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Prior case reports have suggested that treating thoracic outlet syndrome (TOS) may relieve intractable migraine headaches, but there has been no case series large enough to show when underlying TOS should be suspected as a contributor to migraine burden. This observational followed by questionnaire study was performed in an outpatient neurology practice to identify clinical features of patients with migraine in which TOS contributed to migraine burden. We report the clinical features of 50 consecutive patients (48 women, 2 men, age = 43.9+/12.7 years) who were treated for chronic migraine and TOS (20 migraine with aura, 28 migraine without aura, two hemiplegic migraines). Headaches had become chronic within 1 year of onset in 21 patients (42%) with characteristics as follows (percentages are based on known data): greater severity ipsilateral to TOS limb pain (38/50=76%), presence of limb swelling (32/48=67%), and worsened by recumbency (32/38=84%). Thirty-two patients eventually needed surgery, which included percutaneous transluminal venoplasty, 1st rib removal, scalenectomy, pectoralis minor tenotomy, and/or vein patching. The mean improvement of headaches on the treated side was 72 ± 26.7%; 12 patients experienced complete resolution of headaches after treatment of TOS (follow-up 7.2 ± 5.2 months). Questionnaire responders reported significant reductions in headache days (18.3 ± 8.6 to 11.1 ± 10.8 days/month, p < 0.0016), severity (7.8+/2.5 to 5.4 ± 2.9, p < 0.00079), and need for emergency care (3.6 ± 4.0 to 0.71 ± 1.3 visits/year, p < 0.0029). Chronic migraines can be important manifestations of TOS. Early transition to a chronic state, lateralized limb pain, and headaches worsened by recumbency are clues to the contribution of TOS pathology. Addressing the TOS contribution to migraine can significantly reduce migraine headache burden., (© 2024 The Author(s). Clinical Anatomy published by Wiley Periodicals LLC on behalf of American Association of Clinical Anatomists and British Association of Clinical Anatomists.)

Global increases in the occurrence of harmful algal blooms (HABs) are of major concern in water quality and resource management. A predictive model capable of quantifying the spatiotemporal associations between HABs and their influencing factors is required for effective preventive management. In this study, a feature stream network (FSN) model is proposed to provide daily forecasts of cyanobacteria abundance at multiple monitoring sites simultaneously in a river network. The spatial connectivity between monitoring sites was expressed as a directed acyclic graph comprising edges and nodes representing flows and monitoring sites, respectively. Furthermore, a segment-wise node connection structure was developed to extract the latent features of a river segment comprising individual nodes and sequentially transfer them to the downstream segment(s). In addition, a feature engineering-attention hybrid mechanism was employed to address temporal mismatches among different monitoring schemes while adding explainability to the model. Consequently, the FSN showed improved predictive performance, temporal resolution, and explainability for multi-site forecasts of HAB in a single model framework. The developed model was applied to a bloom-prone middle course of the Nakdong River, South Korea. Various hydrological, environmental, and biological factors were utilized for forecasting the cyanobacteria abundance. The FSN exhibited a high degree of accuracy across the sites for the test data with a coefficient of determination in the range of 0.64-0.71 and root mean square error in the range of 2.06-2.26 cells/mL on natural log scales. Although the relative importance of input features varied across the sites, the features extracted from nearby nodes consistently exhibited high importance in forecasting the cyanobacteria abundance. These explanations indicate that the proposed model can successfully characterize the spatial hierarchy of a river network. A scenario analysis suggested that reduced total nitrogen loads in the effluents from the wastewater treatment plant and the combined operations of upstream and downstream weirs were effective in managing HABs., 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: We aimed to examine the regional disparities in secondary fracture incidence among patients with hip fractures in South Korea., Methods: This observational, retrospective, cohort study was conducted using data of 6,213 South Korean nationals from the National Health Insurance Service-National Sample Cohort (2004-2019). Secondary fractures included hip, wrist, humerus, spine, ankle, and pelvis fractures that occurred 6 months after hip fracture. The position value for relative composite index was used to identify medically vulnerable regions. Cox proportional hazards models were used for statistical analysis., Results: Among the 6,213 (1,949 male, 4,264 female) patients with hip fracture, 981 lived in medically vulnerable areas and 5,232 in non-vulnerable areas. Patients residing in vulnerable areas had a higher risk of secondary fractures than did those residing in non-vulnerable areas (hazard ratio [HR]: 1.24, 95 % confidence interval [CI]: 1.05-1.47); the factors that increased their risk included female sex (HR: 1.30, 95 % CI: 1.08-1.57), age ≥71 years (HR: 1.23, 95 % CI: 1.01-1.44), and not receiving osteoporosis medication (HR: 1.47, 95 % CI: 1.14-1.89). Ten years after hip fracture surgery, the risk of secondary fracture more than tripled in the vulnerable areas than that in the non-vulnerable areas., Conclusion: Patients living in vulnerable regions had a higher risk of secondary fractures than that of those in non-vulnerable regions. Prevention and medication policies should thus be implemented to reduce regional healthcare disparities., Competing Interests: Declaration of competing interest Minah Park, Younghan Cha, Jae-hyun Kim, Seung Hoon Kim declare that they have no conflict of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Iodoform (CHI 3 ) has garnered significant attention for its unique ability to induce photo-cyclopropanation of olefins by releasing an iodine radical through C-I bond cleavage. However, the detailed mechanism underlying CHI 3 photodissociation is still not fully understood. Here, we elucidate the ultrafast structural dynamics of CHI 3 upon photoexcitation using femtosecond time-resolved X-ray liquidography (fs-TRXL) at an X-ray free-electron laser facility. The fs-TRXL data was decomposed into the isotropic and anisotropic data. The isotropic data reveal that the formation of CHI 2 and I radicals upon photolysis precedes the emergence of iso -CHI 2 -I. After a short induction period, two competing geminate recombination pathways of CHI 2 and I radicals take place: one pathway leads to the recovery of CHI 3 , while the other results in the formation of iso -CHI 2 -I. Additionally, the anisotropic data show how the transient anisotropic distribution of both the species formed upon photoexcitation and the ground-state species depleted upon photoexcitation decays through rotational dephasing. Furthermore, the observed structural dynamics of CHI 3 has distinctive differences with that of BiI 3 , which can be attributed to differences in their central moieties, CH and Bi. Our findings provide insights into the photoinduced reaction dynamics of CHI 3 , enhancing the understanding of its role in photochemical reactions., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

α-Synuclein (α-syn) strains can serve as discriminators between Parkinson's disease (PD) from other α-synucleinopathies. The relationship between α-syn strain dynamics and clinical performance as patients transition from normal cognition (NC) to cognitive impairment (CI) is not known. Here, we show that the biophysical properties and neurotoxicity of α-syn strains change as PD cognitive status transitions from NC to mild cognitive impairment (PD-MCI) and dementia (PD-D). Both cross-sectional and longitudinal analyses reveal distinct α-syn strains in PD patients correlating to their level of cognitive impairment. This study presents evidence that individuals with PD have different α-syn strains that change in accordance with their cognitive status and highlights the potential of α-syn strain dynamics to guide future diagnosis, management, and stratification of PD patients.

Whole blood donors who donate more frequency are more likely to develop iron deficiency, which could potentially affect the quality of the red blood cell (RBC) components during storage. Additional donor factors such as sex, age at donation, donor body mass index (BMI), as well as the manufacturing method could also affect RBC component quality, particularly haemolysis. The aim of this study was to examine the relationship between donation frequency, donor ferritin levels and BMI status on an extensive set of RBC characteristics in vitro, during storage at 2-6 °C for 42 days. A whole blood donation was collected from 787 Australian blood donors, held overnight, before top-and-bottom separation to produce RBC components. RBC components were tested using a panel of in vitro assays. Serum ferritin was tested from a sample taken at the time of donation, and donor demographic data was collected. Haemolysis in RBC components was not found to be associated with donation frequency. Increased red cell haemolysis, lactate concentration, extracellular potassium and RBC-derived microparticle numbers were significantly associated with a high BMI in male donors. There was also a trend towards increased red cell haemolysis in donors with ferritin concentrations in the upper range. Our findings indicate that although older male donors with potentially higher BMI are able to donate whole blood quite frequently, the resultant RBC components may have poorer in vitro quality., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Previous studies with large data have been widely reported that exposure to fine particulate matter (PM2.5) is associated with all-cause mortality; however, most of these studies adopted ecological time-series designs or have included limited study areas or individuals residing in well-monitored urban areas. However, nationwide cohort studies including cause-specific mortalities with different age groups were sparse. Therefore, this study examined the association between PM2.5 and cause-specific mortality in South Korea using the nationwide cohort., Methods: A longitudinal cohort with 187 917 National Health Insurance Service-National Sample Cohort participants aged 50-79 years in enrolment between 2002 and 2019 was used. Annual average PM2.5 was collected from a machine learning-based ensemble model (a test R2 = 0.87) as an exposure. We performed a time-varying Cox regression model to examine the association between long-term PM2.5 exposure and mortality. To reduce the potential estimation bias, we adopted generalized propensity score weighting method., Results: The association with long-term PM2.5 (2-year moving average) was prominent in mortalities related to diabetes mellitus [hazard ratio (HR): 1.03 (95% CI: 1.01, 1.06)], circulatory diseases [HR: 1.02 (95% CI: 1.00, 1.03)] and cancer [HR: 1.01 (95% CI: 1.00, 1.02)]. Meanwhile, circulatory-related mortalities were associated with a longer PM2.5 exposure period (1 or 2-year lags), whereas respiratory-related mortalities were associated with current-year PM2.5 exposure. In addition, the association with PM2.5 was more evident in people aged 50-64 years than in people aged 65-79 years, especially in heart failure-related deaths., Conclusions: This study identified the hypothesis that long-term exposure to PM2.5 is associated with mortality, and the association might be different by causes of death. Our result highlights a novel vulnerable population: the middle-aged population with risk factors related to heart failure., (© The Author(s) 2024; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.)

Background: The co-occurrence of Lemierre's syndrome, primarily triggered by Fusobacterium necrophorum following oropharyngeal infection, with diabetic ketoacidosis (DKA) in diabetes mellitus (DM) patients, underscores a rare but life-threatening clinical scenario. Lemierre's syndrome induced DKA is extremely rare, with only one case report in adult and no case yet reported in elderly., Case Presentation: We reported a case of a 69-year-old female who presented with DKA triggered by deep neck space infection (DNSI), leading to rapid clinical deterioration within 6 h that necessitated high flow nasal cannula (HFNC) and antibiotic administration. Laboratory findings included leukocytosis, elevated serum C-reactive protein, hyperglycemia, ketonemia, and severe metabolic acidosis. Culture of the fluid from a neck mass puncture drainage and blood were positive for Klebsiella pneumoniae. The patient was further complicated by thrombosis of the left internal jugular vein with extension to the sigmoid and a neck abscess surrounding the carotid artery sheath, consistent with Lemierre's syndrome. This condition was managed aggressively with fluid resuscitation, insulin therapy, surgical drainage, antibiotics, and anticoagulation led to a significant improvement in her condition. Following a 13-day hospitalization, there was significant clinical improvement, culminating in the patient's discharge., Conclusions: The case highlights the need for greater awareness and understanding of the interrelated and mutually promoting conditions of DKA and Lemierre's syndrome among clinicians. Early recognition and treatment are crucial to prevent mortality in such complex cases., (© 2024. The Author(s).)

Does residential mobility change cultures, or is it merely a downstream indicator for other forces? Using large-scale surveys of citizens of 18 industrialized nations, we find that increased rates of residential mobility predict living in a more dynamic society at least 10 years in the future: one in which residents are more satisfied with their lives, have greater optimism, endorse more individualistic concepts, are more open to new ideas, have a greater sense of freedom of action, feel able to make friends more easily, express a more cosmopolitan identity, believe that their society rewards merit, and hold their community to a higher standard for treatment of minorities. These findings are echoed in the experience of Americans who have themselves recently moved, where we find that having successfully moved predicts a future sense of personal thriving, optimism, and a belief that merit is rewarded., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Next-generation sequencing (NGS) has become widely available but molecular profiling-guided therapy (MGT) had not been well established in the real world due to lack of available therapies and expertise to match treatment. Our study was designed to test the feasibility of a nationwide platform of NGS-guided MGT recommended by a central molecular tumor board (cMTB) for metastatic solid tumors., Patients and Methods: Patients with advanced or metastatic solid tumors with available NGS results and without standard treatment were enrolled. The cMTB interpreted the patients' NGS reports and recommended the following: (i) investigational medicinal products (IMPs) approved in other indications; (ii) alternative treatments; (iii) clinical trials. The primary variables were the proportion of patients with actionable genomic alterations and those receiving MGT as per cMTB recommendations. Others included treatment duration (TD), overall response rate (ORR), disease control rate (DCR), and safety., Results: From February 2021 to February 2022, 193 cases [99 (51.3%) men; median age 58 years (range 24-88 years); median line of previous treatment 3 (range 0-9)] from 29 sites were enrolled for 60 cMTB sessions. The median time from case submission to cMTB discussion was 7 days (range 2-20 days), and to IMP treatment initiation was 28 days (range 14-90 days). Actionable genetic alterations were found in 145 patients (75.1%). A total of 89 (46.1%) patients received actual dosing of IMPs, and 10 (5.2%) were enrolled in cMTB-recommended clinical trials, achieving an MGT rate of 51.3%. ORR and DCR of IMPs were 10.1% and 72.5%, respectively. The median TD was 3.5 months [95% confidence interval (CI) 2.8-5.5 months], and the 4-month TD rate was 44.9%. The median overall survival of patients who received IMPs was 6.9 months (95% CI 5.2-10.0 months)., Conclusion: KOSMOS confirmed the feasibility of MGT recommended by the cMTB, achieving a high MGT match rate and promising effectiveness in heavily pretreated advanced cancer patients., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The importance of the complex interplay between the microbiome and mucosal immunity, particularly within the respiratory tract, has gained significant attention due to its potential implications for the severity and progression of lung diseases. Therefore, this review summarizes the specific interactions through which the respiratory tract-specific microbiome influences mucosal immunity and ultimately impacts respiratory health. Furthermore, we discuss how the microbiome affects mucosal immunity, considering tissue-specific variations, and its capacity in respiratory diseases containing asthma, chronic obstructive pulmonary disease, and lung cancer. Additionally, we investigate the external factors which affect the relationship between respiratory microbiome and mucosal immune responses. By exploring these intricate interactions, this review provides valuable insights into the potential for microbiome-based interventions to modulate mucosal immunity and alleviate the severity of respiratory diseases., (© 2024. The Author(s), under exclusive licence to Microbiological Society of Korea.)

Amomum tsao-ko Crevost et Lemarie (Zingiberaceae), an aromatic plant, has been considered to have diverse medicinal values and economic significance. It has been reported to possess antibacterial, antioxidant, and antidiabetic effects. With the increasing risk of diseases in aquaculture, there is a need for alternative solutions to chemical antibiotics. Plant extracts have shown promise as natural feed additives for aquatic animals. In this study, the antibacterial effect of Amomum tsao-ko crude extracts was evaluated using the Oxford cup method. The extracts exhibited significant antimicrobial activity against Salmonella typhimurium and Salmonella enteritidis. Furthermore, the addition of Amomum tsao-ko to fish feed resulted in notable changes in the gut structure of zebrafish and tilapia. The length and morphology of intestinal villi were enhanced, promoting improved digestion. Analysis of the gut microbial community revealed that Amomum tsao-ko supplementation induced key changes in the gut microbial community composition of both zebrafish and tilapia. Notably, a 1% inclusion of Amomum tsao-ko resulted in a marked rise in Proteobacteria levels in zebrafish, which diminished at 10% dosage. The supplement elicited mixed reactions among other bacterial phyla like Actinobacteria and Verrucomicrobiota. Fluctuations were also observed at the genus level, pointing to the concentration of Amomum tsao-ko playing a pivotal role in influencing the structure of intestinal bacteria. The findings of this study suggest that Amomum tsao-ko has antibacterial properties and can positively influence the gut health of fish. The potential use of Amomum tsao-ko as a natural feed additive holds promise for improving aquaculture practices and reducing reliance on chemical antibiotics. Further research is needed to explore the full potential and applications of Amomum tsao-ko in fish feed development., (© 2024 Fisheries Society of the British Isles.)

Background: Trastuzumab deruxtecan has shown encouraging activity in patients with treatment-refractory HER2-positive, RAS wild-type and BRAF wild-type metastatic colorectal cancer. Dose optimisation and further antitumour assessments in patients with RAS mutations and those with previous anti-HER2 therapy are warranted. We aimed to evaluate two doses of trastuzumab deruxtecan (5·4 mg/kg and 6·4 mg/kg) to establish the recommended dose in patients with pretreated HER2-positive, RAS wild-type or mutant metastatic colorectal cancer., Methods: DESTINY-CRC02 was a multicentre, randomised, two-stage, two-arm, phase 2 study done in 53 research hospitals and medical centres in Australia, Belgium, France, Italy, Japan, South Korea, Spain, Taiwan, the UK, and the USA. Eligible patients were aged 18 years and older or 20 years and older (depending on region) with pretreated pathologically documented, unresectable, recurrent, or metastatic HER2-positive, and RAS wild-type or mutant colorectal cancer. Patients were required to have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and have received previous chemotherapy, and anti-EGFR, anti-VEGF, or anti-PD-L1 therapy, if clinically indicated. In stage 1, patients were randomly assigned (1:1), via a secure interactive response technology system, to receive 5·4 mg/kg or 6·4 mg/kg trastuzumab deruxtecan administered intravenously every 21 days. Stratification factors were ECOG performance status, HER2 status, and RAS status. In stage 2, patients were assigned into the 5·4 mg/kg treatment group only. The primary endpoint was confirmed objective response rate by blinded independent central review, assessed in all patients for whom treatment was assigned (full analysis set). Safety was assessed in all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, NCT04744831, and is ongoing (not recruiting)., Findings: Between March 5, 2021, and March 29, 2022, 135 patients were centrally screened, 122 of whom were enrolled. In stage 1, 40 patients each were randomly assigned to receive trastuzumab deruxtecan 5·4 mg/kg and 6·4 mg/kg. In stage 2, an additional 42 patients were enrolled in the 5·4 mg/kg group. 64 (52%) participants were male and 58 (48%) were female. The median duration of follow-up was 8·9 months (IQR 6·7-10·5) in the 5·4 mg/kg group and 10·3 months (5·9-12·7) in the 6·4 mg/kg group. The confirmed objective response rate by blinded independent central review was 37·8% (31/82 [95% CI 27·3-49·2]) in the 5·4 mg/kg group and 27·5% (11/40 [14·6-43·9]) in the 6·4 mg/kg group. 34 (41%) of 83 patients in the 5·4 mg/kg group and 19 (49%) of 39 in the 6·4 mg/kg group had grade 3 or worse drug-related treatment-emergent adverse events. The most common grade 3 or worse drug-related treatment-emergent adverse events were neutrophil count decreased (13 [16%] of 83 patients), anaemia (six [7%]), nausea (six [7%]), and white blood cell count decreased (five [6%]) in the 5·4 mg/kg group; and were neutrophil count decreased (10 [26%] of 39 patients), anaemia (eight [21%]), platelet count decreased (four [10%]), and white blood cell count decreased (four [10%]) in the 6·4 mg/kg group. Drug-related serious adverse events occurred in 11 (13%) of 83 patients in the 5·4 mg/kg group and six (15%) of 39 patients in the 6·4 mg/kg group; the most common in the 5·4 mg/kg group was nausea (three [4%] patients) and the most common in the 6·4 mg/kg group were fatigue (two [5%] patients), neutropenia (two [5%]), and thrombocytopenia (two [5%]). A drug-related treatment-emergent adverse event related to death occurred in one (1%) patient in the 5·4 mg/kg group (due to hepatic failure). Adjudicated drug-related interstitial lung disease or pneumonitis events were observed in seven (8%) patients in the 5·4 mg/kg group (all grade 1 or 2) and in five (13%) patients in the 6·4 mg/kg group (four grade 1 or 2; one grade 5)., Interpretation: The promising antitumour activity and favourable safety profile support trastuzumab deruxtecan 5·4 mg/kg as the optimal single-agent dose for patients with pretreated HER2-positive metastatic colorectal cancer, including those with RAS mutations, previous anti-HER2 therapy, or both., Funding: Daiichi Sankyo and AstraZeneca., Competing Interests: Declaration of interests KR has received research grants from Bayer, UCB BioSciences, Hibercell, Eisai, Merck, Janssen Pharmaceuticals, AbbVie, Daiichi Sankyo, Guardant Health, Innovent Biologics, and Xencor; has received payment or honoraria from Bayer, Daiichi Sankyo, and Seagen; and has participated on a data safety monitoring board or advisory board for Bayer, Eisai/Merck, SAGA Diagnostics, Daiichi Sankyo, Seagen, Pfizer, and AstraZeneca. SS has participated on a data safety monitoring board or advisory board for Agenus, AstraZeneca, Bayer, Bristol Myers Squibb, CheckmAb, Daiichi Sankyo, GlaxoSmithKline, MSD, Merck, Novartis, Pierre Fabre, Seagen, and T-One Therapeutics. AT has received research grants from Daiichi Sankyo, Ono Pharmaceutical, Bristol Myers Squibb, Pfizer, Merck Sharp & Dome, Isofol Medical, Incyte Corporation, and Hutchison Medipharma; and has received payment or honoraria from Eli Lilly, Taiho Pharmaceutical, Ono Pharmaceutical, Chugai Pharma, Merck Serono, and Takeda. TKat has received payment or honoraria from Chugai Pharmaceutical, Ono Pharmaceutical, Takeda Pharmaceutical, and Eli Lilly. FP has received payment or honoraria from Amgen, Merck-Serono, MSD, BMS, Astellas, Johnson & Johnson, Takeda, Bayer, Servier, Pierre Fabre, Ipsen, GSK, and Rottapharm. YK has received royalties or licenses from Ono Pharmaceutical, Chugai Pharmaceutical, Taiho Pharmaceutical, Shionogi, Nippon Zoki Pharmaceuticals, Asahi Kasei Pharma Corporation, Nippon, Kayaku, Daiichi Sankyo, IQVIA Services Japan, MSD, Astellas Pharma, Incyte Corporation, Eisai, National Cancer Center Japan, Syneos Health Clinical, ShiftZero, Parexel International, Japan Clinical Cancer Research Organization, EPS Holdings, Sysmex Corporation, Public Health Research Foundation, Aichi Cancer Center, and Kyushu Study group of Clinical Cancer; and has received payment or honoraria from Ono Pharmaceutical, TAIHO Pharmaceutical, Astellas Pharma, EA Pharma, Daiichi Sankyo, Nippon, Kayaku, Pfizer, Nippon Zoki Pharmaceuticals, Sanofi, NIPRO, MOROO, Alfresa Pharma Corporation, Boehringer Ingelheim, Hakodate National Hospital, Asahi Kasei Pharma Corporation, Chugai Pharmaceutical, MSD, Zeria Pharmaceutical, Bayer Yakuhin, Eli Lilly, Yakult Honsha, Sumitomo Dainippon Pharma, Incyte Corporation, Merck Biopharma, The Japanese Gastroenterological Association, Sapporo Minami Tokushukai Hospital, and Pancan Japan. HK has received consulting or advisory fees from Astellas Pharma, Daiichi-Sankyo, and AbbVie; honoraria from Bristol Myers Squibb, Bayer Yakuhin, Ono Pharmaceutical, Eli Lilly Japan, MSD, Chugai Pharmaceutical, Daiichi-Sankyo, Merck Biopharma, Teijin Pharma, Takeda Pharmaceutical, Yakult Pharmaceutical Industry, Taiho Pharmaceutical, Amgen, Otsuka Pharmaceutical, GlaxoSmithKline, and Nippon Kayaku; and research funding from Bristol Myers Squibb, Kobayashi Pharmaceutical, and Eisai. MP has received research grants from Amgen, Bayer, Bristol Myers Squibb, Ipsen, Novartis, and Roche; has received payment or honoraria from Amgen, Bayer, Bristol Myers Squibb, Merck, MSD, Roche, Sanofi, Servier, and Sirtex; has received consulting fees from Amgen, Bayer, Ipsen, Merck, MSD, Qurin, Remedus, Sanofi, Sirtex, and Terumo; and has participated on a data safety monitoring board or advisory board for Basilea. TA has received payment or honoraria from AstraZeneca, Bristol Myers Squibb, Gritstone Oncology, GlaxoSmithKline, Merck, Pierre Fabre, Seagen, and Servier Transgéne; has received support for attending meetings or travel from Bristol Myers Squibb and Merck; has received consulting fees from Aptitude Health, Astellas, Bristol Myers Squibb, Gritstone Oncology, GamaMabs Pharma, GlaxoSmithKline, Kaleido Oncology, Merck, Pierre Fabre, Seagen, Servier, and Transgène; and is president of the ARCAD Foundation. SL has received research grants from Amgen, Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Daiichi Sankyo, Hutchinson, Incyte, Merck Serono, Mirati, MSD, Pfizer, Roche, and Servier; has received payment or honoraria from Amgen, Bristol Myers Squibb, Incyte, GlaxoSmithKline, Eli Lilly, Merck Serono, MSD, Pierre Fabre, Roche, and Servier; and has received consulting fees from Amgen, Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Daiichi Sankyo, GSK, Incyte, Eli Lilly, Merck Serono, MSD, Pierre Fabre, Roche, Takeda, and Servier. KY has received research grants from Taiho Pharm; and has received honoraria from Daiichi Sankyo, Chugai Pharmaceutical, Bristol Myers Squibb, Eli Lilly Japan, Taiho Pharmaceutical, Ono Pharmaceutical, Takeda Pharmaceutical, and Merck. JT has received honoraria from Servier and Pierre Fabre; has received consulting fees from Haystack Oncology; has participated on a data safety monitoring board or advisory board for Gilead, MSD, Bristol Myers Squibb, Pierre Fabre, Novartis, and Daiichi Sankyo; and has participated with leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid for Australasian Gastro-Intestinal Trials Group and European Society for Medical Oncology. CGC has received honoraria from Amgen, Merck, Servier, Pierre Fabre, and Incyte; has received support for attending meetings or travel from Merck, Servier, and Pierre Fabre; and is the Secretary of the Spanish Group for Treatment of Gastrointestinal Tumours (TTD). JHS has received research grants from AbbVie, Amgen, AStar D3, Bayer, Curegenix, Daiichi Sankyo, Eli Lilly, Erasca, Gossamer Bio, Leap Therapeutics, Nektar, Roche/Genentech, Sanofi, Seagen, and Silverback Therapeutics; has received payment or honoraria from Seagen, Bayer, and Natera; has received consulting fees from AbbVie, Amgen, AstraZeneca, Bayer, Beigene, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Natera, Pfizer, Roche/Genentech, Seagen, Silverback Therapeutics, Takeda, and Viatris; has participated on a data safety monitoring board or advisory board for AbbVie, Pionyr Immunotherapeutics, and Beigene; and has received support for attending meetings or travel from Seagen. YC has received consulting fees from IMBdx, Ono Pharmaceutical, Boryung Pharmaceutical, Interpark Bioconvergence, and GC Genome Corporation; and has received honoraria from Roche and MSD Korea. DB is an employee of Daiichi Sankyo. QY has received employee benefits (stocks or other financial or non-financial interests) from Daiichi Sankyo. TKam has received employee benefits (financial or non-financial interests) from Daiichi Sankyo. KK is an employee of Daiichi Sankyo. AB has received employee benefits (stocks or other financial or non-financial interests) from Daiichi Sankyo; and has received support for attending meetings or travel from Daiichi Sankyo. MK is an employee of Daiichi Sankyo. JDA has received employee benefits (stocks or other financial or non-financial interests) from Daiichi Sankyo. TY has received research grants from Amgen, Chugai Pharmaceutical, Daiichi Sankyo, Eisai, FALCO Biosystems, Genomedia, Molecular Health, MSD, Nippon Boehringer Ingelheim, Ono Pharmaceutical, Pfizer Japan, Roche Diagnostics, Sanofi, Sysmex, and Taiho Pharmaceutical; has received honoraria from Chugai Pharmaceutical, Takeda Pharmaceutical, Merck Biopharma, Bayer Yakuhin, Ono Pharmaceutical, and MSD; and has received consulting fees from Sumitomo Corporation. MVdE, H-CH, and T-YK declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Toys are useful resources for structural inspiration in science and engineering. Their fascinating structures provide new strategies for robotics, particularly in overcoming challenging obstacles and increasing adaptability to unstructured environments. Recent advances in actuators made of soft materials have enabled robots to exhibit safer and more adaptive behaviors during locomotion. However, it is still difficult to descend quickly without falling off at the drop point. In the same context, we recall playing with spring toys descending on stairs. In this paper, we introduce an electrohydraulic-based soft robot inspired by the structure of spring toys. The robot demonstrated a novel and previously unreported ability to descend a series of stairs. Specifically, the soft robot consisted of a helical structure and multiple electrohydraulic actuators. A helical structure was used to accommodate the expansion of the electrohydraulic actuators and to operate a wider range of bending motions. This design prevents unpredictable falls and achieves operation while maintaining a sufficient level of flexibility. We also experimentally investigated the actuation characteristics of the soft robot in terms of motion and force. Additionally, we demonstrated a soft gripper using the spring toy-inspired robot as another potential application., (© 2024. The Author(s).)

Background: Premature ovarian failure (POF) is a clinical condition characterized by the cessation of ovarian function, leading to infertility. The underlying molecular mechanisms remain unclear, and no predictable biomarkers have been identified. This study aimed to investigate the protein and metabolite contents of serum extracellular vesicles to investigate underlying molecular mechanisms and explore potential biomarkers., Methods: This study was conducted on a cohort consisting of 14 POF patients and 16 healthy controls. The extracellular vesicles extracted from the serum of each group were subjected to label-free proteomic and unbiased metabolomic analysis. Differentially expressed proteins and metabolites were annotated. Pathway network clustering was conducted with further correlation analysis. The biomarkers were confirmed by ROC analysis and random forest machine learning., Results: The proteomic and metabolomic profiles of POF patients and healthy controls were compared. Two subgroups of POF patients, Pre-POF and Pro-POF, were identified based on the proteomic profile, while all patients displayed a distinguishable metabolomic profile. Proteomic analysis suggested that inflammation serves as an early factor contributing to the infertility of POF patients. For the metabolomic analysis, despite the dysfunction of metabolism, oxidative stress and hormone imbalance were other key factors appearing in POF patients. Signaling pathway clustering of proteomic and metabolomic profiles revealed the progression of dysfunctional energy metabolism during the development of POF. Moreover, correlation analysis identified that differentially expressed proteins and metabolites were highly associated, with six of them being selected as potential biomarkers. ROC curve analysis, together with random forest machine learning, suggested that AFM combined with 2-oxoarginine was the best diagnostic biomarker for POF., Conclusions: Omics analysis revealed that inflammation, oxidative stress, and hormone imbalance are factors that damage ovarian tissue, but the progressive dysfunction of energy metabolism might be the critical pathogenic pathway contributing to the development of POF. AFM combined with 2-oxoarginine serves as a precise biomarker for clinical POF diagnosis., (© 2024. The Author(s).)

Background: Hip fractures are a common and debilitating condition, particularly among older adults. Loss of muscle mass and strength is a common consequence of hip fractures, which further contribute to functional decline and increased disability. Assessing changes in individual thigh muscles volume in follow-up patients can provide valuable insights into the quantitative recovery process and guide rehabilitation interventions. However, accurately measuring anatomical individual thigh muscle volume can be challenging due to various, labor intensive and time-consuming., Materials and Methods: This study aimed to evaluate differences in thigh muscle volume in followed-up hip fracture patients computed tomography (CT) scans using an AI based automatic muscle segmentation model. The study included a total of 18 patients at Gyeongsang National University, who had undergone surgical treatment for a hip fracture. We utilized the automatic segmentation algorithm which we have already developed using UNETR (U-net Transformer) architecture, performance dice score = 0.84, relative absolute volume difference 0.019 ± 0.017%., Results: The results revealed intertrochanteric fractures result in more significant muscle volume loss (females: -97.4 cm 3 , males: -178.2 cm 3 ) compared to femoral neck fractures (females: -83 cm 3 , males: -147.2 cm 3 ). Additionally, the study uncovered substantial disparities in the susceptibility to volume loss among specific thigh muscles, including the Vastus lateralis, Adductor longus and brevis, and Gluteus maximus, particularly in cases of intertrochanteric fractures., Conclusions: The use of an automatic muscle segmentation model based on deep learning algorithms enables efficient and accurate analysis of thigh muscle volume differences in followed up hip fracture patients. Our findings emphasize the significant muscle loss tied to sarcopenia, a critical condition among the elderly. Intertrochanteric fractures resulted in greater muscle volume deformities, especially in key muscle groups, across both genders. Notably, while most muscles exhibited volume reduction following hip fractures, the sartorius, vastus and gluteus groups demonstrated more significant disparities in individuals who sustained intertrochanteric fractures. This non-invasive approach provides valuable insights into the extent of muscle atrophy following hip fracture and can inform targeted rehabilitation interventions., Competing Interests: The authors declare no competing interests., (© 2024 Kim et al.)

Silicon (Si) has been widely studied as one of the promising anodes for lithium-ion batteries (LIBs) because of its ultrahigh theoretical specific capacity and low working voltage. However, the poor interfacial stability of silicon against conventional liquid electrolytes has largely impeded its practical use. Therefore, the combination of silicon-based anodes and solid electrolytes has attracted a great deal of attention in recent years. Here, we demonstrate three types of microsized porous silicon/carbon (Si/C) electrodes (i.e., pristine, prelithiated by liquid electrolyte, and preinfiltrated by polymer electrolyte) that are paired with poly(ethylene) oxide (PEO)-based electrolytes for all-solid-state lithium batteries (ASSLBs). We found that when compared with ionic conductivity, the mechanical stability of the PEO electrolyte dominates the electrochemical performance of ASSLBs using Si/C electrodes at elevated temperature. Additionally, both prelithiated and preinfiltrated Si/C electrodes show higher specific capacity in comparison to the pristine electrode, which is attributed to continuous lithium-ion conducting pathways within the electrode and thus improved utilization of active material. Moreover, owing to good interfacial lithium-ion transport in the electrode, a solid-state half-cell with preinfiltrated Si/C electrode and PEO-lithium bis (trifluoromethanesulfonyl)imide electrolyte delivers a specific capacity of ∼1,000 mAh g -1 after 100 cycles under 800 mA g -1 at 60 °C with average Coulombic efficiency >98.9%. This work provides a strategy for rationally designing the microstructure of silicon-based electrodes with solid electrolytes for high-performance all-solid-state lithium batteries.

High levels of environmental H 2 O 2 represent a threat to many freshwater bacterial species, including toxic-bloom-forming Microcystis aeruginosa, particularly under high-intensity light conditions. The highest extracellular catalase activity-possessing Pseudoduganella aquatica HC52 was chosen among 36 culturable symbiotic isolates from the phycosphere in freshly collected M. aeruginosa cells. A zymogram for catalase activity revealed the presence of only one extracellular catalase despite the four putative catalase genes (katA1, katA2, katE, and srpA) identified in the newly sequenced genome (∼6.8 Mb) of P. aquatica HC52. Analysis of secreted catalase using liquid chromatography-tandem mass spectrometry was identified as KatA1, which lacks a typical signal peptide, although the underlying mechanism for its secretion is unknown. The expression of secreted KatA1 appeared to be induced in the presence of H 2 O 2 . Proteomic analysis also confirmed the presence of KatA1 inside the outer membrane vesicles secreted by P. aquatica HC52 following exposure to H 2 O 2 . High light intensities (> 100 µmol m -2 s -1 ) are known to kill catalase-less axenic M. aeruginosa cells, but the present study found that the presence of P. aquatica cells supported the growth of M. aeruginosa, while the extracellular catalases in supernatant or purified form also sustained the growth of M. aeruginosa under the same conditions. Our results suggest that the extracellular catalase secreted by P. aquatica HC52 enhances the tolerance of M. aeruginosa to H 2 O 2 , thus promoting the formation of M. aeruginosa blooms under high light intensities., 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 B.V. All rights reserved.)

Background: ArtiSential, a new articulating laparoscopic instruments, addresses the limited movement associated with conventional laparoscopic instruments. This study was conducted to assess the clinical effectiveness of ArtiSential in detailed steps of various renal surgery., Methods: This study was approved by the Institutional Review Board of our institution and registered on the Clinical Research Information Service site of the Korea Disease Control and Prevention Agency. Participants meeting all inclusion and exclusion criteria were included in the clinical trial and underwent renal surgery. The clinical effectiveness of ArtiSential was assessed in terms of the feasibility and objective and subjective parameters across 9 detailed steps., Results: Of the 15 potential candidates enrolled from October 2021 to November 2021, 1 patient dropped out due to anaphylaxis from an anesthetic agent, and 14 patients underwent laparoscopic surgery using ArtiSential. Of the 14 patients, 2 patients were converted to laparoscopic surgery using straight-shaped instruments due to the ischemia time exceeding 30 min, and 1 patient due to excessive bleeding. The feasibility for most steps was more than 90%, except the renorrhaphy step. The median total operation time and ischemia time were 161 and 23 min, respectively. The median estimated blood loss was 58.5 mL. Two cases of venous injury occurred during renal pedicle dissection step. The accuracy of the procedure judged by reviewers and usability judged by the operator were acceptable in all steps. The surgeon's quantitatively measured stress score was the highest during renorrhaphy step., Conclusions: Laparoscopic surgery using ArtiSential is feasible for most steps except the renorrhaphy step. The difficulty of performing renorrhaphy is attributed to prolonged ischemia time, which could be addressed by overcoming the learning curve., Trial Registration: Clinical Research Information Service site of the Korea Disease Control and Prevention Agency, KCT0006532. Registered 03/09/2021, https://cris.nih.go.kr/cris/search/detailSearch.do?seq=24071 ., (© 2024. The Author(s).)

Objective/background: Conservative ideology, broadly speaking, has been widely linked to greater happiness and meaning in life. Is that true of all forms of a good life? We examined whether a psychologically rich life is associated with political orientation, system justification, and Protestant work ethic, independent of two other traditional forms of a good life: a happy life and a meaningful life., Method: Participants completed a questionnaire that assessed conservative worldviews and three aspects of well-being (N = 583 in Study 1; N = 348 in Study 2; N = 436 in Study 3; N = 1,217 in Study 4; N = 2,176 in Study 5; N = 516 in Study 6)., Results: Happiness was associated with political conservatism and system justification, and meaning in life was associated with Protestant work ethic. In contrast, zero-order correlations showed that psychological richness was not associated with conservative worldviews. However, when happiness and meaning in life were included in multiple regression models, the nature of the association shifted: Psychological richness was consistently inversely associated with system justification and on average less political conservatism, suggesting that happiness and meaning in life were suppressor variables., Conclusions: These findings suggest that happiness and meaning in life are associated with conservative ideology, whereas psychological richness is not., (© 2024 The Author(s). Journal of Personality published by Wiley Periodicals LLC.)

In clinical settings, among individuals diagnosed with borderline personality disorder (BPD), typically 75% are female and 25% male, although this discrepancy is not reported in the community. In the literature, little is known of the effectiveness and experiences of treatment of men with BPD. We aimed to review the effectiveness and experiences of treatment for men with BPD and outline future research priorities to promote better recovery. We searched Ovid MEDLINE and PsycINFO for eligible studies from inception until July 29, 2022. Peer-reviewed primary research articles on treatment effectiveness or experience for men with BPD were included. Data from eligible studies were synthesized in a narrative review. The protocol of our review was pre-registered on PROSPERO (CRD42022351908). Seventeen studies met the inclusion criteria, and men with BPD from eight countries were represented. Psychological therapies included Dialectical Behavioral Therapy, Systems Training for Emotional Predictability and Problem Solving, Mentalization Based Therapy, and psychoanalytic therapy. Pharmacologic treatment included topiramate, divalproex Extended-Release, and high-dose baclofen. Five studies investigated the service utilization of men with BPD. Compared to women, men were less likely to access treatment for BPD or find treatment helpful. Our findings demonstrated the potential efficacy of psychotherapy and pharmacologic interventions in reducing anger, aggression, and rule-breaking behavior, with limited evidence for reduction in suicide-related outcomes. Our findings are limited by inadequate power and heterogeneity of the included studies. Further research with larger sample sizes and qualitative studies is needed to better understand the treatment experience for men with BPD., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Dr. Paul Links receives book royalties from the American Psychiatric Association Publishing.

Employees in today's workplace express strong desire for policies allowing for temporal flexibility (e.g., paid time off, schedule change, working from home), yet these policies are underutilized even when employees have them. We argue that an occupational norm that emphasizes long work hours is a key to understanding this puzzle. Using individual-level data from the Leave Module of the 2011 American Time Use Survey (supplemented with the 2017-2018 version), matched with occupation-level data constructed from O*NET and the American Community Surveys, we show that individuals working in occupations with higher prevalence of "overwork" (defined by working 50 or more hours per week) are less likely to use paid leave. For flexible work policies, the same pattern is found for childless men, fathers, and childless women, but mothers are more likely to use them in occupations with higher prevalence of overwork. Our decomposition analysis shows that widespread overwork in professional and managerial occupations offsets much of what makes them amenable to the use of leave and flexible work policies, relative to other occupations. These findings suggest that even when policies are available, the success of flexible work policies largely depends on how organizations tackle the overwork norm., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Parkinson's disease (PD) stands as the second most common neurodegenerative disorder after Alzheimer's disease, and its prevalence continues to rise with the aging global population. Central to the pathophysiology of PD is the specific degeneration of midbrain dopamine neurons (mDANs) in the substantia nigra. Consequently, cell replacement therapy (CRT) has emerged as a promising treatment approach, initially supported by various open-label clinical studies employing fetal ventral mesencephalic (fVM) cells. Despite the initial favorable results, fVM cell therapy has intrinsic and logistical limitations that hinder its transition to a standard treatment for PD. Recent efforts in the field of cell therapy have shifted its focus towards the utilization of human pluripotent stem cells, including human embryonic stem cells and induced pluripotent stem cells, to surmount existing challenges. However, regardless of the transplantable cell sources (e.g., xenogeneic, allogeneic, or autologous), the poor and variable survival of implanted dopamine cells remains a major obstacle. Emerging evidence highlights the pivotal role of host immune responses following transplantation in influencing the survival of implanted mDANs, underscoring an important area for further research. In this comprehensive review, building upon insights derived from previous fVM transplantation studies, we delve into the functional ramifications of host immune responses on the survival and efficacy of grafted dopamine cells. Furthermore, we explore potential strategic approaches to modulate the host immune response, ultimately aiming for optimal outcomes in future clinical applications of CRT for PD., (© 2024. The Author(s).)

In recent years, next-generation sequencing (NGS)-based genetic testing has become crucial in cancer care. While its primary objective is to identify actionable genetic alterations to guide treatment decisions, its scope has broadened to encompass aiding in pathological diagnosis and exploring resistance mechanisms. With the ongoing expansion in NGS application and reliance, a compelling necessity arises for expert consensus on its application in solid cancers. To address this demand, the forthcoming recommendations not only provide pragmatic guidance for the clinical use of NGS but also systematically classify actionable genes based on specific cancer types. Additionally, these recommendations will incorporate expert perspectives on crucial biomarkers, ensuring informed decisions regarding circulating tumor DNA panel testing.

In recent years, next-generation sequencing (NGS)-based genetic testing has become crucial in cancer care. While its primary objective is to identify actionable genetic alterations to guide treatment decisions, its scope has broadened to encompass aiding in pathological diagnosis and exploring resistance mechanisms. With the ongoing expansion in NGS application and reliance, a compelling necessity arises for expert consensus on its application in solid cancers. To address this demand, the forthcoming recommendations not only provide pragmatic guidance for the clinical use of NGS but also systematically classify actionable genes based on specific cancer types. Additionally, these recommendations will incorporate expert perspectives on crucial biomarkers, ensuring informed decisions regarding circulating tumor DNA panel testing.

Eco-friendly reagents derived from plants represent a promising strategy to mitigate the occurrence of toxic cyanobacterial blooms. The use of an amentoflavone-containing Selaginella tamariscina extract (STE) markedly decreased the number of Microcystis aeruginosa cells, thus demonstrating significant anti-cyanobacterial activity. In particular, the Microcystis-killing fraction obtained from pulverized S. tamariscina using hot-water-based extraction at temperatures of 40 °C induced cell disruption in both axenic and xenic M. aeruginosa. Liquid chromatographic analysis was also conducted to measure the concentration of amentoflavone in the STE, thus supporting the potential M. aeruginosa-specific killing effects of STE. Bacterial community analysis revealed that STE treatment led to a reduction in the relative abundance of Microcystis species while also increasing the 16S rRNA gene copy number in both xenic M. aeruginosa NIBR18 and cyanobacterial bloom samples isolated from a freshwater environment. Subsequent testing on bacteria, cyanobacteria, and algae isolated from freshwater revealed that STE was not toxic for other taxa. Furthermore, ecotoxicology assessment involving Aliivibrio fischeri, Daphnia magna, and Danio rerio found that high STE doses immobilized D. magna but did not impact the other organisms, while there was no change in the water quality. Overall, due to its effective Microcystis-killing capability and low ecotoxicity, aqueous STE represents a promising practical alternative for the management of Microcystis blooms., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: The objective of this study was to assess postoperative direct medical expenses and medical utilization of elderly patients who underwent either hemiarthroplasty (HA) or internal fixation (IF) for treatment of a femoral intertrochanteric fracture and to analyze differences according to surgical methods and age groups., Materials and Methods: Data from the 2011 to 2018 Korean National Health Insurance Review & Assessment Service database were used. Risk-set matching was performed for selection of controls representing patients with the same sex, age, and year of surgery. A comparative interrupted time series analysis was performed for evaluation of differences in medical expenses and utilization between the two groups., Results: A total of 10,405 patients who underwent IF surgery and 10,405 control patients who underwent HA surgery were included. Medical expenses were 18% lower in the IF group compared to the HA group during the first year after the fracture (difference-in-difference [DID] estimate ratio 0.82, 95% confidence interval [CI] 0.77-0.87, P <0.001), and 9% lower in the second year (DID estimate ratio 0.91, 95% CI 0.85-0.99, P =0.018). Length of hospital stay was significantly shorter in the IF group compared to the HA group during the first two years after time zero in the age ≥80 group., Conclusion: A noticeable increase in medical expenses was observed for patients who underwent HA for treatment of intertrochanteric fractures compared to those who underwent IF over a two-year period after surgery. Therefore, consideration of such findings is critical when designing healthcare policy support for management of intertrochanteric fractures.

Crystalline systems consisting of small-molecule building blocks have emerged as promising materials with diverse applications. It is of great importance to characterize not only their static structures but also the conversion of their structures in response to external stimuli. Femtosecond time-resolved crystallography has the potential to probe the real-time dynamics of structural transitions, but, thus far, this has not been realized for chemical reactions in non-biological crystals. In this study, we applied time-resolved serial femtosecond crystallography (TR-SFX), a powerful technique for visualizing protein structural dynamics, to a metal-organic framework, consisting of Fe porphyrins and hexazirconium nodes, and elucidated its structural dynamics. The time-resolved electron density maps derived from the TR-SFX data unveil trifurcating structural pathways: coherent oscillatory movements of Zr and Fe atoms, a transient structure with the Fe porphyrins and Zr 6 nodes undergoing doming and disordering movements, respectively, and a vibrationally hot structure with isotropic structural disorder. These findings demonstrate the feasibility of using TR-SFX to study chemical systems., (© 2024. The Author(s).)

Total joint arthroplasty (TJA) is a surgical procedure, in which parts of damaged joints are removed and replaced with a prosthesis. The main indication of TJA is osteoarthritis, and the volume of TJA is rising annually along with the increase of aged population. Hip and knee are the most common joints, in which TJAs are performed. The TJA prosthesis is composed of metal, plastic, or ceramic device. Even though TJA is the most successful treatment for end-stage osteoarthritis, it is associated with various complications, and periprosthetic joint infection (PJI) is the most serious complication after TJA. With the increasing volume of TJAs, there is a simultaneous rise in the incidence of PJI. Contamination of the surgical wound and the adherence of bacteria to the surface of prosthetic component represent the initial step in the pathogenesis of PJI. The main sources of the contamination are 1) patient's own flora, 2) droplets in the operation room air, and 3) surgical gloves and instruments. Even though modern techniques have markedly reduced the degree of contamination, TJAs cannot be done in completely germ-free conditions and some degree of contamination is inevitable in all surgical procedures. However, not all contamination leads to PJI. It develops when the burden of contamination exceeds the immune threshold or the colony forming units (CFUs) and various factors contribute to a decrease in the CFU level. Surgeons should be aware of the germ burden/CFU concept and should monitor sources of contamination to maintain the germ burden below the CFU to prevent PJI., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Background: The objective of our study was to analyze the postoperative direct medical expenses and hospital lengths of stay (LOS) of elderly patients who had undergone either hemiarthroplasty (HA) or total hip arthroplasty (THA) for femoral neck fractures and to determine the indication of THA by comparing those variables between the 2 groups by time., Methods: In this comparative large-sample cohort study, we analyzed data from the 2011 to 2018 Korean National Health Insurance Review and Assessment Service database. The included patients were defined as elderly individuals aged 60 years or older who underwent HA or THA for a femoral neck fracture. A 1:1 risk-set matching was performed on the propensity score, using a nearest-neighbor matching algorithm with a maximum caliper of 0.01 of the hazard components. In comparative interrupted time series analysis, time series were constructed using the time unit of one-quarter before and after 3 years from time zero. For the segmented regression analysis, we utilized a generalized linear model with a gamma distribution and logarithmic link function., Results: A total of 4,246 patients who received THA were matched and included with 4,246 control patients who underwent HA. Although there was no statistically significant difference in direct medical expense and hospital LOS for the first 6 months after surgery, direct medical expenses and hospital LOS in THA were relatively reduced compared to the HA up to 24 months after surgery ( p < 0.05). In the subgroup analysis, the THA group's hospital LOS decreased significantly compared to that of the HA group during the 7 to 36 months postoperative period in the 65 ≤ age < 80 age group ( p < 0.05). Direct medical expenses of the THA group significantly decreased compared to those of the HA group during the period from 7 to 24 months after surgery in the men group ( p < 0.05)., Conclusions: When performing THA in elderly patients with femoral neck fractures, the possibility of survival for at least 2 years should be considered from the perspective of medical expense and medical utilization. Additionally, in healthy and active male femoral neck fracture patients under the age of 80 years, THA may be more recommended than HA., Competing Interests: CONFLICT OF INTEREST: No potential conflict of interest relevant to this article was reported., (Copyright © 2024 by The Korean Orthopaedic Association.)

Competing Interests: CONFLICT OF INTEREST: No potential conflict of interest relevant to this article was reported.

Purpose: GC1118 is a novel antibody targeting epidermal growth factor receptor (EGFR) with enhanced blocking activity against both low- and high-affinity EGFR ligands. A phase 1b/2a study was conducted to determine a recommended phase 2 dose (RP2D) of GC1118 in combination with 5-fluorouracil, leucovorin, and irinotecan (FOLFIRI) (phase 1b) and to assess the safety and efficacy of GC1118 plus FOLFIRI as a second-line therapy for recurrent/metastatic colorectal cancer (CRC) (phase 2a)., Materials and Methods: Phase 1b was designed as a standard 3+3 dose-escalation study with a starting dose of GC1118 (3 mg/kg/week) in combination with biweekly FOLFIRI (irinotecan 180 mg/m2; leucovorin 400 mg/m2; 5-fluorouracil 400 mg/m2 bolus and 2,400 mg/m2 infusion over 46 hours) in patients with solid tumors refractory to standard treatments. The subsequent phase 2a part was conducted with objective response rate (ORR) as a primary endpoint. Patients with KRAS/NRAS/BRAF wild-type, EGFR-positive, recurrent/metastatic CRC resistant to the first-line treatment were enrolled in the phase 2a study., Results: RP2D of GC1118 was determined to be 3 mg/kg/wk in the phase 1b study (n=7). Common adverse drug reactions (ADRs) observed in the phase 2a study (n=24) were acneiform rash (95.8%), dry skin (66.7%), paronychia (58.3%), and stomatitis (50.0%). The most common ADR of ≥ grade 3 was neutropenia (33.3%). ORR was 42.5% (95% confidence interval [CI], 23.5 to 62.0), and median progression-free survival was 6.7 months (95% CI, 4.0-8.0)., Conclusion: GC1118 administered weekly at 3 mg/kg in combination with FOLFIRI appears as an effective and safe treatment option in recurrent/metastatic CRC.

Templating is essential in hip arthroplasty preparation, facilitating implant size prediction and surgical rehearsal. It ensures the selection of suitable implants according to patient anatomy and disease, aiming to minimize post-operative complications. Various templating methods exist, including traditional acetate templating on both analog and digital images, alongside digital templating on digital images, which is categorized into 2D and 3D approaches. Despite the popularity of acetate templating on digital images, challenges such as the requirement for physical templates and result preservation persist. To address these limitations, digital templating with software like OrthoSize and Orthoview has been suggested, although not universally accessible. This technical note advocates for Microsoft PowerPoint as an effective alternative for 2D digital templating, highlighting its user-friendly features for image manipulation without needing specialized software. The described method involves scanning acetate templates, adjusting the images in PowerPoint 365 for size, position, and calibration on patient radiographs, and demonstrating reliability through preliminary assessments, with intraclass correlation coefficient (ICC) values indicating a high level of agreement for cup and stem size (ICC = 0.860, 0.841, respectively) but moderate for neck length (ICC = 0.592). We have introduced a method for performing 2D digital templating in the clinical field without the need for specialized software dedicated to digital templating. We believe this method significantly improves the accessibility to 2D digital templating, which was previously limited by the need for digital templating software. Additionally, it enables surgeons to easily establish arthroplasty plans and share them, overcoming the limitations of acetate templates.

Gout is triggered by the accumulation of uric acid in the body, leading to hyperuricemia. Genetic, metabolic, and environmental factors can influence this condition. Excessive uric acid buildup results in the formation of monosodium urate (MSU) crystals, which precipitate in specific areas of the body, including the joints, where they can cause symptoms of gout. While the acute and chronic symptoms of gout have been well-documented, diagnosis of gout affecting the hip joint poses significant challenges. The global incidence of gout, the most prevalent form of inflammatory arthritis, is on the rise. Evaluation of the clinical signs, laboratory results, and imaging results is generally required for diagnosis of gout in cases where MSU crystals have not been detected. Hyperuricemia is considered a primary cause of arthritis symptoms, and comprehensive guidelines for treatment are available. Therefore, the choice of medication is straightforward, and moderate effectiveness of treatment has been demonstrated. Gout is a chronic disease, requiring lifelong uric acid-lowering medications, thus application of a treatment strategy based on the target blood uric acid concentration is necessary. Consequently, cases of gout will likely be observed more frequently by hip surgeons in clinical scenarios in the future. The objective of this review is to provide an overview of the pathophysiology of gout and subsequently examine recent advances in diagnostic methods and therapeutic agents based on an understanding of its underlying mechanisms. In addition, literature on gout-related issues affecting the hip joint, providing a useful reference for hip surgeons is examined.

Recent advances in remote sensing techniques provide a new horizon for monitoring the spatiotemporal variations of harmful algal blooms (HABs) using hyperspectral data in inland water. In this study, a hierarchical concatenated variational autoencoder (HCVAE) is proposed as an efficient and accurate deep learning (DL) based bio-optical model. To demonstrate its usefulness in retrieving algal pigments, the HCVAE is applied to bloom-prone regions in Daecheong Lake, South Korea. By abstracting the similarity between highly related features using layer-wise clique-based latent-feature extraction, HCVAE reduces the computational loads in deriving outputs while preventing performance degradation. Graph-based clique-detection uses information theory-based criteria to group the related reflectance spectra. Consequently, six latent features were extracted from 79 spectral bands to consist of a multilevel hierarchy of HCVAE that can simultaneously estimate concentrations of chlorophyll-a (Chl-a) and phycocyanin (PC). Despite the parsimonious model architecture, the Chl-a and PC concentrations estimated by HCVAE closely agree with the measured concentrations, with test R 2 values of 0.76 and 0.82, respectively. In addition, spatial distribution maps of algal pigments obtained from HCVAE using drone-borne reflectance successfully capture the blooming spots. Based on its multilevel hierarchical architecture, HCVAE can provide the importance of latent features along with their individual wavelengths using Shapley additive explanations. The most important latent features covered the spectral regions associated with both Chl-a and PC. The lightweight neural network DNN sel , which uses only the spectral bands of highest importance in latent-feature extraction, performed comparably to HCVAE. The study results demonstrate the utility of the multilevel hierarchical architecture as a comprehensive assessment model for near-real-time drone-borne sensing of HABs. Moreover, HCVAE is applicable to a wide range of environmental big data, as it can handle numerous sets of features., 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 © 2023 Elsevier B.V. All rights reserved.)

The study aims to develop a deep learning based automatic segmentation approach using the UNETR(U-net Transformer) architecture to quantify the volume of individual thigh muscles(27 muscles in 5 groups) for Sarcopenia assessment. By automating the segmentation process, this approach improves the efficiency and accuracy of muscle volume calculation, facilitating a comprehensive understanding of muscle composition and its relationship to Sarcopenia. The study utilized a dataset of 72 whole thigh CT scans from hip fracture patients, annotated by two radiologists. The UNETR model was trained to perform precise voxel-level segmentation and various metrics such as dice score, average symmetric surface distance, volume correlation, relative absolute volume difference and Hausdorff distance were employed to evaluate the model's performance. Additionally, the correlation between Sarcopenia and individual thigh muscle volumes was examined. The proposed model demonstrated superior segmentation performance compared to the baseline model, achieving higher dice scores (DC = 0.84) and lower average symmetric surface distances (ASSD = 1.4191 ± 0.91). The volume correlation between Sarcopenia and individual thigh muscles in the male group. Furthermore, the correlation analysis of grouped thigh muscles also showed negative associations with Sarcopenia in the male participants. This thesis presents a deep learning based automatic segmentation approach for quantifying individual thigh muscle volume in sarcopenia assessment. The results highlights the associations between Sarcopenia and specific individual muscles as well as grouped thigh muscle regions, particularly in males. The proposed method improves the efficiency and accuracy of muscle volume calculation, contributing to a comprehensive evaluation of Sarcopenia. This research enhances our understanding of muscle composition and performance, providing valuable insights for effective interventions in Sarcopenia management., (© 2024. The Author(s).)

Superior antagonistic activity against axenic Microcystis aeruginosa PCC7806 was observed with Paucibacter sp. B51 isolated from cyanobacterial bloom samples among 43 tested freshwater bacterial species. Complete genome sequencing, analyzing average nucleotide identity and digital DNA-DNA hybridization, designated the B51 strain as Paucibacter aquatile. Electron and fluorescence microscopic image analyses revealed the presence of the B51 strain in the vicinity of M. aeruginosa cells, which might provoke direct inhibition of the photosynthetic activity of the PCC7806 cells, leading to perturbation of cellular metabolisms and consequent cell death. Our speculation was supported by the findings that growth failure of the PCC7806 cells led to low pH conditions with fewer chlorophylls and down-regulation of photosystem genes (e.g., psbD and psaB) during their 48-h co-culture condition. Interestingly, the concentrated ethyl acetate extracts obtained from B51-grown supernatant exhibited a growth-inhibitory effect on PCC7806. The physical separation of both strains by a filter system led to no inhibitory activity of the B51 cells, suggesting that contact-mediated anti-cyanobacterial compounds might also be responsible for hampering the growth of the PCC7806 cells. Bioinformatic tools identified 12 gene clusters that possibly produce secondary metabolites, including a class II lasso peptide in the B51 genome. Further chemical analysis demonstrated anti-cyanobacterial activity from fractionated samples having a rubrivinodin-like lasso peptide, named paucinodin. Taken together, both contact-mediated inhibition of photosynthesis and the lasso peptide secretion of the B51 strain are responsible for the anti-cyanobacterial activity of P. aquatile B51., (© 2023 Phycological Society of America.)

Climate warming is linked to earlier onset and extended duration of cyanobacterial blooms in temperate rivers. This causes an unpredictable extent of harm to the functioning of the ecosystem and public health. We used Microcystis spp. cell density data monitored for seven years (2016-2022) in ten sites across four temperate rivers of the Republic of Korea to define the phenology of cyanobacterial blooms and elucidate the climatic effect on their pattern. The day of year marking the onset, peak, and end of Microcystis growth were estimated using a Weibull function, and linear mixed-effect models were employed to analyze their relationships with environmental variables. These models identified river-specific temperatures at the beginning and end dates of cyanobacterial blooms. Furthermore, the most realistic models were employed to project future Microcystis bloom phenology, considering downscaled and quantile-mapped regional air temperatures from a general circulation model. Daily minimum and daily maximum air temperatures (mintemp and maxtemp) primarily drove the timing of the beginning and end of the bloom, respectively. The models successfully captured the spatiotemporal variations of the beginning and end dates, with mintemp and maxtemp predicted to be 24℃ (R 2  = 0.68) and 16℃ (R 2  = 0.35), respectively. The beginning and end dates were projected to advance considerably in the future under the Representative Concentration Pathway 2.6, 4.5, and 8.5. The simulations suggested that the largest uncertainty lies in the timing of when the bloom ends, whereas the timing of when blooming begins has less variation. Our study highlights the dependency of cyanobacterial bloom phenology on temperatures and earlier and prolonged bloom development., 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 © 2023. Published by Elsevier Ltd.)

Controlled assembly of nanoparticles into well-defined assembled architectures through precise manipulation of spatial arrangement and interactions allows the development of advanced mesoscale materials with tailored structures, hierarchical functionalities, and enhanced properties. Despite remarkable advancements, the controlled assembly of highly anisotropic 2Dnanosheets is significantly challenging, primarily due to the limited availability of selective edge-to-edge connectivity compared to the abundant large faces. Innovative strategies are needed to unlock the full potential of 2D-nanomaterialsin self-assembled structures with distinct and desirable properties. This research unveils the discovery of controlled self-assembly of 2D-silica nanosheets (2D-SiNSs) into hollow micron-sized soccer ball-like shells (SA-SiMS). The assembly is driven by the physical flexibility of the 2D-SiNSs and the differential electricdouble-layer charge gradient creating electrostatic bias on the edge and face regions. The resulting SA-SiMS structures exhibit high mechanical stability, even at high-temperatures, and exhibit excellent performance as catalyst support in the dry reforming of methane. The SA-SiMS structures facilitate improved mass transport, leading to enhanced reaction rates, while the thin silica shell prevents sintering of small catalyst nanocrystals, thereby preventing coke formation. This discovery sheds light on the controllable self-assembly of 2D nanomaterials and provides insights into the design and synthesis of advanced mesoscale materials with tailored properties., (© 2023 Wiley-VCH GmbH.)

Recent advances in machine learning hold tremendous potential for enhancing the way we develop new medicines. Over the years, machine learning has been adopted in nearly all facets of drug discovery, including patient stratification, lead discovery, biomarker development, and clinical trial design. In this review, we will discuss the latest developments linking machine learning and CNS drug discovery. While machine learning has aided our understanding of chronic diseases like Alzheimer's disease and Parkinson's disease, only modest effective therapies currently exist. We highlight promising new efforts led by academia and emerging biotech companies to leverage machine learning for exploring new therapies. These approaches aim to not only accelerate drug development but to improve the detection and treatment of neurodegenerative diseases.

Molecular ions are ubiquitous and play pivotal roles 1-3 in many reactions, particularly in the context of atmospheric and interstellar chemistry 4-6 . However, their structures and conformational transitions 7,8 , particularly in the gas phase, are less explored than those of neutral molecules owing to experimental difficulties. A case in point is the halonium ions 9-11 , whose highly reactive nature and ring strain make them short-lived intermediates that are readily attacked even by weak nucleophiles and thus challenging to isolate or capture before they undergo further reaction. Here we show that mega-electronvolt ultrafast electron diffraction (MeV-UED) 12-14 , used in conjunction with resonance-enhanced multiphoton ionization, can monitor the formation of 1,3-dibromopropane (DBP) cations and their subsequent structural dynamics forming a halonium ion. We find that the DBP + cation remains for a substantial duration of 3.6 ps in aptly named 'dark states' that are structurally indistinguishable from the DBP electronic ground state. The structural data, supported by surface-hopping simulations 15 and ab initio calculations 16 , reveal that the cation subsequently decays to iso-DBP + , an unusual intermediate with a four-membered ring containing a loosely bound 17,18 bromine atom, and eventually loses the bromine atom and forms a bromonium ion with a three-membered-ring structure 19 . We anticipate that the approach used here can also be applied to examine the structural dynamics of other molecular ions and thereby deepen our understanding of ion chemistry., (© 2024. The Author(s).)

Background/aim: This study investigated the treatment patterns and prognosis of patients with metastatic or unresectable colorectal cancer (mCRC) treated with chemotherapy with targeting agents., Patients and Methods: This longitudinal multicenter study included 963 patients with mCRC who were treated in Korea between 2016 and 2020. Treatment patterns and efficacy were compared according to the mutation status and clinical factors., Results: As first-line therapy, most of the patients (83.5%) received FOLFOX plus bevacizumab (35.4%), followed by FOLFIRI plus bevacizumab (18.8%), FOLFIRI plus cetuximab (17.0%), and FOLFOX plus cetuximab (12.3%). Bevacizumab was the most frequent agent (78.8%) combined with chemotherapy in RAS-mutated CRC, while cetuximab (57.2%) in RAS wild-type CRC. Cetuximab was frequently combined with a doublet regimen in patients with left-sided CRC than in those with right-sided CRC (34.4% vs. 16%). As second-line therapy, most patients (63.4%) also received doublet regimens with bevacizumab, and FOLFIRI plus aflibercept was administered in 15.1%. The objective response rate with FOLFIRI plus cetuximab was significantly higher in patients with left-sided CRC than in those with right-sided CRC (59.2% vs. 30.8%, p=0.008) and marginally higher in patients with RAS wild-type CRC than in those with RAS-mutated CRC (55.6% vs. 0.0%, p=0.092). Progression-free survival (PFS) with FOLFOX plus bevacizumab was significantly shorter than that with FOLFIRI plus bevacizumab (p=0.030) in RAS-mutated CRC, whereas there were no significant differences between regimens in RAS wild-type CRC., Conclusion: In patients with unresectable metastatic colorectal cancer, doublet chemotherapy with targeting agents is the most common therapy and efficacy depends on the mutation status as well as clinical factors., (Copyright © 2024 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background and Objectives : Hip fractures are commonly found in elderly patients, and often result in chronic pain and decreased physical function, as well as worsening of overall health. It is known that early surgical intervention during the acute phase and rehabilitation are important for improving clinical outcomes for these patients. However, the importance of management for improving the quality of life of these patients is becoming more emphasized. Studies on changes in sleep patterns after hip fractures are rare overseas. Therefore, the aim of this study is to investigate the prevalence of sleep disturbance in patients with hip fractures and to analyze the changes in sleep disturbance after surgery by comparing the preoperative and postoperative results. Materials and Methods : During the period from August 2022 to January 2023, patients who underwent surgical treatment for hip fractures and were recruited into the REAL Hip Cohort were selected as research subjects. The sleep survey was conducted using the Pittsburgh Sleep Quality Index (PSQI). The PSQI is composed of 18 questions, each divided into areas of sleep quality, sleep latency, duration, efficiency, disturbance, use of medication, and daytime dysfunction. Each area is scored 0-3 points and the total is 0-21. A score greater than five indicates sleep disorder. The PSQI was surveyed during hospitalization and three months after surgery for post-fracture sleep status. To analyze changes before and after the fracture, paired T-tests and chi-square tests were performed. Results : From August 2022 to January 2023, a total of 40 patients who were recruited into the REAL Hip Cohort responded to the PSQI survey. The average age was 77.4 years and 36 were female. Sleep quality worsened from 0.75 ± 1.0 before surgery to 1.4 ± 1.0 three months after surgery ( p = 0.019), and sleep efficiency also worsened from 0.4 ± 0.6 to 1.4 ± 1.0 ( p < 0.001). The PSQI increased from an average of 5.2 ± 2.8 before surgery to 8.2 ± 4.2 three months after surgery ( p = 0.007), and the number of patients who could be diagnosed with sleep disorders also increased from 12 (40%) to 24 (60%) ( p = 0.030). Conclusions : A decline in overall sleep status was observed in patients in a survey on sleep patterns three months after hip fracture. Additional management is needed to improve their sleep patterns.

Objective: Perioperative hypothermia can lead to various complications. Although various warming techniques have been used to prevent perioperative hypothermia, the effect of these techniques on surgical site infection (SSI) during posterior fusion surgery is unclear. The effects of warming devices on SSI rates were therefore analyzed using data complied by the Health Insurance and Review Assessment (HIRA) Service in Korea., Methods: This study included 5,406 patients in the HIRA Service database who underwent posterior fusion surgery during the years 2014, 2015, and 2017. Factors related to SSI in these patients, including warming devices, antibiotics, and transfusion, were analyzed., Results: The incidence of SSI was higher in patients who underwent forced air warming than in those who did not undergo active warming (odds ratio [OR], 1.73; p = 0.039), especially above 70 years old (OR, 4.11; p = 0.014). By contrast, the incidence of SSI was not significantly higher in patients who underwent device using conduction. Infection rates were higher in patients who received prophylactic antibiotics within 20 minutes before incision, than within 21 to 60 minutes (OR, 2.07; p = 0.001) and who received more blood transfusions (1 pint < volume ≤ 2 pint; OR, 1.75; p = 0.008, > 2 pint; OR, 2.73; p = 0.004)., Conclusion: SSI rates were higher in patients who underwent warming with forced air devices than with devices using conduction, as well as being higher in patients who older age, received blood transfusions and administered antibiotics within 20 minutes before incision. Devices using conduction have more advantages in preventing SSI than forced air warming device. In addition, the reduction of other risk factors for SSI may improve postoperative results.

Background: The objective of this study was to analyze the direct medical expenses of a vertebral fracture cohort (VC) and a matched cohort (MC) over 5 years preceding and following the fracture, analyze the duration of the rise in medical expenses due to the fracture, and examine whether the expenses vary with age group, utilizing a national claims database., Methods: Subjects with vertebral fractures and matched subjects were chosen from the National Health Insurance Service Sample cohort (NHIS-Sample) of South Korea. Patients with vertebral fractures were either primarily admitted to acute care hospitals (index admissions) or those who received kyphoplasty or vertebroplasty during the follow-up period (2002-2015). A risk-set matching was performed using 1 : 5 random sampling to simulate a real-world situation. Individual-level direct medical expenses per quarter were calculated for 5 years prior and subsequent to the vertebral fracture. In this analysis using a comparative interrupted time series design, we examined the direct medical expenses of a VC and an MC., Results: A total of 3,923 incident vertebral fracture patients and 19,615 matched subjects were included in this study. The mean age was 75.5 ± 7.4 years, and 69.5% were women. The mean difference in medical expenses between the two groups increased steadily before the fracture. The medical expenses of the VC peaked in the first quarter following the fracture. The cost changes were 1.82 times higher for the VC than for the MC (95% confidence interval, 1.62-2.04; p < 0.001) in the first year. Subsequently, there were no differential changes in medical expenses between the two groups ( p > 0.05). In the < 70-year subgroup, there were no differential changes in medical expenses between the two groups ( p > 0.05). However, in the ≥ 80-year subgroup, the cost changes for the VC were higher than those for the MC up to 5 years after time zero., Conclusions: Based on our study results, we suggest that health and medical policies for vertebral fractures should be designed to last up to approximately 1 year after the fracture. Health policies should be differentiated according to age group., Competing Interests: CONFLICT OF INTEREST: No potential conflict of interest relevant to this article was reported., (Copyright © 2023 by The Korean Orthopaedic Association.)

Introduction: The aim of our study is to analyze the association of usage and type of warming device with the risk of surgical site infection (SSI) in patients who underwent hip arthroplasty, and to analyze the factors that increase the risk of SSI if the warming device is not used., Materials and Methods: This retrospective cross-sectional study identified subjects from data of "Evaluation of the Appropriate Use of Prophylactic Antibiotics". Included patients were defined as those who underwent elective unilateral hip hemiarthroplasty or total hip arthroplasty (THA). Patients were classified into no intraoperative warming device, forced air warming devices, and devices using conduction. Multiple logistic regression analysis was conducted to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) to assess the association between warming devices and SSI., Results: A total of 3945 patients met the inclusion criteria. Compared to those who received an intraoperative warming device, the odds of developing SSI were 1.9 times higher in those who did not receive intraoperative warming devices (aOR 1.9; 95% CI 1.1-3.6). The risk of SSI was 2.2 times higher with forced air warming devices compared to devices using conduction but this difference was not statistically significant (aOR 2.2; 95% CI 0.7-6.8). The risk of SSI increased in males (aOR 2.8; 95% CI 1.1-7.2), in patients under 70 years of age (aOR 4.4; 95% CI 1.6-10.4), in patients with a Charlson`s comorbidity index of 2 or higher (aOR 3.3; 95% CI 1.3-8.7), and in patients who underwent THA (aOR 3.8; 95% CI 1.7-8.3) when intraoperative warming devices were not used., Conclusions: The use of intraoperative active warming devices is highly recommended to prevent SSI during elective hip arthroplasty. In particular, male patients younger than 70 years, those with a high CCI, and those undergoing THA are at significantly increased risk of SSI if intraoperative active warming devices are not used. Intraoperative warming device using conduction is likely superior to forced air warming device, but further studies are needed to confirm this., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

[Ce(III)Cl 6 ] 3- , with its earth-abundant metal element, is a promising photocatalyst facilitating carbon-halogen bond activation. Still, the structure of the reaction intermediate has yet to be explored. Here, we applied time-resolved X-ray liquidography (TRXL), which allows for direct observation of the structural details of reaction intermediates, to investigate the photocatalytic reaction of [Ce(III)Cl 6 ] 3- . Structural analysis of the TRXL data revealed that the excited state of [Ce(III)Cl 6 ] 3- has Ce-Cl bonds that are shorter than those of the ground state and that the Ce-Cl bond further contracts upon oxidation. In addition, this study represents the first application of TRXL to both photocatalyst-only and photocatalyst-and-substrate samples, providing insights into the substrate's influence on the photocatalyst's reaction dynamics. This study demonstrates the capability of TRXL in elucidating the reaction dynamics of photocatalysts under various conditions and highlights the importance of experimental determination of the structures of reaction intermediates to advance our understanding of photocatalytic mechanisms.

Introduction: Cholesterol is an irreplaceable nutrient in pulmonary metabolism; however, studies on high-density lipoprotein cholesterol (HDL-C) levels have shown conflicting results regarding lung function. Therefore, we investigated the association between lung function and HDL-C levels in three cross-sectional studies conducted in the USA and South Korea., Methods: US National Health and Nutrition Examination Survey (NHANES) III, US NHANES 2007-2012, and Korea National Health and Nutrition Examination Survey (KNHANES) IV-VII performed spirometry and met the American Thoracic Society recommendations. Multiple linear regression models were used to determine the relationship between serum lipid levels and lung function. The models were adjusted for age, sex, household income, body mass index, smoking pack year, use of lipid-lowering medication and race. Serum HDL-C levels were classified into three groups to assess the dose-response relationship according to the guideline from the National Cholesterol Education Program-Adult Treatment Panel III., Results: The adult participants of the KNHANES (n=31 288), NHANES III (n=12 182) and NHANES 2007-2012 (n=9122) were analysed. Multivariate linear regression analysis of the serum cholesterol profiles revealed that only serum HDL-C was associated with forced vital capacity (FVC) and forced expiratory volume in 1 s (FEV 1 ) in all three studies. A 1 SD increase in the HDL-C level increased the percent predicted FVC by 0.5%-1.5% p, and the per cent predicted FEV 1 by 0.5%-1.7% p. In terms of HDL-C levels, correlations between the HDL-C groups and the per cent predicted FVC and FEV 1 showed dose-response relationships. Compared with the normal group, high HDL-C levels increased FVC by 0.75%-1.79% p and FEV 1 by 0.55%-1.90% p, while low levels led to 0.74%-2.19% p and 0.86%-2.68% p reductions in FVC and FEV 1 , respectively. Subgroup analyses revealed weaker associations in females from KNHANES and NHANES III., Conclusion: In the three nationwide cross-sectional studies, high HDL-C levels were associated with improved FVC and FEV 1 . However, future studies are needed to confirm this correlation and elucidate the underlying mechanisms., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: The objective of this study was to evaluate the effects of a strong cytochrome P450 family (CYP) 3A4 inhibitor (itraconazole) and inducer (carbamazepine) on the pharmacokinetics and safety of nirmatrelvir/ritonavir., Methods: Pharmacokinetics were measured in two phase 1, open-label, fixed-sequence studies in healthy adults. During Period 1, oral nirmatrelvir/ritonavir 300 mg/100 mg twice daily was administered alone; during Period 2, it was administered with itraconazole or carbamazepine. Nirmatrelvir/ritonavir was administered as repeated doses or one dose in the itraconazole and carbamazepine studies, respectively. Nirmatrelvir and ritonavir plasma concentrations and adverse event (AE) rates in both periods were analysed., Results: Each study included 12 participants. Following administration of nirmatrelvir/ritonavir with itraconazole (Test) or alone (Reference), test/reference ratios of the adjusted geometric means (90% CIs) for nirmatrelvir AUC tau and C max were 138.82% (129.25%, 149.11%) and 118.57% (112.50%, 124.97%), respectively. After administration of nirmatrelvir/ritonavir with carbamazepine (Test) or alone (Reference), test/reference ratios (90% CIs) of the adjusted geometric means for nirmatrelvir AUC inf and C max were 44.50% (33.77%, 58.65%) and 56.82% (47.04%, 68.62%), respectively. Nirmatrelvir/ritonavir was generally safe when administered with or without itraconazole or carbamazepine. No serious or severe AEs were reported., Conclusions: Coadministration of a strong CYP3A4 inhibitor with a strong CYP3A inhibitor used for pharmacokinetic enhancement (i.e., ritonavir) resulted in small increases in plasma nirmatrelvir exposure, whereas coadministration of a strong inducer substantially decreased systemic nirmatrelvir and ritonavir exposures suggesting a contraindication in the label with CYP3A4 strong inducers. Administration of nirmatrelvir/ritonavir alone or with itraconazole or carbamazepine was generally safe., (© 2023 British Pharmacological Society.)

Objective: The objective of this study was to evaluate the accuracy of pedicle screw placement in patients undergoing percutaneous pedicle screw fixation with robotic guidance, using a newly developed 3-dimensional quantitative measurement system. The study also aimed to assess the clinical feasibility of the robotic system in the field of spinal surgery., Methods: A total of 113 patients underwent pedicle screw insertion using the CUVIS-spine pedicle screw guide system (CUREXO Inc.). Intraoperative O-arm images were obtained, and screw insertion pathways were planned accordingly. Image registration was performed using paired-point registration and iterative closest point methods. The accuracy of the robotic-guided pedicle screw insertion was assessed using 3-dimensional offset calculation and the Gertzbein-Robbins system (GRS)., Results: A total of 448 screws were inserted in the 113 patients. The image registration success rate was 95.16%. The average error of entry offset was 2.86 mm, target offset was 2.48 mm, depth offset was 1.99 mm, and angular offset was 3.07°. According to the GRS grading system, 88.39% of the screws were classified as grade A, 9.60% as grade B, 1.56% as grade C, 0.22% as grade D, and 0.22% as grade E. Clinically acceptable screws (GRS grade A or B) accounted for 97.54% of the total, with no reported neurologic complications., Conclusion: Our study demonstrated that pedicle screw insertion using the novel robot-assisted navigation method is both accurate and safe. Further prospective studies are necessary to explore the potential benefits of this robot-assisted technique in comparison to conventional approaches.