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BACKGROUND: Clostridium innocuum, previously considered a commensal microbe, is a spore-forming anaerobic bacterium. C. innocuum displays inherent resistance to vancomycin and is associated with extra-intestinal infections, antibiotic-associated diarrhea, and inflammatory bowel disease. This study seeks to establish a multilocus sequence typing (MLST) scheme to explore the correlation between C. innocuum genotyping and its potential pathogenic phenotypes. METHODS: Fifty-two C. innocuum isolates from Linkou Chang Gung Memorial Hospital (CGMH) in Taiwan and 60 sequence-available C. innocuum isolates from the National Center for Biotechnolgy Information Genome Database were included. The concentrated sequence of housekeeping genes in C. innocuum was determined by amplicon sequencing and used for MLST and phylogenetic analyses. The biofilm production activity of the C. innocuum isolates was determined by crystal violet staining. RESULTS: Of the 112 C. innocuum isolates, 58 sequence types were identified. Maximum likelihood estimation categorized 52 CGMH isolates into two phylogenetic clades. These isolates were found to be biofilm producers, with isolates in clade I exhibiting significantly higher biofilm production than isolates in clade II. The sub-inhibitory concentration of vancomycin seemed to minimally influence biofilm production by C. innocuum isolates. Nevertheless, C. innocuum embedded in the biofilm structure demonstrated resistance to vancomycin treatments at a concentration greater than 256 µg/mL. CONCLUSIONS: This study suggests that a specific genetic clade of C. innocuum produces a substantial amount of biofilm. Furthermore, this phenotype assists C. innocuum in resisting high concentrations of vancomycin, which may potentially play undefined roles in C. innocuum pathogenesis.

Asunto(s)

Antibacterianos , Biopelículas , Infecciones por Clostridium , Clostridium , Variación Genética , Pruebas de Sensibilidad Microbiana , Tipificación de Secuencias Multilocus , Filogenia , Resistencia a la Vancomicina , Vancomicina , Biopelículas/crecimiento & desarrollo , Biopelículas/efectos de los fármacos , Humanos , Clostridium/genética , Clostridium/efectos de los fármacos , Clostridium/aislamiento & purificación , Clostridium/clasificación , Antibacterianos/farmacología , Vancomicina/farmacología , Resistencia a la Vancomicina/genética , Infecciones por Clostridium/microbiología , Taiwán , Genotipo , Genes Esenciales

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Due to the transformation of artificial intelligence (AI) tools and technologies, AI-driven drug discovery has come to the forefront. It reduces the time and expenditure. Due to these advantages, pharmaceutical industries are concentrating on AI-driven drug discovery. Several drug molecules have been discovered using AI-based techniques and tools, and several newly AI-discovered drug molecules have already entered clinical trials. In this review, we first present the data and their resources in the pharmaceutical sector for AI-driven drug discovery and illustrated some significant algorithms or techniques used for AI and ML which are used in this field. We gave an overview of the deep neural network (NN) models and compared them with artificial NNs. Then, we illustrate the recent advancement of the landscape of drug discovery using AI to deep learning, such as the identification of drug targets, prediction of their structure, estimation of drug-target interaction, estimation of drug-target binding affinity, design of de novo drug, prediction of drug toxicity, estimation of absorption, distribution, metabolism, excretion, toxicity; and estimation of drug-drug interaction. Moreover, we highlighted the success stories of AI-driven drug discovery and discussed several collaboration and the challenges in this area. The discussions in the article will enrich the pharmaceutical industry.

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Hand-held ultrasound devices have been widely used in the field of healthcare and power-efficient, real-time imaging is essential. This work presents the world's first ultrasound imaging processor supporting advanced modes, including vector flow imaging and elastography imaging. Plane-wave beamforming is utilized to ensure that the pulse repetition frequency (PRF) is sufficiently high for the advanced mode. The storage size and power consumption are minimized through algorithm-architecture co-optimization. The proposed plane-wave beamforming reduces the storage size of the required delay values by 43.7%. By exchanging the processing order, the storage size is reduced by 78.1% for elastography imaging. Parallel beamforming and interleaved firing are employed to achieve real-time imaging for all the supported modes. Fabricated in 40-nm CMOS technology, the proposed processor integrates 4.7M logic gates in core area of 3.24mm2. This work achieves a 20.3× higher beamforming rate with 5.3-to-29.1× lower power consumption than the state-of- the-art design. It also has 60% lower hardware complexity (in terms of gate count), in addition to the capability for supporting the advanced mode.

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The transcription factor PsrA regulates fatty acid metabolism, the type III secretion system, and quinolone signaling quorum sensing system in Pseudomonas aeruginosa. To explore additional roles of PsrA in P. aeruginosa, this study engineered a P. aeruginosa PAO1 strain to carry a recombinant plasmid with the psrA gene (pMMBpsrA) and examined the impact of elevated psrA expression to the bacterium. Transcriptomic analysis revealed that PsrA significantly downregulated genes encoding the master quorum-sensing regulators, RhlR and LasR, and influenced many quorum-sensing-associated genes. The role of PsrA in quorum sensing was further corroborated by testing autoinducer synthesis in PAO1 [pMMBpsrA] using two reporter bacteria strains Chromobacterium violaceum CV026 and Escherichia coli [pSB1075], which respond to short- and long-chain acyl homoserine lactones, respectively. Phenotypic comparisons of isogenic ΔpsrA, ΔlasR, and ΔpsrAΔlasR mutants revealed that the reduced elastase, caseinase, and swarming activity in PAO1 [pMMBpsrA] were likely mediated through LasR. Additionally, electrophoretic mobility shift assays demonstrated that recombinant PsrA could bind to the lasR promoter at a 5'-AAACGTTTGCTT-3' sequence, which displays moderate similarity to the previously reported consensus PsrA binding motif. Furthermore, the PsrA effector molecule oleic acid inhibited PsrA binding to the lasR promoter and restored several quorum sensing-related phenotypes to wild-type levels. These findings suggest that PsrA regulates certain quorum-sensing phenotypes by negatively regulating lasR expression, with oleic acid acting as a crucial signaling molecule.

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Padina minor is a seaweed rich in polysaccharides often used in food, feed, fertilizers, and antibacterial drugs. This study is the first to evaluate the effect of feeding zebrafish with Padina minor extract on preventing and treating C. albicans infections. This study evaluated the growth, survival, and disease resistance effects of P. minor extract on zebrafish. The fish were divided into four groups: three groups treated with 1%, 5%, or 10% P. minor extract and one untreated group (c, control). Subsequently, we analyzed how the extract affected the immune function of zebrafish infected with C. albicans. Based on the lethal concentration (LC50) calculated in the first stage, 1% was used as the effective therapeutic concentration. The results showed that the growth rate of the 1% feed group was the best, and no significant difference in survival rates between the four groups was observed. Feeding with 1% P. minor extract downregulated the expression of key inflammatory genes like tumor necrosis factor-alpha (TNF-α), interleukin-1ß (IL-1ß), and IL-10, effectively preventing and treating C. albicans infections in zebrafish. This study is a preliminary evaluation of the therapeutic efficacy of P. minor extracts against C. albicans.

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Tumor-to-normal ratio (T/N) measurement of 18F-FBPA is crucial for patient eligibility to receive boron neutron capture therapy. This study aims to compare the difference in standard uptake value ratios on brain tumors and normal brains using PET/MR ZTE and atlas-based attenuation correction with the current standard PET/CT attenuation correction. Regarding the normal brain uptake, the difference was not significant between PET/CT and PET/MR attenuation correction methods. The T/N ratio of PET/CT-AC, PET/MR ZTE-AC and PET/MR AB-AC were 2.34 ± 0.95, 2.29 ± 0.88, and 2.19 ± 0.80, respectively. The T/N ratio comparison showed no significance using PET/CT-AC and PET/MR ZTE-AC. As for the PET/MRI AB-AC, significantly lower T/N ratio was observed (- 5.18 ± 9.52%; p < 0.05). The T/N difference between ZTE-AC and AB-AC was also significant (4.71 ± 5.80%; p < 0.01). Our findings suggested PET/MRI imaging using ZTE-AC provided superior quantification on 18F-FBPA-PET compared to atlas-based AC. Using ZTE-AC on 18F-FBPA-PET /MRI might be crucial for BNCT pre-treatment planning.

Asunto(s)

Terapia por Captura de Neutrón de Boro , Neoplasias Encefálicas , Imagen por Resonancia Magnética , Tomografía Computarizada por Tomografía de Emisión de Positrones , Humanos , Terapia por Captura de Neutrón de Boro/métodos , Neoplasias Encefálicas/radioterapia , Neoplasias Encefálicas/diagnóstico por imagen , Femenino , Masculino , Imagen por Resonancia Magnética/métodos , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , Persona de Mediana Edad , Tomografía de Emisión de Positrones/métodos , Adulto , Anciano , Encéfalo/diagnóstico por imagen , Radioisótopos de Flúor , Compuestos de Boro , Fenilalanina/análogos & derivados

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Dietary emulsifiers are linked to various diseases. The recent discovery of the role of gut microbiota-host interactions on health and disease warrants the safety reassessment of dietary emulsifiers through the lens of gut microbiota. Lecithin, sucrose fatty acid esters, carboxymethylcellulose (CMC), and mono- and diglycerides (MDG) emulsifiers are common dietary emulsifiers with high exposure levels in the population. This study demonstrates that sucrose fatty acid esters and carboxymethylcellulose induce hyperglycemia and hyperinsulinemia in a mouse model. Lecithin, sucrose fatty acid esters, and CMC disrupt glucose homeostasis in the in vitro insulin-resistance model. MDG impairs circulating lipid and glucose metabolism. All emulsifiers change the intestinal microbiota diversity and induce gut microbiota dysbiosis. Lecithin, sucrose fatty acid esters, and CMC do not impact mucus-bacterial interactions, whereas MDG tends to cause bacterial encroachment into the inner mucus layer and enhance inflammation potential by raising circulating lipopolysaccharide. Our findings demonstrate the safety concerns associated with using dietary emulsifiers, suggesting that they could lead to metabolic syndromes.

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Disbiosis , Emulsionantes , Microbioma Gastrointestinal , Enfermedades Metabólicas , Animales , Disbiosis/inducido químicamente , Disbiosis/microbiología , Microbioma Gastrointestinal/efectos de los fármacos , Ratones , Masculino , Enfermedades Metabólicas/inducido químicamente , Enfermedades Metabólicas/microbiología , Enfermedades Metabólicas/metabolismo , Enfermedades Metabólicas/etiología , Ratones Endogámicos C57BL , Carboximetilcelulosa de Sodio , Sacarosa/efectos adversos , Sacarosa/administración & dosificación , Sacarosa/metabolismo , Resistencia a la Insulina , Lecitinas

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ABSTRACTIntentional forgetting of unwanted information is a crucial cognitive function that is often studied with directed forgetting (DF) procedure, whereby cuing some study materials with Forget (F) instruction impairs their memory compared to cuing with Remember (R) instruction. This study investigates how the nature of information (verbal or pictorial), its semantic significance (meaningful or meaningless), and the degree of prior episodic familiarity influence DF. Before the DF phase, stimuli were familiarised by pre-exposing them 0, 2, or 6 times in a prior preview phase. Finally, memory for all items was assessed with old/new recognition test. Experiment 1 employed words, Experiment 2 utilised fractal images, Experiment 3 featured both meaningful and meaningless object images, and Experiment 4 used words and nonwords. Our results indicate that materials that produced better memory performance are not always harder to intentionally forget. Previewed items showed reduced DF compared to non-previewed items regardless of the nature of information, and meaningless stimuli are challenging to intentionally forget regardless of their degrees of familiarisation unless they are meaningless verbal materials. Collectively, the results highlight the importance of joint consideration of the stimulus format, its meaningfulness, and its episodic familiarity in understanding conditions that interact with intentional forgetting.

Asunto(s)

Estimulación Luminosa , Reconocimiento en Psicología , Humanos , Reconocimiento en Psicología/fisiología , Masculino , Femenino , Adulto Joven , Adulto , Señales (Psicología) , Recuerdo Mental/fisiología , Semántica , Memoria Episódica

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Prussian blue analogues (PBAs) have gained tremendous attention as promising low-cost electrochemically-tunable electrode materials, which can accommodate large Na+ ions with attractive specific capacity and charge-discharge kinetics. However, poor cycling stability caused by lattice strain and volume change remains to be improved. Herein, metal-doping strategy has been demonstrated in FeNiHCF, Na1.40Fe0.90Ni0.10[Fe(CN)6]0.85 ⋅ 1.3H2O, delivering a capacity as high as 148 mAh g-1 at 10 mA g-1. At an exceptionally high rate of 25.6 A g-1, a reversible capacity of ~55 mAh g-1 still can be obtained with a very small capacity decay rate of 0.02 % per cycle for 1000 cycles, considered one of the best among all metal-doped PBAs. This exhibits the stabilizing effect of Ni doping which enhances structural stability and long-term cyclability. In situ synchrotron X-ray diffraction reveals an extremely small (~1 %) change in unit cell parameters. The Ni substitution is found to increase the electronic conductivity and redox activity, especially at the low-spin (LS) Fe center due to inductive effect. This larger capacity contribution from LS Fe2+C6/Fe3+C6 redox couple is responsible for stable high-rate capability of FeNiHCF. The insight gained in this work may pave the way for the design of other high-performance electrode materials for sustainable sodium-ion batteries.

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The chemical screening of an octocoral identifed as Junceella fragilis has led to the isolation of five chlorinated briarane-type diterpenoids, including three known metabolites, gemmacolide X (1), frajunolide I (2), and fragilide F (3), along with two new analogs, 12α-acetoxyfragilide F (4) and 12α-acetoxyjunceellin (5). Single-crystal X-ray diffraction analysis was carried out to determine the absolute configurations of 1 and 2, while the structures of new compounds 4 and 5 were ascertained with 2D NMR experiments. Briaranes 1 and 3-5 were active in enhancing alkaline phosphatase (ALP) activity.

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OBJECTIVE: Postoperative pain remains one of the most common complaints after surgery, and appropriate treatments are limited. METHODS: We therefore investigated the effect of the anti-nociceptive properties of magnesium sulfate (MgSO4), an N-methyl-D-aspartate (NMDA) receptor antagonist, on incision-induced postoperative pain and peripheral and central nervous system inflammation. RESULTS: We found that local MgSO4 administration dose-dependently increases paw withdrawal latency, indicating reduced peripheral postoperative pain. Furthermore, MgSO4 inhibited the expression of interleukin-1ß (IL-1ß) and inducible nitric oxide synthase (iNOS) and phosphorylation of the NMDA receptor NR1 subunit in injured paw tissue and significantly attenuated microglial and astrocytic activation in the ipsilateral lumbar spinal cord dorsal horn. CONCLUSION: Locally administered MgSO4 has potential for development as an adjunctive therapy for preventing central nociceptive sensitization.

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Inflamación , Sulfato de Magnesio , Nocicepción , Dolor Postoperatorio , Ratas Sprague-Dawley , Animales , Sulfato de Magnesio/farmacología , Sulfato de Magnesio/administración & dosificación , Masculino , Nocicepción/efectos de los fármacos , Dolor Postoperatorio/tratamiento farmacológico , Dolor Postoperatorio/metabolismo , Inflamación/tratamiento farmacológico , Inflamación/metabolismo , Ratas , Modelos Animales de Enfermedad , Médula Espinal/efectos de los fármacos , Médula Espinal/metabolismo , Receptores de N-Metil-D-Aspartato/metabolismo , Receptores de N-Metil-D-Aspartato/antagonistas & inhibidores , Sensibilización del Sistema Nervioso Central/efectos de los fármacos , Sensibilización del Sistema Nervioso Central/fisiología , Microglía/efectos de los fármacos , Microglía/metabolismo , Analgésicos/farmacología , Analgésicos/administración & dosificación , Interleucina-1beta/metabolismo , Óxido Nítrico Sintasa de Tipo II/metabolismo

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Parkinson's disease (PD) is a common neurodegenerative disorder characterized by the gradual loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc), resulting in reduced dopamine levels in the striatum and eventual onset of motor symptoms. Linalool (3,7-dimethyl-1,6-octadien-3-ol) is a monoterpene in aromatic plants exhibiting antioxidant, antidepressant, and anti-anxiety properties. The objective of this study is to evaluate the neuroprotective impacts of linalool on dopaminergic SH-SY5Y cells, primary mesencephalic and cortical neurons treated with 1-methyl-4-phenylpyridinium ion (MPP+), as well as in PD-like mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Cell viability, α-tubulin staining, western blotting, immunohistochemistry and behavioral experiments were performed. In MPP+-treated SH-SY5Y cells, linalool increased cell viability, reduced neurite retraction, enhanced antioxidant defense by downregulation of apoptosis signaling (B-cell lymphoma 2 (Bcl-2), cleaved caspase-3 and poly ADP-ribose polymerase (PARP)) and phagocyte NADPH oxidase (gp91phox), as well as upregulation of neurotrophic signaling (brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF)) and nuclear factor-erythroid 2 related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway. In MPP+-treated primary mesencephalic neurons, linalool enhanced the expressions of tyrosine hydroxylase (TH), Sirtuin 1 (SirT1), and parkin. In MPP+-treated primary cortical neurons, linalool upregulated protein expression of SirT1, γ-Aminobutyric acid type A-α1 (GABAA-α1), and γ-Aminobutyric acid type B (GABAB). In PD-like mice, linalool attenuated the loss of dopamine neurons in SNpc. Linalool improved the motor and nonmotor behavioral deficits and muscle strength of PD-like mice. These findings suggest that linalool potentially protects dopaminergic neurons and improves the impairment symptoms of PD.

Asunto(s)

Monoterpenos Acíclicos , Neuroblastoma , Fármacos Neuroprotectores , Enfermedad de Parkinson , Humanos , Ratones , Animales , Enfermedad de Parkinson/metabolismo , Neuronas Dopaminérgicas/metabolismo , Antioxidantes/metabolismo , Odorantes , Sirtuina 1/metabolismo , Fármacos Neuroprotectores/farmacología , Neuroblastoma/metabolismo , 1-Metil-4-fenilpiridinio , Fuerza Muscular , Modelos Teóricos , Ácido gamma-Aminobutírico/metabolismo

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BACKGROUND: Whole-body magnetic resonance imaging (WB-MRI) has emerged as a valuable tool for cancer detection. This study evaluated the prevalence rates of cancer in asymptomatic individuals undergoing WB-MRI according to the Oncologically Relevant Findings Reporting and Data System (ONCO-RADS) classifications in order to assess the reliability of the classification method. METHODS: We retrospectively enrolled 2064 asymptomatic individuals who participated in a WB-MRI cancer screening program between 2017 and 2022. WB-MRI was acquired on a 3-T system with a standard protocol, including regional multisequence and gadolinium-based contrast agent-enhanced oncologic MRI. Results of further examinations, including additional imaging and histopathology examinations, performed at our institute were used to validate the WB-MRI findings. Two radiologists blinded to the clinical outcome classified the WB-MRI findings according to the ONCO-RADS categories as follows: 1 (normal), 2 (benign finding highly likely), 3 (benign finding likely), 4 (malignant finding likely), and 5 (malignant finding highly likely). Firth logistic regression analysis was performed to determine the associations between participant characteristics and findings of ONCO-RADS category ≥ 4. RESULTS: Of the 2064 participants with median age of 55 years, 1120 (54.3%) were men, 43 (2.1%) had findings of ONCO-RADS category ≥ 4, and 24 (1.2%) had confirmed cancer. The cancer prevalence rates were 0.1%, 5.4%, 42.9%, and 75% for ONCO-RADS categories 2, 3, 4, and 5, respectively. In the multivariable model, older age (OR: 1.035, p = 0.029) and history of hypertension (OR: 2.051, p = 0.026), hepatitis B carrier (OR: 2.584, p = 0.013), or prior surgery (OR: 3.787, p < 0.001) were independently associated with the findings for ONCO-RADS category ≥ 4. CONCLUSIONS: The ONCO-RADS categories for cancer risk stratification were validated and found to be positively correlated with cancer risk. The application of ONCO-RADS facilitates risk-based management after WB-MRI for cancer screening.

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Detección Precoz del Cáncer , Neoplasias , Masculino , Humanos , Persona de Mediana Edad , Femenino , Estudios Retrospectivos , Detección Precoz del Cáncer/métodos , Imagen por Resonancia Magnética/métodos , Reproducibilidad de los Resultados , Imagen de Cuerpo Entero/métodos , Neoplasias/diagnóstico por imagen , Neoplasias/epidemiología

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INTRODUCTION: The population of Taiwan has a long history of ethno-cultural evolution. The Taiwanese population was isolated from other large populations such as the European, Han Chinese, and Japanese population. The Taiwan Biobank (TWB) project has built a nationwide database, particularly for personal whole-genome sequence (WGS) to facilitate basic and clinical collaboration nationally and internationally, making it one of the most valuable public datasets of the East Asian population. OBJECTIVES: This study provides comprehensive medical genomic findings from TWB WGS data, for better characterization of disease susceptibility and the choice of ideal treatment regimens in Taiwanese population. METHODS: We reanalyzed 1496 WGS using a PrecisionFDA Truth challenge winner method Sentieon DNAscope. Single nucleotide variants (SNV) and small insertions/deletions (INDEL) were benchmarked. We also analyzed pharmacogenomic (PGx) drug-associated alleles, and copy number variants (CNV). Multiple practicing clinicians reviewed and curated the clinically significant variants. Variant annotations can be browsed at TaiwanGenomes (https://genomes.tw). RESULTS: We found that each participant had an average of 6,870.7 globally novel variants and 75.3% (831/1103) of the participants harbored at least one PharmGKB-selected high evidence level human leukocyte antigen (HLA) risk allele. 54 PharmGKB-reported high-level instances of evidence of Cytochrome P450 variant-drug pairs, with a population frequency of over 13.2%. We also identified 23 variants in the ACMG secondary finding V3 gene list from 25 participants, suggesting that 1.67% (25/1496) of the population is harboring at least one medical actionable variant. Our carrier status analyses suggest that one in 25 couples (3.94%) would risk having offspring with at least one pathogenic variant, which is in line with rates found in Japan and Singapore. For pathogenic CNV, we detected 6.88% and 2.02% carrier rates for alpha thalassemia and spinal muscular atrophy, respectively. CONCLUSION: Our study highlights the overall medical insights of a complete Taiwanese genomic profile.

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Background: Older Chinese immigrants constitute the largest older Asian ethnic population in New Zealand. Aging in a foreign land can be complex, presenting increasing challenges for gerontology scholars, practitioners, and policy makers. Older Chinese immigrants are more susceptible to experiencing loneliness and social isolation compared to native older people, primarily due to language, transportation, and cultural barriers. These factors subsequently impact their physical and mental health. With advancements in robotic technology, aged care robots are being applied to support older people with their daily living needs. However, studies on using robots with older immigrants living in the community are sparse. Their preferences for the appearance and function of aged care robots are unclear, which impacts the acceptance and usability of robots, highlighting the need for a user-centered design approach. Objective: This study aims to explore older Chinese immigrants' needs and preferences toward the appearance and function of aged care robots and to examine their relationships with the demographic characteristics of participants. Methods: A cross-sectional design was used in this study, which was undertaken between March and May 2020. A total of 103 participants completed a web-based survey. Results: The average age of participants was 68.7 (SD 5.5) years. The results suggest that 41.7% (n=43) of the 103 participants preferred a humanlike adult appearance, while 32% (n=33) suggested an animallike appearance. These participants reported higher scores in both rigorousness and friendliness compared to others who preferred different robot appearances. Participants expressed a greater preference for the functions of housework assistance (n=86, 83.5%), language translation (n=79, 76.7%), health monitoring (n=78, 75.7%), facial expressions (n=77, 74.8%), news reading (n=66, 64.1%), and security monitoring (n=65, 63.1%). These preferences were found to be significantly associated with marital status, financial status, and duration of immigration. Conclusions: To support immigrant populations to age well in a foreign country and address the growing shortage of health and social professionals, it is important to develop reliable robotic technology services that are tailored based on the needs and preferences of individuals. We collected and compared the perspectives of immigrant and nonimmigrant participants on using robots to support aging in place. The results on users' needs and preferences inform robotic technology services, indicating a need to prioritize older Chinese immigrants' preference toward aged care robots that perform housework assistance, language translation, and health and safety monitoring, and robots with humanlike features.

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BACKGROUND/AIM: Autosomal dominant polycystic kidney disease (ADPKD) is a prevalent genetic disorder primarily caused by mutations in Pkd1 (PC1), which account for the majority of ADPKD cases. These mutations contribute to the formation of cysts in the kidneys and other organs, ultimately leading to renal failure. Unfortunately, there are currently no available preventive treatments for this disease. MATERIALS AND METHODS: In this study, we utilized Pkd1-knockdown mice and cells to investigate the potential involvement of O-GlcNAcylation in the progression of PKD. Additionally, we examined the effects of thiamet G, an inhibitor of O-GlcNAcase (OGA), on PKD mice. RESULTS: Our findings indicate that both O-GlcNAcylation and OGT (O-GlcNAc transferase) were downregulated in the renal tissues of Pkd1-silenced mice. Furthermore, O-GlcNAcylation was shown to regulate the stability and function of the C-terminal cytoplasmic tail (CTT) of PC1. Treatment of PKD mice with thiamet G resulted in a reduction of renal cytogenesis in these animals. CONCLUSION: These results highlight the unique role of O-GlcNAcylation in the development of cyst formation in PKD and propose it as a potential therapeutic target for the treatment of PKD.

Asunto(s)

Enfermedades Renales Poliquísticas , Riñón Poliquístico Autosómico Dominante , Ratones , Animales , Riñón Poliquístico Autosómico Dominante/tratamiento farmacológico , Riñón Poliquístico Autosómico Dominante/genética , Enfermedades Renales Poliquísticas/tratamiento farmacológico , Enfermedades Renales Poliquísticas/genética , Riñón

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BACKGROUND AND AIMS: Peptic ulcer recurrent bleeding occurs in 20% to 30% of patients after standard endoscopic hemostasis, particularly within 4 days after the procedure. The application of additional tranexamic acid (TXA) to the ulcer may enhance hemostasis. This study investigated the effectiveness of TXA powder application on bleeding ulcers during endoscopic hemostasis. METHODS: This study enrolled patients who had peptic ulcer bleeding between March 2022 and February 2023. After undergoing standard endoscopic therapy, the patients were randomly assigned to either the TXA group or the standard group. In the TXA group, an additional 1.25 g of TXA powder was sprayed endoscopically on the ulcer. Both groups then received 3 days of high-dose (8 mg/h) continuous infusion proton pump inhibitor therapy. Second-look endoscopy was conducted on days 3 to 4. The primary end point of early treatment failure was defined as ulcer recurrent bleeding within 4 days or major stigmata of recent hemorrhage on the second-look endoscopy. RESULTS: Sixty patients (30 in each group) with peptic ulcer bleeding and balanced baseline characteristics were randomly assigned to a treatment group. The early treatment failure rate was lower in the TXA group (6.7%) than in the standard group (30%) (P = .042). The freedom from treatment failure periods for 4 and 28 days was significantly longer in the TXA group than in the standard group (P = .023). No adverse events from TXA were recorded. CONCLUSIONS: The precise delivery of topical TXA alongside standard endoscopic hemostasis reduced the early treatment failure rate in patients with bleeding peptic ulcers. (Clinical trial registration number: NCT05248321.).

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Acute pancreatitis is a common disease, but peripancreatic pseudoaneurysm is rare. Bleeding from peripancreatic pseudoaneurysm without connection to GI tract may delay treatment and cause mortality. Being aware of this rare complication after acute pancreatitis is important.

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SCOPE: The aging biomarkers are alternatives and none of them can act as a strong predictor of frailty during the progression of aging. Several studies reveal the relationship between metabolites and frailty or gut microbiota and frailty. However, the connection between metabolites and gut microbiota in non-robust older adults has not been discussed yet. The study aims to combine the findings of serum metabolites and gut microbiota in non-robust subjects as a possible diagnostic biomarker. METHODS AND RESULTS: Frailty-related assessments are conducted to ensure the discrimination of non-robustness. The serum and fecal are collected for serum metabolomics and gut microbiota analysis. Robust and non-robust subjects show very different gut microbial compositions. Among the gut microbial differences, Escherichia/Shigella and its higher taxonomic ranks are found to have the most discriminative abundance among compared groups. More importantly, the abundance of Escherichia/Shigella is found to be positively correlated (p < 0.05) with the level of discriminant metabolites, such as serum oxoglutarate, glutamic acid, and 1-methyladenosine. CONCLUSION: These results indicate the obvious interrelation between gut microbiota and serum metabolites in non-robust older adults. Besides, the findings suggest that Escherichia/Shigella can be a potential biomarker candidate for robustness sub-phenotypic identification.

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Fragilidad , Microbioma Gastrointestinal , Humanos , Anciano , Estudios Transversales , Envejecimiento , Heces , Biomarcadores , ARN Ribosómico 16S