aims to refine the diagnostic method of FLIT and increase the accuracy of prognostic assessment by using next-generation sequencing to check for anaplastic lymphoma receptor tyrosine kinase (anaplastic lymphoma kinase) gene rearrangement. Although the initial prognosis for FLIT has been promising since its first report in 2010, certain pathological features are associated with poorer outcomes. Therefore, achieving an accurate diagnosis of FLIT is crucial for avoiding unnecessary treatments beyond surgical resection.

Abstract Electrochemical CO2 reduction reaction (CO2RR) to produce value‐added multi‐carbon chemicals has been an appealing approach to achieving environmentally friendly carbon neutrality in recent years. Despite extensive research focusing on the use of CO2 to produce high‐value chemicals like high‐energy‐density hydrocarbons, there have been few reports on the production of propane (C3H8), which requires carbon chain elongation and protonation. A rationally designed 0D/2D hybrid Cu2O anchored‐Ti3C2Tx MXene catalyst (Cu2O/MXene) is demonstrated with efficient CO2RR activity in an aqueous electrolyte to produce C3H8. As a result, a significantly high Faradaic efficiency (FE) of 3.3% is achieved for the synthesis of C3H8 via the CO2RR with Cu2O/MXene, which is ≈26 times higher than that of Cu/MXene prepared by the same hydrothermal process without NH4OH solution. Based on in‐situ attenuated total reflection‐Fourier transform infrared spectroscopy (ATR‐FTIR) and density functional theory (DFT) calculations, it is proposed that the significant electrocatalytic conversion originated from the synergistic behavior of the Cu2O nanoparticles, which bound the *C2 intermediates, and the MXene that bound the *CO coupling to the C3 intermediate. The results disclose that the rationally designed MXene‐based hybrid catalyst facilitates multi‐carbon coupling as well as protonation, thereby manipulating the CO2RR pathway.

Objectives Arthroscopic treatment is indicated for external snapping hip (ESH) syndrome in patients refractory to conservative treatment, but snapping does not disappear completely in some case. No previous studies have described the clinical course of ESH syndrome in patients who presented with persistent snapping after an arthroscopic procedure. We demonstrated the clinical outcomes following an incomplete arthroscopic iliotibial band (ITB) release for ESH syndrome. Methods This retrospective observational study was performed at two teaching hospitals between October 2015 and December 2021. We reviewed the data of 33 patients (34 hips) aged ≥18 years, diagnosed with ESH syndrome, who were treated with arthroscopic ITB release. Patients who presented with persistent snapping despite sufficient arthroscopic ITB release following systematic order were defined as having an incomplete release. We collected the data for recurrent symptomatic snapping hip as the primary outcome after a minimum 2‐year follow‐up. The visual analogue scale (VAS) and modified Harris hip (mHHS) scores were measured as secondary outcome. Results “Incomplete release” was identified in three of the 34 hips (8.9%). Cases of recurrent symptomatic snapping or conversion to open surgery were not observed. The symptoms of residual snapping spontaneously disappeared in all cases following routine postoperative rehabilitation within a 3‐month follow‐up period. The VAS (4 ± 1) and mHHS (17 ± 6) scores of all the patients improved. Conclusion When refractory ESH syndrome is identified during arthroscopic surgery, appropriate ITB release and removal of the major lesion causing snapping are expected to lead to resolution of residual symptoms without conversion to open surgery.

Colorectal cancer is the third most common cancer in Korea and the third leading cause of death from cancer. Treatment outcomes for colon cancer are steadily improving due to national health screening programs with advances in diagnostic methods, surgical techniques, and therapeutic agents. The Korea Colon Cancer Multidisciplinary (KCCM) Committee intends to provide professionals who treat colon cancer with the most up-to-date, evidence-based practice guidelines to improve outcomes and help them make decisions that reflect their patients’ values and preferences. These guidelines have been established by consensus reached by the KCCM Guideline Committee based on a systematic literature review and evidence synthesis and by considering the national health insurance system in real clinical practice settings. Each recommendation is presented with a recommendation strength and level of evidence based on the consensus of the committee.

Summary: While most dizygotic twins have a dichorionic placenta, rare cases of dizygotic twins with a monochorionic placenta have been reported. The monochorionic placenta in dizygotic twins allows in utero exchange of embryonic cells, resulting in chimerism in the twins. In practice, this chimerism is incidentally identified in mixed ABO blood types or in the presence of cells with a discordant sex chromosome. Here, we applied whole-genome sequencing to one triplet and one twin family to precisely understand their zygotic compositions, using millions of genomic variants as barcodes of zygotic origins. Peripheral blood showed asymmetrical contributions from two sister zygotes, where one of the zygotes was the major clone in both twins. Single-cell RNA sequencing of peripheral blood tissues further showed differential contributions from the two sister zygotes across blood cell types. In contrast, buccal tissues were pure in genetic composition, suggesting that in utero cellular exchanges were confined to the blood tissues. Our study illustrates the cellular history of twinning during human development, which is critical for managing the health of chimeric individuals in the era of genomic medicine.

In contrast to all-time flooded small modular reactor (SMR) systems, an in-kind flooding safety system (FSS) has been proposed as a passive safety system applicable to small modular reactors (SMRs) that adopt a metal containment vessel (MCV). Under transient conditions, the FSS can provide emergency cooling to dry reactor cavities and sustain long-term coolability using re-acquired evaporated steam in the reactor building on demand. When designing an FSS, the effect of the flooding flow area is vital as it affects the overall accident sequence and safety. Therefore, in this study, a MELCOR model of a reference SMR is developed and numerical analysis is performed under postulated accident scenarios. Without flooding, the MCV pressure of the reactor module exceeds the design pressure before core damage. To prevent core damage, an emergency flooding strategy is devised using various flow path parameters and requirements to ensure an adequate emergency coolant supply before the core damage is investigated. The results indicate that a flow area exceeding 0.02 m2 is required in the FSS to prevent MCV overpressure and core damage. This study is the first to report a strategic analysis for appropriately sizing an FSS flooding valve applicable to innovative SMRs.

Silybin, which belongs to the flavonolignan group, is the major component of the fruit extract of Silybum marianum (common name: milk thistle). Silybin is a medicinal compound with hepatoprotective, antioxidant, and anticancer properties. In this study, silybin derivatives were produced through γ-radiolysis, and their tyrosinase inhibitory activities were evaluated to explore the enhanced activities of silybin derivatives compared to silybin (1). Isosilandrin (2) and 2,3-dehydrosilybin (3) were obtained from a silybin sample irradiated at 300 kGy. The optimal dose showed significant changes in radiolysis product content. Compounds 2 and 3 exhibited an IC50 of 274.6 and 109.5 μM, respectively, which are more potent than that of 1 (IC50 > 500 μM). In addition, a molecular docking simulation revealed the binding affinity of these compounds to tyrosinase and their mechanisms of inhibition. Thus, γ-irradiation is an effective method for structural modification of silybin. We also demonstrated that 2,3-dehydrosilybin is a potential tyrosinase inhibitor.

Background and Objectives: Robotic-assisted total knee arthroplasty (TKA) is gaining popularity worldwide, leading to a potential increase in the number of pin tracker–related complications. This study determined the effectiveness of periarticular pin tracker placement in the distal femur and proximal tibia through a single main incision during robotic-assisted TKA over a minimum follow-up period of 6 months. Materials and Methods: A consecutive series of 149 TKAs was performed in 108 patients using the triathlon posterior-stabilized total knee prosthesis with a robotic-assisted system at our hospital from December 2023 to February 2024. Clinical outcomes and complications associated with pin tracker sites, including pin-site infection, neurovascular injury, hematoma, soft-tissue morbidity, and pin-site fracture, were assessed. Results: The mean Knee Society knee score improved from 42.5 preoperatively to 76.3 points at the final follow-up, whereas the mean Knee Society function score improved from 43.1 preoperatively to 78.1 points at the final follow-up (both p < 0.05). No patient experienced any minor or major complications related to the use of pin trackers in the distal femur and proximal tibia. Conclusions: This periarticular technique that uses pin trackers in the distal femur and proximal tibia through a single main incision could be a useful option for orthopedic surgeons while performing robotic-assisted TKA.

Morchella fluvialis, a morel mushroom, is one of the most famous edible mushrooms all over the world. Interest in this mushroom is steadily increasing due to its organoleptic properties and nutritional value. The methanolic extract of M. fluvialis showed α-glucosidase inhibitory and antioxidant activities in an assay system. Therefore, the purification and characterisation of bioactive metabolites and evaluation of biological activity were conducted. Fractionation of the M. fluvialis extract resulted in the isolation of nine compounds, namely, three fatty acids, (9Z,12Z)-octadecadienoic acid (linoleic acid, 1), (9Z,12Z)-3-hydroxyoctadecadienoic acid (2) and (6Z,9Z)-13-hydroxyoctadecadienoic acid (3); four sterols, stellasterol (4), ergosterol peroxide (5), ergosterol (6) and brassicasterol (7); one sugar alcohol, arabitol (8); and nicotinamide (9). Among them, compounds 2–3 and 7 were first reported from Morchella. In addition, compound 1 exhibited potent α-glucosidase inhibition, with an IC50 value of 14.8 μM. The content of compound 1, the major compound, was 1.2 mg · g–1 extract, as quantitated by HPLC analysis, which was lower than the IC50 value of compound 1. Therefore, M. fluvialis can benefit from diabetes and related diseases through the synergistic effect of linoleic acid (1) and other ingredients.

Abstract Among countries that are a part of the Organization for Economic Co-operation and Development, South Korea is the most exposed to PM2.5. Despite the country having implemented various strategies to limit PM2.5 emissions, its concentrations are still high enough to pose serious environmental and health concerns. Herein, we monitored various physiochemical properties of PM2.5 across different regions in South Korea from January 1 to December 31, 2021. Specifically, the study area consisted of the city center, industrial complexes, and suburban areas. Before analyzing dynamics of emissions specific to each site, the Clean Air Policy Support System data for the three areas were compared to elucidate their respective primary emission sources. The particle concentrations for the three areas were 21.8–26.44 µg/m3, with the highest concentrations being observed in March. All the three areas exhibited high ratios of NO3 − across all seasons. The particle number concentrations in the three sites were 1.3–1.5 × 107, and the peak points of the concentrations were different in every site: city center (40 nm), industrial complexes (60 nm), and suburban areas (80 nm). We also conducted potential source contribution function and conditional bivariate probability function analyses. These analyses were conducted to determine the inflow direction of the pollution sources for high PM2.5 episodes. For the episodes that occurred in spring and winter, there were no differences in the PM2.5 concentrations between the three sites. Overall, the insights gained from this study offer a framework for developing air-quality management policies in South Korea, specifically in the context of PM2.5 emissions.

Abstract Background Preoperative (chemo)radiotherapy has been widely used as an effective treatment for locally advanced rectal cancer (LARC), leading to a significant reduction in pelvic recurrence rates. Because early administration of intensive chemotherapy for LARC has more advantages than adjuvant chemotherapy, total neoadjuvant therapy (TNT) has been introduced and evaluated to determine whether it can improve tumor response or treatment outcomes. This study aims to investigate whether short-course radiotherapy (SCRT) followed by intensive chemotherapy improves oncologic outcomes compared with traditional preoperative long-course chemoradiotherapy (CRT). Methods A multicenter randomized phase II trial involving 364 patients with LARC (cT3–4, cN+, or presence of extramural vascular invasion) will be conducted. Patients will be randomly assigned to the experimental or control arm at a ratio of 1:1. Participants in the experimental arm will receive SCRT (25 Gy in 5 fractions, daily) followed by four cycles of FOLFOX (oxaliplatin, 5-fluorouracil, and folinic acid) as a neoadjuvant treatment, and those in the control arm will receive conventional radiotherapy (45–50.4 Gy in 25–28 fractions, 5 times a week) concurrently with capecitabine or 5-fluorouracil. As a mandatory surgical procedure, total mesorectal excision will be performed 2–5 weeks from the last cycle of chemotherapy in the experimental arm and 6–8 weeks after the last day of radiotherapy in the control arm. The primary endpoint is 3-year disease-free survival, and the secondary endpoints are tumor response, overall survival, toxicities, quality of life, and cost-effectiveness. Discussion This is the first Korean randomized controlled study comparing SCRT-based TNT with traditional preoperative LC-CRT for LARC. The involvement of experienced colorectal surgeons ensures high-quality surgical resection. SCRT followed by FOLFOX chemotherapy is expected to improve disease-free survival compared with CRT, with potential advantages in tumor response, quality of life, and cost-effectiveness. Trial registration This trial is registered at Clinical Research Information under the identifier Service KCT0004874 on April 02, 2020, and at Clinicaltrial.gov under the identifier NCT05673772 on January 06, 2023.

Background: The concept of oligo-recurrence has not been generally applied in esophageal cancer. This study aimed to determine the prognostic significance of the number of recurrences in esophageal cancer. Methods: Patients with squamous cell carcinoma who underwent curative esophagectomy with R0 or R1 resection and who experienced a confirmed recurrence were included. The study included 321 eligible participants from March 2001 to December 2019. The relationship between the number of recurrences and post-recurrence survival was investigated. Results: The mean age was 63.8±8.1 years, and the majority of the participants (97.5%) were men. The median time to recurrence was 10.7 months, and the median survival time after recurrence was 8.8 months. Multiple recurrences with simultaneous local, regional, and distant locations were common (38%). In terms of the number of recurrences, single recurrences were the most common (38.3%) and had the best post-recurrence survival rate (median, 17.1 months; p

Abstract Background Thymic epithelial tumors (TET) are rare malignancies and lack well‐defined biomarkers for neoadjuvant therapy. This study aimed to evaluate the clinical utility of artificial intelligence (AI)‐powered tumor‐infiltrating lymphocyte (TIL) analysis in TET. Methods Patients initially diagnosed with unresectable thymoma or thymic carcinoma who underwent neoadjuvant therapy between January 2004 and December 2021 formed our study population. Hematoxylin and eosin‐stained sections from the initial biopsy and surgery were analyzed using an AI‐powered spatial TIL analyzer. Intratumoral TIL (iTIL) and stromal TIL (sTIL) were quantified and their immune phenotype (IP) was identified. Results Thirty‐five patients were included in this study. The proportion of patients with partial response to neoadjuvant therapy was higher in the group with nondesert IP in preneoadjuvant biopsy (63.6% vs. 17.6%, p = 0.038). A significant increase in both iTIL (median 22.18/mm2 vs. 340.69/mm2, p 147/mm2) exhibited longer disease‐free survival (median, 29 months vs. 12 months, p = 0.009) and overall survival (OS) (median, 62 months vs. 45 months, p = 0.002). Patients with higher sTIL (>232.1/mm2) exhibited longer OS (median 62 months vs. 30 months, p = 0.021). Conclusions Nondesert IP in initial biopsy was associated with a better response to neoadjuvant therapy. Increased infiltration of both iTIL and sTIL in surgical specimens were associated with longer OS in patients with TET who underwent resection followed by neoadjuvant therapy.

Abstract Background Interest in complications and sequelae following Coronavirus disease 2019 (COVID-19) is increasing. Several articles have reported COVID-19-associated autoimmune diseases and the association between autoantibodies and the severity of COVID-19. Thromboembolic complications are frequent in patients with COVID-19, and the anti-phospholipid antibodies (aPL) is frequently detected. We conducted this study to investigate the prevalence, clinical significance, and persistence of anti-nuclear antibodies (ANA) and aPLs in COVID-19. Methods We enrolled patients diagnosed with COVID-19 with oxygen demand and admitted to a tertiary hospital in South Korea between July 2020 and March 2022. ANA and aPLs levels were assessed using an immunoassay kit. Results A total of 248 patients were enrolled in the study. Among them, five patients were ANA-positive, and 41 were aPL-positive (IgM anti-cardiolipin (aCL) antibody in seven patients, IgG aCL in seven patients, IgM anti-β2Glycoprotein1 antibody (aβ2-GPI) in 32 patients, and IgG aβ2-GPI in one patient). Two of five ANA-positive patients, 13 of 32 IgM aβ2-GPI-positive patients, 5 of 7 IgM aCL-positive patients, and 2 of 7 IgG aCL-positive patients were eligible for follow-up analysis, and 100%, 69.2%, 40%, and 50% of the patients remained autoantibody-positive, respectively. There were no differences in clinical outcomes between the autoantibody-positive and autoantibody-negative groups, except for the IgG aCL group showing a tendency for worse outcomes. Conclusion A significant proportion of COVID-19 patients with oxygen demand were autoantibody-positive, and autoantibodies persisted for several months after symptom onset. Whether these autoantibodies are related to long-term sequelae in COVID-19 patients requires further investigation.

Magnaporthe oryzae, a devastating pathogen of finger millet (Eleusine coracana), secretes effector molecules during infection to manipulate host immunity. This study determined the presence of avirulence effector genes PWL1 and PWL2 in 221 Eleusine blast isolates from eastern Africa. Most Ethiopian isolates carried both PWL1 and PWL2. Kenyan and Ugandan isolates largely lacked both genes, and Tanzanian isolates carried either PWL1 or lacked both. The roles of PWL1 and PWL2 towards pathogenicity on alternative chloridoid hosts, including weeping lovegrass (Eragrostis curvula), were also investigated. PWL1 and PWL2 were cloned from Ethiopian isolate E22 and were transformed separately into Ugandan isolate U34, which lacked both genes. Resulting transformants harboring either gene gained varying degrees of avirulence on Eragrostis curvula but remained virulent on finger millet. Strains carrying one or both PWL1 and PWL2 infected the chloridoid species Sporobolus phyllotrichus and Eleusine tristachya, indicating the absence of cognate resistance (R) genes for PWL1 and PWL2 in these species. Other chloridoid grasses, however, were fully resistant, regardless of the presence of one or both PWL1 and PWL2, suggesting the presence of effective R genes against PWL and other effectors. Partial resistance in some Eragrostis curvula accessions to some blast isolates lacking PWL1 and PWL2 also indicated the presence of other interactions between fungal avirulence (AVR) genes and host resistance (R) genes. Related chloridoid species thus harbor resistance genes that could be useful to improve finger millet for blast resistance. Conversely, loss of AVR genes in the fungus could expand its host range, as demonstrated by the susceptibility of Eragrostis curvula to finger millet blast isolates that had lost PWL1 and PWL2. [Graphic: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY 4.0 International license.

Abstract Background The effect of fecal stream diversion on the gut microbiota is still uncertain. The present study was designed to assess the effect of fecal stream diversion on the composition of the gut microbiota in patients with colorectal cancer. We included patients undergoing left-sided colorectal cancer surgery with (ileostomy group) or without (control group) diverting ileostomy. Fecal samples were collected from 10 patients in each group before surgery (t 1 ) and after ileostomy repair in the ileostomy group and 6–12 months after the initial surgery in the control group (t 2 ). The fecal microbiota was assessed using 16S rRNA sequencing, and changes in the composition of the fecal microbiota were compared between the two groups. Results Alpha diversity analysis revealed that the complexity of fecal microbiota decreased between t 1 and t 2 only in the ileostomy group. Beta diversity analysis also showed dissimilarity between t 1 and t 2 only in the ileostomy group. The composition of the microbiota was similar between the two groups at t 1 . However, at t 2 , the ileostomy group had lower proportion of beneficial bacteria (Lachnospiraceae, 3.8% vs. 29.9%, p

Abstract Ulmus macrocarpa Hance bark (UmHb) has been used as a traditional herbal medicine in East Asia for bone concern diseases for a long time. To find a suitable solvent, we, in this study, compared the efficacy of UmHb water extract and ethanol extract which can inhibit osteoclast differentiation. Compared with two ethanol extracts (70% and 100% respectively), hydrothermal extracts of UmHb more effectively inhibited receptor activators of nuclear factor κB ligand-induced osteoclast differentiation in murine bone marrow-derived macrophages. We identified for the first time that (2R,3R)-epicatechin-7-O-β-D-apiofuranoside (E7A) is a specific active compound in UmHb hydrothermal extracts through using LC/MS, HPLC, and NMR techniques. In addition, we confirmed through TRAP assay, pit assay, and PCR assay that E7A is a key compound in inhibiting osteoclast differentiation. The optimized condition to obtain E7A-rich UmHb extract was 100 mL/g, 90 °C, pH 5, and 97 min. At this condition, the content of E7A was 26.05 ± 0.96 mg/g extract. Based on TRAP assay, pit assay, PCR, and western blot, the optimized extract of E7A-rich UmHb demonstrated a greater inhibition of osteoclast differentiation compared to unoptimized. These results suggest that E7A would be a good candidate for the prevention and treatment of osteoporosis-related diseases.

IntroductionBrain computer interface-based action observation (BCI-AO) is a promising technique in detecting the user's cortical state of visual attention and providing feedback to assist rehabilitation. Peripheral nerve electrical stimulation (PES) is a conventional method used to enhance outcomes in upper extremity function by increasing activation in the motor cortex. In this study, we examined the effects of different pairings of peripheral nerve electrical stimulation (PES) during BCI-AO tasks and their impact on corticospinal plasticity.Materials and methodsOur innovative BCI-AO interventions decoded user's attentive watching during task completion. This process involved providing rewarding visual cues while simultaneously activating afferent pathways through PES. Fifteen stroke patients were included in the analysis. All patients underwent a 15 min BCI-AO program under four different experimental conditions: BCI-AO without PES, BCI-AO with continuous PES, BCI-AO with triggered PES, and BCI-AO with reverse PES application. PES was applied at the ulnar nerve of the wrist at an intensity equivalent to 120% of the sensory threshold and a frequency of 50 Hz. The experiment was conducted randomly at least 3 days apart. To assess corticospinal and peripheral nerve excitability, we compared pre and post-task (post 0, post 20 min) parameters of motor evoked potential and F waves under the four conditions in the muscle of the affected hand.ResultsThe findings indicated that corticospinal excitability in the affected hemisphere was higher when PES was synchronously applied with AO training, using BCI during a state of attentive watching. In contrast, there was no effect on corticospinal activation when PES was applied continuously or in the reverse manner. This paradigm promoted corticospinal plasticity for up to 20 min after task completion. Importantly, the effect was more evident in patients over 65 years of age.ConclusionThe results showed that task-driven corticospinal plasticity was higher when PES was applied synchronously with a highly attentive brain state during the action observation task, compared to continuous or asynchronous application. This study provides insight into how optimized BCI technologies dependent on brain state used in conjunction with other rehabilitation training could enhance treatment-induced neural plasticity.

We developed machine learning algorithms for distinguishing scintillation signals from a plastic-liquid coupled detector known as a phoswich. The challenge lies in discriminating signals from organic scintillators with similar shapes and short decay times. Using a single-readout phoswich detector, we successfully identified γ radiation signals from two scintillating components. Our Boosted Decision Tree algorithm demonstrated a maximum discrimination power of 3.02 ± 0.85 standard deviation in the 950 keV region, providing an efficient solution for self-shielding and enhancing radiation detection capabilities.

Abstract Atomically precise metal nanoclusters (NCs) have emerged as a promising frontier in the field of electrochemical CO2 reduction reactions (CO2RR) because of their distinctive catalytic properties. Although numerous metal NCs are developed for CO2RR, their use in practical applications has suffered from their low‐yield synthesis and insufficient catalytic activity. In this study, the large‐scale synthesis and electrocatalytic performance of ClAg14(C≡CtBu)12+ NCs, which exhibit remarkable efficiency in catalyzing CO2‐to‐CO electroreduction with a CO selectivity of over 99% are reported. The underlying mechanisms behind this extraordinary CO2RR activity of ClAg14(C≡CtBu)12+ NCs are investigated by a combination of electrokinetic and theoretical studies. These analyses reveal that different active sites, generated through electrochemical activation, have unique adsorption properties for the reaction intermediates, leading to enhanced CO2RR and suppressed hydrogen production. Furthermore, industrially relevant CO2‐to‐CO electroreduction using ClAg14(C≡CtBu)12+ NCs in a zero‐gap CO2 electrolyzer, achieving high energy efficiency of 51% and catalyst activity of over 1400 A g−1 at a current density of 400 mA cm−2 is demonstrated.

PurposeThis study aimed to compare the clinical outcomes, mechanical axis, component positioning, leg length discrepancy (LLD), and polyethylene liner thickness between robotic-assisted total knee arthroplasty (TKA) and conventional TKA in patients with failed high tibial osteotomy (HTO).MethodsA total of 30 patients (30 knees) with failed HTO who underwent TKA using a robot-assisted system between June 2020 and December 2023 were included in this study (robotic group). Additionally, 60 patients (60 knees) with failed HTO who underwent conventional TKA were included as controls (conventional group). Propensity score matching was performed using a 2:1 ratio between the matched participants. The mean follow-up period was 2.1 years in the robotic group and 2.2 years in the conventional group. Clinical evaluations were performed using the Knee Society Score (KSS) rating system. Mechanical axis, component coronal and sagittal positioning, and LLD were evaluated using postoperative radiographs. The thickness of the polyethylene liner was also determined. The mean error values and outliers were calculated and compared between the two groups to determine the accuracy of the mechanical axis, postoperative component positioning, and LLD.ResultsThe postoperative KSSs in the robotic and conventional groups were not statistically different. The robotic group achieved better accuracy than the conventional group in terms of postoperative mean mechanical axis (1.7° vs. 2.4°, p < 0.05), femur coronal inclination (90.0° vs. 91.6°, p < 0.05), tibial coronal inclination (90.3° vs. 91.3°, p < 0.05), tibial sagittal inclination (90.5° vs. 91.4°, p < 0.05), and LLD (2.2 vs. 7.0 mm, p < 0.05). A significant difference in polyethylene liner thickness was observed between the two groups (p < 0.05).ConclusionsRobotic-assisted TKA showed improved mechanical axis, higher accuracy of component positioning and polyethylene liner thickness, and reduced LLD compared with those of conventional TKA in patients with failed HTO. Further studies with a larger sample size and long-term follow-up are warranted to ascertain whether the accuracy of robotic-assisted TKA can translate into better clinical outcomes and patient satisfaction.

Chronic obstructive pulmonary disease (COPD), an inflammatory lung disease, causes approximately 3 million deaths each year; however, its pathological mechanisms are not fully understood. In this study, we examined whether HX110B, a mixture of Taraxacum officinale, Dioscorea batatas, and Schizonepeta tenuifolia extracts, could suppress porcine pancreatic elastase (PPE)-induced emphysema in mice and its mechanism of action. The therapeutic efficacy of HX110B was tested using a PPE-induced emphysema mouse model and human bronchial epithelial cell line BEAS-2B. In vivo data showed that the alveolar wall and air space expansion damaged by PPE were improved by HX110B administration. HX110B also effectively suppresses the expression levels of pro-inflammatory mediators including IL-6, IL-1β, MIP-2, and iNOS, while stimulating the expression of lung protective factors such as IL-10, CC16, SP-D, and sRAGE. Moreover, HX110B improved the impaired OXPHOS subunit gene expression. In vitro analysis revealed that HX110B exerted its effects by activating the PPAR-RXR signaling pathways. Overall, our data demonstrated that HX110B could be a promising therapeutic option for COPD treatment.

Abstract Several programs are widely used for clinical and research purposes to automatically quantify the degree of amyloid deposition in the brain using positron emission tomography (PET) images. Given that very few studies have investigated the use of Heuron, a PET image quantification software approved for clinical use, this study aimed to compare amyloid deposition values quantified from 18F-flutemetamol PET images using PMOD and Heuron. Amyloid PET data obtained from 408 patients were analysed using each quantitative program; moreover, the standardized uptake value ratios (SUVRs) of target areas were obtained by dividing the standardized uptake value (SUV) of the target region by the SUV of cerebellar grey matter as a reference. Compared with PMOD, Heuron yielded significantly higher SUVRs for all target areas (paired sample t-test, p

Abstract Congenital lung malformations (CLM) are most commonly treated with a pulmonary lobectomy. However, due to technological advancement, video-assisted thoracoscopic surgery (VATS) segmentectomy is becoming an attractive alternative to VATS lobectomy. This study aimed to evaluate the safety, feasibility, and efficacy of VATS segmentectomy as a lung parenchyma-saving strategy in children with CLM. A retrospective analysis was performed on 85 children, for whom VATS segmentectomy was tried for CLM between January 2010 and July 2020. We compared the surgical outcomes of VATS segmentectomy with the outcomes of 465 patients who underwent VATS lobectomy. Eighty-four patients received VATS segmentectomy and thoracotomy conversion was necessary for one patient for CLM. The mean age was 3.2 ± 2.5 (range 1.2–11.6) years. The mean operative time was 91.4 ± 35.6 (range 40–200) minutes. The median duration of chest tube drainage was 1 (range 1–21) day, and the median length of postoperative hospital stay was 4 (range 3–23) days. There were no postoperative mortality and postoperative complications developed in 7 patients (8.2%), including persistent air leakage in 6 patients (7.1%) and postoperative pneumonia in 1 patient (1.2%). The median follow-up period was 33.5 (interquartile range 31–57) months and there were no patients requiring re-intervention or reoperation during the follow-up period. In the VATS segmentectomy group, the persistent air leakage rate was higher than in the VATS lobectomy group (7.1 vs. 1.1%, p = 0.003). Otherwise, postoperative outcomes were comparable between the two groups. VATS segmentectomy in children with CLM is a technically feasible alternative to VATS lobectomy with acceptable early and mid-term outcomes. However, the persistent air-leakage rate was higher in VATS segmentectomy.

Abstract Platinum single-atom catalysts hold promise as a new frontier in heterogeneous electrocatalysis. However, the exact chemical nature of active Pt sites is highly elusive, arousing many hypotheses to compensate for the significant discrepancies between experiments and theories. Here, we identify the stabilization of low-coordinated PtII species on carbon-based Pt single-atom catalysts, which have rarely been found as reaction intermediates of homogeneous PtII catalysts but have often been proposed as catalytic sites for Pt single-atom catalysts from theory. Advanced online spectroscopic studies reveal multiple identities of PtII moieties on the single-atom catalysts beyond ideally four-coordinated PtII–N4. Notably, decreasing Pt content to 0.15 wt.% enables the differentiation of low-coordinated PtII species from the four-coordinated ones, demonstrating their critical role in the chlorine evolution reaction. This study may afford general guidelines for achieving a high electrocatalytic performance of carbon-based single-atom catalysts based on other d 8 metal ions.

Abstract Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (Pinteraction = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications.

Background: Hepatocellular carcinoma (HCC) has a high incidence and is one of the highest mortality cancers when advanced stage is proceeded. However, Anti-cancer drugs available for treatment are limited and new anti-cancer drugs and new ways to treat them are minimal. We examined that the effects and possibility of Red Ginseng (RG, Panax ginseng Meyer) as new anti-cancer drug on HCC by combining network pharmacology and molecular biology. Materials and Methods: Network pharmacological analysis was employed to investigate the systems-level mechanism of RG focusing on HCC. Cytotoxicity of RG was determined by MTT analysis, which were also stained by annexin V/PI staining for apoptosis and acridine orange for autophagy. For the analyze mechanism of RG, we extracted protein and subjected to immunoblotting for apoptosis or autophagy related proteins. Results: We constructed compound-target network of RG and identified potential pathways related to HCC. RG inhibited growth of HCC through acceleration of cytotoxicity and reduction of wound healing ability of HCC. RG also increased apoptosis and autophagy through AMPK induction. In addition, its ingredients, 20S-PPD (protopanaxadiol) and 20S-PPT (protopanaxatriol), also induced AMPK mediated apoptosis and autophagy. Conclusion: RG effectively inhibited growth of HCC cells inducing apoptosis and autophagy via ATG/AMPK in HCC cells. Overall, our study suggests possibility as new anti-cancer drug on HCC by proof for the mechanism of the anti-cancer action of RG.

Objectives To confirm both efficiency and sustainability of algal growth inhibition, various laboratory-scale experiments were conducted and the growth inhibitory effect of Microcystis aeruginosa (M. aeruginosa) was investigated through ultrasonic re-irradiation during the regrowth period after the first ultrasound irradiation. Methods Experiments with different times of irradiation [i.e., control group A (0 hr), experimental group B (2 hr) applied with only the first ultrasound irradiation, and experimental group C (0.5 hr), D (1 hr), and E (1.5 hr) applied with both first and second irradiations] were performed. Results and Discussion As a result of both Chlorophyll-a (Chl-a) concentration and cell number of M. aeruginosa, the experimental group (B) with only first ultrasound irradiation (2 hr) displayed rapid regrowth of algae after initial decrease whereas the experimental group (C, D, and E) with both first ultrasound irradiation (2 hr) and second ultrasound irradiation (0.5 hr, 1 hr, and 1.5 hr) confirmed the delay of algae regrowth. Based on the specific growth rate constant (µ) and first order decay rate constant (k), algal growth from the experimental groups (C, D, E) with the secondary ultrasound irradiation was more significantly inhibited due to repetitive inactivation of algae growth. According to the SEM and TEM results, damages to algae cells were clearly observed under the influence of ultrasound, and both decrease in gas vesicles and rupture of cell membrane in M. aeruginosa were also monitored. Conclusion Through this study, the algae growth inhibitory effect by ultrasonic irradiations was confirmed, and the re-irradiation of ultrasound contributed to the repetitive inactivation of algae growth, indicating that the second ultrasonic irradiation time required to inhibit algal regrowth can be reduced compared to the first irradiation. Therefore, periodic ultrasonic irradiation is required for long-term inhibition of algae growth in stagnant waters, but the appropriate frequency of ultrasonic irradiation may vary depending on the influence of various complex factors such as the size of the stagnant waters, the frequency of algal blooms, water temperature, light irradiation, nutrients, flow rate, etc. Finally, many field studies under various conditions are warranted to establish an optimized ultrasound irradiation protocol.

Background As a side effect of interscalene brachial plexus block (ISBPB), stellate ganglion block (SGB) causes reductions in pupil size (Horner’s syndrome) and cardiac sympathetic nervous activity (CSNA). Reduced CSNA is associated with hemodynamic instability when patients are seated. Therefore, instantaneous measurements of CSNA are important in seated patients presenting with Horner’s syndrome. However, there are no effective tools to measure real-time CSNA intraoperatively. To evaluate the usefulness of pupillometry in measuring CSNA, we investigated the relationship between pupil size and CSNA. Methods Forty-two patients undergoing right arthroscopic shoulder surgery under ISBPB were analyzed. Pupil diameters were measured at 30 Hz for 2 s using a portable pupillometer. Bilateral pupil diameters and CSNA (natural-log-transformed low-frequency power [0.04–0.15 Hz] of heart rate variability [lnLF]) were measured before ISBPB (pre-ISBPB) and 15 min after transition to the sitting position following ISBPB (post-sitting). Changes in the pupil diameter ([right pupil diameter for post-sitting – left pupil diameter for post-sitting] – [right pupil diameter for pre-ISBPB – left pupil diameter for pre-ISBPB]) and CSNA (lnLF for post-sitting – lnLF for pre-ISBPB) were calculated. Results Forty-one patients (97.6%) developed Horner’s syndrome. Right pupil diameter and lnLF significantly decreased upon transition to sitting after ISBPB. In the linear regression model (R2 = 0.242, P = 0.001), a one-unit decrease (1 mm) in the extent of changes in the pupil diameter reduced the extent of changes in lnLF by 0.659 ln(ms2/Hz) (95% CI [0.090, 1.228]). Conclusions Pupillometry is a useful tool to measure changes in CSNA after the transition to sitting following ISBPB.

Sargassum horneri (SH) is widely consumed as a healthy seaweed food in the Asia–Pacific region. However, the bioactive components contributing to its biological activity remain unknown. Herein, we optimized multifrequency ultrasonic-assisted extraction conditions to achieve higher antioxidant activity using a response surface methodology and an artificial neural network. High-resolution mass spectrometry (HRMS; negative mode) was used to tentatively identify the secondary metabolites in the optimized SH extract, which were further tested against oxidative stress in RAW264.7 cells. Additionally, the identified compounds were analyzed in silico to determine their binding energies with the Keap1 protein (4L7B). We identified 89 compounds using HRMS, among which 19 metabolites (8 polyphenolics, 2 flavonoids, 2 lignans, 2 terpenes, 2 tannins, 2 sulfolipids, and 1 phospholipid) were putatively reported for the first time in SH. The in vitro results revealed that optimized SH extract inhibited oxidative stress via the Nrf2/MAPKs/HO-1 pathway in a dose-dependent manner. This result was validated by performing in silico simulation, indicating that sargaquinoic acid and glycitein-7-O-glucuronide had the highest binding energies (−9.20 and −9.52 Kcal/mol, respectively) toward Keap1 (4L7B). This study offers a unique approach for the scientific community to identify potential bioactive compounds by optimizing the multivariant extraction processing conditions, which could be used to develop functional and nutraceutical foods.

This study aimed to identify the effectiveness and potential complications on the harvest site and knee of bone marrow aspirate concentrate (BMAC) treatment of patients with Kellgren–Lawrence (K–L) grades II–III knee osteoarthritis (OA) over a minimum follow-up period of 6 months. This study retrospectively evaluated data from 231 patients (285 knees) with knee OA treated with BMAC articular injection at a single center from August 2023 to October 2023. The inclusion criteria were a longstanding knee pain unresponsive to conservative treatments for at least 6 weeks with K–L grades II–III OA. The exclusion criteria were age of 80 years, previous knee surgery, rheumatological or other systemic disease, malignancy, uncontrolled diabetes mellitus, or infections. Bone marrow was aspirated from the anterior iliac crest and concentrated by the single-spin centrifugation technique. The visual analog scale (VAS) pain score and Knee Society Score were used to evaluate the clinical outcomes and complications associated with harvest and injection sites were evaluated. The mean follow-up period was 7.2 months (range: 6–8 months). The pretreatment VAS pain score decreased from 4.3 to 0.4 points at the final follow-up (p < 0.05). Pretreatment Knee Society knee and function scores were improved from 86.9 to 98.1 (p < 0.05) and from 68.4 to 83.3 points (p < 0.05), respectively. A total of 15 complications (5.3%, 15/285) were observed, including 3 hematomas, 2 numbness, 2 contact dermatitis, and 1 superficial infection in the harvest site and 4 mild and moderate swelling and 3 severe swelling and pain in the injection site. BMAC is a reliable and effective treatment for patients with K–L grades II–III knee OA, but the orthopedic surgeon should consider that bleeding tendency by heparin causes severe joint swelling and pain after intra-articular knee injection.

Wheat (Triticum aestivum Linn.; Poaceae) is the second most cultivated food crop among all global cereal crop production. The high carbohydrate content of its grains provides energy, multiple nutrients, and dietary fiber. After threshing, a substantial amount of wheat hull is produced, which serves as the non-food component of wheat. For the valorization of these by-products as a new resource from which functional components can be extracted, the hull from the seeds of cultivated wheat mutant lines bred after γ-irradiation were collected. Untargeted metabolite analysis of the hull of the original cultivar (a crossbreeding cultivar., Woori-mil × D-7) and its 983 mutant lines were conducted using ultra-performance liquid chromatography–electrospray ionization quadrupole time-of-flight mass spectrometry technique. A total of 55 molecules were tentatively identified, including 21 compounds found in the Triticum species for the first time and 13 compounds not previously described. Among them, seven flavonolignans with a diastereomeric structure, isolated as a single compound from the hull of T. aestivum in our previous study, were used as the standards in the metabolite analysis. The differences in their collision cross-section values were shown to contribute to the clear distinction between tricine-lignan stereoisomers. To select functionally active agents with anti-inflammatory activity among the identified compounds, the wheat hull samples were evaluated for their inhibitory effect on nitric oxide production in lipopolysaccharide-stimulated RAW 264.7 cells. As a result of multivariate analysis based on the results of chemical and biological profiles of the wheat hull samples, 10 metabolites were identified as key markers, contributing to the distinction between active and inactive mutant lines. Considering that one of the four key markers attributed to anti-inflammatory activity has been identified to be a flavonolignan, the wheat hull could be a valuable source of diverse tricin-lignan type compounds and used as a natural health-promoting product in food supplements.

BackgroundThe SoUth Korean study to PrEvent cognitive impaiRment and protect BRAIN health through lifestyle intervention in at-risk elderly people (SUPERBRAIN) is a part of the World-Wide Finnish Geriatric Intervention Study to Prevent Cognitive Impairment and Disability (WW-FINGERS) network. This study aimed to demonstrate the effects of the SUPERBRAIN-based multidomain intervention with nutritional supplements in amyloid positive emission tomography (PET) proven early symptomatic Alzheimer’s disease patients.MethodsForty-six participants who were diagnosed with mild cognitive impairment or mild dementia and were positive in the amyloid PET study randomized into three groups: group A, the multidomain intervention with nutritional supplements; group B, nutritional supplements only; and a control group. The primary outcome was a change in the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) total scale index score after an 8-week intervention. Secondary outcomes, including gut microbiome data, were also analyzed.ResultsThe RBANS total scale index score improved significantly in group A compared with group B (p

BackgroundA genome-wide association study (GWAS) is a valuable tool for investigating genetic and phenotypic variation in many diseases.ObjectiveThe objective of this study was to identify variations in the genomes of Maltese dogs that are associated with the mammary gland tumor (MGT) phenotype and to assess the association between each biological condition and MGT phenotype in Maltese dogs.MethodsDNA was extracted from 22 tumor samples and 11 whole blood samples from dogs with MGTs. Genome-wide single-nucleotide polymorphism (SNP) genotyping was performed, and the top 20 SNPs associated with various conditions and genetic variations were mapped to their corresponding gene locations.ResultsThe genotyping process successfully identified 173,662 loci, with an overall genotype completion rate of 99.92%. Through the quality control analysis, 46,912 of these SNPs were excluded. Allelic tests were conducted to generate Manhattan plots, which showed several significant SNPs associated with MGT phenotype in intergenic region. The most prominent SNP, located within a region associated with transcription and linked to the malignancy grade of MGT, was identified on chromosome 5 (p = 0.00001) though there may be lack of statistical significance. Other SNPs were also found in several genes associated with oncogenesis, including TNFSF18, WDR3, ASIC5, STAR, and IL1RAP.ConclusionTo our knowledge, this is the first GWAS to analyze the genetic predisposition to MGT in Maltese dogs. Despite the limited number of cases, these analyzed data could provide the basis for further research on the genetic predisposition to MGTs in Maltese dogs.

Abstract The DAMA/LIBRA collaboration has reported the observation of an annual modulation in the event rate that has been attributed to dark matter interactions over the last two decades. However, even though tremendous efforts to detect similar dark matter interactions were pursued, no definitive evidence has been observed to corroborate the DAMA/LIBRA signal. Many studies assuming various dark matter models have attempted to reconcile DAMA/LIBRA’s modulation signals and null results from other experiments, however no clear conclusion can be drawn. Apart from the dark matter hypothesis, several studies have examined the possibility that the modulation is induced by variations in detector’s environment or their specific analysis methods. In particular, a recent study presents a possible cause of the annual modulation from an analysis method adopted by the DAMA/LIBRA experiment in which the observed annual modulation could be reproduced by a slowly varying time-dependent background. Here, we study the COSINE-100 data using an analysis method similar to the one adopted by the DAMA/LIBRA experiment and observe a significant annual modulation, however the modulation phase is almost opposite to that of the DAMA/LIBRA data. Assuming the same background composition for COSINE-100 and DAMA/LIBRA, simulated experiments for the DAMA/LIBRA without dark matter signals also provide significant annual modulation with an amplitude similar to DAMA/LIBRA with opposite phase. Even though this observation does not directly explain the DAMA/LIBRA results directly, this interesting phenomenon motivates more profound studies of the time-dependent DAMA/LIBRA background data.