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.

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).

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.

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.

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.

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.

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.

Correction to: Stage-dependent piRNAs in chicken implicated roles in modulating male germ cell development.

Following publication of the original article [1], the authors reported that one of the authors' names is spelled incorrectly.

Stage-dependent piRNAs in chicken implicated roles in modulating male germ cell development.

BACKGROUND: The PIWI/piRNA pathway is a conserved machinery important for germ cell development and fertility. This piRNA-guided molecular machinery is best known for repressing derepressed transposable elements (TE) during epigenomic reprogramming. The extent to which piRNAs are involved in modulating transcripts beyond TEs still need to be clarified, and it may be a stage-dependent event. We chose chicken germline as a study model because of the significantly lower TE complexity in the chicken genome compared to mammalian species. RESULTS: We generated high-confidence piRNA candidates in various stages across chicken germline development by 3'-end-methylation-enriched small RNA sequencing and in-house bioinformatics analysis. We observed a significant developmental stage-dependent loss of TE association and a shifting of the ping-pong cycle signatures. Moreover, the stage-dependent reciprocal abundance of LINE retrotransposons, CR1-C, and its associated piRNAs implicated the developmental stage-dependent role of piRNA machinery. The stage dependency of piRNA expression and its potential functions can be better addressed by analyzing the piRNA precursors/clusters. Interestingly, the new piRNA clusters identified from embryonic chicken testes revealed evolutionary conservation between chickens and mammals, which was previously thought to not exist. CONCLUSIONS: In this report, we provided an original chicken RNA resource and proposed an analytical methodology that can be used to investigate stage-dependent changes in piRNA compositions and their potential roles in TE regulation and beyond, and also revealed possible conserved functions of piRNAs in developing germ cells.

CHA2 DS2 -VASc scores for outcome prediction in acute ischaemic stroke.

BACKGROUND: The CHADS2 and CHA2 DS2 -VASc scores are clinical risk stratification instruments that are used clinically to assess the risk of stroke in patients with atrial fibrillation (AF). The aim of this study was to evaluate whether the prestroke CHADS2 and CHA2 DS2 -VASc scores could be useful for predicting infarction severity and long-term outcomes in patients with acute ischaemic stroke. MATERIALS AND METHODS: This prospective study included all 1494 patients who had acute ischaemic stroke without haemorrhagic transformation which was evidenced with magnetic resonance (MR) imaging during hospitalization. Total infarction volume and arterial stenosis score were calculated based on MR imaging. National Institutes of Health Stroke Scale scores (NIHSSs) were obtained at admission and discharge by board-certified neurologists. The clinical outcomes were defined as composite endpoints of restroke and mortality and were recorded with the mean follow-up period of 37.5 months. RESULTS: There were 195 (13.1%) patients with AF. The patients with AF had significantly higher median CHADS2 and CHA2 DS2 -VASc scores than the patients without AF (P < .001). Patients with higher CHADS2 and CHA2 DS2 -VASc scores had significantly higher total infarction volume, arterial stenosis score and NIHSS scores at discharge and poorer clinical outcomes. After adjusting for age, gender and AF, only CHA2 DS2 -VASc scores could predict both restroke and composite endpoints. CONCLUSIONS: Prestroke CHA2 DS2 -VASc scores appear to have better clinical value for predicting the severity of infarction and long-term clinical outcomes in acute ischaemic stroke patients with and without AF.

An automated microfluidic DNA microarray platform for genetic variant detection in inherited arrhythmic diseases.

In this study, we developed an automated microfluidic DNA microarray (AMDM) platform for point mutation detection of genetic variants in inherited arrhythmic diseases. The platform allows for automated and programmable reagent sequencing under precise conditions of hybridization flow and temperature control. It is composed of a commercial microfluidic control system, a microfluidic microarray device, and a temperature control unit. The automated and rapid hybridization process can be performed in the AMDM platform using Cy3 labeled oligonucleotide exons of SCN5A genetic DNA, which produces proteins associated with sodium channels abundant in the heart (cardiac) muscle cells. We then introduce a graphene oxide (GO)-assisted DNA microarray hybridization protocol to enable point mutation detection. In this protocol, a GO solution is added after the staining step to quench dyes bound to single-stranded DNA or non-perfectly matched DNA, which can improve point mutation specificity. As proof-of-concept we extracted the wild-type and mutant of exon 12 and exon 17 of SCN5A genetic DNA from patients with long QT syndrome or Brugada syndrome by touchdown PCR and performed a successful point mutation discrimination in the AMDM platform. Overall, the AMDM platform can greatly reduce laborious and time-consuming hybridization steps and prevent potential contamination. Furthermore, by introducing the reciprocating flow into the microchannel during the hybridization process, the total assay time can be reduced to 3 hours, which is 6 times faster than the conventional DNA microarray. Given the automatic assay operation, shorter assay time, and high point mutation discrimination, we believe that the AMDM platform has potential for low-cost, rapid and sensitive genetic testing in a simple and user-friendly manner, which may benefit gene screening in medical practice.

Analysis of the Sensing Properties of a Highly Stable and Reproducible Ozone Gas Sensor Based on Amorphous In-Ga-Zn-O Thin Film.

In this study, the sensing properties of an amorphous indium gallium zinc oxide (a-IGZO) thin film at ozone concentrations from 500 to 5 ppm were investigated. The a-IGZO thin film showed very good reproducibility and stability over three test cycles. The ozone concentration of 60-70 ppb also showed a good response. The resistance change (ΔR) and sensitivity (S) were linearly dependent on the ozone concentration. The response time (T90-res), recovery time (T90-rec), and time constant (τ) showed first-order exponential decay with increasing ozone concentration. The resistance-time curve shows that the maximum resistance change rate (dRg/dt) is proportional to the ozone concentration during the adsorption. The results also show that it is better to sense rapidly and stably at a low ozone concentration using a high light intensity. The ozone concentration can be derived from the resistance change, sensitivity, response time, time constant (τ), and first derivative function of resistance. However, the time of the first derivative function of resistance is shorter than other parameters. The results show that a-IGZO thin films and the first-order differentiation method are promising candidates for use as ozone sensors for practical applications.

Layer-separable and gap-tunable topological insulators.

The way in which states of a topological insulator (TI) transform from monolayer to bulk is an important issue for applications in spintronics. However, unlike graphite, most layered materials are difficult to exfoliate. Using first-principles calculations, we predict that thallium selenide (TlSe) will be a layered TI with rather weak interlayer coupling and thus it should be exfoliated easily. The evolution of the topological states can also be driven by doping with indium (In) atoms or applying lateral strains. A comparison of TlSe and ß-InSe shows that the influences of structural and chemical components on the electronic structures determine the topological phase. Effects of van der Waals interactions in this TlSe material are also addressed.

Emergence of differentially regulated pathways associated with the development of regional specificity in chicken skin.

BACKGROUND: Regional specificity allows different skin regions to exhibit different characteristics, enabling complementary functions to make effective use of the integumentary surface. Chickens exhibit a high degree of regional specificity in the skin and can serve as a good model for when and how these regional differences begin to emerge. RESULTS: We used developing feather and scale regions in embryonic chickens as a model to gauge the differences in their molecular pathways. We employed cosine similarity analysis to identify the differentially regulated and co-regulated genes. We applied low cell techniques for expression validation and chromatin immunoprecipitation (ChIP)-based enhancer identification to overcome limited cell availabilities from embryonic chicken skin. We identified a specific set of genes demonstrating a high correlation as being differentially expressed during feather and scale development and maturation. Some members of the WNT, TGF-beta/BMP, and Notch family known to be involved in feathering skin differentiation were found to be differentially regulated. Interestingly, we also found genes along calcium channel pathways that are differentially regulated. From the analysis of differentially regulated pathways, we used calcium signaling pathways as an example for further verification. Some voltage-gated calcium channel subunits, particularly CACNA1D, are expressed spatio-temporally in the skin epithelium. These calcium signaling pathway members may be involved in developmental decisions, morphogenesis, or epithelial maturation. We further characterized enhancers associated with histone modifications, including H3K4me1, H3K27ac, and H3K27me3, near calcium channel-related genes and identified signature intensive hotspots that may be correlated with certain voltage-gated calcium channel genes. CONCLUSION: We demonstrated the applicability of cosine similarity analysis for identifying novel regulatory pathways that are differentially regulated during development. Our study concerning the effects of signaling pathways and histone signatures on enhancers suggests that voltage-gated calcium signaling may be involved in early skin development. This work lays the foundation for studying the roles of these gene pathways and their genomic regulation during the establishment of skin regional specificity.

Dnmt3l-knockout donor cells improve somatic cell nuclear transfer reprogramming efficiency.

Nuclear transfer (NT) is a technique used to investigate the development and reprogramming potential of a single cell. DNA methyltransferase-3-like, which has been characterized as a repressive transcriptional regulator, is expressed in naturally fertilized egg and morula/blastocyst at pre-implantation stages. In this study, we demonstrate that the use of Dnmt3l-knockout (Dnmt3l-KO) donor cells in combination with Trichostatin A treatment improved the developmental efficiency and quality of the cloned embryos. Compared with the WT group, Dnmt3l-KO donor cell-derived cloned embryos exhibited increased cell numbers as well as restricted OCT4 expression in the inner cell mass (ICM) and silencing of transposable elements at the blastocyst stage. In addition, our results indicate that zygotic Dnmt3l is dispensable for cloned embryo development at pre-implantation stages. In Dnmt3l-KO mouse embryonic fibroblasts, we observed reduced nuclear localization of HDAC1, increased levels of the active histone mark H3K27ac and decreased accumulation of the repressive histone marks H3K27me3 and H3K9me3, suggesting that Dnmt3l-KO donor cells may offer a more permissive epigenetic state that is beneficial for NT reprogramming.

Identification and cytoprotective function of a novel nestin isoform, Nes-S, in dorsal root ganglia neurons.

In this study, the first nestin isoform, Nes-S, was identified in neurons of dorsal root ganglia (DRG) of adult rats. Nes-S cannot form filaments by itself in cytoplasmic intermediate filament-free SW13 cells. Instead, it co-assembles into filaments with vimentin when transfected into vimentin(+) SW13 cells, and with peripherin and neurofilament proteins when transfected into N2a cells. In primary DRG neurons, endogenous Nes-S co-assembles with peripherin and neurofilament proteins. The expression of Nes-S first appears in DRG at postnatal day 5 and persists to adulthood. Among the adult tissues we examined, the expression of Nes-S is restricted to the sensory and motor neurons. Finally, exogenous Nes-S enhances viability when transfected into N2a cells, and knockdown of endogenous Nes-S impairs the survival of DRG neurons in primary cultures. Taken together, Nes-S is a new neuronal intermediate filament protein that exerts a cytoprotective function in mature sensory and motor neurons.

Myocardial Infarction with Normal Coronary Arteries in a Patient with Heroin Use and Infective Endocarditis.

UNLABELLED: Myocardial infarction with normal coronary arteries typically occurs in patients under 50 years of age. There is usually no history of angina or previous myocardial infarction, and risk factors for ischemic heart disease are frequently absent. We report a 27-year-old heroin user with normal coronary arteries and inferior wall infarction secondary to infective endocarditis. The left ventricular dysfunction normalized after antibiotic and surgical treatments for infective endocarditis. He was followed at our outpatient clinic for one year without recurrence. KEY WORDS: Heroin; Infective endocarditis; Left ventricular ballooning syndrome; Myocardial infarction with normal coronary arteries.

Velocity-Encoded Phase-Contrast Magnetic Resonance Imaging for Diagnosing Severe Bilateral Subclavian Steal Syndrome with Complete Vertebral Reversal.

UNLABELLED: Subclavian steal syndrome (SSS) involves changes in hemodynamics secondary to proximal subclavian artery stenosis and/or occlusion where the subclavian artery "drains" the blood from the vertebral artery. It sometimes induces neuromuscular symptoms, especially in cases with bilateral involvement. We report the case of a 65-year-old symptomatic male with severe bilateral SSS with complete vertebral reversal. Doppler ultrasonography yielded inconclusive results because of a scar in the left lower neck region leading to poor acoustic windows. Subsequent magnetic resonance imaging with contrast-enhanced magnetic resonance angiography and velocity-encoded phase-contrast magnetic resonance imaging provided the vascular morphology and blood flow pattern which allowed subsequent interventions to be successfully performed. KEY WORDS: Angioplasty; Phase-contrast magnetic resonance imaging; Subclavian steal syndrome.