A cell-free biosensor for multiplexed and sensitive detection of biological warfare agents.

The rapid and precise detection of pathogenic agents is critical for public health and societal stability. The detection of biological warfare agents (BWAs) is especially vital within military and counter-terrorism contexts, essential in defending against biological threats. Traditional methods, such as polymerase chain reaction (PCR), are limited by their need for specific settings, impacting their adaptability and versatility. This study introduces a cell-free biosensor for BWA detection by converting the 16S rRNA of targeted pathogens into detectable functional protein molecules. The modular nature of this approach allows for the flexible configuration of pathogen detection, enabling the simultaneous identification of multiple pathogenic 16S rRNAs through customized reporter proteins for each targeted sequence. Furthermore, we demonstrate how this method integrates with techniques utilizing retroreflective Janus particles (RJPs) for facile and highly sensitive pathogen detection. The cell-free biosensor, employing RJPs to measure the reflection of non-chromatic white light, can detect 16S rRNA from BWAs at femtomolar levels, corresponding to tens of colony-forming units per milliliter of pathogenic bacteria. These findings represent a significant advancement in pathogen detection, offering a more efficient and accessible alternative to conventional methodologies.

Dynamic three-dimensional structures of a metal-organic framework captured with femtosecond serial crystallography.

Crystalline systems consisting of small-molecule building blocks have emerged as promising materials with diverse applications. It is of great importance to characterize not only their static structures but also the conversion of their structures in response to external stimuli. Femtosecond time-resolved crystallography has the potential to probe the real-time dynamics of structural transitions, but, thus far, this has not been realized for chemical reactions in non-biological crystals. In this study, we applied time-resolved serial femtosecond crystallography (TR-SFX), a powerful technique for visualizing protein structural dynamics, to a metal-organic framework, consisting of Fe porphyrins and hexazirconium nodes, and elucidated its structural dynamics. The time-resolved electron density maps derived from the TR-SFX data unveil trifurcating structural pathways: coherent oscillatory movements of Zr and Fe atoms, a transient structure with the Fe porphyrins and Zr6 nodes undergoing doming and disordering movements, respectively, and a vibrationally hot structure with isotropic structural disorder. These findings demonstrate the feasibility of using TR-SFX to study chemical systems.

Feasibility and usefulness of cognitive monitoring using a new home-based cognitive test in mild cognitive impairment: a prospective single arm study.

BACKGROUND: The risk of dementia is increased in subjects with mild cognitive impairment (MCI). Despite the plethora of in-person cognitive tests, those that can be administered over the phone are lacking. We hypothesized that a home-based cognitive test (HCT) using phone calls would be feasible and useful in non-demented elderly. We aimed to assess feasibility and validity of a new HCT as an optional cognitive monitoring tool without visiting hospitals. METHODS: Our study was conducted in a prospective design during 24 weeks. We developed a new HCT consisting of 20 questions (score range 0-30). Participants with MCI (n = 38) were consecutively enrolled and underwent regular HCTs during 24 weeks. Associations between HCT scores and in-person cognitive scores and Alzheimer's disease (AD) biomarkers were evaluated. In addition, HCT scores in MCI participants were cross-sectionally compared with age-matched cognitively normal (n = 30) and mild AD dementia (n = 17) participants for discriminative ability of the HCT. RESULTS: HCT had good intra-class reliability (test-retest Cronbach's alpha 0.839). HCT scores were correlated with the Mini-Mental State Examination (MMSE), verbal memory delayed recall, and Stroop test scores but not associated with AD biomarkers. HCT scores significantly differed among cognitively normal, MCI, and mild dementia participants, indicating its discriminative ability. Finally, 32 MCI participants completed follow-up evaluations, and 8 progressed to dementia. Baseline HCT scores in dementia progressors were lower than those in non-progressors (p = 0.001). CONCLUSION: The feasibility and usefulness of the HCT were demonstrated in elderly subjects with MCI. HCT could be an alternative option to monitor cognitive decline in early stages without dementia.

Sensitive Methods to Detect Single-Stranded Nucleic Acids of Food Pathogens Based on Cell-Free Protein Synthesis and Retroreflection Signal Detection.

Cell-free protein synthesis (CFPS) has recently gained considerable attention as a new platform for developing methods to detect various molecules, ranging from small chemicals to biological macromolecules. Retroreflection has been used as an alternative signal to develop analytical methods because it can be detected by using a simple instrument comprising a white light source and a camera. Here, we report a novel reporter protein that couples the capability of CFPS and the simplicity of retroreflection signal detection. The design of the reporter was based on two pairs of protein-peptide interactions, SpyCatcher003-SpyTag003 and MDM2-PMI(N8A). MDM2-MDM2-SpyCatcher003 was decided as the reporter protein, and the two peptides, SpyTag003 and PMI(N8A), were immobilized on the surfaces of retroreflective Janus particles and microfluidic chips, respectively. The developed retroreflection signal detection system was combined with a previously reported CFPS reaction that can transduce the presence of a single-stranded nucleic acid into protein synthesis. The resulting methods were applied to detect 16S rRNAs of several foodborne pathogens. Concentration-dependent relationships were observed over a range of 10° fM to 102 pM, with the limits of detection being single-digit femtomolar concentrations. Considering the designability of the CFPS system for other targets, the retroreflection signal detection method will enable the development of novel methods to detect various molecules.

Usefulness of longitudinal nodule-matching algorithm in computer-aided diagnosis of new pulmonary metastases on cancer surveillance CT scans.

Background: Detecting new pulmonary metastases by comparing serial computed tomography (CT) scans is crucial, but a repetitive and time-consuming task that burdens the radiologists' workload. This study aimed to evaluate the usefulness of a nodule-matching algorithm with deep learning-based computer-aided detection (DL-CAD) in diagnosing new pulmonary metastases on cancer surveillance CT scans. Methods: Among patients who underwent pulmonary metastasectomy between 2014 and 2018, 65 new pulmonary metastases missed by interpreting radiologists on cancer surveillance CT (Time 2) were identified after a retrospective comparison with the previous CT (Time 1). First, DL-CAD detected nodules in Time 1 and Time 2 CT images. All nodules detected at Time 2 were initially considered metastasis candidates. Second, the nodule-matching algorithm was used to assess the correlation between the nodules from the two CT scans and to classify the nodules at Time 2 as "new" or "pre-existing". Pre-existing nodules were excluded from metastasis candidates. We evaluated the performance of DL-CAD with the nodule-matching algorithm, based on its sensitivity, false-metastasis candidates per scan, and positive predictive value (PPV). Results: A total of 475 lesions were detected by DL-CAD at Time 2. Following a radiologist review, the lesions were categorized as metastases (n=54), benign nodules (n=392), and non-nodules (n=29). Upon comparison of nodules at Time 1 and 2 using the nodule-matching algorithm, all metastases were classified as new nodules without any matching errors. Out of 421 benign lesions, 202 (48.0%) were identified as pre-existing and subsequently excluded from the pool of metastasis candidates through the nodule-matching algorithm. As a result, false-metastasis candidates per CT scan decreased by 47.9% (from 7.1 to 3.7, P<0.001) and the PPV increased from 11.4% to 19.8% (P<0.001), while maintaining sensitivity. Conclusions: The nodule-matching algorithm improves the diagnostic performance of DL-CAD for new pulmonary metastases, by lowering the number of false-metastasis candidates without compromising sensitivity.

Capturing the generation and structural transformations of molecular ions.

Molecular ions are ubiquitous and play pivotal roles1-3 in many reactions, particularly in the context of atmospheric and interstellar chemistry4-6. However, their structures and conformational transitions7,8, particularly in the gas phase, are less explored than those of neutral molecules owing to experimental difficulties. A case in point is the halonium ions9-11, whose highly reactive nature and ring strain make them short-lived intermediates that are readily attacked even by weak nucleophiles and thus challenging to isolate or capture before they undergo further reaction. Here we show that mega-electronvolt ultrafast electron diffraction (MeV-UED)12-14, used in conjunction with resonance-enhanced multiphoton ionization, can monitor the formation of 1,3-dibromopropane (DBP) cations and their subsequent structural dynamics forming a halonium ion. We find that the DBP+ cation remains for a substantial duration of 3.6 ps in aptly named 'dark states' that are structurally indistinguishable from the DBP electronic ground state. The structural data, supported by surface-hopping simulations15 and ab initio calculations16, reveal that the cation subsequently decays to iso-DBP+, an unusual intermediate with a four-membered ring containing a loosely bound17,18 bromine atom, and eventually loses the bromine atom and forms a bromonium ion with a three-membered-ring structure19. We anticipate that the approach used here can also be applied to examine the structural dynamics of other molecular ions and thereby deepen our understanding of ion chemistry.

Use of artificial intelligence in triaging of chest radiographs to reduce radiologists' workload.

OBJECTIVES: To evaluate whether deep learning-based detection algorithms (DLD)-based triaging can reduce outpatient chest radiograph interpretation workload while maintaining noninferior sensitivity. METHODS: This retrospective study included patients who underwent initial chest radiography at the outpatient clinic between June 1 and June 30, 2017. Readers interpreted radiographs with/without a commercially available DLD that detects nine radiologic findings (atelectasis, calcification, cardiomegaly, consolidation, fibrosis, nodules, pneumothorax, pleural effusion, and pneumoperitoneum). The reading order was determined in a randomized, crossover manner. The radiographs were classified into negative and positive examinations. In a 50% worklist reduction scenario, radiographs were sorted in descending order of probability scores: the lower half was regarded as negative exams, while the remaining were read with DLD by radiologists. The primary analysis evaluated noninferiority in sensitivity between radiologists reading all radiographs and simulating a 50% worklist reduction, with the inferiority margin of 5%. The specificities were compared using McNemar's test. RESULTS: The study included 1964 patients (median age [interquartile range], 55 years [40-67 years]). The sensitivity was 82.6% (195 of 236; 95% CI: 77.5%, 87.3%) when readers interpreted all chest radiographs without DLD and 83.5% (197 of 236; 95% CI: 78.8%, 88.1%) in the 50% worklist reduction scenario. The difference in sensitivity was 0.8% (95% CI: - 3.8%, 5.5%), establishing noninferiority of 50% worklist reduction (p = 0.01). The specificity increased from 86.7% (1498 of 1728) to 90.4% (1562 of 1728) (p < 0.001) with DLD-based triage. CONCLUSION: Deep learning-based triaging may substantially reduce workload without lowering sensitivity while improving specificity. CLINICAL RELEVANCE STATEMENT: Substantial workload reduction without lowering sensitivity was feasible using deep learning-based triaging of outpatient chest radiograph; however, the legal responsibility for incorrect diagnoses based on AI-standalone interpretation remains an issue that should be defined before clinical implementation. KEY POINTS: • A 50% workload reduction simulation using deep learning-based detection algorithm maintained noninferior sensitivity while improving specificity. • The CT recommendation rate significantly decreased in the disease-negative patients, whereas it slightly increased in the disease-positive group without statistical significance. • In the exploratory analysis, the noninferiority of sensitivity was maintained until 70% of the workload was reduced; the difference in sensitivity was 0%.

Association of milk and dairy product consumption with the incidence of cardio-cerebrovascular disease incidence in middle-aged and older Korean adults: a 16-year follow-up of the Korean Genome and Epidemiology Study.

BACKGROUND/OBJECTIVES: Unhealthy dietary behaviors constitute one of risk the factors for chronic and cardiovascular diseases, which are prevalent in middle-aged and older populations. Milk and dairy products are high-quality foods and important sources of calcium. Calcium protects against osteoporosis and cardiovascular disease. Therefore, this study investigated the association of milk and dairy product consumption with cardio-cerebrovascular disease incidence in middle-aged and older Korean adults. SUBJECTS/METHODS: Data were derived from the Ansan-Anseong cohort study, and a total of 8,009 individuals aged 40-69 years were selected and followed up biennially. Cox proportional hazard models were used to examine the association of milk and dairy product consumption with cardio-cerebrovascular disease incidence. RESULTS: During a mean follow-up period of 96.5 person-months, 552 new cases of cardio-cerebrovascular disease were documented. Milk consumers (< 1 serving/day) exhibited a 23% lower risk of cardio-cerebrovascular disease incidence than non-milk consumers (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.61-0.97; P for trend = 0.842). High yogurt consumption was associated with a 29% lower incidence risk (≥ 0.5 servings/day vs. none: HR, 0.71; 95% CI, 0.53-0.96; P for trend = 0.049), whereas high ice cream consumption was associated with a 70% higher risk of cardio-cerebrovascular disease incidence (≥ 0.5 servings/day vs. none: HR, 1.70; 95% CI, 1.01-2.88; P for trend = 0.070). CONCLUSIONS: This study indicates that less than one serving of milk and high yogurt consumption are associated with a lower cardio-cerebrovascular disease risk in the middle-aged and older populations.

Cerium Photocatalyst in Action: Structural Dynamics in the Presence of Substrate Visualized via Time-Resolved X-ray Liquidography.

[Ce(III)Cl6]3-, with its earth-abundant metal element, is a promising photocatalyst facilitating carbon-halogen bond activation. Still, the structure of the reaction intermediate has yet to be explored. Here, we applied time-resolved X-ray liquidography (TRXL), which allows for direct observation of the structural details of reaction intermediates, to investigate the photocatalytic reaction of [Ce(III)Cl6]3-. Structural analysis of the TRXL data revealed that the excited state of [Ce(III)Cl6]3- has Ce-Cl bonds that are shorter than those of the ground state and that the Ce-Cl bond further contracts upon oxidation. In addition, this study represents the first application of TRXL to both photocatalyst-only and photocatalyst-and-substrate samples, providing insights into the substrate's influence on the photocatalyst's reaction dynamics. This study demonstrates the capability of TRXL in elucidating the reaction dynamics of photocatalysts under various conditions and highlights the importance of experimental determination of the structures of reaction intermediates to advance our understanding of photocatalytic mechanisms.

The Association of Nocturnal Seizures and Interictal Cardiac/Central Autonomic Function in Frontal Lobe Epilepsy: Heart Rate Variability and Central Autonomic Network Analysis.

Purpose: Patients with epilepsy frequently experience autonomic dysfunction, closely related to sudden unexplained death in epilepsy (SUDEP). SUDEP occurs most often at night or during sleep, and frequent nocturnal seizures are an established risk factor. This study investigated the influence of nocturnal seizures on autonomic dysfunction in epilepsy. Patients and Methods: This retrospective study enrolled frontal lobe epilepsy (FLE) patients who performed 24-hour EEG monitoring. All participants were divided into nocturnal FLE (NFLE, > 90% of seizures occurring during sleep) or diurnal FLE (DFLE) groups. EEG and ECG signals were simultaneously obtained during waking and sleep stages. EEG current density source and connectivity analysis of the autonomic network were performed. ECG was analyzed across time and frequency domains heart rate variability (HRV) analysis method was used. The obtained parameters were compared between the NFLE and DFLE groups. Results: Fifteen NFLE and 16 DFLE patients were enrolled with no significant difference in age, sex, disease duration, seizure frequency, or the number of anti-seizure medications between the two groups. During sleep, a decrease in HRV parameters and an increase of the beta-1 (13-22 Hz) current source density power in the bilateral paracentral lobule (BA4,5,6), precuneus (BA7), and cingulate (BA31) were observed in the NFLE group compared to DFLE group. The NFLE group also showed hyperconnectivity in the central autonomic (12 edges distributed over 10 nodes), sympathetic (2 edges distributed over 3 nodes), and parasympathetic (4 edges distributed over 6 nodes) beta-1 frequency band networks during sleep. During wakefulness, central and cardiac autonomic variables were not significantly different between the NFLE and DFLE groups. Conclusion: Interictal cardiac and central autonomic dysfunction occurred simultaneously and can be attributed to the brain-heart autonomic axis. Our findings suggest that nocturnal seizures may contribute to interictal autonomic dysfunction during sleep in people with epilepsy.

Prospective Associations between Dietary Patterns and Abdominal Obesity in Middle-Aged and Older Korean Adults.

This study aimed to identify major dietary patterns associated with abdominal obesity in middle-aged and older Korean adults. Data from the Korean Genome and Epidemiology Study were used. A total of 48,037 Korean adults aged ≥40 years without abdominal obesity at baseline were followed-up. Dietary assessment was conducted using a validated 106-item food-frequency questionnaire, and dietary patterns were identified using factor analysis. Abdominal obesity was defined as a waist circumference of ≥90 cm for men and ≥85 cm for women, according to the Korean Society for the Study of Obesity. Multivariable Cox proportional-hazards models were used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the future risk of abdominal obesity for each dietary pattern after adjusting for potential covariates. After an average follow-up of 4.89 years, we reported 5878 cases (1932 men and 3946 women) of abdominal obesity. Based on factor analysis, three major dietary patterns were identified in both men and women: the "healthy", "coffee and sweets", and "multi-grain" patterns. In the fully adjusted model, the "healthy" pattern was inversely associated with the incidence of abdominal obesity (HR for fourth vs. first quartile: 0.86; 95% CI: 0.75-0.98; p for trend = 0.0358 for men; HR for fourth vs. first quartile: 0.90; 95% CI: 0.83-0.99; p for trend = 0.0188 for women), whereas the "coffee and sweets" pattern was positively associated with it (HR for fourth vs. first quartile: 1.23; 95% CI: 1.08-1.40; p for trend = 0.0495 for men; HR for fourth vs. first quartile: 1.14; 95% CI: 1.04-1.25; p for trend = 0.0096 for women). In contrast, the "multi-grain" pattern in men and women showed no significant association with the incidence of abdominal obesity. Diets rich in colorful vegetables, seaweeds, mushrooms, tubers, fruits, soy products, and fish and low in coffee, sweets, and oils/fats might be favorable for reducing the future risk of abdominal obesity, particularly in middle-aged and older Korean adults.

Coupling hCG-based protease sensors with a commercial pregnancy test strip for simple analyses of protease activities.

Proteases play an essential role in many cellular processes, and consequently, abnormalities in their activities are related to various diseases. Methods have been developed to measure the activity of these enzymes, but most involve sophisticated instruments or complicated procedures, which hampers the development of a point-of-care test (POCT). Here, we propose a strategy for developing simple and sensitive methods to analyze protease activity using commercial pregnancy test strips that detect human chorionic gonadotropin (hCG). hCG was engineered to have site-specific conjugated biotin and a peptide sequence, which can be cleaved by a target protease, between hCG and biotin. hCG protein was immobilized on streptavidin-coated beads, resulting in a protease sensor. The hCG-immobilized beads were too large to flow through the membrane of the hCG test strip and yielded only one band in the control line. When the peptide linker was hydrolyzed by the target protease, hCG was released from the beads, and the signal appeared in both the control and test lines. Three protease sensors for matrix metalloproteinase-2, caspase-3, and thrombin were constructed by replacing the protease-cleavable peptide linker. The combination of the protease sensors and a commercial pregnancy strip enabled the specific detection of each protease in the picomolar range, with a 30-min incubation of the hCG-immobilized beads and samples. The modular design of the protease sensor and simple assay procedure will facilitate the development of POCTs for various protease disease markers.

Radiologic Extranodal Extension of Metastatic Lymph Nodes in Patients With Non-Small Cell Lung Cancer: Prognostic Utility and Diagnostic Performance.

BACKGROUND. Pathologic extranodal extension (ENE) in metastatic lymph nodes (LNs) has been associated with unfavorable prognosis in patients with non-small cell lung cancer (NSCLC). OBJECTIVE. The purpose of this article was to evaluate the prognostic utility of radiologic ENE and its diagnostic performance in predicting pathologic ENE in patients with NSCLC. METHODS. This retrospective study included 382 patients (mean age, 67 ± 10 [SD] years; 297 men, 85 women) diagnosed with NSCLC and clinical N1 or N2 disease between January 2010 and December 2016. Two thoracic radiologists reviewed staging chest CT examinations to record subjective overall impression for radiologic ENE (no ENE, possible/probable ENE, or unambiguous ENE), reviewing 30 examinations in consensus and the remaining examinations independently. Kaplan-Meier survival analysis and multivariable Cox proportional hazards model were used to evaluate the utility of radiologic ENE in predicting overall survival (OS). Prognostic utility of radiologic ENE was also assessed in patients with clinical N2a disease. In patients who underwent surgery, sensitivity and specificity were determined of radiologic unambiguous ENE in predicting pathologic ENE. RESULTS. The 5-year OS rates for no ENE, possible/probable ENE, and unambiguous ENE were 44.4%, 39.1%, and 20.9% for reader 1 and 45.7%, 36.6%, and 25.6% for reader 2, respectively. Unambiguous ENE was an independent prognostic factor for worse OS (reader 1: adjusted HR, 1.72, p = .008; reader 2: adjusted HR, 1.56, p = .03), whereas possible/probable ENE was not (reader 1: adjusted HR, 1.18, p = .33; reader 2: adjusted HR, 1.21, p = .25). In patients with clinical N2a disease, 5-year OS rate in patients with versus without unambiguous ENE for reader 1 was 22.2% versus 40.6% (p = .59) and for reader 2 was 27.6% versus 41.0% (p = .49). In 203 patients who underwent surgery (66 with pathologic ENE), sensitivity and specificity of radiologic unambiguous ENE for predicting pathologic ENE were 11% and 93% for reader 1 and 23% and 87% for reader 2. CONCLUSION. Radiologic unambiguous ENE was an independent predictor of worse OS in patients with NSCLC. The finding had low sensitivity but high specificity for pathologic ENE. CLINICAL IMPACT. Radiologic ENE may have a role in NSCLC staging workup and treatment selection.

Association of main meal frequency and skipping with metabolic syndrome in Korean adults: a cross-sectional study.

BACKGROUND: Reduced meal frequency can increase the risk of metabolic syndrome (MetS). However, limited studies have examined the association between meal frequency and skipping meals with MetS. This study aims to analyze the association between main meal frequency and meal skipping with MetS in Korean adults aged ≥ 19 years. METHODS: In this study, we included data from 22,699 Korean adult participants from the 2016-2020 Korea National Health and Nutrition Examination Survey (KNHANES). The 24-h dietary recall method was used to classify the participants into three groups based on main meal frequency (one, two, or three meals per day) and seven groups based on the type of main meal they skipped. Multivariable logistic regression analysis was conducted to determine the association between main meal frequency and the types of main meals skipped with the odds of MetS and its associated components. Appropriate estimates were accounted for using sampling weights, stratification, and clustering. RESULTS: The prevalence of MetS in the study population was 33.8%. The average age of the participants was 47.2 years with 42.6% being men, and 57.4% being women. Men who consumed two meals per day had higher odds of MetS than those who consumed three meals per day (odds ratio [OR] 1.16, 95% confidence interval [CI] 1.01-1.33). Women who consumed two meals per day, and skipped breakfast had increased odds of having elevated fasting blood glucose levels (OR 1.18, 95% CI 1.02-1.35), and elevated triglycerides (OR 1.19, 95% CI 1.02-1.39). However, women who skipped dinner had reduced odds of having elevated fasting blood glucose levels (OR 0.74, 95% CI 0.58-0.94). CONCLUSIONS: Our findings suggest that meal frequency and the type of main meal skipped may be associated with MetS and emphasize the importance of consuming breakfast to prevent MetS.

Identifying the Associations of Nightly Fasting Duration and Meal Timing with Type 2 Diabetes Mellitus Using Data from the 2016-2020 Korea National Health and Nutrition Survey.

Nightly fasting duration and meal timing are associated with metabolic disorders. This study aimed to investigate the relationships of nightly fasting duration and meal timing with type 2 diabetes mellitus (T2DM) using data from the 2016-2020 Korea National Health and Nutrition Survey. A total of 22,685 adults ≥ 19 years were included in this study. Nightly fasting duration was calculated by subtracting the interval between the day's first and last meal eating times from 24 h. The meal timing were analyzed using various parameters, including the times of the first and last eating episodes and the percentage of energy intake during the morning (05:00 to 9:00 a.m.), evening (06:00 to 09:00 p.m.), and night (after 09:00 p.m.). Men who fasted nightly for ≥ 12 h had lower odds of T2DM (odds ratio (OR): 0.86; 95% confidence interval (CI): 0.75-0.99) than those who fasted for < 12 h. Individuals who had their last meal after 09:00 p.m. had higher odds of T2DM (OR: 1.19, 95% CI: 1.03-1.38, men; OR: 1.19, 95% CI: 1.01-1.40, women). Additionally, the percentage of energy intake during the evening was associated with increased odds of T2DM (OR: 1.41, 95% CI: 1.08-1.84, men; OR: 1.32, 95% CI: 1.02-1.70, women). These findings emphasize the importance of nightly fasting duration and meal timing in modulating the risk of T2DM among Korean adults.

Interactions between Bitter Taste Receptor Gene Variants and Dietary Intake Are Associated with the Incidence of Type 2 Diabetes Mellitus in Middle-Aged and Older Korean Adults.

The relationship between the variants of bitter taste receptor gene TAS2R4, dietary intake, and incidence of type 2 diabetes mellitus (T2DM) remains unclear. Hence, we aimed to examine the association of TAS2R4 rs2233998 variants with T2DM incidence in middle-aged and older Korean adults to understand if their association was modulated by dietary intake. Data of the Ansan-Ansung cohort from the Korean Genome and Epidemiology Study were used in this study. A total of 4552 Korean adults aged 40-69 years with no history of T2DM or cancer at baseline were followed-up for 16 years. Dietary intake was assessed using a 103-item food frequency questionnaire, and new T2DM cases were defined based on the World Health Organization and International Diabetes Federation criteria. Multivariate Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for T2DM incidence. During the mean follow-up period of 11.97 years, 1082 (23.77%) new T2DM cases were identified. Women carrying the TT genotype of TAS2R4 rs2233998 exhibited 1.48 times higher incidence of T2DM (HR: 1.48; 95 CI: 1.13-1.93) than those carrying the CC genotype. TAS2R4 rs2233998 variants were positively associated with the incidence of T2DM among Korean women with high intakes of carbohydrates or sugars and low intakes of fruits or vegetables. TT carrier women in the highest tertile of carbohydrate or sugar intake exhibited an increased incidence of T2DM (HR: 2.08, 95% CI: 1.33-3.27 for carbohydrates; HR: 2.31, 95% CI: 1.53-3.51 for sugars) than CC carrier women. Women carrying the TT genotype in the lowest tertile exhibited an increased incidence of T2DM (HR: 1.55, 95% CI: 1.02-2.37 for vegetables; HR: 1.62, 95% CI: 1.06-2.48 for fruits) than women carrying the CC genotype in the highest tertile of vegetable or fruit consumption. However, no association was observed between TAS2R4 rs2233998 variants and dietary intake with T2DM incidence in Korean men. Our findings suggest that variants of TAS2R4 rs2233998 are associated with T2DM incidence, and their associations are strengthened by excessive intake of carbohydrates or sugars and inadequate intake of fruits or vegetables. Diet encompassing optimal intake of carbohydrates or sugars and high intake of fruits or vegetables may minimize the risk of developing T2DM.

CD8α+ dendritic cells potentiate antitumor and immune activities against murine ovarian cancers.

Dendritic cell (DC)-based immunotherapies have been shown to be a potential treatment option for various cancers; however, the exact strategies in ovarian cancer remain unknown. Here, we report the effectiveness of mouse CD8α+ DCs derived from bone marrow hematopoietic stem cells (BM-HSCs), equivalent to human CD141+ DCs, which have proven to be a highly superior subset. Mono-DCs from monocytes and stem-DCs from HSCs were characterized by CD11c+ CD80+ CD86+ and CD8α+ Clec9a+ expression, respectively. Despite a lower dose compared with Mono-DCs, mice treated with pulsed Stem-DCs showed a reduced amount of ascitic fluid and lower body weights compared with those of vehicle-treated mice. These mice treated with pulsed stem-DCs appeared to have fewer tumor implants, which were usually confined in the epithelium of tumor-invaded organs. All mice treated with DCs showed longer survival than the vehicle group, especially in the medium/high dose pulsed Stem-DC treatment groups. Moreover, the stem-DC-treated group demonstrated a low proportion of myeloid-derived suppressor cells and regulatory T cells, high interleukin-12 and interferon-γ levels, and accumulation of several tumor-infiltrating lymphocytes. Together, these results indicate that mouse CD8α+ DCs derived from BM-HSCs decrease tumor progression and enhance antitumor immune responses against murine ovarian cancer, suggesting that better DC vaccines can be used as an effective immunotherapy in EOC treatment. Further studies are necessary to develop potent DC vaccines using human CD141+ DCs.

Fruit and Vegetable Consumption Interacts With HNF1A Variants on the C-Reactive Protein.

Epidemiological studies have demonstrated the inverse association between the intake of fruits and vegetables and inflammation. However, the mechanisms by which inflammation-related genes interact with fruit and vegetable intake and the role of these combinations in inflammation remain unclear. Therefore, we assessed the effect of interactions between fruit and vegetable intake and the hepatic nuclear factor 1 alpha (HNF1A) genetic variants on the C-reactive protein (CRP) levels. Baseline data from the Ansan and Ansung Cohort Study of the Korean Genome and Epidemiology Study (KoGES) were used. A total of 7,634 participants (3,700 men and 3,934 women) were included in the analyses. Fruit and vegetable intake was assessed using semi-quantitative food frequency questionnaire data. Genotyping information for HNF1A was extracted from the Affymetrix Genome-Wide Human SNP array 5.0. Inflammation was determined after overnight fasting by measuring CRP levels using automated analyzers. Multivariable logistic regression was used to estimate the adjusted odds ratio (AOR) with a 95% confidence interval (CI). In the fully adjusted model, men and women with the GG genotype of HNF1A rs2393791 and high fruit intake had lower odds of elevated CRP levels compared to those with the AA genotype and low fruit intake (AOR 0.50, 95% CI 0.38-0.67; AOR 0.73, 95% CI 0.55-0.97, respectively). Men and women with the rs2393791 GG genotype and high vegetable intake had lower odds of having elevated CRP levels compared to those with the AA genotype and low fruit intake (AOR 0.57, 95% CI 0.43-0.75; AOR 0.65, 95% CI 0.49-0.86, respectively). Men and women with the GG genotype and high total fruit and vegetable intake had lower odds of having elevated CRP levels. These findings indicate that fruit and vegetable intake interacts with HNF1A genetic polymorphisms, consequently influencing the inflammation levels.

Pro-inflammatory diet associated with low back pain in adults aged 50 and older.

AIMS: To investigate the association between pro-inflammatory diets and low back pain in a nationally representative sample of Korean adults. BACKGROUND: Low back pain is one of the most common health issues. Evidence suggests a potential association between systemic inflammation and the development of low back pain, and the role of diet in mitigating the inflammation that, in turn, can alleviate low back pain. METHODS: This cross-sectional, correlational study used data from the 6th Korea National Health and Nutrition Examination Survey involving health interviews, examinations, and nutritional surveys. Dietary inflammatory index scores were generated based on 24-hour dietary recalls. Respondents were asked if they had experienced low back pain for at least 30 days in the past three months. Multiple logistic regression analyses were conducted to investigate the independent association between pro-inflammatory diets and low back pain. RESULTS: Of 7346 respondents, most participants were middle-aged, married, and non-/ex-smokers, lived in 2+ person households, consumed alcohol less than once a week, and had no allergies or underlying medical conditions. Respondents in the highest inflammatory diet quintile had nearly 0.25 higher odds of reporting low back pain than those in the lowest quintile (adjusted ORquintile5vs1: 1.25, 95%CI [1.01-1.54]; p = .043). CONCLUSIONS: Results from this study indicate a role of pro-inflammatory diets in the development of low back pain. Nurses can screen for those consuming pro-inflammatory foods, and thus, are vulnerable to back pain, and aid in the delivery of tailored nutritional education. Future studies should investigate how diet affects low back pain diagnosis and chronicity relative to pain phenotypes.

Association of Seaweed Consumption with Metabolic Syndrome and Its Components: Findings from the Korean Genome and Epidemiology Study.

This study aimed to investigate the association between seaweed consumption and the odds of developing metabolic syndrome in middle-aged and elderly Koreans. The study included 5777 adults aged 40-69 years from 2001 to 2002 in the Ansan and Ansung cohorts of the Korean Genome and Epidemiology Study. Data on the consumption of seaweed, including laver and kelp/sea mustard, were obtained using a semiquantitative food frequency questionnaire. Multivariable logistic regression models were used to assess the association between seaweed consumption and the odds of developing metabolic syndrome and its components. Women in the highest tertile of laver consumption had lower odds of developing metabolic syndrome than those in the lowest tertile (adjusted odds ratio [AOR]: 0.70; 95% confidence interval [CI]: 0.54-0.92). Both men and women in the highest tertile of laver consumption had lower odds of abdominal obesity than those in the lowest tertile (AOR: 0.64, 95% CI: 0.42-0.98 for men; AOR: 0.53, 95% CI: 0.39-0.72 for women). These findings suggest that laver consumption is inversely associated with the odds of developing metabolic syndrome and abdominal obesity in Korean adults.