Miracle-dz/UniFAR-FTUs huggingface dataset:
Synthesis and Molecular Modelling Studies of New 1,3-Diaryl-5-Oxo-Proline Derivatives as Endothelin Receptor Ligands

The synthesis of seventeen new 1,3-diaryl-5-oxo-proline derivatives as endothelin receptor (ETR) ligands is described. The structural configuration of the new molecules was determined by analyzing selected signals in proton NMR spectra. In vitro binding assays of the human ETA and ETB receptors allowed us to identify compound 31h as a selective ETAR ligand. The molecular docking of the selected compounds and the ETA antagonist atrasentan in the ETAR homology model provided insight into the structural elements required for the affinity and the selectivity of the ETAR subtype.
Electrically-Conductive Polyketone Nanocomposites Based on Reduced Graphene Oxide

In this work, we investigated the functionalization of polyketone 30 (PK30) with glycyl-glycine (Gly-Gly) via the Paal–Knorr reaction with the aim of homogenously dispersing two types of reduced graphene oxide (rGO, i.e., lrGO and hrGO, the former characterized by a lower degree of reduction in comparison to the latter) by non-covalent interactions. The functional PK30-Gly-Gly polymer was effective in preparing composites with homogeneously distributed rGO characterized by an effective percolation threshold at 5 wt. %. All the composites showed a typical semiconductive behavior and stable electrical response after several heating/cooling cycles from 30 to 115 °C. Composites made by hrGO displayed the same resistive behaviour even if flanked by a considerable improvement on conductivity, in agreement with the more reduced rGO content. Interestingly, no permanent percolative network was shown by the composite with 4 wt. % of lrGO at temperatures higher than 45 °C. This material can be used as an ON–OFF temperature sensor and could find interesting applications as sensing material in soft robotics applications.
The Lipopeptide MALP-2 Promotes Collateral Growth

Beyond their role in pathogen recognition and the initiation of immune defense, Toll-like receptors (TLRs) are known to be involved in various vascular processes in health and disease. We investigated the potential of the lipopeptide and TLR2/6 ligand macrophage activating protein of 2-kDA (MALP-2) to promote blood flow recovery in mice. Hypercholesterolemic apolipoprotein E (Apoe)-deficient mice were subjected to microsurgical ligation of the femoral artery. MALP-2 significantly improved blood flow recovery at early time points (three and seven days), as assessed by repeated laser speckle imaging, and increased the growth of pre-existing collateral arteries in the upper hind limb, along with intimal endothelial cell proliferation in the collateral wall and pericollateral macrophage accumulation. In addition, MALP-2 increased capillary density in the lower hind limb. MALP-2 enhanced endothelial nitric oxide synthase (eNOS) phosphorylation and nitric oxide (NO) release from endothelial cells and improved the experimental vasorelaxation of mesenteric arteries ex vivo. In vitro, MALP-2 led to the up-regulated expression of major endothelial adhesion molecules as well as their leukocyte integrin receptors and consequently enhanced the endothelial adhesion of leukocytes. Using the experimental approach of femoral artery ligation (FAL), we achieved promising results with MALP-2 to promote peripheral blood flow recovery by collateral artery growth.
Protective effects and chemical composition of Corchorus olitorius leaf fractions against isoproterenol-induced myocardial injury through p65NFkB-dependent anti-apoptotic pathway in rats

Abstract Background The fractions of Corchorus olitorius leaf (COLF) were evaluated against oxidative stress, inflammation and apoptosis in isoproterenol (ISO)-induced myocardial injury (MI) Wistar rats. Methods The n-hexane, dichloromethane, ethylacetate and ethanol fractions were obtained from COLF extract. Male Wistar strains were randomly grouped into 11 groups (n = 6 in each group), which comprises normal control group, MI control group, 4 fraction groups with two doses (50 and 100 mg/kg) and enalapril (10 mg/kg). The sera were obtained for biochemical studies like AOPP (advance oxidized protein product), CRP (C-reactive protein), LDH (lactate dehydrogenase), CKMB (creatine kinase-MB) and myocardial tissue obtained for GSH, p65NFkB, bax, bcl2, p53 and p65NFkB assays. Results The subcutaneous administration of ISO increased the serum level of CRP, LDH and CKMB significantly (p < 0.05) and decreased serum AOPP, tissue GSH and p65NFkB (p < 0.05) in the infarction control rats. Pretreatment with COLF and enalapril increased the tissue GSH and p65NFkB levels (p < 0.05) and significantly reduced serum CRP, AOPP, LDH and CKMB. The dichloromethane fraction (CODCM) being the most active was chosen to evaluate the anti-apoptotic effect. CODCM (50 and 100 mg/kg) and enalapril showed a significant (p < 0.05) effect through severe expression of p65NFkB, which correlates with increased bcl2 protein expression, decreased bax protein and p53 expression. Gas chromatography mass spectrometry revealed the presence of 26 compounds in CODCM. Conclusions From the present study, COLF protected the myocardial tissue against ischemic injury in rats probably via the p65NFkB-dependent anti-apoptotic pathway and attenuation of pro-inflammatory marker level.
Knowledge, Attitude, and Practices of Antibiotics and Antibiotic Resistance Among Chinese Pharmacy Customers: A Multicenter Survey Study

Background: Resistance to antibiotics is one of the major global health challenges. An adequate understanding of the public regarding rational antibiotic use is a prerequisite to limit progression in antibiotic resistance. This study aimed to investigate the knowledge, attitude, and practices (KAP) of antibiotics and antibiotic resistance among customers visiting community pharmacies. Methods: This study was undertaken in three capital cities in China during March 2019 and July 2019 by using a questionnaire of 28 items. The questionnaire had four parts, including sociodemographic characteristics, KAP about antibiotics, and antibiotic resistance. A systematic random sampling approach was used to recruit the participants. Kruskal–Wallis and Mann–Whitney tests were carried out for data analysis. Results: The response rate was 66.7% (1800/2700). Out of the total, only 9.7% of the customers had good knowledge about antibiotics. Nearly half of the participants were unable to differentiate between antibiotics, and anti-inflammatory drugs (n = 820, 45.6%, Median = 2, IQR = 1). Most of the customers were of the view that the use of over the counter antibiotics in pregnant women is unsafe (n = 1307, 72.6%, Median = 2, IQR = 0). Almost half of the participants disagreed that costly antibiotics are more effective and have fewer side effects (n = 897, 49.9%, Median = 3, IQR = 1). Only 22.3% of participants said that they always finish the course of antibiotic treatment (n = 401, 22.3%, Median = 3, IQR = 1). Conclusion: The knowledge of Chinese pharmacy consumers was inadequate, and a lack of good attitudes and practices in certain aspects of antibiotic use was observed. Educational interventions are needed to increase public knowledge of antibiotics.
The depressive state of Denmark during the COVID-19 pandemic

1Department of Political Science, Aarhus University, Aarhus, Denmark; 2Department of Political Science, University of Copenhagen, Copenhagen, Denmark; 3The Danish National Institute of Public Health, University of Southern Denmark, Copenhagen, Denmark; 4Department of Affective Disorders, Aarhus University Hospital – Psychiatry, Aarhus, Denmark and 5Department of Clinical Medicine, Aarhus University, Aarhus, Denmark
In Vitro Wound Healing Potential of Flavonoid C-Glycosides from Oil Palm (Elaeis guineensis Jacq.) Leaves on 3T3 Fibroblast Cells

Oil palm (Elaeis guineensis Jacq.) leaves (OPL) are widely available at zero cost in Southeast Asia countries, especially in Malaysia and Indonesia due to large scale oil palm plantations. OPLs contain a large amount of flavonoids in particular flavonoid C-glycosides, which are known to possess useful biological properties including antioxidant and wound healing properties. The present study aimed at evaluating the wound healing efficacy of OPL in various solvent extracts and flavonoid enriched fractions and to determine the contribution of flavonoid C-glycosides (orientin, isoorientin, vitexin and isovitexin) using in-vitro scratch assay on 3T3 fibroblast cells. Solvent crude extracts with different polarity were screened and the most active extract was subjected to acid hydrolysis. The crude and acid hydrolysed extracts were further enriched using macroporous resins, XAD7HP. UHPLC-UV/PDA and LC-MS/MS analysis were applied for identification and confirmation of flavonoid C-glycosides. The wound healing properties comprised of cell viability, cell proliferation and cell migration were studied. Allantoin was used as a positive control to compare the efficacy among the tested samples. The results revealed all OPL crude extracts, flavonoid enriched fractions and flavonoid C-glycosides were non-toxic at concentrations below 25 µg/mL and showed better cell proliferation and migration activities at low concentrations than higher concentrations. This study also demonstrated orientin, isoorientin, vitexin and isovitexin presented in OPL extracts and flavonoid enriched fractions stimulated proliferation and migration of 3T3 fibroblast cells. Hence, these findings may pose potential therapeutic bioactive agents for wound healing by enhancing fibroblast proliferation and migration.
mGWAS Uncovers Gln-Glucosinolate Seed-Specific Interaction and its Role in Metabolic Homeostasis1[OPEN]

mGWAS of Gln-related traits reveals an unexpected seed-specific interaction between glutamine and glucosinolates and in shaping the metabolic homeostasis in Arabidopsis seeds. Gln is a key player in plant metabolism. It is one of the major free amino acids that is transported into the developing seed and is central for nitrogen metabolism. However, Gln natural variation and its regulation and interaction with other metabolic processes in seeds remain poorly understood. To investigate the latter, we performed a metabolic genome-wide association study (mGWAS) of Gln-related traits measured from the dry seeds of the Arabidopsis (Arabidopsis thaliana) diversity panel using all potential ratios between Gln and the other members of the Glu family as traits. This semicombinatorial approach yielded multiple candidate genes that, upon further analysis, revealed an unexpected association between the aliphatic glucosinolates (GLS) and the Gln-related traits. This finding was confirmed by an independent quantitative trait loci mapping and statistical analysis of the relationships between the Gln-related traits and the presence of specific GLS in seeds. Moreover, an analysis of Arabidopsis mutants lacking GLS showed an extensive seed-specific impact on Gln levels and composition that manifested early in seed development. The elimination of GLS in seeds was associated with a large effect on seed nitrogen and sulfur homeostasis, which conceivably led to the Gln response. This finding indicates that both Gln and GLS play key roles in shaping the seed metabolic homeostasis. It also implies that select secondary metabolites might have key functions in primary seed metabolism. Finally, our study shows that an mGWAS performed on dry seeds can uncover key metabolic interactions that occur early in seed development.
The emergence of a novel coronavirus (SARS‐CoV‐2) disease and their neuroinvasive propensity may affect in COVID‐19 patients

An outbreak of a novel coronavirus (SARS‐CoV‐2) infection has recently emerged and rapidly spreading in humans causing a significant threat to international health and the economy. Rapid assessment and warning are crucial for an outbreak analysis in response to serious public health. SARS‐CoV‐2 shares highly homological sequences with SARS‐CoVs causing highly lethal pneumonia with respiratory distress and clinical symptoms similar to those reported for SARS‐CoV and MERS‐CoV infections. Notably, some COVID‐19 patients also expressed neurologic signs like nausea, headache, and vomiting. Several studies have reported that coronaviruses are not only causing respiratory illness but also invade the central nervous system through a synapse‐connected route. SARS‐CoV infections are reported in both patients and experimental animals' brains. Interestingly, some COVID‐19 patients have shown the presence of SARS‐CoV‐2 virus in their cerebrospinal fluid. Considering the similarities between SARS‐CoV and SARS‐CoV‐2 in various aspects, it remains to clarify whether the potent invasion of SARS‐CoV‐2 may affect in COVID‐19 patients. All these indicate that more detailed criteria are needed for the treatment and the prevention of SARS‐CoV‐2 infected patients. In the absence of potential interventions for COVID‐19, there is an urgent need for an alternative strategy to control the spread of this disease.
Sepsis and Septic Shock in Patients With Malignancies: A Groupe de Recherche Respiratoire en Réanimation Onco-Hématologique Study*

Supplemental Digital Content is available in the text. Objectives: Cancer affects up to 20% of critically ill patients, and sepsis is one of the leading reasons for ICU admission in this setting. Early signals suggested that survival might be increasing in this population. However, confirmation studies have been lacking. The goal of this study was to assess trends in survival rates over time in cancer patients admitted to the ICU for sepsis or septic shock over the last 2 decades. Data Source: Seven European ICUs. Study Selection: A hierarchical model taking into account the year of admission and the source dataset as random variables was used to identify risk factors for day 30 mortality. Data Extraction: Data from cancer patients admitted to ICUs for sepsis or septic shock were extracted from the Groupe de Recherche Respiratoire en Réanimation Onco-Hématologique database (1994–2015). Data Synthesis: Overall, 2,062 patients (62% men, median [interquartile range] age 59 yr [48–67 yr]) were included in the study. Underlying malignancies were solid tumors (n = 362; 17.6%) or hematologic malignancies (n = 1,700; 82.4%), including acute leukemia (n = 591; 28.7%), non-Hodgkin lymphoma (n = 461; 22.3%), and myeloma (n = 244; 11.8%). Two-hundred fifty patients (12%) underwent allogeneic hematopoietic stem cell transplantation and 640 (31.0%) were neutropenic at ICU admission. Day 30 mortality was 39.9% (823 deaths). The year of ICU admission was associated with significant decrease in day 30 mortality over time (odds ratio, 0.96; 95% CI, 0.93–0.98; p = 0.001). Mechanical ventilation (odds ratio, 3.25; 95% CI, 2.52–4.19; p < 0.01) and vasopressors use (odds ratio, 1.42; 95% CI, 1.10–1.83; p < 0.01) were independently associated with day 30 mortality, whereas underlying malignancy, allogeneic hematopoietic stem cell transplantation, and neutropenia were not. Conclusions: Survival in critically ill oncology and hematology patients with sepsis improved significantly over time. As outcomes improve, clinicians should consider updating admission policies and goals of care in this population.
Validation of multicolor imaging signatures of central serous chorioretinopathy lesions vis-a-vis conventional color fundus photographs

Purpose: The current study compares the ability of multicolor imaging (MCI) to detect the lesions of central serous chorioretinopathy against conventional color fundus photographs (CFP). Methods: It was a retrospective, observational case series of 93 eyes of 58 patients of central serous chorioretinopathy who underwent MCI and CFP. MCI and spectral-domain optical coherence tomography (SD-OCT) were performed using Spectralis SD-OCT system (HRA + OCT). CFP was obtained using FF 450 Plus fundus camera (Carl Zeiss Meditec, Jena, Germany). SD-OCT was considered gold standard for subretinal fluid (SRF) and retinal pigment epithelium detachment (PED). CFP was considered confirmatory investigation for fibrin and blue autofluorescence image (BAF) was considered gold standard to detect retinal pigment epithelium (RPE) atrophy. Results: CFP could detect SRF in 41 (44.1%) eyes. MCI detected SRF in 43 (46.2%) eyes. The sensitivity and specificity of MCI to detect SRF were 70.7% and 94.3%, respectively. PED was detected by CFP in 21 (22.6%) eyes and MCI in 27 (29%) eyes. The sensitivity and specificity of MCI to detect PED were 70% and 97.7% respectively. CFP could pick RPE atrophy in 52 (55.9%) eyes whereas MCI was picked it in 78 (83.9%) of eyes. Conclusion: Both MCI and CFP were inferior to a gold standard in identifying the SRF, PED, and RPE atrophy. However, MCI was better than CFP in comparison with gold standard for these clinical findings in CSC. Thus, MCI seems to be a more valuable imaging tool compared to CFP.
Pancreatic Cancer Molecular Classifications: From Bulk Genomics to Single Cell Analysis

Pancreatic cancer represents one of the most lethal disease worldwide but still orphan of a molecularly driven therapeutic approach, although many genomic and transcriptomic classifications have been proposed over the years. Clinical heterogeneity is a hallmark of this disease, as different patients show different responses to the same therapeutic regimens. However, genomic analyses revealed quite a homogeneous disease picture, with very common mutations in four genes only (KRAS, TP53, CDKN2A, and SMAD4) and a long tail of other mutated genes, with doubtful pathogenic meaning. Even bulk transcriptomic classifications could not resolve this great heterogeneity, as many informations related to small cell populations within cancer tissue could be lost. At the same time, single cell analysis has emerged as a powerful tool to dissect intratumoral heterogeneity like never before, with possibility of generating a new disease taxonomy at unprecedented molecular resolution. In this review, we summarize the most relevant genomic, bulk and single-cell transcriptomic classifications of pancreatic cancer, and try to understand how novel technologies, like single cell analysis, could lead to novel therapeutic strategies for this highly lethal disease.
Explanatory preferences for complexity matching

People are adept at generating and evaluating explanations for events around them. But what makes for a satisfying explanation? While some scholars argue that individuals find simple explanations to be more satisfying (Lombrozo, 2007), others argue that complex explanations are preferred (Zemla, et al. 2017). Uniting these perspectives, we posit that people believe a satisfying explanation should be as complex as the event being explained–what we term the complexity matching hypothesis. Thus, individuals will prefer simple explanations for simple events, and complex explanations for complex events. Four studies provide robust evidence for the complexity-matching hypothesis. In studies 1–3, participants read scenarios and then predicted the complexity of a satisfying explanation (Study 1), generated an explanation themselves (Study 2), and evaluated explanations (Study 3). Lastly, in Study 4, we explored a different manipulation of complexity to demonstrate robustness across paradigms. We end with a discussion of mechanisms that might underlie this preference-matching phenomenon.
Fostering Health Literacy Responsiveness in a Remote Primary Health Care Setting: A Pilot Study

Primary healthcare organisations have an important role in addressing health literacy as this is a barrier to accessing and utilising health care. Until recently, no organisational development tool operationalising health literacy in an Australian context existed. This research evaluated the efficacy of the Organisational Health Literacy Responsiveness (Org-HLR) tool and associated assessment process in a primary healthcare organisation in the Pilbara region of Western Australia. This study utilised a sequential explanatory mixed methods research design incorporating the collection and analysis of data in two phases: (1) Pre- and post-survey data and; (2) seven semi-structured interviews. Survey results showed that participants’ confidence in core health literacy concepts improved from baseline following the intervention. Analysis of the interview data revealed participants’ initial understanding of health literacy was limited, and this impeded organisational responsiveness to health literacy needs. Participants reported the workshop and tool content were relevant to their organisation; they valued involving members from all parts of the organisation and having an external facilitator to ensure the impartiality of the process. External barriers to improving their internal organisational health literacy responsiveness were identified, with participants acknowledging the management style and culture of open communication within the organisation as enablers of change. Participants identified actionable changes to improve their organisational health literacy responsiveness using the process of organisational assessment and change.
Surveillance of COVID-19 in the General Population Using an Online Questionnaire: Report From 18,161 Respondents in China

Background The recent outbreak of the coronavirus disease (COVID-19) has become an international pandemic. So far, little is known about the role of an internet approach in COVID-19 participatory surveillance. Objective The aim of this study is to investigate whether an online survey can provide population-level information for observing prevalence trends during the early phase of an outbreak and identifying potential risk factors of COVID-19 infection. Methods A 10-item online questionnaire was developed according to medical guidelines and relevant publications. It was distributed between January 24 and February 17, 2020. The characteristics of respondents and temporal changes of various questionnaire-derived indicators were analyzed. Results A total of 18,161 questionnaires were returned, including 6.45% (n=1171) from Wuhan City. Geographical distributions of the respondents were consistent with the population per province (R2=0.61, P<.001). History of contact significantly decreased with time, both outside Wuhan City (R2=0.35, P=.002) and outside Hubei Province (R2=0.42, P<.001). The percentage of respondents reporting a fever peaked around February 8 (R2=0.57, P<.001) and increased with a history of contact in the areas outside Wuhan City (risk ratio 1.31, 95% CI 1.13-1.52, P<.001). Male sex, advanced age, and lung diseases were associated with a higher risk of fever in the general population with a history of contact. Conclusions This study shows the usefulness of an online questionnaire for the surveillance of outbreaks like COVID-19 by providing information about trends of the disease and aiding the identification of potential risk factors.