Metastable hexagonal close-packed palladium hydride in liquid cell TEM.

Metastable phases-kinetically favoured structures-are ubiquitous in nature1,2. Rather than forming thermodynamically stable ground-state structures, crystals grown from high-energy precursors often initially adopt metastable structures depending on the initial conditions, such as temperature, pressure or crystal size1,3,4. As the crystals grow further, they typically undergo a series of transformations from metastable phases to lower-energy and ultimately energetically stable phases1,3,4. Metastable phases sometimes exhibit superior physicochemical properties and, hence, the discovery and synthesis of new metastable phases are promising avenues for innovations in materials science1,5. However, the search for metastable materials has mainly been heuristic, performed on the basis of experiences, intuition or even speculative predictions, namely 'rules of thumb'. This limitation necessitates the advent of a new paradigm to discover new metastable phases based on rational design. Such a design rule is embodied in the discovery of a metastable hexagonal close-packed (hcp) palladium hydride (PdHx) synthesized in a liquid cell transmission electron microscope. The metastable hcp structure is stabilized through a unique interplay between the precursor concentrations in the solution: a sufficient supply of hydrogen (H) favours the hcp structure on the subnanometre scale, and an insufficient supply of Pd inhibits further growth and subsequent transition towards the thermodynamically stable face-centred cubic structure. These findings provide thermodynamic insights into metastability engineering strategies that can be deployed to discover new metastable phases.

Threshold of somatic mosaicism leading to brain dysfunction with focal epilepsy.

Somatic mosaicism in a fraction of brain cells causes neurodevelopmental disorders, including childhood intractable epilepsy. However, the threshold for somatic mosaicism leading to brain dysfunction is unknown. In this study, we induced various mosaic burdens in focal cortical dysplasia type II (FCD II) mice, featuring mTOR somatic mosaicism and spontaneous behavioral seizures. The mosaic burdens ranged from approximately 1,000 to 40,000 neurons expressing the mTOR mutant in the somatosensory (SSC) or medial prefrontal (PFC) cortex. Surprisingly, approximately 8,000 to 9,000 neurons expressing the MTOR mutant, which are extrapolated to constitute 0.08-0.09% of total cells or roughly 0.04% of variant allele frequency (VAF) in the mouse hemicortex, were sufficient to trigger epileptic seizures. The mutational burden was correlated with seizure frequency and onset, with a higher tendency for electrographic inter-ictal spikes and beta- and gamma-frequency oscillations in FCD II mice exceeding the threshold. Moreover, mutation-negative FCD II patients in deep sequencing of their bulky brain tissues revealed somatic mosaicism of the mTOR pathway genes as low as 0.07% in resected brain tissues through ultra-deep targeted sequencing (up to 20 million reads). Thus, our study suggests that extremely low levels of somatic mosaicism can contribute to brain dysfunction.

Fracture Risk Among Stroke Survivors According to Poststroke Disability Status and Stroke Type.

BACKGROUND: Stroke survivors face physical and cognitive challenges, leading to an increased dependency and a higher fall risk. We aimed to investigate the impact of poststroke disability and stroke type on fracture risk at various sites compared with matched controls. METHODS: This retrospective cohort study used data from the Korean National Health Insurance System database (2010-2018), including patients with stroke and 1:1 matched controls. Stroke survivors were grouped based on the presence and severity of their poststroke disability and stroke type. The primary outcome was a newly diagnosed fracture, analyzed by Cox proportional hazard regression analyses adjusting for potential confounders. RESULTS: Among 223 358 stroke survivors (mean age, 64.8±10.9 years; 61.2% men), 16 344 fractures occurred during a mean follow-up of 3.7±2.5 years. In matched controls (n=322 161; mean age, 65.4±11.2 years; 61.3% men), 20 398 fractures were identified. Stroke survivors had increased overall fracture risk compared with matched controls (adjusted hazard ratio [aHR], 1.40 [95% CI, 1.37-1.43]). Specifically, hip fracture risk was even greater in stroke survivors (incidence rate per 1000 person-years, 4.7 [95% CI, 4.5-4.8]; aHR, 2.42 [95% CI, 2.30-2.55]) than controls (incidence rate, 2.2 [95% CI, 2.1-2.3]). The risk of vertebral fractures (aHR, 1.29 [95% CI, 1.25-1.34]) and other fractures (aHR, 1.19 [95% CI, 1.15-1.23]) was also higher than that of the control group. Hip fracture risk was the highest among stroke survivors with severe poststroke disability (aHR, 4.82 [95% CI, 4.28-5.42]), although vertebral or other fracture risk was the highest among those with mild poststroke disability. No significant difference in fracture risk was found between hemorrhagic and ischemic stroke survivors when stratified by disability status. CONCLUSIONS: Our findings showed increased subsequent fracture risk among stroke survivors, particularly those with poststroke disability and for hip fracture. Bone health assessment and treatment should be emphasized as an essential part of stroke management.

Correlations in abnormal synergies between the upper and lower extremities across various phases of stroke.

The flexion synergy and extension synergy are a representative consequence of a stroke and appear in the upper extremity and the lower extremity. Since the ipsilesional corticospinal tract (CST) is the most influential neural pathway for both extremities in motor execution, damage by a stroke to this tract could lead to similar motor pathological features (e.g., abnormal synergies) in both extremities. However, less attention has been paid to the interlimb correlations in the flexion synergy and extension synergy across different recovery phases of a stroke. We used results of the Fugl-Meyer assessment (FMA) to characterize those correlations in a total of 512 participants with hemiparesis after stroke from the acute phase to 1 year. The FMA provides indirect indicators of the degrees of the flexion synergy and extension synergy after stroke. We found that, generally, strong interlimb correlations (r > 0.65 with all P values < 0.0001) between the flexion synergy and extension synergy appeared in the acute-to-subacute phase (<90 days). However, the correlations of the lower-extremity extension synergy with the upper-extremity flexion synergy and extension synergy decreased (down to r = 0.38) 360 days after stroke (P < 0.05). These results suggest that the preferential use of alternative neural pathways after damage by a stroke to the CST enhances the interlimb correlations between the flexion synergy and extension synergy. At the same time, the results imply that the recovery of CST integrity or/and the fragmentation (remodeling) of the alternative neural substrates in the chronic phase may contribute to diversity in neural pathways in motor execution, eventually leading to reduced interlimb correlations.NEW & NOTEWORTHY For the first time, this article addresses the asynchronous relationships in the strengths of flexion and extension synergy expressions between the paretic upper extremity and lower extremity across various phases of stroke.

Evidence of the existence of multiple modules for the stroke-caused flexion synergy from Fugl-Meyer assessment scores.

Stroke-caused synergies may result from the preferential use of the reticulospinal tract (RST) due to damage to the corticospinal tract. The RST branches multiple motoneuron pools across the arm together resulting in gross motor control or abnormal synergies, and accordingly, the controllability of individual muscles decreases. However, it is not clear whether muscles involuntarily activated by abnormal synergy vary depending on the muscles voluntarily activated when motor commands descend through the RST. Studies showed that abnormal synergies may originate from the merging and reweighting of synergies in individuals without neurological deficits. This leads to a hypothesis that those abnormal synergies are still selectively excited depending on the context. In this study, we test this hypothesis, leveraging the Fugl-Meyer assessment that could characterize the neuroanatomical architecture in individuals with a wide range of impairments. We examine the ability to perform an out-of-synergy movement with the flexion synergy caused by either shoulder or elbow loading. The results reveal that about 14% [8/57, 95% confidence interval (5.0%, 23.1%)] of the participants with severe impairment (total Fugl-Meyer score <29) in the chronic phase (6 months after stroke) are able to keep the elbow extended during shoulder loading and keep the shoulder at neutral during elbow loading. Those participants underwent a different course of neural reorganization, which enhanced abnormal synergies in comparison with individuals with mild impairment (P < 0.05). These results provide evidence that separate routes and synergy modules to motoneuron pools across the arm might exist even if the motor command is mediated possibly via the RST.NEW & NOTEWORTHY We demonstrate that abnormal synergies are still selectively excited depending on the context.

Comparison of Four Diagnostic Guidelines for Hepatocellular Carcinoma Using Gadoxetic Acid-enhanced Liver MRI.

Background Noninvasive diagnostic guidelines for hepatocellular carcinoma (HCC) vary across different global geographic areas, especially regarding criteria about gadoxetic acid-enhanced MRI. Purpose To compare the diagnostic performance of four different international HCC diagnosis guidelines and readers' judgment in diagnosing HCC using gadoxetic acid-enhanced MRI in patients at high risk for HCC. Materials and Methods This retrospective study included patients who had not undergone treatment, were at risk for HCC, and who underwent gadoxetic acid-enhanced MRI from January 2015 to June 2018 from 11 tertiary hospitals in South Korea. Four radiologists independently reviewed focal liver lesions (FLLs) according to four guidelines: American Association for the Study of Liver Diseases (AASLD)/Liver Imaging Reporting and Data System (LI-RADS), Korean Liver Cancer Association-National Cancer Center (KLCA-NCC), European Association for the Study of the Liver (EASL), and Asian Pacific Association for the Study of the Liver (APASL). Reader judgment (HCC or not HCC) was also recorded. Malignant FLLs were confirmed at pathology, and histologic and clinical follow-up data were used for benign FLLs. The guidelines' diagnostic performance was compared using generalized estimating equations. Additionally, the diagnostic odds ratio was assessed. Results A total of 2445 FLLs (median size, 27.4 mm) were analyzed in 2237 patients (mean age, 59 years ± 11 [SD]; 1666 male patients); 69.3% (1694 of 2445) were HCCs. KLCA-NCC showed the highest accuracy (80.0%; 95% CI: 78.7, 81.2; P = .001), with high sensitivity in Eastern guidelines (APASL, 89.1% [95% CI: 87.8, 90.3]; KLCA-NCC, 78.2% [95% CI: 76.6, 79.7]) and high specificity in Western guidelines (AASLD/LI-RADS, 89.6% [95% CI: 87.8, 91.2]; EASL, 88.1% [95% CI: 86.2, 89.9]) (P = .001). The diagnostic odds ratios were 20.7 (95% CI: 17.0, 25.3) for AASLD/LI-RADS, 18.9 (95% CI: 15.8, 22.6) for KLCA-NCC, 16.8 (95% CI: 13.8, 20.4) for EASL, and 8.9 (95% CI: 7.4, 10.7) for APASL. The readers' judgment demonstrated higher accuracy than that of the guidelines (accuracy, 86.0%; 95% CI: 84.9, 86.9; P = .001). Conclusion Among four different international HCC diagnosis guidelines, Eastern guidelines demonstrated higher sensitivity, whereas Western guidelines displayed higher specificity. KLCA-NCC achieved the highest accuracy, and AASLD/LI-RADS exhibited the highest diagnostic odds ratio. © RSNA, 2024 Supplemental material is available for this article.

Attojoule Hexagonal Boron Nitride-Based Memristor for High-Performance Neuromorphic Computing.

In next-generation neuromorphic computing applications, the primary challenge lies in achieving energy-efficient and reliable memristors while minimizing their energy consumption to a level comparable to that of biological synapses. In this work, hexagonal boron nitride (h-BN)-based metal-insulator-semiconductor (MIS) memristors operating is presented at the attojoule-level tailored for high-performance artificial neural networks. The memristors benefit from a wafer-scale uniform h-BN resistive switching medium grown directly on a highly doped Si wafer using metal-organic chemical vapor deposition (MOCVD), resulting in outstanding reliability and low variability. Notably, the h-BN-based memristors exhibit exceptionally low energy consumption of attojoule levels, coupled with fast switching speed. The switching mechanisms are systematically substantiated by electrical and nano-structural analysis, confirming that the h-BN layer facilitates the resistive switching with extremely low high resistance states (HRS) and the native SiOx on Si contributes to suppressing excessive current, enabling attojoule-level energy consumption. Furthermore, the formation of atomic-scale conductive filaments leads to remarkably fast response times within the nanosecond range, and allows for the attainment of multi-resistance states, making these memristors well-suited for next-generation neuromorphic applications. The h-BN-based MIS memristors hold the potential to revolutionize energy consumption limitations in neuromorphic devices, bridging the gap between artificial and biological synapses.

Ultra-Low Level Somatic Mutations and Structural Variations in Focal Cortical Dysplasia Type II.

OBJECTIVE: Brain somatic mutations in mTOR pathway genes are a major genetic etiology of focal cortical dysplasia type II (FCDII). Despite a greater ability to detect low-level somatic mutations in the brain by deep sequencing and analytics, about 40% of cases remain genetically unexplained. METHODS: We included 2 independent cohorts consisting of 21 patients with mutation-negative FCDII without apparent mutations on conventional deep sequencing of bulk brain. To find ultra-low level somatic variants or structural variants, we isolated cells exhibiting phosphorylation of the S6 ribosomal protein (p-S6) in frozen brain tissues using fluorescence-activated cell sorting (FACS). We then performed deep whole-genome sequencing (WGS; >90×) in p-S6+ cells in a cohort of 11 patients with mutation-negative. Then, we simplified the method to whole-genome amplification and target gene sequencing of p-S6+ cells in independent cohort of 10 patients with mutation-negative followed by low-read depth WGS (10×). RESULTS: We found that 28.6% (6 of 21) of mutation-negative FCDII carries ultra-low level somatic mutations (less than 0.2% of variant allele frequency [VAF]) in mTOR pathway genes. Our method showed ~34 times increase of the average mutational burden in FACS mediated enrichment of p-S6+ cells (average VAF = 5.84%) than in bulky brain tissues (average VAF = 0.17%). We found that 19% (4 of 21) carried germline structural variations in GATOR1 complex undetectable in whole exome or targeted gene sequencing. CONCLUSIONS: Our method facilitates the detection of ultra-low level somatic mutations, in specifically p-S6+ cells, and germline structural variations and increases the genetic diagnostic rate up to ~80% for the entire FCDII cohort. ANN NEUROL 2023;93:1082-1093.

Independent association of thigh muscle fat density with vascular events in Korean adults.

BACKGROUND: We aimed to explore the associations between thigh muscle fat density and vascular events. METHODS: A total of 3,595 adults (mean age, 57.2 years; women, 1,715 [47.7%]) without baseline cardiovascular events from the Korean Atherosclerosis Study-2 were included. Muscle and fat area at the mid-thigh level were measured by computed tomography (CT) using the following Hounsfield Unit range: 0-30 for low density muscle (LDM); 31-100 for normal density muscle (NDM); and - 250 to - 50 for fat. RESULTS: During a median follow-up period of 11.8 (4.3-13.9) years, vascular events occurred in 11.6% of men and 5.9% of women. Individuals with vascular events had a larger LDM area (men: 48.8 ± 15.5 cm2 vs. 44.6 ± 14.5 cm2; women: 39.4 ± 13.2 cm2 vs. 35.0 ± 11.8 cm2, both P < 0.001) compared with those who did not have vascular events during the follow-up of at least 5 years. The LDM/NDM ratio was also independently associated with vascular events after adjusting for cardiometabolic risk factors. Moreover, the LDM/NDM ratio improved the prognostic value for vascular events when added to conventional risk factors. CONCLUSIONS: The current study suggests that a higher thigh muscle fat infiltration is associated with an increased risk of developing vascular events among Korean adults.

Investigation of Neuromodulatory Effect of Anodal Cerebellar Transcranial Direct Current Stimulation on the Primary Motor Cortex Using Functional Near-Infrared Spectroscopy.

Cerebellar brain inhibition (CBI), a neural connection between the cerebellum and primary motor cortex (M1), has been researched as a target pathway for neuromodulation to improve clinical outcomes in various neurological diseases. However, conflicting results of anodal cerebellar transcranial direct current stimulation (acb-tDCS) on M1 excitability indicate that additional investigation is required to examine its precise effect. This study aimed to gather evidence of the neuromodulatory effect of acb-tDCS on the M1 using functional near-infrared spectroscopy (fNIRS). Sixteen healthy participants were included in this cross-over study. Participants received real and sham acb-tDCS randomly, with a minimum 1-week washout period between them. The anode and cathode were placed on the right cerebellum and the right buccinator muscle, respectively. Stimulation lasted 20 min at an intensity of 2 mA, and fNIRS data were recorded for 42 min (including a 4-min baseline before stimulation and an 18-min post-stimulation duration) using eight channels attached bilaterally on the M1. acb-tDCS induced a significant decrease in oxyhemoglobin (HbO) concentration (inhibitory effect) in the left (contralateral) M1, whereas it induced a significant increase in HbO concentration (excitatory effect) in the right (ipsilateral) M1 compared to sham tDCS during (p < 0.05) and after stimulation (p < 0.01) in a group level analysis. At the individual level, variations in response to acb-tDCS were observed. Our findings demonstrate the neuromodulatory effects of acb-tDCS on the bilateral M1 in terms of neuronal hemodynamics.

Nonparametric predictive model for sparse and irregular longitudinal data.

We propose a kernel-based estimator to predict the mean response trajectory for sparse and irregularly measured longitudinal data. The kernel estimator is constructed by imposing weights based on the subject-wise similarity on L2 metric space between predictor trajectories, where we assume that an analogous fashion in predictor trajectories over time would result in a similar trend in the response trajectory among subjects. In order to deal with the curse of dimensionality caused by the multiple predictors, we propose an appealing multiplicative model with multivariate Gaussian kernels. This model is capable of achieving dimension reduction as well as selecting functional covariates with predictive significance. The asymptotic properties of the proposed nonparametric estimator are investigated under mild regularity conditions. We illustrate the robustness and flexibility of our proposed method via extensive simulation studies and an application to the Framingham Heart Study.

A Bayesian convolutional neural network-based generalized linear model.

Convolutional neural networks (CNNs) provide flexible function approximations for a wide variety of applications when the input variables are in the form of images or spatial data. Although CNNs often outperform traditional statistical models in prediction accuracy, statistical inference, such as estimating the effects of covariates and quantifying the prediction uncertainty, is not trivial due to the highly complicated model structure and overparameterization. To address this challenge, we propose a new Bayesian approach by embedding CNNs within the generalized linear models (GLMs) framework. We use extracted nodes from the last hidden layer of CNN with Monte Carlo (MC) dropout as informative covariates in GLM. This improves accuracy in prediction and regression coefficient inference, allowing for the interpretation of coefficients and uncertainty quantification. By fitting ensemble GLMs across multiple realizations from MC dropout, we can account for uncertainties in extracting the features. We apply our methods to biological and epidemiological problems, which have both high-dimensional correlated inputs and vector covariates. Specifically, we consider malaria incidence data, brain tumor image data, and fMRI data. By extracting information from correlated inputs, the proposed method can provide an interpretable Bayesian analysis. The algorithm can be broadly applicable to image regressions or correlated data analysis by enabling accurate Bayesian inference quickly.

Improving radiomics reproducibility using deep learning-based image conversion of CT reconstruction algorithms in hepatocellular carcinoma patients.

OBJECTIVES: CT reconstruction algorithms affect radiomics reproducibility. In this study, we evaluate the effect of deep learning-based image conversion on CT reconstruction algorithms. METHODS: This study included 78 hepatocellular carcinoma (HCC) patients who underwent four-phase liver CTs comprising non-contrast, late arterial (LAP), portal venous (PVP), and delayed phase (DP), reconstructed using both filtered back projection (FBP) and advanced modeled iterative reconstruction (ADMIRE). PVP images were used to train a convolutional neural network (CNN) model to convert images from FBP to ADMIRE and vice versa. LAP, PVP, and DP images were used for validation and testing. Radiomic features were extracted for each patient with a semi-automatic segmentation tool. We used concordance correlation coefficients (CCCs) to evaluate the radiomics reproducibility for original FBP (oFBP) vs. original ADMIRE (oADMIRE), oFBP vs. converted FBP (cFBP), and oADMIRE vs. converted ADMIRE (cADMIRE). RESULTS: In the test group including 30 patients, the CCC and proportion of reproducible features (CCC ≥ 0.85) for oFBP vs. oADMIRE were 0.65 and 32.9% (524/1595) for LAP, 0.65 and 35.9% (573/1595) for PVP, and 0.69 and 43.8% (699/1595) for DP. For oFBP vs. cFBP, the values increased to 0.92 and 83.9% (1339/1595) for LAP, 0.89 and 71.0% (1133/1595) for PVP, and 0.90 and 79.7% (1271/1595) for DP. Similarly, for oADMIRE vs. cADMIRE, the values increased to 0.87 and 68.1% (1086/1595) for LAP, 0.91 and 82.1% (1309/1595) for PVP, and 0.89 and 76.2% (1216/1595) for DP. CONCLUSIONS: CNN-based image conversion between CT reconstruction algorithms improved the radiomics reproducibility of HCCs. CLINICAL RELEVANCE STATEMENT: This study demonstrates that using a CNN-based image conversion technique significantly improves the reproducibility of radiomic features in HCCs, highlighting its potential for enhancing radiomics research in HCC patients. KEY POINTS: Radiomics reproducibility of HCC was improved via CNN-based image conversion between two different CT reconstruction algorithms. This is the first clinical study to demonstrate improvements across a range of radiomic features in HCC patients. This study promotes the reproducibility and generalizability of different CT reconstruction algorithms in radiomics research.

Risk of Parkinson disease in stroke patients: A nationwide cohort study in South Korea.

BACKGROUND AND PURPOSE: Previous studies have examined the risk of stroke in patients with Parkinson disease (PD), but the incidence of PD onset among stroke patients and its risk according to severity of poststroke disabilities have scarcely been investigated. This study aims to determine whether the risk of PD is increased among stroke patients using a retrospective cohort with a large population-based database. METHODS: We used data collected by the Korean National Health Insurance Service from 2010 to 2018 and examined 307,361 stroke patients and 380,917 sex- and age-matched individuals without stroke to uncover the incidence of PD. Cox proportional hazards regression was used to calculate the hazard ratio (HR) and 95% confidence interval (CI), and the risk of PD was compared according to presence and severity of disability. RESULTS: During 4.31 years of follow-up, stroke patients had a 1.67 times higher risk of PD compared to individuals without stroke (adjusted HR = 1.67, 95% CI = 1.57-1.78). The risk of PD was greater among stroke patients with disabilities than among those without disabilities, even after adjustment for multiple covariates (adjusted HR = 1.72, 95% CI = 1.55-1.91; and adjusted HR = 1.66, 95% CI = 1.56-1.77, respectively). CONCLUSIONS: Our study demonstrated an increased risk of PD among stroke patients. Health professionals need to pay careful attention to detecting movement disorders as clues for diagnosing PD.

Sex-dependent different clinicopathological characterization of Epstein-Barr virus-associated gastric carcinoma: a large-scale study.

BACKGROUND: Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC) has been reported to account for approximately 5-16% of all GCs with good prognosis compared to EBV-negative GC. We evaluated the clinicopathological characteristics of EBVaGC including survival rate in South Korea. METHODS: A total of 4,587 patients with GC who underwent EBV in situ hybridization (EBV-ISH) were prospectively enrolled at the Seoul National University Bundang Hospital from 2003 to 2021. Age, sex, smoking status, cancer type and stage, tumor size and location, histological type, molecular features and survival information were analyzed. RESULTS: A total of 456 patients with GC (9.9%) were positive for EBV. The EBVaGC group displayed a higher proportion of males (P < 0.001), a predominant presence in the proximal stomach (P < 0.001), a higher proportion of undifferentiated cancer (P < 0.001), and a lower cancer stage (P = 0.004) than the EBV-negative group. Cox multivariate analyses revealed age (hazard ratio [HR] = 1.025, P < 0.001), tumor size (HR = 1.109, P < 0.001), and cancer stage (stage2 HR = 4.761, P < 0.001; stage3 HR = 13.286, P < 0.001; stage4 HR = 42.528, P < 0.001) as significant risk factors for GC-specific mortality, whereas EBV positivity was inversely correlated (HR = 0.620, P = 0.022). Furthermore, the EBVaGC group displayed statistically significant survival advantages over the EBV-negative cancer group in terms of both overall (P = 0.021) and GC-specific survival (P = 0.007) on the Kaplan-Meier survival curve. However, this effect was evident only in males. CONCLUSIONS: EBVaGC patients showed better prognoses despite their association with proximal location and poorly differentiated histology in male, probably due to the difference in immunity between males and females.

Antifungal mechanisms investigation of lactic acid bacteria against Aspergillus flavus: through combining microbial metabolomics and co-culture system.

AIMS: To develop antifungal lactic acid bacteria (LAB) and investigate their antifungal mechanisms against Aspergillus flavus in aflatoxin (AF) production. METHODS AND RESULTS: We isolated 179 LABs from cereal-based fermentation starters and investigated their antifungal mechanism against A. flavus through liquid chromatography-mass spectrometry and co-culture analysis techniques. Of the 179 isolates, antifungal activity was identified in Pediococcus pentosaceus, Lactobacillus crustorum, and Weissella paramesenteroides. These LABs reduced AF concentration by (i) inhibiting mycelial growth, (ii) binding AF to the cell wall, and (iii) producing antifungal compounds. Species-specific activities were also observed, with P. pentosaceus inhibiting AF production and W. paramesenteroides showing AF B1 binding activity. In addition, crucial extracellular metabolites for selecting antifungal LAB were involved in the 2',3'-cAMP-adenosine and nucleoside pathways. CONCLUSIONS: This study demonstrates that P. pentosaceus, L. crustorum, and W. paramesenteroides are key LAB strains with distinct antifungal mechanisms against A. flavus, suggesting their potential as biological agents to reduce AF in food materials.

Safety and dose escalation of the targeted oncolytic adenovirus OBP-301 for refractory advanced liver cancer: Phase I clinical trial.

OBP-301 is an oncolytic adenovirus modified to replicate within cancer cells and lyse them. This open-label, non-comparative, phase I dose-escalation trial aimed to assess its safety and optimal dosage in 20 patients with advanced hepatocellular carcinoma. Good tolerance was shown with a maximum tolerated dose of 6 × 1012 viral particles. The most common treatment-emergent adverse events were influenza-like illness, pyrexia, fatigue, decreased platelet count, abdominal distension, and anemia. Cohorts 4 and 5 had approximately 50% higher levels of CD8+ T cells in the peripheral blood after injection. The best target response occurred in 14 patients, 4 of whom had progressive disease. Multiple intratumoral injections of OBP-301 were well tolerated in patients with advanced hepatocellular carcinoma. The stable disease rate for the injected tumors was greater than the overall response rate, even with no obvious tumor response. OBP-301 might have a greater impact on local response as histological examination revealed that the presence of OBP-301 was consistent with the necrotic area at the injection site. Increased infiltration of CD8+ T cells and <1% PD-L1 expression were observed in tumors after injection. Improved antitumor efficacy might be achieved in future studies via viral injection with volume adjustment and in combination with other immuno-therapeutics.

Effects of resistance training and nutritional support on osteosarcopenia in older, community-dwelling postmenopausal Korean females (ERTO-K study): a study protocol.

BACKGROUND: Osteosarcopenia is geriatric syndrome defined as the concomitant occurrence of osteopenia/osteoporosis, and sarcopenia. Osteosarcopenia is a relatively new concept in geriatric medicine; however, it may increase the risk of fragility fractures, several morbidities and mortalities, and socioeconomic costs. Although resistance exercises and nutritional support-including protein, calcium, and vitamin D-are potential non-pharmacological management procedures, evidence is still lacking. The objective of this study was therefore to evaluate the effect of combined resistance exercise and nutritional support on the quality and quantity of bone and muscle in postmenopausal females with osteosarcopenia. METHODS: This research proposal presents the protocol for a prospective, single-center, single-blinded, two-armed randomized controlled trial. Thirty-four participants with osteosarcopenia will be recruited and randomly divided into intervention and control groups; both groups will receive nutritional supplements (protein, 40 g; vitamin D, 1600 IU; calcium, 600 mg) daily. The intervention group will undergo 24 weeks of resistance exercise of increasing intensity, achieved through a three-phase step-up process. The primary outcomes will be the changes in skeletal muscle index and bone marrow density of the lumbar spine and femoral neck between the baseline and end of intervention (24 weeks). The secondary outcomes will be the body composition, whole body phase angle, physical function assessment, quality of life, psychological assessment, and bone turnover markers of participants, surveyed at multiple time points. DISCUSSION: This randomized controlled trial may reveal the effect of resistance exercise and nutritional support on older postmenopausal women with osteosarcopenia. The results will provide evidence for developing proper non-pharmacological management guidelines for postmenopausal women. TRIAL REGISTRATION: Clinical Research Information Service of Republic of Korea, KCT0008291, Registered on 16 March 2023, https://cris.nih.go.kr/cris/search/detailSearch.do/25262 .

Comparison of anticholinergic burden with chronic polypharmacy on functional decline and mortality in Korean older people: a retrospective nationwide cohort study.

BACKGROUND: We aimed to evaluate the association of anticholinergic burden and chronic polypharmacy with the incidence of functional decline and all-cause mortality, and to determine the difference between anticholinergic burden and chronic polypharmacy among Korean older people. METHODS: This nationwide cohort study included 42,132 older people aged ≥ 65 years who underwent Korean National Health Insurance Service health examinations from 2007 to 2008. Odds ratios (ORs) and 95% confidence intervals (CIs) for abnormal Timed Up and Go (TUG) test results were assessed using multivariate logistic regression analyses. Hazard ratios (HRs) and 95% CIs for all-cause mortality until the end of 2015 were estimated using multivariable Cox proportional hazards regression analysis. RESULTS: Of the participants, 37.19% had abnormal TUG test results, and 7.66% of those died during the 5.7-year mean follow-up. The abnormal TUG test results OR increased by 27% among individuals with Korean Anticholinergic Burden Scale (KABS) scores ≥ 3 (OR 1.27, 95% CI 1.02-1.58) compared to those with KABS scores of 0. The HRs for all-cause mortality increased for individuals with higher KABS scores (P for trend < 0.001) or chronic polypharmacy (P for trend < 0.001) compared to those for individuals without these conditions. The combination of a higher KABS or chronic polypharmacy and abnormal TUG test results increased the risk of all-cause mortality (All P for trend < 0.001). CONCLUSION: Anticholinergic drug burden shows a better association with functional decline than chronic polypharmacy, and the use of medications and functional decline may be important risk factors for all-cause mortality among older people.

The roles of health literacy and social support in the association between smartphone ownership and frailty in older adults: a moderated mediation model.

BACKGROUND: Understanding the role of smartphones to promote the health status of older adults is important in the digital society. Little is known about the effects of having smartphones on physical frailty despite its positive effect on the well-being of older adults. This study aimed to explore the association between smartphone ownership and frailty in community-dwelling older adults and its underlying mechanism. METHODS: We used data from the Korean Frailty and Aging Cohort Study and analyzed 2,469 older adults aged 72-86 years. Frailty, health literacy, and social support were assessed by Fried's frailty phenotype, the Behavioral Risk Factor Surveillance System health literacy module, and the Enhancing Recovery in Coronary Heart Disease (ENRICHD) Social Support Instrument, respectively. The mediation model and moderated mediation model were estimated, where the mediator was health literacy and the moderator was social support, to explore the relationship between smartphone ownership and frailty. RESULTS: Of our study participants, 58.9% owned smartphones, and 10.9% were classified as frail. Smartphone ownership was negatively associated with frailty (ß = -0.623, p < 0.001). Health literacy mediated the relationship between smartphone ownership and frailty (ß = -0.154, boot confidence interval [CI] = - 0.222, - 0.096), and social support moderated the mediation effect (ß = -0.010, Boot CI = - 0.016, - 0.004). CONCLUSIONS: Owning smartphones among older adults could reduce the risk of frailty. Promoting health literacy and social support among older adults with smartphones would be effective to prevent frailty.