Blood-Based Multiomics-Guided Detection of a Precancerous Pancreatic Tumor.

Over a decade ago, longitudinal multiomics analysis was pioneered for early disease detection and individually tailored precision health interventions. However, high sample processing costs, expansive multiomics measurements along with complex data analysis have made this approach to precision/personalized medicine impractical. Here we describe in a case report, a more practical approach that uses fewer measurements, annual sampling, and faster decision making. We also show how this approach offers promise to detect an exceedingly rare and potentially fatal condition before it fully manifests. Specifically, we describe in the present case report how longitudinal multiomics monitoring (LMOM) helped detect a precancerous pancreatic tumor and led to a successful surgical intervention. The patient, enrolled in an annual blood-based LMOM since 2018, had dramatic changes in the June 2021 and 2022 annual metabolomics and proteomics results that prompted further clinical diagnostic testing for pancreatic cancer. Using abdominal magnetic resonance imaging, a 2.6 cm lesion in the tail of the patient's pancreas was detected. The tumor fluid from an aspiration biopsy had 10,000 times that of normal carcinoembryonic antigen levels. After the tumor was surgically resected, histopathological findings confirmed it was a precancerous pancreatic tumor. Postoperative omics testing indicated that most metabolite and protein levels returned to patient's 2018 levels. This case report illustrates the potentials of blood LMOM for precision/personalized medicine, and new ways of thinking medical innovation for a potentially life-saving early diagnosis of pancreatic cancer. Blood LMOM warrants future programmatic translational research with the goals of precision medicine, and individually tailored cancer diagnoses and treatments.

Dietary Magnesium Intake Is Inversely Associated With Ulcerative Colitis: A Case-Control Study.

Background: Ulcerative colitis (UC) causes long-lasting inflammation and ulcers in the gut. Limited observational data are available linking dietary magnesium intake and UC. In the present study, we aimed to investigate the association between dietary magnesium intake and UC in adults. Methods: The current population-based case-control study was performed on 109 UC patients and 218 age (±2 years) and sex-matched controls. The diagnosis of UC was made according to the standard criteria by a gastroenterology specialist. Dietary intakes were assessed using a validated self-administrated 106-item dish-based Food Frequency Questionnaire (FFQ). We also used a pretested questionnaire to collect data on potential confounders. Results: Individuals in the top tertile of magnesium intake were less likely to have UC compared with those in the bottom tertile. A significant inverse relationship was found between dietary magnesium intake and UC (odds ratio [OR]: 0.32, 95% confidence interval [CI]: 0.18-0.59) in the crude model. This relationship was also observed when we took several potential confounding into account (OR: 0.30, 95% CI: 0.14-0.68). Conclusions: Adherence to a magnesium-rich diet may have a role in preventing UC. However, further studies are needed to confirm our findings.

Nutrient patterns in relation to insulin resistance and endothelial dysfunction in Iranian women.

Prior studies have mainly focused on the association of one specific nutrient with insulin resistance (IR) and endothelial dysfunction and limited studies have assessed the association with different nutrient patterns (NPs). We examined the association between various NPs and IR and endothelial dysfunction among Iranian women. This cross-sectional study was carried out on a sample of 368 female nurses. A 106-items food frequency questionnaire (FFQ) was applied for dietary assessments. Using factor analysis, the relationships between NPs and markers of insulin resistance (HOMA-IR, HOMA-ß, and QUICKY), and endothelial dysfunction (E-selectin, sICAM-1, and sVCAM-1) were assessed. Mean age and body mass index of participants were respectively 35.21 years and 24.04 kg/m2. Three major NPs were identified. NP1, named as "dairy, fruits, and vegetables" had high values of potassium, folate, vitamins A and C, magnesium, and beta carotene. No significant association was observed between this NP and insulin resistance or endothelial dysfunction indices. The second NP was full of chromium, selenium, copper, vitamin B6, monounsaturated fatty acid (MUFA), thiamin, vitamin D, and iron. Adherence to NP2 (named "legumes, nuts, and protein foods") was associated with lower values of insulin (6.8 ± 1.1 versus 8.4 ± 1.1, P = 0.01), homeostasis model assessment-Insulin resistance (HOMA-IR) (1.3 ± 0.2 versus 1.7 ± 0.2, P = 0.02), and vascular adhesion molecule 1 (VCAM-1) (444.2 ± 27.9 versus 475.8 ± 28.4, P = 0.03). However, adherence to the third NP, rich in saturated fatty acid (SFA), cholesterol, sodium, zinc, vitamin E, and B12, described as "animal fat and meat + vitamin E", was associated with higher amounts of homeostasis model assessment-ß (HOMA-ß) (531.3 ± 176.2 versus 48.7 ± 179.8, P = 0.03). In conclusion, following the NP2, correlated with higher intakes of chromium, selenium, copper, vitamin B6, MUFA and thiamin was associated with lower values of insulin, HOMA-IR, and sVCAM-1. Adherence to NP3, rich in SFA, cholesterol, vitamin E, vitamin B12, and zinc was associated with higher levels of HOMA-ß.

Exploring new subgroups for irritable bowel syndrome using a machine learning algorithm.

Irritable bowel syndrome (IBS) is a complicated gut-brain axis disorder that has typically been classified into subgroups based on the major abnormal stool consistency and frequency. The presence of components other than lower gastrointestinal (GI) symptoms, such as psychological burden, has also been observed in IBS manifestations. The purpose of this research is to redefine IBS subgroups based on upper GI symptoms and psychological factors in addition to lower GI symptoms using an unsupervised machine learning algorithm. The clustering of 988 individuals who met the Rome III criteria for diagnosis of IBS was performed using a mixed-type data clustering algorithm. Nine sub-groups emerged from the proposed clustering: (I) High diarrhea, pain, and psychological burden, (II) High upper GI, moderate lower GI, and psychological burden, (III) High psychological burden and moderate overall GI, (IV) High constipation, moderate upper GI, and high psychological burden, (V) moderate constipation and low psychological burden, (VI) High diarrhea and moderate psychological burden, (VII) moderate diarrhea and low psychological burden, (VIII) Low overall GI, and psychological burden, (IX) Moderate lower GI, and low psychological burden. The proposed procedure led to the discovery of new homogeneous clusters in addition to certain well-known Rome sub-types for IBS.

Dietary intake of phytochemicals in association with irritable bowel syndrome in adults.

BACKGROUND & AIM: There is limited data regarding the association between phytochemical-rich diets and irritable bowel syndrome (IBS). The current study aimed to cross-sectionally evaluate the association of dietary phytochemical index (DPI) with the odds and severity of IBS. METHODS: In this study, which included 3362 Iranian healthcare staffs, a dish-based semi-quantitative food frequency questionnaire (DS-FFQ) was utilized to collect dietary information. The DPI was defined as the daily percentage of calories consumed from phytochemical-rich foods. The IBS assessment was performed using a revised Iranian version of the Rome III questionnaire. We applied the restricted cubic spline (RCS) to detect the possible non-linear dependency of the relationship between DPI and the odds of IBS. RESULTS: The mean age, Body Mass Index (BMI), and DPI scores of the participants were 36.29 ± 7.8 years, 24.90 ± 3.8 kg/m2, and 16.07 ± 9.01, respectively. After adjusting for possible confounders, no significant association was observed between DPI and odds of IBS in the whole study population or in gender- and BMI-stratified analyses. We found a significant inverse association between DPI and IBS severity in the study population (OR: 0.70; 95% CI: 0.51-0.98). Concerning gender, such an association was only found in women (OR: 0.65; 95% CI: 0.44-0.96). However, there was no significant relationship between DPI and IBS severity in BMI subgroups. In addition, we found no meaningful relationship between DPI and IBS subtypes. The RCS model showed that there is no non-linear relationship between DPI classification and IBS (non-linear test, χ2 = 1.14, Pnon-linearity = 0.513). CONCLUSIONS: Higher phytochemical intake was associated with reduced IBS severity, particularly in women. Further prospective studies are required to confirm these findings.

Re-investigation of functional gastrointestinal disorders utilizing a machine learning approach.

BACKGROUND: Functional gastrointestinal disorders (FGIDs), as a group of syndromes with no identified structural or pathophysiological biomarkers, are currently classified by Rome criteria based on gastrointestinal symptoms (GI). However, the high overlap among FGIDs in patients makes treatment and identifying underlying mechanisms challenging. Furthermore, disregarding psychological factors in the current classification, despite their approved relationship with GI symptoms, underlines the necessity of more investigation into grouping FGID patients. We aimed to provide more homogenous and well-separated clusters based on both GI and psychological characteristics for patients with FGIDs using an unsupervised machine learning algorithm. METHODS: Based on a cross-sectional study, 3765 (79%) patients with at least one FGID were included in the current study. In the first step, the clustering utilizing a machine learning algorithm was merely executed based on GI symptoms. In the second step, considering the previous step's results and focusing on the clusters with a diverse combination of GI symptoms, the clustering was re-conducted based on both GI symptoms and psychological factors. RESULTS: The first phase clustering of all participants based on GI symptoms resulted in the formation of pure and non-pure clusters. Pure clusters exactly illustrated the properties of most pure Rome syndromes. Re-clustering the members of the non-pure clusters based on GI and psychological factors (i.e., the second clustering step) resulted in eight new clusters, indicating the dominance of multiple factors but well-discriminated from other clusters. The results of the second step especially highlight the impact of psychological factors in grouping FGIDs. CONCLUSIONS: In the current study, the existence of Rome disorders, which were previously defined by expert opinion-based consensus, was approved, and, eight new clusters with multiple dominant symptoms based on GI and psychological factors were also introduced. The more homogeneous clusters of patients could lead to the design of more precise clinical experiments and further targeted patient care.

The association of plant-based dietary pattern with general and abdominal obesity: a large cross-sectional study.

Purpose: Only a few studies have studied the association between plant-based dietary index (PDI) and the prevalence of obesity. The purpose of this study was to investigate the association between PDI and the prevalence of general and abdominal obesity in a large sample of Iranian adults. Methods: The current cross-sectional study was performed from 2010 to 2012 in Isfahan, Iran. This study comprised 6,724 adults between the ages of 18 and 55. We analyzed data from 6,724 participants who were classified as having general obesity and 5,203 individuals who were classified as having abdominal obesity. Dietary intake was assessed using a validated food frequency questionnaire. We determined the PDI by assigning plant foods positive scores and animal foods negative values using the method of Satija et al. General obesity was defined as having a body mass index (BMI) greater than 30 kg/m2, whereas abdominal obesity was classified as having a waist circumference (WC) greater than 88 cm for women and 102 cm for men. Data was examined using Chi-squared test and the analysis of variance (ANOVA and ANCOVA). Multivariable binary logistic regression analyses were performed to evaluate the association between PDI and risk of general as well as abdominal obesity. Results: The mean age of the study participants was 36.8 ± 8.08 years, and 57% of them were female. General obesity prevalence was 9.6%, while abdominal obesity was 26.8%. In all the unadjusted and multivariable adjusted models of the total population, there was no significant association between highest vs. lowest adherence to the PDI and general obesity or abdominal obesity. No significant association was found when men and women were analyzed separately as well. Conclusion: In the present study, no association was observed between PDI and general and abdominal obesity in the Iranian adult population.

Association between food-based dietary inflammatory potential and ulcerative colitis: a case-control study.

Despite several studies on the link between dietary inflammatory potential and risk of several conditions, limited studies investigated the association between pro-inflammatory diet and ulcerative colitis (UC). The objective of the present study was to examine the link between food-based dietary inflammatory potential (FDIP) and odds of UC in Iranian adults. This case-control study was carried out among 109 cases and 218 randomly chosen healthy controls. UC was diagnosed and confirmed by a gastroenterologist. Patients with this condition were recruited from Iranian IBD registry. Age- and sex-matched controls were selected randomly from participants of a large cross-sectional study. Dietary data were obtained using a validated 106-item semi-quantitative food frequency questionnaire (FFQ). We calculated FDIP score using subjects' dietary intakes of 28 pre-defined food groups. In total 67% of subjects were female. There was no significant difference in mean age between cases and controls (39.5 vs. 41.5y; p = 0.12). The median (interquartile range) of FDIP scores for cases and controls were - 1.36(3.25) and - 1.54(3.15), respectively. We found no significant association between FDIP score and UC in the crude model (OR 0.93; 95% CIs 0.53-1.63). Adjustment for several potential confounders in multivariate model did not change this association (OR 1.12; 95% CIs 0.46-2.71). We failed to observe any significant association between greater adherence to a pro-inflammatory diet and risk of UC in this study. Prospective cohort studies are needed to further assess this relationship.

Face-to-face interviews versus Internet surveys: Comparison of two data collection methods in the Rome foundation global epidemiology study: Implications for population-based research.

BACKGROUND AND AIMS: The Rome Foundation Global Epidemiology Study (RFGES) assessed the prevalence, burden, and associated factors of Disorders of Gut-Brain Interaction (DGBI) in 33 countries around the world. Achieving worldwide sampling necessitated use of two different surveying methods: In-person household interviews (9 countries) and Internet surveys (26 countries). Two countries, China and Turkey, were surveyed with both methods. This paper examines the differences in the survey results with the two methods, as well as likely reasons for those differences. METHODS: The two RFGES survey methods are described in detail, and differences in DGBI findings summarized for household versus Internet surveys globally, and in more detail for China and Turkey. Logistic regression analysis was used to elucidate factors contributing to these differences. RESULTS: Overall, DGBI were only half as prevalent when assessed with household vs Internet surveys. Similar patterns of methodology-related DGBI differences were seen within both China and Turkey, but prevalence differences between the survey methods were dramatically larger in Turkey. No clear reasons for outcome differences by survey method were identified, although greater relative reduction in bowel and anorectal versus upper gastrointestinal disorders when household versus Internet surveying was used suggests an inhibiting influence of social sensitivity. CONCLUSIONS: The findings strongly indicate that besides affecting data quality, manpower needs and data collection time and costs, the choice of survey method is a substantial determinant of symptom reporting and DGBI prevalence outcomes. This has important implications for future DGBI research and epidemiological research more broadly.

Dietary riboflavin intake in relation to psychological disorders in Iranian adults: an observational study.

Findings of earlier investigations on association between dietary riboflavin intake and psychological disorders are contradictory. Therefore, the relation between dietary riboflavin intake and depression, anxiety, and psychological distress was assessed in Iranian adults. In this cross-sectional study, dietary intakes of 3362 middle-aged adults were collected using a validated dish-based food frequency questionnaire. Daily intake of riboflavin for each participant was calculated by summing up the amount of riboflavin contents of all foods and dishes. Hospital Anxiety and Depression Scale (HADS) and General Health Questionnaire (GHQ), as validated questionnaires among Iranians, have been applied to assess depression, anxiety, and psychological distress. After considering potential confounders, adults in the top energy-adjusted quartile of riboflavin intake, compared to the bottom quartile, had decreased odds of depression (OR = 0.66; 95%CI 0.49, 0.88), anxiety (OR = 0.64; 95%CI 0.44, 0.94) and high psychological distress (OR = 0.65; 95%CI 0.48, 0.89). Stratified analysis by sex revealed that men in the forth quartile of riboflavin intake, compared with those in the first quartile, had respectively 51 and 55% lower odds of depression (OR = 0.49; 95%CI 0.29, 0.83) and anxiety (OR = 0.45; 95%CI 0.21, 0.95). In women, riboflavin intake was significantly associated with lower odds of psychological distress (OR = 0.67; 95%CI 0.46, 0.98). An inverse relation was observed between dietary riboflavin intake and chance of psychological disorders in Iranian adults. High intake of riboflavin decreased the chance of depression and anxiety in men and high psychological distress in women. More prospective studies are needed to confirm these findings.