Roles of endogenous retroviral elements in the establishment and maintenance of imprinted gene expression.

DNA methylation (DNAme) has long been recognized as a host defense mechanism, both in the restriction modification systems of prokaryotes as well as in the transcriptional silencing of repetitive elements in mammals. When DNAme was shown to be implicated as a key epigenetic mechanism in the regulation of imprinted genes in mammals, a parallel with host defense mechanisms was drawn, suggesting perhaps a common evolutionary origin. Here we review recent work related to this hypothesis on two different aspects of the developmental imprinting cycle in mammals that has revealed unexpected roles for long terminal repeat (LTR) retroelements in imprinting, both canonical and noncanonical. These two different forms of genomic imprinting depend on different epigenetic marks inherited from the mature gametes, DNAme and histone H3 lysine 27 trimethylation (H3K27me3), respectively. DNAme establishment in the maternal germline is guided by transcription during oocyte growth. Specific families of LTRs, evading silencing mechanisms, have been implicated in this process for specific imprinted genes. In noncanonical imprinting, maternally inherited histone marks play transient roles in transcriptional silencing during preimplantation development. These marks are ultimately translated into DNAme, notably over LTR elements, for the maintenance of silencing of the maternal alleles in the extraembryonic trophoblast lineage. Therefore, LTR retroelements play important roles in both establishment and maintenance of different epigenetic pathways leading to imprinted expression during development. Because such elements are mobile and highly polymorphic among different species, they can be coopted for the evolution of new species-specific imprinted genes.

Photoacoustic imaging of squirrel monkey cortical responses induced by peripheral mechanical stimulation.

Non-human primates (NHPs) are crucial models for studies of neuronal activity. Emerging photoacoustic imaging modalities offer excellent tools for studying NHP brains with high sensitivity and high spatial resolution. In this research, a photoacoustic microscopy (PAM) device was used to provide a label-free quantitative characterization of cerebral hemodynamic changes due to peripheral mechanical stimulation. A 5 × 5 mm area within the somatosensory cortex region of an adult squirrel monkey was imaged. A deep, fully connected neural network was characterized and applied to the PAM images of the cortex to enhance the vessel structures after mechanical stimulation on the forelimb digits. The quality of the PAM images was improved significantly with a neural network while preserving the hemodynamic responses. The functional responses to the mechanical stimulation were characterized based on the improved PAM images. This study demonstrates capability of PAM combined with machine learning for functional imaging of the NHP brain.

AI-Assisted Summarization of Radiologic Reports: Evaluating GPT3davinci, BARTcnn, LongT5booksum, LEDbooksum, LEDlegal, and LEDclinical.

BACKGROUND AND PURPOSE: The review of clinical reports is an essential part of monitoring disease progression. Synthesizing multiple imaging reports is also important for clinical decisions. It is critical to aggregate information quickly and accurately. Machine learning natural language processing (NLP) models hold promise to address an unmet need for report summarization. MATERIALS AND METHODS: We evaluated NLP methods to summarize longitudinal aneurysm reports. A total of 137 clinical reports and 100 PubMed case reports were used in this study. Models were 1) compared against expert-generated summary using longitudinal imaging notes collected in our institute and 2) compared using publicly accessible PubMed case reports. Five AI models were used to summarize the clinical reports, and a sixth model, the online GPT3davinci NLP large language model (LLM), was added for the summarization of PubMed case reports. We assessed the summary quality through comparison with expert summaries using quantitative metrics and quality reviews by experts. RESULTS: In clinical summarization, BARTcnn had the best performance (BERTscore = 0.8371), followed by LongT5Booksum and LEDlegal. In the analysis using PubMed case reports, GPT3davinci demonstrated the best performance, followed by models BARTcnn and then LEDbooksum (BERTscore = 0.894, 0.872, and 0.867, respectively). CONCLUSIONS: AI NLP summarization models demonstrated great potential in summarizing longitudinal aneurysm reports, though none yet reached the level of quality for clinical usage. We found the online GPT LLM outperformed the others; however, the BARTcnn model is potentially more useful because it can be implemented on-site. Future work to improve summarization, address other types of neuroimaging reports, and develop structured reports may allow NLP models to ease clinical workflow.

Gendered Patterns in Manifest and Latent Mental Health Indicators Among Suicide Decedents: 2003-2020 National Violent Death Reporting System (NVDRS).

Objectives. To investigate differences in the documentation of mental health symptomology between male and female suicide decedents in the 2003-2020 US National Violent Death Reporting System (NVDRS). Methods. Using information on 271 998 suicides in the 2003-2020 NVDRS, we evaluated precoded mental health-related variables and topic model-derived latent mental health themes in the law enforcement and coroner or medical examiner death narratives compiled by trained public health workers. Results. Public health records of male compared with female suicides were less likely to include notations of mental health conditions or treatment interventions. However, topic modeling of death summaries revealed that male suicide decedents were more likely to evidence several subclinical cognitive and emotional indicators of distress. Conclusions. Suicide death records vary by gender, both in recorded evidence for mental health conditions at time of death and in accompanying narratives describing proximal circumstances surrounding these deaths. Our findings hint that patterns of subclinical mental health changes among men might be less well captured in commonly used mental health indicators, suggesting that prevention efforts may benefit from measures that also target assessment of subclinical distress. (Am J Public Health. 2024;114(S3):S268-S277. https://doi.org/10.2105/AJPH.2023.307427).

Resting pulmonary function and artery pressure and cardiopulmonary exercise testing in chronic heart failure patients in Taiwan - a prospective observational cross-sectional study comparing healthy subjects and interstitial lung disease patients.

BACKGROUND: Restrictive ventilatory defects and elevated pulmonary artery pressure (PAP) are common in patients with chronic heart failure (CHF) and those with interstitial lung disease (ILD). However, as oxyhemoglobin desaturation seldom occurs in stable CHF patients at peak exercise, we hypothesized that the pathophysiology may be different between them. This study aimed to investigate: (1) PAP and lung function at rest, (2) pulmonary gas exchange (PGX) and breathing patterns at peak exercise, (3) mechanisms of dyspnea at peak exercise in patients with CHF compared to healthy subjects and ILD patients. METHODS: We consecutively enrolled 83 participants (27 with CHF, 23 with ILD, and 33 healthy controls). The CHF and ILD groups had similar functional status. Lung function and cardiopulmonary exercise tests with Borg Dyspnea Score were performed. PAP was estimated using echocardiography. Resting lung function, PAP and peak exercise data in the CHF group were compared to the healthy and ILD groups. Correlation analysis was performed to elucidate the mechanisms of dyspnea in the CHF and ILD groups. RESULTS: Compared to the healthy group, the CHF group had normal lung function, PAP at rest, and normal dyspnea score and PGX at peak exercise, whereas the ILD group had abnormal values compared to the CHF group. Dyspnea score was positively correlated with pressure gradient, lung expansion capabilities, and expiratory tidal flow in the CHF group (all p < 0.05), but inversely correlated with inspiratory time-related variables in the ILD group (all p < 0.05). CONCLUSION: Normal lung function and PAP at rest, and dyspnea scores and PGX at peak exercise indicated that pulmonary hypertension and fibrosis were insignificant in the patients with CHF. The factors affecting dyspnea at peak exercise were different between the CHF and ILD groups. As the sample size in this study was small, large-scale studies are warranted to confirm our findings.

Normal lung function and pulmonary arterial pressure at rest, and dyspnea scores and pulmonary gas exchange at peak exercise indicated that pulmonary hypertension and fibrosis in the patients with chronic heart failure were not significant.Dyspnea score was correlated with different physiological variables between the groups with chronic heart failure and interstitial lung disease.

Safety and efficacy of early varenicline prescription in hospitalized patients with acute myocardial infarction: East Asian population.

BACKGROUND: Smoking is a strong risk factor for patients with acute myocardial infarction (AMI). Varenicline is commonly used as a smoking cessation medication, but little is known about its usage in patients with AMI, particularly in hospitalized patients. METHODS: This is a prospective observational, single-center study collected from May 2018 to July 2021. Study patients underwent percutaneous coronary intervention for AMI. The primary end point was set as safety of varenicline, focusing on any serious adverse cardiac events within 24 weeks after treatment. Efficacy of smoking abstinence was also assessed through self-reports of complete abstinence over a week before the 24- week clinic visit. RESULTS: A total of 162 patients hospitalized with AMI were enrolled in our study. Mean age was 56.7 ± 9.95 years and 97% of the patients were male. Most patients (93.2%) received their first dose of varenicline during hospitalization. Time from admission to first dose of study medication was 2.31 ± 2.73 days and duration of drug intake was 7.41 ± 5.18 weeks. At week 24, only one patient had recurrent myocardial infarction, five patients had undergone revascularization for target lesion failure, and no additional patients developed stroke or died. In terms of efficacy, the rate of smoking abstinence was 79%. Light smokers found it easier to quit smoking than heavy smokers. CONCLUSION: This study may represent the first report on the safety and efficacy of early initiation of varenicline treatment in East Asian population hospitalized due to AMI who recently underwent percutaneous coronary intervention.

Real-time, volumetric imaging of radiation dose delivery deep into the liver during cancer treatment.

Ionizing radiation acoustic imaging (iRAI) allows online monitoring of radiation's interactions with tissues during radiation therapy, providing real-time, adaptive feedback for cancer treatments. We describe an iRAI volumetric imaging system that enables mapping of the three-dimensional (3D) radiation dose distribution in a complex clinical radiotherapy treatment. The method relies on a two-dimensional matrix array transducer and a matching multi-channel preamplifier board. The feasibility of imaging temporal 3D dose accumulation was first validated in a tissue-mimicking phantom. Next, semiquantitative iRAI relative dose measurements were verified in vivo in a rabbit model. Finally, real-time visualization of the 3D radiation dose delivered to a patient with liver metastases was accomplished with a clinical linear accelerator. These studies demonstrate the potential of iRAI to monitor and quantify the 3D radiation dose deposition during treatment, potentially improving radiotherapy treatment efficacy using real-time adaptive treatment.

Photoacoustic imaging of visually evoked cortical and subcortical hemodynamic activity in mouse brain: feasibility study with piezoelectric and capacitive micromachined ultrasonic transducer (CMUT) arrays.

This study investigates the feasibility of capturing visually evoked hemodynamic responses in the mouse brain using photoacoustic tomography (PAT) and ultrasound (US) dual-modality imaging. A commercial piezoelectric transducer array and a capacitive micromachined ultrasonic transducer (CMUT) array were compared using a programmable PAT-US imaging system. The system resolution was measured by imaging phantoms. We also tested the ability of the system to capture visually evoked hemodynamic responses in the superior colliculus as well as the primary visual cortex in wild-type mice. Results show that the piezoelectric transducer array and the CMUT array exhibit comparable imaging performance, and both arrays can capture visually evoked hemodynamic responses in subcortical as well as cortical regions of the mouse brain.

A Houttuynia cordata-based Chinese herbal formula improved symptoms of allergic rhinitis during the COVID-19 pandemic.

BACKGROUND: The symptoms of coronavirus disease 2019 (COVID-19) such as hyposmia, rhinorrhea, nasal obstruction, and cough are similar to those of chronic allergic rhinitis (AR). Such symptoms can easily lead AR patients to unnecessary anxiety, misdiagnosis, and invasive diagnostic tests in the COVID-19 pandemic. Interleukin-6 (IL-6) is an important mediator for chronic AR and plays a crucial role in the inflammation of COVID-19. Houttuynia cordata (HC) has been shown to reduce nasal congestion and swelling by suppressing the activation of IL-6 and is used to fight COVID-19. A novel HC-based Chinese herbal formula, Zheng-Yi-Fang (ZYF), was developed to test effects on nasal symptoms of patients with AR in the COVID-19 pandemic. METHODS: Participants aged between 20 and 60 years with at least a 2-year history of moderate to severe perennial AR were enrolled. Eligible participants were randomly allocated to either the intervention group (taking ZYF) or the control group (using regular western medicine) for 4 weeks. The Chinese version of the Rhinosinusitis Outcome Measures was used to evaluate impacts on quality of life and nasal symptoms of participants with AR. In addition, the effect of ZYF on lipopolysaccharide (LPS)-induced IL-6 was investigated. RESULTS: Participants with AR taking ZYF improved their symptoms of nasal obstruction, nasal secretion, hyposmia, and postnasal drip in comparison with those of the control group. Meanwhile, ZYF exhibited inhibition of IL-6 secretion in the LPS-induced inflammatory model. CONCLUSION: ZYF has potential effects to relieve nasal symptoms for AR during the COVID-19 pandemic.

Label-free photoacoustic computed tomography of mouse cortical responses to retinal photostimulation using a pair-wise correlation map.

The lack of a non-invasive or minimally invasive imaging technique has long been a challenge to investigating brain activities in mice. Functional magnetic resonance imaging and the more recently developed diffuse optical imaging both suffer from limited spatial resolution. Photoacoustic (PA) imaging combines the sensitivity of optical excitation to hemodynamic changes and ultrasound detection's relatively high spatial resolution. In this study, we evaluated the feasibility of using a label-free, real-time PA computed tomography (PACT) system to measure visually evoked hemodynamic responses within the primary visual cortex (V1) in mice. Photostimulation of the retinas evoked significantly faster and stronger V1 responses in wild-type mice than in age-matched rod/cone-degenerate mice, consistent with known differences between rod/cone- vs. melanopsin-mediated photoreception. In conclusion, the PACT system in this study has sufficient sensitivity and spatial resolution to resolve visual cortical hemodynamics during retinal photostimulation, and PACT is a potential tool for investigating visually evoked brain activities in mouse models of retinal diseases.

Integrating topic modeling and word embedding to characterize violent deaths.

SignificanceWe introduce an approach to identify latent topics in large-scale text data. Our approach integrates two prominent methods of computational text analysis: topic modeling and word embedding. We apply our approach to written narratives of violent death (e.g., suicides and homicides) in the National Violent Death Reporting System (NVDRS). Many of our topics reveal aspects of violent death not captured in existing classification schemes. We also extract gender bias in the topics themselves (e.g., a topic about long guns is particularly masculine). Our findings suggest new lines of research that could contribute to reducing suicides or homicides. Our methods are broadly applicable to text data and can unlock similar information in other administrative databases.

Mouse hybrid genome mediates diverse brain phenotypes with the specificity of reciprocal crosses.

Hybrid species have more genetic diversity than their parents. However, the impact of the hybrid genome of reciprocal crosses on brain function remains largely unknown. We performed behavioral, molecular, and neuronal analyses on C57BL/6J mice (B6), CAST/EiJ mice (CAST), and hybrid mice resulting from reciprocal crosses of the two strains, B6/CAST F1i and B6/CAST F1r, respectively. Hybrid mice displayed greater motor strength and coordination, food grinding, social dominance, and less sociability compared to their parental strains. Parental origin influenced body weight, locomotor speed, and heat nociception of hybrid mice. Parental origin, cell type, and the interaction of both affected expression patterns of hybrid genomes including imprinted genes. There was a correlation between affected genes and corresponding behavioral phenotypes. Hybrid genomes mediated neuronal activity in the locus coeruleus, a brain region implicated in arousal, adaptive behaviors, and sleep-wake cycle due to its norepinephrine projections throughout the central nervous system. The comprehensive brain phenotypes in these hybrid mice reveal important functional readouts associated with interactions of hybrid genomes and impacts of parental genomes.

Photoacoustic imaging of squirrel monkey cortical and subcortical brain regions during peripheral electrical stimulation.

The investigation of neuronal activity in non-human primate models is of critical importance due to their genetic similarity to human brains. In this study, we tested the feasibility of using photoacoustic imaging for the detection of cortical and subcortical responses due to peripheral electrical stimulation in a squirrel monkey model. Photoacoustic computed tomography and photoacoustic microscopy were applied on squirrel monkeys for real-time deep subcortical imaging and optical-resolution cortical imaging, respectively. The electrically evoked hemodynamic changes in primary somatosensory cortex, premotor cortices, primary motor cortex, and underlying subcortical areas were measured. Hemodynamic responses were observed in both cortical and subcortical brain areas at the cortices during external stimulation, demonstrating the feasibility of photoacoustic technique for functional imaging of non-human primate brain.

BERTHop: An Effective Vision-and-Language Model for Chest X-ray Disease Diagnosis.

Vision-and-language (V&L) models take image and text as input and learn to capture the associations between them. These models can potentially deal with the tasks that involve understanding medical images along with their associated text. However, applying V&L models in the medical domain is challenging due to the expensiveness of data annotations and the requirements of domain knowledge. In this paper, we identify that the visual representation in general V&L models is not suitable for processing medical data. To overcome this limitation, we propose BERTHop, a transformer-based model based on PixelHop++ and VisualBERT for better capturing the associations between clinical notes and medical images. Experiments on the OpenI dataset, a commonly used thoracic disease diagnosis benchmark, show that BERTHop achieves an average Area Under the Curve (AUC) of 98.12% which is 1.62% higher than state-of-the-art while it is trained on a 9× smaller dataset.

Atractylodin Suppresses TGF-ß-Mediated Epithelial-Mesenchymal Transition in Alveolar Epithelial Cells and Attenuates Bleomycin-Induced Pulmonary Fibrosis in Mice.

Idiopathic pulmonary fibrosis (IPF) is characterized by fibrotic change in alveolar epithelial cells and leads to the irreversible deterioration of pulmonary function. Transforming growth factor-beta 1 (TGF-ß1)-induced epithelial-mesenchymal transition (EMT) in type 2 lung epithelial cells contributes to excessive collagen deposition and plays an important role in IPF. Atractylodin (ATL) is a kind of herbal medicine that has been proven to protect intestinal inflammation and attenuate acute lung injury. Our study aimed to determine whether EMT played a crucial role in the pathogenesis of pulmonary fibrosis and whether EMT can be utilized as a therapeutic target by ATL treatment to mitigate IPF. To address this topic, we took two steps to investigate: 1. Utilization of anin vitro EMT model by treating alveolar epithelial cells (A549 cells) with TGF-ß1 followed by ATL treatment for elucidating the underlying pathways, including Smad2/3 hyperphosphorylation, mitogen-activated protein kinase (MAPK) pathway overexpression, Snail and Slug upregulation, and loss of E-cadherin. Utilization of an in vivo lung injury model by treating bleomycin on mice followed by ATL treatment to demonstrate the therapeutic effectiveness, such as, less collagen deposition and lower E-cadherin expression. In conclusion, ATL attenuates TGF-ß1-induced EMT in A549 cells and bleomycin-induced pulmonary fibrosis in mice.

Convective forcing of the North American Monsoon anticyclone at intraseasonal and interannual time scales.

In the upper troposphere and lower stratosphere (UTLS), large-scale anticyclones associated with monsoons play major roles in tropospheric and stratospheric transport and mixing. To understand the forcing of the North American monsoon anticyclone (NAMA), this study examines the connection between precipitation over the tropics and subtropics of the North American longitude sector and the variability of the troposphere and lower stratosphere. Using ERA5 reanalysis and outgoing longwave radiation (OLR) data from 1979âAS2019, we assess the relationship at the intraseasonal time scale using pentad-mean time series. We show that OLR anomalies are correlated with circulation anomalies northwest and northeast of the region of precipitation. Decreased OLR (increased precipitation) corresponds to increased geopotential heights and anticyclonic circulation anomalies in the 300 - 100 hPa layer and an opposite response in the lower tropospheric 850 - 600 hPa layer. The results are consistent with the established theory of the Rossby wave response to latent heating. The increase in height, which is strongest near 150 hPa, indicates that increased precipitation is associated with a strengthened NAMA. UTLS temperatures also have significant correlations with OLR, with cold (warm) anomalies occurring above (below) the core of the anticyclonic anomaly consistent with large-scale balance. The vertical structure of geopotential and temperature anomalies is compared to simulations using an idealized general circulation model, which shows that such a vertical structure is a consistent response to diabatic heating. Correlations at the interannual time scale resemble those at the intraseasonal time scale, demonstrating that precipitation is related to the NAMA at both time scales.

Aggression, Escalation, and Other Latent Themes in Legal Intervention Deaths of Non-Hispanic Black and White Men: Results From the 2003‒2017 National Violent Death Reporting System.

Objectives. To investigate racial/ethnic differences in legal intervention‒related deaths using state-of-the-art topic modeling of law enforcement and coroner text summaries drawn from the 2003-2017 US National Violent Death Reporting System (NVDRS). Methods. Employing advanced topic modeling, we identified 8 topics consistent with dangerousness in death incidents in the NVDRS death narratives written by public health workers (PHWs). Using logistic regression, we then evaluated racial/ethnic differences in PHW-coded variables and narrative topics among 4981 males killed by legal intervention, while adjusting for age, county-level characteristics, and year. Results. Black, as compared with White, decedents were younger and their deaths were less likely to include PHW-coded mental health or substance use histories, weapon use, or positive toxicology for alcohol or psychoactive drugs, but more likely to include "gangs-as-an-incident-precipitant" coding. Topic modeling revealed less frequent thematic representation of "physical aggression" or "escalation" but more of "gangs or criminal networks" among Black versus White decedents. Conclusions. While Black males were more likely to be victims of legal intervention deaths, PHW-coded variables in the NVDRS and death narratives suggest lower threat profiles among Black versus similar White decedents. The source of this greater risk remains undetermined.

Multifaceted protein-protein interaction prediction based on Siamese residual RCNN.

MOTIVATION: Sequence-based protein-protein interaction (PPI) prediction represents a fundamental computational biology problem. To address this problem, extensive research efforts have been made to extract predefined features from the sequences. Based on these features, statistical algorithms are learned to classify the PPIs. However, such explicit features are usually costly to extract, and typically have limited coverage on the PPI information. RESULTS: We present an end-to-end framework, PIPR (Protein-Protein Interaction Prediction Based on Siamese Residual RCNN), for PPI predictions using only the protein sequences. PIPR incorporates a deep residual recurrent convolutional neural network in the Siamese architecture, which leverages both robust local features and contextualized information, which are significant for capturing the mutual influence of proteins sequences. PIPR relieves the data pre-processing efforts that are required by other systems, and generalizes well to different application scenarios. Experimental evaluations show that PIPR outperforms various state-of-the-art systems on the binary PPI prediction problem. Moreover, it shows a promising performance on more challenging problems of interaction type prediction and binding affinity estimation, where existing approaches fall short. AVAILABILITY AND IMPLEMENTATION: The implementation is available at https://github.com/muhaochen/seq_ppi.git. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Antibiotic Susceptibility Test with Surface-Enhanced Raman Scattering in a Microfluidic System.

Antibiotic susceptibility test (AST) is essential in clinical diagnosis of serious bacterial infection, such as sepsis, while it typically takes 2-5 days for sample culture, antibiotic treatment, and reading result. Detecting metabolites secreted from bacteria with surface-enhanced Raman scattering (SERS) enables rapid determination of antibiotic susceptibility, reducing the AST time to 1-2 days. However, it still requires 1 day of culture time to obtain sufficient quantity of bacteria for sample washing, bacterial extraction, and antibiotic treatment. Additionally, the whole procedure, manually performed in open environment, often suffers from contamination and human error. To address the above problems, a microfluidic system integrating membrane filtration and the SERS-active substrate (MF-SERS) was developed to perform on-chip bacterial enrichment, metabolite collection, and in situ SERS measurements for antibiotic susceptibility test. Using Escherichia coli as the prototype bacterium, the lowest SERS detection limit of bacterial concentration of the MF-SERS system is 103 CFU/mL, which is 4 orders of magnitude lower than that using centrifugation-purification procedure, significantly shortening the bacterial culture time. The bacteria and secreted metabolites are enclosed during bacterial trapping, metabolite filtration, and SERS detection, thus minimizing possible contamination and human errors. Finally, the successful demonstration of AST on E. coli with a concentration of 103 CFU/mL is presented. Overall, the MF-SERS system with a miniature size and well-confined microenvironment allows the integration of multiple bacteria processes for bacterial enrichment, culture, and determination of AST.