Miracle-dz/UniFAR-FTUs huggingface dataset:
Single-cell gene regulatory network prediction by explainable AI

Abstract The molecular heterogeneity of cancer cells contributes to the often partial response to targeted therapies and relapse of disease due to the escape of resistant cell populations. While single-cell sequencing has started to improve our understanding of this heterogeneity, it offers a mostly descriptive view on cellular types and states. To obtain more functional insights, we propose scGeneRAI, an explainable deep learning approach that uses layer-wise relevance propagation (LRP) to infer gene regulatory networks from static single-cell RNA sequencing data for individual cells. We benchmark our method with synthetic data and apply it to single-cell RNA sequencing data of a cohort of human lung cancers. From the predicted single-cell networks our approach reveals characteristic network patterns for tumor cells and normal epithelial cells and identifies subnetworks that are observed only in (subgroups of) tumor cells of certain patients. While current state-of-the-art methods are limited by their ability to only predict average networks for cell populations, our approach facilitates the reconstruction of networks down to the level of single cells which can be utilized to characterize the heterogeneity of gene regulation within and across tumors.
Racial and Ethnic Disparities in Opioid Access and Urine Drug Screening Among Older Patients With Poor-Prognosis Cancer Near the End of Life

PURPOSE To characterize racial and ethnic disparities and trends in opioid access and urine drug screening (UDS) among patients dying of cancer, and to explore potential mechanisms. METHODS Among 318,549 non-Hispanic White (White), Black, and Hispanic Medicare decedents older than 65 years with poor-prognosis cancers, we examined 2007-2019 trends in opioid prescription fills and potency (morphine milligram equivalents [MMEs] per day [MMEDs]) near the end of life (EOL), defined as 30 days before death or hospice enrollment. We estimated the effects of race and ethnicity on opioid access, controlling for demographic and clinical factors. Models were further adjusted for socioeconomic factors including dual-eligibility status, community-level deprivation, and rurality. We similarly explored disparities in UDS. RESULTS Between 2007 and 2019, White, Black, and Hispanic decedents experienced steady declines in EOL opioid access and rapid expansion of UDS. Compared with White patients, Black and Hispanic patients were less likely to receive any opioid (Black, –4.3 percentage points, 95% CI, –4.8 to –3.6; Hispanic, –3.6 percentage points, 95% CI, –4.4 to –2.9) and long-acting opioids (Black, –3.1 percentage points, 95% CI, –3.6 to –2.8; Hispanic, –2.2 percentage points, 95% CI, –2.7 to –1.7). They also received lower daily doses (Black, –10.5 MMED, 95% CI, –12.8 to –8.2; Hispanic, –9.1 MMED, 95% CI, –12.1 to –6.1) and lower total doses (Black, –210 MMEs, 95% CI, –293 to –207; Hispanic, –179 MMEs, 95% CI, –217 to –142); Black patients were also more likely to undergo UDS (0.5 percentage points; 95% CI, 0.3 to 0.8). Disparities in EOL opioid access and UDS disproportionately affected Black men. Adjustment for socioeconomic factors did not attenuate the EOL opioid access disparities. CONCLUSION There are substantial and persistent racial and ethnic inequities in opioid access among older patients dying of cancer, which are not mediated by socioeconomic variables.
Middle-Range Theory of Ineffective Breathing Pattern in children with Congenital Heart Disease

Abstract Objective: to develop and evaluate a middle-range theory for the Nursing Diagnosis of Ineffective Breathing Pattern in children with congenital heart disease. Method: a methodological study carried out in two stages: 1) development of a middle- range theory for Ineffective Breathing Pattern in children with congenital heart diseases from the analysis of the NANDA-International taxonomy, Callista Roy’s Adaptation Model and a literature review; and 2) assessment of the middle-range theory developed using expert panel evaluation. Results: after three panel evaluations, the final version of the middle-range theory resulted in four metaparadigms, two key concepts, two pictorial diagrams, two propositions and a description of the interrelationships between the key concepts of Ineffective Breathing Pattern in children with congenital heart diseases and evidence for the Nursing practice. Conclusion: the middle-range theory developed and evaluated by experts identified stimuli and behaviors that can assist nurses in identifying the reasons why Ineffective Breathing Pattern is diagnosed and how it manifests itself in children with congenital heart disease, increasing understanding of the relationships between the causes and their temporality.
Effectiveness of Kurtosis-Adjusted Cumulative Noise Exposure in Assessing Occupational Hearing Loss Associated With Complex Noise

Objectives: Occupational noise-induced hearing loss (NIHL) is one of the most prevalent occupational diseases worldwide. Few studies have been reported on applying kurtosis-adjusted noise energy (e.g., kurtosis-adjusted cumulative noise exposure, CNE-K) as a joint indicator for assessing NIHL. This study aimed to analyze the effectiveness of CNE-K in assessing occupational hearing loss associated with complex noise in typical manufacturing industries. Design: A cross-sectional survey of 1404 Chinese manufacturing workers from typical manufacturing industries was conducted. General demographic characteristics, noise exposure data, and noise-induced permanent threshold shifts (NIPTS) at 3, 4, and 6 kHz (NIPTS346) were collected and analyzed. The role of kurtosis in high-frequency noise-induced hearing loss (HFNIHL) was also analyzed. The degree of overlap of the two logistic curves (i.e., between complex noise CNE-K and HFNIHL%, and between Gaussian noise CNE and HFNIHL%) was used to evaluate the effectiveness of CNE-K, using a stratified analysis based on age, sex, industry, or job type. Results: The binary logistic regression analysis showed that in addition to age, sex, exposure duration, and Eight-hour Continuous Equivalent A-weighted Sound Pressure Level (LAeq,8h), kurtosis was a key factor influencing HFNIHL% in workers (odds ratio = 1.18, p < 0.05), and its odds ratio increased with an increase in kurtosis value. Multiple linear regression analysis demonstrated that the contribution of kurtosis to NIPTS346 was second to LAeq,8h. Complex noise led to a higher risk of NIHL than Gaussian noise at frequencies of 3, 4, 6, and 8 kHz after adjusting for age, sex, and CNE (p < 0.05). As kurtosis increased, the notch in the audiogram became deeper, and the frequency at which the notch began to deepen shifted from 3 to 1 kHz. The logistic curve between complex noise CNE-K and HFNIHL% nearly overlapped with that between Gaussian noise CNE and HFNIHL%, and the average difference in HFNIHL% between the two curves decreased from 8.1 to 0.4%. Moreover, the decrease of average difference in HFNIHL% between the two logistic curves was evident in several subgroups, such as male workers, aged <30 and 30 to 50 years, furniture and woodworking industries and gunning and nailing job types with relatively high kurtosis values. Conclusions: Kurtosis, as an indirect metric of noise temporal structure, was an important risk factor for occupational NIHL. Kurtosis-adjusted CNE metric could be more effective than CNE alone in assessing occupational hearing loss risk associated with complex noise.
Establishment of methods to analyze the structural and functional integrity of the quail (Coturnix coturnix japonica) sperm plasma membrane

ABSTRACT 1. The objectives of this study were to establish the use of the fluorophores Hoechst 33342 and propidium iodide for the evaluation of sperm plasma membrane integrity and to identify an adequate hypoosmotic solution for the evaluation of sperm membrane functionality in quails. 2. Sperm samples were collected from the vas deferens of nine quails. After initial evaluation, the samples were subjected to a flash-frozen assay. Three treatments with the following proportions of fresh sperm and sperm subjected to flash freezing were prepared as follows: 100:0 (T100), 50:50 (T50), and 0:100 (T0). The hypoosmotic swelling test used distilled water (0 mOsm/l) and fructose solutions (50, 100, and 200 mOsm/l). 3. Immediately after recovery, the samples showed 75.6 ± 5.0% motility with vigour of 3.7 ± 0.3 and 96.1 ± 0.5% of the sperm appeared normal. The membrane integrity test showed 62.2 ± 5.2% intact sperm at T100, 29.0 ± 4.1% at T50 and 0.1 ± 0.1% at T0. Moreover, a greater number of reactive sperm (74.7 ± 6.7%) were observed when incubated in distilled water (0 mOsm/l) in comparison to other solutions (P < 0.05). 4. The association of fluorescent probes composed of Hoechst 33342 and propidium iodide provided an efficient assessment of the integrity of the plasmatic membrane of quail spermatozoa. However, the study identified that the hypoosmotic swelling test has little predictive value regarding sperm membrane functionality in this species.
Short-range structure of solid and liquid AgBr determined by multiple-edge x-ray absorption spectroscopy

X-ray absorption measurements of solid and liquid AgBr in the $T=30\char21{}927K$ range of temperature have been performed using synchrotron radiation. Accurate short-range structural parameters are determined using simultaneous Ag and Br K-edge EXAFS refinement in the framework of the GNXAS method for data analysis. Results are discussed in light of the peculiar structural and ionic conduction properties of AgBr and taking into account previous x-ray, neutron diffraction (ND), molecular-dynamics (MD), and EXAFS results. Detailed information about the asymmetry of the first-neighbor $g(r)$ distribution is given, showing that anharmonic effects are important even at moderate temperatures. The foot and the most probable value of the first neighbor $g(r)$ are found to shift up to about $0.25\AA{}$ toward shorter distances from 30 K to 670 K, while the long-range part of the distribution broadens at high temperatures. The average bondlength is found to be in agreement with known thermal expansion diffraction data correcting previous EXAFS results. Accurate EXAFS measurements of liquid AgBr as a function of temperature are presented and compared with existing ND and MD structural models. The reconstructed EXAFS signals related to previous structural models are shown to differ considerably with present experimental data, due to the extreme EXAFS sensitivity to short-range correlations. The first-neighbor peak of the Ag-Br partial distribution function is accurately determined in this work. The short-distance side of the distribution, probing the repulsive part of the interaction, shows a steeper onset located at about $2.4\AA{},$ clearly shifted toward shorter distances with respect to previous broader MD simulations. The reconstructed $g(r)$ broadens gradually at higher temperatures (up to 927 K). Existence of short-range Ag-Ag correlations resulting in a well-defined Ag-Ag short-distance peak in solid and liquid AgBr as suggested by recent ND reverse Monte Carlo data analysis is not confirmed.
Deletion of first noncoding exon in ANKRD11 leads to KBG syndrome

Phenotypic features of KBG syndrome include craniofacial anomalies, short stature, cognitive disability and behavioral findings. The syndrome is caused by heterozygous pathogenic single nucleotide variants and indels in ANKRD11, or a heterozygous deletion of 16q24.3 that includes ANKRD11. We performed genome sequencing on a patient with clinical manifestations of KBG syndrome including distinct craniofacial features as well as a history of mild intellectual disability and attention‐deficit hyperactivity disorder. This led to the identification of a 43 kb intragenic deletion of ANKRD11 affecting the first noncoding exon while leaving the coding regions intact. Review of the literature shows that this is the smallest 5′ deletion affecting only the noncoding exons of ANKRD11. Real‐time polymerase chain reaction demonstrated that the copy number variant was not present in either of the proband's parents, suggesting it occurred de novo. RNA expression analysis demonstrated significantly decreased transcript abundance compared to controls. This provides new evidence for haploinsufficiency as a mechanism of disease in KBG syndrome.
What is the impact of forced displacement on health? A scoping review

Abstract While there is a broad literature analysing the effects of migration on health, important knowledge gaps persist particularly on the causal effects of forced displacement on health outcomes. We undertake a scoping review of applied epidemiological, statistical and econometric studies examining causal health impacts of forced displacement, which initially identified 1454 studies from the health and social sciences disciplines published up to May 2021. Our study makes two key contributions. First, we offer a comprehensive overview of the evidence generated, methodologies adopted and analytical challenges faced by current research examining the causal relationship between forced displacement and health. Second, we present concrete examples of how key challenges around study design and estimation approaches influence the strength of the evidence-base on the topic, using as a case study the broad domain of reproductive health. We find that, beyond the increased mortality risk that can be attributed to forced displacement, most of the available empirical evidence for a wide range of health outcomes is prone to substantial bias, making it difficult to draw firm conclusions. Our synthesis of credible studies conducted in different settings indicates that current research practice in the field could be strengthened through selection of valid control groups and application of more appropriate causal inference methods. Our findings are useful to promote the generation of further evidence on the topic that can reliably inform the design of policies to protect the health of displaced populations.
Numerical Simulations of Nonlinear Interaction of Space Charge Waves in Microwave and Millimeter Wave Range in n-InN Films Using Negative Differential Conductivity

Numerical simulations of nonlinear interaction of space charge waves in microwave and millimeter wave range in n-InN films have been carried out. A micro- and millimeter-waves frequency conversion using the negative differential conductivity phenomenon is carried out when the harmonics of the input signal are generated. An increment in the amplification is observed in n-InN films at essentially at high-frequencies f < 450 GHz, when compared with n-GaAs films f < 44 GHz. This work provides a way to achieve a frequency conversion and amplification of micro- and millimeter-waves.
Cytochrome P450s genes CYP321A9 and CYP9A58 contribute to host plant adaptation in the fall armyworm Spodoptera frugiperda.

BACKGROUND The fall armyworm, Spodoptera frugiperda is one of the most destructive agricultural pests, which can complete their entire life cycle on various plants. At present, some detoxification genes have been proved to be involved in the adaptability to plants in insects. However, the genetics behind insect pest responses to host switches, and their ability to adapt to new host plants, remain poorly understood. This study was conducted to evaluate the adaptation of S. frugiperda to host plant and determine the roles of CYP321A9 and CYP9A58 in the detoxification metabolism of the fall armyworm. RESULTS The results revealed that feeding on maize was more suitable for S. frugiperda to develop compared with rice. In addition, knocking down of SfCYP321A9 and SfCYP9A58 resulted in a prolonged developmental time of S. frugiperda larvae that fed on rice. Meanwhile, RNAi knockdown of SfCYP321A9 resulted in significantly higher mortality of S. frugiperda larvae when exposed to the rice allelochemicals, ferulic acid, gramine and tricin. Furthermore, overexpression of SfCYP321A9 significantly reduced mortality in Drosophila melanogaster when exposed to gramine and tricin. CONCLUSION Our results suggest that CYP321A9 and CYP9A58 genes play a key role in host plant adaptation in S. frugiperda, which contribute to a greater understanding of the molecular basis of host plant adaptation and provide the means to develop effective management tools for S. frugiperda resistance.
MAGNET: A web-based application for gene set enrichment analysis using macrophage data sets

Characterization of gene lists obtained from high-throughput genomic experiments is an essential task to uncover the underlying biological insights. A common strategy is to perform enrichment analyses that utilize standardized biological annotations, such as GO and KEGG pathways, which attempt to encompass all domains of biology. However, this approach provides generalized, static results that may fail to capture subtleties associated with research questions within a specific domain. Thus, there is a need for an application that can provide precise, relevant results by leveraging the latest research. We have therefore developed an interactive web application, Macrophage Annotation of Gene Network Enrichment Tool (MAGNET), for performing enrichment analyses on gene sets that are specifically relevant to macrophages. Using the hypergeometric distribution, MAGNET assesses the significance of overlapping genes with annotations that were curated from published manuscripts and data repositories. We implemented numerous features that enhance utility and user-friendliness, such as the simultaneous testing of multiple gene sets, different visualization options, option to upload custom datasets, and downloadable outputs. Here, we use three example studies compared against our current database of ten publications on mouse macrophages to demonstrate that MAGNET provides relevant and unique results that complement conventional enrichment analysis tools. Although specific to macrophage datasets, we envision MAGNET will catalyze developments of similar applications in other domains of interest. MAGNET can be freely accessed at the URL https://magnet-winterlab.herokuapp. com. Website implemented in Python and PostgreSQL, with all major browsers supported. The source code is available at https://github.com/sychen9584/MAGNET.
Experimental Evaluation of a Perspective Tunnel Display for Three-Dimensional Helicopter Approaches

A computer-gener ated perspective tunnel display for a steep and strongly curved three-dimensional helicopter approach is studied. The necessary control variables for following a curved trajectory are analyzed, the effectiveness of superimposed predictor symbology is investigated, and a suitable predictor law is formulated. The theoretical considerations are validated by an extensive fixed-base simulator program. The tunnel display with a superimposed predictor symbol is shown to outperform conventional-type displays in its abilities to follow a curved trajectory in the presence of gust disturbances, to enter the trajectory from an unknown position outside this trajectory, as well as to monitor automatic approaches. The feasibility of the tunnel display for operation in actual flight has been demonstrated in an exploratory flight test.
The efficacy and safety of ceftolozane-tazobactam in the treatment of GNB infections: a systematic review and meta-analysis of clinical studies

ABSTRACT Background Ceftolozane-tazobactam is a novel cephalosporin/β-lactamase inhibitor combination with activity against Gram-negative bacteria (GNB). We aimed to comprehensively evaluate the clinical efficacy and safety of ceftolozane-tazobactam in treating GNB infections in adult patients. Research design and methods PubMed, Embase, and Cochrane databases were retrieved until August 2022. Randomized trials and non-randomized controlled studies evaluating ceftolozane-tazobactam and its comparators in adult patients with GNB infections were included. Results A total of 13 studies were included. Overall, patients receiving ceftolozane-tazobactam had significant advantages in clinical cure (odds ratio [OR], 1.62; 95% CI, 1.05–2.51) and microbiological eradication (OR, 1.43; 95% CI, 1.19–1.71), especially in Pseudomonas aeruginosa-infected patients. Ceftolozane-tazobactam had a significant advantage in clinical success or microbial eradication compared with polymyxin/aminoglycosides (PL/AG) or levofloxacin. There were no significant differences in adverse events (AEs), Clostridium difficile infection (CDI), and mortality between ceftolozane-tazobactam and comparators. Notably, ceftolozane-tazobactam showed a significantly lower risk of acute kidney injury compared with PL/AG. Conclusions Ceftolozane-tazobactam showed excellent clinical and microbiological efficacy in treating GNB, especially P. aeruginosa-induced infections. The overall safety profile of ceftolozane-tazobactam was comparable to other antimicrobials, with no increased risk of CDI and obvious advantage over antibacterial agents with high nephrotoxicity.
User's image perception improved strategy and application of augmented reality systems in smart medical care: A review

Augmented reality (AR) is a new human‐computer interaction technology that combines virtual reality, computer vision, and computer networks. With the rapid advancement of the medical field towards intelligence and data visualisation, AR systems are becoming increasingly popular in the medical field because they can provide doctors with clear enough medical images and accurate image navigation in practical applications. However, it has been discovered that different display types of AR systems have different effects on doctors' perception of the image after virtual‐real fusion during the actual medical application. If doctors cannot correctly perceive the image, they may be unable to correctly match the virtual information with the real world, which will have a significant impact on their ability to recognise complex structures.
Exposure to Pro and Anti-Cannabis Social Media Messages and Teens’ and College Students’ Intentions to Use Cannabis

ABSTRACT Content analyses have documented that posts about cannabis are increasingly common on social media. The relationship between the cannabis-related content to which teens and college students are exposed on social media and how such content may be associated with intentions to use and use of cannabis is less known, however. We conducted an online survey with teens (N = 350) who lived in Washington state using online survey panel participants in June 2018 and with college students (N = 966) in a Washington state-wide university system in February and March 2019. Participants in both samples reported seeing both pro-cannabis and anti-cannabis messages on social media platforms. Exposure to pro-cannabis messages on social media was associated with an increased intention to use cannabis. Exposure to anti-cannabis messages on social media was indirectly associated with decreased intentions to use cannabis through negative outcome beliefs of cannabis use and, among college students, through perceived norms. Among college students specifically, exposure to pro-cannabis messages on social media was also associated with more frequent cannabis use. Health communicators could focus anti-cannabis messaging on negative outcome beliefs among teens and college students as well as norms among college students to potentially influence constructs associated with intentions and use.