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

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

Preventive effect of Helicobacter pylori eradication on the coronary heart diseases depending on age and sex with a median follow-up of 51 months.

BACKGROUND: The association between Helicobacter pylori (HP) infection and coronary heart disease (CHD) is controversial. This study aimed to investigate the effect of H. pylori eradication on CHD, especially in terms of age and sex. MATERIALS AND METHODS: From May 2003 to March 2022, 4765 subjects with H. pylori infection and without CHD (median follow-up: 51 months) were prospectively enrolled. The participants were categorized into two groups: H. pylori eradication and H. pylori non-eradication. After propensity-score matching (PSM), the effect of H. pylori eradication on CHD was analyzed using Cox proportional hazards. RESULTS: There were no significant differences in age, sex, alcohol consumption, smoking habits, history of diabetes, hypertension, and dyslipidemia, and aspirin intake between the eradication and non-eradication groups (3783 vs. 982) before and after PSM. Multivariate analysis after PSM showed that H. pylori eradication (HR: 0.489, CI: 0.314-0.761, p = .002), age (HR: 1.027, CI: 1.007-1.047, p = .007), hypertension (HR: 2.133, CI: 1.337-3.404, p = 001), dyslipidemia (HR: 1.758, CI: 1.086-2.848, p = .022), and aspirin intake (HR: 2.508, CI: 1.566-4.017, p < .001) were associated with CHD development. H. pylori eradication prevented CHD in males ≤65 years (HR: 0.133, CI: 0.039-0.455, p = .001), but not in those aged >65 years (p = .078) (p for interaction = .022). In contrast, females aged >65 years (HR: 0.260, CI: 0.110-0.615, p = .002) were protected by H. pylori eradication and not those ≤65 years (p = .485) (p for interaction = .003). This preventive effect increased more after PSM, particularly in males ≤65 years and females >65 years. CONCLUSIONS: H. pylori eradication prevented CHD and this effect was different depending on age and sex.

Staging Chest CT in Patients With Early-Stage Colon Cancer: Analysis of Impact on Survival Using Inverse Probability Weighting and Causal Diagram.

BACKGROUND. Staging chest CT has been shown to have negligible diagnostic yield for detecting lung metastases in patients with early-stage colon cancer. Nonetheless, staging chest CT may have potential survival benefits, including opportunistic screening of comorbidity and provision of a baseline examination for future comparisons. Evidence is lacking regarding the impact of staging chest CT on survival in patients with early-stage colon cancer. OBJECTIVE. The purpose of this study was to determine whether the performance of staging chest CT affects survival in patients with early-stage colon cancer. METHODS. This retrospective study included patients with early-stage colon cancer (defined as clinical stage 0 or I on staging abdominal CT) at a single tertiary hospital between January 2009 and December 2015. Patients were divided into two groups according to the presence of a staging chest CT examination. To ensure comparability between the two groups, inverse probability weighting was applied to adjust for the confounders derived from a causal diagram. The between-group differences in adjusted restricted mean survival time at 5 years were measured for overall survival, relapse-free survival, and thoracic metastasis-free survival. Sensitivity analyses were performed. RESULTS. A total of 991 patients (618 men and 373 women; median age, 64 years [IQR, 55-71 years]) were included: 606 patients (61.2%) had staging chest CT. For overall survival, the difference between groups in restricted mean survival time at 5 years was not significant (0.4 months [95% CI, -0.8 to 2.1 months]). The differences between groups in restricted mean survival at 5 years were also not significant for relapse-free survival (0.4 months [95% CI, -1.1 to 2.3 months]) and for thoracic metastasis-free survival (0.6 months [95% CI, -0.8 to 2.4 months]). Similar results were observed in sensitivity analyses that tested 3- and 10-year RMST differences, excluded patients who underwent FDG PET/CT during staging workup, and added treatment decision (surgery vs no surgery) to the causal diagram. CONCLUSION. The use of staging chest CT did not affect survival in patients with early-stage colon cancer. CLINICAL IMPACT. Staging chest CT may be omitted from the staging workup for patients with colon cancer of clinical stage 0 or I.

Effect of Clostridium butyricum on High-Fat Diet-Induced Intestinal Inflammation and Production of Short-Chain Fatty Acids.

BACKGROUND/AIMS: A high-fat diet (HFD) can cause intestinal inflammation and alter the gut microbiota; probiotics, however, are known to have anti-inflammatory effects. This study aimed to investigate the response of rat colon to HFD and the effect of Clostridium butyricum on HFD-induced intestinal inflammation and production of short-chain fatty acids (SCFAs) according to sex. METHODS: Male and female 6-week-old Fischer-344 rats were fed a chow diet or HFD for 8 weeks, and Biovita or three different concentrations of C. butyricum were orally gavaged. The levels of tight junction proteins (TJPs), inflammatory markers in the ascending colonic mucosa, and bile acids (BAs) and SCFAs in stool were measured. RESULTS: HFD significantly increased the histological inflammation scores and fat proportions. Fecal BA levels were higher in the HFD group than in the control group, with a more prominent increase in deoxycholic acid/cholic acid after probiotics administration in females; however, no statistically significant differences were observed. TJPs showed an opposite response to HFD depending on sex, and tended to increase and decrease after HFD in males and females, respectively. The HFD-reduced TJPs were recovered by probiotics, with some statistical significance in females. HFD-decreased butyric acid in stools appeared to be recovered by probiotics in males, but not in females. The expression of inflammatory markers (TNF-α) was increased by HFD in males and decreased with medium-concentration probiotic supplementation. The opposite was observed in females. MPO was increased by HFD in both sexes and decreased by probiotic supplementation. CONCLUSIONS: The probiotic C. butyricum improved indicators of HFD-induced colonic inflammation such as levels of inflammatory markers and increased the production of SCFAs and the expression of TJPs. These effects tended to be more pronounced in male rats, showing sex difference.

Intelligent Complementary Multi-Modal Fusion for Anomaly Surveillance and Security System.

Recently, security monitoring facilities have mainly adopted artificial intelligence (AI) technology to provide both increased security and improved performance. However, there are technical challenges in the pursuit of elevating system performance, automation, and security efficiency. In this paper, we proposed intelligent anomaly detection and classification based on deep learning (DL) using multi-modal fusion. To verify the method, we combined two DL-based schemes, such as (i) the 3D Convolutional AutoEncoder (3D-AE) for anomaly detection and (ii) the SlowFast neural network for anomaly classification. The 3D-AE can detect occurrence points of abnormal events and generate regions of interest (ROI) by the points. The SlowFast model can classify abnormal events using the ROI. These multi-modal approaches can complement weaknesses and leverage strengths in the existing security system. To enhance anomaly learning effectiveness, we also attempted to create a new dataset using the virtual environment in Grand Theft Auto 5 (GTA5). The dataset consists of 400 abnormal-state data and 78 normal-state data with clip sizes in the 8-20 s range. Virtual data collection can also supplement the original dataset, as replicating abnormal states in the real world is challenging. Consequently, the proposed method can achieve a classification accuracy of 85%, which is higher compared to the 77.5% accuracy achieved when only employing the single classification model. Furthermore, we validated the trained model with the GTA dataset by using a real-world assault class dataset, consisting of 1300 instances that we reproduced. As a result, 1100 data as the assault were classified and achieved 83.5% accuracy. This also shows that the proposed method can provide high performance in real-world environments.

Reduced acoustic resonator dimensions improve focusing efficiency of bacteria and submicron particles.

In this study, we demonstrate an acoustofluidic device that enables single-file focusing of submicron particles and bacteria using a two-dimensional (2D) acoustic standing wave. The device consists of a 100 µm × 100 µm square channel that supports 2D particle focusing in the channel center at an actuation frequency of 7.39 MHz. This higher actuation frequency compared with conventional bulk acoustic systems enables radiation-force-dominant motion of submicron particles and overcomes the classical size limitation (≈2 µm) of acoustic focusing. We present acoustic radiation force-based focusing of particles with diameters less than 0.5 µm at a flow rate of 12 µL min-1, and 1.33 µm particles at flow rates up to 80 µL min-1. The device focused 0.25 µm particles by the 2D acoustic radiation force while undergoing a channel cross-section centered, single-vortex acoustic streaming. A suspension of bacteria was also investigated to evaluate the biological relevance of the device, which demonstrated the alignment of bacteria in the channel at a flow rate of up to 20 µL min-1. The developed acoustofluidic device can align submicron particles within a narrow flow stream in a highly robust manner, validating its use as a flow-through focusing chamber to perform high-throughput and accurate flow cytometry of submicron objects.

The Difference of Endoscopic and Histologic Improvements of Atrophic Gastritis and Intestinal Metaplasia After Helicobacter pylori Eradication.

BACKGROUND/AIMS: Helicobacter pylori (H. pylori) is an important risk factor of atrophic gastritis (AG), intestinal metaplasia (IM), and gastric cancer (GC). However, no report to date has described the endoscopic improvement of AG and IM after H. pylori eradication. Thus, the aim of this study was to evaluate the improvement of AG and IM after H. pylori eradication using endoscopic and histologic analyses. METHODS: A total of 380 subjects were prospectively enrolled for up to 12 years and grouped by their H. pylori infection status: negative, non-eradicated, and eradicated. Endoscopic and histologic analyses of AG and IM were performed in the antrum and the corpus, by annual follow-up endoscopy. RESULTS: Endoscopic AG and IM in the antrum and corpus in the eradicated group improved compared to that in the non-eradicated group (AG, P = 0.002 and P = 0.005; IM, P = 0.038 and P = 0.048, respectively). Histologic AG and IM in the antrum and corpus in the eradicated group also improved compared to that in the non-eradicated group (all P < 0.001). Time taken to the endoscopic improvement of AG and IM after H. pylori eradication was significantly longer than time taken to the histologic improvement in the antrum and corpus (AG in antrum: 3.47 ± 2.60 vs. 2.34 ± 1.71 years, P = 0.004; AG in corpus: 3.19 ± 2.30 vs. 1.87 ± 1.48 years, P = 0.002; IM in antrum: 4.40 ± 2.38 vs. 3.62 ± 2.35 years, P = 0.043; and IM in corpus: 4.82 ± 1.08 vs. 3.61 ± 2.22 years, P = 0.007, respectively). CONCLUSIONS: Both endoscopic and histologic improvements of AG and IM were observed after H. pylori eradication, while endoscopic improvement took significantly longer time than histologic improvement.

Favorable outcomes of rescue second- or third-line culture-based Helicobacter pylori eradication treatment in areas of high antimicrobial resistance.

BACKGROUND: Failure of second or third-line eradication treatment against Helicobacter pylori (H. pylori) is principally caused by antimicrobial resistance and reduced treatment adherence. AIMS: To evaluate the efficacy and safety of culture-based rescue eradication treatments in patients who have previously experienced failed eradication treatment. METHODS: Patients who had persistent H. pylori infection following at least one eradication treatment were recommended to undergo culture analysis to determine the minimal inhibitory concentrations of various antimicrobials via endoscopic resection. Consenting patients were assigned one of four therapeutic treatments based on an algorithm determined by antimicrobial resistance. These treatments consisted of 7 or 14-day administration of clarithromycin-containing proton pump inhibitor (PPI) triple therapy; esomeprazole, moxifloxacin, and amoxicillin (MEA) therapy; esomeprazole, bismuth, metronidazole, and tetracycline (quadruple) therapy; or lansoprazole, rifabutin, and amoxicillin (RLA) therapy. Eradication efficacy, adherence, and adverse events were assessed aside clinical outcomes. RESULTS: A total of 132 patients were enrolled, with 84 patients completing the study. The overall resistance rates to amoxicillin, clarithromycin, metronidazole, and moxifloxacin were 13.1%, 83.3%, 47.6%, and 71.4%, respectively. The patients were allocated to the PPI triple (n = 11), MEA (n = 15), quadruple (n = 53), or RLA triple (n = 5) therapy group. The eradication rates in the intention-to-treat and per-protocol analyses were 90.5% (76 of 84 patients) and 93.8% (76 of 81 patients), respectively. Nausea was the most frequent adverse event (25.0%). CONCLUSIONS: As a rescue therapy, culture-based susceptibility-guided eradication treatment was both effective and safe, even for patients exhibiting high antimicrobial resistance.

Different effects of p53 protein overexpression on the survival of gastric cancer patients according to Lauren histologic classification: a retrospective study.

BACKGROUND: Inactivation of TP53, a tumor suppressor gene, is associated with the development of several malignancies, including gastric cancer (GC). The present study aimed to evaluate the correlation between the overexpression of p53 and survival in different Lauren-type GCs. METHODS: From May 2003 to December 2019, 3608 GC patients treated endoscopically or surgically at the Seoul National University Bundang Hospital were enrolled for the study. Immunohistochemical staining for p53 was performed on all endoscopic and surgical gastric specimens. Clinicopathologic characteristics with Lauren classification, survival rate, and cancer recurrence were analyzed according to p53 overexpression. RESULTS: Among 3608 GC patients, p53 overexpression was seen in 1334 patients (37%). p53 overexpression was associated with lower depth of invasion (P = 0.026) and Early gastric cancer (P = 0.044) in intestinal-type GC, and with advanced TNM stage (P < 0.001) and Advanced gastric cancer (P < 0.001) in diffuse-type GC. The overall survival (OS) and GC-specific survival (GCSS) were significantly lower in p53 overexpression positive patients. This significance was more pronounced and enhanced in the diffuse-type GC and was absent in the intestinal-type GC. In multivariate analyses, p53 overexpression was associated with poor OS in both subtypes of GC and cancer recurrence in diffuse-type GC. (OS in intestinal-type: adjusted hazard ratio [aHR] = 1.423, P = 0.022; OS in diffuse-type: aHR = 1.401 P = 0.035; cancer recurrence in diffuse-type: aHR = 1.502, P = 0.039). CONCLUSION: p53 overexpression was associated with poor prognosis in GC, especially in diffuse-type. In addition, p53 overexpression was associated with early stage disease in intestinal-type GC and with advanced stage disease in diffuse-type GC.

Wintertime Nitrous Oxide Emissions in the San Joaquin Valley of California Estimated from Aircraft Observations.

Nitrous oxide (N2O) is a long-lived greenhouse gas that also destroys stratospheric ozone. N2O emissions are uncertain and characterized by high spatiotemporal variability, making individual observations difficult to upscale, especially in mixed land use source regions like the San Joaquin Valley (SJV) of California. Here, we calculate spatially integrated N2O emission rates using nocturnal and convective boundary-layer budgeting methods. We utilize vertical profile measurements from the NASA DISCOVER-AQ (Deriving Information on Surface Conditions from COlumn and VERtically Resolved Observations Relevant to Air Quality) campaign, which took place January-February, 2013. For empirical constraints on N2O source identity, we analyze N2O enhancement ratios with methane, ammonia, carbon dioxide, and carbon monoxide separately in the nocturnal boundary layer, nocturnal residual layer, and convective boundary layer. We find that an established inventory (EDGAR v4.3.2) underestimates N2O emissions by at least a factor of 2.5, that wintertime emissions from animal agriculture are important to annual totals, and that there is evidence for higher N2O emissions during the daytime than at night.

Energy-Efficient Optimal Power Allocation for SWIPT Based IoT-Enabled Smart Meter.

This paper presents an internet of things (IoTs) enabled smart meter with energy-efficient simultaneous wireless information and power transfer (SWIPT) for the wireless powered smart grid communication network. The SWIPT technique with energy harvesting (EH) is an attractive solution for prolonging the battery life of ultra-low power devices. The motivation for energy efficiency (EE) maximization is to increase the efficient use of energy and improve the battery life of the IoT devices embedded in smart meter. In the system model, the smart meter is equipped with an IoT device, which implements the SWIPT technique in power splitting (PS) mode. This paper aims at the EE maximization and considers the orthogonal frequency division multiplexing distributed antenna system (OFDM-DAS) for the smart meters in the downlink with IoT enabled PS-SWIPT system. The EE maximization is a nonlinear and non-convex optimization problem. We propose an optimal power allocation algorithm for the non-convex EE maximization problem by the Lagrange method and proportional fairness to optimal power allocation among smart meters. The proposed algorithm shows a clear advantage, where total power consumption is considered in the EE maximization with energy constraints. Furthermore, EE vs. spectral efficiency (SE) tradeoff is investigated. The results of our algorithm reveal that EE improves with EH requirements.

Movement Path Data Generation from Wi-Fi Fingerprints for Recurrent Neural Networks.

The recurrent neural network (RNN) model, which is a deep-learning network that can memorize past information, is used in this paper to memorize continuous movements in indoor positioning to reduce positioning error. To use an RNN model in Wi-Fi-fingerprint based indoor positioning, data set must be sequential. However, Wi-Fi fingerprinting only saves the received signal strength indicator for a location, so it cannot be used as RNN data. For this reason, we propose a movement path data generation technique that generates data for an RNN model for sequential positioning from Wi-Fi fingerprint data. Movement path data can be generated by creating an adjacency list for Wi-Fi fingerprint location points. However, creating an adjacency matrix for all location points requires a large amount of computation. This problem is solved by dividing indoor environment by K-means clustering and creating a cluster transition matrix based on the center of each cluster.

Calculation of AeroMACS Spectrum Requirements Based on Traffic Simulator.

In this paper, we propose a methodology for calculating the necessary spectrum requirements of aeronautical mobile airport communication system (AeroMACS) to provide various airport communication services. To accurately calculate the spectrum requirement, it is necessary to evaluate the AeroMACS traffic demand of the peak time and statistical data on the packet traffic generated at the airport. Because there is no AeroMACS traffic model and real trace data, we have developed the AeroMACS traffic simulator based on the report of Single European Sky Air Traffic Management Research (SESAR). To calculate the spectrum requirements, the AeroMACS traffic simulator is combined with the methodology of ITU-R M.1768-1. The developed traffic simulator reflects AeroMACS traffic priorities and can generate the required traffic according to its location in the airport. We observed the spectrum requirement by changing the number of sectors and the spectral efficiency. To show the feasibility of our methodology, we applied it to the case of Incheon International Airport in Korea. The simulation results show that the average bandwidth of 0.94 MHz is required in the ground area and 8.59 MHz is required in the entire airport.

Effect of Helicobacter pylori eradication after subtotal gastrectomy on the survival rate of patients with gastric cancer: follow-up for up to 15 years.

OBJECTIVE: Helicobacter pylori (HP) is known to play an important role in the development of gastric cancer (GC). The aim of this study was to analyze the effect of HP eradication on the survival rate and cancer recurrence in patients who underwent subtotal gastrectomy for GC. DESIGN: Totally 1,031 patients diagnosed with gastric adenocarcinoma who received surgical treatment at the Seoul National University Bundang Hospital from 2003 to 2017 and positive for HP infection were analyzed. The overall and GC-related survival according to HP eradication were compared; risk factors for GC-specific death and cancer recurrence were analyzed, and propensity score matching (PSM) was performed. RESULTS: Statistically significant benefits of overall and GC-specific survival were observed in the eradicated group compared to the non-eradicated group (P < 0.001), and these benefits were maintained after PSM (P < 0.001) in both of early and advance stage. In Cox proportional hazards multivariate analyses, cancer stage (stage II, adjusted hazard ratio [aHR] = 9.33, P < 0.001; stage III or IV, aHR = 26.17, P < 0.001), and HP positivity (aHR = 3.41, P = 0.001) were independent risk factors for GC-specific death; cancer stage (cancer stage II, aHR = 7.08, P < 0.001; cancer stage III or IV, aHR = 19.64, P < 0.001) and HP positivity (aHR = 2.70; P = 0.005) were independent risk factors for cancer recurrence. CONCLUSION: Our results suggest that HP needed to be conducted more intensively in patients who are surgically treated for GC, regardless of cancer stage.

Long-term follow up of serum pepsinogens in patients with gastric cancer or dysplasia after Helicobacter pylori eradication.

BACKGROUND AND AIM: Few studies have evaluated the change in serum pepsinogen (sPG) levels after the eradication of Helicobacter pylori. The aim of this study was to evaluate the effect of H. pylori eradication on sPG levels in patients with gastric cancer/dysplasia in comparison to a control group. METHODS: We prospectively enrolled 368 patients with gastric cancer/dysplasia and 610 control subjects. H. pylori status and sPG levels were measured before and after eradication. The follow-up time points were classified as < 12, 12-23, 24-35, and ≥ 36 months. RESULTS: In 179 H. pylori-eradicated patients with gastric cancer/dysplasia and 168 control group subjects, sPG I significantly decreased, and the sPG I/II ratio significantly increased after eradication compared to baseline, and this improvement in sPG values was maintained during all follow-up time points. Significant differences in sPG I and the sPG I/II ratio were observed between the gastric cancer/dysplasia group and the control group < 24 months after eradication. However, these differences in sPG values disappeared after ≥ 24 months of follow up. Moreover, significant differences in the intestinal metaplasia grade were observed between these two groups before eradication until < 24 months after eradication. However, these differences in the intestinal metaplasia grade disappeared after ≥ 24 months of follow up in the corpus. CONCLUSION: The sPG values and intestinal metaplasia grade (corpus) in the gastric cancer/dysplasia group became similar to those in the control group at long-term follow up after H. pylori eradication. It might be related with the reduction of metachronous gastric neoplasm.

A QoS aware resource allocation strategy for 3D A/V streaming in OFDMA based wireless systems.

Three-dimensional (3D) video is expected to be a "killer app" for OFDMA-based broadband wireless systems. The main limitation of 3D video streaming over a wireless system is the shortage of radio resources due to the large size of the 3D traffic. This paper presents a novel resource allocation strategy to address this problem. In the paper, the video-plus-depth 3D traffic type is considered. The proposed resource allocation strategy focuses on the relationship between 2D video and the depth map, handling them with different priorities. It is formulated as an optimization problem and is solved using a suboptimal heuristic algorithm. Numerical results show that the proposed scheme provides a better quality of service compared to conventional schemes.

Sex Difference of Colon Adenoma Pathway and Colorectal Carcinogenesis.

Colorectal cancer (CRC) is one of the most common causes of cancer morbidity in both sexes but shows sex differences. First, sex-specific differences in tumor recurrence and survival rates have been reported. For example, the development of CRC is found about 1.5 times higher and 4-8 years earlier in males compared to females, suggesting the protective role of estrogen in the disease. Furthermore, female patients have a higher risk of developing right-sided (proximal) colon cancer than male patients, which is known to have more aggressive clinical character compared to left-sided (distal) colon cancer. That is, left and right CRCs show differences in carcinogenic mechanism, that the chromosomal instability pathway is more common in left colon cancer while the microsatellite instability and serrated pathways are more common in right colon cancer. It is thought that there are sex-based differences on the background of carcinogenesis of CRC. Sex differences of CRC have two aspects, sexual dimorphism (biological differences in hormones and genes) and gender differences (non-biological differences in societal attitudes and behavior). Recently, sex difference of colon adenoma pathway and sexual dimorphism in the biology of gene and protein expression, and in endocrine cellular signaling in the CRC carcinogenesis have been accumulated. In addition, behavioral patterns can lead to differences in exposure to risk factors such as drinking or smoking, diet and physical activity. Therefore, understanding sex/gender-related biological and sociocultural differences in CRC risk will help in providing strategies for screening, treatment and prevention protocols to reduce the mortality and improve the quality of life. In this review, sex/gender differences in colon adenoma pathway and various aspects such as clinicopathological, biological, molecular, and socio-cultural aspects of CRC were described.

The Effect of A2 Milk on Gastrointestinal Symptoms in Comparison to A1/A2 Milk: A Single-center, Randomized, Double-blind, Cross-over Study.

ß-Casein, a major protein in cow's milk, is divided into the A1 and A2 type variants. Digestion of A1 ß-casein yields the peptide ß-casomorphin-7 which could cause gastrointestinal (GI) discomfort but A2 milk containing only A2 ß-casein might be more beneficial than A1/A2 (regular) milk. The aim of this study was to evaluate the differences in GI discomfort after ingestion of A2 milk and A1/A2 milk. A randomized, double-blind, cross-over human trial was performed with 40 subjects who experienced GI discomfort following milk consumption. For each intervention period, either A2 milk first (A2→A1/A2) or A1/A2 milk was first consumed for 2 weeks (A1/A2→A2) following a 2-week washout period. GI symptom rating scale (GSRS) scores, questionnaire for digestive symptoms, and laboratory tests including fecal calprotectin were evaluated. For symptom analysis, generalized estimating equations gamma model was used. A2 milk increased bloating (P = 0.041) and loose stools (P = 0.026) compared to A1/A2 milk in GSRS. However, A2 milk caused less abdominal pain (P = 0.050), fecal urgency (P < 0.001) and borborygmus (P = 0.007) compared to A1/A2 milk in questionnaire for digestive symptoms. In addition, fecal calprotectin also decreased or less increased after consumption of A2 milk compared to A1/A2 milk (P = 0.030), and this change was more pronounced in males (P = 0.005) than in females. There were no significant adverse reactions during the trial. A2 milk alleviated digestive discomfort in Koreans following A2 milk consumption (ClinicalTrials.gov NCT06252636 and CRIS KCT0009301).

The Effect of Clostridium butyricum on Gut Microbial Changes and Functional Profiles of Metabolism in High-fat Diet-fed Rats Depending on Age and Sex.

Background/Aims: A high-fat diet (HFD) causes dysbiosis and promotes inflammatory responses in the colon. This study aims to evaluate the effects of Clostridium butyricum on HFD-induced gut microbial changes in rats. Methods: Six-week-old Fischer-344 rats with both sexes were given a control or HFD during 8 weeks, and 1-to-100-fold diluted Clostridium butyricum were administered by gavage. Fecal microbiota analyses were conducted using 16S ribosomal RNA metagenomic sequencing and predictive functional profiling of microbial communities in metabolism. Results: A significant increase in Ruminococcaceae and Lachnospiraceae, which are butyric acid-producing bacterial families, was observed in the probiotics groups depending on sex. In contrast, Akkermansia muciniphila, which increased through a HFD regardless of sex, and decreased in the probiotics groups. A. muciniphila positively correlated with Claudin-1 expression in males (P < 0.001) and negatively correlated with the expression of Claudin-2 (P = 0.042), IL-1ß (P = 0.037), and IL-6 (P = 0.044) in females. In terms of functional analyses, a HFD decreased the relative abundances of M00131 (carbohydrate metabolism module), M00579, and M00608 (energy metabolism), and increased those of M00307 (carbohydrate metabolism), regardless of sex. However, these changes recovered especially in male C. butyricum groups. Furthermore, M00131, M00579, and M00608 showed a positive correlation and M00307 showed a negative correlation with the relative abundance of A. muciniphila (P < 0.001). Conclusion: The beneficial effects of C. butyricum on HFD-induced gut dysbiosis in young male rats originate from the functional profiles of carbohydrate and energy metabolism.