Miracle-dz/UniFAR-FTUs huggingface dataset:
Fibroblast Growth Factor Type 2 (FGF2) Administration Attenuated the Clinical Manifestations of Preeclampsia in a Murine Model Induced by L-NAME

Background: In preeclampsia, a hypertensive disorder of pregnancy, the poor remodeling of spiral arteries leads to placental hypoperfusion and ischemia, provoking generalized maternal endothelial dysfunction and, in severe cases, death. Endothelial and placental remodeling is important for correct pregnancy evolution and is mediated by cytokines and growth factors such as fibroblast growth factor type 2 (FGF2). In this study, we evaluated the effect of human recombinant FGF2 (rhFGF2) administration in a murine model of PE induced by NG-nitro-L-arginine methyl ester (L-NAME) to test if rhFGF2 administration can lessen the clinical manifestations of PE. Methods: Pregnant rats were administrated with 0.9% of NaCl (vehicle), L-NAME (60 mg/kg), FGF2 (666.6 ng/kg), L-NAME+FGF2 or L-NAME + hydralazine (10 mg/kg) from the 10th to 19th days of gestation. Blood pressure (BP), urine protein concentrations and anthropometric values both rat and fetuses were assessed. Histological evaluation of organs from rats delivered by cesarean section was carried out using hematoxylin and eosin staining. Results: A PE-like model was established, and it included phenotypes such as maternal hypertension, proteinuria, and fetal growth delay. Compared to the groups treated with L-NAME, the L-NAME + FGF2 group was similar to vehicle: the BP remained stable and the rats did not develop enhanced proteinuria. Both the fetuses and placentas from rats treated with L-NAME + FGF2 had similar values of weight and size compared with the vehicle. Conclusion: The intravenous administration of rhFGF2 showed beneficial and hypotensive effects, reducing the clinical manifestations of PE in the evaluated model.
Body Adiposity, But Not Elements of Objectively Measured Sedentary Behavior or Physical Activity, Is Associated With Circulating Liver Enzymes in Adults With Overweight and Obesity

Objective We studied the associations between accelerometer-measured sedentary behavior (SB) and habitual physical activity (PA) as well as markers of body adiposity and other cardiometabolic risk factors with liver enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST) and γ-glutamyltransferase (GGT). Methods A total of 144 middle-aged adults (mean age 57 (SD 6.5) years) with overweight or obesity (mean body mass index [BMI] 31.8 [SD 3.9] kg/m2) participated. Different components of SB (sitting, lying) and PA (standing, breaks in SB, daily steps, light PA, moderate-to-vigorous PA and total PA) were measured with validated hip-worn accelerometers for four consecutive weeks (mean 25 days, [SD 4]). Fasting venous blood samples were analysed using standard assays. The associations were examined with Pearson’s partial correlation coefficient test and linear mixed model. Results Among 102 women and 42 men accelerometer measured SB or the elements of PA were not associated with circulating liver enzymes. When adjusted for age and sex, liver enzymes correlated positively with BMI and waist circumference (WC) (ALT r=0.34, p<0.0001, r=0.41, < 0.0001, AST r=0.17, p=0.049, r=0.26, p=0.002, GGT r=0.29, p=0.0005, r=0.32, p < 0.0001, respectively). SB proportion associated positively with BMI (r=0.21, p=0.008) and WC (r=0.27, p=0.001). Components of PA associated negatively with BMI (MVPA r=-0.23, p=0.005, daily steps r=-0.30, p<0.0001 and breaks in sedentary time r=-0.32, p<0.0001), as well as with WC (breaks in SB r=-0.35, p<0.0001, MVPA r=-0.26, p=0.002, daily steps r=-0.31, p<0.0001, standing time r=-0.27, p=0.001). Liver enzymes associated positively with common cardiometabolic markers such as resting heart rate (ALT; β=0.17, p=0.03, AST; β=0.25, p=0.002, GGT; β=0.23, p=0.004) and systolic/diastolic blood pressure (ALT β=0.20, p=0.01, β=0.22, p=0.005, AST (only diastolic) β=0.23, p=0.006, GGT β=0.19, p=0.02, = 0.23, p=0.004, respectively), fasting insulin (ALT β=0.41, p<0.0001, AST β=0.36, p=0.0003, GGT β=0.20, p=0.04) and insulin resistance index (ALT β=0.42, p<0.0001, AST β=0.36, p=0.0003, GGT β=0.21, p=0.03), even after adjustment with BMI. Conclusions Liver enzymes correlate with body adiposity and appear to cluster with other common cardiometabolic risk factors, even independently of body adiposity. SB and PA appear not to be essential in modulating the levels of circulating liver enzymes.
Cost-Effectiveness Analysis of Olaparib Maintenance Treatment for Germline BRCA-Mutated Metastatic Pancreatic Cancer

Background: The PARP inhibitor olaparib has been shown to have clinical efficacy in patients with a germline BRCA mutation and ovarian or breast cancer. However, the high treatment cost associated with this drug limits its viability as a clinical treatment option. This work aims to evaluate the cost-effectiveness of olaparib as a maintenance treatment for metastatic pancreatic cancer from the perspective of the United States and China healthcare systems and provides valuable suggestions for clinical decision making. Method: A three-state Markov model (progression-free, progressed disease, death) was constructed using TreeAge Pro 2020 software to evaluate the economic value of olaparib vs. placebo maintenance treatment for metastatic pancreatic cancer based on the clinical data derived from phase III randomized controlled trial (POLO, ClinicalTrials.gov number, NCT02184195). Total costs, quality-adjusted life years and incremental cost-effectiveness ratio were used as economic indicators for this analysis. A 5-years horizon and 5%/year discount rates were used. One-way sensitivity analysis and probabilistic sensitivity analysis (PSA) were performed to assess the model uncertainty. Results: The incremental cost-effectiveness ratios (ICERs) of the use of olaparib vs. placebo in China and the United States were $6,694/QALY and $13327/QALY, respectively. All ICERs were far below the thresholds of $30829 in China and $50000 in the United States. Sensitivity analysis confirmed a stable economic advantage in the use of olaparib vs. placebo as maintenance therapy in China and the United States. Conclusion: Olaparib was estimated to be more cost effective than placebo for the maintenance therapy of patients with a germline BRCA mutation and pancreatic cancer in China and the United States at thresholds of $30829 and $50000 per QALY, respectively.
Emoji as Affective Symbols: Affective Judgments of Emoji, Emoticons, and Human Faces Varying in Emotional Content

An important function of emoji as communicative symbols is to convey emotional content from sender to receiver in computer-mediated communication, e. g. , WhatsApp. However, compared with real faces, pictures or words, many emoji are ambiguous because they do not symbolize a discrete emotion or feeling state. Thus, their meaning relies on the context of the message in which they are embedded. Previous studies investigated affective judgments of pictures, faces, and words suggesting that these stimuli show a typical distribution along the big two emotion dimensions of valence and arousal. Also, emoji and emoticons have been investigated recently for their affective significance. The present study extends previous research by investigating affective ratings of emoji, emoticons and human faces and by direct comparison between them. In total, 60 stimuli have been rated by 83 participants (eight males, age: 18–49 years), using the non-verbal Self-Assessment Manikin Scales for valence and arousal. The emotionality of the stimuli was measured on a 9-point Likert scale. The results show significant main effects of the factors “stimulus category” and “discrete emotion” including emotionality, valence and arousal. Also, the interaction between these two main factors was significant. Emoji elicited highest arousal, whereas stimuli related to happiness were rated highest in valence across stimulus categories. Angry emoji were rated highest in emotionality. Also, the discrete emotion was best recognized in emoji, followed by human face stimuli and lastly emoticons.
Supplemental Learning in Respiratory Physiology for Healthcare Professionals Towards Successful Treatment of COVID-19

The immunological and pathophysiological response to COVID-19 can cause severe respiratory impairment affecting gas exchange and lung mechanics. Such was the scale of the respiratory support needed during the first wave of the pandemic, that recruitment of non-respiratory clinical staff was essential to help deal with the growing number of cases. It quickly became apparent that it was vital to rapidly equip these healthcare professionals with appropriate physiological knowledge and practical skills if therapies were to be applied effectively. Furthermore, the unravelling of unusual clinical features of COVID-19, further highlighted a need for knowledge of long-established principles of respiratory physiology. An online digital educational resource, or “respiratory learning tool kit” was developed with interactive material including visualisations, animations, and pathophysiological examples to facilitate understanding. The learning outcomes were centred on physiological principles, essential for understanding the pathophysiology relating to COVID-19, and management and treatment. Topics included principles of gas exchange, gas transport, homeostasis and central control of respiration. These basic physiological principles were linked to pathophysiology and clinical skills around oxygen administration and non-invasive supports such as Continuous Positive Airway Pressure (CPAP). From the degree of engagement and evaluation comments, it was clear that the resource successfully achieved its aim—to increase physiological knowledge and its practical understanding, enabling healthcare professionals to practice with confidence in such an uncertain environment.
Energetics of intrinsic point defects in aluminium via orbital-free density functional theory

Abstract The formation and migration energies for various point defects, including vacancies and self-interstitials, in aluminium are systematically reinvestigated using the supercell approximation in the framework of orbital-free density functional theory. In particular, the finite-size effects and the accuracy of various kinetic energy density functionals are examined. It is demonstrated that as the supercell size increases, the finite-size errors asymptotically decrease as . Notably, the formation energies of self-interstitials converge much more slowly than that of vacancies. With carefully chosen kinetic energy density functionals, the calculated results agree quite well with the available experimental data and those obtained through Kohn–Sham density functional theory, which has an exact kinetic term.
Knock-Down of Mucolipin 1 Channel Promotes Tumor Progression and Invasion in Human Glioblastoma Cell Lines

Among cancers that affect the central nervous system, glioblastoma is the most common. Given the negative prognostic significance of transient receptor potential mucolipin 1 (TRPML1) channel reduction in patients with glioblastoma, as discussed in previous publications, the aim of the current study was to investigate the biological advantage of TRPML1 loss for glioma cells. Human glioblastoma primary cancer cells (FSL and FCL) and glioblastoma cell lines (T98 and U251) were used for that purpose. TRPML1 silencing in T98 cells induces defective autophagy, nitric oxide (NO) production, and cathepsin B-dependent apoptosis in the first 48 h and then apoptotic-resistant cells proliferate with a high growth rate with respect to control cells. In U251 cells, knock-down of TRPML1 stimulates NO generation and protein oxidation, arrests cell cycle at G2/M phase, and induces autophagy leading to cathepsin B-dependent senescence. Finally, in both cell lines, the long-term effects of TRPML1 silencing promote survival and invasion capacity with respect to control cells. Silencing of TRPML1 also affects the phenotype of glioblastoma primary cells. FSL cells show increased proliferation ability, while FCL cells enter into senescence associated with an increased invasion ability. In conclusion, although the molecular heterogeneity among different glioblastoma cell lines mirrors the intercellular heterogeneity in cancer cells, our data support TRPML1 downregulation as a negative prognostic factor in glioblastoma.
Distinguishing Pseudoprogression From True Early Progression in Isocitrate Dehydrogenase Wild-Type Glioblastoma by Interrogating Clinical, Radiological, and Molecular Features

Background: Pseudoprogression (PsP) mimics true early progression (TeP) in conventional imaging, which poses a diagnostic challenge in glioblastoma (GBM) patients who undergo standard concurrent chemoradiation (CCRT). This study aimed to investigate whether perioperative markers could distinguish and predict PsP from TeP in de novo isocitrate dehydrogenase (IDH) wild-type GBM patients. Methods: New or progressive gadolinium-enhancing lesions that emerged within 12 weeks after CCRT were defined as early progression. Lesions that remained stable or spontaneously regressed were classified as PsP, otherwise persistently enlarged as TeP. Clinical, radiological, and molecular information were collected for further analysis. Patients in the early progression subgroup were divided into derivation and validation sets (7:3, according to operation date). Results: Among 234 consecutive cases enrolled in this retrospective study, the incidences of PsP, TeP, and neither patterns of progression (nP) were 26.1% (61/234), 37.6% (88/234), and 36.3% (85/234), respectively. In the early progression subgroup, univariate analysis demonstrated female (OR: 2.161, P = 0.026), gross total removal (GTR) of the tumor (OR: 6.571, P < 001), located in the frontal lobe (OR: 2.561, P = 0.008), non-subventricular zone (SVZ) infringement (OR: 10.937, P < 0.001), and methylated O-6-methylguanine-DNA methyltransferase (MGMT) promoter (mMGMTp) (OR: 9.737, P < 0.001) were correlated with PsP, while GTR, non-SVZ infringement, and mMGMTp were further validated in multivariate analysis. Integrating quantitative MGMTp methylation levels from pyrosequencing, GTR, and non-SVZ infringement showed the best discriminative ability in the random forest model for derivation and validation set (AUC: 0.937, 0.911, respectively). Furthermore, a nomogram could effectively evaluate the importance of those markers in developing PsP (C-index: 0.916) and had a well-fitted calibration curve. Conclusion: Integrating those clinical, radiological, and molecular features provided a novel and robust method to distinguish PsP from TeP, which was crucial for subsequent clinical decision making, clinical trial enrollment, and prognostic assessment. By in-depth interrogation of perioperative markers, clinicians could distinguish PsP from TeP independent from advanced imaging.
Virus Detection: A Review of the Current and Emerging Molecular and Immunological Methods

Viruses are ubiquitous in the environment. While many impart no deleterious effects on their hosts, several are major pathogens. This risk of pathogenicity, alongside the fact that many viruses can rapidly mutate highlights the need for suitable, rapid diagnostic measures. This review provides a critical analysis of widely used methods and examines their advantages and limitations. Currently, nucleic-acid detection and immunoassay methods are among the most popular means for quickly identifying viral infection directly from source. Nucleic acid-based detection generally offers high sensitivity, but can be time-consuming, costly, and require trained staff. The use of isothermal-based amplification systems for detection could aid in the reduction of results turnaround and equipment-associated costs, making them appealing for point-of-use applications, or when high volume/fast turnaround testing is required. Alternatively, immunoassays offer robustness and reduced costs. Furthermore, some immunoassay formats, such as those using lateral-flow technology, can generate results very rapidly. However, immunoassays typically cannot achieve comparable sensitivity to nucleic acid-based detection methods. Alongside these methods, the application of next-generation sequencing can provide highly specific results. In addition, the ability to sequence large numbers of viral genomes would provide researchers with enhanced information and assist in tracing infections.
Early Exposure to High-Sucrose Diet Leads to Deteriorated Ovarian Health

Background The metabolic syndrome (MetS) is correlated with disorders of the reproductive system, such as the polycystic ovary syndrome (PCOS). While consumption of a diet rich in carbohydrates is linked to the development of MetS, it is still unclear if this diet leads to ovarian dysfunction and PCOS. Objectives We investigated the influence of a high-sucrose diet (HSD) on the ovarian milieu of Wistar rats and studied the correlation between high consumption of sugary drinks and the prevalence of PCOS in women. Methods Wistar rats were given a standard laboratory diet (CTR, 10% sucrose, n = 8) or HSD (HSD, 25% sucrose, n = 8) from postnatal day 21 to 120. Animals were evaluated weekly to calculate food intake, feed efficiency and weight gain. Both onset of puberty and estrous cycle were monitored. Metabolic serum biochemistry, organ morphometry and ovarian histology were performed upon euthanasia. In parallel, a fixed-effects multiple linear regression analysis was performed using data from Brazilian states (459 state-year observations) to test the correlation between the consumption of sugar-sweetened beverages (surrogate for HSD intake) and the prevalence of PCOS (surrogate for ovarian dysfunction). Results HSD animals showed increased adipose tissue accumulation, hyperglycaemia and insulin resistance when compared to CTR. Interestingly HSD rats also entered puberty earlier than CTR. Moreover, ovaries from HSD animals had an increased number of atretic antral follicles and cystic follicles, which were correlated with the hypertrophy of periovarian adipocytes. Finally, there was a positive correlation between the intake of sugary drinks and prevalence of PCOS in women of reproductive age. Conclusions HSD ingestion leads to ovarian dysfunction in rats and could be correlated with PCOS in women, suggesting these alterations could lead to public health issues. Therefore, we reinforce the deleterious impact of HSD to the ovarian system and suggest that the reduction of added sugars intake could be beneficial to ovarian health.
mcr-1 Identified in Fecal Escherichia coli and Avian Pathogenic E. coli (APEC) From Brazil

Colisitin-associated resistance in bacteria of food producing animals has gained significant attention with the mcr gene being linked with resistance. Recently, newer variants of mcr have emerged with more than nine variants currently recognized. Reports of mcr associated resistance in Escherichia coli of poultry appear to be relatively limited, but its prevalence requires assessment since poultry is one of the most important and cheapest sources of the world’s protein and the emergence of resistance could limit our ability to treat disease outbreaks. Here, 107 E. coli isolates from production poultry were screened for the presence of mcr 1–9. The isolates were collected between April 2015 and June 2016 from broiler chickens and free-range layer hens in Rio de Janeiro, Brazil. All isolates were recovered from the trachea and cloaca of healthy birds and an additional two isolates were recovered from sick birds diagnosed with colibacillosis. All isolates were screened for the presence of mcr-1 to 9 using PCR and Sanger sequencing for confirmation of positive genes. Additionally, pulse field gel electrophoresis (PFGE) analysis, avian fecal E. coli (APEC) virulence associated gene screening, plasmid replicon typing and antimicrobial resistance phenotype and resistance gene screening, were also carried out to further characterize these isolates. The mcr-1 gene was detected in 62 (57.9%) isolates (61 healthy and 1 APEC) and the mcr-5 gene was detected in 3 (2.8%) isolates; mcr-2, mcr-3, mcr-4, mcr-6, mcr-7, mcr-8, and mcr-9 were not detected in any isolate. In addition, mcr 1 and 5 positive isolates were phenotypically resistant to colistin using the agar dilution assay (> 8ug/ml). PFGE analysis found that most of the isolates screened had unique fingerprints suggesting that the emergence of colistin resistance was not the result of clonal dissemination. Plasmid replicon types IncI2, FIB, and B/O were found in 38, 36, and 34% of the mcr positive isolates and were the most prevalent replicon types detected; tetA and tetB (32 and 26%, respectively) were the most prevalent antimicrobial resistance genes detected and iutA, was the most prevalent APEC virulence associated gene, detected in 50% of the isolates. Approximately 32% of the isolates examined could be classified as APEC-like, based on the presence of 3 or more genes of APEC virulence associated path panel (iroN, ompT, hlyF, iss, iutA). This study has identified a high prevalence of mcr-1 in poultry isolates in Brazil, suggesting that animal husbandry practices could result in a potential source of resistance to the human food chain in countries where application of colistin in animal health is practiced. Emergence of the mcr gene and associated colisitin resistance in production poultry warrants continued monitoring from the animal health and human health perspective.
Evaluation of the Microba Community Profiler for Taxonomic Profiling of Metagenomic Datasets From the Human Gut Microbiome

A fundamental goal of microbial ecology is to accurately determine the species composition in a given microbial ecosystem. In the context of the human microbiome, this is important for establishing links between microbial species and disease states. Here we benchmark the Microba Community Profiler (MCP) against other metagenomic classifiers using 140 moderate to complex in silico microbial communities and a standardized reference genome database. MCP generated accurate relative abundance estimates and made substantially fewer false positive predictions than other classifiers while retaining a high recall rate. We further demonstrated that the accuracy of species classification was substantially increased using the Microba Genome Database, which is more comprehensive than reference datasets used by other classifiers and illustrates the importance of including genomes of uncultured taxa in reference databases. Consequently, MCP classifies appreciably more reads than other classifiers when using their recommended reference databases. These results establish MCP as best-in-class with the ability to produce comprehensive and accurate species profiles of human gastrointestinal samples.