Miracle-dz/UniFAR-FTUs huggingface dataset:
Use of Dupilumab in Glucocorticoid-Dependent Asthma

Severe asthma constitutes illness in a relatively small proportion of all patients with asthma, but it is a major public health problem, with considerable effect on morbidity and mortality, and a high burden on healthcare resources. Regardless of the multiple treatments being widely available, a large population of severe asthma cases remain uncontrolled. Achieving and maintaining asthma control in this group of patients are, therefore, of the utmost importance. Dupilumab is an evolving biologic that shows effectiveness in uncontrolled asthma. Abstract Of the patients with asthma, 20% to 25% progress to severe symptoms, resulting in poor quality of life and increased episodes of exacerbation. There is a broad range of drugs used for asthma; the most used medications for severe asthma are inhaled glucocorticoids with or without long-acting β-agonists. Systemic glucocorticoids and other treatments as add-on therapies are also given as needed. Chronic glucocorticoid use is associated with numerous adverse effects, including diabetes mellitus, osteoporosis, anxiety, depression, and cataracts. The occurrence of these side effects has been reduced because of the emergence of new biological therapies. One such treatment is dupilumab, which helps in the reduction of type 2 inflammation involved in the pathophysiology of asthma. We conducted a literature review to assess the efficacy, adverse effects, and pharmacological benefits of dupilumab in glucocorticoid-dependent asthma. In most randomized controlled trials, dupilumab has shown significant efficacy and safety profile in patients with severe asthma with corticosteroid dependence. Associated adverse effects such as injection site reaction and transient eosinophilia have been reported. Our review of the literature indicates that dupilumab has proven to improve lung function, reduce the rate of asthma exacerbations, and reduce the use of corticosteroids.
Smoke Exposure in Mice Immune Cell Recruitment after Cigarette Leptin Modulates Innate and Adaptive

Leptin, a pleiotropic type I cytokine, was recently demonstrated to be expressed by resident lung cells in chronic obstructive pulmonary disease patients and asymptomatic smokers. To elucidate the functional role of leptin in the onset of chronic obstructive pulmonary disease, we tested leptin-deﬁcient ob/ob mice (C57BL/6), leptin receptor-deﬁcient db/db mice (C57BKS), and littermates in a model of cigarette smoke (CS)-induced pulmonary inﬂammation. Wild-type (WT) C57BL/6 mice were exposed for 4 or 24 wk to control air or CS. Pulmonary leptin expression was analyzed by immunohistochemistry and real-time PCR. Pulmonary inﬂammation upon 4 wk CS exposure was evaluated in bronchoalveolar lavage ﬂuid (BALF) and lung tissue of WT, ob/ob , and db/db mice. Immunohistochemical analysis revealed leptin expression in bronchial epithelial cells, pneumocytes, alveolar macrophages, and bronchial/vascular smooth muscle cells. The 4 and 24 wk CS exposure increased leptin expression in bronchial epithelial cells and pneumocytes versus air-exposed WT mice ( p , 0.05). The 4 wk CS exposure resulted in increased accumulation of neutrophils, dendritic cells, macrophages, and lymphocytes in BALF and lung tissue of WT, ob/ob , and db/db mice. CS-exposed ob/ob and db/db mice showed in general higher numbers of neutrophils and lower numbers of CD4 + , CD8 + , and dendritic cells versus CS-exposed WT mice. Consistently, CXCL1 levels were enhanced in BALF of CS-exposed ob/ob and db/db mice versus WT mice ( p , 0.05). Exogenous leptin administration completely restored the skewed inﬂammatory proﬁle in ob/ob mice. These data reveal an important role of leptin in modulating innate and adaptive immunity after CS inhalation in mice. The Journal of Immunology , 2010, 184: 000–000. anti-CD3 (145-2C11) mAbs. The additional marker used for activation was PE-conjugated anti-CD69 (H1.2F3). The additional marker used for activation was PE-conjugated anti-CD69 (H1.2F3). PE-conjugated anti-GR1 (Ly-6G) and allophycocya-nin-conjugated anti-CD11c Abs were used to characterize pulmonary granulocytes. All of the mAbs were obtained from BD Pharmingen (San CA). As a last step before analysis, cells were incubated with 7- aminoactinomycin D (Via-Probe, BD Pharmingen) for dead cell exclusion. was ﬂow CellQuest software Biosciences,
Grapevine and Arabidopsis cation-chloride cotransporters localise to the Golgi 14 and trans -Golgi network and indirectly influence long-distance ion transport 15 and plant salt tolerance

Summary: A protein from grapevine that Abstract 43 Plant cation-chloride cotransporters (CCCs) have been implicated in conferring salt tolerance. 44 They are predicted to improve shoot salt exclusion by directly catalysing the retrieval of 45 sodium (Na + ) and chloride ions (Cl – ) from the root xylem. We investigated whether VviCCC 46 from grapevine ( Vitis vinifera L.) has a role in salt tolerance by cloning and functionally 47 characterising the gene from Cabernet Sauvignon. Amino acid sequence analysis revealed 48 that VviCCC shares a high degree of similarity with other plant CCCs. A VviCCC-YFP 49 translational fusion protein localised to the Golgi and trans -Golgi network (TGN), not the 50 plasma membrane, when expressed transiently in tobacco ( Nicotiana benthamiana ) leaves 51 and Arabidopsis thaliana mesophyll protoplasts. AtCCC-GFP from Arabidopsis also 52 localised to Golgi and TGN. In Xenopus laevis oocytes, VviCCC targeted to the plasma 53 membrane where it catalysed bumetanide sensitive 36 Cl – , 22 Na + and 86 Rb + uptake, suggesting 54 that VviCCC (like AtCCC) belongs to the NKCC class of CCCs. Expression of VviCCC in an 55 Arabidopsis ccc knockout mutant abolished the mutant’s stunted growth phenotypes, and 56 reduced shoot Cl – and Na + content to wild-type levels after growing plants in 50 mM NaCl. 57 In Vitis vinifera roots, VviCCC transcript abundance was not regulated by Cl – treatment and 58 was present at similar levels in both the root stele and cortex of three Vitis genotypes that 59 exhibit differential shoot salt exclusion. Our findings indicate that CCC function is conserved 60 between grapevine and Arabidopsis, but neither protein is likely to directly mediate ion 61 transfer with the xylem or have a direct role in salt tolerance.
Effects of cooperative and competitive incentives on agility, quality, and speed in an experimental setting

Inter‐ and intraorganizational cooperation have been identified as essential characteristics of agile manufacturing. For this research, agility was compared using two experimental treatments: cooperative versus competitive. Student teams performed a task and were confronted with random changes to simulate a dynamic environment. Although differences were not statistically significant, the results show that cooperative incentives do not result in greater agility. Speed also decreased with cooperative incentives but quality improved. The experiment provides a preliminary understanding of how competition, cooperation, and agility interrelate and suggest that intra‐organizational cooperation may not be the best means of achieving manufacturing agility. © 2004 Wiley Periodicals, Inc. Hum Factors Man 14: 403–413, 2004.
Patient Quality of Life Improvement in Bullous Disease: A Review of Primary Literature and Considerations for the Clinician

: Autoimmune and inherited bullous disorders are rare skin diseases that may have a profound negative impact on quality of life (QOL). Common symptoms include pain, pruritus, and scarring, and complications may result in the loss of the ability to perform daily tasks. Diagnosis may have a negative psychological impact, and ongoing management may require a significant allocation of time and resources by both patients and providers. To provide patient-centered care, consideration of these factors is of utmost importance for the dermatologist treating patients with bullous disorders. Herein, we present a review of the primary literature evaluating QOL in autoimmune and inherited bullous disorders, including pemphigus, pemphigoid, epidermolysis bullosa, and Hailey-Hailey disease.
Using the TLR7/8 Agonist CL075 Generation of Th1-Polarizing Dendritic Cells

In this paper, we describe a new method for preparation of human dendritic cells (DCs) that secrete bioactive IL-12(p70) using synthetic immunostimulatory compounds as TLR7/8 agonists. Monocyte-derived DCs were generated using a procedure that provided mature cells within 3 d. Several maturation mixtures that contained various cytokines, IFN- g , different TLR agonists, and PGE 2 were compared for impact on cell recovery, phenotype, cytokine secretion, migration, and lymphocyte activation. Mixtures that included the TLR7/8 agonists R848 or CL075, combined with the TLR3 agonist polyinosinic:polycytidylic acid, yielded 3-d mature DCs that secreted high levels of IL-12(p70), showed strong chemotaxis to CCR7 ligands, and had a positive costimulatory potential. They also had excellent capacity to activate NK cells, effectively polarized CD4 + and CD8 + T cells to secrete IFN- g and to induce T cell-mediated cytotoxic function. Thereby, mature DCs prepared within 3 d using such maturation mixtures displayed optimal functions required for vaccine development. The Journal of Immunology , 2010, 185: 738–747.
OPTH_A_275977 3331..3342

1Ophthalmology, Royal Free London NHS Foundation Trust, London, UK; 2Macular Research Group, Save Sight Institute, Sydney University, Sydney, Australia; 3Service d’ophtalmologie, Hospices Civils de Lyon, Groupement Hospitalier Nord, Hôpital de la CroixRousse, Lyon, France; 4Laboratoire UMRCNRS 5510 Matéis, Université Lyon 1, Villeurbanne, Lyon, France; 5Ophthalmology, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK; 6Academic Ophthalmology and Vision Sciences, Division of Clinical Neurosciences, Eye and ENT Centre, Queen’s Medical Centre, University of Nottingham, Nottingham, UK Purpose: To report trends in real-world outcomes of anti-vascular endothelial growth factor (anti-VEGF) therapy for neovascular age-related macular degeneration (nAMD) in the United Kingdom (UK) over the last decade. Design: Systematic review. Methods: Medline, PubMed, and Embase databases were searched from 9 April 2010 to 8 April 2020 for publications that met the inclusion criteria: treatment-naïve eyes, UK-only data and ≥1 year of follow-up. ICHOM (International Consortium for Health Outcome Measures) outcomes and study quality were assessed. Visual acuity (VA) trends were assessed in studies with ≥100 eyes at baseline. Results: Twenty-six studies (n=25,761 eyes) were included, meeting 14–17 out of 20 Institute of Health Economics Quality Appraisal of Case Series checklist domains. Only ranibizumab and aflibercept outcome data were available. The mean injection number in the first year of treatment was 5.9 in publications from 2010 to 2015 and 7.1 from 2015 to 2020. Average baseline VA and mean one-year, two-year and three-year VA gains gradually improved over the last decade. Longer-term studies reported that the visual gains achieved in the first year of treatment were rarely maintained, with under-treatment a likely contributing factor. Conclusion: UK real-world outcomes have improved over the last decade with improved service delivery and the adoption of more proactive treatment regimens but are still not always as impressive as registration clinical trial results. Access to longer-acting anti-VEGF therapies would reduce the treatment burden for patients, carers, and the healthcare system, potentially making replication of clinical trial results possible in the NHS.
T. cruzi CYP51 complexes with UDO and UDD Complexes of Trypanosoma cruzi sterol 14a-demethylase (CYP51) with two pyridine-based drug candidates for Chagas disease: Structural basis for pathogen-selectivity*

Chagas disease, caused by the eukaryotic (protozoan) parasite Trypanosoma cruzi , is an alarming emerging global health problem with no clinical drugs available to treat the chronic stage. were proven effective against Chagas, and antifungal Here we present the X-ray structures of T. CYP51 in complexes with
* I.J.A.S. Imp. 01/03

The recent literature dealing with the effect of the diet on the quality of milk and meat fat is reviewed. Some aspects of the rumen metabolism of lipids are dealt with: lipolysis, bio-hydrogenation, synthesis of microbial fatty acids and inhibition mechanisms on fermentation. Firstly, the influence of forage is considered. Pasture is the best forage, better if high hill pasture, as compared to hay and silage: short chain fatty acids (SCFA) (shorter than C10) are increased, medium chain fatty acids (MCFA) (C12 through C16) are decreased, oleic (OA), linoleic (LA) and linolenic (LNA) acids are increased and so are the conjugated linoleic acid pool of isomers (CLA) and n-3 polyunsaturated fatty acids (n-3 PUFA). Secondly, the energy supplementation of diets with fats is looked at. Animal fats depress milk yield and SCFA, while OA is increased because of the enhanced activity of mammary ∆ desaturase. Fish oil depresses milk yield as well, but promotes CLA and n-3 PUFA. If animal fats are protected against rumen bacteria, milk yield and milk fat depression are avoided. Vegetable fats are richer in unsaturated fatty acids (UFA), thus more susceptible to the rumen bio-hydrogenation. As calcium soaps or inside whole seeds, plant fats are protected and CLA is increased. CLA is an important component of fat. In ruminants it comes from the desaturation of vaccenic acid (VA) both in rumen and udder; and the yield of VA depends on the diet quality. In conclusion, simple directions are given on how to improve the quality of animal fat by dietary means, without
Staring at My Body

K E Y W O R D S Body image Breast cancer Objectification Qualitative research Recovery Self-identity Background: Breast cancer takes time for its survivors after a mastectomy to adjust to their changed bodies. There are limited studies about the process of how those survivors accept the changes of their bodies and how they reestablish their new selves. Objective: The aim of this study was to understand the perception of body from women diagnosed with breast cancer more than 5years previously and whose treatment included a mastectomy. Methods: A phenomenological method was applied to this study. Women who received a mastectomy at least 5years previously were invited to participate. Eight participants were recruited from southern Taiwan. Results: Twenty transcripts were obtained and analyzed using Colaizzi’s method. Three themes were obtained from the data analysis: ‘‘restoration of the body image,’’ ‘‘abandonment of objectification,’’ and ‘‘redefinition of self. ’’ Subthemes were also identified and described. Conclusion: The results indicate that women with breast cancer have embodied the recovering experience to a new self and have adapted to identify their new bodies. They overcome being a female body with an absent breast(s) by discovering the value of their existence and being free from self-objectification. Implications for Practice: This study contributes to the understanding of the perception of body in long-term breast cancer survivors, which reflects the process of adjusting to the loss of a breast/breasts to reconstructing a new body experience. Health professionals could help and encourage women undergoing a mastectomy to engage in self-recovery by searching for and affirming self-value.
Variability among the Isolates of Broad Bean Mottle Virus and Encapsidation of Host RNAs

Broad bean mottle bromovirus infects legume plants and is transmissible by insects. Several broad bean mottle virus (BBMV) isolates have been identified, including one in England (isolate Ba) and five in the Mediterranean countries: Libya (LyV), Morocco (MV), Syria (SV), Sudan (TU) and Tunisia (TV). Previously, we analyzed the nucleotide sequence of the Ba RNA and here we report on and compare it with another five Mediterranean variants. The RNA segments in the latter ones were extensively homologous, with some SNPs, single nucleotide deletions and insertions, while the number of mutations was higher in isolate Ba. Both the 5′ and 3′ untranslated terminal regions (UTRs) among the corresponding RNAs are highly conserved, reflecting their functionality in virus replication. The AUG initiation codons are within suboptimal contexts, possibly to adjust/regulate translation. The proteins 1a, 2a, 3a and coat protein (CP) are almost identical among the five isolates, but in Ba they have more amino acid (aa) substitutions. Phylogenetic analysis revealed the isolates from Morocco and Syria clustering with the isolate from England, while the variants from Libya, Tunisia and Sudan created a different clade. The BBMV isolates encapsidate a high content of host (ribosomal and messenger) RNAs. Our studies present BBMV as a useful model for bromoviruses infecting legumes.
Female CEO and internal control weaknesses

This study examines how the gender of CEOs affects internal controls over financial reporting. According to the upper echelon theory, managers’ demographics can determine the choices of strategies. Prior literature documents the characteristics of CEOs relevant to internal controls, such as the CEO’s age, entrenchment (Lin, Wang, Chiou, & Huang, 2014), and experience (Oradi, Asiaei, & Rezaee, 2020); however, the impact of the CEO’s gender on internal controls has not been explored. We hypothesize that female CEOs are negatively associated with internal control weaknesses because they are reported to act more conservatively and ethically than male CEOs. We use logit and Poisson regression models to test the association between the CEO’s gender and internal control weaknesses of U.S. public companies from 2004 to 2020. Our results show that female CEOs are less likely to report an internal control weakness both in the current year and in the future years. We follow You (2021) and use a two-stage model to address the potential endogeneity concerns and show that our findings are not biased. Our study documents an important factor that influences internal controls, and we provide evidence of the benefits of female CEOs on the quality of financial reports
Five new endemic eucalypts for Victoria

Eucalyptus bunyip, a tall swamp gum from the Bunyip State Park in west Gippsland, E. conferta, a small-leaved scentbark from the Fryers Range near Castlemaine in north-central Victoria, E. carolaniae , a rough-barked mountain grey gum from Mt Martha on the Mornington Peninsula, E. yarriambiack, an umbrageous mallee-box from near Brim in the southern part of the Mallee region , and E. aurifodina , a small-fruited brown stringybark from the Victorian goldfields in the Avoca-Castlemaine area, are described as new Victorian endemic species. The affinities, ecologies, distributions and conservation statuses of each new taxon are discussed.
First-Principles Study of the Effect of Titanium Doping on Carbon Monoxide Poisoning Properties of Zirconium-Cobalt Alloys

It is very important to study impurity gas poisoning in ZrCo alloy because it is associated directly with the performance of ZrCo alloy as a hydrogen storage material. In this work, the effects of atomic replacement on the mechanism and properties of CO impurity gas poisoning in doped (Ti) ZrCo hydrogen storage alloys were investigated using the first principles method, based on the pseudopotential plane wave method. The adsorption energy, lattice constant, density of states, and charge density difference of the compounds before and after doping were calculated. Then, surface adsorption models of the ZrCo and Zr0.8Ti0. 2Co alloys were established with the assistance of a conventional model. The resulting adsorption energy values of the clean surface and the surface adsorption energy values in the presence of CO impurity gases manifested that the Ti element-doped Zr0.8Ti0. 2Co alloy was more susceptible to CO gas poisoning compared to ZrCo, which was consistent with the existing experimental results. In addition, by analyzing the conventional model, the electrons from the doped atoms overlapped with the surrounding electrons of C atoms, the phenomenon of orbital hybridization occurred, and the interactions increased. Consequently, Ti doping was not conducive to ZrCo to improve the ability to resist CO poisoning. The research results of this paper have laid a good foundation for the study of the effect of Ti doping on the antitoxicity performance.
Data-Driven Leading Vehicle Speed Forecast and Its Application to Ecological Predictive Cruise Control

In this article, we propose an ecological predictive cruise control method for connected and automated vehicles (CAVs) using data-driven predicted leading vehicle speed in a car-following scenario. Many existing studies assume that the leading vehicle's behavior is known when planning the trajectory of the ego vehicle. Unfortunately, predicting the future behavior of adjacent vehicles is extremely uncertain and inaccurate for use in control. To overcome this, we adopt the vector autoregressive model (VAR) that is well suited for generating simultaneous forecasts of the response variables when predicting the short-term behavior of the vehicle ahead. As many human drivers behave similarly in a car-following situation, vehicle connectivity is specifically used to drop hints of the behaviors of the cars following the connected car. Once the leading vehicle's future trajectory is predicted, the ego vehicle is controlled in a way that minimizes energy consumption by optimizing its speed trajectory while remaining safe. Through simulation case studies, we demonstrate that our approach can achieve improved energy efficiency considerably than the conventional strategy that cannot predict the speed of vehicles ahead. Given the recent market penetration of vehicle connectivity technologies and advanced driving assistance systems (ADAS), the proposed method is expected to have a high commercialization potential.
Mitigation of MAFLD in High Fat-High Sucrose-Fructose Fed Mice by a Combination of Genistein Consumption and Exercise Training

Purpose Metabolic dysfunction-associated fatty liver disease (MAFLD) is fueled by escalations in both sedentary behavior and caloric intake and is noted in obese type 2 diabetic (T2DM) patients. This study aimed to examine the effects of exercise and the phytoestrogen genistein in mice fed a high fat (60% fat) high sugar (55% fructose with 45% sucrose), HFHS diet. Methods Male C57BL/6J mice were assigned to five groups: HFHS, HFHS with genistein (600 mg/kg diet, HFHS+Gen), HFHS with moderate exercise (HFHS+Ex), and HFHS with combined genistein and moderate exercise (HFHS-Gen+Ex). Control lean mice were fed standard chow and water. Exercise consisted of 30-minute sessions of treadmill running five days/week for the 12-week study duration. Body weight was assessed weekly. Liver, kidney, fecal pellets and serum were extracted at the end of the study and maintained at −80°C. Results After 12 weeks of treatment, mice in the HFHS group had the highest hepatic lipid content. Plasma levels of glucose, insulin, leptin, cholesterol, amylin, and total fat content were significantly elevated in HFHS mice compared to control mice. HFHS feeding increased protein expression of carnitine palmitoyltransferase 1b (CPT-1b isoform) in gastrocnemius, CPT1a, glucose transporter protein 2 (GLUT2), glucocorticoid receptor (GR), and fructose 1,6-bisphosphate 1 (FBP1) expression in liver. Exercise alone had minor effects on these metabolic abnormalities. Genistein alone resulted in improvements in body weight, fat content, amylin, insulin sensitivity, and liver histopathology, GR, FBP1, and acetyl-CoA carboxylase 1 (ACC1). Combination treatment resulted in additional metabolic improvements, including reductions in hepatic lipid content and lipid area, alanine transferase activity, CPT1b, and CPT1a. Conclusion Our results indicate that a HFHS diet is obesogenic, inducing metabolic perturbations consistent with T2DM and MAFLD. Genistein alone and genistein combined with moderate intensity exercise were effective in reducing MAFLD and the aberrations induced by chronic HFHS feeding.