Nanotopology-Enabled On-Site Pathogen Detection for Managing Atopic Dermatitis.

Atopic dermatitis (AD), a prevalent skin condition often complicated by microbial infection, poses a significant challenge in identifying the responsible pathogen for its effective management. However, a reliable, safe tool for pinpointing the source of these infections remains elusive. In this study, a novel on-site pathogen detection that combines chemically functionalized nanotopology with genetic analysis is proposed to capture and analyze pathogens closely associated with severe atopic dermatitis. The chemically functionalized nanotopology features a 3D hierarchical nanopillar array (HNA) with a functional polymer coating, tailored to isolate target pathogens from infected skin. This innovative nanotopology demonstrates superior pathogenic capture efficiency, favorable entrapment patterns, and non-cytotoxicity. An HNA-assembled stick is utilized to directly retrieve bacteria from infected skin samples, followed by extraction-free quantitative loop-mediated isothermal amplification (direct qLAMP) for validation. To mimic human skin conditions, porcine skin is employed to successfully capture Staphylococcus aureus, a common bacterium exacerbating AD cases. The on-site detection method exhibits an impressive detection limit of 103 cells mL-1 . The HNA-assembled stick represents a promising tool for on-site detection of bacteria associated with atopic dermatitis. This innovative approach enables to deepen the understanding of AD pathogenesis and open avenues for more effective management strategies for chronic skin conditions.

Synchronous Diagnosis of Respiratory Viruses Variants via Receptonics Based on Modeling Receptor-Ligand Dynamics.

The transmission and pathogenesis of highly contagious fatal respiratory viruses are increasing, and the need for an on-site diagnostic platform has arisen as an issue worldwide. Furthermore, as the spread of respiratory viruses continues, different variants have become the dominant circulating strains. To prevent virus transmission, the development of highly sensitive and accurate on-site diagnostic assays is urgently needed. Herein, a facile diagnostic device is presented for multi-detection based on the results of detailed receptor-ligand dynamics simulations for the screening of various viral strains. The novel bioreceptor-treated electronics (receptonics) device consists of a multichannel graphene transistor and cell-entry receptors conjugated to N-heterocyclic carbene (NHC). An ultrasensitive multi-detection performance is achieved without the need for sample pretreatment, which will enable rapid diagnosis and prevent the spread of pathogens. This platform can be applied for the diagnosis of variants of concern in clinical respiratory virus samples and primate models. This multi-screening platform can be used to enhance surveillance and discriminate emerging virus variants before they become a severe threat to public health.

Use of real-time monitors to evaluate the potential exposure of secondhand electronic cigarette particulate matter inside vehicles.

Electronic cigarette (ECIG) use continues to be highly prevalent, especially among youth and young adults. Potential exposure from secondhand ECIG particulate matter (PM) places bystanders in danger of inhaling harmful substances, especially in confined spaces. This study was conducted to measure the potential exposure from secondhand ECIG PM exposure in vehicles, with participants completing a 30-min ECIG use session in their own vehicle with their preferred ECIG device. Sessions included a 5-min, 10-puff directed bout (30-s interpuff interval), followed by a 25-min ad libitum bout in which participants could take as many puffs as desired. Real-time PM1, PM2.5, and PM10 (the 50% efficiency mass cut-off of that passes through a size-selective inlet at 1 µm, 2.5 µm, and 10 µm aerodynamic diameters, respectively) measurements were captured during the sessions using portable PM monitors (MiniWRAS, pDR, SidePak, and GeoAir2 low-cost monitors). A total of 56 participants with valid measurements were included in the study, with a total of 13 unique ECIG device brands, including Vuse Alto, Box Air Bar, ElfBar, Esco Bar, Aegis Legend, Hyde Edge, JUUL, Kang Onee Stick, Kang Onee Stick Plus, Nord X, Nord 2, Nord 3, and Vaporesso. During the 5-min directed bout, the highest real-time PM2.5 mean concentrations were 175 µg/m3 for the MiniWRAS, 1050 µg/m3 for pDR and 3314 µg/m3 for SidePak. The filter measurements were not detectable in most experiments, except for two participants, with one taking 205 puffs and the other taking 285 puffs, approximately 10 times the mean (30) puffs of all participants. The evaluation of GeoAir2 with the MiniWRAS showed a wide range of Pearson correlation coefficient (r) values, ranging from -0.03 to 1.00, for the 13 ECIG brands. The mass median diameter (0.31 µm-3.42 µm) and geometric standard deviation (2.47-8.21) were different based on the participants for the same ECIG brand.

Polyaniline-based 3D network structure promotes entrapment and detection of drug-resistant bacteria.

Sensitive and accurate capture, enrichment, and identification of drug-resistant bacteria on human skin are important for early-stage diagnosis and treatment of patients. Herein, we constructed a three-dimensional hierarchically structured polyaniline nanoweb (3D HPN) to capture, enrich, and detect drug-resistant bacteria on-site by rubbing infected skins. These unique hierarchical nanostructures enhance bacteria capture efficiency and help severely deform the surface of the bacteria entrapped on them. Therefore, 3D HPN significantly contributes to the effective and reliable recovery of drug-resistant bacteria from the infected skin and the prevention of potential secondary infection. The recovered bacteria were successfully identified by subsequent real-time polymerase chain reaction (PCR) analysis after the lysis process. The molecular analysis results based on a real-time PCR exhibit excellent sensitivity to detecting target bacteria of concentrations ranging from 102 to 107 CFU/mL without any fluorescent signal interruption. To confirm the field applicability of 3D HPN, it was tested with a drug-resistant model consisting of micropig skin similar to human skin and Klebsiella pneumoniae carbapenemase-producing carbapenem-resistant Enterobacteriaceae (KPC-CRE). The results show that the detection sensitivity of this assay is 102 CFU/mL. Therefore, 3D HPN can be extended to on-site pathogen detection systems, along with rapid molecular diagnostics through a simple method, to recover KPC-CRE from the skin.

Reusable Electronic Tongue Based on Transient Receptor Potential Vanilloid 1 Nanodisc-Conjugated Graphene Field-Effect Transistor for a Spiciness-Related Pain Evaluation.

The sense of spiciness is related to the stimulation of vanilloid compounds contained in the foods. Although, the spiciness is commonly considered as the part of taste, it is more classified to the sense of pain stimulated on a tongue, namely, pungency, which is described as a tingling or burning on the tongue. Herein, first, a reusable electronic tongue based on a transient receptor potential vanilloid 1 (TRPV1) nanodisc conjugated graphene field-effect transistor is fabricated and spiciness-related pain evaluation with reusable electrode is demonstrated. The pungent compound reactive receptor TRPV1 is synthesized in the form of nanodiscs to maintain stability and reusability. The newly developed platform shows highly selective and sensitive performance toward each spiciness related vanilloid compound repeatably: 1 aM capsaicin, 10 aM dihydrocapsaicin, 1 fM piperine, 10 nM allicin, and 1 pM AITC. The binding mechanism is also examined by simulation. Furthermore, the elimination of the burning sensation on the tongue after eating spicy foods is not investigated. Based on the synthesis of micelles composed of casein protein (which is contained in skim milk) that remove pungent compounds bound to TRPV1 nanodisc, the deactivation of TRPV1 is investigated, and the electrode is reusable that mimics electronic tongue.

Regenerative Strategy of Gold Electrodes for Long-Term Reuse of Electrochemical Biosensors.

Gold is of considerable interest for electrochemical active surfaces because thiol-modified chemicals and biomolecules can be easily immobilized with a simple procedure. However, most gold surfaces are damaged with repetitive measurements, so they are difficult to reuse. Here we demonstrate a novel electrochemical cleaning method of gold surfaces to reuse electrodes with a simple protocol that is easy and nontoxic. This electrochemical cleaning consists of two steps by using different solutions. The 1st step is a cyclic voltammetry sweep using a very low concentration of sulfuric acid, and the 2nd step is a cyclic voltammetry sweep using potassium ferricyanide. Different cleaning methods were also considered for comparison. Consequently, after assembling and desorption of the cell and antigen, the changes in gold electrode performance, as immunosensor and cytosensor, were investigated by electrochemical impedance and cyclic voltammetry. It was found that repetitive measurement is possible until five times while maintaining the reproducibility. It is believed that this method is capable of enabling reuse of gold electrodes and can be used for long-term and accurate monitoring of biological effects, especially at a low cost.

Spatiotemporal non-stationarity in green space and stress relationships: Recent evidence from South Korea.

A growing body of literature has linked exposure to "green space" (vegetation-rich areas) and other forms of nature to mental health. Exposure-outcome associations at regional or national scales can overlook local associations that define how geographically distinct populations may experience nature differently. Large-scale results might downplay the importance of lived experiences and heterogeneity of human-nature relationships at local scales. The current study examines three types of vegetative cover and identifies how they are associated with perceived stress in South Korea during and before the COVID-19 pandemic. We find forest cover is consistently negatively associated with perceived stress at nationwide scales. In contrast, grass cover and the normalized difference vegetation index (NDVI) show mixed associations with perceived stress at nationwide scales. Models accounting for spatial and temporal variability demonstrate that associations of forest cover, grass cover, and NDVI with perceived stress varies across the country and the study's four-year time horizon. Local governments may need divergent urban greening strategies for health promotion that respond to their specific sociodemographic and pre-existing environmental conditions.

Personal exposure monitoring using GPS-enabled portable air pollution sensors: A strategy to promote citizen awareness and behavioral changes regarding indoor and outdoor air pollution.

BACKGROUND: Little is known about how individuals are exposed to air pollution in various daily activity spaces due to a lack of data collected in the full range of spatial contexts in which they spend their time. The limited understanding makes it difficult for people to act in informed ways to reduce their exposure both indoors and outdoors. OBJECTIVE: This study aimed to (1) assess whether personalized air quality data collected using GPS-enabled portable monitors (GeoAir2), coupled with travel-activity diaries, promote people's awareness and behavioral changes regarding indoor and outdoor air pollution and (2) demonstrate the effect of places and activities on personal exposure by analyzing individual exposure profiles. METHODS: 44 participants carried GeoAir2 to collect geo-referenced air pollution data and completed travel-activity diaries for three days. These data were then combined for spatial data analysis and visualization. Participants also completed pre- and post-session surveys about awareness and behaviors regarding air pollution. Paired-sample t-tests were performed to evaluate changes in knowledge, attitudes/perceptions, and behavioral intentions/practices, respectively. Lastly, follow-up interviews were conducted with a subset of participants. RESULTS: Most participants experienced PM2.5 peaks indoors, especially when cooking at home, and had the lowest exposure in transit. Participants reported becoming more aware of air quality in their surroundings and more concerned about its health effects (t = 3.92, p = 0.000) and took more action or were more motivated to alter their behaviors to mitigate their exposure (t = 3.40, p = 0.000) after the intervention than before. However, there was no significant improvement in knowledge (t = 0.897; p = 0.187). SIGNIFICANCE: Personal exposure monitoring, combined with travel-activity diaries, leads to positive changes in attitudes, perceptions, and behaviors related to air pollution. This study highlights the importance of citizen engagement in air monitoring for effective risk communication and air pollution management.

Benefits of Flavored Lactose-Free Milk for Korean Adults with Lactose Intolerance.

Although lactose-free dairy products for the clinical management of lactose intolerance (LI) are widely available, scientific evidence on their efficacy is still lacking. This study comparatively analyzed the efficacy of flavored lactose-free milk (LFM) and whole milk (WM) in reducing symptoms in South Korean adults with LI. This prospective study was conducted in adults suspected of LI. All screened participants underwent the hydrogen breath test (HBT) using 570 mL of chocolate-flavored WM (20 g of lactose) and responded to a symptom questionnaire. LI was confirmed when the ΔH2 peak exceeded 16 ppm above baseline values and with the occurrence of symptoms after WM consumption. The participants who were diagnosed with LI underwent the HBT again with 570 mL of chocolate-flavored LFM (0 g of lactose), followed by the symptom questionnaire survey after 1 week. After excluding 40 participants who did not meet the diagnostic criteria for LI and 2 who were lost to follow-up, a total of 28 lactose-intolerant individuals were enrolled in the study. The ΔH2 values in the first HBT were significantly higher than those in the second HBT (33.3 ± 21.6 ppm vs. 8.6 ± 6.3 ppm, P < .001). Similarly, there was a significant reduction in the total symptom score in the second HBT (4.18 ± 1.51 vs. 0.61 ± 0.98, P < .001). Flavored LFM is well tolerated in South Korean adults diagnosed with LI based on the HBT and symptom questionnaire results. Therefore, LFM may be a viable alternative to WM.

Open-Bandgap Graphene-Based Field-Effect Transistor Using Oligo(phenylene-ethynylene) Interfacial Chemistry.

Organic interfacial compounds (OICs) are required as linkers for the highly stable and efficient immobilization of bioprobes in nanobiosensors using 2D nanomaterials such as graphene. Herein, we first demonstrated the fabrication of a field-effect transistor (FET) via a microelectromechanical system process after covalent functionalization on large-scale graphene by introducing oligo(phenylene-ethynylene)amine (OPE). OPE was compared to various OICs by density functional theory simulations and was confirmed to have a higher binding energy with graphene and a lower band gap than other OICs. OPE can improve the immobilization efficiency of a bioprobe by forming a self-assembly monolayer via anion-based reaction. Using this technology, Magainin I-conjugated OGMFET (MOGMFET) showed a high sensitivity, high selectivity, with a limit of detection of 100  cfu mL-1 . These results indicate that the OPE OIC can be applied for stable and comfortable interfacing technology for biosensor fabrication.

Laboratory and Field Evaluations of the GeoAir2 Air Quality Monitor for Use in Indoor Environments.

Low-cost aerosol sensors open routes to exposure assessment and air monitoring in various indoor and outdoor environments. This study evaluated the accuracy of GeoAir2--a recently developed low-cost particulate matter (PM) monitor--using two types of aerosols (salt and dust), and the effect of changes in relative humidity on its measurements in laboratory settings. For the accuracy experiments, 32 units of GeoAir2 were used, and for the humidity experiments, 3 units of GeoAir2 were used, alongside the OPC-N3 low-cost sensor and MiniWRAS reference instrument. The normal distribution of slopes between the salt and dust aerosols was compared for the accuracy experiments. In addition, the performance of GeoAir2 in indoor environments was evaluated compared to the pDR-1500 reference instrument by collocating GeoAir2 and pDR-1500 at three different homes for five days. For salt and dust aerosols smaller than 2.5 µm (PM2.5), both GeoAir2 (r = 0.96-0.99) and OPC-N3 (r = 0.98-0.99) were highly correlated with the MiniWRAS reference instrument. However, GeoAir2 was less influenced by changes in humidity than OPC-N3. While GeoAir2 reported an increase in mass concentrations ranging from 100% to 137% for low and high concentrations, an increase between 181% and 425% was observed for OPC-N3. The normal distribution of the slopes for the salt aerosols was narrower than dust aerosol, which shows closer slope similarities for salt aerosols. This study also found that GeoAir2 was highly correlated with the pDR-1500 reference instrument in indoor environments (r = 0.80-0.99). These results demonstrate potential for GeoAir2 for indoor air monitoring and exposure assessments.

3D Hierarchical Polyaniline-Metal Hybrid Nanopillars: Morphological Control and Its Antibacterial Application.

Effective and reliable antibacterial surfaces are in high demand in modern society. Although recent works have shown excellent antibacterial performance by combining unique hierarchical nanotopological structures with functional polymer coating, determining the antibacterial performance arising from morphological changes is necessary. In this work, three-dimensional (3D) hierarchical polyaniline-gold (PANI/Au) hybrid nanopillars were successfully fabricated via chemical polymerization (i.e., dilute method). The morphology and structures of the PANI/Au nanopillars were controlled by the reaction time (10 min to 60 h) and the molar concentrations of the monomer (0.01, 0.1, and 1 M aniline), oxidant (0.002, 0.0067, 0.01, and 0.02 M ammonium persulfate), and acid (0.01, 0.1, 1, and 2 M perchloric acid). These complex combinations allow controlling the hierarchical micro- to nanostructure of PANI on a nanopillar array (NPA). Furthermore, the surface of the 3D PANI/Au hierarchical nanostructure can be chemically treated while maintaining the structure using initiated chemical vapor deposition. Moreover, the excellent antibacterial performance of the 3D PANI/Au hierarchical nanostructure (HNS) exceeds 99% after functional polymer coating. The excellent antibacterial performance of the obtained 3D PANI/Au HNS is mainly because of the complex topological and physicochemical surface modification. Thus, these 3D PANI/Au hierarchical nanostructures are promising high-performance antibacterial materials.

COVID-19 Deaths in the United States: Shifts in Hot Spots over the Three Phases of the Pandemic and the Spatiotemporally Varying Impact of Pandemic Vulnerability.

The geographic areas most impacted by COVID-19 may not remain static because public health measures/behaviors change dynamically, and the impacts of pandemic vulnerability also may vary geographically and temporally. The nature of the pandemic makes spatiotemporal methods essential to understanding the distribution of COVID-19 deaths and developing interventions. This study examines the spatiotemporal trends in COVID-19 death rates in the United States from March 2020 to May 2021 by performing an emerging hot spot analysis (EHSA). It then investigates the effects of the COVID-19 time-dependent and basic social vulnerability factors on COVID-19 death rates using geographically and temporally weighted regression (GTWR). The EHSA results demonstrate that over the three phases of the pandemic (first wave, second wave, and post-vaccine deployment), hot spots have shifted from densely populated cities and the states with a high percentage of socially vulnerable individuals to the states with relatively relaxed social distancing requirements, and then to the states with low vaccination rates. The GTWR results suggest that local infection and testing rates, social distancing interventions, and other social, environmental, and health risk factors show significant associations with COVID-19 death rates, but these associations vary over time and space. These findings can inform public health planning.

Laboratory Evaluation of Low-Cost Optical Particle Counters for Environmental and Occupational Exposures.

Low-cost optical particle counters effectively measure particulate matter (PM) mass concentrations once calibrated. Sensor calibration can be established by deriving a linear regression model by performing side-by-side measurements with a reference instrument. However, calibration differences between environmental and occupational settings have not been demonstrated. This study evaluated four commercially available, low-cost PM sensors (OPC-N3, SPS30, AirBeam2, and PMS A003) in both settings. The mass concentrations of three aerosols (salt, Arizona road dust, and Poly-alpha-olefin-4 oil) were measured and compared with a reference instrument. OPC-N3 and SPS30 were highly correlated (r = 0.99) with the reference instrument for all aerosol types in environmental settings. In occupational settings, SPS30, AirBeam2, and PMS A003 exhibited high correlation (>0.96), but the OPC-N3 correlation varied (r = 0.88-1.00). Response significantly (p < 0.001) varied between environmental and occupational settings for most particle sizes and aerosol types. Biases varied by particle size and aerosol type. SPS30 and OPC-N3 exhibited low bias for environmental settings, but all of the sensors showed a high bias for occupational settings. For intra-instrumental precision, SPS30 exhibited high precision for salt for both settings compared to the other low-cost sensors and aerosol types. These findings suggest that SPS30 and OPC-N3 can provide a reasonable estimate of PM mass concentrations if calibrated differently for environmental and occupational settings using site-specific calibration factors.

An Integrated Individual Environmental Exposure Assessment System for Real-Time Mobile Sensing in Environmental Health Studies.

The effects of environmental exposure on human health have been widely explored by scholars in health geography for decades. However, recent advances in geospatial technologies, especially the development of mobile approaches to collecting real-time and high-resolution individual data, have enabled sophisticated methods for assessing people's environmental exposure. This study proposes an individual environmental exposure assessment system (IEEAS) that integrates objective real-time monitoring devices and subjective sensing tools to provide a composite way for individual-based environmental exposure data collection. With field test data collected in Chicago and Beijing, we illustrate and discuss the advantages of the proposed IEEAS and the composite analysis that could be applied. Data collected with the proposed IEEAS yield relatively accurate measurements of individual exposure in a composite way, and offer new opportunities for developing more sophisticated ways to measure individual environmental exposure. With the capability to consider both the variations in environmental risks and human mobility in high spatial and temporal resolutions, the IEEAS also helps mitigate some uncertainties in environmental exposure assessment and thus enables a better understanding of the relationship between individual environmental exposure and health outcomes.

GeoAir-A Novel Portable, GPS-Enabled, Low-Cost Air-Pollution Sensor: Design Strategies to Facilitate Citizen Science Research and Geospatial Assessments of Personal Exposure.

The rapid evolution of air sensor technologies has offered enormous opportunities for community-engaged research by enabling citizens to monitor the air quality at any time and location. However, many low-cost portable sensors do not provide sufficient accuracy or are designed only for technically capable individuals by requiring pairing with smartphone applications or other devices to view/store air quality data and collect location data. This paper describes important design considerations for portable devices to ensure effective citizen engagement and reliable data collection for the geospatial analysis of personal exposure. It proposes a new, standalone, portable air monitor, GeoAir, which integrates a particulate matter (PM) sensor, volatile organic compound (VOC) sensor, humidity and temperature sensor, LTE-M and GPS module, Wi-Fi, long-lasting battery, and display screen. The preliminary laboratory test results demonstrate that the PM sensor shows strong performance when compared to a reference instrument. The VOC sensor presents reasonable accuracy, while further assessments with other types of VOC are needed. The field deployment and geo-visualization of the field data illustrate that GeoAir collects fine-grained, georeferenced air pollution data. GeoAir can be used by all citizens regardless of their technical proficiency and is widely applicable in many fields, including environmental justice and health disparity research.

COVID-19: A Vaccine Priority Index Mapping Tool for Rapidly Assessing Priority Populations in North Carolina.

BACKGROUND: The initial limited supply of COVID-19 vaccine in the U.S. presented significant allocation, distribution, and delivery challenges. Information that can assist health officials, hospital administrators and other decision makers with readily identifying who and where to target vaccine resources and efforts can improve public health response. OBJECTIVE: The objective of this project was to develop a publicly available geographical information system (GIS) web mapping tool that would assist North Carolina health officials readily identify high-risk, high priority population groups and facilities in the immunization decision making process. METHODS: Publicly available data were used to identify 14 key health and socio-demographic variables and 5 differing themes (social and economic status; minority status and language; housing situation; at risk population; and health status). Vaccine priority population index (VPI) scores were created by calculating a percentile rank for each variable over each N.C. Census tract. All Census tracts (N = 2,195) values were ranked from lowest to highest (0.0 to 1.0) with a non-zero population and mapped using ArcGIS. RESULTS: The VPI tool was made publicly available (https://enchealth.org/) during the pandemic to readily assist with identifying high risk population priority areas in N.C. for the planning, distribution, and delivery of COVID-19 vaccine. DISCUSSION: While health officials may have benefitted by using the VPI tool during the pandemic, a more formal evaluation process is needed to fully assess its usefulness, functionality, and limitations. CONCLUSION: When considering COVID-19 immunization efforts, the VPI tool can serve as an added component in the decision-making process.

Flexible nanopillar-based immunoelectrochemical biosensor for noninvasive detection of Amyloid beta.

The noninvasive early detection of biomarkers for Alzheimer's disease (AD) is essential for the development of specific treatment strategies. This paper proposes an advanced method for fabricating highly ordered and flexible nanopillar-based electrochemical biosensors by the combination of soft/photolithography and metal evaporation. The nanopillar array (NPA) exhibits high surface area containing 1500 nm height and 500 nm diameter with 3:1 ratio. In regard with physical properties of polyurethane (PU) substrate, the developed NPA is sustainable and durable to external pressure such as bending and twisting. To manipulate the NPA surface to biocompatible, the gold was uniformly deposited on the PU substrate. The thiol chemistry which is stably modified on the gold surface as a form of self-assembled monolayer was employed for fabricating the NPA as a biocompatible chip by covalently immobilize the antibodies. The proposed nanopillar-based immunoelectrochemical biosensor exhibited good and stable electrochemical performance in ß-amyloid (Aß) detection. Moreover, we successfully confirmed the performance of the as-developed sensor using the artificial injection of Aß in human tear, with sensitivity of 0.14 ng/mL and high reproducibility (as a standard deviation below 10%). Our findings show that the developed nanopillar-based sensor exhibits reliable electrochemical characteristics and prove its potential for application as a biosensor platform for testing at the point of care.

Host Genetic and Gut Microbial Signatures in Familial Inflammatory Bowel Disease.

INTRODUCTION: The family history of inflammatory bowel disease (IBD) has been strongly associated with risk of developing IBD. This study aimed to identify the host genetic and gut microbial signatures in familial IBD. METHODS: Genetic analyses using genome-wide single nucleotide polymorphism genotyping and whole exome sequencing were performed to calculate weighted genetic risk scores from known IBD-associated common variants and to identify rare deleterious protein-altering variants specific to patients with familial IBD in 8 Korean families that each included more than 2 affected first-degree relatives (FDRs) and their unaffected FDR(s). In parallel, gut microbial community was analyzed by 16S rRNA sequencing of stools from the sample individuals. RESULTS: The risk of familial IBD was not well explained by the genetic burden from common IBD-risk variants, suggesting the presence of family-shared genetic and environmental disease-risk factors. We identified 17 genes (AC113554.1, ACE, AKAP17A, AKAP9, ANK2, ASB16, ASIC3, DNPH1, DUS3L, FAM200A, FZD10, LAMA5, NUTM2F, PKN1, PRR26, WDR66, and ZC3H4) that each contained rare, potentially deleterious variants transmitted to the affected FDRs in multiple families. In addition, metagenomic analyses revealed significantly different diversity of gut microbiota and identified a number of differentially abundant taxa in affected FDRs, highlighting 22 novel familial disease-associated taxa with large abundance changes and the previously reported gut dysbiosis including low alpha diversity in IBD and 16 known IBD-specific taxa. DISCUSSION: This study identified familial IBD-associated rare deleterious variants and gut microbial dysbiosis in familial IBD.

Adenocarcinoma and Neuroendocrine Collision Tumor in a Giant Gastric Hyperplastic Polyp.

Screening esophagogastroduodenoscopy of a 65-year-old man revealed a 4.7-cm polypoid in the gastric high body. Clinical and laboratory findings, including serum gastrin level (460 pg/mL) and biopsy findings, were consistent with a diagnosis of type I neuroendocrine tumor (NET). Histologically, the mass consisted of dilated tortuous glands at the surface and grade 1 NET in deeper tissue. Some hyperplastic glands exhibited a transition to adenocarcinoma, which invaded the NET, simulating a "tumor in tumor" appearance. Next-generation sequencing revealed that the adenocarcinoma component harbored a TP53 mutation, whereas the NET component showed no pathogenic mutation. To our knowledge, this unusual collision of adenocarcinoma and NET within a single gastric hyperplastic polyp has not been previously described. This case suggests that large gastric hyperplastic polyps should be carefully examined because of the possibility of underlying NET and malignant transformation of surface epithelium.