GPR55 Antagonist CID16020046 Attenuates Obesity-Induced Airway Inflammation by Suppressing Chronic Low-Grade Inflammation in the Lungs.

GPR55 is a receptor for lysophosphatidylinositols (LPIs) in digestive metabolites. Overnutrition leads to obesity, insulin resistance, and increased LPI levels in the plasma. The involvement of LPIs and GPR55 in adiposity, hepatic steatosis, and atherosclerosis has been previously elucidated. However, the therapeutic efficacy of GPR55 antagonists against obesity-induced airway inflammation has not been studied. The present study investigated whether CID16020046, a selective antagonist of GPR55, could modulate obesity-induced airway inflammation caused by a high-fat diet (HFD) in C57BL/6 mice. Administration of CID16020046 (1 mg/kg) inhibits HFD-induced adiposity and glucose intolerance. Analysis of immune cells in BALF showed that CID16020046 inhibited HFD-induced increase in immune cell infiltration. Histological analysis revealed the HFD induced hypersecretion of mucus and extensive fibrosis in the lungs. CID16020046 inhibited these HFD-induced pathological features. qRT-PCR revealed the HFD-induced increase in the expression of Ifn-γ, Tnf-α, Il-6, Il-13, Il-17A, Il-1ß, Nlrp3, and Mpo mRNAs in the lungs. CID16020046 inhibited the HFD-induced increases in these genes. The expression levels of adipokines were regulated by the HFD and CID16020046. AdipoQ in the lungs and gonadal white adipose tissue was decreased by the HFD and reversed by CID16020046. In contrast, Lep was increased by the HFD and suppressed by CID16020046. The findings suggest the potential application of the GPR55 antagonist CID16020046 in obesity-induced airway inflammation.

Effects of Dietary Protein Intake Levels on Peripheral Circadian Rhythm in Mice.

The regulation of the circadian clock plays an important role in influencing physiological conditions. While it is reported that the timing and quantity of energy intake impact circadian regulation, the underlying mechanisms remain unclear. This study investigated the impact of dietary protein intake on peripheral clocks. Firstly, transcriptomic analysis was conducted to investigate molecular targets of low-protein intake. Secondly, mPer2::Luc knock-in mice, fed with either a low-protein, normal, or high-protein diet for 6 weeks, were analyzed for the oscillation of PER2 expression in peripheral tissues and for the expression profiles of circadian and metabolic genes. Lastly, the candidate pathway identified by the in vivo analysis was validated using AML12 cells. As a result, using transcriptomic analysis, we found that the low-protein diet hardly altered the circadian rhythm in the central clock. In animal experiments, expression levels and period lengths of PER2 were different in peripheral tissues depending on dietary protein intake; moreover, mRNA levels of clock-controlled genes and endoplasmic reticulum (ER) stress genes were affected by dietary protein intake. Induction of ER stress in AML12 cells caused an increased amplitude of Clock and Bmal1 and an advanced peak phase of Per2. This result shows that the intake of different dietary protein ratios causes an alteration of the circadian rhythm, especially in the peripheral clock of mice. Dietary protein intake modifies the oscillation of ER stress genes, which may play key roles in the regulation of the circadian clock.

Clinical evaluation of a one-piece polyetheretherketone removable partial denture fabricated using a novel digital workflow: A self-controlled clinical trial.

PURPOSE: To explore the clinical application of one-piece polyetheretherketone (PEEK) removable partial dentures (RPDs) fabricated using a novel digital workflow and to evaluate their weights and fits in vivo and patient satisfaction. MATERIALS AND METHODS: Fifteen cases with posterior partially edentulous situations were selected, and each patient received two types of RPDs, including a novel digital workflow (test group) and a conventional workflow (control group). For the test group, one-piece RPDs were designed through three-dimensional (3D) methods by scanning stone casts and fabricated by milling PEEK discs. Each RPD was weighed. The gaps between the oral tissue and RPDs in each group were duplicated using a polyvinylsiloxane (PVS) replica and measured by 3D analysis. A visual analog scale (VAS) was used to evaluate the patient's satisfaction. Paired t-tests were used to compare the differences in the weight, the gaps of each RPD, and VAS values between the two groups. One-way analysis of variance tests was used to compare the differences in the gap among different components in each group. RESULTS: The RPD in the test group weighed less than that in the control group (p < 0.01). No statistically significant differences in the gaps of denture bases and rests (p > 0.05) were found between the two groups, but the gaps of major connectors in the test group were significantly smaller than in the control group (p < 0.05). The VAS scores for comfortableness and masticatory efficiency were not significantly different between the two groups (p > 0.05) but the scores for the aesthetic appearance of the clasps in the test group were significantly higher than that in the control group (p < 0.05). CONCLUSIONS: One-piece PEEK RPDs manufactured using a novel digital workflow weighed less than conventional RPDs and exhibited a clinically acceptable internal fit. Although the aesthetic appearance of the PEEK clasps was superior to the control, there is still room for improvement.

Incidence and Characteristics of Multiple Primary Cancers: A 20-Year Retrospective Study of a Single Cancer Center in Korea.

Rising cancer survival rates have led to an increased risk of multiple primary cancers (MPCs). Data on MPCs in South Korea are limited. This study aimed to address incidence and clinical characteristics of MPCs in a single cancer center in Korea during a 20-year period. We retrospectively analyzed 96,174 cancer patients at the Korea Cancer Center Hospital between 2003 and 2022, identifying 2167 patients with metachronous MPCs based on Surveillance, Epidemiology, and End Results SEER criteria. We categorized patients by cancer type (15 major solid cancer groups and 3 major hematologic cancer groups), including pathological diagnosis, assessed latency periods, and relative risks (RRs) for developing MPCs. The overall MPC incidence was 2.3%. Breast cancer (15.7%) was the most common primary cancer, and lung cancer (15.2%) was the most frequent second primary cancer. The median latency period for second primary cancers was 4.1 years. Decreasing latency periods for third and fourth primary cancers were observed (2.1 years and 1.6 years, respectively). Most cancers maintained their dominant pathological type despite notable changes in the prevalence of specific pathologies for certain types of second primaries. Lymphoma showed the highest RR (2.1) for developing MPCs. Significant associations were found between specific primary and subsequent cancers, including breast-ovary, thyroid-breast, stomach-pancreas, colorectal-head and neck, lung-prostate, and lymphoma-myeloid neoplasms. These findings contribute to a better understanding of MPC occurrence. They can inform future research on their etiology and development of improved management strategies.

Factors Associated With Continuous Use of a Cancer Education Metaverse Platform: Mixed Methods Study.

BACKGROUND: Early detection of cancer and provision of appropriate treatment can increase the cancer cure rate and reduce cancer-related deaths. Early detection requires improving the cancer screening quality of each medical institution and enhancing the capabilities of health professionals through tailored education in each field. However, during the COVID-19 pandemic, regional disparities in educational infrastructure emerged, and educational accessibility was restricted. The demand for remote cancer education services to address these issues has increased, and in this study, we considered medical metaverses as a potential means of meeting these needs. In 2022, we used Metaverse Educational Center, developed for the virtual training of health professionals, to train radiologic technologists remotely in mammography positioning. OBJECTIVE: This study aims to investigate the user experience of the Metaverse Educational Center subplatform and the factors associated with the intention for continuous use by focusing on cases of using the subplatform in a remote mammography positioning training project. METHODS: We conducted a multicenter, cross-sectional survey between July and December 2022. We performed a descriptive analysis to examine the Metaverse Educational Center user experience and a logistic regression analysis to clarify factors closely related to the intention to use the subplatform continuously. In addition, a supplementary open-ended question was used to obtain feedback from users to improve Metaverse Educational Center. RESULTS: Responses from 192 Korean participants (male participants: n=16, 8.3%; female participants: n=176, 91.7%) were analyzed. Most participants were satisfied with Metaverse Educational Center (178/192, 92.7%) and wanted to continue using the subplatform in the future (157/192, 81.8%). Less than half of the participants (85/192, 44.3%) had no difficulty in wearing the device. Logistic regression analysis results showed that intention for continuous use was associated with satisfaction (adjusted odds ratio 3.542, 95% CI 1.037-12.097; P=.04), immersion (adjusted odds ratio 2.803, 95% CI 1.201-6.539; P=.02), and no difficulty in wearing the device (adjusted odds ratio 2.020, 95% CI 1.004-4.062; P=.049). However, intention for continuous use was not associated with interest (adjusted odds ratio 0.736, 95% CI 0.303-1.789; P=.50) or perceived ease of use (adjusted odds ratio 1.284, 95% CI 0.614-2.685; P=.51). According to the qualitative feedback, Metaverse Educational Center was useful in cancer education, but the experience of wearing the device and the types and qualities of the content still need to be improved. CONCLUSIONS: Our results demonstrate the positive user experience of Metaverse Educational Center by focusing on cases of using the subplatform in a remote mammography positioning training project. Our results also suggest that improving users' satisfaction and immersion and ensuring the lack of difficulty in wearing the device may enhance their intention for continuous use of the subplatform.

Effects of photobiomodulation on colon cancer cell line HT29 according to mitochondria.

BACKGROUND/AIM: Although photobiomodulation therapy (PBMt) is available to alleviate post-operative side effects of malignant diseases, its application is still controversial due to some potential of cancer recurrence and occurrence of a secondary malignancy. We investigated effect of PBMt on mitochondrial function in HT29 colon cancer cells. METHODS: HT29 cell proliferation was determined with MTT assay after PBMt. Immunofluorescent staining was performed to determine mitochondrial biogenesis and reactive oxygen species (ROS). Mitochondrial membrane potential was measured with Mitotracker. Western blotting was executed to determine expression of fission, fusion, UCP2, and cyclin B1 and D1 proteins. In vivo study was performed by subcutaneously inoculating cancer cells into nude mice and immunohistochemistry was done to determine expression of FIS1, MFN2, UCP2, and p-AKT. RESULTS: The proliferation and migration of HT29 cells reached maximum with PBMt (670 nm, light emitting diode, LED) at 2.0 J/cm2 compared to control (P < 0.05) with more expression of cyclin B1 and cyclin D1 (P < 0.05). Immunofluorescent staining showed that ROS and mitochondrial membrane potential were enhanced after PBMt compared to control. ATP synthesis of mitochondria was also higher in the PBMt group than in the control (P < 0.05). Expression levels of fission and fusion proteins were significantly increased in the PBMt group than in the control (P < 0.05). Electron microscopy revealed that the percentage of mitochondria showing fission was not significantly different between the two groups. Oncometabolites including D-2-hydoxyglutamate in the supernatant of cell culture were higher in the PBMt group than in the control with increased UCP2 expression (P < 0.05). Both tumor size and weight of xenograft in nude mice model were bigger and heavier in the PBMt group than in the control (P < 0.05). Immunohistologically, mitochondrial biogenesis proteins UCP2 and p-AKT in xenograft of nude mice were expressed more in the PBMt group than in the control (P < 0.05). CONCLUSIONS: Treatment with PBM using red light LED may induce proliferation and progression of HT29 cancer cells by increasing mitochondrial activity and fission.

Evaluating myelophil, a 30% ethanol extract of Astragalus membranaceus and Salvia miltiorrhiza, for alleviating fatigue in long COVID: a real-world observational study.

Background: Persistent post-infectious symptoms, predominantly fatigue, characterize Long COVID. This study investigated the efficacy of Myelophil (MYP), which contains metabolites extracted from Astragalus membranaceus and Salvia miltiorrhiza using 30% ethanol, in alleviating fatigue among subjects with Long COVID. Methods: In this prospective observational study, we enrolled subjects with significant fatigue related to Long COVID, using criteria of scores of 60 or higher on the modified Korean Chalder Fatigue scale (mKCFQ11), or five or higher on the Visual Analog Scale (VAS) for brain fog. Utilizing a single-arm design, participants were orally administered MYP (2,000 mg daily) for 4 weeks. Changes in fatigue severity were assessed using mKCFQ11, Multidimensional Fatigue Inventory (MFI-20), and VAS for fatigue and brain fog. In addition, changes in quality of life using the short form 12 (SF-12) were also assessed along with plasma cortisol levels. Results: A total of 50 participants (18 males, 32 females) were enrolled; 49 were included in the intention-to-treat analysis with scores of 66.9 ± 11.7 on mKCFQ11 and 6.3 ± 1.5 on the brain fog VAS. After 4 weeks of MYP administration, there were statistically significant improvements in fatigue levels: mKCFQ11 was measured at 34.8 ± 17.1 and brain fog VAS at 3.0 ± 1.9. Additionally, MFI-20 decreased from 64.8 ± 9.8 to 49.3 ± 10.8, fatigue VAS dropped from 7.4 ± 1.0 to 3.4 ± 1.7, SF-12 scores rose from 53.3 ± 14.9 to 78.6 ± 14.3, and plasma cortisol levels also elevated from 138.8 ± 50.1 to 176.9 ± 62.0 /mL. No safety concerns emerged during the trial. Conclusion: Current findings underline MYP's potential in managing Long COVID-induced fatigue. However, comprehensive studies remain imperative. Clinical Trial Registration: https://cris.nih.go.kr, identifier KCT0008948.

Factors Affecting Life-Sustaining Treatment Decisions and Changes in Clinical Practice after Enforcement of the Life-Sustaining Treatment Decision (LST) Act: A Tertiary Hospital Experience in Korea.

Purpose: In Korea, the act on hospice and palliative care and decisions on life-sustaining treatment (LST) was implemented on February 4, 2018. We aimed to investigate relevant factors and clinical changes associated with LST decisions after law enforcement. Materials and Methods: This single-center retrospective study included patients who completed LST documents using legal forms at Asan Medical Center from February 5, 2018, to June 30, 2020. Results: 5896 patients completed LST documents, of which 2704 (45.8%) signed the documents in person, while family members of 3,192 (54%) wrote the documents on behalf of the patients. Comparing first year and following year of implementation of the act, the self-documentation rate increased (43.9% to 47.2%, p=0.014). Moreover, the number of LST decisions made during or after ICU admission decreased (37.8% vs. 35.2%, p=0.045), and the completion rate of LST documents during chemotherapy increased (6.6% vs. 8.9%, p=0.001). In multivariate analysis, age < 65 (OR, 1.724; 95% CI, 1.538-1.933; p<0.001), unmarried status (OR, 1.309; 95% CI, 1.097-1.561; p=0.003), palliative care consultation (OR, 1.538; 95% CI, 1.340-1.765; p<0.001), malignancy (OR, 1.864; 95% CI, 1.628-2.133; p<0.001), and changes in timing on the first year versus following year (OR, 1.124, 95% CI, 1.003-1.260, p=0.045) were related to a higher self-documentation rate. Conclusion: Age < 65, unmarried status, malignancy, and referral to a palliative care team were associated with patients making LST decisions themselves. Furthermore, the subject and timing of LST decisions have changed with the LST act.

Lactiplantibacillus argentoratensis AGMB00912 alleviates salmonellosis and modulates gut microbiota in weaned piglets: a pilot study.

This study aimed to evaluate the efficacy of Lactiplantibacillus argentoratensis AGMB00912 (LA) in reducing Salmonella Typhimurium infection in weaned piglets. The investigation focused on the influence of LA on the gut microbiota composition, growth performance, and Salmonella fecal shedding. The results indicated that LA supplementation significantly improved average daily gain and reduced the prevalence and severity of diarrhea. Fecal analysis revealed reduced Salmonella shedding in the LA-supplemented group. Furthermore, LA notably altered the composition of the gut microbiota, increasing the levels of beneficial Bacillus and decreasing those of harmful Proteobacteria and Spirochaetes. Histopathological examination showed less intestinal damage in LA-treated piglets than in the controls. The study also observed that LA affected metabolic functions related to carbohydrate, amino acid, and fatty acid metabolism, thereby enhancing gut health and resilience against infection. Short-chain fatty acid concentrations in the feces were higher in the LA group, suggesting improved gut microbial activity. LA supplementation enriched the population of beneficial bacteria, including Streptococcus, Clostridium, and Bifidobacterium, while reducing the number of harmful bacteria, such as Escherichia and Campylobacter. These findings indicate the potential of LA as a probiotic alternative for swine nutrition, offering protective effects to the gut microbiota against Salmonella infection.

The impact of assisted reproductive technologies on ADHD: A systematic review and meta-analysis.

BACKGROUND: The escalating utilization of assisted reproductive technology (ART) in response to global infertility rates has spurred research into its complications. Short-term and long-term outcomes have been extensively studied, particularly the neurological concerns surrounding attention-deficit/hyperactivity disorder (ADHD) among ART-conceived children. This study aims investigate the association between ART and ADHD. METHODS: Medline, Embase, Scopus, and Web of Science databases were searched through April 4, 2023. Cohort, case-control, and cross-sectional studies were eligible for inclusion. primary summary measures included the unadjusted relative risk (RR) and adjusted hazard ratio (HR) with 95 % confidence intervals. Both fixed-effects and random-effects models were utilized for meta-analysis data pooling to determine the overall effect size. The onset of ADHD in children conceived through ART compared to those conceived naturally. RESULTS: The systematic search yielded 8 studies with 10,176,148 individuals included in the meta-analysis. The meta-analysis revealed a pooled RR of 0.93 (0.68-1.26) for cohort studies and a pooled RR of 0.97 (0.41-2.29) for cross-sectional studies, along with a pooled HR of 1.08 (1.03-1.13) for ADHD in the ART group compared to the non-ART group. CONCLUSION: While this study identifies some potential association between ART and ADHD, the limited effect size and inherent heterogeneity underscore the need for cautious interpretation.

Lack of association between early on-treatment HBeAg seroclearance and development of hepatocellular carcinoma or decompensated cirrhosis.

Background & Aims: The association between hepatitis B envelope antigen (HBeAg) seroclearance during long-term nucleos(t)ide analogue (NA) treatment and the risk of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB) remains unclear. Here, we aimed to investigate the association of HBeAg seroclearance during potent NA treatment with the development of HCC and decompensated cirrhosis. Methods: Using a multicenter historical cohort including 2,392 non-cirrhotic adult patients with HBeAg-positive CHB who initiated NA treatment with tenofovir or entecavir, the risk of HCC and decompensated cirrhosis was compared between patients who achieved HBeAg seroclearance within 36 months of NA treatment (the HBeAg-loss group) and those who did not (the HBeAg-maintained group), using inverse probability of treatment weighting. Results: Over a median of 6.6 years of NA treatment, 1,077 patients achieved HBeAg seroclearance (HBeAg loss rate = 6.0 per 100 person-years), 64 patients developed HCC (HCC incidence rate = 0.39 per 100 person-years), and 46 patients developed decompensated cirrhosis (decompensation incidence rate = 0.28 per 100 person-years). The HBeAg-loss and HBeAg-maintained groups had a similar risk of developing HCC (hazard ratio 0.89; 95% CI 0.47-1.68; p = 0.72) and decompensated cirrhosis (hazard ratio 0.98; 95% CI 0.48-1.81; p = 0.91). Compared with delayed HBeAg seroclearance beyond 10 years of NA treatment, the risk of HCC was comparable in those who achieved earlier HBeAg seroclearance at any time point within 10 years, regardless of baseline age and fibrotic burden. Conclusions: Early HBeAg seroclearance during NA treatment was not associated with a reduced risk of development of HCC or decompensated cirrhosis in non-cirrhotic HBeAg-positive patients with CHB. Impact and implications: The association between hepatitis B envelope antigen (HBeAg) seroclearance during long-term nucleos(t)ide analogue treatment and the risk of hepatocellular carcinoma in patients with chronic hepatitis B remains unclear. Our findings indicate that early on-treatment HBeAg seroclearance within 3 years was not associated with the development of hepatocellular carcinoma or decompensated cirrhosis. Achieving HBeAg seroclearance may not be an appropriate surrogate endpoint for preventing the development of liver-related outcomes in non-cirrhotic patients with HBeAg-positive chronic hepatitis B treated with nucleos(t)ide analogues.

Exploring the potential effect of electroacupuncture on cardiovascular function and lipid profiles in spontaneously hypertensive rats.

Background: Investigating the effects of electroacupuncture (EA) treatment on cardiovascular function and aortic lipid profiles in spontaneously hypertensive rats (SHR) constitutes the foundational focus of this study. The overarching goal is to comprehensively elucidate the alterations brought about by EA treatment and to assess its potential as an alternative therapy for hypertension. Methods: Consecutive EA treatments were administered to SHR, and the effects on systolic blood pressure, cardiac function, and hypertension-related neuronal signals were assessed. Aortic lipid profiles in vehicle-treated SHR and EA-treated SHR groups were analyzed using mass spectrometry-based lipid profiling. Additionally, the expression of Cers2 and GNPAT, enzymes involved in the synthesis of specific aortic lipids, was examined. Results: The study demonstrated that consecutive EA treatments restored systolic blood pressure, improved cardiovascular function, and normalized hypertension-related neuronal signals in SHR. Analysis of the aortic lipid profiles revealed distinct differences between the vehicle-treated SHR group and the EA-treated SHR group. Specifically, EA treatment significantly altered the levels of aortic sphingomyelin and phospholipids, including very long-chain fatty acyl-ceramides and ether phosphatidylcholines. These changes in aortic lipid profiles correlated significantly with systolic blood pressure and cardiac function indicators. Furthermore, EA treatment significantly altered the expression of Cers2 and GNPAT. Conclusions: The findings suggest that EA may influence cardiovascular functions and aortic lipid profiles in SHR.

Comparison of Catheter Malposition Between Left and Right Ultrasound-Guided Infraclavicular Subclavian Venous Catheterizations: A Randomized Controlled Trial.

OBJECTIVES: Catheter malposition after subclavian venous catheterization (SVC) is not uncommon and can lead to serious complications. This study hypothesized that the left access is superior to the right access in terms of catheter malposition after ultrasound-guided infraclavicular SVC due to the asymmetry of the bilateral brachiocephalic veins. DESIGN: Parallel-armed randomized controlled trial. SETTING: A tertiary referral hospital in Korea. PATIENTS: Patients 20-79 years old who were scheduled to undergo SVC under general anesthesia. INTERVENTIONS: Patients were randomly assigned to either the left (n = 224) or right (n = 225) SVC group. The primary outcome measure was the overall catheter malposition rate. The secondary outcome measures included catheter malposition rates into the ipsilateral internal jugular and contralateral brachiocephalic veins, other catheterization-related complications, and catheterization performance. MEASUREMENTS AND MAIN RESULTS: The catheter malposition rate was lower (10 [4.5%] vs. 31 [13.8%], p = 0.001), especially in the ipsilateral internal jugular vein (9 [4.0%] vs. 24 [10.7%], p = 0.007), in the left SVC group than in the right SVC group. In the left SVC group, catheterization success rates on the first pass (88 [39.3%] vs. 65 [28.9%], p = 0.020) and first-catheterization attempt (198 [88.4%] vs. 181 [80.4%], p = 0.020) were higher whereas times for vein visualization (30 s [18-50] vs. 20 s [13-38], p < 0.001) and total catheterization (134 s [113-182] vs. 132 s [103-170], p = 0.034) were longer. There were no significant differences in other catheterization performance and catheterization-related complications between the two groups. CONCLUSIONS: These findings strengthen the rationale for choosing the left access over the right access for ultrasound-guided infraclavicular SVC.

Long-term clinical outcomes of image-guided percutaneous coronary intervention in acute myocardial infarction from the Korea Acute Myocardial Infarction Registry.

Imaging modalities for percutaneous coronary intervention (PCI), such as intravascular ultrasound (IVUS) or optical coherence tomography (OCT), have increased in the current PCI era. However, their clinical benefits in acute myocardial infarction (AMI) have not been fully elucidated. This study investigated the long-term outcomes of image-guided PCI in patients with AMI using data from the Korean Acute Myocardial Infarction Registry. A total of 9,271 patients with AMI, who underwent PCI with second-generation drug-eluting stents between November 2011 and December 2015, were retrospectively examined, and target lesion failure (TLF) at 3 years (defined as the composite of cardiac death, target vessel myocardial infarction, and ischemia-driven target lesion revascularization) was evaluated. From the registry, 2,134 patients (23.0%) underwent image-guided PCI (IVUS-guided: n = 1,919 [20.6%]; OCT-guided: n = 215 patients [2.3%]). Based on propensity score matching, image-guided PCI was associated with a significant reduction in TLF (hazard ratio: 0.76; 95% confidence interval: 0.59-0.98, p = 0.035). In addition, the TLF incidence in the OCT-guided PCI group was comparable to that in the IVUS-guided PCI group (5.3% vs 4.7%, p = 0.903). Image-guided PCI, including IVUS and OCT, is associated with favorable clinical outcomes in patients with AMI at 3 years post-intervention. Additionally, OCT-guided PCI is not inferior to IVUS-guided PCI in patients with AMI.

Artificial sensory system based on memristive devices.

In the biological nervous system, the integration and cooperation of parallel system of receptors, neurons, and synapses allow efficient detection and processing of intricate and disordered external information. Such systems acquire and process environmental data in real-time, efficiently handling complex tasks with minimal energy consumption. Memristors can mimic typical biological receptors, neurons, and synapses by implementing key features of neuronal signal-processing functions such as selective adaption in receptors, leaky integrate-and-fire in neurons, and synaptic plasticity in synapses. External stimuli are sensitively detected and filtered by "artificial receptors," encoded into spike signals via "artificial neurons," and integrated and stored through "artificial synapses." The high operational speed, low power consumption, and superior scalability of memristive devices make their integration with high-performance sensors a promising approach for creating integrated artificial sensory systems. These integrated systems can extract useful data from a large volume of raw data, facilitating real-time detection and processing of environmental information. This review explores the recent advances in memristor-based artificial sensory systems. The authors begin with the requirements of artificial sensory elements and then present an in-depth review of such elements demonstrated by memristive devices. Finally, the major challenges and opportunities in the development of memristor-based artificial sensory systems are discussed.

2023 Survey on User Experience of Artificial Intelligence Software in Radiology by the Korean Society of Radiology.

OBJECTIVE: In Korea, radiology has been positioned towards the early adoption of artificial intelligence-based software as medical devices (AI-SaMDs); however, little is known about the current usage, implementation, and future needs of AI-SaMDs. We surveyed the current trends and expectations for AI-SaMDs among members of the Korean Society of Radiology (KSR). MATERIALS AND METHODS: An anonymous and voluntary online survey was open to all KSR members between April 17 and May 15, 2023. The survey was focused on the experiences of using AI-SaMDs, patterns of usage, levels of satisfaction, and expectations regarding the use of AI-SaMDs, including the roles of the industry, government, and KSR regarding the clinical use of AI-SaMDs. RESULTS: Among the 370 respondents (response rate: 7.7% [370/4792]; 340 board-certified radiologists; 210 from academic institutions), 60.3% (223/370) had experience using AI-SaMDs. The two most common use-case of AI-SaMDs among the respondents were lesion detection (82.1%, 183/223), lesion diagnosis/classification (55.2%, 123/223), with the target imaging modalities being plain radiography (62.3%, 139/223), CT (42.6%, 95/223), mammography (29.1%, 65/223), and MRI (28.7%, 64/223). Most users were satisfied with AI-SaMDs (67.6% [115/170, for improvement of patient management] to 85.1% [189/222, for performance]). Regarding the expansion of clinical applications, most respondents expressed a preference for AI-SaMDs to assist in detection/diagnosis (77.0%, 285/370) and to perform automated measurement/quantification (63.5%, 235/370). Most respondents indicated that future development of AI-SaMDs should focus on improving practice efficiency (81.9%, 303/370) and quality (71.4%, 264/370). Overall, 91.9% of the respondents (340/370) agreed that there is a need for education or guidelines driven by the KSR regarding the use of AI-SaMDs. CONCLUSION: The penetration rate of AI-SaMDs in clinical practice and the corresponding satisfaction levels were high among members of the KSR. Most AI-SaMDs have been used for lesion detection, diagnosis, and classification. Most respondents requested KSR-driven education or guidelines on the use of AI-SaMDs.

Pediococcus pentosaceus KF159 alleviates house dust mite-induced atopic dermatitis by promoting IL10 production and regulatory T cell induction.

Atopic dermatitis (AD) is a chronic immune disease that requires long-term management owing to its relative ease of recurrence. However, steroid treatment is limited owing to the side effects. Therefore, research on therapeutics with proven safety is required. Here, we evaluated the anti-allergic activity of the probiotic strain Pediococcus pentosaceus KF159 (PPKF159) with an ex vivo mouse model sensitized with ovalbumin (OVA) and a mouse model of AD induced by house dust mites. Changes in pathological symptoms were confirmed based on the clinical status of the AD-induced lesion site and the levels of T helper type 2 (Th2)-derived cytokines and immunoglobulin E (IgE). In addition, cell-mediated responses and related mechanisms were elucidated using various kinds of primary cells including splenocytes, mesenteric lymph nodes, Peyer's patch, and bone marrow-derived dendritic cells (BMDCs) in vitro and ex vivo. Oral administration of PPKF159 alleviated AD-like clinical symptoms such as erythema, edema, hemorrhage, and increased tissue thickness, and suppressed the production of Th2-associated cytokines and serum IgE while increasing T helper type 1 (Th1)-mediated cytokine production. PPKF159 induced tolerogenic dendritic cells (tol-DCs) by increasing the expression of ICOS-L, PD-L1, and IDO which were closely related to Treg induction in PPKF159-treated BMDCs. In addition, BMDCs and naive T cells co-cultured in the presence of PPKF159 had elevated IL10 production and increased proportions of CD4+CD25+Foxp3+ Tregs compared to the absence of PPKF159. This study showed that PPKF159 relieved AD-like clinical symptoms, modulated the Th1/Th2 immune balance, and inhibited IgE production in a mouse AD model. PPKF159 induced the transformation of dendritic cells into tolerogenic versions. These induced tol-DCs directly enhanced the production of IL10 or improved the secretion of IL10 through the induction of CD4+CD25+Foxp3+ Treg cells, thereby improving AD. These results suggest that PPKF159 can be applied as a functional food material for the treatment and prevention of AD.

Probiotic LB101 alleviates dry eye in mice by suppressing matrix metalloproteinase-9 expression through the regulation of gut microbiota-involved NF-κB signaling.

Tear matrix metalloproteinase (MMP)-9 is an inflammatory signal in patients with dry eye (DE). In the present study, to understand the action mechanism of probiotic LB101 (Lactobacillus plantarum NK151 and Bifidobacterium bifidum NK175 [4:1] mix) against DE, we investigated its effect on tear amount and inflammatory marker expression levels in mice with unilateral exorbital lacrimal gland excision/atropine-benzalkonium chloride application (EB) or fecal microbiota transplantation from mice with EB (eFMT). Oral gavage of LB101 increased EB-suppressed tear amount and decreased EB-induced blinking number. Furthermore, LB101 decreased EB-induced TNF-α, IL-1ß, and MMP-9 expression, TNF-α+ and NF-κB+CD11c+ cell populations, and edema in the conjunctiva, while EB-suppressed IL-10 and occludin expression increased. LB101 also decreased EB-induced TNF-α and IL-1ß expression and NF-κB+CD11c+ cell population in the colon. eFMT also decreased tear amount and increased blinking number in the transplanted mice. eFMT increased TNF-α, IL-1ß, and MMP-9 expression and TNF-α+ and NF-κB+CD11c+ cell populations in the conjunctiva and TNF-α and IL-1ß expression and NF-κB+CD11c+ cell populations in the colon. Oral gavage of LB101 increased eFMT-suppressed tear amount and decreased eFMT-induced blinking number. Furthermore, LB101 decreased TNF-α, IL-1ß, and MMP-9 expression, TNF-α+ and NF-κB+CD11c+ cell populations, and edema in the conjunctiva and TNF-α and IL-1ß expression and NF-κB+CD11c+ cell population in the colon, while eFMT-suppressed IL-10 and occludin expression decreased. Furthermore, LB101 increased eFMT-suppressed Muribaculaceae, Prevotellaceae, and Lactobacillaceae populations in the gut microbiota, while eFMT-induced Bacteroidaceae population decreased. These findings suggest that DE may cause gut dysbiosis, which may be a risk factor for DE, and LB101 may alleviate DE with gut inflammation by suppressing the expression of MMP-9 and proinflammatory cytokines TNF-α and IL-1ß with the regulation of gut microbiota-involved NF-κB signaling.

Liver cancer initiation requires translational activation by an oncofetal regulon involving LIN28 proteins.

It is unknown which post-transcriptional regulatory mechanisms are required for oncogenic competence. Here, we show that the LIN28 family of RNA-binding proteins (RBPs), which facilitate post-transcriptional RNA metabolism within ribonucleoprotein networks, are essential for the initiation of diverse oncotypes of hepatocellular carcinoma (HCC). In HCC models driven by NRASG12V/Tp53, CTNNB1/YAP/Tp53, or AKT/Tp53, mice without Lin28a and Lin28b were markedly impaired in cancer initiation. We biochemically defined an oncofetal regulon of 15 factors connected to Lin28 through direct mRNA and protein interactions. Interestingly, all were RBPs and only 1 of 15 is a Let-7 target. Polysome profiling and reporter assays showed that LIN28B directly increased the translation of 8 of these 15 RBPs. As expected, overexpression of LIN28B and IGFBP1-3 were able to genetically rescue cancer initiation. Using this platform to probe components downstream of LIN28, we found that 8 target RBPs were able to restore NRASG12V/Tp53 cancer formation in Lin28a/b deficient mice. Furthermore, these LIN28B targets promote cancer initiation through an increase in protein synthesis. LIN28B, central to an RNP regulon that increases translation of RBPs, is important for tumor initiation in the liver.