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Grace Y Lee,1 Calvin CK Yip,2 Edwin CS Yu,3 David WK Man4 1Occupational Therapy Department, Kwai Chung Hospital, 2CY Functional Recovery Services, 3Psychogeriatric Team, Kwai Chung Hospital, 4Department of Rehabilitation Sciences, the Hong Kong Polytechnic University, Hong Kong, People’s Republic of China Background: Improving the situation in older adults with cognitive decline and evidence of cognitive rehabilitation is considered crucial in long-term care of the elderly. The objective of this study was to implement a computerized errorless learning-based memory training program (CELP) for persons with early Alzheimer’s disease, and to compare the training outcomes of a CELP group with those of a therapist-led errorless learning program (TELP) group and a waiting-list control group. Methods: A randomized controlled trial with a single-blind research design was used in the study. Chinese patients with early Alzheimer’s disease screened by the Clinical Dementia Rating (score of 1) were recruited. The subjects were randomly assigned to CELP (n = 6), TELP (n = 6), and waiting-list control (n = 7) groups. Evaluation of subjects before and after testing, and at three-month follow-up was achieved using primary outcomes on the Chinese Mini-Mental State Examination, Chinese Dementia Rating Scale, Hong Kong List Learning Test, and the Brief Assessment of Prospective Memory-Short Form. Secondary outcomes were the Modified Barthel Index, Hong Kong Lawton Instrumental Activities of Daily Living Scale, and Geriatric Depression Scale-Short Form. The data were analyzed using Friedman's test for time effect and the Kruskal-Wallis test for treatment effect. Results: Positive treatment effects on cognition were found in two errorless learning-based memory groups (ie, computer-assisted and therapist-led). Remarkable changes were shown in cognitive function for subjects receiving CELP and emotional/daily functions in those receiving TELP. Conclusion: Positive changes in the cognitive function of Chinese patients with early Alzheimer's disease were initially found after errorless training through CELP. Further enhancement of the training program is recommended. Keywords: Alzheimer’s disease, memory training, errorless learning, computerized, early dementia

Objectives: There is currently a lack of evidence regarding the optimal revascularization method for Takayasu arteritis (TA). This study compares outcomes between endovascular treatment and surgical therapy in TA patients requiring revascularization. Method: From September 1994 to January 2011, 235 patients were diagnosed with TA according to the diagnostic criteria of the 1990 American College of Rheumatology, and of these, arterial revascularizations were performed in 65 (27.7%). Symptomatic or angiographic recurrence and peri-operative use of immunosuppressive drugs were investigated by retrospectively reviewing medical records. Results: A total of 111 arterial lesions in the 65 (27.7%) patients were revascularized during the follow-up period (median 3.2 years, range 0.01-12.7 years). At the 2-year follow-up, the symptomatic recurrence rate was significantly higher in the endovascular treatment group (32.3% vs. 11.5%, p = 0.016), as was the incidence of angiographic recurrence (32.1% vs. 11.1%, p = 0.026). The symptomatic recurrence rate was not influenced by the need for peri-operative immunosuppressive drugs (20% vs. 34.1%, p = 0.34). Conclusions: In TA patients, surgical revascularization seems to be superior to endovascular treatment with regard to patency. Further investigation to identify novel and optimal arterial revascularization methods for TA patients should be undertaken. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the MR-based outcome predictors of lumbar transforaminal epidural steroid injection (ESI) for lumbar radiculopathy caused by herniated intervertebral disc (HIVD).Methods: A total of 149 patients (male/female 75:74; mean age 51.5 years) with the very worst (87 patients) or the very best outcome (62 patients) after ESI were enrolled in this study. They were selected from 1,881 patients who underwent lumbar transforaminal ESI for lumbar radiculopathy caused by HIVD from January 2007 to December 2008. Two radiologists reviewed MR in consensus. Chi-square test and Fisher's exact test were used to evaluate the difference between the two groups.Results: HIVD in the foraminal-extraforaminal zone were significantly more common in the very best outcome group (16/24, 66.6 %) than HIVD in the central-subarticular zone (46/125, 36.8 %) (P = 0.012). Other factors such as HIVD zone, T2-high signal, relation to nerve root, corner change, Modic change, disc height loss, grade of disc degeneration, and osteophyte were not statistically significant.Conclusion: HIVD in the foraminal or extraforaminal zone is the only good MR-based outcome predictor of lumbar transforamial ESI for lumbar radiculopathy. [ABSTRACT FROM AUTHOR]

PURPOSE: The aim of this study is to analyze implant survival in patients who received radiotherapy treatment for oral malignancies and in patients who had suffered mandibular osteoradionecrosis. MATERIALS AND METHODS: We reviewed retrospectively 225 implants placed in 30 patients who had received radiotherapy as part of the oncologic treatment. Radiation doses ranged between 50 and 70 Gy. 39 implants were placed after a combined treatment of radiotherapy and chemotherapy. Data referred to tumour type and reconstruction, presence of osteoradionecrosis, region of implant installation and type of prostheses were recorded. Survival rates were calculated with cumulative Kaplan-Meier survival curves and compared between different groups with a log-rank test. RESULTS: 152 osseointegrated implants were placed in patients who presented previous reconstruction procedure. Five patients developed osteorradionecrosis as a complication of the radiotherapy treatment. Once osteoradionecrosis had healed in these patients, 41 implants were installed. The overall 5 year survival rate in irradiated patients was 92.6%. Irradiated patients had a marginally significantly higher implant loss than non-irradiated patients. (p = 0.063). The 5 year survival rate in the osteoradionecrosis group was of 48.3% and in the non-osteoradionecrosis group 92.3%, with a statistically significant difference between both groups. (p = 0.002). CONCLUSION: Osseointegrated implants enhance oral rehabilitation in most irradiated patients, even being an acceptable option for patients who had suffered osteoradionecrosis. Totally implantsupported prostheses are recommended after irradiation providing functional, stable and aesthetically satisfactory rehabilitation. [ABSTRACT FROM AUTHOR]

Lymph node metastasis is an important prognostic factor in oral squamous cell carcinoma. However, the lack of significant biomarkers for lymph node metastasis can cause patients to be inappropriately treated and produce a poor prognosis. Therefore, there is a need to identify gene sets that are associated with lymph node metastasis. In this study, we used three expression datasets obtained from a public database and selected candidate gene sets that were related with lymph node metastasis from two datasets and a combined dataset. We evaluated the selected gene set using OOB error rates in a validation dataset. The gene set detected from the combined dataset classified the lymph node status more accurately in the validation dataset and clear expression patterns classifying the lymph node status based on chromosomal location were observed. The combined dataset holds promise for use as a more accurate candidate gene set for the diagnosis of lymph node metastasis and the selected gene set could be used for biological validation in further studies. [ABSTRACT FROM AUTHOR]

Objective: Peroxisome proliferator-activated receptor (PPAR)-α/γ dual agonists have been developed to alleviate metabolic disorders. However, several PPARα/γ dual agonists are accompanied with unwanted side effects, including body weight gain, edema, and tissue failure. This study investigated the effects of a novel PPARα/γ dual agonist, CG301269, on metabolic disorders both in vitro and in vivo.Research Design and Methods: Function of CG301269 as a PPARα/γ dual agonist was assessed in vitro by luciferase reporter assay, mammalian one-hybrid assay, and analyses of PPAR target genes. In vitro profiles on fatty acid oxidation and inflammatory responses were acquired by fatty acid oxidation assay and quantitative (q)RT-PCR of proinflammatory genes. In vivo effect of CG301269 was examined in db/db mice. Total body weight and various tissue weights were measured, and hepatic lipid profiles were analyzed. Systemic glucose and insulin tolerance were measured, and the in vivo effect of CG301269 on metabolic genes and proinflammatory genes was examined by qRT-PCR.Results: CG301269 selectively stimulated the transcriptional activities of PPARα and PPARγ. CG301269 enhanced fatty acid oxidation in vitro and ameliorated insulin resistance and hyperlipidemia in vivo. In db/db mice, CG301269 reduced inflammatory responses and fatty liver, without body weight gain.Conclusions: We demonstrate that CG301269 exhibits beneficial effects on glucose and lipid metabolism by simultaneous activation of both PPARα and PPARγ. Our data suggest that CG301269 would be a potential lead compound against obesity and related metabolic disorders. [ABSTRACT FROM AUTHOR]

Objective: This study is performed for the purpose of examining into the efficacy of the scolopendrid(Scolopendra morsitans L) which has been used among the Korean people for the H.I.V.D of lumbar spine. Methods & Results: Using the herbal acupuncture made of scolopendrid(Scolopendra morsitans L), we treated the 10 H.l. V.D patients for 1 week and operated 4 pre and post treatment test ; D.I.T.I, 6 kind of physical test, Oswestry disability index, and self-conscious pain rate. Trough Lite test, we saw 50-100% of efficacy rate in each test. Otherwise, only 5 of the 7 point in D.I.T.I and self-conscious pain rate showed statistically valuable change. Conclusion: we brought to the conclusion that the scolopendrid herbal acupuncture has possibility to be efficient to cure the H.I.V.D patients. So we suggest the possibility to use this new remedy for the H.I.V.D.

Objectives: To suggest an optimal energy level of virtual monochromatic images (VMIs) in dual-energy CT arthrography of the wrist., Methods: This retrospective study included 53 patients with wrist CT arthrography. Conventional polychromatic images and VMIs at four energy levels (40 to 70 keV at 10 keV intervals) were obtained. Image noise, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR) were measured, and qualitative analysis of image quality and diagnostic confidence was performed. For each patient, an energy level with the best image quality was chosen by consensus. Comparisons of quantitative and qualitative parameters between VMI sets were performed., Results: The image noise of bone and muscle were increased with decreasing energy level (p < 0.001). The noise of contrast was highest on 60 keV VMI. SNR and CNR (between contrast and muscle) were increased with decreasing energy level and were markedly increased between 60 and 50 keV (p < 0.001). The 60 keV VMI demonstrated the highest image quality and diagnostic confidence, chosen as the best diagnostic image (n = 31/53). Given that the attenuation of the contrast material was low on the conventional image, the optimal energy level of the best VMI tended to be low., Conclusion: Wrist dual-energy CT arthrography with VMIs at 60 keV or less could improve image quality and diagnostic performance by increasing SNR and CNR in cases with low contrast attenuation., Advances in Knowledge: Wrist dual-energy CT arthrography with VMIs at variable keV could be utilised to enhance SNR and CNR, thereby achieving diagnostic images of high quality., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Institute of Radiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background/objectives: There are scant established data on the cause, distribution, treatment options, and recurrence rate of pediatric keloids in Asian populations. We characterized clinical features by comprehensively categorizing pediatric keloid patients into prepubertal and postpubertal groups at a single tertiary center., Methods: We searched the database of Kangbuk Samsung Hospital for pediatric patients (< 18 years) with clinically proven keloids who underwent outpatient-based treatment from 2007 to 2021. Clinical features, including demographics, distribution, underlying cause, treatment modality, and recurrence, were analyzed., Results: Of the 93 patients (total 110 keloids), 42 females (45.2%) and 51 males (54.8%), with a mean age of 14.5 ± 4.1 years (range, 1-18 years), were retrospectively analyzed. The mean length of follow-up was 22.0 ± 14.2 months (range, 6-63). Of the 100 keloids with assessable causes, piercing (22%) and acne (19%) were the most common. In the prepubertal group, the lower and upper limbs (n = 7, 28%; n = 6, 24%) were the two most common locations, suggesting that post-traumatic keloids are common during this developmental period. In the postpubertal group, the ear (n = 25, 29.4%) was the most common site, which corresponds to the frequency of cosmetic piercing at this age. No differences were found between the effects of treatment methods on relapse rate., Conclusions: Understanding the clinical features of pediatric keloids is important in the therapeutic considerations for pediatric keloids. Future studies should analyze a larger number of children with keloids over longer observation periods., (© 2024 Wiley Periodicals LLC.)

Background: Livestock-associated Staphylococcus aureus (LA-SA) has gained global attention because of its ability to colonize farm animals and transmit to the environment and humans, leading to symptomatic infections and the spread of antimicrobial resistance (AMR). In the last decade, numerous studies have reported a high prevalence of S. aureus clonal complex (CC) 398 in pig farms., Results: In this study, 163 S. aureus isolates were collected from healthy pigs (n = 110), farm environments (n = 42), and farm workers (n = 11), and their AMR profiles and epidemiological characteristics were analyzed. We identified 51 (31.3%) methicillin-resistant S. aureus (MRSA) and 112 (68.7%) methicillin-susceptible S. aureus (MSSA), with 161 (98.8%) isolates belonging to the CC398 lineage. The highest prevalence of spa type t571 was observed among the CC398 isolates. All 47 sequence type (ST) 398 MRSA isolates carried staphylococcal cassette chromosome mec (SCCmec) V, while four ST541 isolates carried SCCmec IV. High levels of resistance to commonly used antibiotics, including phenicols, quinolones, lincosamides, macrolides, aminoglycosides, and tetracyclines, have been observed on Korean pig farms. Notably, 21 cfr-positive CC398 isolates (four ST541-SCCmec IV MRSA and 17 ST398 MSSA) displaying increased resistance to linezolid were identified in healthy pigs., Conclusions: In summary, these findings suggest that the multidrug-resistant CC398 S. aureus lineage predominantly colonizes healthy pigs and farm environments in Korea. The emergence of cfr-positive S. aureus at human-animal interfaces presents a significant threat to food safety and public health., (© 2024. The Author(s).)

Slim cameras are essential in state-of-the-art consumer electronics such as smartphones or augmented/virtual reality devices. However, reducing the camera thickness faces challenges primarily due to the thick lens systems. Current lens systems, composed of stacked refractive lenses, are fundamentally constrained from becoming thinner due to the presence of empty spaces between lenses and the excessive volume of each lens. Here, we present a lens system using metasurface folded optics to overcome these pervasive issues. In our design, metasurfaces are arranged horizontally on a glass wafer and direct light along multifolded paths inside the substrate. This approach achieves an ultra-slim lens system with a thickness of 0.7 millimeters and 2× thinner relative to the EFL, thereby overcoming the inherent limitations of conventional optical platforms. It delivers quasi-diffraction-limited imaging quality with a 10° field of view and an f number of 4 at an operational wavelength of 852 nanometers. Our findings provide a compelling platform for compact cameras using folded nano-optics.

Background and Purpose: To train and validate a deep learning (DL)-based segmentation model for cerebral microbleeds (CMB) on susceptibility-weighted MRI; and to find associations between CMB, cognitive impairment, and vascular risk factors., Materials and Methods: Participants in this single-institution retrospective study underwent brain MRI to evaluate cognitive impairment between January-September 2023. For training the DL model, the nnU-Net framework was used without modifications. The DL model's performance was evaluated on independent internal and external validation datasets. Linear regression analysis was used to find associations between log-transformed CMB numbers, cognitive function (mini-mental status examination [MMSE]), white matter hyperintensity (WMH) burden, and clinical vascular risk factors (age, sex, hypertension, diabetes, lipid profiles, and body mass index)., Results: Training of the DL model (n = 287) resulted in a robust segmentation performance with an average dice score of 0.73 (95% CI, 0.67-0.79) in an internal validation set, (n = 67) and modest performance in an external validation set (dice score = 0.46, 95% CI, 0.33-0.59, n = 68). In a temporally independent clinical dataset (n = 448), older age, hypertension, and WMH burden were significantly associated with CMB numbers in all distributions (total, lobar, deep, and cerebellar; all P <.01). MMSE was significantly associated with hyperlipidemia (β = 1.88, 95% CI, 0.96-2.81, P <.001), WMH burden (β = -0.17 per 1% WMH burden, 95% CI, -0.27-0.08, P <.001), and total CMB number (β = -0.01 per 1 CMB, 95% CI, -0.02-0.001, P = .04) after adjusting for age and sex., Conclusions: The DL model showed a robust segmentation performance for CMB. In all distributions, CMB had significant positive associations with WMH burden. Increased WMH burden and CMB numbers were associated with decreased cognitive function., Abbreviations: CMB = cerebral microbleed; DL = deep learning, DSC = dice similarity coefficient; MMSE = mini-mental status examination; SVD = small vessel disease; SWI = susceptibility-weighted image; WMH = white matter hyperintensity., Competing Interests: The authors declare no conflicts of interest related to the content of this article, (© 2024 by American Journal of Neuroradiology.)

Background/objectives: We investigated the effects of ultraprocessed food (UPF) consumption on metabolic disorders (e.g., adiposity, metabolic associated steatotic liver disease [MASLD], and insulin resistance) in children and adolescents with obesity to improve dietary guidelines and public health strategies., Methods: The dietary intake of 149 participants (aged 8-17 years) was assessed with food diaries. The NOVA classification system was used to classify food according to the degree of processing. Metabolic outcomes, including the fat mass index (FMI), hepatic fat percentage, and insulin resistance, were measured via dual-energy X-ray absorptiometry (DXA), magnetic resonance imaging proton density fat fraction (MRI-PDFF), and biochemical analysis, respectively., Results: Greater UPF consumption from baseline to the 6-month follow-up was significantly associated with increased insulin and decreased total cholesterol and LDL-cholesterol. UPF consumption was positively associated with the prevalence of MASLD (liver MRI-PDFF ≥ 5%; odds ratio T3 vs. T1 = 1.75; 95% confidence interval [CI] 1.03, 3.00), moderate-to-severe MASLD (liver MRI-PDFF ≥ 10%; OR T3 vs. T1 = 4.19; 95% CI 1.72, 10.22), and insulin resistance (OR T3 vs. T1 = 2.44; 95% CI 1.33, 4.48), after adjusting for covariates. A linear dose-response relationship was observed between UPF consumption and the odds of moderate-to-severe MASLD and insulin resistance., Conclusions: Greater UPF consumption was strongly associated with MASLD and insulin resistance in children and adolescents with obesity, underscoring the importance of reducing UPF consumption through dietary guidelines and public health interventions to mitigate the risk of obesity-related metabolic conditions in young populations., Competing Interests: The authors declare no conflicts of interest.

In this study, the nutrients, phytochemicals (including isoflavone and ginsenoside derivatives), and antioxidant activities of cheonggukjang with different ratios (0%, 2.5%, 5%, and 10%) of mountain-cultivated ginseng (MCG) were compared and analyzed using microorganisms isolated from traditional cheonggukjang . The IDCK 30 and IDCK 40 strains were confirmed as Bacillus licheniformis and Bacillus subtilis , respectively, based on morphological, biological, biochemical, and molecular genetic identification, as well as cell wall fatty acid composition. The contents of amino acids and fatty acids showed no significant difference in relation to the ratio of MCG. After fermentation, isoflavone glycoside (such as daidzin, glycitin, and genistin) contents decreased, while aglycone (daidzein, glycitein, and genistein) contents increased. However, total ginsenoside contents were higher according to the ratio of MCG. After fermentation, ginsenoside Rg2, F2, and protopanaxadiol contents of cheonggukjang decreased. Conversely, ginsenoside Rg3 (2.5%: 56.51 → 89.43 μg/g, 5.0%: 65.56 → 94.71 μg/g, and 10%: 96.05 → 166.90 μg/g) and compound K (2.5%: 28.54 → 69.43 μg/g, 5.0%: 41.63 → 150.72 μg/g, and 10%: 96.23 → 231.33 μg/g) increased. The total phenolic and total flavonoid contents were higher with increasing ratios of MCG and fermentation (fermented cheonggukjang with 10% MCG: 13.60 GAE and 1.87 RE mg/g). Additionally, radical scavenging activities and ferric reducing/antioxidant power were significantly increased in fermented cheonggukjang . This study demonstrates that the quality of cheonggukjang improved, and cheonggukjang with MCG as natural antioxidants may be useful in food and pharmaceutical applications.

Background: Previous randomized controlled trials have established the efficacy of dupilumab among patients with chronic obstructive pulmonary disease (COPD) treated with triple therapy over 52 weeks of follow-up., Objective: This population-based cohort study aimed to explore the long-term safety and effectiveness of dupilumab in patients with COPD., Methods: The study included US patients with COPD who were seen between April 2017 and August 2024. Patients initiating dupilumab and therapies that incorporated long-acting β 2 -agonist (LABA) inhalers were included. Patients with asthma or lung cancer were excluded. The risk of outcomes occurring after initiation of dupilumab versus LABA-containing therapies was measured. For detailed methods, please see the Methods section in this article's Online Repository at www.jacionline.org., Results: A total of 1521 dupilumab initiators and 1521 propensity score-matched patients who were receiving LABA-based therapies were included. Receiving dupilumab was associated with lower all-cause mortality (hazard ratio [HR] = 0.53, 95% CI = 0.43-0.65), fewer emergency department visits (HR = 0.78, 95% CI =0.69-0.89), and lower acute exacerbation rates (HR = 0.59, 95% CI = 0.53-0.65). Dupilumab was also associated with reductions in the requirement for short-acting β 2 -agonists (HR = 0.48, 95% CI = 0.43-0.52) and short-acting muscarinic antagonists (HR = 0.43, 95% CI = 0.37-0.49) for symptom control. Additionally, dupilumab decreased rates of subsequent pneumonia (HR = 0.65, 95% CI = 0.50-0.86), and COPD-relevant comorbidities, including new-onset heart failure (HR = 0.69, 95% CI = 0.53-0.90) and new-onset anxiety (HR = 0.70, 95% CI =0.53-0.93)., Conclusions: In patients with COPD, dupilumab was associated with a lower mortality rate, fewer emergency department visits, and a reduced risk of acute exacerbations, respiratory symptoms, and respiratory infections. More studies are needed to validate the efficacy of dupilumab among patients with COPD of various severities., Competing Interests: Disclosure statement This study was supported by the National Heart, Lung, and Blood Institute (grant HL161362 [to S.T.W.]). Disclosure of potential conflict of interest: S. T. Weiss receives royalties from UpToDate and serves on the board of Histolix, a digital pathology company. The rest of the authors declare no relevant conflicts of interest., (Copyright © 2024 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)

The clonal transmission of fluconazole-resistant Candida glabrata isolates within hospitals has seldom been analyzed by whole-genome sequencing (WGS). We performed WGS on 79 C . glabrata isolates, comprising 31 isolates from three premature infants with persistent C. glabrata bloodstream infection despite antifungal treatment in the same neonatal intensive care unit (NICU) in 2022 and 48 (27 fluconazole-resistant and 21 fluconazole-susceptible dose-dependent) bloodstream isolates from 48 patients in 15 South Korean hospitals from 2010 to 2022. Phylogenetic analysis based on WGS single-nucleotide polymorphisms (SNPs) distinguished the 79 isolates according to multilocus sequence typing (MLST) (17 sequence type [ST]3, 13 ST7, two ST22, 41 ST26, four ST55, and two ST59 isolates) and unveiled two possible clusters of nosocomial transmission among ST26 isolates. One cluster from two premature infants with overlapping NICU hospitalizations in 2022 encompassed 15 fluconazole-resistant isolates harboring pleiotropic drug-resistance transcription factor (Pdr1p) P258L (13 isolates) or N1086I (two isolates), together with 10 fluconazole-susceptible dose-dependent isolates lacking Pdr1p SNPs. The other cluster indicated unforeseen clonal transmission of fluconazole-resistant bloodstream isolates among five patients (four post-lung transplantation and one with diffuse interstitial lung disease) in the same hospital over 8 months. Among these five isolates, four obtained after exposure to azole antifungals harbored distinct Pdr1p SNPs (N1091D, E388Q, K365E, and R376Q). The findings reveal the transmission patterns of clonal bloodstream isolates of C. glabrata among patients undergoing antifungal treatment, exhibiting different levels of fluconazole susceptibility or distinct Pdr1p SNP profiles., Importance: The prevalence of fluconazole-resistant bloodstream infections caused by Candida glabrata is increasing globally, but the transmission of these resistant strains within hospitals has rarely been documented. Through whole-genome sequencing and epidemiological analyses, this study identified two potential clusters of C. glabrata bloodstream infections within the same hospital, revealing the transmission of clonal C. glabrata strains with different levels of fluconazole susceptibility or distinct transcription factor pleiotropic drug resistance protein 1 (Pdr1p) single-nucleotide polymorphism profiles among patients receiving antifungal therapy., Competing Interests: The authors declare no conflict of interest.

Early-life experiences play a crucial role in the development of the fronto-limbic regions, influencing both macro- and microstructural changes in the brain. These alterations profoundly impact cognitive, social-emotional functions. Recently, early limbic structural alterations have been associated with numerous neurological and psychiatric morbidities. Although identifying normative developmental trajectories is essential for determining brain alterations, only a few studies have focused on examining the normative trajectories in the fronto-limbic regions during preschool-aged children. The aim of this study was to investigate the structural-developmental trajectory of the fronto-limbic regions using the cortical thickness, volume, and subcortical volume in 57 healthy and typical preschool-aged children between 1 and 5 years and examined the early lateralization patterns during the development of the fronto-limbic regions. Regarding brain lateralization, remarkable asymmetry was detected in the volume of thalamus and the cortical regions excluding the lateral orbitofrontal cortex in the fronto-limbic regions. This study of preschool-aged children may fill the knowledge gaps regarding the developmental patterns and hemispheric asymmetries of the fronto-limbic regions between newborns and adolescents., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Lee, Youn, Jang, Kim, Lee, Lee, Jung and Lee.)

Ischemic stroke segmentation at an acute stage is vital in assessing the severity of patients' impairment and guiding therapeutic decision-making for reperfusion. Although many deep learning studies have shown attractive performance in medical segmentation, it is difficult to use these models trained on public data with private hospitals' datasets. Here, we demonstrate an ensemble model that employs two different multimodal approaches for generalization, a more effective way to perform on external datasets. First, after we jointly train a segmentation model on diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) MR modalities, the model is inferred on the DWI images. Second, a channel-wise segmentation model is trained by concatenating the DWI and ADC images as input, and then is inferred using both MR modalities. Before training with ischemic stroke data, we utilized BraTS 2021, a public brain tumor dataset, for transfer learning. An extensive ablation study evaluates which strategy learns better representations for ischemic stroke segmentation. In our study, nnU-Net well-known for robustness is selected as our baseline model. Our proposed method is evaluated on three different datasets: the Asan Medical Center (AMC) I and II, and the 2022 Ischemic Stroke Lesion Segmentation (ISLES). Our experiments are widely validated over a large, multi-center, and multi-scanner dataset with a huge amount of 846 scans. Not only stroke lesion models can benefit from transfer learning using brain tumor data, but combining the MR modalities using different training schemes also highly improves segmentation performance. The method achieved a top-1 ranking in the ongoing ISLES'22 challenge and performed particularly well on lesion-wise metrics of interest to neuroradiologists, achieving a Dice coefficient of 78.69% and a lesion-wise F1 score of 82.46%. Also, the method was relatively robust on the AMC I (Dice, 60.35%; lesion-wise F1, 68.30%) and II (Dice; 74.12%; lesion-wise F1, 67.53%) datasets in different settings. The high segmentation accuracy of our proposed method could improve radiologists' ability to detect ischemic stroke lesions in MRI images. Our model weights and inference code are available on https://github.com/MDOpx/ISLES22-model-inference ., (© 2024. The Author(s) under exclusive licence to Society for Imaging Informatics in Medicine.)

Dendritic cells (DCs) undergo glycolytic reprogramming, a metabolic conversion process essential for their activation. Vitamin D has been reported to affect the function of DCs, but studies in metabolic diseases are insufficient. This study investigates the effects of in vitro 1,25-dihydroxyvitamin D3 (1,25(OH) 2 D 3 ) treatment on glycolytic reprogramming of bone marrow-derived dendritic cells (BMDCs) from control, obese, and atherosclerosis mice. Six-week-old male C57BL/6J mice were fed a control diet (CON) or a Western diet (WD), and B6.129S7-Ldlr tm1Her /J mice were fed a Western diet (LDLR -/- ) for 16 weeks. BMDCs were cultured in a medium containing 1,25(OH) 2 D 3 (10 nM) for 7 days and stimulated with lipopolysaccharide (LPS, 50 ng/mL) for 24 h. In mature BMDCs, 1,25(OH) 2 D 3 treatment decreased basal and compensatory glycolytic proton efflux rates (glycoPER), the expression of surface markers related to immune function of DCs (MHC class II, CD80, and CD86), and IL-12p70 production. In addition, mTORC1 activation and nitric oxide (NO) production were suppressed by 1,25(OH) 2 D 3 treatment in mature BMDCs. The effect of 1,25(OH) 2 D 3 treatment on IL-12p70 production and mTORC1 activity in the LDLR -/- group was greater than in the CON group. These findings suggest that vitamin D can affect the metabolic environment of BMDCs by regulating glycolytic reprogramming as well as by inducing tolerogenic phenotypes of DCs., Competing Interests: Declaration of competing interest The authors declare no conflict of interests., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background : Distal bile duct cancer is an aggressive malignancy. Tumor-infiltrating immune cells (TIICs) in the tumor microenvironment are crucial for predicting prognosis in various cancers. In this study, we analyzed TIICs based on CD11b, CD163, and CD8 expression, and evaluated their association with clinicopathologic factors and prognosis in distal bile duct cancer. Methods: A total of 90 patients who underwent curative resection for distal bile duct cancer were enrolled. We analyzed CD11b+ tumor-infiltrating myeloid cells (TIMs), CD163+ tumor-infiltrating macrophages (TAMs), and CD8+ tumor-infiltrating lymphocytes (TILs) using immunohistochemistry and tissue microarrays. The correlation between TIICs and clinicopathologic characteristics was assessed. Results: Low levels of CD11b+ TIMs ( p < 0.001) and high levels of CD8+ TILs ( p = 0.003) were significantly associated with improved overall survival (OS). A combined low level of CD11b+ TIMs and high level of CD8+ TILs was identified as an independent favorable prognostic factor (hazard ratio, 0.159; confidence interval, 0.061-0.410; p < 0.001). Conclusions: CD11b+ TIMs play a crucial role in the tumor microenvironment and the prognosis of distal bile duct cancer. The combined analysis of CD11b+ TIMs and CD8+ TILs can predict survival in patients with distal bile duct cancer., Competing Interests: The authors declare no conflicts of interest.

Background: Emergency departments (EDs) are often the front door for urgent mental health care, especially when demand exceeds capacity. Long waits in EDs exert strain on hospital resources and worsen distress for individuals experiencing a mental health crisis. We used as a test case the Australian Capital Territory (ACT), with a population surge of over 27% across 2011-2021 and a lagging increase in mental health care capacity, to evaluate population-based approaches to reduce mental health-related ED presentations., Methods: We developed a system dynamics model for the ACT region using a participatory approach involving local stakeholders, including health planners, health providers and young people with lived experience of mental health disorders. Outcomes were projected over 2023-2032 for youth (aged 15-24) and for the general population., Results: Improving the overall mental health care system through strategies such as doubling the annual capacity growth rate of mental health services or leveraging digital technologies for triage and care coordination is projected to decrease youth mental health-related ED visits by 4.3% and 4.8% respectively. Implementation of mobile crisis response teams (consisting of a mental health nurse accompanying police or ambulance officers) is projected to reduce youth mental health-related ED visits by 10.2% by de-escalating some emergency situations and directly transferring selected individuals to community mental health centres. Other effective interventions include limiting re-presentations to ED by screening for suicide risk and following up with calls post-discharge (6.4% reduction), and limiting presentations of frequent users of ED by providing psychosocial education to families of people with schizophrenia (5.1% reduction). Finally, combining these five approaches is projected to reduce youth mental health-related ED presentations by 26.6% by the end of 2032., Conclusions: Policies to decrease youth mental health-related ED presentations should not be limited to increasing mental health care capacity, but also include structural reforms., (© 2024. The Author(s).)

T cell-based immunotherapies are a promising therapeutic approach for multiple malignancies, but their efficacy is limited by tumor hypoxia arising from dysfunctional blood vessels. Here, we report that cell-intrinsic properties of a single vascular component, namely the pericyte, contribute to the control of tumor oxygenation, macrophage polarization, vessel inflammation, and T cell infiltration. Switching pericyte phenotype from a synthetic to a differentiated state reverses immune suppression and sensitizes tumors to adoptive T cell therapy, leading to regression of melanoma in mice. In melanoma patients, improved survival is correlated with enhanced pericyte maturity. Importantly, pericyte plasticity is regulated by signaling pathways converging on Rho kinase activity, with pericyte maturity being inducible by selective low-dose therapeutics that suppress pericyte MEK, AKT, or notch signaling. We also show that low-dose targeted anticancer therapy can durably change the tumor microenvironment without inducing adaptive resistance, creating a highly translatable pathway for redosing anticancer targeted therapies in combination with immunotherapy to improve outcome.

Drug-resistance (DR) in many bacterial pathogens often arises from the repetitive formation of drug-tolerant bacilli, known as persisters. However, it is unclear whether Mycobacterium tuberculosis (Mtb), the bacterium that causes tuberculosis (TB), undergoes a similar phenotypic transition. Recent metabolomics studies have identified that a change in trehalose metabolism is necessary for Mtb to develop persisters and plays a crucial role in metabolic networks of DR-TB strains. The present study used Mtb mutants lacking the trehalose catalytic shift and showed that the mutants exhibited a significantly lower frequency of the emergence of DR mutants compared to wildtype, due to reduced persister formation. The trehalose catalytic shift enables Mtb persisters to survive under bactericidal antibiotics by increasing metabolic heterogeneity and drug tolerance, ultimately leading to development of DR. Intriguingly, rifampicin (RIF)-resistant bacilli exhibit cross-resistance to a second antibiotic, due to a high trehalose catalytic shift activity. This phenomenon explains how the development of multidrug resistance (MDR) is facilitated by the acquisition of RIF resistance. In this context, the heightened risk of MDR-TB in the lineage 4 HN878 W-Beijing strain can be attributed to its greater trehalose catalytic shift. Genetic and pharmacological inactivation of the trehalose catalytic shift significantly reduced persister formation, subsequently decreasing the incidence of MDR-TB in HN878 W-Beijing strain. Collectively, the trehalose catalytic shift serves as an intrinsic factor of Mtb responsible for persister formation, cross-resistance to multiple antibiotics, and the emergence of MDR-TB. This study aids in the discovery of new TB therapeutics by targeting the trehalose catalytic shift of Mtb.

Introduction: Children who have experienced the coronavirus disease 2019 (COVID-19) pandemic are at an increased risk of adverse neurologic developmental outcomes. Limited data exist on the environmental influences of during the COVID-19 pandemic on preterm infant development. This study aimed to investigate whether COVID-19 exposure affects the neurodevelopmental outcomes in preterm children up to 3 years of age., Methods: This prospective cohort study included all very low birth weight (VLBW) infants from the Korean Neonatal Network who had undergone a neurodevelopmental assessment between January 2015, and May 2022. The neurodevelopmental outcomes along with the scores on the Bayley Scales of Infant and Toddler Development (BSID) and the Korean Developmental Screening Test for Infants and Children of pediatric patients aged 18-24 and 33-39 months who were exposed to COVID-19 were compared with those of VLBW children born and tested before the pandemic., Results: The cohort included 1,683 VLBW infants. The pandemic group had significantly lower language scores on the BSID-III at ages 18-24 months ( p  = 0.021) and 33-39 months ( p  = 0.023) than the pre-pandemic group after adjusting for gestational age, morbidity, and environmental factors. At 2nd follow-up period, the pandemic group showed significantly lower scores in the cognitive ( p  = 0.026) domains with a mean difference of 7 points and had a significantly higher percentage of ≤-1SD in the gross motor domain ( p  < 0.001) compared with the pre-pandemic group., Conclusion: Preterm children who experienced the COVID-19 pandemic are at higher risk of abnormal neurodevelopmental outcomes in the first 3 years of life than preterm infants born before the COVID-19 pandemic., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Kim, Jang, Lee, Lee, Sung, Kim, Lee, Yang, Kim, Yoon, Ahn and Lee.)

Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M24-0019.

Chronic dermatitis is a disease with large unmet need for pharmacological improvement. Dermatitis conditions are maintained and exacerbated by various cytokine actions in the context of inflammation. Interleukin 6 signal transducer (Il6st), also known as glycoprotein 130 (Gp130), is a key component for surface reception of a multitude of cytokines and transduction and amplification of their pro-inflammatory signals. We hypothesized accordingly that pharmacological inhibition of Il6st can alter dermatitis pathology. Treatment with SC-144 and bazedoxifene, two representative small molecule Il6st inhibitors with different binding modes led to moderate but significant improvement of skin conditions in a 1-chloro-2,4-dinitrobenzene animal model. Part of cytokine expressions indicating the dermatological index were normalized particularly when treated with SC-144. Pruritic behaviors were blunted, also possibly giving limited contribution to disease improvement. In psoriatic skin and itch of an imiquimod animal model, those two treatments appeared to be relatively moderate. Collectively, pharmacological inhibition of Il6st seems to lessen pathological irritation. Inversely, this experimental attempt newly implies that Il6st participates in pathological mechanisms. In conclusion, we suggest Il6st as a novel target for improving dermatitis, and that agents with suitable efficacy and safety for its modulation are translatable., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest regarding the publication of this article., (Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

This study compared the nutritional components, isoflavones, and antioxidant activities by solid-sate fermentation of Apios americana Medikus (AAM) with seven different fungi. The total fatty acid contents increased from 120.5 mg/100 g (unfermented AAM, UFAAM) to 242.0 to 3167.5 mg/100 g (fermented AAM, FAAM) with all fungi. In particular, the values of total fatty acids were highest (26.3-fold increase) in the FAAM with Monascus purpureus. The amount of total free amino acids increased from 591.69 mg/100 g (UFAAM) to 664.38 to 1603.07 mg/100 g after fermentation except for Monascus pilosus and Lentinula edodes. The total mineral contents increased evidently after fermentation with M. purpureus, F. velutipes, and Tricholoma matsutake (347.36 → 588.29, 576.59, and 453.32 mg/100 g, respectively). The UFAAM predominated isoflavone glycosides, whereas glycoside forms were converted into aglycone forms after fermentation by fungi. The bioconversion rates of glycoside to aglycone were excellent in the FAAM with M. pilosus, M. purpureus, F. velutipes, and T. matsutake (0.01 → 0.69, 0.50, 0.27, and 0.31 mg/g, respectively). Furthermore, the total phenolic contents, total flavonoid contents, and antioxidant activities by the abovementioned FAAM were high except for L.edodes. This FAAM can be used as a potential food and pharmaceutical materials., 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.)

In this study, we present the development of an innovative electrochemical biosensor integrated into a microneedle-based system for non-invasive and sensitive quantification of cholesterol levels in interstitial fluid (ISF). The biosensor employs a graphene-based electrode with a polyelectrolyte interlayer to immobilize cholesterol oxidase (ChOx), enabling selective cholesterol detection. Graphene oxide is electrochemically reduced to form a conductive layer, and PANI is chosen as the optimal polyelectrolyte for ChOx immobilization. The biosensor's performance is thoroughly evaluated, demonstrating excellent sensitivity, stability, and selectivity. Furthermore, the biosensor is successfully applied to skin-mimicking agarose gel and porcine skin, showcasing its potential for real-world interstitial fluid extraction and cholesterol monitoring. The integrated microneedle-based system offers a promising approach for non-invasive monitoring of cholesterol levels, with implications for personalized healthcare diagnostics., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)