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Yoonha Hwang,1 Hwa Reung Lee,2 Hyunjin Jo,3,4 Dongyeop Kim,3,4 Eun Yeon Joo,3,4 Dae-Won Seo,3,4 Seung Bong Hong,3,4 Young-Min Shon3– 5 1Department of Neurology, The Catholic University of Korea Eunpyeong St. Mary’s Hospital, Seoul, Republic of Korea; 2Department of Neurology, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea; 3Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea; 4Neuroscience Center, Samsung Medical Center, Seoul, Republic of Korea; 5Department of Medical Device Management and Research, Samsung Advanced Institute for Health Sciences & Technology (SAHIST), Sungkyunkwan University, Seoul, KoreaCorrespondence: Young-Min ShonDepartment of Neurology, Samsung Medical Center, Sungkyunkwan, University School of Medicine, 81 Irwonro, Gangnam-gu, Seoul, 06351, Republic of KoreaTel +82-2-3410-2701Fax +82-2-3410-0052Email sonogung@gmail.comBackground and Objective: Subtraction of ictal SPECT coregistered to MRI (SISCOM) provides complementary information for detecting the ictal onset zone, especially in patients with MRI-negative focal epilepsy, and provides additional useful information for predicting long-term postresection outcomes. This study sought to investigate the relationship between surgical failure and increased cerebral blood flow (CBF) pattern using SPECT in patients with mesial temporal lobe epilepsy with unilateral hippocampal sclerosis (MTLE-HS).Methods: Among 42 subjects who underwent anterior temporal lobectomy with amygdalohippocampectomy (ATL-AH) for MTLE-HS, 29 (69.0%) were seizure-free (SF group). Hyperperfusion was compared in 14 ipsilateral and contralateral brain regions in SISCOM images between the two groups.Results: The pattern of ictal hyperperfusion in temporal regions did not vary significantly between the SF and non-seizure-free (NSF) groups. However, CBF increases in the contralateral occipital area was more frequent in the NSF group than in the SF group. Furthermore, ictal hyperperfusion of the ipsilateral occipital and contralateral parietal areas tended to be more frequent in the NSF group.Conclusion: The results indicate that poor ATL-AH surgical outcome is associated with a tendency of ictal hyperperfusion of the contralateral occipital cortex based on SISCOM analysis. The pattern of early ictal CBF changes implicating the propagation from temporal to occipital cortices can be considered a marker of poor surgical outcomes of ATL-AH in MTLE-HS patients.Keywords: temporal lobe epilepsy, ictal hyperperfusion, SISCOM, contralateral occipital

Sa-Bin Hong, Jiakun Yu, Sihan Chen Department of Medicine, Imperial College London, London, UKCorrespondence: Sa-Bin HongImperial College London, London, UKTel +44 7943 061774Email sh3413@ic.ac.uk View the original paper by Dr Cooper and colleagues

Seong Hoon Kim,1 Sung Chul Lim,1 Dong Won Yang,1 Jeong Hee Cho,1 Byung-Chul Son,2 Jiyeon Kim,3 Seung Bong Hong,4 Young-Min Shon4 1Department of Neurology, 2Department of Neurosurgery, Catholic Neuroscience Institute, College of Medicine, The Catholic University of Korea, Seoul, 3Department of Neurology, Korea University Ansan Hospital, College of Medicine, Korea University, Ansan, 4Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea Objective: Deep brain stimulation (DBS) of the centromedian thalamic nucleus (CM) can be an alternative treatment option for intractable epilepsy patients. Since CM may be involved in widespread cortico-subcortical networks, identification of the cortical sub-networks specific to the target stimuli may provide further understanding on the underlying mechanisms of CM DBS. Several brain structures have distinguishing brain connections that may be related to the pivotal propagation and subsequent clinical effect of DBS.Methods: To explore core structures and their connections relevant to CM DBS, we applied electroencephalogram (EEG) and diffusion tensor imaging (DTI) to 10 medically intractable patients – three generalized epilepsy (GE) and seven multifocal epilepsy (MFE) patients unsuitable for resective surgery. Spatiotemporal activation pattern was mapped from scalp EEG by delivering low-frequency stimuli (5 Hz). Structural connections between the CM and the cortical activation spots were assessed using DTI.Results: We confirmed an average 72% seizure reduction after CM DBS and its clinical efficiency remained consistent during the observation period (mean 21 months). EEG data revealed sequential source propagation from the anterior cingulate, followed by the frontotemporal regions bilaterally. In addition, maximal activation was found in the left cingulate gyrus and the right medial frontal cortex during the right and left CM stimulation, respectively. From DTI data, we confirmed concrete structural connections between CM and those maximal activation spots identified from EEG data.Conclusion: These results suggest that the anterior cingulate can be a core cortical structure for the bilateral propagation of CM stimulation. Our DTI findings also indicate that the propagation of CM stimulation may rely upon integrity of structural connections between CM and these key cortical regions. Structures and their connections found in this study may be relevant in the interpretation of the clinical outcomes of CM DBS. Keywords: deep brain stimulation, intractable epilepsy, centromedian thalamic nucleus, structural connectivity, cortical recruiting response, anterior cingulate

A prospective cohort study was performed to determine the optimal dose of vancomycin to maintain a serum trough concentration of at least 15 to 20 mg/l and to assess the efficacy of this target vancomycin concentration in the treatment of methicillin-resistant Staphylococcus aureus pneumonia. Vancomycin pharmacokinetic parameters were estimated using a CAPSIL software program from serum concentrations of 141 patients with pneumonia treated with vancomycin, regardless of methicillin-resistant Staphylococcus aureus status, at a 28-bed medical intensive care unit. Vancomycin trough concentrations and other pharmacokinetic parameters were compared between five groups of patients differing in their renal function: (1) creatinine clearance > or =60 ml/minute, (2) creatinine clearance 30 to 60 ml/minute, (3) creatinine clearance <30 ml/minute, (4) on intermittent haemodialysis, and (5) on continuous renal replacement therapy. More than 70% of patients failed to reach the recommended therapeutic serum trough concentrations: a higher dose of vancomycin is necessary to maintain serum trough concentration at 15 to 20 mg/l, particularly in critically ill patients with creatinine clearance above 60 ml/minute and in those on intermittent haemodialysis. Among patients with methicillin-resistant Staphylococcus aureus pneumonia, no significant differences were observed in the treatment success rate, length of intensive care unit stay, and intensive care unit mortality rate between patients with vancomycin trough concentrations of >20 mg/l, 15 to 20 mg/l and <15 mg/l. [ABSTRACT FROM AUTHOR]

RATIONALE: Administration of adjuvant corticosteroids to patients with pandemic influenza A/H1N1 2009 (pH1N1) may reduce inflammation and improve outcomes. OBJECTIVES: To assess the effect of adjuvant corticosteroid treatment on the outcome of critically ill patients with pH1N1 infection. METHODS: All adult patients with confirmed pH1N1 admitted to the intensive care unit of 28 hospitals in South Korea from September 2009 to February 2010 were enrolled. Patients with and without adjuvant corticosteroid treatment were retrospectively compared by two risk stratification models: (1) a retrospective cohort study that used propensity score analysis to adjust for confounding by treatment assignment and (2) a propensity-matched case-control study. MEASUREMENTS AND MAIN RESULTS: A total of 245 patients were enrolled in the cohort study, 107 of whom (44%) received adjuvant steroid treatment. In the cohort study, the 90-day mortality rate of patients given steroids (58%, 62 of 107) was significantly higher than that of those not given steroids (27%, 37 of 138) (P < 0.001). The steroid group was more likely to have superinfection such as secondary bacterial pneumonia or invasive fungal infection, and had more prolonged intensive care unit stays than the no-steroid group. Multivariate analysis indicated that steroid treatment was associated with increased 90-day mortality when independent predictors for 90-day mortality and propensity score were considered (adjusted odds ratio, 2.20; 95% confidence interval, 1.03-4.71). In the case-control study, the 90-day mortality rate in the steroid group was 54% (35 of 65) and 31% (20 of 65) in the no-steroid group (McNemar test, P = 0.004). CONCLUSIONS: Adjuvant corticosteroids were significantly associated with higher mortality in critically ill patients with pH1N1 infection. [ABSTRACT FROM AUTHOR]

Chronically critically ill patients are defined as those who survive initial life-threatening, possibly reversible organ failure(s) but are unable to recover rapidly to a point at which they are fully independent of life support. Accordingly, these patients require mechanical ventilation and medical resources for a long time in an intensive care unit (ICU). The present study analysed demographic, clinical and survival data of chronically critically ill patients, to identify condition(s) related to poor prognosis. A total of 141 chronically critically ill patients were studied retrospectively over a two-year period (July 1, 2003 to June 30, 2005). Their mean lengths of stay in the ICU and in the hospital were 42.9+/-36.4 and 83.9+/-100.5 days respectively. ICU and six-month cumulative mortality rates were 42.6% and 75.9% respectively. Non-survivors had a significantly higher Sequential Organ Failure Assessment (SOFA) score than survivors on day 21 of ICU admission, as well as having significantly lower changes of SOFA scores between days three and 21. Multivariate analysis demonstrated that the SOFA score on day 21 and the Charlson Comorbidity Index were the best predictor of survival for six months after hospital discharge. The SOFA score on day 21 and comorbidity in the ICU appears to be a valuable prognostic indicators in chronically critically ill patients. [ABSTRACT FROM AUTHOR]

Background: Patients with Birt-Hogg-Dubé (BHD) syndrome harbor germline mutations in the BHD tumor suppressor gene that are associated with an increased risk for kidney cancer. BHD encodes folliculin, a protein that may interact with the energy- and nutrient-sensing 5'-AMP-activated protein kinase-mammalian target of rapamycin (AMPK-mTOR) signaling pathways.Methods: We used recombineering methods to generate mice with a conditional BHD allele and introduced the cadherin 16 (KSP)-Cre transgene to target BHD inactivation to the kidney. Kidney cell proliferation was measured by BrdU incorporation and phospho-histone H3 staining. Kidney weight data were analyzed with Wilcoxon's rank-sum, Student's t, and Welch's t tests. Hematoxylin and eosin staining and immunoblot analysis and immunohistochemistry of cell cycle and signaling proteins were performed on mouse kidney cells and tissues. BHD knockout mice and kidney cells isolated from BHD knockout and control mice were treated with the mTOR inhibitor rapamycin. Mouse survival was evaluated by Kaplan-Meier analyses. All statistical tests were two-sided.Results: BHD knockout mice developed enlarged polycystic kidneys and died from renal failure by 3 weeks of age. Targeted BHD knockout led to the activation of Raf-extracellular signal-regulated protein kinase (Erk)1/2 and Akt-mTOR pathways in the kidneys and increased expression of cell cycle proteins and cell proliferation. Rapamycin-treated BHD knockout mice had smaller kidneys than buffer-treated BHD knockout mice had (n = 4-6 mice per group, relative kidney/body weight ratios, mean = 4.64% vs 12.2%, difference = 7.6%, 95% confidence interval = 5.2% to 10.0%; P < .001) and longer median survival time (n = 4-5 mice per group, 41.5 vs 23 days; P = .0065 ).Conclusions: Homozygous loss of BHD may initiate renal tumorigenesis in the mouse. The conditional BHD knockout mouse may be a useful research model for dissecting multistep kidney carcinogenesis, and rapamycin may be considered as a potential treatment for Birt-Hogg-Dubé syndrome. [ABSTRACT FROM AUTHOR]

The ability to generate visceral sensory neurons (VSN) from induced pluripotent stem (iPS) cells may help to gain insights into how the gut-nerve-brain axis is involved in neurological disorders. We established a protocol to differentiate human iPS-cell-derived visceral sensory ganglion organoids (VSGOs). VSGOs exhibit canonical VSN markers, and single-cell RNA sequencing revealed heterogenous molecular signatures and developmental trajectories of VSGOs aligned with native VSN. We integrated VSGOs with human colon organoids on a microfluidic device and applied this axis-on-a-chip model to Alzheimer's disease. Our results suggest that VSN could be a potential mediator for propagating gut-derived amyloid and tau to the brain in an APOE4- and LRP1-dependent manner. Furthermore, our approach was extended to include patient-derived iPS cells, which demonstrated a strong correlation with clinical data., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background/aims: With the global increase in patients with solid malignancies, it is helpful to understand the outcomes of intensive care unit (ICU) admission for these patients. This study evaluated the risk factors for ICU mortality and the shortand long-term outcomes in patients with solid malignancies who had unplanned ICU admission., Methods: This retrospective cohort study included patients with solid malignancies treated at the medical ICU of a single tertiary center in South Korea between 2016 and 2022., Results: Among the 955 patients, the ICU mortality rate was 23.5%. Lung cancer was the most common cancer type (34.2%) and was significantly associated with increased ICU mortality (odd ratio [OR] 1.58, p = 0.030). Higher Sequential Organ Failure Assessment scores at ICU admission (OR 1.11, p < 0.001), the need for mechanical ventilation (OR 6.74, p < 0.001), or renal replacement therapy during the ICU stay (OR 2.49, p < 0.001) were significantly associated with higher ICU mortality. The 1-year survival rate after ICU admission was 29.3%, with a median survival of 37 days for patients requiring mechanical deviaventilation, and 23 days for patients requiring renal replacement therapy., Conclusion: This study showed that critically ill patients with solid malignancies had poor 1-year survival despite relatively low ICU mortality. These findings highlight the need for careful consideration of ICU admission in patients with solid malignancy, and decision-making should be based on an understanding of the expected short- and long-term prognosis of ICU admission after an informed discussion among patients, families, and physicians.

Background: Patients with respiratory disease often need oxygen supplements through a High-flow nasal cannula (HFNC), both hypoxia and hyperoxia can be harmful. Proper oxygen therapy requires careful monitoring of oxygen levels and adjustments to oxygen levels. A new automated system called Targeted SpO2 Feedback (TSF) improved the oxygen delivery system compared to manual adjustments. [Correction added on 25 October 2024, after first online publication: Background subsection in Abstract has been added on this version.] AIM: To test whether targeted SpO2 feedback (TSF), an automatic control system for fraction of inspired oxygen (FiO2), achieves more time in the optimal SpO2 range and/or reduces the frequency of manual adjustments to administered FiO2 compared with conventional manual titration in patients with hypoxia on high-flow nasal cannula (HFNC) therapy., Study Design: Twenty-two patients were recruited from two hospitals. For each, two sessions of manual mode and two sessions of TSF were applied in a random order, each session lasting 2 h. The target SpO2 on TSF was 95%. Oxygen monitoring levels were classified into four SpO2 ranges: hypoxia (≤ 89%), borderline (90%-93%), optimal (94%-96%) and hyperoxia (≥ 97%). The two modes were compared based on the proportion of time spent in each SpO2 range and the number of manual FiO2 adjustments., Results: The proportion of time in the optimal SpO2 range was 20.5% under manual titration mode and 65.4% under TSF (p < .01). The proportions of time in the hypoxia range were 1.1% and 0.4%, respectively (p = .31), in the borderline range 4.7% and 3.5%, respectively (p = .54), and in the hyperoxia range 73.7% and 30.7%, respectively (p < .01). There were statistical differences only in the optimal and hyperoxia SpO2 ranges. During the 8 h, the frequency of manual FiO2 adjustment was 0.7 times for the manual mode and 0.2 times for TSF, showing no statistically significant difference (p = 0.076)., Conclusion: Compared with manual titration, TSF achieved greater time of the optimal SpO2 and less time of hyperoxia during HFNC. The frequency of manual adjustments on TSF tended to be less than on manual titration mode., Relevance to Clinical Practice: Automatic closed-loop algorithm FiO2 monitoring systems can achieve better oxygen treatments than conventional monitoring and may reduce nurse workloads. In the era of pandemic respiratory diseases, this system can also facilitate contactless SpO2 monitoring during HFNC therapy., (© 2024 British Association of Critical Care Nurses.)

The inevitable dealumination process of zeolite Y is closely related to ultrastabilization, enhanced Bro̷nsted acidity, and deactivation throughout its life cycle, producing complex aluminum and acidic hydroxyl species. Most investigations on dehydrated zeolites have focused on the Bro̷nsted acidity of tetra-coordinated Al (Al(IV)) and Lewis acidity associated with tricoordinated Al (Al(III)) sites, which has left the penta-coordinated Al (Al(V)) in dealuminated zeolites scarcely discussed. This is largely due to the oversimplified view of detectable Al(V) as an exclusively extra-framework species with Lewis acidity. Here we report the formation of Bro̷nsted acidic penta-coordinated Al species (Al(V)-BAS) in the dealumination process. Two-dimensional (2D) through-bond and multiquantum 1 H-{ 27 Al} correlation solid-state NMR experiments demonstrate the presence of a bridging Si-OH-Al(V) structure in dealuminated Y zeolites. Different from the conventional belief that water attack leads to the breaking of zeolite framework Al-O bonds in the initial stage of zeolite dealumination, the observed Al(V) as a dealumination intermediate is directly correlated with a BAS pair because of the direct dissociation of water on the framework tetrahedral aluminum (Al(IV)), thus bypassing the cleavage of Al-O bonds. 1 H double-quantum solid-state NMR experiments and theoretical calculations provide further evidence for this mechanism, whereas pyridine adsorption experiments confirm stronger acidity of Al(V)-BASs than the traditional bridging hydroxyl groups associated with Al(IV). We were also able to detect the Al(V)-BAS site from dealuminated SSZ-13 zeolite with CHA topology, suggesting that its creation is not specific to the framework structure of zeolites.

Background: In children with autism spectrum disorder (ASD), problem behaviors play a dysfunctional role, causing as much difficulty with daily living and adjustment as the core symptoms. If such behaviors are not effectively addressed, they can result in physical, economic, and psychological issues not only for the individual but also for family members., Objective: We aimed to develop and evaluate the feasibility of a mobile app-assisted parent training program for reducing problem behaviors in children with ASD., Methods: This open-label, single-center, randomized controlled trial was conducted among parents of children with ASD aged 36-84 months. Participants were recruited from the Department of Psychiatry at Seoul National University Hospital. Participants were randomly assigned (1:1) by a blinded researcher. Randomization was performed using a stratified block randomization (with a block size of 4). Parents in the intervention group completed the mobile app-assisted parent training program at home over a 12-week period. They continued to receive their usual nondrug treatment in addition to the mobile app-assisted parent training program. The control group continued to receive their usual nonpharmaceutical treatment for 12 weeks without receiving the parent training program intervention. The primary outcome measure was the median change in the Korean Child Behavior Checklist (K-CBCL) scores from before to after the intervention. Lower scores on the K-CBCL indicated a decrease in overall problem behavior., Results: Between November 9, 2022, and December 8, 2022, 64 participants were enrolled. Overall, 42 children (intervention group median age: 49, IQR 41-52.5 months; control group median age: 49, IQR 42-58 months) of the participants joined the program. The intervention group included 20 (48%) participants and the control group included 22 (52%) participants. In the intervention group, the K-CBCL total scores showed a decrease after the intervention, with a median difference of -0.5 (95% CI -4.5 to 3). Pervasive developmental disorder scores also showed a decrease, with a median difference of -2.1 (95% CI -8.5 to 2.5). However, there was no significant difference in Clinical Global Impression-Severity of Illness scores after the intervention for both the control and intervention groups. Scores on the Korean version of the Social Communication Questionnaire showed a further decrease after the intervention in the intervention group (median difference -2, 95% CI -4 to 1). Caregivers' stress evaluated using the Korean Parenting Stress Index Fourth Edition-Short Form did not show any significant differences between the control and intervention groups. There were no adverse events related to study participation., Conclusions: The findings demonstrated the feasibility of using mobile devices for evidence-based parent training to reduce problem behaviors in children with ASD. Mobile devices' accessibility and flexibility may provide a viable alternative for offering early intervention for problem behaviors in children with ASD., Trial Registration: CRIS KCT0007841; https://cris.nih.go.kr/cris/search/detailSearch.do?&seq=23112., (©JooHyun Lee, JaeHyun Lim, Soyeon Kang, Sujin Kim, So Yoon Jung, Sujin Kim, Soon-Beom Hong, Yu Rang Park. Originally published in JMIR Human Factors (https://humanfactors.jmir.org), 28.10.2024.)

The rapid response system (RRS) is associated with a reduction in in-hospital mortality. This study aimed to determine the characteristics and outcomes of patients transferred to the intensive care unit (ICU) by a rapid response team (RRT). This retrospective, multicenter cohort study included patients from nine hospitals in South Korea. Adult patients who were admitted to the general ward (GW) and required RRS activation were included. Patients with do-not-resuscitate orders and without lactate level or Sequential Organ Failure Assessment score were excluded. A total of 8228 patients were enrolled, 3379 were transferred to the ICU. The most common reasons for RRT activation were respiratory distress, sepsis and septic shock. The number of patients who underwent interventions, the length of hospital stays, 28-day mortality, and in-hospital mortality were higher in the ICU group than in the GW group. Factors that could affect both 28-day and in-hospital mortality included the severity score, low PaO 2 /FiO 2 ratio, higher lactate and C-reactive protein levels, and hospitalization time prior to RRT activation. Patients admitted to the ICU after RRT activation generally face more challenging clinical situations, which may affect their survival outcomes., (© 2024. The Author(s).)

Despite extensive efforts over the past several decades, the current mechanistic understanding of zeolite crystallization is still far from satisfactory, thus precluding the synthesis of designer zeolites. Here we show that the nucleation and in situ transformation pathways during the synthesis of medium-pore zeolite TNU-9 can be altered by controlling the extent of cooperative structure direction between Na + and Cs + ions in the presence of 1,4-bis( N -methylpyrrolidinium)butane cations as an organic structure-directing agent. The intermediate phase selectivity was found to change from bikitaite to analcime to layered MCM-22 precursor when the gel Na/Cs ratio was adjusted to 7, 15, and 20, respectively. We also show that the transformation of bikitaite into TNU-9 begins at the surface of intermediate crystals, unlike that of analcime and MCM-22 precursor by a dissolution-recrystallization process. The force field simulation results suggest that the nucleation of different intermediate phases is not thermodynamically but kinetically controlled. This study provides a new basis for advancing the fundamental understanding of zeolite crystallization pathways.

Polyhexamethylene guanidine (PHMG) is a positively charged polymer used as a disinfectant that kills microbes but can cause pulmonary fibrosis if inhaled. After the long-term risks were confirmed in South Korea, it became crucial to measure toxicity through diverse surrogate biomarkers, not only proteins, especially after these hazardous chemicals had cleared from the body. These biomarkers, identified by their biological functions rather than simple numerical calculations, effectively explained the imbalance of pulmonary surfactant caused by fibrosis from PHMG exposure. These long-term studies on children exposed to PHMG has shown that blood protein indicators, primarily related to apolipoproteins and extracellular matrix, can distinguish the degree of exposure to humidifier disinfectants (HDs). We defined the extreme gradient boosting models and computed reflection scores based on just ten selected proteins, which were also verified in adult women exposed to HD. The reflection scores successfully discriminated between the HD-exposed and unexposed groups in both children and adult females (AUROC: 0.957 and 0.974, respectively) and had a strong negative correlation with lung function indicators. Even after an average of more than 10 years, blood is still considered a meaningful specimen for assessing the impact of environmental exposure to toxic substances, with proteins providing in identifying the pathological severity of such conditions., 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.)

A large number of species in the genus Colletotrichum have been reported as causal agents of anthracnose on crops and wild plants in Korea. Many Colletotrichum isolates from the country preserved in the Korean Agricultural Culture Collection (KACC) were previously identified based on host plants and morphological characteristics, and it may lead to species misidentification. Thus, accurate fungal species identification using multilocus sequence analyses is essential for understanding disease epidemiology and disease management strategies. In this study, combined DNA sequence analyses of internal transcribed spacer, gapdh, chs-1, his3, act, tub2, and gs were applied to re-identify 27 Colletotrichum isolates in KACC. The phylogenetic analyses showed that the isolates resulted in 11 known species, they belong to the C. dematium species complex (C. hemerocallidis, C. jinshuiense, and C. spinaciae), the C. magnum complex (C. kaifengense and C. cf. ovatense), the C. orchidearum complex (C. cattleyicola, C. plurivorum, C. reniforme, and C. sojae) and the C. orbiculare complex (C. malvarum and C. orbiculare). Of them, C. cattleyicola, C. hemerocallidis, C. kaifengense, and C. reniforme were unrecorded species in Korea. In the view of host-fungus combinations, 10 combinations are newly reported in the world and 12 are new reports in Korea, although their pathogenicity on the host was not confirmed.

Study Objectives: This study assessed the current state of sleep medicine accreditation and training in Asia by conducting a comprehensive survey across 29 Asian countries and regions facilitated by the Asian Society of Sleep Medicine to identify existing gaps and provide recommendations for future enhancements., Methods: The Asian Society of Sleep Medicine Education Task Force Committee designed a survey to gather data on accreditation, education, and training standards in sleep medicine, including information on challenges in enhancing education in the field., Results: With an 86% (25 countries/regions) response rate, the survey showed that sleep medicine is recognized as an independent specialty in just 9 countries/regions (36% of the countries/regions surveyed). Ten countries/regions have established sleep medicine training programs, with Japan and Saudi Arabia offering it as a distinct specialty. Significant disparities in training and accreditation standards were identified, with many countries/regions lacking formalized training and practice guidelines. The survey also revealed that most local sleep societies across Asia support the development of an Asian Sleep Medicine Training Curriculum led by the Asian Society of Sleep Medicine. However, several barriers significantly impede the establishment and development of sleep medicine training programs, including the scarcity of trained specialists and technologists and the absence of national accreditation for sleep medicine., Conclusions: The survey highlights the need for standardized sleep medicine training and accreditation across Asia. Developing an Asian Sleep Medicine Training Curriculum and promoting Asian Society of Sleep Medicine accreditation guidelines are key recommendations. Implementing these strategies is essential for advancing sleep medicine as a widely recognized discipline throughout Asia., Citation: BaHammam AS, Al-Abri MA, Abd Rashid R, et al. Mapping the landscape of sleep medicine training across Asia. J Clin Sleep Med . 2024;20(10):1647-1656., (© 2024 American Academy of Sleep Medicine.)

Background: Biological valve prostheses in rapid-deployment aortic valve replacement (RD AVR) procedures have demonstrated excellent outcomes. However, previous studies indicate a lack of specific surgical outcomes for the bicuspid aortic valve (BAV) or recommend RD AVR implementation. The existing literature comparing the clinical and hemodynamic outcomes of patients with BAV and those with tricuspid aortic valves (TAVs) after RD AVR is limited. Therefore, this study evaluated the safety and feasibility of RD AVR in BAV, including Sievers type 0, and compared the early clinical and hemodynamic outcomes of patients who underwent RD AVR at a single center based on aortic valve type., Methods: Our institution officially commenced performing RD AVR using Intuity valves in September 2022. The medical records of 80 patients who underwent aortic valve replacement (AVR) between September 1, 2022, and July 31, 2023 were retrospectively analyzed. In this set, 30 patients underwent RD AVR for aortic stenosis. Among the 30 RD AVR cases, groups A and B comprised 16 (53.3%) patients with TAV and 14 (46.7%) with BAV, respectively. The preoperative characteristics and postoperative echocardiographic data were compared between the two groups., Results: No statistically significant differences in preoperative characteristics, including mean age and sex distribution, were found between groups A and B. Notably, no patient in both groups exhibited mild- or higher-grade aortic regurgitation. The postoperative transvalvular mean pressure gradients showed significantly lower values in group B than in group A (12.20±4.64 vs. 16.26±5.49 mmHg, P=0.03). The necessity to insert a permanent pacemaker was not found in any of the patients (0%) in group A but was found in one (7.1%) patient in group B (P=0.46). Among the BAV cases, six (20%) were categorized as Sievers type 0. Of the 14 patients in group B, six with Sievers type 0 and the remaining eight with other bicuspid valve types were designated as groups B0 and B1, respectively. Similarly, no significant difference in postoperative transvalvular mean pressure gradient was observed between the two groups (11.33±4.49 vs. 12.86±4.94 mmHg, P=0.56). No in-hospital mortality was observed among all 30 patients., Conclusions: In this study, RD AVR was considered feasible in a small, carefully selected cohort of patients with aortic stenosis, even in BAV, including Sievers type 0, as observed from the standpoint of postoperative hemodynamic outcomes and the incidence of aortic regurgitation., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jtd.amegroups.com/article/view/10.21037/jtd-23-1942/coif). The authors have no conflicts of interest to declare., (2024 AME Publishing Company. All rights reserved.)

Myelocytomatosis (MYC) transcription factors (TFs) belong to the basic helix-loop-helix (bHLH) family in plants and play a central role in governing a wide range of physiological processes. These processes encompass plant growth, development, adaptation to biotic and abiotic stresses, as well as secondary metabolism. In recent decades, significant strides have been made in comprehending the multifaceted regulatory functions of MYCs. This advancement has been achieved through the cloning of MYCs and the characterization of plants with MYC deficiencies or overexpression, employing comprehensive genome-wide 'omics' and protein-protein interaction technologies. MYCs act as pivotal components in integrating signals from various phytohormones' transcriptional regulators to orchestrate genome-wide transcriptional reprogramming. In this review, we have compiled current research on the role of MYCs as molecular switches that modulate signal transduction pathways mediated by phytohormones and phytochromes. This comprehensive overview allows us to address lingering questions regarding the interplay of signals in response to environmental cues and developmental shift. It also sheds light on the potential implications for enhancing plant resistance to diverse biotic and abiotic stresses through genetic improvements achieved by plant breeding and synthetic biology efforts., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The historical climate variability in East Antarctica inferred from ice cores remains under debate owing to the vastness and complexity of the region. This study evaluates the potential climate variabilities in the Styx-M ice core records (δ 18 O, d-excess, and snow accumulation) from northern Victoria Land adjacent to the Ross Sea sector of East Antarctica during 1979-2014. Results show that the primary moisture source in this area is the Pacific Ocean sector. Although the annual mean δ 18 O values was limited to directly indicate the temperature changes, a weak relevance between the average δ 18 O values and the temperature signal during the austral summer season is detectable. δ 18 O, d-excess, and snow accumulation correlate with sea surface temperature and sea ice extent in the Ross Sea sector. A coupled influence of the SAM, ASL, and ENSO climate indices is expected, because the oceanic environment in this region is influenced by them. The pronounced intrusion of oceanic moisture coupled with atmospheric circulation patterns over the Ross Sea region makes the Styx-M ice core a promising record of the local oceanic conditions, with the snow accumulation rate being a direct proxy. Additionally, the analysis of trace elements from 1979 to 1999 revealed the presence of crustal dust sourced from the Transantarctic Mountains, as well as non-crustal sources, both intricately linked with atmospheric transport. These results demonstrate that the contributions of-and variations in-oceanic conditions associated with atmospheric circulation changes are detectable and dominant in the Styx-M ice core. This study serves as a basis for interpreting longer parts of the Styx-M ice core., Competing Interests: Declaration of competing interest Jeonghoon Lee reports financial support and administrative support were provided by Ewha Womans University. Jeonghoon Lee reports a relationship with Ewha Womans University that includes: employment. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Microbes are critical contributors in main areas of biotechnology, including green, red, and white biotechnology. This is why the importance of the preservation of microbial resources cannot be emphasized enough. Culture collections are repositories not only for the preservation and maintenance of a large variety of microbial resources and the associated data but also for their distribution in a quality-controlled manner. The mission of culture collections facilitates and supports utilization of microbial resources for research, education, and industrial purposes. Led by the World Federation for Culture Collections, an international organization committed to fostering the activities of culture collections of microorganisms and cell lines, more than 850 culture collections from 80 countries and regions work together to ensure the perpetuation of microbial resources. In addition, domestic networks, such as Japan Society for Culture Collections and United States Culture Collection Network along with regional networks for Europe, Latin America, and Asia thrive to ensure the long-term viability of microbial resources. The Republic of Korea recently took the first step in networking through the coordination of six ministries which house nine national microbial culture collections. With an explosion in microbiome research and a dramatic increase in the number of microbiome samples, the considerable challenge of culture collections will therefore be implementing the biobanking infrastructure of microbiome samples. Creating a domestic network of national culture collections is a key factor in efficiently and comprehensively managing nation-led microbiome research projects, particularly resulting microbiome samples. In this context, this review aims to provide an overview of microbial culture collection network and their future role to address the challenge in the microbiome era., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group on behalf of the Korean Society of Mycology.)

We evaluated the risk of being diagnosed with various psychiatric disorders after an attention-deficit/hyperactivity disorder (ADHD) diagnosis using data from South Korea's National Health Insurance Service from 2002 to 2019, which covers approximately 97% of the country's population. ADHD and control groups were selected after propensity score matching was performed for individuals diagnosed with ADHD and their age- and sex-matched counterparts from the general population. Comorbid psychiatric disorders included depressive disorder, bipolar disorder, tic disorder, and schizophrenia. The incidence of newly diagnosed psychiatric disorders was compared between the groups. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated and adjusted for ADHD medication prescription. After matching, 353,898 individuals were assigned to each of the two groups. Compared to the control group, the ADHD group showed a significantly higher risk of being subsequently diagnosed with depressive disorder, bipolar disorder, schizophrenia, and tic disorder. The onset age of depressive disorder, bipolar disorder, and schizophrenia in the ADHD group was 16-17 years, approximately 5 years earlier than that in the control group. The risk for depression was the highest in individuals with high income levels, and that for schizophrenia was the highest among rural patients. The median length of the follow-up time until the diagnosis of each comorbid psychiatric disorder was 7.53, 8.43, 8.53, and 8.34 years for depressive disorder, bipolar disorder, schizophrenia, and tic disorder, respectively. Individuals with ADHD had an overall higher risk of being diagnosed with subsequent psychiatric disorders than did the controls. Hence, they should be carefully screened for other psychiatric symptoms from an early age and followed up for an extended duration, along with appropriate interventions for ADHD symptoms, including psychosocial treatments and educational approaches., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The occurrence of type II endoleaks after endovascular repair of aortic aneurysm has gradually gained increasing attention. We present a case of a patient with an expanding aneurysm after thoracic endovascular aortic repair (TEVAR) for a type II endoleak, in which successful direct ligations of the intercostal artery were performed using a sac incision without cardiopulmonary bypass (CPB) or graft replacement., Case Presentation: A 62-year-old male patient, previously treated with TEVAR for a descending thoracic aortic aneurysm, presented with ongoing chest discomfort. Based on the diagnosis of a growing aneurysm and type II endoleak, the patient was prepared for CPB and aortic cross-clamping, as a precautions against the possibility of a type I endoleak. A longitudinal opening of the thoracic aortic aneurysm sac was performed following left thoracotomy. Visual confirmation identified the T5 level intercostal artery as the source of the endoleak, and after confirming the absence of a type I endoleak, multiple ligations were applied to the intercostal artery. Follow-up computed tomography confirmed the absence of endoleaks or sac growth., Conclusion: In a case involving TEVAR for a thoracic aortic aneurysm, open suture ligations were used to treat type II endoleaks without having to resort to CPB, resulting in successful outcomes., (© 2024. The Author(s).)

Objective: Restless legs syndrome (RLS) is a common sleep disorder among adolescents. This study aimed to investigate the lifestyle factors and sleep disturbances associated with the symptoms suggestive of RLS in Korean adolescents., Methods: In this cross-sectional study, we investigated a total of 25,789 adolescents (mean age, 15.8 ± 1.7 years; male, 48.5 %). The presence of symptoms suggestive of RLS was assessed with a single question about RLS in the Global Sleep Assessment Questionnaire. We performed multiple logistic regression analysis to estimate the odds ratios (ORs) and 95 % confidence intervals (CIs) of lifestyle factors and sleep disturbances that were independently associated with adolescent RLS., Results: The prevalence of RLS-suggestive symptoms was 5.1 % among adolescents. After adjustment, lifestyle factors associated with symptoms suggestive of RLS were occasional alcohol consumption (OR, 1.245; 95 % CI, 1.006-1.540) and proneness to Internet addiction (OR, 1.027; 95 % CI, 1.021-1.033). Bedtime behaviors associated with RLS-suggestive symptoms were sleeping with a doll or pet (OR, 1.194; 95 % CI, 1.032-1.381) and sleeping with a TV or radio on (OR, 1.366; 95 % CI, 1.156-1.614). Male sex, frequent snoring and witnessed apnea, perceived sleep insufficiency, excessive daytime sleepiness were also associated with RLS-suggestive symptoms in adolescents., Conclusions: Adolescents with symptoms suggestive of RLS were associated with different lifestyle factors compared to adults with RLS. Further research is needed to determine the clinical implications of lifestyle factors in adolescent RLS., 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: Increasing age has been observed among patients admitted to the intensive care unit (ICU). Age traditionally considered a risk factor for ICU mortality. We investigated how the epidemiology and clinical outcomes of older ICU patients have changed over a decade., Methods: We analyzed patients admitted to the ICU at a university hospital in Seoul, South Korea. We defined patients aged 65 and older as older patients. Changes in age groups and mortality risk factors over the study period were analyzed., Results: A total of 32,322 patients were enrolled who aged ≥65 years admitted to the ICUs between January 1, 2007, and December 31, 2017. Patients aged ≥65 years accounted for 35% and of these, the older (O, 65 to 74 years) comprised 19,630 (66.5%), very older (VO, 75 to 84 years) group 8,573 (29.1%), and very very older (VVO, ≥85 years) group 1,300 (4.4%). The mean age of ICU patients over the study period increased (71.9±5.6 years in 2007 vs. 73.2±6.1 years in 2017) and the proportions of the VO and VVO group both increased. Over the period, the proportion of female increased (37.9% in 2007 vs. 43.3% in 2017), and increased ICU admissions for medical reasons (39.7% in 2007 vs. 40.2% in 2017). In-hospital mortality declined across all older age groups, from 10.3% in 2007 to 7.6% in 2017. Hospital length of stay (LOS) decreased in all groups, but ICU LOS decreased only in the O and VO groups., Conclusion: The study indicates a changing demographic in ICUs with an increase in older patients, and suggests a need for customized ICU treatment strategies and resources.

The Chinese quince (Chaenomeles sinensis (Thouin) Koehne), belongs to the Rosaceae family, is widely distributed throughout Asia, including Republic of Korea. It is used as a traditional treatment for asthma, common cold, and dry pharynx. Numerous recent pharmacological studies on antiinfluenza, antioxidant, and antidiabetic properties have confirmed the medicinal properties of the Chinese quince fruit (Chun et al., 2012). In March 2022, leaf spots on Chinese quince, resulting in defoliation, were observed in Andong, Gyeongsangbuk Province, Korea (Fig. 1A). The disease symptoms are dark brown spots on leaves. Later, the chlorophyll is lost, causing the entire leaf to become wilted and fell off (Fig. 1B). To identify the pathogen, symptomatic leaves were brought to the laboratory, cut into small pieces, and surface-disinfected in 70% ethanol for 15 s and rinsed with sterile distilled water (SDW). The specimens were then treated with 1% NaOCl for 15 s, followed by rinsing with SDW. Thus, surface-disinfected tissues were placed onto potato dextrose agar (PDA) plates and incubated at 25°C for 7 d. A total of four isolates were obtained from the infected leaves. The colonies were transferred onto freshly prepared PDA plates by the single spore method for further purification. GYUN-10746 isolate was selected as the representative strain among the four isolates and deposited in the Korean Agricultural Culture Collection (KACC 410367). They initially produced white mycelia, which turned dark brown or pale brown at the center and beige at the periphery after 7 d (Fig. 1C and D). Conidiophores were pyriform, sometimes ovoid, or ellipsoidal and brown, measuring 30.8 ± 0.49 × 12.9 ± 0.26 µm (length × width) (n=100) (Fig. 1E). The morphological characteristics were consistent with those of Alternaria alternata (Woudenberg et al. 2015). For molecular identification, DNA was amplified using the following primers: ITS1/ITS4 (White et al. 1990), EF1-728F/EF1-986R (Carbone et al. 1999), Gpd-R/Gpd-F (Berbee et al. 1999), Alt a1-F/Alt a1-R (Hong et al. 2005) and rpb2F/rpb2R (Liu et al. 1999) by PCR. DNA sequences from all 4 isolates (GYUN-10746, GYUN-11193, GYUN-11194 and GYUN-11195) were identical. The ITS (OP594615), TEF1-α (OR327062), GAPDH (OR372157), Alt a 1 (OR327061), and RPB2 (OR352741) sequences from the representative isolate GYUN-10746 were 100% identical to those of previously identified A. alternate isolates. A phylogenetic tree was constructed using sequences of ITS, TEF1-α, GAPDH, Alt a l, and RPB2 to illustrate their relationship with A. alternata and related Alternaria species (Fig. 2). For the pathogenicity test, healthy Chinese quince branch containing leaves were inoculated with 7-day-old mycelial plugs of A. alternata, while leaves on a branch inoculated with PDA plugs alone served as a control group. Thus inoculated branches were incubated at 25°C for 7 d. Disease symptoms were developed on leaves of the branches inoculated with mycelial plugs of the fungal pathogen (Fig. 1F), while no symptoms developed on control group. The resulting leaf spots resembled those on the original infected plants. To confirm Koch's postulates, the pathogen was re-isolated from inoculated leaves with identical morphological and molecular characteristics. To the best of our knowledge, this is the first report of leaf spot caused by A. alternata in C. sinensis in Korea. The identification of the pathogen may provide pertinent information for the development of disease controlling strategies.

Background: Anti-PD-1 therapy and chemotherapy is a recommended first-line treatment for recurrent or metastatic nasopharyngeal carcinoma, but the role of PD-1 blockade remains unknown in patients with locoregionally advanced nasopharyngeal carcinoma. We assessed the addition of sintilimab, a PD-1 inhibitor, to standard chemoradiotherapy in this patient population., Methods: This multicentre, open-label, parallel-group, randomised, controlled, phase 3 trial was conducted at nine hospitals in China. Adults aged 18-65 years with newly diagnosed high-risk non-metastatic stage III-IVa locoregionally advanced nasopharyngeal carcinoma (excluding T3-4N0 and T3N1) were eligible. Patients were randomly assigned (1:1) using blocks of four to receive gemcitabine and cisplatin induction chemotherapy followed by concurrent cisplatin radiotherapy (standard therapy group) or standard therapy with 200 mg sintilimab intravenously once every 3 weeks for 12 cycles (comprising three induction, three concurrent, and six adjuvant cycles to radiotherapy; sintilimab group). The primary endpoint was event-free survival from randomisation to disease recurrence (locoregional or distant) or death from any cause in the intention-to-treat population. Secondary endpoints included adverse events. This trial is registered with ClinicalTrials.gov (NCT03700476) and is now completed; follow-up is ongoing., Findings: Between Dec 21, 2018, and March 31, 2020, 425 patients were enrolled and randomly assigned to the sintilimab (n=210) or standard therapy groups (n=215). At median follow-up of 41·9 months (IQR 38·0-44·8; 389 alive at primary data cutoff [Feb 28, 2023] and 366 [94%] had at least 36 months of follow-up), event-free survival was higher in the sintilimab group compared with the standard therapy group (36-month rates 86% [95% CI 81-90] vs 76% [70-81]; stratified hazard ratio 0·59 [0·38-0·92]; p=0·019). Grade 3-4 adverse events occurred in 155 (74%) in the sintilimab group versus 140 (65%) in the standard therapy group, with the most common being stomatitis (68 [33%] vs 64 [30%]), leukopenia (54 [26%] vs 48 [22%]), and neutropenia (50 [24%] vs 46 [21%]). Two (1%) patients died in the sintilimab group (both considered to be immune-related) and one (<1%) in the standard therapy group. Grade 3-4 immune-related adverse events occurred in 20 (10%) patients in the sintilimab group., Interpretation: Addition of sintilimab to chemoradiotherapy improved event-free survival, albeit with higher but manageable adverse events. Longer follow-up is necessary to determine whether this regimen can be considered as the standard of care for patients with high-risk locoregionally advanced nasopharyngeal carcinoma., Funding: National Natural Science Foundation of China, Key-Area Research and Development Program of Guangdong Province, Natural Science Foundation of Guangdong Province, Overseas Expertise Introduction Project for Discipline Innovation, Guangzhou Municipal Health Commission, and Cancer Innovative Research Program of Sun Yat-sen University Cancer Center., Translation: For the Chinese translation of the abstract see Supplementary Materials section., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Although medical emergency teams (METs) have been widely introduced, studies on the importance of a dedicated intensivist staffing to METs are lacking. A single-center retrospective before-and-after study was performed. Deteriorating patients who required emergency airway management in general wards by MET were included in this study. We divided the study period according to the presence of a dedicated intensivist staff in MET: (1) non-staffed period (from January 2016 to February 2018, n = 971) and (2) staffed period (from March 2018 to December 2019, n = 651), and compared emergency airway management-related variables and outcomes between the periods. Among 1622 patients included, mean age was 63.0 years and male patients were 64.2% (n = 1042). The first-pass success rate was significantly increased in the staffed period (85.9% in the non-staffed vs 89.2% in the staffed; P = .047). Compliance to rapid sequence intubation was increased (9.4% vs 34.4%; P < .001) and vocal cords were more clearly open (P < .001) in the staffed period. The SpO2/FiO2 ratio (median [interquartile range], 125 [113-218] vs 136 [116-234]; P = .007) and the ROX index (4.6 [3.4-7.6] vs 5.1 [3.6-8.5]; P = .013) at the time of intubation was higher in the staffed period, suggesting the decision on intubation was made earlier. The post-intubation hypoxemia was less commonly occurred in the staffed period (7.2% vs 4.2%, P = .018). In multivariate analysis, the rank of operator was a strong predictor of the first-pass success (adjusted OR [95% CI], 2.280 [1.639-3.172]; P < .001 for fellow and 5.066 [1.740-14.747]; P < .001 for staff, relative to resident). In our hospital, a dedicated intensivist staffing to MET was associated with improved emergency airway management in general wards. Staffing an intensivist to MET needs to be encouraged to improve the performance of MET and the patient safety., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: Mucins play a pivotal role in epithelial carcinogenesis; however, their role remains elusive in ampulla of Vater (AoV) cancer, regardless of histological subtype. Therefore, we investigated the clinical significance of MUC1, MUC2, MUC5AC, and MUC6 expression in AoV cancer. Methods : Using samples from 68 patients with AoV cancer, we performed immunohistochemical staining for MUC1, MUC2, MUC5AC, and MUC6 using a tissue microarray. Subsequently, we analyzed their expression patterns in relation to clinicopathological parameters and patient outcomes. Results : Of the patients, 98.5% exhibited positive expression for MUC1, while MUC2, MUC5AC, and MUC6 were expressed in 44.1%, 47.1%, and 41.2% of the patients, respectively. Correlation analyses between mucin expression and clinicopathological factors revealed no significant associations, except between MUC5AC expression and N stage. Univariate analysis demonstrated significant associations between MUC5AC expression and overall survival (OS). Multivariate analysis further confirmed that MUC5AC expression was a significant predictor of OS, along with the N stage. However, MUC5AC expression was not meaningfully associated with recurrence-free survival (RFS). The patients positive for MUC5AC expression had a considerably shorter OS than those with negative expression. Conclusions : Our study provides insights into the clinical impact of mucins on AoV cancer, regardless of the histological subtype. Although MUC1 expression is universal, MUC5AC expression is a significant prognostic indicator that correlates with lymph node metastasis and poor OS. These results emphasize the possible utility of MUC5AC as a biomarker for extensive lymph node dissection and the prognostic evaluation of patients with AoV cancer.