The association between ultra-processed food consumption and health-related quality of life differs across lifestyle and socioeconomic strata.

BACKGROUND: In this prospective study, we aimed to examine the association between ultra-processed foods and health-related quality of life (HRQoL) and to evaluate the effect of lifestyle and socioeconomic factors on this association. METHODS: This study included 1766 adults (aged 18 to 78, 54.3% women), who took part in the Tehran Lipid and Glucose study. The Short-Form 12-Item Health Survey version 2 was used to determine HRQoL, which includes the physical component summary (PCS) and mental component summary (MCS) scores. Ultra-processed food consumption was assessed using a validated semi-quantitative food frequency questionnaire. Lifestyle (physical activity and smoking status) and socioeconomic factors (education level and employment status) were also determined. General linear models (GLM) were applied to estimate the mean (95% confidence interval) for MCS and PCS scores across the ultra-processed foods tertiles. Additionally, the effect of lifestyle and socioeconomic factors on the relationship between ultra-processed foods and HRQoL was examined using GLM. RESULTS: The median consumption of ultra-processed foods was 11.9% (IQR: 8.2 to 16.8) of total energy intake. There was a significant inverse association between ultra-processed foods consumption and PCS, but not MCS, after adjustment for confounding factors. Significant interactions were observed between ultra-processed food consumption, sex, and occupation on PCS score (all P values < 0.001). The interaction test tended to be significant for smoking status, education levels, and physical activity levels. As ultra-processed food consumption increased, the PCS score significantly decreased in women (P = 0.043), low physical active subjects (P = 0.014), smokers (P = 0.015), and lower-educated individuals (P = 0.022). Non-employed individuals with higher ultra-processed food intake showed a decline in their PCS and MCS scores. While there was no significant difference in MCS score among different strata of lifestyle and socioeconomic status across tertiles of ultra-processed foods. CONCLUSIONS: Higher intake of ultra-processed foods was associated with poorer physical health, particularly among women, those with unhealthy lifestyles, and low socioeconomic conditions.

Association between ultra-processed food consumption, sociodemographic characteristics, malnutrition and obesity among urban school-aged children in Lilongwe, Malawi: a cross-sectional study.

INTRODUCTION: The escalating consumption of ultra-processed foods (UPFs) among school-aged children in developing countries poses a significant threat to public health, contributing to the dual burden of malnutrition. In Malawi, where undernutrition coexists with a burgeoning obesity epidemic, understanding the determinants of UPF consumption and its impact on children's nutritional status is imperative. This study, conducted in Lilongwe, Malawi, aimed to investigate the association between UPF consumption, sociodemographic factors and the nutritional status of school-aged children. MATERIALS AND METHODS: 511 children aged 7-14 were recruited from 2 densely populated townships using systematic random sampling. Data on sociodemographic factors, UPF consumption and nutritional status were collected through face-to-face interviews and anthropometric measurements. UPF consumption was assessed using a validated Food Frequency Questionnaire while multinomial logistic regression was employed to analyse associations. RESULTS: Results revealed alarmingly high UPF consumption among children, particularly those high in sugar. Multinomial logistic regression identified significant predictors of malnutrition outcomes. Notably, children consuming UPFs more than three times a week were more likely to be malnourished. Overweight status was positively associated with sausage intake (ß=0.226, adjusted OR 1.254, 95% CI 1.004 to 1.566, p=0.046) and age (ß=0.020, adjusted OR=0.257, 95% CI 0.156 to 0.28, p=0.003). Conversely, underweight status was linked with residential location (ß=4.507, adjusted OR 0.01, 95% CI 0.000 to 0.281, p=0.006) and fizzy drinks (ß=1.071, adjusted OR 2.919, 95% CI 1.413 to 6.028, p=0.004). CONCLUSION: The high prevalence of UPF consumption among school-aged children is significantly associated with malnutrition. Moreover, sociodemographic factors influence UPF consumption, highlighting the need for targeted interventions to reduce malnutrition. These findings may inform public health policies to mitigate malnutrition among children in Malawi's urban communities.

Stress and the Consumption of Ultra-Processed Foods during COVID-19's Social Distancing: Are Mental Disorders Mediators in This Association? ELSA-Brasil Results.

The COVID-19 pandemic exacerbated various determinants of mental disorders. Several behavioral changes were observed given this increase, including harmful health consequences, such as excessive consumption of ultra-processed foods (UPFs). To assess this relationship, we investigated the meditational role of symptoms of mental disorders (anxiety and depression) in the association between stress resulting from social distancing during the COVID-19 pandemic and the consumption of UPFs in 3884 Brazilian public employees in a supplementary study of the ELSA-Brasil study. Structural equation models (SEMs) were estimated to assess the direct and indirect effects mediated by symptoms of mental disorders. The results suggested a significant and positive mediational effect of the symptoms of mental disorders on the association between the stress resulting from social distancing and the consumption of UPFs. These findings contribute to informing the need for policies and early interventions in potentially stressful situations, with a focus on the promotion of mental health, and may thus help prevent or reduce the consumption of unhealthy foods.

Consumption of Ultra-Processed Foods in the Brazilian Amazon during COVID-19.

BACKGROUND: A COVID-19 pandemic erupted, causing a global viral pneumonia outbreak, marking the most significant public health crisis of the 21st century. These changes profoundly impacted population health and well-being, leading to shifts in dietary habits. This study aimed to evaluate the consumption of ultra-processed foods in the Brazilian Amazon before, during, and after the COVID-19 pandemic. METHODS: This is a secondary data analysis study derived from the Surveillance System of Risk and Protective Factors for Chronic Diseases by Telephone Survey (Vigitel, 2019-2021) of the Brazilian Ministry of Health. All statistical analyses were performed using the Stata 17 statistical program in the survey module (svy). RESULTS: We found an increased frequency in the subgroups of consumption of ultra-processed foods in the capital of the Brazilian Amazon region between the years 2019 and 2021. In the cities of Boa Vista and Macapá, there was a significant increase in the consumption of snacks, salty snacks, cookies, and meat products. Boa Vista and Macapá showed an increase in the percentage difference in the consumption ≥5 of ultra-processed subgroups, being 30.4% (p = 0.014) and 53.7% (p = 0.014), respectively. CONCLUSIONS: The study indicated an increase in the consumption of ultra-processed foods in the Brazilian Amazon region during and after social distancing.

Which domestic refrigerator temperatures in Europe? - Focus on shelf-life studies regarding Listeria monocytogenes (Lm) in ready-to-eat (RTE) foods.

Listeria monocytogenes (Lm) is a pathogenic bacteria able to grow at refrigerated temperatures, widely distributed in the environment. This bacteria is susceptible to contaminate various food products of which refrigerated ready-to-eat foods (RTEF) may pose a risk for public health. In Europe, food business operators (FBOs) shall ensure that foodstuffs comply with the relevant microbiological criteria set out in the Regulation (EC) N°2073/2005. Food safety criteria for Lm are defined in RTEF throughout their shelf-life. FBOs should implement studies to demonstrate that the concentration of Lm does not exceed 100 CFU/g at the end of the shelf-life, taking into account foreseeable conditions of distributions, storage and use, including the use by consumers. However, this last part of the cold chain for food products is the most difficult to capture and control. For this purpose, the European Union Reference Laboratory for Lm (EURL Lm) launched an inquiry to its National Reference Laboratory network and reviewed the scientific literature from 2002 to 2020. The outcomes were integrated in the technical guidance document of the EURL Lm to assess shelf-life of RTEF which resulted in the recommendation to use 10 °C as the reference temperature to simulate the reasonably foreseen storage conditions in domestic refrigerators.

Ultra-Processed Food Consumption as a Risk Factor for Gastrointestinal Cancer and Other Causes of Mortality in Southern Italy: A Competing Risk Approach.

BACKGROUND: Ultra-Processed Foods (UPFs) are increasingly consumed worldwide, even in regions with strong dietary traditions like the Mediterranean and can play a crucial role in the development of chronic diseases, including cancer. This population-based prospective cohort study investigates the association between UPF consumption and gastrointestinal cancers and other causes of mortality in Southern Italy. METHODS: Data were collected from 4870 participants in the MICOL and NUTRIHEP cohorts. The EPIC questionnaire was used to elicit information on food and drink consumption and UPFs were categorized by degree of processing according to the NOVA classification. Cox proportional hazards regression and competing risk models were employed for statistical analysis. RESULTS: UPF consumption was positively associated with all-cause mortality: participants in the 3rd UFP quartile, as compared to the lowest, had a 27% higher risk of death (SHR 1.27 95% CI, 1.03; 1.57), while in the highest quartile as compared to the lowest, the risk was 34% higher (SHR 1.34 95% CI, 1.00; 1.79). Higher UPFs intake was also correlated with an increased gastrointestinal cancers mortality risk, especially the 2nd (SHR 1.65, 95% CI: 1.01; 2.71) and 4th quartile (SHR 3.14 95% CI: 1.56; 6.32), with a dose-dependent effect. For the other cancers, a SHR 1.61 (95% CI 1.03; 2.54) was observed for the 3rd quartile. CONCLUSIONS: Our results reinforce the link between UPF consumption and cancer risk, emphasizing the urgent need for interventions targeting dietary patterns.

Isocaloric replacement of ultraprocessed foods was associated with greater weight loss in the POUNDS Lost trial.

OBJECTIVE: Higher intake of ultraprocessed foods (UPFs) is associated with obesity. We examined whether replacing UPFs (NOVA 4) with minimally processed foods and culinary ingredients (NOVA 1 + 2) was associated with differential weight change in this secondary prospective analysis of the Preventing Overweight Using Novel Dietary Strategies (POUNDS) Lost trial. METHODS: We estimated percent energy intake (%kcal) from the four NOVA groups using 24-h dietary recalls in a subset of 356 participants. Multivariable-adjusted substitution models examined whether replacing %kcal from UPFs with NOVA 1 + 2 was associated with greater weight, body fat percentage, trunk fat, and waist circumference reduction at 6 months; changes in parameters were compared among NOVA 1 + 2 tertiles (T). RESULTS: Participants were on average 52.3 years of age, 85% White, 55% female, and 58.2% nonsmoking, with a mean BMI of 32.7 kg/m2. Replacing 10%kcal of UPFs with NOVA 1 + 2 was associated with greater 6-month weight (ß = 0.51, 95% CI: -0.93 to -0.09, p = 0.02), body fat percentage (ß = 2.7, 95% CI: -5.10 to -0.43, p = 0.02), and trunk fat reduction (ß = 3.9, 95% CI: -7.01 to -0.70, p = 0.02), but not waist circumference reduction. Participants in T3 (-8.33 kg) versus T1 (-5.32 kg) of NOVA 1 + 2 had greater weight loss (p < 0.001). CONCLUSIONS: Isocaloric substitution of UPFs with NOVA 1 + 2 was associated with marginally greater weight loss under energy restriction. These modest findings support more research exploring the mechanisms linking UPFs with body weight regulation beyond energy intake.

Association of maternal ultra-processed food consumption during pregnancy with atopic dermatitis in infancy: Korean Mothers and Children's Environmental Health (MOCEH) study.

BACKGROUND: Maternal diet during pregnancy might influence the development of childhood allergic disorders. There are few studies on the association between processed food intake and infant atopic dermatitis (AD) during pregnancy. The aim of the present study was to investigate the association of ultra-processed food (UPF) intake during pregnancy with infantile AD. METHODS: This study involved 861 pairs of pregnant women and their offspring from the Mothers' and Children's Environmental Health (MOCEH) study, a multi-center birth cohort project conducted in Korea. Dietary intake was estimated using a 24-h recall method at 12-28 weeks gestation. The NOVA classification was used to identify UPF, and UPF intake was calculated as the percentage of total energy consumption and categorized into quartiles. Infantile AD was assessed based on medical history and the criteria of the International Study of Asthma and Allergies in Childhood (ISAAC). Associations were assessed by logistic regression with adjustment for confounding factors. RESULTS: Children born to mothers in the highest quartile of UPF consumption (15.5% or more of the total energy) compared to the lowest quartile (6.8% or less) showed a higher risk of AD within 12 months [odds ratio (OR) = 1.69; 95% confidence interval (CI): 1.07-2.66, P for trend 0.0436]. After adjustment for the confounding factors under study, the association was strengthened; the adjusted OR between extreme quartiles was 2.19 (95% CI: 1.11-4.32, P for trend = 0.0418). This association was maintained even after an additional adjustment based on the Korean Healthy Eating Index (KHEI), an indicator of diet quality. CONCLUSIONS: Higher maternal consumption of UPF during pregnancy was associated with a greater risk of infantile AD within the first year of life.

Shape variety of food can boost its visual appeal.

We investigated whether food shape and its variety within a group affect visual appeal using a four-shaped fast-food chicken product known as Chicken McNuggets®. In Experiment 1, participants rated the visual appeal of each nugget shape both individually and when presented in groups of variously shaped nuggets. The results revealed that the rounder nugget was less visually appealing than those of other shapes. Additionally, assortments featuring various shapes were rated as more appealing than those of a single shape. In Experiment 2, the visual appeal of individual nuggets presented in groups and alone was assessed using a visual analog scale. The visual appeal of one specific nugget (target nugget) was higher when presented in a group than alone. Furthermore, a target nugget presented in a group with various shapes was more visually appealing than when presented in a group with the same shape, regardless of the shape of the target nugget. These results suggest that a food product with low visual appeal can be perceived as more appealing when it is presented alongside various food shapes. Indeed, the variety of food shapes presented in a group affected the perceived appeal both of the group and of the individual food item. These findings offer novel insights into the impact of food's visual variation on its appeal.

Ultra-Processed Foods and Mental Health: Where Do Eating Disorders Fit into the Puzzle?

Ultra-processed foods (UPFs) like pastries, packaged snacks, fast foods, and sweetened beverages have become dominant in the modern food supply and are strongly associated with numerous public health concerns. While the physical health consequences of UPF intake have been well documented (e.g., increased risks of cardiometabolic conditions), less empirical discussion has emphasized the mental health consequences of chronic UPF consumption. Notably, the unique characteristics of UPFs (e.g., artificially high levels of reinforcing ingredients) influence biological processes (e.g., dopamine signaling) in a manner that may contribute to poorer psychological functioning for some individuals. Importantly, gold-standard behavioral lifestyle interventions and treatments specifically for disordered eating do not acknowledge the direct role that UPFs may play in sensitizing reward-related neural functioning, disrupting metabolic responses, and motivating subsequent UPF cravings and intake. The lack of consideration for the influences of UPFs on mental health is particularly problematic given the growing scientific support for the addictive properties of these foods and the utility of ultra-processed food addiction (UPFA) as a novel clinical phenotype endorsed by 14-20% of individuals across international samples. The overarching aim of the present review is to summarize the science of how UPFs may affect mental health, emphasizing contributing biological mechanisms. Specifically, the authors will (1) describe how corporate-sponsored research and financial agendas have contributed to contention and debate about the role of UPFs in health; (2) define UPFs and their nutritional characteristics; (3) review observed associations between UPF intake and mental health conditions, especially with depression; (4) outline the evidence for UPFA; and (5) describe nuanced treatment considerations for comorbid UPFA and eating disorders.

Association between junk food consumption and mental health problems in adults: a systematic review and meta-analysis.

BACKGROUND: Anxiety and depression can seriously undermine mental health and quality of life globally. The consumption of junk foods, including ultra-processed foods, fast foods, unhealthy snacks, and sugar-sweetened beverages, has been linked to mental health. The aim of this study is to use the published literature to evaluate how junk food consumption may be associated with mental health disorders in adults. METHODS: A systematic search was conducted up to July 2023 across international databases including PubMed/Medline, ISI Web of Science, Scopus, Cochrane, Google Scholar, and EMBASE. Data extraction and quality assessment were performed by two independent reviewers. Heterogeneity across studies was assessed using the I2 statistic and chi-square-based Q-test. A random/fixed effect meta-analysis was conducted to pool odds ratios (ORs) and hazard ratios (HRs). RESULTS: Of the 1745 retrieved articles, 17 studies with 159,885 participants were suitable for inclusion in the systematic review and meta-analysis (seven longitudinal, nine cross-sectional and one case-control studies). Quantitative synthesis based on cross-sectional studies showed that junk food consumption increases the odds of having stress and depression (OR = 1.15, 95% CI: 1.06 to 1.23). Moreover, pooling results of cohort studies showed that junk food consumption is associated with a 16% increment in the odds of developing mental health problems (OR = 1.16, 95% CI: 1.07 to 1.24). CONCLUSION: Meta-analysis revealed that consumption of junk foods was associated with an increased hazard of developing depression. Increased consumption of junk food has heightened the odds of depression and psychological stress being experienced in adult populations.

Association between watching eating shows and unhealthy food consumption in Korean adolescents.

BACKGROUND: Eating habits formed during adolescence greatly influence the maintenance of health in adulthood. With the recent development of social media and easy access to the Internet, adolescents watch plenty of food videos, particularly Mukbang and Cookbnag(eating show)content. This media genre's impact on food choices has been covered in several studies; however, studies on unhealthy eating habits directly related to adolescents' exposure to eating shows are insufficient. METHODS: For this study, we used data from the 18th Korea Youth Risk Behavior Survey conducted in 2022 and finalized 50,451 participants. The extent of exposure to eating show media over the course of a week, as well as the consumption of fast food, sugar-sweetened beverages (SSBs), and high caffeinated beverages within that week were measured through self-reporting questionnaires. We classified the participants into two groups based on their frequency of watching eating shows. A multiple logistic regression analysis was performed to investigate the association between eating show and unhealthy food consumption. RESULTS: For both males and females, eating show exposure was strongly associated with the consumption of fast food (male: OR:1.37, 95% CI:1.26-1.49; female: OR:1.46, 95% CI:1.36-1.57), SSB (male: OR:1.42, 95% CI:1.26-1.60; female: OR:1.51, 95% CI:1.35-1.70), and high caffeinated beverage (male: OR:1.30, 95% CI:1.23-1.37; female: OR:1.24, 95% CI:1.18-1.31). It was observed that both sexes were more likely to frequently eat unhealthy food than students who did not watch eating shows. CONCLUSION: Among Korean adolescents, students exposed to eating shows, which primarily aim to entertain, were more likely to consume fast food, SSBs, and high caffeinated beverages. Therefore, this study's findings suggest that eating show could influence adolescents' food choices, highlighting the need for interest in emerging cultures and corresponding health policies.

Analysis of the Nutritional Composition of Ready-to-Use Meat Alternatives in Belgium.

BACKGROUND: The interest in meat alternatives has increased over the years as people embrace more varied food choices because of different reasons. This study aims to analyse the nutritional composition of ready-to-use meat alternatives and compare them with meat (products). METHODS: Nutritional composition values were collected in 2022 of all ready-to-use meat alternatives in Belgian supermarkets, as well as their animal-based counterparts. A one-sample t-test was performed to test the nutritional composition of ready-to-use meat alternatives against norm values, while an independent samples t-test was used to make the comparison with meat. RESULTS: Minced meat and pieces/strips/cubes scored favourably on all norm values. Cheeseburgers/schnitzels, nut/seed burgers and sausages contained more than 10 g/100 g total fat. The saturated fat and salt content was lower than the norm value in each category. Legume burgers/falafel contained less than 10 g/100 g protein. Vegetarian/vegan minced meat and bacon contained fewer calories, total and saturated fat, and more fibre compared to their animal-based counterparts. CONCLUSIONS: Minced meat and pieces/strips/cubes came out as the most favourable categories regarding nutritional composition norm values. Vegetarian/vegan steak came out the least favourable compared to steak, while vegetarian/vegan minced meat and vegetarian/vegan bacon came out the most favourable compared to their animal-based counterparts.

High-Protein Processed Foods: Impact on Diet, Nutritional Status, and Possible Effects on Health.

Proteins are macronutrients with multiple health benefits, but excessive consumption can negatively affect health. This study aimed to evaluate the characteristics of a sample of high-protein processed foods (HPPFs), describe how their consumption affects dietary balance, and acquire knowledge of the consumption patterns of these products in a Spanish population. A sample of HPPFs available in supermarkets and on websites was collected. The contribution to recommended protein intakes was calculated using national and international references and considering the single consumption of the HPPFs and the product plus 150 g of meat. Furthermore, an online survey was conducted among a convenience sample. A total of 36 enriched protein products were evaluated. The percentage of proteins in these products ranges from 10 to 88%. The contribution of the protein recommended intake was within a range of 87.4-306.6% and 66.4-232.8% (women and men, respectively), only considering the additional proteins from 150 g of meat. One hundred thirty-nine participants completed the survey; 67.6% affirmed that they had consumed HPPFs, and half consumed them without following any consumption control. Since these products are accessible to everyone in supermarkets and protein intake is generally higher than the recommended limits, regulating the mass sale of HPPFs is essential to ensure they do not lead to protein overconsumption.

Ultra-Processed Foods: A Narrative Review of the Impact on the Human Gut Microbiome and Variations in Classification Methods.

Ultra-processed foods (UPFs) are foods that are industrially processed and are often pre-packaged, convenient, energy-dense, and nutrient-poor. UPFs are widespread in the current Western diet and their proposed contribution to non-communicable diseases such as obesity and cardiovascular disease is supported by numerous studies. UPFs are hypothesized to affect the body in multiple ways, including by inducing changes in the gut microbiome. This review summarizes the available research on the effect of UPFs on the gut microbiome. We also review current usage of the NOVA food classification system in randomized controlled trials and observational studies and how its implementation effects UPF research. Despite some differences in methodology between studies, results often associate UPF consumption with a number of negative health consequences. There are attempts to standardize a UPF classification system; however, reaching and implementing a consensus is difficult. Future studies focusing on the mechanisms by which UPFs effect the body, including through the microbiome and metabolome, will be essential to refine our understanding of the effects of UPFs on human health.

Evaluation of the Consumption of Junk Food Products and Lifestyle among Teenagers and Young Population from Romania.

BACKGROUND: The long-term consumption of junk food products can lead to nutritional and metabolic imbalances, especially when it is associated with a lack of physical activity and the consumption of alcohol or other high-calorie products. METHODS: The evaluation of junk food consumption among teenagers and young people in Romania was carried out with the help of a cross-sectional study based on a questionnaire. RESULTS: A total number of 1017 respondents participated in this study, comprising 470 males and 547 females aged between 16 and 25 years. Although the majority of young people fell into the normal-weight category (607 of them, p < 0.0001), some aspects can be noted that in the long term can produce a series of nutritional imbalances: an increased tendency toward sedentarism, with 553 (p = 0.613) of the respondents declaring that they performed sports rarely or not at all, and a tendency toward relatively high consumption of foods high in calories (fast food products and especially fried potatoes, hamburgers, shawarma, pastries, and snacks, along with sweetened drinks and even alcoholic beverages). The respondents participating in this study even indicated a perceived addiction to the consumption of certain products: coffee (50.48%), fried potatoes (38.9%), hamburgers (37.05%), shawarma (31.65%), and snacks (30.08%). Many of these products are rich in calories, saturated fat, and even trans fat. CONCLUSIONS: This study highlights a series of aspects that can have long-term negative effects related to the excess weight associated with other imbalances: consumption preferences among young people for hypercaloric fast food products, sweetened drinks associated with reduced physical activity, and even the development of some forms of food addictions for a series of hypercaloric foods.

Ultra-Processed Food Consumption and Gastrointestinal Cancer Risk: A Systematic Review and Meta-Analysis.

INTRODUCTION: Ultra-processed food (UPF) intake has been associated with a higher risk of obesity, hypertension, type 2 diabetes, and cardiovascular diseases. The initial data on the relationship between UPF consumption and cancer risk were derived from retrospective observational studies with conflicting results. This systematic review and meta-analysis of prospective cohort studies aimed to investigate the association between UPF consumption and gastrointestinal cancer risk. METHODS: PubMed, Embase, and Cochrane databases were searched for prospective cohort studies that compared the highest vs the lowest level of UPF consumption according to NOVA food classification and reported the risk of gastrointestinal cancers by subsite. The association with cancer was quantified as hazard ratios (HR) using a random-effects model. RESULTS: Five prospective cohort studies were included in this review comprising 1,128,243 participants (241,201 participants in the highest and 223,366 in the lowest levels of UPF consumption). The mean follow-up ranged from 5.4 to 28 years. The highest UPF consumption was significantly associated with an increased risk of colorectal cancer (HR 1.11; 95% confidence interval [CI] 1.03-1.21; P = 0.01; I2 = 31%), colon cancer (HR 1.12; 95% CI 1.02-1.23; P = 0.02; I2 = 0%), and non-cardia gastric cancer (HR 1.43; 95% CI 1.02-2.00; P = 0.04; I2 = 0%) compared with the lowest UPF intake. However, no association was found between high UPF consumption and hepatocellular, esophageal, pancreatic, gastric cardia, and rectal cancer. DISCUSSION: The highest level of UPF consumption was significantly associated with colorectal and non-cardia gastric cancer.