Effects of game-based digital therapeutics on attention deficit hyperactivity disorder in children and adolescents as assessed by parents or teachers: a systematic review and meta-analysis.

Attention-deficit/hyperactivity disorder (ADHD) is a childhood-onset disorder characterized by pharmacological and non-pharmacological interventions. Despite the available treatment options and prevention measures, conventional treatments have several limitations. Digital therapeutics (DTx) like EndeavorRx® is an emerging alternative to overcome these limitations. EndeavorRx® is the first FDA-approved, game-based DTx approved for the treatment of pediatric ADHD. We investigated the effects of game-based DTx in randomised controlled trials (RCTs) on children and adolescents with ADHD. In this systematic review and meta-analysis, we searched PubMed, Embase, and PsycINFO databases up to January 2022. The protocol was registered (CRD42022299866). The assessor was defined as parents and teachers. The primary outcome was differences in inattention reported by the assessor, and the secondary outcome was differences in hyperactivity and hyperactivity/impulsivity reported by the assessor and the relative comparisons between game-based DTx, medicine, and control with indirect meta-analysis. Game-based DTx improved inattention more than the control upon assessment by assessors (standard mean difference (SMD) 0.28, 95% confidence interval (CI) 0.14-0.41; SMD 0.21, 95% CI 0.03-0.39, respectively), while medication improved inattention more than game-based DTx (SMD - 0·62, 95% CI - 1·04 to - 0·20) upon assessment by the teacher. Game-based DTx improved hyperactivity/impulsivity than the control upon assessment by assessors (SMD 0.28, 95% CI 0.03-0.53; SMD 0.30, 95% CI 0.05-0.55, respectively), and medication improved hyperactivity/impulsivity significantly than game-based DTx upon assessment by the teacher. Hyperactivity has not been reported extensively. As a result, game-based DTx had a more significant effect than the control, however medication was more effective.

Fibroblast growth factor receptor 4 increases epidermal growth factor receptor (EGFR) signaling by inducing amphiregulin expression and attenuates response to EGFR inhibitors in colon cancer.

Fibroblast growth factor receptor 4 (FGFR4) is known to induce cancer cell proliferation, invasion, and antiapoptosis through activation of RAS/RAF/ERK and PI3K/AKT pathways, which are also known as major molecular bases of colon cancer carcinogenesis related with epidermal growth factor receptor (EGFR) signaling. However, the interaction between FGFR4 and EGFR signaling in regard to colon cancer progression is unclear. Here, we investigated a potential cross-talk between FGFR4 and EGFR, and the effect of anti-EGFR therapy in colon cancer treatment. To explore the biological roles of FGFR4 in cancer progression, RNA sequencing was carried out using FGFR4 transfected colon cell lines. Gene ontology data showed the upregulation of genes related to EGFR signaling, and we identified that FGFR4 overexpression secretes EGFR ligands such as amphiregulin (AREG) with consequent activation of EGFR and ErbB3. This result was also shown in in vivo study and the cooperative interaction between EGFR and FGFR4 promoted tumor growth. In addition, FGFR4 overexpression reduced cetuximab-induced cytotoxicity and the combination of FGFR4 inhibitor (BLU9931) and cetuximab showed profound antitumor effect compared to cetuximab alone. Clinically, we found the positive correlation between FGFR4 and AREG expression in tumor tissue, but not in normal tissue, from colon cancer patients and these expressions were significantly correlated with poor overall survival in patients treated with cetuximab. Therefore, our results provide the novel mechanism of FGFR4 in connection with EGFR activation and the combination of FGFR4 inhibitor and cetuximab could be a promising therapeutic option to achieve the optimal response to anti-EGFR therapy in colon cancer.

Supervised Physical Rehabilitation in the Treatment of Patients with Advanced Cancer: a Systematic Review and Meta-analysis.

BACKGROUND: As the survival rate of cancer patients increases, the clinical importance of rehabilitation provided by healthcare professionals also increases. However, the evidence supporting the relevance of rehabilitation programs is insufficient. This study aimed to review the literature on effectiveness in physical function, quality of life (QOL) or fatigue of supervised physical rehabilitation in patients with advanced cancer. METHODS: A systematic review and meta-analysis was conducted following the Cochrane guidelines. We narratively described the results when meta-analysis was not applicable or appropriate. Literature databases including Ovid-MEDLINE, Ovid-EMBASE, and the Cochrane Library, as well as several Korean domestic databases, were searched up to June 2017 for studies that investigated the effectiveness of supervised physical rehabilitation programs on physical function, QOL or fatigue in patients with advanced cancer. The quality of the selected studies was evaluated independently by paired reviewers. RESULTS: Eleven studies with 922 participants were finally selected among 2,459 articles. The meta-analysis revealed that after physical exercise, the physical activity level and strength of patients with advanced cancer increased significantly. The QOL showed a statistically significant improvement after physical rehabilitation according to the European Organization for Research and Treatment of Cancer version C30. Though some of measurements about cardiovascular endurance or strength in several studies were not able to be synthesized, each study reported that they were significantly improved after receiving rehabilitation. CONCLUSION: Supervised physical rehabilitation for patients with advanced cancer is effective in improving physical activity, strength, and QOL. However, more trials are needed to prove the effectiveness of supervised exercise and to strengthen the evidence.

Enhancing Personalized Ads Using Interest Category Classification of SNS Users Based on Deep Neural Networks.

The classification and recommendation system for identifying social networking site (SNS) users' interests plays a critical role in various industries, particularly advertising. Personalized advertisements help brands stand out from the clutter of online advertisements while enhancing relevance to consumers to generate favorable responses. Although most user interest classification studies have focused on textual data, the combined analysis of images and texts on user-generated posts can more precisely predict a consumer's interests. Therefore, this research classifies SNS users' interests by utilizing both texts and images. Consumers' interests were defined using the Curlie directory, and various convolutional neural network (CNN)-based models and recurrent neural network (RNN)-based models were tested for our user interest classification system. In our hybrid neural network (NN) model, CNN-based classification models were used to classify images from users' SNS postings while RNN-based classification models were used to classify textual data. The results of our extensive experiments show that the classification of users' interests performed best when using texts and images together, at 96.55%, versus texts only, 41.38%, or images only, 93.1%. Our proposed system provides insights into personalized SNS advertising research and informs marketers on making (1) interest-based recommendations, (2) ranked-order recommendations, and (3) real-time recommendations.

Metabolic influence of walnut phenolic extract on mitochondria in a colon cancer stem cell model.

PURPOSE: Walnut phenolic extract (WPE) reduces proliferation and enhances differentiation of colon cancer stem cells (CSCs). The present study investigated the metabolic influence of WPE on the mitochondrial function of colon CSCs to determine its underlying mechanism. METHODS: CD133+CD44+ HCT116 colon cancer cells were selected by fluorescence-activated cell sorting and were treated with or without 40 µg/mL WPE. RNA-sequencing (RNA-Seq) was performed to identify differentially expressed genes (DEGs), which were further validated with RT-PCR. WPE-induced alterations in mitochondrial function were investigated through a mitochondrial stress test by determining cellular oxygen consumption rate (OCR), an indicator of mitochondrial respiration, and extracellular acidification rate (ECAR), an indicator of glycolysis, which were further confirmed by glucose uptake and lactate production tests. RESULTS: RNA-Seq analysis identified two major functional clusters: metabolic and mitochondrial clusters. WPE treatment shifted the metabolic profile of cells towards the glycolysis pathway (ΔECAR = 36.98 mpH/min/ptn, p = 0.02) and oxidative pathway (ΔOCR = 29.18 pmol/min/ptn, p = 0.00001). Serial mitochondrial stimulations using respiration modulators, oligomycin, carbonyl cyanide-4 (trifluoromethoxy) phenylhydrazone, and rotenone/antimycin A, found an increased potential of mitochondrial respiration (ΔOCR = 111.5 pmol/min/ptn, p = 0.0006). WPE treatment also increased glucose uptake (Δ = 0.39 pmol/µL, p = 0.002) and lactate production (Δ = 0.08 nmol/µL, p = 0.005). CONCLUSIONS: WPE treatment shifts the mitochondrial metabolism of colon CSC towards more aerobic glycolysis, which might be associated with the alterations in the characteristics of colon CSC.

Optical design of dental light using a remote phosphor light-emitting diode package for improving illumination uniformity.

The projection-type dental lighting based on the remote phosphor light-emitting diode (LED) package is designed to enhance uniformity of illuminance and correlated color temperature (CCT) on a target plane and to remove glare in the eyes of the patient. This dental lighting enables dentists to illuminate effectively the patient's mouth by increasing the inner area (50 mm×25 mm) described in ISO 9680. The optical module comprised of the LED package and optical lens is modeled to satisfy the inner area wider than 100 mm×50 mm and illuminance over 5,000 lx per the designed optical module. The fabricated prototype dental lighting contains four optical modules, and the maximum illuminance is 22,786 lx. The measured inner area is 105 mm×74 mm, and the ratio of inner area to outer area is about 76%. Also, the CCT variation is below 450 K in total illuminance pattern.

Glaucoma diagnostic ability of ganglion cell-inner plexiform layer thickness differs according to the location of visual field loss.

OBJECTIVE: To determine whether the ganglion cell-inner plexiform layer (GCIPL) or circumpapillary retinal nerve fiber layer (cpRNFL) is better at distinguishing eyes with early glaucoma from normal eyes on the basis of the the initial location of the visual field (VF) damage. DESIGN: Retrospective, observational study. PARTICIPANTS: Eighty-four patients with early glaucoma and 43 normal subjects were enrolled. The patients with glaucoma were subdivided into 2 groups according to the location of VF damage: (1) an isolated parafoveal scotoma (PFS, N = 42) within 12 points of a central 10 degrees in 1 hemifield or (2) an isolated peripheral nasal step (PNS, N = 42) within the nasal periphery outside 10 degrees of fixation in 1 hemifield. METHODS: All patients underwent macular and optic disc scanning using Cirrus high-definition optical coherence tomography (Carl Zeiss Meditec, Dublin, CA). The GCIPL and cpRNFL thicknesses were compared between groups. Areas under the receiver operating characteristic curves (AUCs) were calculated. MAIN OUTCOME MEASURES: Comparison of diagnostic ability using AUCs. RESULTS: The average and minimum GCIPL of the PFS group were significantly thinner than those of the PNS group, whereas there was no significant difference in the average retinal nerve fiber layer (RNFL) thickness between the 2 groups. The AUCs of the average (0.962) and minimum GCIPL (0.973) thicknesses did not differ from that of the average RNFL thickness (0.972) for discriminating glaucomatous changes between normal and all glaucoma eyes (P =0.566 and 0.974, respectively). In the PFS group, the AUCs of the average (0.988) and minimum GCIPL (0.999) thicknesses were greater than that of the average RNFL thickness (0.961, P =0.307 and 0.125, respectively). However, the AUCs of the average (0.936) and minimum GCIPL (0.947) thicknesses were lower than that of the average RNFL thickness (0.984) in the PNS group (P =0.032 and 0.069, respectively). CONCLUSIONS: The GCIPL parameters were more valuable than the cpRNFL parameters for detecting glaucoma in eyes with parafoveal VF loss, and the cpRNFL parameters were better than the GCIPL parameters for detecting glaucoma in eyes with peripheral VF loss. Clinicians should know that the diagnostic capability of macular GCIPL parameters depends largely on the location of the VF loss.

Glaucoma diagnostic accuracy of optical coherence tomography parameters in early glaucoma with different types of optic disc damage.

PURPOSE: To compare the initial visual field (VF) defect pattern and the spectral-domain optical coherence tomography (OCT) parameters and investigate the effects of distinct types of optic disc damage on the diagnostic performance of these OCT parameters in early glaucoma. DESIGN: Retrospective, observational study. PARTICIPANTS: A total of 138 control eyes and 160 eyes with early glaucoma were enrolled. The glaucomatous eyes were subdivided into 4 groups according to the type of optic disc damage: focal ischemic (FI) group, myopic (MY) group, senile sclerotic (SS) group, and generalized enlargement (GE) group. METHODS: The values of total deviation (TD) maps were analyzed, and superior-inferior (S-I) differences of TD were calculated. The optic nerve head (ONH) parameters, peripapillary retinal nerve fiber layer (pRNFL), and ganglion cell-inner plexiform layer (GCIPL) thicknesses were measured. MAIN OUTCOME MEASURES: Comparison of diagnostic ability using area under the receiver operating characteristic curves (AUCs). RESULTS: The S-I and central S-I difference of the FI group were larger than those of the GE group. The rim area of the SS group was larger than those of the 3 other groups, and the vertical cup-to-disc ratio (CDR) of the GE group was larger than that of the MY group. In addition, the minimum and inferotemporal GCIPL thicknesses of the FI group were smaller than those of the GE group. The AUC of the rim area (0.89) was lower than that of the minimum GCIPL (0.99) in the SS group, and the AUC of the vertical CDR (0.90) was lower than that of the minimum GCIPL (0.99) in the MY group. Furthermore, the AUCs of the minimum GCIPL thicknesses of the FI and MY group were greater than those of the average pRNFL thickness for detecting glaucoma, as opposed to the SS and GE. CONCLUSIONS: The OCT parameters differed among the 4 groups on the basis of the distinct optic disc appearance and initial glaucomatous damage pattern. Clinicians should be aware that the diagnostic capability of OCT parameters could differ according to the type of optic disc damage in early glaucoma.

Macular ganglion cell-inner plexiform layer thinning in patients with visual field defect that respects the vertical meridian.

The aim of this work is to compare the thinning patterns of the ganglion cell inner-plexiform layer (GCIPL) and peripapillary retinal nerve fiber layer (pRNFL) as measured using Cirrus high-definition optical coherence tomography (HD-OCT) in patients with visual field (VF) defects that respect the vertical meridian. Twenty eyes of 11 patients with VF defects that respect the vertical meridian were enrolled retrospectively. The thicknesses of the macular GCIPL and pRNFL were measured using Cirrus HD-OCT. The 5 and 1% thinning area index (TAI) was calculated as the proportion of abnormally thin sectors at the 5 and 1% probability level within the area corresponding to the affected VF. The 5 and 1% TAI were compared between the GCIPL and pRNFL measurements. The color-coded GCIPL deviation map showed a characteristic vertical thinning pattern of the GCIPL, which is also seen in the VF of patients with brain lesions. The 5 and 1% TAI were significantly higher in the GCIPL measurements than in the pRNFL measurements (all p < 0.01). Macular GCIPL analysis clearly visualized a characteristic topographic pattern of retinal ganglion cell (RGC) loss in patients with VF defects that respect the vertical meridian, unlike pRNFL measurements. Macular GCIPL measurements provide more valuable information than pRNFL measurements for detecting the loss of RGCs in patients with retrograde degeneration of the optic nerve fibers.

In vitro evaluation of the tooth bleaching efficacy and safety of high-concentration hydrogen peroxide with cold atmospheric plasma.

BACKGROUND: Using hydrogen peroxide (HP) for tooth bleaching may induce various side effects. Cold atmospheric plasma (CAP) is a promising solution. We aimed to evaluate and compare the efficacy and safety of tooth bleaching using high-concentration HP with CAP with conventional in-office bleaching. METHODS: Fifty-one discolored extracted human teeth were assigned to three groups: Group 1 (light-emitting diode with 35 % HP), Group 2 (CAP with 35 % HP), and Group 3 (only CAP). Bleaching was conducted over three sessions for a total of 20 min. The bleaching effect was evaluated based on the changes in color (ΔE00 and WID) and lightness (ΔL⁎ and ΔG). Safety was assessed by examining the dark areas on the enamel and monitoring the pulp chamber temperature. The study analyzed how different bleaching methods and durations affected ΔE00 and ΔWID using repeated-measures analysis of variance (ANOVA). The Kruskal-Wallis and Mann-Whitney tests were used for ΔL⁎ and dark areas, and one-way ANOVA for ΔG after 20 min of bleaching. RESULTS: The ΔE00 and WID demonstrated an interaction based on the bleaching method and time, with Group 1 exhibiting the highest ΔE00 and WID at all treatment times (p < 0.001). ΔL⁎ and ΔG did not differ significantly between Groups 1 and 2 (p = 0.056 and 0.062, respectively) and were lowest in Group 3 (p < 0.001). Group 1 exhibited the darkest areas and highest pulp chamber temperatures (p < 0.001). Group 1 exhibited statistically significant color changes. Group 2 demonstrated similar effects, but with enhanced safety profiles. CONCLUSIONS: Group 2, although displaying a slightly less pronounced color change compared with Group 1, achieved a color alteration readily discernible to the naked eye. This suggests that CAP with 35 % HP could be an interesting area for further investigation as an alternative to traditional in-office bleaching methods.

Performance of ECG-Derived Digital Biomarker for Screening Coronary Occlusion in Resuscitated Out-of-Hospital Cardiac Arrest Patients: A Comparative Study between Artificial Intelligence and a Group of Experts.

Acute coronary syndrome is a significant part of cardiac etiology contributing to out-of-hospital cardiac arrest (OHCA), and immediate coronary angiography has been proposed to improve survival. This study evaluated the effectiveness of an AI algorithm in diagnosing near-total or total occlusion of coronary arteries in OHCA patients who regained spontaneous circulation. Conducted from 1 July 2019 to 30 June 2022 at a tertiary university hospital emergency department, it involved 82 OHCA patients, with 58 qualifying after exclusions. The AI used was the Quantitative ECG (QCG™) system, which provides a STEMI diagnostic score ranging from 0 to 100. The QCG score's diagnostic performance was compared to assessments by two emergency physicians and three cardiologists. Among the patients, coronary occlusion was identified in 24. The QCG score showed a significant difference between occlusion and non-occlusion groups, with the former scoring higher. The QCG biomarker had an area under the curve (AUC) of 0.770, outperforming the expert group's AUC of 0.676. It demonstrated 70.8% sensitivity and 79.4% specificity. These findings suggest that the AI-based ECG biomarker could predict coronary occlusion in resuscitated OHCA patients, and it was non-inferior to the consensus of the expert group.

Artificial intelligence predicts undiagnosed atrial fibrillation in patients with embolic stroke of undetermined source using sinus rhythm electrocardiograms.

BACKGROUND: Artificial intelligence (AI)-enabled sinus rhythm (SR) electrocardiogram (ECG) interpretation can aid in identifying undiagnosed paroxysmal atrial fibrillation (AF) in patients with embolic stroke of undetermined source (ESUS). OBJECTIVE: The purpose of this study was to assess the efficacy of an AI model in identifying AF based on SR ECGs in patients with ESUS. METHODS: A transformer-based vision AI model was developed using 737,815 SR ECGs from patients with and without AF to detect current paroxysmal AF or predict the future development of AF within a 2-year period. Probability of AF was calculated from baseline SR ECGs using this algorithm. Its diagnostic performance was further tested in a cohort of 352 ESUS patients from 4 tertiary hospitals, all of whom were monitored using an insertable cardiac monitor (ICM) for AF surveillance. RESULTS: Over 25.1-month follow-up, AF episodes lasting ≥1 hour were identified in 58 patients (14.4%) using ICMs. In the receiver operating curve (ROC) analysis, the area under the curve for the AI algorithm to identify AF ≥1 hour was 0.806, which improved to 0.880 after integrating the clinical parameters into the model. The AI algorithm exhibited greater accuracy in identifying longer AF episodes (ROC for AF ≥12 hours: 0.837, for AF ≥24 hours: 0.879) and a temporal trend indicating that the AI-based AF risk score increased as the ECG recording approached the AF onset (P for trend <.0001). CONCLUSIONS: Our AI model demonstrated excellent diagnostic performance in predicting AF in patients with ESUS, potentially enhancing patient prognosis through timely intervention and secondary prevention of ischemic stroke in ESUS cohorts.

Prospective validation of a mobile health application for blood pressure management in patients with hypertensive disorders of pregnancy: study protocol for a randomized controlled trial.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) pose significant risks to both maternal and fetal health, contributing to global morbidity and mortality. Management of HDP is complex, particularly because of concerns regarding potential negative effects on utero-placental circulation and limited therapeutic options due to fetal safety. Our study investigates whether blood pressure monitoring through a mobile health (mHealth) application can aid in addressing the challenges of blood pressure management in pregnant individuals with HDP. Additionally, we aim to assess whether this intervention can improve short-term maternal and fetal outcomes and potentially mitigate long-term cardiovascular consequences. METHODS: This prospective, randomized, single-center trial will include 580 pregnant participants who meet the HDP criteria or who have a heightened risk of pregnancy-related hypertension due to factors such as multiple pregnancies, obesity, diabetes, or a history of HDP in prior pregnancies leading to preterm birth. Participants will be randomized to either the mHealth intervention group or the standard care group. The primary endpoint is the difference in systolic blood pressure from enrollment to 1 month after childbirth. The secondary endpoints include various blood pressure parameters, obstetric outcomes, body mass index trajectory, step counts, mood assessment, and drug adherence. CONCLUSIONS: This study emphasizes the potential of mHealth interventions, such as the Heart4U application, to improve blood pressure management in pregnant individuals with HDP. By leveraging technology to enhance engagement, communication, and monitoring, this study aims to positively impact maternal, fetal, and postpartum outcomes associated with HDP. This innovative approach demonstrates the potential of personalized technology-driven solutions for managing complex health conditions. TRIAL REGISTRATION: ClinicalTrials.gov NCT05995106. Registered on 16 August 2023.

Soy milk suppresses cholesterol-induced inflammatory gene expression and improves the fatty acid profile in the skin of SD rats.

Recently, an elevation in skin cholesterol level has been implicated in skin inflammation. Given the potential therapeutic effects of soy on low grade inflammatory diseases, we hypothesized that a CHOL diet could promote an inflammatory response in skin and that soy milk (SM) or fermented soy milk (F.SM) could prevent this cholesterol-induced skin inflammation. To test this hypothesis, freeze-dried SM or F.SM was provided as a protein replacement for 20% of the casein in the diets of Sprague-Dawley (SD) rats. The animals were divided into the following groups: (1) control group (CTRL), AIN76A diet without cholesterol, (2) high cholesterol (CHOL) group, AIN76A with 1% (w/w) cholesterol, (3) SM group, CHOL diet with freeze-dried SM, and (4) F.SM group, CHOL diet with F.SM. In the CHOL group, the expression levels of pro-inflammatory genes, including IL-1ß, IL-1α, iNOS, and COX-2, were elevated. In comparison, the SM and F.SM groups displayed the lowered expression of IL-1ß, COX-2, F4/80, and Cd68, an increase of a n-3/n-6 ratio, and a reduction in the estimated desaturase activities of delta 5 desaturase (D5D) and steaoryl CoA desaturase (SCD-1). In particular, F.SM significantly increased the proportion of dihomo-γ-linolenic acid (DGLA) in skin fatty acid (FA) composition compared with the CHOL group. Here we present evidence that SM or F.SM could alleviate the inflammatory response in the skin that is triggered by excess dietary cholesterol by reducing the expression of pro-inflammatory genes. This response could be partly associated with a decreased in macrophages in skin and/or by modulation of the skin's FA composition.

Influence of location-dependent sex difference on PD-L1, MMR/MSI, and EGFR in colorectal carcinogenesis.

BACKGROUND: The incidence and mortality rates of colorectal cancer (CRC) has been reported to be strongly associated to sex/gender difference. CRC shows sexual dimorphism, and sex hormones have been shown to affect the tumor immune microenvironment. This study aimed to investigate location-dependent sex differences in tumorigenic molecular characteristics in patients with colorectal tumors, including adenoma and CRC. METHODS: A total of 231 participants, including 138 patients with CRC, 55 patients with colorectal adenoma, and 38 healthy controls, were recruited between 2015 and 2021 at Seoul National University Bundang Hospital. All patients underwent colonoscopy and acquired tumor lesion samples were further analyzed for programmed death-ligand 1 (PD-L1), epidermal growth factor receptor (EGFR) expression, deficient mismatch repair (dMMR), and microsatellite instability (MSI) status. This study was registered with ClinicalTrial.gov, number NCT05638542. RESULTS: The average of combined positive score (CPS) was higher in serrated lesions and polyps (lesions/polyps) compared to conventional adenomas (5.73 and 1.41, respectively, P < 0.001). No significant correlation was found between sex and PD-L1 expression within the groups, regardless of histopathological diagnosis. In multivariate analysis where each sex was further stratified by tumor location due to their interaction in CRC, PD-L1 expression was inversely correlated with males having proximal CRC with a CPS cutoff of 1 (Odds ratio (OR) 0.28, P = 0.034). Females with proximal CRC showed a significant association with dMMR/MSI-high (OR 14.93, P = 0.032) and high EGFR expression (OR 4.17, P = 0.017). CONCLUSION: Sex and tumor location influenced molecular features such as PD-L1, MMR/MSI status and EGFR expression in CRC, suggesting a possible underlying mechanism of sex-specific colorectal carcinogenesis.

Anti-PD-L1 Antibody and/or 17ß-Estradiol Treatment Induces Changes in the Gut Microbiome in MC38 Colon Tumor Model.

PURPOSE: 17ß-Estradiol (E2) supplementation suppresses MC38 tumor growth by downregulating the expression of programmed death-ligand 1 (PD-L1). This study aims to figure out the gut microbiota that respond to anti-PD-L1 and/or estrogen treatment in MC38 colon cancer model. Materials and Methods: A syngeneic colon tumor model was developed by injection of MC38 cells into C57BL/6 background male and female mice. Three days before MC38 cells injection, E2 was supplemented to male mice daily for 1 week. Male and female mice with MC38 tumors (50-100 mm3) were injected with anti-PD-L1 antibody. Fresh feces were collected 26 days after injection of MC38 cells and 16S rRNA metagenomics sequencing of DNA extracted from feces was used to assess gut microbial composition. RESULTS: At the taxonomic family level, Muribaculaceae was enriched only in the MC38 male control group. In male mice, linear discriminant analysis effect size analysis at the species level revealed that the four microorganisms were commonly regulated in single and combination treatment with anti-PD-L1 and/or E2; a decrease in PAC001068_g_uc and PAC001070_s (family Muribaculaceae) and increase in PAC001716_s and PAC001785_s (family Ruminococcaceae). Interestingly, in the anti-PD-L1 plus E2 group, a decrease in opportunistic pathogens (Enterobacteriaceae group) and an increase in commensal bacteria (Lactobacillus murinus group and Parabacteroides goldsteinii) were observed. Furthermore, the abundance of Parabacteroides goldsteinii was increased in both males and females in the anti-PD-L1 group. CONCLUSION: Our results suggest that gut microbial changes induced by the pretreatment of estrogen before anti-PD-L1 might contribute to treatment of MC38 colon cancer.

The Possible Preventative Role of Lactate- and Butyrate-Producing Bacteria in Colorectal Carcinogenesis.

Background/Aims: : The gut microbiome has emerged as a key player that mechanistically links various risk factors to colorectal cancer (CRC) etiology. However, the role of the gut microbiome in CRC pathogenesis remains unclear. This study aimed to characterize the gut microbiota in healthy controls (HCs) and patients with colorectal adenoma (AD) and CRC in subgroups based on sex and age. Methods: : Study participants who visited the hospital for surveillance of CRC or gastrointestinal symptoms were prospectively enrolled, and the gut microbiome was analyzed based on fecal samples. Results: : In terms of HC-AD-CRC sequence, commensal bacteria, including lactate-producing (Streptococcus salivarius) and butyrate-producing (Faecalibacterium prausnitzii, Anaerostipes hadrus, and Eubacterium hallii) bacteria, were more abundant in the HC group than in the AD and CRC groups. In the sex comparison, the female HC group had more lactate-producing bacteria (Bifidobacterium adolescentis, Bifidobacterium catenulatum, and Lactobacillus ruminis) than the male HC group. In age comparison, younger subjects had more butyrate-producing bacteria (Agathobaculum butyriciproducens and Blautia faecis) than the older subjects in the HC group. Interestingly, lactate-producing bacteria (B. catenulatum) were more abundant in females than males among younger HC group subjects. However, these sex- and age-dependent differences were not observed in the AD and CRC groups. Conclusions: : The gut microbiome, specifically lactate- and butyrate-producing bacteria, which were found to be abundant in the HC group, may play a role in preventing the progression of CRC. In particular, lactate-producing bacteria, which were found to be less abundant in healthy male controls may contribute to the higher incidence of CRC in males.

Optimization of Fermentation Conditions of Artemisia capillaris for Enhanced Acetylcholinesterase and Butyrylcholinesterase.

In this study, the fermentation of Artemisia capillaris by probiotic Leuconostoc mesenteroides MKJW (MKJW) was optimized to increase the acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) inhibitory and antioxidant activities using the response surface method (RSM). The independent variables were the contents of A. capillaris, Gryllus bimaculatus, and yeast extract, while the dependent variables were AChE inhibitory activity, BuChE inhibitory activity, and antioxidant activities such as FRAP, reducing power, and DPPH radical scavenging ability. Seventeen experimental runs were designed with RSM and analyzed after fermentation with MKJW. Quadratic models were used to analyze the inhibition of AChE and BuChE, and a linear model was used to analyze the FRAP. The three models were significantly appropriate (p < 0.0001). The highest optimal condition of the AChE inhibitory activity was derived by a multiple regression equation. When the optimum fermentation conditions were A. capillaris 6.75%, G. bimaculatus 0.18%, and yeast extract 1.27%, 91.1% was reached for AChE inhibitory, 74.0% for BuChE inhibitory, and 34.1 mM FeSO4 for FRAP. The predicted dependent variables were not significantly different from the experimental values (p > 0.05). In conclusion, the A. capillaris fermented by MKJW might be used as a natural antidementia improving agent with AChE inhibitory, BuChE inhibitory, and antioxidant activities.

An epifluidic electronic patch with spiking sweat clearance for event-driven perspiration monitoring.

Sensory neurons generate spike patterns upon receiving external stimuli and encode key information to the spike patterns, enabling energy-efficient external information processing. Herein, we report an epifluidic electronic patch with spiking sweat clearance using a sensor containing a vertical sweat-collecting channel for event-driven, energy-efficient, long-term wireless monitoring of epidermal perspiration dynamics. Our sweat sensor contains nanomesh electrodes on its inner wall of the channel and unique sweat-clearing structures. During perspiration, repeated filling and abrupt emptying of the vertical sweat-collecting channel generate electrical spike patterns with the sweat rate and ionic conductivity proportional to the spike frequency and amplitude over a wide dynamic range and long time (> 8 h). With such 'spiking' sweat clearance and corresponding electronic spike patterns, the epifluidic wireless patch successfully decodes epidermal perspiration dynamics in an event-driven manner at different skin locations during exercise, consuming less than 0.6% of the energy required for continuous data transmission. Our patch could integrate various on-skin sensors and emerging edge computing technologies for energy-efficient, intelligent digital healthcare.

Structure-Function Relationship and Vision-Related Quality of Life in Glaucoma Secondary to Anterior Uveitis: Comparison with Open Angle Glaucoma.

PURPOSE: The aim of this study is to investigate the structure-function characteristics and vision-related quality of life (VR-QoL) in uveitic glaucoma (UG) compared with open-angle glaucoma (OAG). METHOD: The study included 69 patients with UG and 138 patients with primary open angle glaucoma, normal-tension glaucoma. A 25-item National Eye Institute Visual Function Questionnaire (VFQ-25) was used to evaluate the patients' VR-QoL. The retinal nerve fiber layer thickness (RNFLT) was measured using optical coherence tomography, and the integrated visual field (IVF) was determined using the best location method. RESULTS: There were no significant differences in the binocular IVF and mean deviation (MD) of the affected eye between the OAG and UG group, whereas the average RNFLT was significant thinner in the OAG group (p = 0.008). The patients with UG showed a significantly lower composite score and five subscales of the VFQ-25, compared with those with OAG (p < 0.05, for all, general linear model). Multivariate linear regression analyses showed that the composite score showed the strongest associations with the whole IVF (ß = 1.240, p < 0.001) in the OAG group, whereas in the UG group, a significant association was seen only with the inferior VF of the affected eye (ß = 0.596, p = 0.038). CONCLUSIONS: The eyes with UG exhibited distinctive structure-function characteristics and worse VR-QoL that differentiated them from OAG eyes.