Miracle-dz/UniFAR-FTUs huggingface dataset:
Interception Targets of Angelica Gigas Nakai Root Extract versus Pyranocoumarins in Prostate Early Lesions and Neuroendocrine Carcinomas in TRAMP Mice

This study explores potential molecular targets associated with invivo activity of AGN root alcoholic extract and its major pyranocoumarins to intercept precancerous epithelial lesions and early malignancies of the prostate. Without an ethically-acceptable, clearly defined cancer initiation risk reduction strategy available for the prostate, using natural products like AGN to delay formation of malignant tumors could be a plausible approach for prostate cancer prevention. We reported efficacy of Angelica gigas Nakai (AGN) root ethanol extract and equimolar decursin (D)/decursinol angelate (DA) through daily gavage starting at 8 weeks of age (WOA) to male transgenic adenocarcinoma of mouse prostate (TRAMP) mice such that these modalities suppressed precancerous epithelial lesions in their dorsolateral prostate (DLP) to similar extent, but AGN extract was better than the D/DA mixture at promoting the survival of mice bearing prostate neuroendocrine carcinomas to 28 WOA. Here, we compared by microarray hybridization the mRNA levels in pooled DLP tissues and individual neuroendocrine carcinomas to characterize potential molecular targets of AGN extract and D/DA. Clustering and principal component analyses supported distinct gene expression profiles of TRAMP DLP versus neuroendocrine carcinomas. Pathway Enrichment, Gene Ontology, and Ingenuity Pathway Analyses of differential genes indicated that AGN and D/DA affected chiefly processes of lipid and mitochondrial energy metabolism and oxidation-reduction in TRAMP DLP, while AGN affected neuronal signaling, immune systems and cell cycling in neuroendocrine carcinomas. Protein–Protein Interaction Network analysis predicted and reverse transcription-PCR verified multiple hub genes common in the DLP of AGN- and D/DA-treated TRAMP mice at 28 WOA and select hub genes attributable to the non-D/DA AGN components. The vast majority of hub genes in the AGN-treated neuroendocrine carcinomas differed from those in TRAMP DLP. In summary, the transcriptomic approach illuminated vastly different signaling pathways and networks, cellular processes, and hub genes of two TRAMP prostate malignancy lineages and their associations with the interception efficacy of AGN and D/DA. Prevention Relevance: This study explores potential molecular targets associated with in vivo activity of AGN root alcoholic extract and its major pyranocoumarins to intercept precancerous epithelial lesions and early malignancies of the prostate. Without an ethically-acceptable, clearly defined cancer initiation risk reduction strategy available for the prostate, using natural products like AGN to delay formation of malignant tumors could be a plausible approach for prostate cancer prevention.
CDNet: Complementary Depth Network for RGB-D Salient Object Detection

Current RGB-D salient object detection (SOD) methods utilize the depth stream as complementary information to the RGB stream. However, the depth maps are usually of low-quality in existing RGB-D SOD datasets. Most RGB-D SOD networks trained with these datasets would produce error-prone results. In this paper, we propose a novel Complementary Depth Network (CDNet) to well exploit saliency-informative depth features for RGB-D SOD. To alleviate the influence of low-quality depth maps to RGB-D SOD, we propose to select saliency-informative depth maps as the training targets and leverage RGB features to estimate meaningful depth maps. Besides, to learn robust depth features for accurate prediction, we propose a new dynamic scheme to fuse the depth features extracted from the original and estimated depth maps with adaptive weights. What’s more, we design a two-stage cross-modal feature fusion scheme to well integrate the depth features with the RGB ones, further improving the performance of our CDNet on RGB-D SOD. Experiments on seven benchmark datasets demonstrate that our CDNet outperforms state-of-the-art RGB-D SOD methods. The code is publicly available at https://github.com/blanclist/CDNet.
Structural barriers to implementing recommended tuberculosis preventive treatment in primary care clinics in rural South Africa

ABSTRACT The World Health Organization (WHO) recommends tuberculosis preventive treatment (TPT) in people with HIV (PWH), yet implementation remains poor, especially in rural communities. We examined factors influencing TPT initiation in PWH on antiretroviral therapy (ART) in rural South Africa using the Promoting Action on Research Implementation in Health Services (PARiHS) framework to identify contextual factors and facilitation strategies to successfully implement TPT. Patient and clinical factors were extracted from medical records at two primary healthcare clinics (PHCs). Among 455 TPT eligible indivdiuals, only 263 (57.8%) initiated TPT. Patient-level characteristics (older age and symptoms of fever or weight loss) were significantly associated with TPT initiation in bivariate analysis, but PHC was the only independent correlate of TPT initiation (aOR: 2.24; 95% CI: 1.49–3.38). Clinic-level factors are crucial targets for implementing TPT to reduce the burden of HIV-associated TB. Gaps in knowledge of HCW, staff shortages, and non-integrated HIV/TB services were identified barriers to TPT implementation. Evidence-based strategies for facilitating TPT implementation that might be under-prioritized include ongoing reprioritization, expanding training for primary care providers, and quality improvement strategies (organisational changes, multidisciplinary teams, and monitoring and feedback). Addressing contextual barriers through these facilitation strategies may improve future TPT implementation in this setting.
Cross‐reactivity of the IDEXX Legiolert method with other Gram‐negative bacteria and waterborne pathogens leads to false‐positive assay results

Legionella species are the causative agent of Legionnaires’ disease, a potentially fatal bacterial pneumonia. New regulations and standards have prioritized the development of water safety plans to minimize the growth and spread of Legionella species in buildings. To determine the presence and type of Legionella in a water system, microbiological culturing is the gold standard method. However, recently new methodologies have been developed that claim to be sensitive and specific for Legionella at the genus or L. pneumophila at the species level. Published and anecdotal reports suggest that one of these newer culture‐based, enzyme‐substrate methods, the IDEXX Legiolert test, may exhibit false positivity with other microbes common to water sources. We experimentally evaluated the IDEXX Legiolert method using these other waterborne bacteria including Elizabethkingia meningoseptica, Pseudomonas aeruginosa, Proteus mirabilis and Serratia marcescens at real‐world environmental concentrations. We saw false‐positive results for the Legiolert test with several of these organisms, at sample concentrations as low as 60 CFU per ml. False‐positive Legionella results can trigger costly remediation and water‐use restrictions, that may be implemented while waiting for additional, confirmatory microbiological testing that could, in this case, yield no L. pneumophila.
Human Safety, Tolerability, and Pharmacokinetics of Molnupiravir, a Novel Broad-Spectrum Oral Antiviral Agent with Activity against SARS-CoV-2

Molnupiravir (EIDD-2801/MK-4482), the prodrug of the active antiviral ribonucleoside analog β-d-N4-hydroxycytidine (NHC; EIDD-1931), has activity against a number of RNA viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and seasonal and pandemic influenza viruses. Single and multiple doses of molnupiravir were evaluated in this first-in-human, phase 1, randomized, double-blind, placebo-controlled study in healthy volunteers, which included evaluation of the effect of food on pharmacokinetics. ABSTRACT Molnupiravir (EIDD-2801/MK-4482), the prodrug of the active antiviral ribonucleoside analog β-d-N4-hydroxycytidine (NHC; EIDD-1931), has activity against a number of RNA viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), severe acute respiratory syndrome coronavirus (SARS-CoV), Middle East respiratory syndrome coronavirus (MERS-CoV), and seasonal and pandemic influenza viruses. Single and multiple doses of molnupiravir were evaluated in this first-in-human, phase 1, randomized, double-blind, placebo-controlled study in healthy volunteers, which included evaluation of the effect of food on pharmacokinetics. EIDD-1931 appeared rapidly in plasma, with a median time of maximum observed concentration of 1.00 to 1.75 h, and declined with a geometric half-life of approximately 1 h, with a slower elimination phase apparent following multiple doses or higher single doses (7.1 h at the highest dose tested). Mean maximum observed concentration (Cmax) and area under the plasma concentration versus time curve (AUC) increased in a dose-proportional manner, and there was no accumulation following multiple doses. When administered in a fed state, there was a decrease in the rate of absorption, but no decrease in overall exposure. Molnupiravir was well tolerated. Fewer than half of the subjects reported an adverse event, the incidence of adverse events was higher following administration of placebo, and 93.3% of adverse events were mild. One subject discontinued early due to rash. There were no serious adverse events, and there were no clinically significant findings in clinical laboratory, vital signs, or electrocardiography. Plasma exposures exceeded expected efficacious doses based on scaling from animal models; therefore, dose escalations were discontinued before a maximum tolerated dose was reached. (This study has been registered in ClinicalTrials.gov under identifier NCT04392219.)
Knockdown of RLIM inhibits XIST expression and improves developmental competence of cloned male pig embryos

Ectopic expression of Xist on the putative active X chromosome is a primary cause of the low developmental efficiency of cloned mouse and pig embryos. Suppression of abnormal Xist expression via gene knockout or RNA interference (RNAi) can significantly enhance the developmental competence of cloned mouse and pig embryos. RLIM is a Xist expression activator, whereas REX1 is an Xist transcription inhibitor, as RLIM triggers Xist expression by mediating the proteasomal degradation of REX1 to induce imprinted and random X chromosome inactivation in mice. This study aimed to test whether the knockdown of RLIM and overexpression of REX1 can repress aberrant Xist expression and improve the developmental ability of cloned male pig embryos. Results showed that injection of anti‐RLIM small interfering RNA significantly decreased Xist messenger RNA abundance, increased REX1 protein level, and enhanced the preimplantation development of cloned male porcine embryos. These positive effects were not observed in cloned male pig embryos injected with REX1 expression plasmid, which might be due to the low expression efficiency of injected REX1 plasmid and/or the short half‐life of expressed REX1 protein. The findings from this study indicated that RLIM participated in the ectopic activation of Xist expression in cloned pig embryos by targeting REX1 degradation. Furthermore, this study provided a new method to improve cloned pig embryo development by the inhibition of Xist expression via RNAi of RLIM.
Psychiatric disorders in a population of deceased drug users

Abstract Purpose To estimate the prevalence of psychiatric morbidity and dual diagnosis in a population of decedents with positive drug toxicology and evaluate changes over time between 2001–2002 and 2011–2012. Materials and methods A total of 520 autopsied drug users with positive toxicology were included in the study from 2001 to 2002 and from 2011 to 2012. Materials included autopsy reports, toxicological screening during autopsy and data from the Danish national health registers, including psychiatric diagnoses from psychiatric hospitals and ambulatory functions, dispensed prescription use from pharmacies and registered treatment for drug use disorders. Results In 2001–2002, 63.3% of the decedents had only positive toxicology, 22.5% also had psychiatric morbidity, and 14.2% had a dual diagnosis. In 2011–2012, 56.4% had only positive toxicology, 26.1% also had psychiatric morbidity, and 17.5% had a dual diagnosis. None of the changes were significant. Decedents with only positive toxicology became older at time of death over time; decedents with psychiatric morbidity and a dual diagnosis did not. The prevalence of nonprescribed psychotropic medication, methadone and benzodiazepines increased. Conclusion Decedents with psychiatric morbidity and dual diagnosis did not increase their lifespan over a 10-year period. Decedents with only positive toxicology increasingly consumed nonprescribed psychotropic medication and may have suffered from undiagnosed psychiatric disorders. The prevalence of prescribed and nonprescribed benzodiazepines and methadone increased and may have contributed to premature mortality.
Coulomb-driven convection in electrohydrodynamics

The Coulomb-driven EHD instabilities, chaos, and turbulence generated by unipolar injection in insulating liquids are reviewed. Only systems of the greatest simplicity, well suited for a fundamental study, are considered. As the paper is intended to be introductory, the emphasis is on the physical mechanisms responsible for EHD phenomena. >
Introducing alcohol as a drug in medicine reviews with pharmacists: Findings from a co-design workshop with patients.

INTRODUCTION Alcohol poses a range of potential problems to people taking medications, but health professionals are usually not comfortable talking about drinking with patients. The Medicines and Alcohol Consultation aims to increase the capacity of pharmacists to conduct person-centred reviews in which alcohol is regarded as another drug to be discussed alongside medications. This paper explores sensitivities in discussing alcohol and views on the legitimacy of the Medicines and Alcohol Consultation intervention concept at a pharmacy-user intervention co-design workshop. METHODS A co-design workshop was held with 14 people recruited from UK community pharmacies who regularly drank alcohol and took medications for long-term conditions. This formed one element of a broader, iterative, intervention co-production process. Workshop discussions were audio-recorded and analysed thematically. RESULTS The basic intervention concept resonated well, though not entirely unproblematically. Participants were interested in receiving information on how medications interact with alcohol and how this might affect their own conditions, with which to make their own informed choices. Linking alcohol use to medicines gave legitimacy to pharmacists to raise alcohol in medicines reviews. Sensitivity in talking about alcohol was linked to vulnerability to negative judgement. DISCUSSION AND CONCLUSIONS Changing the framing of alcohol in medicines reviews, away from being regarded as a 'lifestyle issue' to being considered a drug directly linked to medicines use, safety and effectiveness, was welcomed by participants in this study.
Relationship between lymphocyte subsets values and C‐reactive protein in COVID‐19 patients

We enrolled 33 patients with COVID‐19 (23 men and 10 women; age 59 ± 15; males, n = 23; females, n = 10) admitted to the Department of Infectious Diseases of Grande Ospedale Metropolitano “Bianchi‐Melacrino‐Morelli” of Reggio Calabria, Italy, between March and May 2020. Whole blood samples were collected before the start of therapeutic treatment using all virus spread containment measures. Sample preparation protocols were designed in order to minimize operators direct specimen's manipulation. On univariate analysis, circulating levels of CRP were strongly and inversely related to CD3+ (rho = −0.77, p < 0.001), CD3+4+ (rho = −0.74, p < 0.001), and CD3+8+ (rho = −0.66, p = 0.001) implying that the shared variances between absolute values T cells and CRP ranged from 44 to 59%. Of note, the strength of these associations was higher in patients with relatively lower (below the median value) white blood cells (WBC) as compared to those with WBC above the median value. CRP also correlated with NK bright (rho = −0.56, p = 0.005) but failed to be related with CD19+ (rho = −0.38, p = 0.07), CD4+/CD8+ ratio (rho = 0.03, p = 0.89), CD16+ CD56+ (rho = −0.18, p = 0.43), and NKdim (rho = −0.15, p = 0.49). Lymphocyte subsets alteration monitoring in COVID‐19 positive patients may be a valid aid to control treatment efficacy of therapy and to choose better clinical approach. In particular, the negative correlation between CD3+, CD3+CD4+, CD3+CD8+ T cells values and CRP could be a useful tool to predict patient's response to therapy, particularly in patients with relatively lower WBC.
Titratable fixed‐ratio combination of basal insulin plus a glucagon‐like peptide‐1 receptor agonist: A novel, simplified alternative to premix insulin for type 2 diabetes

Despite novel therapeutic options, many people with type 2 diabetes (T2D) do not achieve their HbA1c targets. Given the progressive nature of T2D, many individuals not controlled with oral therapy will require advancement to injectable therapy using either a glucagon‐like peptide‐1 receptor agonist (GLP‐1 RA), recently recommended as a first option, or traditionally a basal insulin. However, premix insulins remain frequently used, either as initial injectable therapy or as intensification from basal insulin. Premix insulin injections can potentially provide significant glycaemic improvements to basal insulin but at the expense of increased hypoglycaemia and weight gain and the need for multiple daily doses, which may affect treatment adherence. Real‐world evidence suggests that glycaemic control often remains suboptimal with premix insulins. Fixed‐ratio combinations (FRCs) of basal insulin and GLP‐1 RAs provide a novel alternative to premix insulin for therapy intensification. While no direct comparisons between premix insulins and FRCs are available, results from meta‐analyses suggest that FRCs may offer better HbA1c reductions, a lower risk of hypoglycaemia and less weight gain compared with premix insulin in a simplified treatment regimen. A head‐to‐head trial of T2D treatment intensification with premix insulin and a FRC of basal insulin plus a GLP‐1 RA is currently in progress, which should help to clarify the outcomes for each treatment option. This review discusses the unmet needs of people with T2D treated with premix insulin and provides evidence supporting FRCs of basal insulin and GLP‐1 RAs as an alternative treatment option.
Genomically Complex Human Angiosarcoma and Canine Hemangiosarcoma Establish Convergent Angiogenic Transcriptional Programs Driven by Novel Gene Fusions

Sporadic angiosarcomas are aggressive vascular sarcomas whose rarity and genomic complexity present significant obstacles in deciphering the pathogenic significance of individual genetic alterations. Numerous fusion genes have been identified across multiple types of cancers, but their existence and significance remain unclear in sporadic angiosarcomas. In this study, we leveraged RNA-sequencing data from 13 human angiosarcomas and 76 spontaneous canine hemangiosarcomas to identify fusion genes associated with spontaneous vascular malignancies. Ten novel protein-coding fusion genes, including TEX2-PECAM1 and ATP8A2-FLT1, were identified in seven of the 13 human tumors, with two tumors showing mutations of TP53. HRAS and NRAS mutations were found in angiosarcomas without fusions or TP53 mutations. We found 15 novel protein-coding fusion genes including MYO16-PTK2, GABRA3-FLT1, and AKT3-XPNPEP1 in 11 of the 76 canine hemangiosarcomas; these fusion genes were seen exclusively in tumors of the angiogenic molecular subtype that contained recurrent mutations in TP53, PIK3CA, PIK3R1, and NRAS. In particular, fusion genes and mutations of TP53 cooccurred in tumors with higher frequency than expected by random chance, and they enriched gene signatures predicting activation of angiogenic pathways. Comparative transcriptomic analysis of human angiosarcomas and canine hemangiosarcomas identified shared molecular signatures associated with activation of PI3K/AKT/mTOR pathways. Our data suggest that genome instability induced by TP53 mutations might create a predisposition for fusion events that may contribute to tumor progression by promoting selection and/or enhancing fitness through activation of convergent angiogenic pathways in this vascular malignancy. Implications: This study shows that, while drive events of malignant vasoformative tumors of humans and dogs include diverse mutations and stochastic rearrangements that create novel fusion genes, convergent transcriptional programs govern the highly conserved morphologic organization and biological behavior of these tumors in both species.
The role of WOX1 genes in blade development and beyond

This article comments on: Wang C, Zhao B, He L, Zhou S, Liu Ye, Zhao W, Guo S, Wang R, Bai Q, Li Y, Wang D, Wu Q, Yang Y, Yan J, Liu Yu, Tadege M, Chen J. 2021. The WOX family transcriptional regulator SlLAM1 controls compound leaf and floral organ development in Solanum lycopersicum. Journal of Experimental Botany 72, 1822–1835.
Cardiac medication management in Duchenne muscular dystrophy

There have been significant improvements in the skeletal muscle and respiratory care for patients with Duchenne muscular dystrophy (DMD) over the last two decades. This has resulted in longer expected survival as many patients will live into their 20s and 30s. This timeline has resulted in a greater proportion of patients experiencing heart failure and cardiac‐related mortality. Herein, we describe the current indications for medical therapy for patients with DMD.