Miracle-dz/UniFAR-FTUs huggingface dataset:
Role of Tissue Factor in the Pathogenesis of COVID-19 and the Possible Ways to Inhibit It

COVID-19 (Coronavirus Disease 2019) is a highly contagious infection and associated with high mortality rates, primarily in elderly; patients with heart failure; high blood pressure; diabetes mellitus; and those who are smokers. These conditions are associated to increase in the level of the pulmonary epithelium expression of angiotensin-converting enzyme 2 (ACE-2), which is a recognized receptor of the S protein of the causative agent SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2). Severe cases are manifested by parenchymal lung involvement with a significant inflammatory response and the development of microvascular thrombosis. Several factors have been involved in developing this prothrombotic state, including the inflammatory reaction itself with the participation of proinflammatory cytokines, endothelial dysfunction/endotheliitis, the presence of antiphospholipid antibodies, and possibly the tissue factor (TF) overexpression. ARS-Cov-19 ACE-2 down-regulation has been associated with an increase in angiotensin 2 (AT2). The action of proinflammatory cytokines, the increase in AT2 and the presence of antiphospholipid antibodies are known factors for TF activation and overexpression. It is very likely that the overexpression of TF in COVID-19 may be related to the pathogenesis of the disease, hence the importance of knowing the aspects related to this protein and the therapeutic strategies that can be derived. Different therapeutic strategies are being built to curb the expression of TF as a therapeutic target for various prothrombotic events; therefore, analyzing this treatment strategy for COVID-19-associated coagulopathy is rational. Medications such as celecoxib, cyclosporine or colchicine can impact on COVID-19, in addition to its anti-inflammatory effect, through inhibition of TF.
[Domestic and international research progress of edible and medicinal Arecae Semen].

Arecae Semen, as the first place among "Four South Medicines" in China, has great dual-use value of medicine and food. The research of Arecae Semen was mainly focused on the active ingredients and efficacy value, and its potential safety hazards were also concerned. Until now, there is still a lack of clear boundaries between medicine and food, resulting in its safety cannot be guaranteed. Therefore, it is of great significance to establish clear boundaries of medicine and food use and health risk assessment. In this paper, the differences of pretreatment and application methods of Arecae Semen were analyzed, and the research progress of Arecae Semen in chemical composition identification and toxicology research and safety evaluation were reviewed emphatically. Finally, the differences of quality control and safety evaluation of Arecae Semen in pharmacopoeias or standards were analyzed at home and abroad. It was expected to provide reference value for quality control, safety evaluation and international standardization research of Arecae Semen.
Targeted inhibition of allergen‐induced histamine production by neutrophils

Histamine is a critical inflammatory mediator in allergic diseases. We showed in a previous work that neutrophils from allergic patients produce histamine in response to allergens to which the patients were sensitized. Here, we investigate the molecular mechanisms involved in this process using peripheral blood neutrophils. We challenged these cells in vitro with allergens and analyzed histamine release in the culture supernatants. We also explored the effect of common therapeutic drugs that ameliorate allergic symptoms, as well as allergen‐specific immunotherapy. Additionally, we examined the expression of histidine decarboxylase and diamine oxidase, critical enzymes in the metabolism of histamine, under allergen challenge. We show that allergen‐induced histamine release is dependent on the activation of the phosphoinositide 3‐kinase, mitogen‐activated protein kinase p38, and extracellular signal‐regulated kinase 1/2 signaling pathways. We also found a contribution of the phosphatase calcineurin to lesser extent. Anti‐histamines, glucocorticoids, anti‐M3‐muscarinic receptor antagonists, and mainly β2‐receptor agonists abolished the allergen‐dependent histamine release. Interestingly, allergen‐specific immunotherapy canceled the histamine release through the downregulation of histidine decarboxylase expression. Our observations describe novel molecular mechanisms involved in the allergen‐dependent histamine release by human neutrophils and provide new targets to inhibit histamine production.
Pursuing germline genome sequencing to reduce illness uncertainty may involve additional uncertainties for cancer patients: A mixed‐methods study

Cancer‐related illness uncertainty has been associated with poorer psychological outcomes for patients. While some cancer patients believe obtaining genomic information will reduce their illness uncertainty, the complexity of genomics has the potential to compound illness uncertainty. The aim of this mixed‐methods study was to investigate uncertainty in patients with a cancer of likely heritable origin immediately following their decision to have germline genome sequencing. Participant (N = 348) negative attitudes toward uncertainty were associated with higher satisfaction with decision to have germline genome sequencing and greater fear of cancer recurrence. Thematic analysis of semi‐structured interviews with a subset of participant (N = 20) revealed the following four themes: (a) germline genome sequencing to reduce illness uncertainty; (b) germline genome sequencing to reduce uncertainty related to relatives’ risk; (c) uncertainty generated by germline genome sequencing; and (d) resilience and coping with uncertainty. This study demonstrated the complexity of uncertainty in germline genome sequencing in cancer patients. These results provide genomic healthcare professionals with important information about cancer patient's motivation to pursue germline genome sequencing, the specific uncertainties generated by germline genome sequencing, and how cancer patients cope with uncertainty.
Aggressive organ penetration and high vector transmissibility of epidemic dengue virus-2 Cosmopolitan genotype in a transmission mouse model

Dengue virus (DENV) causes dengue fever and severe hemorrhagic fever in humans and is primarily transmitted by Aedes aegypti and A. albopictus mosquitoes. The incidence of DENV infection has been gradually increasing in recent years due to global urbanization and international travel. Understanding the virulence determinants in host and vector transmissibility of emerging epidemic DENV will be critical to combat potential outbreaks. The DENV serotype 2 (DENV-2), which caused a widespread outbreak in Taiwan in 2015 (TW2015), is of the Cosmopolitan genotype and is phylogenetically related to the virus strain linked to another large outbreak in Indonesia in 2015. We found that the TW2015 virus was highly virulent in type I and type II interferon-deficient mice, with robust replication in spleen, lung, and intestine. The TW2015 virus also had high transmissibility to Aedes mosquitoes and could be effectively spread in a continuous mosquitoes-mouse-mosquitoes-mouse transmission cycle. By making 16681-based mutants carrying different segments of the TW2015 virus, we identified the structural pre-membrane (prM) and envelope (E) genes as key virulence determinants in the host, with involvement in the high transmissibility of the TW2015 virus in mosquitoes. The transmission mouse model will make a useful platform for evaluation of DENV with high epidemic potential and development of new strategies against dengue outbreaks.
Causal Associations of Anthropometric Measurements With Fracture Risk and Bone Mineral Density: A Mendelian Randomization Study

Uncovering additional causal clinical traits and exposure variables is important when studying osteoporosis mechanisms and for the prevention of osteoporosis. Until recently, the causal relationship between anthropometric measurements and osteoporosis had not been fully revealed. In the present study, we utilized several state‐of‐the‐art Mendelian randomization (MR) methods to investigate whether height, body mass index (BMI), waist‐to‐hip ratio (WHR), hip circumference (HC), and waist circumference (WC) are causally associated with two major characteristics of osteoporosis, bone mineral density (BMD) and fractures. Genomewide significant (p ≤ 5 × 10−8) single‐nucleotide polymorphisms (SNPs) associated with the five anthropometric variables were obtained from previous large‐scale genomewide association studies (GWAS) and were utilized as instrumental variables. Summary‐level data of estimated bone mineral density (eBMD) and fractures were obtained from a large‐scale UK Biobank GWAS. Of the MR methods utilized, the inverse‐variance weighted method was the primary method used for analysis, and the weighted‐median, MR‐Egger, mode‐based estimate, and MR pleiotropy residual sum and outlier methods were utilized for sensitivity analyses. The results of the present study indicated that each increase in height equal to a single standard deviation (SD) was associated with a 9.9% increase in risk of fracture (odds ratio [OR] = 1.099; 95% confidence interval [CI] 1.067–1.133; p = 8.793 × 10−10) and a 0.080 SD decrease of estimated bone mineral density (95% CI −0.106–(−0.054); p = 2.322 × 10−9). We also found that BMI was causally associated with eBMD (beta = 0.129, 95% CI 0.065–0.194; p = 8.113 × 10−5) but not associated with fracture. The WHR adjusted for BMI, HC adjusted for BMI, and WC adjusted for BMI were not found to be related to fracture occurrence or eBMD. In conclusion, the present study provided genetic evidence for certain causal relationships between anthropometric measurements and bone mineral density or fracture risk. © 2021 American Society for Bone and Mineral Research (ASBMR).
The Effect of an Entertainment-Education Intervention on Reproductive Health of Young Women of Color

ABSTRACT While teen pregnancy rates in the United States have been declining for decades, they remain the highest of all western countries. Within the U.S., Black and Latina teens experience disproportionate rates of unplanned pregnancy. Plan A is an entertainment-education video intervention that was developed to help address these disparities, in part by emphasizing the ability of young cisgender women to control when they become pregnant by using an effective contraception method. The intervention was developed in close collaboration with the target audience (Black and Latina women aged 18–19) to ensure that it was relevant, engaging, and motivational. We conducted an online study to: (a) investigate the effects of Plan A on attitudes toward the contraception methods covered in the video; (b) whether these effects varied by race/ethnicity or age, and; (c) if identification with characters in the video mediated these effects. The study used a posttest-only design where participants were randomly assigned to watch Plan A or to a neutral control condition. The sample included Black, Latina, and non-Latina White women aged 16 to 19 (N= 242), with younger and White women included for comparison purposes. Results indicated that exposure to Plan A significantly improved attitudes toward long-acting reversible contraceptives (LARCs) among all age groups and among young Black and Latina women, but not White women. These findings may be explained by participant’s identification with the Black and Latina lead characters – both of whom model positive reproductive health behaviors.
Mercury in the environment: a toxicological and epidemiological appraisal

This book is a review of the toxicity of mercury, and has focused on information considered important for understanding the toxic action of mercury, and on quantitative information on dose-response relationships. The emphasis is on chronic exposure, though acute exposure is also treated. Inhalation and ingestion are both examined as significant exposure pathways. 802 references.
Current perspectives on neuroimaging techniques used to identify stroke mimics in clinical practice

ABSTRACT Introduction Urgent clinical assessment and brain imaging are essential for differentiating stroke mimics from stroke and to avoid unnecessary initiation of reperfusion and other therapies in stroke mimic patients. Areas covered In this article, the authors will review acute stroke imaging and then the imaging patterns of the most common stroke mimics. The authors have focused our review on brain CT scan, and more specifically CT perfusion, as this is the most commonly available and emerging tool in emergency settings. The authors also provide information on acute brain MRI and MR perfusion. Expert opinion Imaging can contribute to the detection and diagnosis of acute stroke mimics. Knowledge of imaging findings in different stroke mimics can help distinguish these from patients with stroke who require timely reperfusion therapy. CT and MRI perfusion and diffusion-weighted imaging (DWI) MRI are useful imaging modalities for the assessment of acute stroke patients as they provide more accurate information than plain CT scan. Some of these modalities should be available in the emergency setting. The authors recommended CT perfusion as a useful tool for stroke management and differentiation with stroke mimics.
HMGB1: An overview of its roles in the pathogenesis of liver disease

High‐mobility group box 1 (HMGB1) is an abundant architectural chromosomal protein that has multiple biologic functions: gene transcription, DNA replication, DNA‐damage repair, and cell signaling for inflammation. HMGB1 can be released passively by necrotic cells or secreted actively by activated immune cells into the extracellular milieu after injury. Extracellular HMGB1 acts as a damage‐associated molecular pattern to initiate the innate inflammatory response to infection and injury by communicating with neighboring cells through binding to specific cell‐surface receptors, including Toll‐like receptors (TLRs) and the receptor for advanced glycation end products (RAGE). Numerous studies have suggested HMGB1 to act as a key protein mediating the pathogenesis of chronic and acute liver diseases, including nonalcoholic fatty liver disease, hepatocellular carcinoma, and hepatic ischemia/reperfusion injury. Here, we provide a detailed review that focuses on the role of HMGB1 and HMGB1‐mediated inflammatory signaling pathways in the pathogenesis of liver diseases.
Chronic Inhibition of Toll‐Like Receptor 9 Ameliorates Pulmonary Hypertension in Rats

Background Recent accumulating evidence suggests that toll‐like receptor 9 (TLR9) is involved in the pathogenesis of cardiovascular diseases. However, its role in pulmonary hypertension remains uncertain. We hypothesized that TLR9 is involved in the development of pulmonary hypertension. Methods and Results A rat model of monocrotaline‐induced pulmonary hypertension was used to investigate the effects of TLR9 on hemodynamic parameters, vascular remodeling, and survival. Monocrotaline‐exposed rats significantly showed increases in plasma levels of mitochondrial DNA markers, which are recognized by TLR9, TLR9 activation in the lung, and interleukin‐6 mRNA level in the lung on day 14 after monocrotaline injection. Meanwhile, monocrotaline‐exposed rats showed elevated right ventricular systolic pressure, total pulmonary vascular resistance index and vascular remodeling, together with macrophage accumulation on day 21. In the preventive protocol, administration (days −3 to 21 after monocrotaline injection) of selective (E6446) or nonselective TLR9 inhibitor (chloroquine) significantly ameliorated the elevations of right ventricular systolic pressure and total pulmonary vascular resistance index as well as vascular remodeling and macrophage accumulation on day 21. These inhibitors also significantly reduced NF‐κB activation and interleukin‐6 mRNA levels to a similar extent. In the short‐term reversal protocol, E646 treatment (days 14–17 after monocrotaline injection) almost normalized NF‐κB activation and interleukin‐6 mRNA level, and reduced macrophage accumulation. In the prolonged reversal protocol, E6446 treatment (days 14–24 after monocrotaline injection) reversed total pulmonary vascular resistance index and vascular remodeling, and improved survival in monocrotaline‐exposed rats. Conclusions TLR9 is involved in the development of pulmonary hypertension concomitant via activation of the NF‐κB‒IL‐6 pathway. Inhibition of TLR9 may be a novel therapeutic strategy for pulmonary hypertension.
Divergent diapause life history timing drives both allochronic speciation and reticulate hybridization in an adaptive radiation of Rhagoletis flies

Divergent adaptation to new ecological opportunities can be an important factor initiating speciation. However, as niches are filled during adaptive radiations, trait divergence driving reproductive isolation between sister taxa may also result in trait convergence with more distantly related taxa, increasing the potential for reticulated gene flow across the radiation. Here, we demonstrate such a scenario in a recent adaptive radiation of Rhagoletis fruit flies, specialized on different host plants. Throughout this radiation, shifts to novel hosts are associated with changes in diapause life history timing, which act as “magic traits” generating allochronic reproductive isolation and facilitating speciation‐with‐gene‐flow. Evidence from laboratory rearing experiments measuring adult emergence timing and genome‐wide DNA‐sequencing surveys supported allochronic speciation between summer‐fruiting Vaccinium spp. ‐infesting Rhagoletis mendax and its hypothesized and undescribed sister taxon infesting autumn‐fruiting sparkleberries. The sparkleberry fly and R. mendax were shown to be genetically discrete sister taxa, exhibiting no detectable gene flow and allochronically isolated by a 2‐month average difference in emergence time corresponding to host availability. At sympatric sites across the southern USA, the later fruiting phenology of sparkleberries overlaps with that of flowering dogwood, the host of another more distantly related and undescribed Rhagoletis taxon. Laboratory emergence data confirmed broadly overlapping life history timing and genomic evidence supported on‐going gene flow between sparkleberry and flowering dogwood flies. Thus, divergent phenological adaptation can drive the initiation of reproductive isolation, while also enhancing genetic exchange across broader adaptive radiations, potentially serving as a source of novel genotypic variation and accentuating further diversification.
Morphology of yolk and pericardial sacs in lecithotrophic and matrotrophic nutrition in poeciliid fishes

We used histological techniques to describe the morphology of the yolk and pericardial sacs in developing embryos of the lecithotrophic species Girardinus creolus, Gambusia puncticulata, Limia vittata, and Quintana atrizona, in comparison with the extreme matrotrophic Heterandria formosa. In lecithotrophic species, the yolk sac was enlarged and lasted until the final stages of development, while in H. formosa it was completely absorbed soon after fertilization. Lecithotrophic poeciliids showed a pericardial sac with a single layer of blood vessels covering the dorsal surface of the cephalic region only, while H. formosa showed a more complex largely vascularized pericardial sac covering the entire dorsal surface, except the caudal region. In advanced gestation of G. creolus, a vascular plexus of the yolk sac reaches the pharyngeal region, behind the gills, suggesting that the pharynx may play a role in embryonic nutrition in lecithotrophic species. These morphological evidences suggest that matrotrophy derives from lecithotrophy.
NELF‐A controls Drosophila healthspan by regulating heat‐shock protein‐mediated cellular protection and heterochromatin maintenance

NELF‐mediated pausing of RNA polymerase II (RNAPII) constitutes a crucial step in transcription regulation. However, it remains unclear how control release of RNAPII pausing can affect the epigenome and regulate important aspects of animal physiology like aging. We found that NELF‐A dosage regulates Drosophila healthspan: Halving NELF‐A level in the heterozygous mutants or via neuronal‐specific RNAi depletion improves their locomotor activity, stress resistance, and lifespan significantly. Conversely, NELF‐A overexpression shortens fly lifespan drastically. Mechanistically, lowering NELF‐A level facilitates the release of paused RNAPII for productive transcription of the heat‐shock protein (Hsp) genes. The elevated HSPs expression in turn attenuates the accumulation of insoluble protein aggregates, reactive oxidative species, DNA damage and systemic inflammation in the brains of aging NELF‐A depleted flies as compared to their control siblings. This pro‐longevity effect is unique to NELF‐A due to its higher expression level and more efficient pausing of RNAPII than other NELF subunits. Importantly, enhanced resistance to oxidative stress in NELF‐A heterozygous mutants is highly conserved such that knocking down its level in human SH‐SY5Y cells attenuates hydrogen peroxide‐induced DNA damage and apoptosis. Depleting NELF‐A reconfigures the epigenome through the maintenance of H3K9me2‐enriched heterochromatin during aging, leading to the repression of specific retrotransposons like Gypsy‐1 in the brains of NELF‐A mutants. Taken together, we showed that the dosage of neuronal NELF‐A affects multiple aspects of aging in Drosophila by regulating transcription of Hsp genes in the brains, suggesting that targeting transcription elongation might be a viable therapeutic strategy against age‐onset diseases like neurodegeneration.
MicroRNA‐targeting in spermatogenesis: Over‐expressions of microRNA‐23a/b‐3p and its affected targeting of the genes ODF2 and UBQLN3 in spermatozoa of patients with oligoasthenozoospermia

Male infertility is a multifactorial syndrome with diverse phenotypic representations. MicroRNAs (miRNAs) are small, non‐coding RNAs that are involved in the post‐transcriptional regulation of gene expression. Altered abundance levels of ODF2 and UBQLN3 have been reported in patients with different spermatogenic impairments. However, the transcriptional regulation of these two genes by miR‐23a/b‐3p is still unclear.
Diagnostic and prognostic capabilities of a biomarker and EMR‐based machine learning algorithm for sepsis

Sepsis is a major cause of mortality among hospitalized patients worldwide. Shorter time to administration of broad‐spectrum antibiotics is associated with improved outcomes, but early recognition of sepsis remains a major challenge. In a two‐center cohort study with prospective sample collection from 1400 adult patients in emergency departments suspected of sepsis, we sought to determine the diagnostic and prognostic capabilities of a machine‐learning algorithm based on clinical data and a set of uncommonly measured biomarkers. Specifically, we demonstrate that a machine‐learning model developed using this dataset outputs a score with not only diagnostic capability but also prognostic power with respect to hospital length of stay (LOS), 30‐day mortality, and 3‐day inpatient re‐admission both in our entire testing cohort and various subpopulations. The area under the receiver operating curve (AUROC) for diagnosis of sepsis was 0.83. Predicted risk scores for patients with septic shock were higher compared with patients with sepsis but without shock (p < 0.0001). Scores for patients with infection and organ dysfunction were higher compared with those without either condition (p < 0.0001). Stratification based on predicted scores of the patients into low, medium, and high‐risk groups showed significant differences in LOS (p < 0.0001), 30‐day mortality (p < 0.0001), and 30‐day inpatient readmission (p < 0.0001). In conclusion, a machine‐learning algorithm based on electronic medical record (EMR) data and three nonroutinely measured biomarkers demonstrated good diagnostic and prognostic capability at the time of initial blood culture.