Search

Youlim Kim,1,&ast; Hyun Lee,2,&ast; Sung Jun Chung,2,&ast; Yoomi Yeo,2 Tai Sun Park,2 Dong Won Park,2 Kyung Hoon Min,3 Sang-Heon Kim,2 Tae-Hyung Kim,2 Jang Won Sohn,2 Ji-Yong Moon,2 Ho Joo Yoon2 1Division of Pulmonary, Allergy and Critical Care Medicine, Department of Internal Medicine, Konkuk University Hospital, School of Medicine, Konkuk University, Seoul, Korea; 2Department of Internal Medicine, College of Medicine, Hanyang University, Seoul, Korea; 3Division of Respiratory and Critical Care Medicine, Department of Internal Medicine, Korea University Medical Center, Guro Hospital, Seoul, Korea&ast;These authors contributed equally to this workCorrespondence: Ji-Yong MoonDepartment of Internal Medicine, Hanyang University Guri Hospital, Gyeongchun-ro 153, Guri-si, Gyeonggi-do, 11923, KoreaTel +82-31-560-2224Fax +82-31-553-7369Email respiry@gmail.comHo Joo YoonDivision of Pulmonary Medicine and Allergy, Department of Internal Medicine, Hanyang University College of Medicine, 222-1, Wangsimni-ro, Seongdong-gu, Seoul, 04763, KoreaTel +82-2-2290-8336Fax +82-2-2298-9183Email hjyoon@hanyang.ac.krBackground and Objective: Despite the usefulness of airway hyperresponsiveness (AHR) testing in diagnosing and monitoring asthma, it is challenging to perform in a real-world setting. Forced expiratory flow between 25% and 75% of vital capacity (FEF25– 75), a pulmonary measurement that can be obtained easily during routine spirometry, represents the status of medium-sized and small airways. However, the performance of FEF25– 75 in predicting AHR has not been well elucidated. Therefore, we investigated whether FEF25– 75 can predict AHR to mannitol.Methods: We performed a retrospective cohort study of 428 patients who visited a single clinic due to cough, wheezing, or dyspnea. All patients underwent spirometry with a mannitol provocation test. We compared the area under the curve (AUC) of the percentage of the predicted values of FEF25– 75 (FEF25– 75 %pred) with that of forced expiratory volume in 1 second (FEV1%pred), FEV1/forced vital capacity (FVC), and FEF25– 75/ FVC for predicting AHR.Results: The rate of AHR to mannitol was 20.3%. In the overall study population, the AUC of FEF25– 75 %pred for predicting AHR (0.772; 95% confidence interval [CI], 0.729– 0.811) was significantly higher than that of FEV1%pred (0.666; 95% CI, 0.619– 0.710; p < 0.001), FEV1/FVC (0.741; 95% CI, 0.697– 0.782; p = 0.047), and FEF25– 75/FVC (0.741, 95% CI = 0.696– 0.782, p = 0.046). The sensitivity, specificity, positive predictive value, and negative predictive value of FEF25– 75 %pred < 81% for predicting AHR in the overall study population were 77.0% (95% CI = 66.8– 85.4%), 63.9% (95% CI = 58.6– 69.0), 35.3%, and 91.6%, respectively. When we restricted the study group to subjects with normal lung function, the results were similar.Conclusion: Our results indicate that FEF25– 75 %pred can be used as a surrogate for predicting AHR in patients with respiratory symptoms.Keywords: forced expiratory flow between 25% and 75% of vital capacity, mannitol, bronchial hyperresponsiveness

Keon-Hyoung Song,1 Sang-Bum Kim,2 Chang-Koo Shim,2 Suk-Jae Chung,2 Dae-Duk Kim,2 Sang-Ki Rhee,1 Guang J Choi,1 Chul-Hyun Kim,3 Kiyoung Kim4 1Department of Pharmaceutical Engineering, Soonchunhyang University, Asan, Republic of Korea; 2College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea; 3Department of Sports Medicine, 4Department of Medical Biotechnology, Soonchunhyang University, Asan, Republic of Korea Background: The identification of permeation enhancers has gained interest in the development of drug delivery systems. A six-mer peptide, H-FCIGRL-OH (AT1002), is a tight junction modulator with promising permeation-enhancing activity. AT1002 enhances the transport of molecular weight markers or agents with low bioavailability with no cytotoxicity. However, AT1002 is not stable in neutral pH or after incubation under physiological conditions, which is necessary to fully uncover its permeation-enhancing effect. Thus, we increased the stability or mitigated the instability of AT1002 by modifying its terminal amino acids and evaluated its subsequent biological activity.Methods: C-terminal-amidated (FCIGRL-NH2, Pep1) and N-terminal-acetylated (Ac-FCIGRL, Pep2) peptides were analyzed by liquid chromatography–mass spectrometry. We further assessed cytotoxicity on cell monolayers, as well as the permeation-enhancing activity following nasal administration of the paracellular marker mannitol.Results: Pep1 was nontoxic to cell monolayers and showed a relatively low decrease in peak area compared to AT1002. In addition, administration of mannitol with Pep1 resulted in significant increases in the area under the plasma concentration–time curve and peak plasma concentration at 3.63-fold and 2.68-fold, respectively, compared to mannitol alone. In contrast, no increase in mannitol concentration was shown with mannitol/AT1002 or mannitol/Pep2 compared to the control. Thus, Pep1 increased the stability or possibly reduced the instability of AT1002, which resulted in an increased permeation-enhancing effect of AT1002.Conclusion: These results suggest the potential usefulness of C-terminal-amidated AT1002 in enhancing nasal drug delivery, which may lead to the development of a practical drug delivery technology for drugs with low bioavailability. Keywords: N-terminal acetylation, stability, permeation enhancer

Background: Little is known regarding genetic factors associated with motor or cognitive outcomes in Parkinson's disease (PD).Objective: To identify common genetic variants associated with motor and cognitive outcomes in PD.Methods: The sample consisted of 443 PD cases included in the first genome-wide association study (GWAS) of PD. Methods included telephone interview assessments of motor and cognitive outcomes, a median 9 years following the initial clinical assessments. Analyses included Cox proportional hazard models to study the association of 198,345 single nucleotide polymorphisms (SNPs) with survival free of Hoehn and Yahr stage ≥ 4 (motor outcome), and either TICS-M ≤ 27 or AD-8 ≥ 2 (cognitive outcomes).Results: The SNP rs10958605 in the C8orf4 gene had the smallest p value in analyses of the motor outcome (HR = 1.81; 95% CI = 1.42-2.31; p = 1.51 × 10(-6)). The SNP rs6482992 in the CLRN3 gene had the smallest p value in analyses of the cognitive outcome (HR = 2.03, 95% CI 1.47-2.79, p = 4.08 × 10(-6)). However, no SNP associations were significant after Bonferroni correction. The C8orf4 gene had small p values for both motor and cognitive outcomes, highlighting inflammation as a possible pathogenesis mechanism for progression in PD.Conclusions: This study suggests that common variants in several genes may be associated with motor and cognitive outcomes in PD, with biological plausibility. [ABSTRACT FROM AUTHOR]

Pure akinesia with gait freezing (PAGF) has characteristic features, including freezing of gait and prominent speech disturbance without rigidity or tremor. The purpose of this study was to investigate changes in brain glucose metabolism and presynaptic dopaminergic function in PAGF. By using [(18)F] fluorodeoxyglucose (FDG) PET, 11 patients with PAGF were compared with 14 patients with probable progressive supranuclear palsy (PSP), 13 patients with Parkinson's disease (PD), and 11 normal controls. [(18)F] N-(3-fluoropropyl)-2beta-carbon ethoxy-3beta-(4-iodophenyl) nortropane (FP-CIT) PET was performed in 11 patients with PAGF and with 10 normal controls. The PAGF patients showed decreased glucose metabolism in the midbrain when compared with normal controls. PSP patients showed a similar topographic distribution of glucose hypometabolism with additional areas, including the frontal cortex, when compared with normal controls. The FP-CIT PET findings in patients with PAGF revealed severely decreased uptake bilaterally in the basal ganglia. These findings suggest that both PAGF and PSP may be part of the same pathophysiologic spectrum of disease. However, the reason why PAGF manifests clinically in a different manner needs to be further elucidated. [ABSTRACT FROM AUTHOR]

Background: Polymorphisms in SNCA, MAPT and LRRK2 genes have recently been confirmed as risk factors for Parkinson's disease (PD), although with small individual attributable risk. Here we investigated the association of PD with interactions between variants of these genes.Methods: As part of a previous study of PD susceptibility genes 119 SNCA, MAPT, and LRRK2 haplotype tagging single nucleotide polymorphisms (SNPs) and two variable number tandem repeats (VNTRs) were genotyped in 1098 PD cases from the upper Midwest, USA and 1098 matched controls. Twenty-six of these SNPs were selected for SNP-SNP (or SNP-VNTR or VNTR-VNTR) interaction analysis (256 interaction pairs). Case-control analyses were performed to study association of pairwise SNP interactions with PD susceptibility.Results: Out of the 256 interaction pairs investigated, 10 had uncorrected p-values <0.05. These represented six SNCA-LRRK2 pairs, three SNCA-MAPT pairs, and one MAPT-LRRK2 pair. However, none of these pairwise interactions were significant after correction for multiple testing. Secondary analyses in strata defined by type of control (sibling or unrelated), sex, or age at onset of the case also did not reveal any significant interactions after accounting for multiple testing.Conclusions: This study provides no statistically significant evidence of gene-gene interaction effects for the three confirmed genetic susceptibility loci for PD. However, this does not exclude the possibility that other genomic loci or environmental risk factors interact with these genes. [ABSTRACT FROM AUTHOR]

The ability of a robot to plan complex behaviors with real-time computation, rather than adhering to predesigned or offline-learned routines, alleviates the need for specialized algorithms or training for each problem instance. Monte Carlo tree search is a powerful planning algorithm that strategically explores simulated future possibilities, but it requires a discrete problem representation that is irreconcilable with the continuous dynamics of the physical world. We present Spectral Expansion Tree Search (SETS), a real-time, tree-based planner that uses the spectrum of the locally linearized system to construct a low-complexity and approximately equivalent discrete representation of the continuous world. We prove that SETS converges to a bound of the globally optimal solution for continuous, deterministic, and differentiable Markov decision processes, a broad class of problems that includes underactuated nonlinear dynamics, nonconvex reward functions, and unstructured environments. We experimentally validated SETS on drone, spacecraft, and ground vehicle robots and one numerical experiment, each of which is not directly solvable with existing methods. We successfully show that SETS automatically discovers a diverse set of optimal behaviors and motion trajectories in real time.

This study investigated the effects of various binary sweetener mixtures on sweetness enhancement and their interactions with sweet or bitter taste receptors, focusing on sensory perception and receptor activity. Acesulfame K or saccharin was mixed with allulose, aspartame, erythritol, fructose, glucose, or sucrose to match a target sucrose sweetness. The effects of the mixtures on sweet and bitter taste receptors (in the human embryonic kidney -293 cells) and sensory taste intensities were evaluated. Sweetness enhancement at the sweet taste receptor level was observed in some cases, with several monosaccharides reducing the acesulfame K- or saccharin-induced bitter taste receptor activity. Combining acesulfame K or saccharin with any of the six sweeteners perceptually enhanced sweetness (60% ∼ 100% in 50:50 ratio), correlating with a reduction in inherent bitterness (-35% ∼ -63% in 50:50 ratio). This finding suggests that sweetness perception likely increased because the monosaccharides mitigate the activation of bitter receptors caused by high-potency sweeteners., 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 Ltd.. All rights reserved.)

Purpose: Deep brain stimulation (DBS) has been performed for various brain disorders. However, spinal surgery in patients with DBS was been approached with cautious trepidation due to risk of thermal brain injury and device damage from coagulation devices during surgery. This study presents the cases of successful spinal surgery performed after DBS implantation., Methods: We retrospectively reviewed the patients who received spinal surgery after DBS implantation between April 2001 and November 2022. We reviewed their demographic data, preoperative evaluations, and surgical strategies employed., Results: Among 348 patients who underwent DBS implantation, eight patients received spinal surgery. The methods used for diagnosing their spinal conditions varied: two cases of computed tomography (CT) myelogram, one case of CT scan with pre-DBS magnetic resonance imaging (MRI), one case of CT scan only, and four cases of post-DBS MRI. The location of the spinal surgery were one case of cervical spinal surgery, three cases of thoracolumbar spinal surgery, and four cases of lumbar spinal surgery. We followed diagnostic study guidelines and safety considerations tailored to each surgical step. Monopolar and bipolar coagulation devices were used when necessary. There were no cases of complications caused by spine surgery regarding DBS function or DBS implanted site., Conclusion: Careful execution of surgical procedures, adherence to safety guidelines, and the use of MRI for diagnosis can ensure safe and successful spinal surgery in patients with DBS implants, minimizing the risk of damage to the DBS system and the brain., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Glioblastoma multiforme (GBM), the most aggressive form of brain cancer, poses substantial challenges to effective treatment due to its complex and infiltrative nature, making it difficult to manage. Photodynamic therapy (PDT) and sonodynamic therapy (SDT), have emerged as promising individual treatment options against GBM due to their least-invasive approach. However, both PDT and SDT have drawbacks that require careful consideration. A combination therapy using light and sound waves has gained attention, offering new avenues to overcome challenges from individual therapies. Sono-photodynamic therapy (SPDT) has been used against various tumours. Researchers are considering SPDT as a favourable alternative to the conventional therapies for GBM. SPDT offers complementary mechanisms of action, including the production of ROS, disruption of cellular structures, and induction of apoptosis, leading to enhanced tumour cell death. This review gives an insight about PDT/SDT and their limitations in GBM treatment and the need for combination therapy. We try to unveil the process of SPDT and explore the mechanism behind improved SPDT-meditated cell death in GBM cells by focusing on the ROS-mediated cell response occurring as a result of SPDT and discussing current modifications in the existing sensitisers for their optimal use in SPDT for GBM therapy.

Parkinson's disease (PD) is an incurable, progressive and common movement disorder that is increasing in incidence globally because of population aging. We hypothesized that the landscape of rare, protein-altering variants could provide further insights into disease pathogenesis. Here we performed whole-exome sequencing followed by gene-based tests on 4,298 PD cases and 5,512 controls of Asian ancestry. We showed that GBA1 and SMPD1 were significantly associated with PD risk, with replication in a further 5,585 PD cases and 5,642 controls. We further refined variant classification using in vitro assays and showed that SMPD1 variants with reduced enzymatic activity display the strongest association (<44% activity, odds ratio (OR) = 2.24, P = 1.25 × 10 -15 ) with PD risk. Moreover, 80.5% of SMPD1 carriers harbored the Asian-specific p.Pro332Arg variant (OR = 2.16; P = 4.47 × 10 -8 ). Our findings highlight the utility of performing exome sequencing in diverse ancestry groups to identify rare protein-altering variants in genes previously unassociated with disease., Competing Interests: Competing interests: Z.G.-O. received consultancy fees from Lysosomal Therapeutics, Idorsia, Prevail Therapeutics, Ono Therapeutics, Denali, Handl Therapeutics, Neuron23, Bial Biotech, Bial, UCB, Capsida, Vanqua Bio, Congruence Therapeutics, Takeda, Jazz Pharmaceuticals, Guidepoint, Lighthouse and Deerfield. R.N.A. received consultation fees from Biogen, Biohaven, Capsida, Gain Therapeutics, Genzyme/Sanofi, Janssen, Servier, SK Biopharmaceuticals, Takeda and Vanqua Bio. Y.X. holds a stock option in NeoCytogen Therapeutics where she is scientific co-founder and Chief Scientific Officer. M.A.N.’s participation in this project was part of a competitive contract awarded to DataTecnica, LLC by the National Institutes of Health to support open science research. M.A.N. also owns stock in Character Bio, Inc. and Neuron23, Inc. The other authors declare no competing interests., (© 2024. The Author(s).)

Chimeric antigen receptor T (CAR-T) cells show remarkable efficacy for some hematological malignancies. However, CAR targets that are expressed at high level and selective to tumors are scarce. Several strategies have been proposed to tackle the on-target off-tumor toxicity of CAR-T cells that arise from suboptimal selectivity, but these are complicated, with many involving dual gene expression for specificity. In this study, we show that switchable CAR-T cells with a tumor targeting adaptor can mitigate on-target off-tumor toxicity against a low selectivity tumor antigen that cannot be targeted by conventional CAR-T cells, such as CD40. Our system is composed of anti-cotinine murine CAR-T cells and cotinine-labeled anti-CD40 single chain variable fragments (scFv), with which we show selective tumor killing while sparing CD40-expressing normal cells including macrophages in a mouse model of lymphoma. Simple replacement of the tumor-targeting adaptor with a suicidal drug-conjugated tag may further enhance safety by enabling permanent in vivo depletion of the switchable CAR-T cells when necessary. In summary, our switchable CAR system can control CAR-T cell toxicity while maintaining therapeutic efficacy, thereby expanding the range of CAR targets., Competing Interests: Competing interests K.C. and E.Y.C. are founders and shareholders of Ticaros Inc. H.B.P., J.E.L., and G.R.J. are currently employees of Ticaros. K.C., J.C., H.B.P., K.H.K., S.I.K., and G.R.J. are co-inventors on the pending patent for anti-CD40 switchable CAR T cells. The other authors declare no competing interests., (© 2024. The Author(s).)

Individual variability exists in parkinsonian motor symptoms despite a similar degree of nigrostriatal dopamine depletion in Parkinson's disease (PD), called motor reserve. We enrolled 397 patients newly diagnosed with PD who underwent dual-phase 18 F-FP-CIT PET upon initial assessment. Individual motor reserve was estimated based on initial parkinsonian motor symptoms and striatal dopamine transporter availability using a residual model. Patients with low motor reserve (the lowest quartile group, n = 100) exhibited decreased uptake in the occipital region compared to those with high motor reserve (the highest quartile group, n = 100) on early-phase 18 F-FP-CIT PET images. Patients with high motor reserve had a lower risk of conversion to dementia than the those with low motor reserve, whereas the effect of PD groups on the risk of dementia conversion was not mediated by occipital hypoperfusion. These findings suggest that cerebral hypoperfusion in the occipital region is associated with low motor reserve in patients with PD., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background and Purpose: To develop and validate a deep learning-based automatic quantification for nigral hyperintensity and a classification algorithm for neurodegenerative parkinsonism using susceptibility map-weighted imaging (SMwI)., Materials and Methods: We retrospectively collected 450 participants (210 with idiopathic Parkinson's disease [IPD] and 240 individuals in the control group) for training data between November 2022 and May 2023, and 237 participants (168 with IPD, 58 with essential tremor, and 11 with drug-induced Parkinsonism) for validation data between July 2021 and January 2022. SMwI data were reconstructed from multi-echo GRE. Diagnostic performance for diagnosing IPD was assessed using deep learning-based automatic quantification (Heuron NI) and classification (Heuron IPD) model. Reference standard for IPD was based on 18 F-FP-CIT PET finding. Additionally, the correlation between the H&Y stage and volume of nigral hyperintensity in patients with IPD was assessed., Results: Quantification of nigral hyperintensity using Heuron NI showed AUC of 0.915 (95% CI, 0.872-0.947) and 0.928 (95% CI, 0.887-0.957) on the left and right, respectively. Classification of nigral hyperintensity abnormality using Heuron IPD showed AUC of 0.967 (95% CI, 0.881-0.991) and 0.976 (95% CI, 0.948-0.992) on the left and right, respectively. H&Y score ≥ 3 showed significant smaller nigral hyperintensity volume (1.43 ± 1.19 mm 3 ) compared to H&Y score 1-2.5 (1.98 ± 1.63 mm 3 ; p = 0.008)., Conclusions: Our deep learning-based model proves rapid, accurate automatic quantification of nigral hyperintensity, facilitating IPD diagnosis, symptom severity prediction, and patient stratification for personalized therapy. Further study is warranted to validate the findings across various clinical settings., Abbreviations: IPD = Idiopathic Parkinson's disease; SN = substantia nigra; SMwI = susceptibility map weighted imaging; QSM = quantitative susceptibility mapping; CNN = convolutional neural network; ICV = intracranial volume., (© 2024 by American Journal of Neuroradiology.)

Background: The age at onset (AAO) of Parkinson's disease (PD) varies widely among individuals and significantly influences disease progression and prognosis. However, few genome-wide association studies (GWASs) have investigated genetic variants determining AAO, particularly in East Asian populations., Objectives: To identify single-nucleotide polymorphisms (SNPs) affecting AAO of PD in Korean patients., Methods: We conducted a GWAS on AAO of PD in 1048 Korean patients using sex-adjusted linear regression models. Additionally, we conducted downstream analyses of our primary GWAS results., Results: rs2134545 demonstrated genome-wide significance (β = -2.459; standard error [SE] = 0.851; P = 1.898 × 10 -8 ) and is an intergenic SNP near the ALCAM gene associated with an average AAO reduction of 3.47 years. Additionally, rs4366309 (LYST; MIR1537) demonstrated suggestive significance (β = 2.949; SE = 1.072; P = 8.68 × 10 -8 ) and was associated with an average delay of 3.05 years. The polygenic risk score based on known PD risk loci also affected the AAO for European and Korean PD risk loci, respectively (β = -0.149; P < 0.001 and β = -0.096; P = 0.002). However, the proportion of variance was small (r 2  = 0.022 and 0.009, respectively)., Conclusion: We identified a novel SNP associated with the AAO of PD near the ALCAM gene, distinct from previously reported PD risk loci. These findings need further functional validation; however, they suggest unique genetic pathways influencing the AAO of PD and highlight the need for further research in diverse populations. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society., (© 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.)

Background: Solid organ transplantation (SOT) has expanded significantly in Asia over past few decades. Donor-derived infections (DDIs) remain a significant concern as they may adversely impact transplant outcomes. We aim to review the existing regulatory frameworks, screening protocols, and management practices for DDIs in Asia., Methods: We reached out to transplant infectious diseases experts in Asia to provide standardized data on annual SOT numbers, incidence of DDIs, regulatory frameworks, donor and recipient screening protocols, and DDI surveillance measures. We present the data from Singapore, Japan, and Thailand., Results: Donor screening for HIV, hepatitis B, hepatitis C, and syphilis is mandatory in all countries. Additionally, Japan screens for HTLV-1 antibody due to its endemicity. We also reviewed the protocols for screening and prevention of endemic infections in Asia. Singapore is the only country implementing universal screening for all donors for dengue, Zika, and chikungunya via blood and urine RT-PCR. Strongyloidiasis screening is not routinely done, although some transplant centers empirically give ivermectin prophylaxis to organ recipients. Tuberculosis screening with a donor questionnaire and chest radiograph is common for deceased donors, and some centers do Interferon Gamma Release Assay test for living donors. We also found a significant gap in the surveillance and reporting of potential DDIs in Asia and the overall incidence of DDIs in Asia is unknown and likely underreported., Conclusion: The experiences of Singapore, Japan, and Thailand offer valuable insights into current practices and the unmet needs regarding a DDI registry and call for coordinated efforts to address this critical issue in the region., (© 2024 Wiley Periodicals LLC.)

Background: Donor-derived dengue infections present significant challenges to organ transplantation, particularly in endemic regions like Singapore. Although primarily transmitted by Aedes mosquitoes, dengue can also be transmitted through organ transplantation, occasionally with fatal outcomes. This study aims to evaluate the outcomes and evolution of dengue screening protocols for potential deceased donors in Singapore from 2006 to 2022., Methods: Initially, screening was done via dengue immunoglobulin M (IgM), targeting donors with specific clinical criteria (thrombocytopenia, drop in platelet count, prolonged prothrombin time/partial thromboplastin time, and discretion of the transplant team), later transitioning to blood dengue reverse transcription-polymerase chain reaction (RT-PCR) in 2007 with similar criteria, and subsequently universal screening in 2016. In 2021, urine dengue RT-PCR was added following a case of donor-derived dengue infection from an aviremic but viruric donor., Results: Out of 431 potential deceased donors, 395 (91.6%) underwent dengue screening, with six (1.5%) testing positive for dengue. In 2006, three positive screens were identified: two through dengue IgM and one via blood dengue RT-PCR; subsequent years saw one positive screen each in 2007, 2008, and 2019 via blood dengue RT-PCR. Potential deceased donors with a positive blood dengue screen were rejected as solid organ and tissue donors. Those with negative blood dengue RT-PCR but positive urine dengue RT-PCR would be rejected as kidney donors, but the use of other organs and tissues was at the discretion of the transplantation team., Conclusion: The optimal screening protocol remains uncertain, but our findings suggest that a universal screening strategy utilizing both blood and urine dengue RT-PCR could be considered in dengue-endemic countries., (© 2024 Wiley Periodicals LLC.)

Aim: To examine the relationship between racial/ethnic disparities and substance use behaviours (alcohol and tobacco use) and their impact on the sleep health of South Korean adolescents., Design: Secondary analysis of cross-sectional study data from the 2021 Korea Youth Risk Behaviour Web-based Survey dataset., Methods: Given that Korean society has historically linked its racial/ethnic identity to a shared bloodline, we categorized 2644 adolescents from the Korea Youth Risk Behaviour Web-based Survey based on their racial/ethnic status, determined by their parents' birthplaces. Using multiple linear regression, we investigated whether the impact of racial/ethnic disparities on sleep health (sleep duration, debt, and timing) varies depending on substance use behaviours (alcohol and tobacco use) after controlling for age, sex, household economic status, depressed mood, suicidal ideation, perceived excessive stress, and anxiety level., Results: Despite no statistical differences in sleep health and the prevalence of substance use between racial/ethnic groups, racial/ethnic minority adolescents experienced greater sleep debt than racial/ethnic majority adolescents when consuming alcohol. Moreover, racial/ethnic minority adolescents were more likely to report psychosocial distress and had lower parental education level., Conclusion: Racial/ethnic minority adolescents were more vulnerable to the detrimental effects of alcohol use on sleep health compared to racial/ethnic majority adolescents. This heightened vulnerability may be attributed to the more pronounced psychosocial challenges and the lower socioeconomic status of parents in the racial/ethnic minority group., Impact: Racial/ethnic disparities are concerning in South Korea, particularly since the negative effects of substance use on sleep health are intensified among racial/ethnic minority adolescents. Nurses and other healthcare providers should recognize the importance of addressing the social disadvantages linked to racial/ethnic disparities. Beyond just advocating for the cessation of substance use, it is crucial to address these underlying issues to reduce sleep disparities among South Korean adolescents., Patient or Public Contribution: No patient or public contribution., (© 2024 John Wiley & Sons Ltd.)

Emotional eating, which refers to eating in response to emotional states, is prevalent in early childhood. Executive function (EF) and sleep problems are related to preschoolers' self-regulatory abilities during the day and night and have been reported to be associated with their emotional eating. These associations can be stronger in emotionally stressful situations, such as controlling feeding practices. This study explored the role of preschoolers' EF and sleep problems as child characteristics, as well as maternal feeding practices as environmental factors influencing emotional eating during the preschool period. Participants included 363 Korean mothers with preschoolers aged 3- to 5-years old (190 boys, 173 girls). Mothers reported on their own feeding practices, and preschoolers' EF, sleep problems, and emotional eating. Results indicated that preschoolers' EF was negatively associated with emotional over- and undereating, and this association was stronger when mothers applied more pressure to eat. Maternal monitoring had a similar effect, with emotional overeating exerting a greater impact with low levels of maternal monitoring. Finally, maternal pressure to eat moderated the influence of preschoolers' sleep problems on emotional overeating, with higher pressure to eat predicting a stronger relationship between sleep problems and emotional overeating. These findings suggest that maternal feeding practices, which are relatively modifiable, should be considered an important element in intervention programs aimed at preventing emotional eating in preschool children., 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.)

Background: Chronic cough is a common symptom encountered by healthcare practitioners. The global prevalence of chronic cough is 9.6%, with a female predominance. The aim of our study is to reveal the sex differences in prevalence and severity of chronic cough in South Korea, stratified by age and etiology., Methods: This study included adult patients with chronic cough who were recruited from 19 respiratory centers in South Korea. Patients completed the cough numeric rating scale (NRS) and COugh Assessment Test (COAT) questionnaire to assess the severity and multidimensional impact of cough., Results: Among the 625 patients, 419 (67.0%) were females, with a male-to-female ratio of 1:2.03. The mean age was 49.4 years, and the median duration of cough was 12 weeks. The mean NRS and COAT scores were 5.5 ± 1.8 and 9.5 ± 3.6, respectively. Female patients were older (45.3 ± 15.4 vs. 51.6 ± 15.2, P < 0.001) and more likely to have asthma/cough variant asthma (CVA) (26.7% vs. 40.8%, P = 0.001) than male patients. There was no difference in the duration or severity of cough between sexes, regardless of the cause. The male-to-female ratio was lower for upper airway cough syndrome (UACS), asthma/CVA, and gastro-esophageal reflux disease (GERD), but not for eosinophilic bronchitis (EB) or unexplained cough. The mean age of female patients was higher in UACS and asthma/CVA, but not in EB, GERD, or unexplained cough. The majority (24.2%) fell within the age category of 50s. The proportion of females with cough increased with age, with a significant rise in the 50s, 60s, and 70-89 age groups. The severity of cough decreased in the 50s, 60s, and 70-89 age groups, with no significant sex differences within the same age group., Conclusion: The sex disparities in prevalence and severity of cough varied significantly depending on the age category and etiology. Understanding the specific sex-based difference could enhance comprehension of cough-related pathophysiology and treatment strategies., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Background: The government of Korea implemented a strategy of prevention and early diagnosis in high-risk groups to reduce the tuberculosis (TB) burden. This study aims to investigate the TB epidemiology and gap in understanding of TB prevalence among homeless individuals by analyzing active TB chest X-ray (CXR) screening results in Korea., Methods: The Korean National Tuberculosis Association conducted active TB screening with CXR for homeless groups from January 1 to December 31, 2021. Sputum acid-fast bacilli smear and culture were performed for the subjects suggestive of TB on CXR. We performed a cross-sectional analysis of the data in comparison with the national health screening results from the general population., Results: Among 17,713 homeless persons, 40 (0.23%), 3,077 (17.37%), and 79 (0.45%) were categorized as suggested TB, inactive TB, and observation required, respectively. Prevalence of suggested TB in the homeless was significantly higher (3-5 fold) than in Univerthe national general health screening based on age category (p&lt;0.005). Twenty-nine cases were confirmed as TB, yielding a prevalence of 164 cases per 100,000 individuals; 19 of these 29 cases showed inactive TB on CXR. Body mass index (p=0.0478) and CXR result (p&lt;0.001) significantly correlated with confirmed TB based on multivariable analysis., Conclusion: Nutrition status and CXR results, especially that of inactive TB, should be considered in active TB screening of the homeless population, where TB prevalence is higher than the general population.

Background and Purpose: The co-occurrence of amyloid-β pathology in Parkinson's disease (PD) is common; however, the role of amyloid-β deposition in motor prognosis remains elusive. This study aimed to investigate the association between striatal amyloid deposition, motor complications and motor prognosis in patients with PD., Methods: Ninety-six patients with PD who underwent 18 F florbetaben (FBB) positron emission tomography were retrospectively assessed. The ratio of the striatum to global (STG) FBB uptake was obtained for each individual, and patients were allotted into low and high STG groups according to the median value. The effect of STG group on regional amyloid deposition, the occurrence of motor complications and longitudinal change in levodopa equivalent dose (LED) requirement were investigated after controlling for age, sex, LED and disease duration at FBB scan., Results: The high STG group was associated with lower cortical FBB uptake in the parietal, occipital and posterior cingulate cortices and higher striatal FBB uptake compared to the low STG group. Patients in the high STG group had a higher risk of developing wearing off and levodopa-induced dyskinesia than those in the low STG group, whereas the risk for freezing of gait was comparable between the two groups. The high STG group showed a more rapid increase in LED requirements over time than the low STG group., Conclusions: These findings suggest that relatively high striatal amyloid deposition is associated with poor motor outcomes in patients with PD., (© 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Low body mass index is closely related to a high risk of Alzheimer's disease (AD) and related biomarkers including amyloid-β (Aβ) deposition. However, the association between sarcopenia and Aβ-confirmed AD remains controversial. Therefore, we investigated the relationship between sarcopenia and the AD continuum. We explored sarcopenia's association with clinical implications of participants on the AD continuum. We prospectively enrolled 142 participants on the AD continuum (19 with preclinical AD, 96 with mild cognitive impairment due to AD, and 28 with AD dementia) and 58 Aβ-negative cognitively unimpaired participants. Sarcopenia, assessed using dual-energy X-ray absorptiometry and hand grip measurements, was considered a predictor. AD continuum, defined by Aβ deposition on positron emission tomography served as an outcome. Clinical severity in participants on the AD continuum assessed using hippocampal volume, Mini-Mental State Examination (MMSE), Seoul Verbal Learning Test (SVLT), and Clinical Dementia Rating Scale Sum of Boxes Scores (CDR-SOB) were also considered an outcome. Sarcopenia (odds ratio = 4.99, p = 0.004) was associated independently with the AD continuum after controlling for potential confounders. Moreover, sarcopenia was associated with poor downstream imaging markers (decreased hippocampal volume, β = - 0.206, p = 0.020) and clinical outcomes (low MMSE, β = - 1.364, p = 0.025; low SVLT, β = - 1.077, p = 0.025; and high CDR-SOB scores, β = 0.783, p = 0.022) in participants on the AD continuum. Sarcopenia was associated with the AD continuum and poor clinical outcome in individuals with AD continuum. Therefore, our results provide evidence for future studies to confirm whether proper management of sarcopenia can effective strategies are required for sarcopenia management to prevent the AD continuum and its clinical implications., (© 2024. The Author(s).)

Background and Purpose: Idiopathic normal pressure hydrocephalus (iNPH) is reversible dementia, that is underdiagnosed. The purpose of this study was to develop an automated diagnostic method for iNPH using artificial intelligence techniques with a T1-weighted MRI scan., Materials and Methods: We quantified iNPH, Parkinson's disease, Alzheimer's disease, and healthy control patients on T1-weighted 3D brain MRI scans using 452 scans for training and 110 scans for testing. Automatic component measurement algorithms were developed for Evans' index, Sylvian fissure enlargement, high-convexity tightness, callosal angle, and normalized lateral ventricle volume. XGBoost models were trained for both automated measurements and manual labels for iNPH prediction., Results: A total of 452 patients (200 men; mean age ± standard deviation, 73.2 ± 6.5 years) were included in the training set. Of the 452 patients, 111 (24.6%) had iNPH. We obtained AUC values of 0.956 for automatically measured high-convexity tightness and 0.830 for Sylvian fissure enlargement. Intra-class correlation values of 0.824 for the callosal angle and 0.924 for Evans' index were measured. Using the decision tree of the XGBoost model, the model trained on manual labels obtained an average cross-validation AUC of 0.988 on the training set and 0.938 on the unseen test set, while the fully automated model obtained a cross-validation AUC of 0.983 and an unseen test AUC of 0.936., Conclusion: We demonstrated a machine-learning algorithm capable of diagnosing iNPH from a 3D T1-weighted MRI scan that is robust to the failure. We propose a method to scan large numbers of 3D T1-weighted MRI scans with minimal human intervention, making possible large-scale iNPH screening., Abbreviations: iNPH = idiopathic normal-pressure hydrocephalus; PD = Parkinson's disease; AD = Alzheimer's disease; HC = healthy control; CSF = cerebrospinal fluid; DESH = disproportionately enlarged subarachnoid space hydrocephalus; 3D = three-dimensional., Competing Interests: The authors declare no conflicts of interest related to the content of this article., (© 2024 by American Journal of Neuroradiology.)

Background: Universal surgical prophylaxis for pancreatoduodenectomy (PD) is practiced, with cephalosporins recommended in most guidelines. Recent studies suggest piperacillin-tazobactam (PTZ) prophylaxis in biliary-stented patients is superior in preventing surgical site infections (SSIs). This study aims to refine surgical prophylaxis recommendations based on the local microbial profile and evaluate the clinical outcomes of biliary-stented compared with non-stented patients., Methods: This was a retrospective study of all consecutive PD patients at Singapore General Hospital between January 2013 to December 2019. The primary outcome was post-operative SSI rates. Secondary outcomes included rates of ceftriaxone-resistant Klebsiella pneumoniae, Escherichia coli, and Enterococcus species from intraoperative bile cultures and 30-day mortality., Results: There were 130 biliary-stented and 211 non-stented patients included. Majority of biliary-stented patients received ceftriaxone ± metronidazole prophylaxis (83/130, 63.8 %) while 30/130 (23.8 %) received PTZ. Most non-stented patients received ceftriaxone ± metronidazole prophylaxis (163/211, 77.3 %). Between biliary-stented and non-stented patients, post-operative SSIs (40.8 % vs 38.4 %, p = 0.662), and 30-day mortality rates (1.5 % vs 1.4 %, p = 1.000) were comparable. The adjusted odds of post-operative SSIs was significantly lower in biliary-stented patients prescribed PTZ as compared to non-PTZ prophylaxis (0.29, 95 % CI (0.10-0.79), p = 0.015). Ceftriaxone-resistant Klebsiella spp. and/or Escherichia coli (27.6 % vs 3.8 %, p < 0.001) as well as Enterococcus species (46.1 % vs 11.5 %, p < 0.001), were more prevalent in intraoperative bile cultures of biliary-stented patients, while frequencies in non-stented patients were low., Conclusion: PTZ prophylaxis effectively reduced SSIs in stented patients post-pancreatoduodenectomy. Based on the local microbial profile, ceftriaxone prophylaxis may be used for prophylaxis in non-stented patients., (Copyright © 2024 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background: Allergic bronchopulmonary aspergillosis (ABPA) is a pulmonary disease caused by a complex hypersensitivity reaction to colonization of the airways with various fungi. ABPA caused by Alternaria alternata, other than Aspergillus spp., is named Allergic bronchopulmonary mycosis (ABPM)., Objective: To describe the first case of ABPM caused by Alternaria alternata in East Asia., Methods: Case report., Results: A 58-year-old female visited our hospital due to an abnormal chest x-ray, following chest computed tomography (CT) revealed consolidation in the left lower lobe. On laboratory finding, eosinophil count and total IgE level were high. The skin prick test and specific IgE for Alternaria alternata were positive. After diagnosis of ABPM, the patient was treated with prednisolone without antifungal agents, and her chest image was much improved., Conclusions: Aspergillus is most common etiology of allergic pulmonary disease, however, Alternaria should be considered even though positive culture of Aspergillus spp.

Autonomous robots operating in uncertain or hazardous environments subject to state safety constraints must be able to identify and isolate faulty components in a time-optimal manner. When the underlying fault is ambiguous and intertwined with the robot's state estimation, motion plans that discriminate between simultaneous actuator and sensor faults are necessary. However, the coupled fault mode and physical state uncertainty creates a constrained optimization problem that is challenging to solve with existing methods. We combined belief-space tree search, marginalized filtering, and concentration inequalities in our method, safe fault estimation via active sensing tree search (s-FEAST), a planner that actively diagnoses system faults by selecting actions that give the most informative observations while simultaneously enforcing probabilistic state constraints. We justify this approach with theoretical analysis showing s-FEAST's convergence to optimal policies. Using our robotic spacecraft simulator, we experimentally validated s-FEAST by safely and successfully performing fault estimation while on a collision course with a model comet. These results were further validated through extensive numerical simulations demonstrating s-FEAST's performance.

Objective: Our study investigates the impact of copy number variations (CNVs) on Parkinson's disease (PD) pathogenesis using genome-wide data, aiming to uncover novel genetic mechanisms and improve the understanding of the role of CNVs in sporadic PD., Methods: We applied a sliding window approach to perform CNV-GWAS and conducted genome-wide burden analyses on CNV data from 11,035 PD patients (including 2,731 early-onset PD (EOPD)) and 8,901 controls from the COURAGE-PD consortium., Results: We identified 14 genome-wide significant CNV loci associated with PD, including one deletion and 13 duplications. Among these, duplications in 7q22.1, 11q12.3 and 7q33 displayed the highest effect. Two significant duplications overlapped with PD-related genes SNCA and VPS13C , but none overlapped with recent significant SNP-based GWAS findings. Five duplications included genes associated with neurological disease, and four overlapping genes were dosage-sensitive and intolerant to loss-of-function variants. Enriched pathways included neurodegeneration, steroid hormone biosynthesis, and lipid metabolism. In early-onset cases, four loci were significantly associated with EOPD, including three known duplications and one novel deletion in PRKN . CNV burden analysis showed a higher prevalence of CNVs in PD-related genes in patients compared to controls (OR=1.56 [1.18-2.09], p=0.0013), with PRKN showing the highest burden (OR=1.47 [1.10-1.98], p=0.026). Patients with CNVs in PRKN had an earlier disease onset. Burden analysis with controls and EOPD patients showed similar results., Interpretation: This is the largest CNV-based GWAS in PD identifying novel CNV regions and confirming the significant CNV burden in EOPD, primarily driven by the PRKN gene, warranting further investigation.