Air Pollution, Built Environment, and Early Cardiovascular Disease.

As the world's population becomes increasingly urbanized, there is growing concern about the impact of urban environments on cardiovascular health. Urban residents are exposed to a variety of adverse environmental exposures throughout their lives, including air pollution, built environment, and lack of green space, which may contribute to the development of early cardiovascular disease and related risk factors. While epidemiological studies have examined the role of a few environmental factors with early cardiovascular disease, the relationship with the broader environment remains poorly defined. In this article, we provide a brief overview of studies that have examined the impact of the environment including the built physical environment, discuss current challenges in the field, and suggest potential directions for future research. Additionally, we highlight the clinical implications of these findings and propose multilevel interventions to promote cardiovascular health among children and young adults.

Discovery of Transacting Long Noncoding RNAs That Regulate Smooth Muscle Cell Phenotype.

BACKGROUND: Smooth muscle cells (SMC), the major cell type in atherosclerotic plaques, are vital in coronary artery diseases (CADs). SMC phenotypic transition, which leads to the formation of various cell types in atherosclerotic plaques, is regulated by a network of genetic and epigenetic mechanisms and governs the risk of disease. The involvement of long noncoding RNAs (lncRNAs) has been increasingly identified in cardiovascular disease. However, SMC lncRNAs have not been comprehensively characterized, and their regulatory role in SMC state transition remains unknown. METHODS: A discovery pipeline was constructed and applied to deeply strand-specific RNA sequencing from perturbed human coronary artery SMC with different disease-related stimuli, to allow for the detection of novel lncRNAs. The functional relevance of a select few novel lncRNAs were verified in vitro. RESULTS: We identified 4579 known and 13 655 de novo lncRNAs in human coronary artery SMC. Consistent with previous long noncoding RNA studies, these lncRNAs overall have fewer exons, are shorter in length than protein-coding genes (pcGenes), and have relatively low expression level. Genomic location of these long noncoding RNA is disproportionately enriched near CAD-related TFs (transcription factors), genetic loci, and gene regulators of SMC identity, suggesting the importance of their function in disease. Two de novo lncRNAs, ZIPPOR (ZEB-interacting suppressor) and TNS1-AS2 (TNS1-antisense 2), were identified by our screen. Combining transcriptional data and in silico modeling along with in vitro validation, we identified CAD gene ZEB2 as a target through which these lncRNAs exert their function in SMC phenotypic transition. CONCLUSIONS: Expression of a large and diverse set of lncRNAs in human coronary artery SMC are highly dynamic in response to CAD-related stimuli. The dynamic changes in expression of these lncRNAs correspond to alterations in transcriptional programs that are relevant to CAD, suggesting a critical role for lncRNAs in SMC phenotypic transition and human atherosclerotic disease.

ZEB2 Shapes the Epigenetic Landscape of Atherosclerosis.

BACKGROUND: Smooth muscle cells (SMCs) transition into a number of different phenotypes during atherosclerosis, including those that resemble fibroblasts and chondrocytes, and make up the majority of cells in the atherosclerotic plaque. To better understand the epigenetic and transcriptional mechanisms that mediate these cell state changes, and how they relate to risk for coronary artery disease (CAD), we have investigated the causality and function of transcription factors at genome-wide associated loci. METHODS: We used CRISPR-Cas 9 genome and epigenome editing to identify the causal gene and cells for a complex CAD genome-wide association study signal at 2q22.3. Single-cell epigenetic and transcriptomic profiling in murine models and human coronary artery smooth muscle cells were used to understand the cellular and molecular mechanism by which this CAD risk gene exerts its function. RESULTS: CRISPR-Cas 9 genome and epigenome editing showed that the complex CAD genetic signals within a genomic region at 2q22.3 lie within smooth muscle long-distance enhancers for ZEB2, a transcription factor extensively studied in the context of epithelial mesenchymal transition in development of cancer. Zeb2 regulates SMC phenotypic transition through chromatin remodeling that obviates accessibility and disrupts both Notch and transforming growth factor ß signaling, thus altering the epigenetic trajectory of SMC transitions. SMC-specific loss of Zeb2 resulted in an inability of transitioning SMCs to turn off contractile programing and take on a fibroblast-like phenotype, but accelerated the formation of chondromyocytes, mirroring features of high-risk atherosclerotic plaques in human coronary arteries. CONCLUSIONS: These studies identify ZEB2 as a new CAD genome-wide association study gene that affects features of plaque vulnerability through direct effects on the epigenome, providing a new therapeutic approach to target vascular disease.

The Cannabinoids, CBDA and THCA, Rescue Memory Deficits and Reduce Amyloid-Beta and Tau Pathology in an Alzheimer's Disease-like Mouse Model.

Most studies related to hemp are focused on Cannabidiol (CBD) and Tetrahydrocannabinol (THC); however, up to 120 types of phytocannabinoids are present in hemp. Hemp leaves contain large amounts of Cannabidiolic acid (CBDA) and Tetrahydrocannabinolic acid (THCA), which are acidic variants of CBD and THC and account for the largest proportion of CBDA. In recent studies, CBDA exhibited anti-hyperalgesia and anti-inflammatory effects. THCA also showed anti-inflammatory and neuroprotective effects that may be beneficial for treating neurodegenerative diseases. CBDA and THCA can penetrate the blood-brain barrier (BBB) and affect the central nervous system. The purpose of this study was to determine whether CBDA and THCA ameliorate Alzheimer's disease (AD)-like features in vitro and in vivo. The effect of CBDA and THCA was evaluated in the Aß1-42-treated mouse model. We observed that Aß1-42-treated mice had more hippocampal Aß and p-tau levels, pathological markers of AD, and loss of cognitive function compared with PBS-treated mice. However, CBDA- and THCA-treated mice showed decreased hippocampal Aß and p-tau and superior cognitive function compared with Aß1-42-treated mice. In addition, CBDA and THCA lowered Aß and p-tau levels, alleviated calcium dyshomeostasis, and exhibited neuroprotective effects in primary neurons. Our results suggest that CBDA and THCA have anti-AD effects and mitigate memory loss and resilience to increased hippocampal Ca2+, Aß, and p-tau levels. Together, CBDA and THCA may be useful therapeutic agents for treating AD.

Ca2+-permeable TRPV1 pain receptor knockout rescues memory deficits and reduces amyloid-ß and tau in a mouse model of Alzheimer's disease.

The transient receptor potential vanilloid 1 (TRPV1) protein is a pain receptor that elicits a hot sensation when an organism eats the capsaicin of red chili peppers. This calcium (Ca2+)-permeable cation channel is mostly expressed in the peripheral nervous system sensory neurons but also in the central nervous system (e.g. hippocampus and cortex). Preclinical studies found that TRPV1 mediates behaviors associated with anxiety and depression. Loss of TRPV1 functionality increases expression of genes related to synaptic plasticity and neurogenesis. Thus, we hypothesized that TRPV1 deficiency may modulate Alzheimer's disease (AD). We generated a triple-transgenic AD mouse model (3xTg-AD+/+) with wild-type (TRPV1+/+), hetero (TRPV1+/-) and knockout (TRPV1-/-) TRPV1 to investigate the role of TRPV1 in AD pathogenesis. We analyzed the animals' memory function, hippocampal Ca2+ levels and amyloid-ß (Aß) and tau pathologies when they were 12 months old. We found that compared with 3xTg-AD-/-/TRPV1+/+ mice, 3xTg-AD+/+/TRPV1+/+ mice had memory impairment and increased levels of hippocampal Ca2+, Aß and total and phosphorylated tau. However, 3xTg-AD+/+/TRPV1-/- mice had better memory function and lower levels of hippocampal Ca2+, Aß, tau and p-tau, compared with 3xTg-AD+/+/TRPV1+/+ mice. Examination of 3xTg-AD-derived primary neuronal cultures revealed that the intracellular Ca2+ chelator BAPTA/AM and the TRPV1 antagonist capsazepine decreased the production of Aß, tau and p-tau. Taken together, these results suggested that TRPV1 deficiency had anti-AD effects and promoted resilience to memory loss. These findings suggest that drugs or food components that modulate TRPV1 could be exploited as therapeutics to prevent or treat AD.

Coronary Disease-Associated Gene TCF21 Inhibits Smooth Muscle Cell Differentiation by Blocking the Myocardin-Serum Response Factor Pathway.

RATIONALE: The gene encoding TCF21 (transcription factor 21) has been linked to coronary artery disease risk by human genome-wide association studies in multiple racial ethnic groups. In murine models, Tcf21 is required for phenotypic modulation of smooth muscle cells (SMCs) in atherosclerotic tissues and promotes a fibroblast phenotype in these cells. In humans, TCF21 expression inhibits risk for coronary artery disease. The molecular mechanism by which TCF21 regulates SMC phenotype is not known. OBJECTIVE: To better understand how TCF21 affects the SMC phenotype, we sought to investigate the possible mechanisms by which it regulates the lineage determining MYOCD (myocardin)-SRF (serum response factor) pathway. METHODS AND RESULTS: Modulation of TCF21 expression in human coronary artery SMC revealed that TCF21 suppresses a broad range of SMC markers, as well as key SMC transcription factors MYOCD and SRF, at the RNA and protein level. We conducted chromatin immunoprecipitation-sequencing to map SRF-binding sites in human coronary artery SMC, showing that binding is colocalized in the genome with TCF21, including at a novel enhancer in the SRF gene, and at the MYOCD gene promoter. In vitro genome editing indicated that the SRF enhancer CArG box regulates transcription of the SRF gene, and mutation of this conserved motif in the orthologous mouse SRF enhancer revealed decreased SRF expression in aorta and heart tissues. Direct TCF21 binding and transcriptional inhibition at colocalized sites were established by reporter gene transfection assays. Chromatin immunoprecipitation and protein coimmunoprecipitation studies provided evidence that TCF21 blocks MYOCD and SRF association by direct TCF21-MYOCD interaction. CONCLUSIONS: These data indicate that TCF21 antagonizes the MYOCD-SRF pathway through multiple mechanisms, further establishing a role for this coronary artery disease-associated gene in fundamental SMC processes and indicating the importance of smooth muscle response to vascular stress and phenotypic modulation of this cell type in coronary artery disease risk.

Environment-Sensing Aryl Hydrocarbon Receptor Inhibits the Chondrogenic Fate of Modulated Smooth Muscle Cells in Atherosclerotic Lesions.

BACKGROUND: Smooth muscle cells (SMC) play a critical role in atherosclerosis. The Aryl hydrocarbon receptor (AHR) is an environment-sensing transcription factor that contributes to vascular development, and has been implicated in coronary artery disease risk. We hypothesized that AHR can affect atherosclerosis by regulating phenotypic modulation of SMC. METHODS: We combined RNA-sequencing, chromatin immunoprecipitation followed by sequencing, assay for transposase-accessible chromatin using sequencing, and in vitro assays in human coronary artery SMCs, with single-cell RNA-sequencing, histology, and RNAscope in an SMC-specific lineage-tracing Ahr knockout mouse model of atherosclerosis to better understand the role of AHR in vascular disease. RESULTS: Genomic studies coupled with functional assays in cultured human coronary artery SMCs revealed that AHR modulates the human coronary artery SMC phenotype and suppresses ossification in these cells. Lineage-tracing and activity-tracing studies in the mouse aortic sinus showed that the Ahr pathway is active in modulated SMCs in the atherosclerotic lesion cap. Furthermore, single-cell RNA-sequencing studies of the SMC-specific Ahr knockout mice showed a significant increase in the proportion of modulated SMCs expressing chondrocyte markers such as Col2a1 and Alpl, which localized to the lesion neointima. These cells, which we term "chondromyocytes," were also identified in the neointima of human coronary arteries. In histological analyses, these changes manifested as larger lesion size, increased lineage-traced SMC participation in the lesion, decreased lineage-traced SMCs in the lesion cap, and increased alkaline phosphatase activity in lesions in the Ahr knockout in comparison with wild-type mice. We propose that AHR is likely protective based on these data and inference from human genetic analyses. CONCLUSIONS: Overall, we conclude that AHR promotes the maintenance of lesion cap integrity and diminishes the disease-related SMC-to-chondromyocyte transition in atherosclerotic tissues.

Coronary artery disease genes SMAD3 and TCF21 promote opposing interactive genetic programs that regulate smooth muscle cell differentiation and disease risk.

Although numerous genetic loci have been associated with coronary artery disease (CAD) with genome wide association studies, efforts are needed to identify the causal genes in these loci and link them into fundamental signaling pathways. Recent studies have investigated the disease mechanism of CAD associated gene SMAD3, a central transcription factor (TF) in the TGFß pathway, investigating its role in smooth muscle biology. In vitro studies in human coronary artery smooth muscle cells (HCASMC) revealed that SMAD3 modulates cellular phenotype, promoting expression of differentiation marker genes while inhibiting proliferation. RNA sequencing and chromatin immunoprecipitation sequencing studies in HCASMC identified downstream genes that reside in pathways which mediate vascular development and atherosclerosis processes in this cell type. HCASMC phenotype, and gene expression patterns promoted by SMAD3 were noted to have opposing direction of effect compared to another CAD associated TF, TCF21. At sites of SMAD3 and TCF21 colocalization on DNA, SMAD3 binding was inversely correlated with TCF21 binding, due in part to TCF21 locally blocking chromatin accessibility at the SMAD3 binding site. Further, TCF21 was able to directly inhibit SMAD3 activation of gene expression in transfection reporter gene studies. In contrast to TCF21 which is protective toward CAD, SMAD3 expression in HCASMC was shown to be directly correlated with disease risk. We propose that the pro-differentiation action of SMAD3 inhibits dedifferentiation that is required for HCASMC to expand and stabilize disease plaque as they respond to vascular stresses, counteracting the protective dedifferentiating activity of TCF21 and promoting disease risk.

Control of the Induced Handedness of Helical Nanofilaments Employing Cholesteric Liquid Crystal Fields.

In this paper, a simple and powerful method to control the induced handedness of helical nanofilaments (HNFs) is presented. The nanofilaments are formed by achiral bent-core liquid crystal molecules employing a cholesteric liquid crystal field obtained by doping a rod-like nematogen with a chiral dopant. Homochiral helical nanofilaments are formed in the nanophase-separated helical nanofilament/cholesteric phase from a mixture with a cholesteric phase. This cholesteric phase forms at a temperature higher than the temperature at which the helical nanofilament in a bent-core molecule appears. Under such conditions, the cholesteric liquid crystal field acts as a driving force in the nucleation of HNFs, realizing a perfectly homochiral domain consisting of identical helical nanofilament handedness.

Immune biomarkers link air pollution exposure to blood pressure in adolescents.

BACKGROUND: Childhood exposure to air pollution contributes to cardiovascular disease in adulthood. Immune and oxidative stress disturbances might mediate the effects of air pollution on the cardiovascular system, but the underlying mechanisms are poorly understood in adolescents. Therefore, we aimed to identify immune biomarkers linking air pollution exposure and blood pressure levels in adolescents. METHODS: We randomly recruited 100 adolescents (mean age, 16 years) from Fresno, California. Using central-site data, spatial-temporal modeling, and distance weighting exposures to the participant's home, we estimated average pollutant levels [particulate matter (PM), polyaromatic hydrocarbons (PAH), ozone (O3), carbon monoxide (CO) and nitrogen oxides (NOx)]. We collected blood samples and vital signs on health visits. Using proteomic platforms, we quantitated markers of inflammation, oxidative stress, coagulation, and endothelial function. Immune cellular characterization was performed via mass cytometry (CyTOF). We investigated associations between pollutant levels, cytokines, immune cell types, and blood pressure (BP) using partial least squares (PLS) and linear regression, while adjusting for important confounders. RESULTS: Using PLS, biomarkers explaining most of the variance in air pollution exposure included markers of oxidative stress (GDF-15 and myeloperoxidase), acute inflammation (C-reactive protein), hemostasis (ADAMTS, D-dimer) and immune cell types such as monocytes. Most of these biomarkers were independently associated with the air pollution levels in fully adjusted regression models. In CyTOF analyses, monocytes were enriched in participants with the highest versus the lowest PM2.5 exposure. In both PLS and linear regression, diastolic BP was independently associated with PM2.5, NO, NO2, CO and PAH456 pollution levels (P ≤ 0.009). Moreover, monocyte levels were independently related to both air pollution and diastolic BP levels (P ≤ 0.010). In in vitro cell assays, plasma of participants with high PM2.5 exposure induced endothelial dysfunction as evaluated by eNOS and ICAM-1 expression and tube formation. CONCLUSIONS: For the first time in adolescents, we found that ambient air pollution levels were associated with oxidative stress, acute inflammation, altered hemostasis, endothelial dysfunction, monocyte enrichment and diastolic blood pressure. Our findings provide new insights on pollution-related immunological and cardiovascular disturbances and advocate preventative measures of air pollution exposure.

TCF21 and the environmental sensor aryl-hydrocarbon receptor cooperate to activate a pro-inflammatory gene expression program in coronary artery smooth muscle cells.

Both environmental factors and genetic loci have been associated with coronary artery disease (CAD), however gene-gene and gene-environment interactions that might identify molecular mechanisms of risk are not easily studied by human genetic approaches. We have previously identified the transcription factor TCF21 as the causal CAD gene at 6q23.2 and characterized its downstream transcriptional network that is enriched for CAD GWAS genes. Here we investigate the hypothesis that TCF21 interacts with a downstream target gene, the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor that mediates the cellular response to environmental contaminants, including dioxin and polycyclic aromatic hydrocarbons (e.g., tobacco smoke). Perturbation of TCF21 expression in human coronary artery smooth muscle cells (HCASMC) revealed that TCF21 promotes expression of AHR, its heterodimerization partner ARNT, and cooperates with these factors to upregulate a number of inflammatory downstream disease related genes including IL1A, MMP1, and CYP1A1. TCF21 was shown to bind in AHR, ARNT and downstream target gene loci, and co-localization was noted for AHR-ARNT and TCF21 binding sites genome-wide in regions of HCASMC open chromatin. These regions of co-localization were found to be enriched for GWAS signals associated with cardio-metabolic as well as chronic inflammatory disease phenotypes. Finally, we show that similar to TCF21, AHR gene expression is increased in atherosclerotic lesions in mice in vivo using laser capture microdissection, and AHR protein is localized in human carotid atherosclerotic lesions where it is associated with protein kinases with a critical role in innate immune response. These data suggest that TCF21 can cooperate with AHR to activate an inflammatory gene expression program that is exacerbated by environmental stimuli, and may contribute to the overall risk for CAD.

Development of an Anti-Corrosion Conductive Nano Carbon Coating Layer on Metal Bipolar Plates.

For automotive applications of polymer electrolyte membrane fuel cells, the enhancement of the corrosion resistance of metal bipolar plates has been a critical issue with regard to the lifespan of fuel cell stacks. In this paper, we present a novel method for increasing the lifespan by means of a conductive carbon coating on bipolar plates. Conductive carbon films were plasma coated onto metal bipolar plates in a vacuum at various temperatures. As a result, 316L stainless plates with a 10-nm-thick carbon coating layer on a 20-nm-thick CrN undercoat layer showed-contact resistance of 10.71 mΩcm2@10 kgf/cm2 and a corrosion current of 0.5 µA/cm2@0.6 V. This thin coating layer with high conductivity and excellent corrosion resistance suggests a new, effective coating method for the mass production of metal bipolar plates.

Characterization of TCF21 Downstream Target Regions Identifies a Transcriptional Network Linking Multiple Independent Coronary Artery Disease Loci.

To functionally link coronary artery disease (CAD) causal genes identified by genome wide association studies (GWAS), and to investigate the cellular and molecular mechanisms of atherosclerosis, we have used chromatin immunoprecipitation sequencing (ChIP-Seq) with the CAD associated transcription factor TCF21 in human coronary artery smooth muscle cells (HCASMC). Analysis of identified TCF21 target genes for enrichment of molecular and cellular annotation terms identified processes relevant to CAD pathophysiology, including "growth factor binding," "matrix interaction," and "smooth muscle contraction." We characterized the canonical binding sequence for TCF21 as CAGCTG, identified AP-1 binding sites in TCF21 peaks, and by conducting ChIP-Seq for JUN and JUND in HCASMC confirmed that there is significant overlap between TCF21 and AP-1 binding loci in this cell type. Expression quantitative trait variation mapped to target genes of TCF21 was significantly enriched among variants with low P-values in the GWAS analyses, suggesting a possible functional interaction between TCF21 binding and causal variants in other CAD disease loci. Separate enrichment analyses found over-representation of TCF21 target genes among CAD associated genes, and linkage disequilibrium between TCF21 peak variation and that found in GWAS loci, consistent with the hypothesis that TCF21 may affect disease risk through interaction with other disease associated loci. Interestingly, enrichment for TCF21 target genes was also found among other genome wide association phenotypes, including height and inflammatory bowel disease, suggesting a functional profile important for basic cellular processes in non-vascular tissues. Thus, data and analyses presented here suggest that study of GWAS transcription factors may be a highly useful approach to identifying disease gene interactions and thus pathways that may be relevant to complex disease etiology.

Coronary Artery Disease Associated Transcription Factor TCF21 Regulates Smooth Muscle Precursor Cells That Contribute to the Fibrous Cap.

Recent genome wide association studies have identified a number of genes that contribute to the risk for coronary heart disease. One such gene, TCF21, encodes a basic-helix-loop-helix transcription factor believed to serve a critical role in the development of epicardial progenitor cells that give rise to coronary artery smooth muscle cells (SMC) and cardiac fibroblasts. Using reporter gene and immunolocalization studies with mouse and human tissues we have found that vascular TCF21 expression in the adult is restricted primarily to adventitial cells associated with coronary arteries and also medial SMC in the proximal aorta of mouse. Genome wide RNA-Seq studies in human coronary artery SMC (HCASMC) with siRNA knockdown found a number of putative TCF21 downstream pathways identified by enrichment of terms related to CAD, including "vascular disease," "disorder of artery," and "occlusion of artery," as well as disease-related cellular functions including "cellular movement" and "cellular growth and proliferation." In vitro studies in HCASMC demonstrated that TCF21 expression promotes proliferation and migration and inhibits SMC lineage marker expression. Detailed in situ expression studies with reporter gene and lineage tracing revealed that vascular wall cells expressing Tcf21 before disease initiation migrate into vascular lesions of ApoE-/- and Ldlr-/- mice. While Tcf21 lineage traced cells are distributed throughout the early lesions, in mature lesions they contribute to the formation of a subcapsular layer of cells, and others become associated with the fibrous cap. The lineage traced fibrous cap cells activate expression of SMC markers and growth factor receptor genes. Taken together, these data suggest that TCF21 may have a role regulating the differentiation state of SMC precursor cells that migrate into vascular lesions and contribute to the fibrous cap and more broadly, in view of the association of this gene with human CAD, provide evidence that these processes may be a mechanism for CAD risk attributable to the vascular wall.

Genetics and Genomics of Coronary Artery Disease.

Coronary artery disease (or coronary heart disease), is the leading cause of mortality in many of the developing as well as the developed countries of the world. Cholesterol-enriched plaques in the heart's blood vessels combined with inflammation lead to the lesion expansion, narrowing of blood vessels, reduced blood flow, and may subsequently cause lesion rupture and a heart attack. Even though several environmental risk factors have been established, such as high LDL-cholesterol, diabetes, and high blood pressure, the underlying genetic composition may substantially modify the disease risk; hence, genome composition and gene-environment interactions may be critical for disease progression. Ongoing scientific efforts have seen substantial advancements related to the fields of genetics and genomics, with the major breakthroughs yet to come. As genomics is the most rapidly advancing field in the life sciences, it is important to present a comprehensive overview of current efforts. Here, we present a summary of various genetic and genomics assays and approaches applied to coronary artery disease research.

The Feasibility and Outcome of Oro-esophageal Tube Feeding in Patients with Various Etiologies.

The oro-esophageal tube (OE tube) is widely used in dysphagia patients although its success rate for transition to oral feeding is reported only in stroke patients. The aim of this study was to evaluate the feasibility and outcome of OE tube feeding for patients with dysphagia resulting from various etiologies. The authors reviewed the medical records of 1995 dysphagic patients that had undergone videofluoroscopic swallowing study (VFSS) in a tertiary hospital from April 2002 through December 2009. Of these, 97 patients were recommended to use OE tube feeding based on the VFSS findings. Follow-up VFSS were performed on 54 patients. The mean duration of tube use at the time of follow-up VFSS was 274 days. We evaluated clinical information including age, sex, diet, etiology of dysphagia, location of lesions, duration of intervention, and complications of OE tube feeding. Initially, all 54 patients were fed using the OE tube. After their last follow-up evaluation, 19 patients (35.2 %) resumed full oral feeding without the OE tube, 12 patients (22.2 %) used partial OE tube feeding, and 23 patients (42.6 %) continued OE tube feeding only. Full oral feeding was achieved again most often in brain tumor, stroke, and head and neck cancer patients (54.5, 27.3, and 20.0 %, respectively). Mild adverse events, such as blood-tinged sputum, nausea, dyspepsia, and regurgitation of food, were reported in 4 patients. OE tube feeding is a feasible feeding method also in conditions other than stroke such as brain tumors, and head and neck cancers.

Validation of the videofluoroscopic dysphagia scale in various etiologies.

The videofluoroscopic dysphagia scale (VDS) was developed as an objective predictor of the prognosis of dysphagia after stroke. We evaluated the clinical validity of the VDS for various diseases. We reviewed the medical records of 1,995 dysphagic patients (1,222 men and 773 women) who underwent videofluoroscopic studies in Seoul National University Hospital from April 2002 through December 2009. Their American Speech­Language­Hearing Association's National Outcome Measurement System (ASHA NOMS) swallowing scale, clinical dysphagia scale (CDS), and VDS scores were evaluated on the basis of the clinical and/or videofluoroscopic findings by the consensus of two physiatrists. The correlations between the VDS and the other scales were calculated. The VDS displayed significant correlations with the ASHA NOMS swallowing scale and the CDS in every disease group (p < 0.001 in all groups, including central and peripheral nervous system disorders), and these correlations were more apparent for spinal cord injury, peripheral nerve system disorders, and neurodegenerative diseases (correlation coefficients between the VDS and the ASHA NOMS swallowing scale: −0.603, −0.602, and −0.567, respectively). This study demonstrated that the VDS is applicable to dysphagic patients with numerous etiologies that cause dysphagia

Using Multimodal Data to Improve Precision of Inpatient Event Timelines.

Textual data often describe events in time but frequently contain little information about their specific timing, whereas complementary structured data streams may have precise timestamps but may omit important contextual information. We investigate the problem in healthcare, where we produce clinician annotations of discharge summaries, with access to either unimodal (text) or multimodal (text and tabular) data, (i) to determine event interval timings and (ii) to train multimodal language models to locate those events in time. We find our annotation procedures, dashboard tools, and annotations result in high-quality timestamps. Specifically, the multimodal approach produces more precise timestamping, with uncertainties of the lower bound, upper bounds, and duration reduced by 42% (95% CI 34-51%), 36% (95% CI 28-44%), and 13% (95% CI 10-17%), respectively. In the classification version of our task, we find that, trained on our annotations, our multimodal BERT model outperforms unimodal BERT model and Llama-2 encoder-decoder models with improvements in F1 scores for upper (10% and 61%, respectively) and lower bounds (8% and 56%, respectively). The code for the annotation tool and the BERT model is available (link).