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The transverse momentum distribution of charged particles formed in Au–Au collisions at Beam Energy Scan (BES) ( S N N = 7. 7 , 1 1. 5 , 1 9. 6 , 2 7 , 3 9 GeV) is investigated. In addition, P T spectra of Λ particle at S N N = 6 2. 4 GeV were examined. Tsallis distribution is used to extract the temperature, volume and the entropic index from the experimental results at mid-rapidity and zero chemical potential. We measure some particle ratios like k + π + and Λ π − which are puzzling horn in the experiment and in the thermal model. We conclude that the horn vanished when we used Tsallis distribution, but this does not confirm a solution to the puzzle, which is primarily visible in the experimental results. [ABSTRACT FROM AUTHOR]

Transverse momentum spectra of different types of identified charged particles in central Gold–Gold (Au–Au) collisions and inelastic (INEL) or nonsingle diffractive (NSD) proton–proton (pp) collisions at the Relativistic Heavy Ion Collider (RHIC), as well as in central and peripheral Lead–Lead (Pb–Pb) collisions, and INEL or NSD pp collisions at the Large Hadron Collider (LHC) are analyzed by the blast-wave model with Tsallis statistics. The model results are approximately in agreement with the experimental data measured by STAR, PHENIX and ALICE Collaborations in special transverse momentum ranges. Kinetic freeze-out (KFO) temperature and transverse flow velocity are extracted from the transverse momentum spectra of the particles. It is shown that KFO temperature of the emission source depends on mass of the particles, which reveals the mass-dependent KFO scenario in collisions at RHIC and LHC. Furthermore, the KFO temperature and transverse flow velocity in central nucleus–nucleus (AA) collisions are larger than in peripheral collisions, and both of them are slightly larger in peripheral nucleus–nucleus collisions or almost equivalent to that in proton–proton collisions at the same center-of-mass energy which shows their similar thermodynamic nature. [ABSTRACT FROM AUTHOR]

Purpose of Review: Molecular drivers are increasingly identified as therapeutic targets for non-small cell lung cancer (NSCLC). This review focuses on the role of ROS1 inhibitors in treating relapsed/metastatic ROS-1 altered (ROS1+) NSCLC. Recent Findings: Four FDA-approved drugs have significant activity against ROS1+ NSCLC: crizotinib, ciritinib, lorlatinib, and entrectinib. Each drug yields an overall response rates exceeding 60% with ciritinib, lorlatinib, and entrectinib possessing intracranial activity. The drugs have manageable toxicity profiles. Summary: ROS1 alterations are rare molecular drivers of NSCLC that can be effectively treated with a variety of ROS1-targetd drugs. New agents are being identified that may treat resistance mutations. [ABSTRACT FROM AUTHOR]

N-substituted-1-phenyl-5,6-dimethyl-1,5-dihydro-4H-pyrazolo [4,3-d]pyrimidine has been synthesized by 1-phenyl-5-amino-4,5-dihydro-1H-pyrazole-4-carbox-amide derivatives as novel series were reacted with ester ethylacetate and aromtised as the pyrimidine ring the carbonyl functional group of the molecules were further halogenated by chlorination with phosphorous oxy chloride and yielded 1-phenyl-4-chloro-5,6-dimethyl-4,5-dihydro-1H-pyrazolo[4,3-d]pyrimidine: which further aminated with alkyl and aromatic amines are substituted chlorines. Compounds prepared were diluted to a concentration 50µL and other dilutions were prepared in 96well plates in triplicate and final volume made up to 100µL using DMSO solvent. 50-100µL of tris-base solution with pH10.5 were added to all wells and shaked in an equipment for shaking called orbital shaker and incubated for a duration of 10 min to stabilise the dye bounded to a protein. Absorbance has been measured at 510nm at a micro plate to obtain observations. Cell % growth = Absorbance sample/Absorbance negative control X 100 % Growth inhibition = 100 - % Cell growth. [ABSTRACT FROM AUTHOR]

Kindergarten has the potential to influence children's food choices and habits at an early age and prevent nutrition-related diseases later in life. This paper comparatively analyzed the goals and requirements for kindergarten food and meal policies and guidelines in Norway and China based on the author's self-constructed 'NES' analytical framework, including nutritional, educational, and social aspects. The findings suggest that while Norway and China both acknowledge the importance of nutritional importance of food and meals in kindergartens, Norway has paid significant attention to the social aspects of meals. There were also a number of differences between Norway and China in terms of specific educational goals related to food and meals. This analysis aimed to inform future policy direction across the fields of public health and educational policy and practice in Norway, China, and beyond. [ABSTRACT FROM AUTHOR]

Toll-like receptor (TLR) agonists have received considerable attention as therapeutic targets for cancer immunotherapy owing to their ability to convert immunosuppressive tumor microenvironments towards a more T-cell inflamed phenotype. However, TLRs differ in their cell expression profiles and intracellular signaling pathways, raising the possibility that distinct TLRs differentially influence the tumor immune microenvironment. Using single-cell RNA-sequencing, we address this by comparing the tumor immune composition of B16F10 melanoma following treatment with agonists of TLR3, TLR7, and TLR9. Marked differences are observed between treatments, including decreased tumor-associated macrophages upon TLR7 agonist treatment. A biased type-1 interferon signature is elicited upon TLR3 agonist treatment as opposed to a type-2 interferon signature with TLR9 agonists. TLR3 stimulation was associated with increased macrophage antigen presentation gene expression and decreased expression of PD-L1 and the inhibitory receptors Pirb and Pilra on infiltrating monocytes. Furthermore, in contrast to TLR7 and TLR9 agonists, TLR3 stimulation ablated FoxP3 positive CD4 T cells and elicited a distinct CD8 T cell activation phenotype highlighting the potential for distinct synergies between TLR agonists and combination therapy agents. [ABSTRACT FROM AUTHOR]

Xinglou Chengqi (XLCQ) decoction, composed of three botanical drugs and one inorganic drug, is used in clinics during the treatment of acute stroke complicated with Tanre Fushi (TRFS) syndrome in China. However, its active ingredients and the molecular mechanism have not been clarified. So, we aimed to preliminarily characterize its chemical constituents and investigate its pharmacological mechanisms using an integrative pharmacology strategy, including component analysis, network prediction, and experimental verification. We employed UPLC-QTOF-MS/MS to describe the chemical profile of XLCQ, Integrative Pharmacology-based Network Computational Research Platform of Traditional Chinese Medicine (TCMIP v2.0, http://www.tcmip.cn/), to assist in identifying the chemical components and predict the putative molecular mechanism against acute stroke complicated with TRFS, and LPS-stimulated BV-2 cells to verify the anti-neuroinflammatory effects of luteolin, apigenin, and chrysoeriol. Altogether, 197 chemical compounds were identified or tentatively characterized in the water extraction of XLCQ, 22 of them were selected as the key active constituents that may improve the pathological state by regulating 27 corresponding targets that are mainly involved in inflammation/immune-related pathways, and furthermore, luteolin, apigenin, and chrysoeriol exhibited good anti-neuroinflammatory effects from both protein and mRNA levels. In summary, it is the first time to employ an integrative pharmacology strategy to delineate 22 constituents that may improve the pathological state of stroke with TRFS by regulating 27 corresponding targets, which may offer a highly efficient way to mine the scientific connotation of traditional Chinese medicine prescriptions. This study might be a supplement for the deficiency of the basic research of XLCQ. [ABSTRACT FROM AUTHOR]

Current conventional treatment strategies for glioblastoma (GBM) have limited efficacy due to the rapid development of resistance to temozolomide (TMZ). It is particularly urgent to develop novel therapeutic strategies that can overcome TMZ resistance and provide patients with better prognoses. Here, a TMZ-resistant GBM cell strain and a mouse model of TMZ resistance are established as valuable tools to explore novel therapeutic strategies against TMZ resistance. Experimentally, p38MAPK inhibitor reduces the accumulation of F4/80+/CD11b+ macrophages/microglia in glioma and prolongs the survivals of glioma-bearing mice. Glioma-associated macrophages/microglia have a significanct expression of PD-L1. p38MAPK inhibitor in combination with PD-L1 antibody can effectively prolongs the survivals of TMZ-resistant GBM-bearing hosts, and differentially reduces the accumulation of circulating monocytes-derived tumor-associated macrophages and PD-L1 abundances of resident glioma-associated microglia. This combination therapy could be a treatment option for patients at the recurrence or chronic TMZ maintenance stages. A clinical study to confirm the safety and effectiveness of this combination therapy is warranted. [ABSTRACT FROM AUTHOR]

As more veterans return home from active duty with injuries or retire with disabilities and seek to reintegrate into the community, adaptive sport programming is an important recreational opportunity. Specifically, improved quality of life, more fluid community reintegration, positive psychosocial outcomes, and overall improved health are all stated benefits of participation in adaptive sport programs for individuals with disabilities. This program engaged veterans or members of the armed forces with disabilities in a unique university-based adaptive soccer camp experience with three main goals in mind: (1) to expose the veterans to the adaptive soccer sports of CP/TBI soccer and blind soccer, (2) to provide U.S. Soccer grassroots coach certification, (3) and to identify talent for the U.S. Soccer Paralympic National Team. In addition to facilitating this experience for veterans, we evaluated the camp program based on three main research questions: (1) How do injured military veterans and professionals serving veterans with disabilities evaluate satisfaction in an importance by performance analysis? (2) To what extent is a university-based VA Adaptive Sport Camp a promising setting for learning soccer related skills? and (3) What do injured military veterans and professionals serving veterans with disabilities identify as barriers to participation? Evaluation findings indicated that veterans wanted more information about coaching, the students, and additional community opportunities and were not concerned about the accommodations or food choices at camp, further highlighting the importance of the adaptive sport nature of the program itself. Veterans identified several camp elements that worked well in a university-based setting such as student interaction, scheduling, and balance between being a participant and learning coaching skills and would encourage other colleagues to attend in the future. Finally, participants identified perceived barriers to future participation were based largely on travel distance and costs. Subsequently, the programmers have sought to provide more programs around the country with partner agencies and in so doing, reduce travel time and costs. Overall, this programming model has significant promise for growth and has already provided results consistent with positive community reintegration and increased veteran participation in soccer-related activities, which can pave the pathway for more in-depth program analysis. [ABSTRACT FROM AUTHOR]

As one of the current global health conundrums, COVID-19 pandemic caused a dramatic increase of cases exceeding 79 million and 1.7 million deaths worldwide. Severe presentation of COVID-19 is characterized by cytokine storm and chronic inflammation resulting in multi-organ dysfunction. Currently, it is unclear whether extrapulmonary tissues contribute to the cytokine storm mediated-disease exacerbation. In this study, we applied systems immunology analysis to investigate the immunomodulatory effects of SARS-CoV-2 infection in lung, liver, kidney, and heart tissues and the potential contribution of these tissues to cytokines production. Notably, genes associated with neutrophil-mediated immune response (e.g. CXCL1) were particularly upregulated in lung, whereas genes associated with eosinophil-mediated immune response (e.g. CCL11) were particularly upregulated in heart tissue. In contrast, immune responses mediated by monocytes, dendritic cells, T-cells and B-cells were almost similarly dysregulated in all tissue types. Focused analysis of 14 cytokines classically upregulated in COVID-19 patients revealed that only some of these cytokines are dysregulated in lung tissue, whereas the other cytokines are upregulated in extrapulmonary tissues (e.g. IL6 and IL2RA). Investigations of potential mechanisms by which SARS-CoV-2 modulates the immune response and cytokine production revealed a marked dysregulation of NF-κB signaling particularly CBM complex and the NF-κB inhibitor BCL3. Moreover, overexpression of mucin family genes (e.g. MUC3A, MUC4, MUC5B, MUC16, and MUC17) and HSP90AB1 suggest that the exacerbated inflammation activated pulmonary and extrapulmonary tissues remodeling. In addition, we identified multiple sets of immune response associated genes upregulated in a tissue-specific manner (DCLRE1C, CHI3L1, and PARP14 in lung; APOA4, NFASC, WIPF3, and CD34 in liver; LILRA5, ISG20, S100A12, and HLX in kidney; and ASS1 and PTPN1 in heart). Altogether, these findings suggest that the cytokines storm triggered by SARS-CoV-2 infection is potentially the result of dysregulated cytokine production by inflamed pulmonary and extrapulmonary (e.g. liver, kidney, and heart) tissues. [ABSTRACT FROM AUTHOR]

The animal immune system mediates host-microbe interactions from the host perspective. Pattern recognition receptors (PRRs) and the downstream signaling cascades they induce are a central part of animal innate immunity. These molecular immune mechanisms are still not fully understood, particularly in terms of baseline immunity vs induced specific responses regulated upon microbial signals. Early-divergent phyla like sponges (Porifera) can help to identify the evolutionarily conserved mechanisms of immune signaling. We characterized both the expressed immune gene repertoire and the induced response to lipopolysaccharides (LPS) in Halichondria panicea , a promising model for sponge symbioses. We exposed sponges under controlled experimental conditions to bacterial LPS and performed RNA-seq on samples taken 1h and 6h after exposure. H. panicea possesses a diverse array of putative PRRs. While part of those PRRs was constitutively expressed in all analyzed sponges, the majority was expressed individual-specific and regardless of LPS treatment or timepoint. The induced immune response by LPS involved differential regulation of genes related to signaling and recognition, more specifically GTPases and post-translational regulation mechanisms like ubiquitination and phosphorylation. We have discovered individuality in both the immune receptor repertoire and the response to LPS, which may translate into holobiont fitness and susceptibility to stress. The three different layers of immune gene control observed in this study, - namely constitutive expression, individual-specific expression, and induced genes -, draw a complex picture of the innate immune gene regulation in H. panicea. Most likely this reflects synergistic interactions among the different components of immunity in their role to control and respond to a stable microbiome, seawater bacteria, and potential pathogens. [ABSTRACT FROM AUTHOR]

Solar‐driven photocatalysis has been developing as a sustainable process and it holds appreciable promise to address the pollutants and risks posed by biohazards. The unique geometrical and electric features of 2D semiconductors have nurtured a variety of advanced photocatalytic bactericides where oxidative oxygen species are generated as the main disinfection reagents. Herein, the state‐of‐the‐art progress of solar‐driven photocatalytic disinfection based on 2D semiconductors with an emphasis on the generation and effects of various reactive oxygen species is summarized. Moreover, the immobility of the photocatalyst for practical applications is discussed. Finally, perspectives and challenges are presented to guide future research on photocatalytic disinfection. [ABSTRACT FROM AUTHOR]

In our research on the quality of ECEC settings in France, we were inspired by the 'Mosaic approach' developed by Clark and Moss to take into account the viewpoint of the children aged 2–3 years, who are welcomed in this study through the 'voice' of photography. The aim of this article is to analyse the results of the children's practices of photography, rather than the content of their photographic images. The range and diversity of children's ways of handling the camera, of how they frame their images and their roles as photographer are all analysed in as much depth as any cultural learning taking place. Through these means, this article demonstrates how to apply critical reflexivity to the methodology used for researching both on and with the children. It explains in conclusion, how our study sheds light on the challenges relating to the definition of quality in ECEC settings. [ABSTRACT FROM AUTHOR]

Summary: Sickle cell disease is a multisystem disease characterised by chronic haemolytic anaemia, painful vaso‐occlusive crises and acute and chronic end‐organ damage. It is one of the most common serious inherited single gene conditions worldwide and has a major impact on the health of affected individuals. Peri‐operative complications are higher in patients with sickle cell disease compared with the general population and may be sickle or non‐sickle‐related. Complications may be reduced by meticulous peri‐operative care and transfusion, but unnecessary transfusion should be avoided, particularly to reduce the risk of allo‐immunisation. Planned surgery and anaesthesia for patients with sickle cell disease should ideally be undertaken in centres with experience in caring for these patients. In an emergency, advice should be sought from specialists with experience in sickle cell disease through the haemoglobinopathy network arrangements. Emerging data suggest that patients with sickle cell disease are at increased risk of COVID‐19 infection but may have a relatively mild clinical course. Outcomes are determined by pre‐existing comorbidities, as for the general population. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has resulted in unprecedented consequences. Transdiagnostic factors, such as anxiety sensitivity, could be an important component to understand how individuals experience COVID-19 specific fear, depression and anxiety. A US representative sample (5,023) completed measures including the Anxiety Sensitivity Index-3, the Fear of COVID-19 Scale, the Generalized Anxiety Disorder-7 and the Patient Health Questionnaire-8. Analyses controlled for age, sex, race, marital status, education level, working status, household income, and COVID-19 exposure. Results were consistent with prediction. First, higher ASI-3 Total scores were associated with above average COVID-19 fear (β = 0.19). Second, the ASI-3 physical concerns subscale was the strongest predictor of COVID-19 fear; one SD increase on the ASI-3 physical concerns subscale was associated with almost a twofold risk of reaching above average levels of COVID-19 (OR = 1.93). Third, higher ASI-3 Total scores were associated with higher anxiety (β = 0.22) and depression (β = 0.20). Finally, COVID-19 fear mediated the relationship between ASI-3 Total scores and anxiety (17% of effect mediated) as well as ASI-3 Total scores and depression (16% of effect mediated). These data support the role of anxiety sensitivity in predicting fear of COVID-19 and resulting mental health. [ABSTRACT FROM AUTHOR]

Introduction: The pathogenesis of basal cell carcinoma (BCC) is multifactorial and not fully elucidated. Previous studies showed that behaviour of the tumour may be influenced by the immune system and identified CD4*CD25*Foxp3* regulatory T cells (Tregs) as dominant immune cells in BCC microenvironment. The function and development of Tregs is regulated by FOXP3, encoding transcription factor Forkhead box P3. FOXP3 regulates transcription of many genes, including up-regulation of cytotoxic lymphocyte-associated antigen-4 gene (CTLA-4). Expressed on Tregs, CTLA-4 interacts with antigen-presenting cells to inhibit T-cell activation. Aim: To investigate the role of two polymorphisms (rs3761548 and rs2232365) of FOXP3 and CTLA-4 polymorphism (rs5742909) in BCC patients from northern Poland. Material and methods: We analysed 280 unrelated patients with BCC of mean age 70.93 ±11.53 (70.54 ±12.55 women, 71.38 ±10.26 men) and 200 healthy, unrelated age- and sex-matched volunteers. Results: The differences in the occurence of BCC between genotypes and alleies of the analysed polymorphisms were not statistically significant. In the studied group, the presence of the CC genotype in CTLA-4 rs5742909 polymorphism was statistically more frequent in patients with multiple BCCs. Conclusions: It seems that the analysed FOXP3 and CTLA-4 polymorphisms do not influence the BCC susceptibility. CTLA-4 rs5742909 polymorphism may influence the susceptibility to multiple BCCs. [ABSTRACT FROM AUTHOR]

The purpose of this study was to investigate the Bcl2, P53 and apoptosis changes against skin cancer in experimental animals. Skin cancer is the most common form of human cancer. It is estimated that over 1 million new cases occur annually. The annual rates of all forms of skin cancer are increasing each year, representing a growing public concern. It has also been estimated that nearly half of all Americans who live to age 65 are likely to develop skin cancer at least once. Skin cancer was induced in rats by Di Methyl Benz (a) Anthracene at the dosage of DMBA (5 µg) per animal, three times a week for 28 weeks after conformation of skin cancer treated with Paclitaxel and Di allyl sulfide for 30 days. The levels of Bcl2 gene expression were significantly decreased and P53gene expression were markedly increased in Paclitaxel and Di allyl sulfide treated animals when compared with cancer bearing animals. The treatment with combination of Paclitaxel and Di allyl sulfide effectively reduced Bcl2 protein expression and also increased P53gene expression. Moreover, the levels of Bcl2 and P53 a good indicators of restoring the skin architecture, were also reversed in skin damage subjects after treatment with the herbal compounds preparation. So, from the obtained results it is concluded that a combination of Paclitaxel and Di allyl sulfide is capable of restoring the skin architecture and can also increase the apoptosis activities in skin cancer rats. [ABSTRACT FROM AUTHOR]

We demonstrated that molybdenum disulfide (MoS2) nanosheets can be an excellent solar disinfection agent for multi-drug resistant (MDR) bacteria with disinfection efficiencies >99.9999% in only 30 min. Distinct from other reactive oxygen species (ROS)-dependent photocatalysts, both ROS generation and size decrease contributed to the high antibacterial efficiencies of MoS2. [ABSTRACT FROM AUTHOR]

Dyestuff substances in textile wastewaters are harmful pollutants which pose serious disposal challenges. A solar photocatalytic treatment combining degradation of structurally diverse dyes (Rhodamine B, Reactive Orange 16 or Auramine O) and energetic valorisation by H2 production on systematically varied M/TiO2 (M=Au, Ag, Cu or Pt) is herein explored. Bleaching was efficient in all cases, and especially rapid for azo (>98 % after 2 h) as compared to poly‐heterocyclic chromophores. Interestingly, dye degradation rates were similar to literature results under aerobic conditions, whereby no energy recovery is possible. Due to the recalcitrant dye structures, H2 production becomes markedly sensitive to metal co‐catalyst chemistry and morphology. The occurrence of active metallic, i. e. M(0), surfaces in sufficiently large nanoparticles are key to ensurie initial H2 evolution. An increase in Au domain sizes from 101 up to 102 nm ranges resulted in 10‐fold site‐specific catalytic activity (TOF) enhancement, whereas growth of Pt nanoparticles well above the sub‐nanometric regime was essential for efficient H2 production. In quest of using affordable metallic elements, bleaching and sustained H2 evolution was proven after prolonged irradiation using Cu/TiO2, owing to the in situ reduction of the copper co‐catalyst. In summary, anaerobic photoreforming can be as efficient as the more common aerobic approach, also allowing energy recovery in the form of waste‐derived hydrogen. [ABSTRACT FROM AUTHOR]

aim,1 Ali Alahmari,1 Abdullah Aljarallah,1 Muhammad Affan Elahi,5 Hana MA Fakhoury51College of Medicine, King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), Riyadh, Saudi Arabia; 2King Abdullah International Medical Research Center (KAIMRC), Riyadh, Saudi Arabia; 3Department of Medicine, Ministry of National Guard Health Affairs (MNG-HA), Riyadh, Saudi Arabia; 4College of Liberal Arts and Sciences, Hofstra University, Hempstead, NY, USA; 5Department of Biochemistry and Molecular Medicine, College of Medicine, Alfaisal University, Riyadh, Saudi ArabiaCorrespondence: Mohammed Al DubayeeCollege of Medicine, King Saud Bin Abdulaziz University for Health Sciences (KSAU-HS), P.O. Box 22490, Riyadh, Saudi ArabiaTel +966 11 801 1111 ext: 53551Email [email protected] Introduction: Insulin resistance in obesity and type 2 diabetes mellitus (T2DM) is associated with cardiovascular complications such as atherosclerosis. On the other hand, the reduction of apoptosis in macrophages has been linked with accelerated atherosclerosis. Apoptosis is controlled by a different family of proteins including Bcl-2 and caspases. Methods: To examine apoptosis in insulin resistance, we assessed the mRNA expression by qRT-PCR of several Bcl-2 family members, as well as caspase-3, − 7, − 8, and − 9 in peripheral blood mononuclear cells (PBMCs) isolated from lean, obese, diabetic, and diabetic on metformin individuals. Results: PBMCs of diabetic individuals exhibited reduced expression of caspase-7 and increased expression of Bcl-10, Bad, Bax, Bid, and caspase-3. T2DM on metformin group had significantly higher Bad, Bax, and caspase-7 expression. Discussion: The moderate up-regulation of pro-apoptotic Bcl-10, Bax, Bad, Bid, and the effector caspase-3 coupled with inhibition of caspase-7 in circulating PBMCs of T2DM could be the result of increased inflammation in T2DM. Metformin treatment significantly inhibited the expression of Bcl-10, Bid, and caspase-3 and upregulated Bad/Bax/caspase-7 pathway suggesting the activation of Bad/Bax/caspase-7 apoptotic pathway. Further studies are warranted to elicit the underlying apoptotic pathways of PBMCs in T2DM and following metformin treatment. [ABSTRACT FROM AUTHOR]

This paper presents how a contemporary lace practice explored the medium of animation as a digital tool for craft research. Research is practice based and theoretically framed around notions of smooth and striated space as a means to articulate how a designer engages in textile thinking to reimagine new expressions for (p)lace in a digital age. The author sought to test out if animation could capture and disseminate an ephemeral lace process. This led to a curious convergence between two disciplines. What was initially to be a tool for efficiency and speed unexpectedly turned out to be a method for abstracting an allusive lace making process. Learning about the idiosyncrasies of another discipline opened new aesthetic opportunities for a contemporary lace practice and introduced novel methods to disseminate future material research. [ABSTRACT FROM AUTHOR]

We search for metal-rich Sausage-kinematic (MRSK) stars with [Fe/H] > −0.8 and −100 < Vφ < 50 km/s in LAMOST DR5 in order to investigate the influence of the Gaia-Sausage-Enceladus (GSE) merger event on the Galactic disk. For the first time, we find a group of low-α MRSK stars, and classify it as a metal-rich tail of the GSE galaxy based on the chemical and kinematical properties. This group has slightly larger Rapo, Zmax and Etot distributions than a previously-reported high-α group. Its low-α ratio does not allow for an origin resulting from the splash process of the GSE merger event, as is proposed to explain the high-α group. A hydrodynamical simulation by Amarante et al. provides a promising solution, in which the GSE galaxy is a clumpy Milky-Way analogue that develops a bimodal disk chemistry. This scenario explains the existence of MRSK stars with both high-α and low-α ratios found in this work. It is further supported by another new feature that a clump of MRSK stars is located at Zmax=3−5 kpc, which corresponds to the widely adopted disk-halo transition at ∣Z∣ ∼ 4 kpc. We suggest that a pile-up of MRSK stars at Zmax contributes significantly to this disk-halo transition, an interesting imprint left by the GSE merger event. These results also provide an important implication on the connection between the GSE and the Virgo Radial Merger. [ABSTRACT FROM AUTHOR]

The indentation problem of a flat circular punch with uniform heat flux distributed at its base, pressed into a semi-infinite transversely isotropic magneto-electro-thermo-elastic space is investigated. The closed-form solution in the full space is obtained by potential theory method. In addition, the factors of indentation stiffness that relates mechanical force, electric charge, magnetic induction with the heat flux are presented. The obtained solution can be degenerated for the corresponding problems of thermopiezoelectric, thermomagnetoelastic, and thermoelastic materials and can also be superposed to construct the solution to the corresponding indentation problems with coupled thermal, electric, magnetic, mechanical effects. In addition, the solution presented in this article can not only help to investigate mechanisms of the image formation in the area of nanoscience and nanotechnology, but also can serve as benchmarks for future numerical studies of multiphase composites. [ABSTRACT FROM AUTHOR]

Formal ethical issues for conducting research are highlighted in national and international guidelines. Even if such strategies are grounded in democratic and rights-based values, their implementation may produce challenges. This article foregrounds dilemmas that were derived from fieldwork conducted in preschool settings with children aged one to five years. These settings are viewed as sensitive environments that demand awareness adjusted to a specific context. Through the use of empirical illustrations, children's voices concerning their participation within a research project and their opportunities to give consent or withdraw are discussed. [ABSTRACT FROM AUTHOR]

Ovarian cancer is the leading cause of death among gynecological neoplasms, with an estimated 14,000 deaths in 2019. First-line treatment options center around a taxane and platinum-based chemotherapy regimen. However, many patients often have recurrence due to late stage diagnoses and acquired chemo-resistance. Recent approvals for bevacizumab and poly (ADP-ribose) polymerase inhibitors have improved treatment options but effective treatments are still limited in the recurrent setting. Immunotherapy has seen significant success in hematological and solid malignancies. However, effectiveness has been limited in ovarian cancer. This may be due to a highly immunosuppressive tumor microenvironment and a lack of tumor-specific antigens. Certain immune cell subsets, such as regulatory T cells and tumor-associated macrophages, have been implicated in ovarian cancer. Consequently, therapies augmenting the immune response, such as immune checkpoint inhibitors and dendritic cell vaccines, may be unable to properly enact their effector functions. A better understanding of the various interactions among immune cell subsets in the peritoneal microenvironment is necessary to develop efficacious therapies. This review will discuss various cell subsets in the ovarian tumor microenvironment, current immunotherapy modalities to target or augment these immune subsets, and treatment challenges. [ABSTRACT FROM AUTHOR]

Ever since the publication of the seminal paper by Lynn Margulis in 1967 proposing the theory of the endosymbiotic origin of organelles, the study of the symbiotic relationships between unicellular eukaryotes and prokaryotes has received ever-growing attention by microbiologists and evolutionists alike. While the evolutionary significance of the endosymbiotic associations within protists has emerged and is intensively studied, the impact of these relationships on human health has been seldom taken into account. Microbial endosymbioses involving human eukaryotic pathogens are not common, and the sexually transmitted obligate parasite Trichomonas vaginalis and the free-living opportunistic pathogen Acanthamoeba represent two unique cases in this regard, to date. The reasons of this peculiarity for T. vaginalis and Acanthamoeba may be due to their lifestyles, characterized by bacteria-rich environments. However, this characteristic does not fully explain the reason why no bacterial endosymbiont has yet been detected in unicellular eukaryotic human pathogens other than in T. vaginalis and Acanthamoeba , albeit sparse and poorly investigated examples of morphological identification of bacteria-like microorganisms associated with Giardia and Entamoeba were reported in the past. In this review article we will present the body of experimental evidences revealing the profound effects of these examples of protist/bacteria symbiosis on the pathogenesis of the microbial species involved, and ultimately their impact on human health. [ABSTRACT FROM AUTHOR]

Ethanoanthracene cycloadducts (5–7) anti, (5–7) syn, and (5–7) dec have been synthesized from the Diels–Alder (DA) reaction of diene 1,8-dichloroanthracene 2, with the dienophiles; acrylonitrile 3, 1-cynavinyl acetate 4, and phenyl vinyl sulfone 5, individually. The steric effect of dienophile substituents were more favorable toward the anti-isomer formation as deduced from 1H-NMR spectrum. The cheminformatics prediction for (5–7) anti and (5–7) syn was investigated. The in silico anticipated anti-depression activity of the (5–7) anti and (5–7) syn compounds were investigated and compared to maprotiline 9 as reference anti-depressant drug. The study showed that steric interactions play a crucial role in the binding affinity of these compounds to the representative models; 4xnx, 2QJU, and 3GWU. The pharmacokinetic and drug-like properties of (5–7) anti and (5–7) syn exhibited that these compounds could be represented as potential candidates for further development into antidepressant-like agents. [ABSTRACT FROM AUTHOR]

Background: Approximately one third of type 2 diabetes mellitus (T2DM) cases present with diabetic nephropathy (DN), the leading cause of end-stage renal disease. Inflammation plays an important role in T2DM disease and DN pathogenesis. NLRP3 inflammasomes are complexes that regulate interleukin-1B (IL-1B) and IL-18 secretion, both involved in inflammatory responses. Activation of NLRP3 is associated with DN onset and progression. Here, we explore whether DN is associated with variants in genes encoding key members of the NLRP3 inflammasome pathway. Methods: Using genome-wide association data, we performed a pilot case-control association study, between 101 DN-T2DM and 185 non-DN-T2DM cases from the Hellenic population across six NLRP3 inflammasome pathway genes. Results: Three common CARD8 variants confer decreased risk for DN, namely rs11665831 (OR = 0.62, p = 0.016), rs11083925 (OR = 0.65, p = 0.021), and rs2043211 (OR = 0.66, p = 0.026), independent of sex or co-inheritance with an IL-1B variant. Conclusion: CARD8 acts as an NLRP3, NF-κB and caspase-1 inhibitor; perhaps, alterations in the cross-talk between CARD8, NF-κB, and NLRP3, which could affect the pro-inflammatory environment in T2DM, render diabetic carriers of certain common CARD8 variants potentially less likely to develop T2DM-related pro-inflammatory responses followed by DN. These preliminary, yet novel, observations will require validation in larger cohorts from several ethnic groups. [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic has sparked a demand for safe and highly effective decontamination techniques for both personal protective equipment (PPE) and hospital and operating rooms. The gradual lifting of lockdown restrictions warrants the expansion of these measures into the outpatient arena. Ultraviolet C (UVC) radiation has well-known germicidal properties and is among the most frequently reported decontamination techniques used today. However, there is evidence that wavelengths beyond the traditional 254 nm UVC – namely far UVC (222 nm), ultraviolet B, ultraviolet A, visible light, and infrared radiation – have germicidal properties as well. This review will cover current literature regarding the germicidal effects of wavelengths ranging from UVC through the infrared waveband with an emphasis on their activity against viruses, and their potential applicability in the healthcare setting for general decontamination during an infectious outbreak. [ABSTRACT FROM AUTHOR]

Osteoarthritis (OA) is a progressive disease causing pain and reduced range of motion (ROM), decreasing function and activity participation. Physiotherapy interventions improve symptoms and quality of life. Goniometry is one method for measuring ROM. To conduct an integrative review investigating use of ROM for participants with knee OA following physiotherapy interventions in clinical trials, including reliability, validity and responsiveness of goniometry for measuring knee ROM. Forty-two articles fulfilled the inclusion criteria. Twenty-six studies used OA patient-reported outcome measures in addition to ROM. Twenty-eight studies reported their own psychometric data, with generally excellent inter- and intra-rater reliability. Nine reported good to excellent criterion validity. Four studies reported limited and variable data on responsiveness. Knee ROM is commonly used as an outcome measure in clinical trials of people with knee OA. Goniometry is a reliable and valid way to measure knee ROM, and is a convenient, accessible outcome measure for clinical trials and physiotherapy practice. We suggest combining patient-reported outcome measures with goniometry may provide a more holistic view of the person's wellbeing, function, and participation. Further research is needed to gain a broader understanding of the validity, and responsiveness specifically for people with knee OA. [ABSTRACT FROM AUTHOR]

Oncogenic gene fusions have been reported in diffuse gliomas and may serve as potential therapeutic targets. Here, using next-generation sequencing analysis (Illumina TruSight Tumor 170 panel), we analyzed a total of 356 diffuse gliomas collected from 2017 to 2019 to evaluate clinical, pathological, and genetic features of gene fusion. We found 53 cases of glioblastomas harboring the following oncogenic gene fusions: MET (n = 18), EGFR (n = 14), FGFR (n = 12), NTRK (n = 5), RET (n = 2), AKT3 (n = 1), and PDGFRA fusions (n = 1). Gene fusions were consistently observed in both IDH-wildtype and IDH-mutant glioblastomas (8.8% and 9.4%, p = 1.000). PTPRZ1–MET fusion was the only fusion that genetically resembled secondary glioblastomas (i.e., high frequency of IDH mutation, ATRX loss, TP53 mutation, and absence of EGFR amplification), whereas other gene fusion types were similar to primary glioblastomas (i.e., high frequency of IDH-wildtype, TERT mutation, EGFR amplification, and PTEN mutation). In IDH-wildtype glioblastoma patients, multivariable analysis revealed that the PTPRZ1–MET fusion was associated with poor progression-free survival (HR [95% CI]: 5.42 (1.72–17.05), p = 0.004). Additionally, we described two novel cases of CCDC6–RET fusion in glioma. Collectively, our findings indicate that targetable gene fusions are associated with aggressive biological behavior and can aid the clinical treatment strategy for glioma patients. [ABSTRACT FROM AUTHOR]

Why and under what conditions do a challenger's legitimation strategies shape decisions for institutional reform? I argue that legitimation strategies are critical in defining how institutional defenders evaluate the costs and benefits of institutional reform, and thus in shaping their reaction to a challenger's demands. Legitimation strategies do so through principled persuasion, where defenders come to believe that accepting a challenger's demands will have both material and symbolic benefits, and rhetorical coercion, where defenders accept change out of fear that they will bear costs by undercutting their own legitimacy. Not all challengers effectively legitimate their demands, however. A challenger's capacity to affect change depends on its position within institutions, which gives it the authority to effectively deploy rhetoric. I demonstrate this argument with a brief case of Japan's challenge to the unequal treaty system in the late 19th century. China's participation in the international order has increased its ability to challenge the status quo. It is precisely because China became increasingly embedded in institutional resources over time that it has proven capable of legitimating demands for reform: the resources of the WTO, IMF, and UNSC not only constrain, but enable, China's ambitions. China's membership in institutions inside the liberal order has given that state increasing authority to pursue far‐reaching challenges through rhetorical challenges. [ABSTRACT FROM AUTHOR]

One of the leading factors of seepage contamination is mine drainage, which creates serious ecological risks on the environment both during operation and post-mining times. In this study, experimental processes have been carried out to determine the occurrence of mine drainage in the Gümüşköy (Kütahya) mineralization area (Northwest Turkey). The prevention method for potential mine drainage occurrence has been also discussed. High enrichment was observed which are directly related to mineralization in trace element concentrations, especially in potentially toxic metals such as Ag, Cd, Mo, Ba, Bi, and Zn. Based on short-term tests, mine drainage formation has not been expected according to the pH (7.36–9.38), contact leaching, and acid-base accounting studies. However, in the long-term, acid generation potential has been expected because of weathering and oxidation in terms of rock type and mineralization in the area. Therefore, in order to prevent groundwater contamination in the event of a possible formation of mine drainage, the hydraulic conductivity of the stock area bedrock was evaluated by the in situ tests performed in the field and it was found to be moderately permeable (K= 1.9 × 10−6 m/s). In order to make the stock area bedrock impermeable, natural clay will be laid and compressed at the base of the stock area. When the finite elements were modeled by seepage analysis, the seepage discharge to be formed on the base rock at a depth of 5 m was determined as 3.17 × 10−19 m3/s. Since the discharge value determined in the seepage analysis after modeling is very close to zero, contamination of possible ground and surface water will be prevented. [ABSTRACT FROM AUTHOR]

We perform an extensive review of the numerous studies and methods used to determine the total mass of the Milky Way. We group the various studies into seven broad classes according to their modeling approaches. The classes include: i) estimating Galactic escape velocity using high velocity objects; ii) measuring the rotation curve through terminal and circular velocities; iii) modeling halo stars, globular clusters and satellite galaxies with the spherical Jeans equation and iv) with phase-space distribution functions; v) simulating and modeling the dynamics of stellar streams and their progenitors; vi) modeling the motion of the Milky Way, M31 and other distant satellites under the framework of Local Group timing argument; and vii) measurements made by linking the brightest Galactic satellites to their counterparts in simulations. For each class of methods, we introduce their theoretical and observational background, the method itself, the sample of available tracer objects, model assumptions, uncertainties, limits and the corresponding measurements that have been achieved in the past. Both the measured total masses within the radial range probed by tracer objects and the extrapolated virial masses are discussed and quoted. We also discuss the role of modern numerical simulations in terms of helping to validate model assumptions, understanding systematic uncertainties and calibrating the measurements. While measurements in the last two decades show a factor of two scatters, recent measurements using Gaia DR2 data are approaching a higher precision. We end with a detailed discussion of future developments in the field, especially as the size and quality of the observational data will increase tremendously with current and future surveys. In such cases, the systematic uncertainties will be dominant and thus will necessitate a much more rigorous testing and characterization of the various mass determination methods. [ABSTRACT FROM AUTHOR]

The Israeli occupation has had a considerable negative impact on the lives of Palestinians, such that achieving an effective, equitable, quality education for all children is far from being realised. Palestinian children are not only adversely affected by the occupation, but also by an educational system that fails fully and systematically to accord them their rights. Using rights-based participatory methods informed by human rights protocols, we explored the experiences of children with disabilities' inclusion in schools. Our findings show that there is continuing failure to understand or implement the provisions of the UNCRC or UNCRPD, and that these children are systematically excluded or marginalised from education. We suggest that children's rights to educational inclusion can be achieved by means of a whole system, whole educational and whole person approach, along with a consideration of a rights-based policy framework. [ABSTRACT FROM AUTHOR]

In this study, geochemical analyses, as well as short-term contact leaching and acid-base accounting tests, were carried out to determine the occurrence of acid mine drainage (AMD) by static tests in the ore stockpile areas at the Mutki Cu-Fe-Cr deposit (Bitlis, SE Turkey). According to the short-term contact leaching tests, the high enrichment in trace element concentrations in ore-bearing samples, especially in potentially toxic metals such as Cr, Cu, Mn, and Zn, were directly related to sulphide and oxide mineralizations. The pH (3.27-4.05) values of water samples, together with the classification of the intracontinental water resources, indicated that the water quality is the fourth class. Leaching tests, paste pH (3.42-4.46) and sulphide-sulphur (3.9-13.4 wt%) values also suggested that there was AMD production potential in the mineralization area. The AMD production potential was supported by the high mobility of several elements, such as Fe, Mg, Cr, As, Cu, S, and Zn. In ore samples, net neutralization potential (NNP) and net potential ratio (NPR) values were less than -20 kg CaCO³/t and 1, respectively. The basalts forming the basement rock of the stockpile area were characterized by permeable to slightly permeable properties that potentially increase the contamination risk of the groundwater due to seepage in the stockpile area. In order to prevent seepage in the stock area, geomembrane (synthetic waterproofing covers) should be laid at the base to ensure impermeability. The improvements planned in the stock area were modeled by the finite element method and seepage discharges at a depth of 5 m were determined as 1.34 × 10-17m³/s. Thanks to these planned applications, surface and groundwater pollution can be efficiently prevented. [ABSTRACT FROM AUTHOR]

Aim: Preclinical evidence suggests that oxidized macrophage migration inhibitory factor (oxMIF) may be involved in carcinogenesis. This phase 1 study (NCT01765790) assessed the safety, tolerability, pharmacokinetics and antitumour activity of imalumab, an oxMIF inhibitor, in patients with advanced cancer using '3 + 3' dose escalation. Methods: In Schedule 1, patients with solid tumours received doses from 1 to 50 mg/kg IV every 2 weeks. In Schedule 2, patients with metastatic colorectal adenocarcinoma, non‐small‐cell lung, or ovarian cancer received weekly doses of 10 or 25 mg/kg IV (1 cycle = 28 days). Treatment continued until disease progression, unacceptable toxicity, dose‐limiting toxicity, or withdrawal of consent. Results: Fifty of 68 enrolled patients received imalumab. The most common treatment‐related adverse events (TRAEs) included fatigue (10%) and vomiting (6%); four grade 3 serious TRAEs (two patients) occurred. The dose‐limiting toxicity was allergic alveolitis (one patient, 50 mg/kg every 2 weeks). The maximum tolerated and biologically active doses were 37.5 mg/kg every 2 weeks and 10 mg/kg weekly, respectively. Of 39 assessed patients, 13 had stable disease (≥4 months in 8 patients). Conclusions: Imalumab had a maximum tolerated dose of 37.5 mg/kg every 2 weeks in patients with advanced solid tumours, with a biologically active dose of 10 mg/kg weekly. Further investigation will help define the role of oxMIF as a cancer treatment target. [ABSTRACT FROM AUTHOR]

We define 17 African land mammal ages, or AFLMAs, covering the Cenozoic record of the Afro-arabian continent, the planet's second largest land mass. While fossiliferous deposits are absent on the eroded plateau of the continent's interior, almost 800 fossil genera from over 350 locations have now been identified in coastal deposits, karst caves, and in the Neogene rift valleys. Given a well-developed geochronologic framework, together with continuing revision to the fossil record—both stimulated by the story of human evolution in Africa—and also to compensate for the variation in fossil ecosystems across such great distances, the AFLMAs are biochronological units defined by type localities, and not biozones to be recognized by the occurrence of certain genera. Disparities are notable: Africa is the highest of all continents, but almost every Paleogene locality was formed at sea level; the fossil record of its great rainforest ecosystem remains virtually unknown; and the Paleogene fauna is relatively isolated, whereas the Neogene begins with open exchange with Laurasia following the Tauride collision, with a simultaneous opening of the East African rift valleys in which the newly revolutionized fauna is abundantly preserved. Notably, the continent-wide and comprehensive documentation of the African mammalian record reveals an unparalleled rate of transformation in the hominin lineage, unmatched by any other group, in response to the Neogene expansion of the open-country ecosystem. [ABSTRACT FROM AUTHOR]

Mycobacterium abscessus is a prevalent pathogenic mycobacterium in cystic fibrosis (CF) patients and one of the most highly drug resistant mycobacterial species to antimicrobial agents. It possesses the property to transition from a smooth (S) to a rough (R) morphotype, thereby influencing the host innate immune response. This transition from the S to the R morphotype takes place in patients with an exacerbation of the disease and a persistence of M. abscessus. We have previously shown that the exacerbation of the Toll-like receptor 2 (TLR2)-mediated inflammatory response, following this S to R transition, is essentially due to overproduction of bacilli cell envelope surface compounds, which we were able to extract by mechanical treatment and isolation by solvent partition in a fraction called interphase. Here, we set up a purification procedure guided by bioactivity to isolate a fraction from the R variant of M. abscessus cells which exhibits a high TLR2 stimulating activity, referred to as TLR2-enriched fraction (TLR2eF). As expected, TLR2eF was found to contain several lipoproteins and proteins known to be stimuli for TLR2. Vaccination with TLR2eF showed no protection toward an M. abscessus aerosol challenge, but provided mild protection in ΔF508 mice and their FVB littermates when intravenously challenged by M. abscessus. Interestingly however, antibodies against TLR2eF compounds were detected during disease in CF patients. In conclusion, we show the potential for compounds in TLR2eF as vaccine and diagnostic candidates, in order to enhance diagnosis, prevent and/or treat M. abscessus -related infections. [ABSTRACT FROM AUTHOR]

There is accumulating evidence indicating that microRNA (miR)-9-3p expression is abnormal in patients with glioma; however, the role of miR-9-3p in glioma remains unclear. In the present study, reverse transcription-quantitative PCR and immunohistochemical assays were conducted to assess miR-9-3p and forkhead box G1 (FOXG1) expression, respectively. A luciferase reporter assay was performed to confirm the target of miR-9-3p. Moreover, cell counting kit-8 and flow cytometry assays were used to assess proliferation and apoptosis, respectively. The present study demonstrated that miR-9-3p is significantly downregulated, and FOXG1 is significantly upregulated, in patients with glioma. miR-9-3p overexpression inhibited proliferation and increased the apoptosis of both U87MG and TG-905 cells. In addition, FOXG1 was identified as a direct target of miR-9-3p, and FOXG1 silencing enhanced the inhibitory effect of miR-9-3p on proliferation and apoptosis in U87 MG and TG-905 cells. In conclusion, the present results suggest that miR-9-3p may suppress malignant biological properties by targeting FOXG1. Thus, miR-9-3p may serve as a diagnostic target and novel prognostic marker in patients with glioma. [ABSTRACT FROM AUTHOR]

Despite ongoing disagreement about what kinds of evidence are most valuable to education, there continues to be an increasing push to make a narrow group of scientific methodologies the basis of educational policy and practice. This has created a growth in the use of randomised control trials (RCTs), which are considered an exemplary example of scientifically rigorous research design. Yet despite the increase in both the prevalence and status of RCTs, this article will argue that the ethics informing this research orientation remains underdeveloped, with the specific need for an agenda that grapples with assent in RCTs in both a philosophical and a methodological way. As a corrective to this, we engage with Biesta's observation of a lack of explicit engagement with the values informing our decisions about the direction of education practice. We begin by examining assent in existing education research literature, focusing on some of the ways that qualitative and praxis‐oriented researchers have grappled with the complexity of assent in research projects involving children and young people in schools. We then consider analogous debates concerning assent in fields such as bioethics and biomedicine, given the established nature of bioethics as a discipline. Finally, we turn our attention to developing an agenda that can work towards a consideration of assent in RCTs in education research, with the purpose of making transparent some of the ethical concerns that warrant attention in the design and conduct of RCT research studies in education. [ABSTRACT FROM AUTHOR]

Halide perovskites have remarkable properties for relatively crudely processed semiconductors, including large optical absorption coefficients and long charge carrier lifetimes. Thanks to such properties, these materials are now competing with established technologies for use in cost‐effective and efficient light‐harvesting and light‐emitting devices. Nevertheless, the fundamental understanding of the behavior of charge carriers in these materials—particularly on the nano‐ to microscale—has, on the whole, lagged behind empirical device performance. Such understanding is essential to control charge carriers, exploit new device structures, and push devices to their performance limits. Among other tools, optical microscopy and spectroscopic techniques have revealed rich information about charge carrier recombination and transport on important length scales. In this progress report, the contribution of time‐resolved optical microscopy techniques to the collective understanding of the photophysics of these materials is detailed. The ongoing technical developments in the field that are overcoming traditional experimental limitations in order to visualize transport properties over multiple time and length scales are discussed. Finally, strategies are proposed to combine optical microscopy with complementary techniques in order to obtain a holistic picture of local carrier photophysics in state‐of‐the‐art perovskite devices. [ABSTRACT FROM AUTHOR]

The WaterCircle (WC) project was implemented in a school, with young adolescents, to address environmental problems. Framed in a participatory research (PR) approach, this school-and-community based intervention includes the use of online tools through which environmental problems in the community are discussed within and by a group of students. Using a quasi-experimental design, with intervention and control groups, the present study involved 361 young adolescents, in grades 7 to 9, from a public school in the northern region of Portugal. Mixed methods were used for data collection and analysis, namely based on questionnaires administered in the pre- and post-test moments, as well as on students' discourses produced in the classroom during planned activities. Statistically significant changes on self-efficacy were found for the experimental group, suggesting that the intervention program has the potential to raise young people's empowerment regarding environmental issues. The WC program seems to foster students' awareness of the socio-political dimensions of environmental problems, since they were able to identify different actors in the community who should be involved in the proposed solutions. Longer-term intervention is required to foster the impact of the PR on the students' experience. [ABSTRACT FROM AUTHOR]

Seminal fluid is often assumed to have just one function in mammalian reproduction, delivering sperm to fertilize oocytes. But seminal fluid also transmits signaling agents that interact with female reproductive tissues to facilitate conception and. pregnancy. Upon seminal fluid contact, female tissues initiate a controlled inflammatory response that affects several aspects of reproductive function to ultimately maximize the chances of a male producing healthy offspring. This effect is best characterized in mice, where the female response involves several steps. Initially, seminal fluid factors cause leukocytes to infiltrate the female reproductive tract, and to selectively target and eliminate excess sperm. Other signals stimulate ovulation, induce an altered transcriptional program in female tract tissues that modulates embryo developmental programming, and initiate immune adaptations to promote receptivity to implantation and placental development. A key result is expansion of the pool of regulatory T cells that assist implantation by suppressing inflammation, mediating tolerance to male transplantation antigens, and promoting uterine vascular adaptation and placental development. Principal signaling agents in seminal fluid include prostaglandins and transforming growth factor-γ. The balance of male signals affects the nature of the female response, providing a mechanism of "cryptic female choice" that influences female reproductive investment. Male-female seminal fluid signaling is evident in all mammalian species investigated including human, and effects of seminal fluid in invertebrates indicate evolutionarily conserved mechanisms. Understanding the female response to seminal fluid will shed new light on infertility and pregnancy disorders and is critical to defining how events at conception influence offspring health. [ABSTRACT FROM AUTHOR]

The application of tumor immunotherapy to glioblastoma (GBM) is limited by an unprecedented degree of immune suppression due to factors that include high numbers of immune suppressive myeloid cells, the blood brain barrier, and T cell sequestration to the bone marrow. We previously identified an increase in immune suppressive myeloid-derived suppressor cells (MDSCs) in GBM patients, which correlated with poor prognosis and was dependent on macrophage migration inhibitory factor (MIF). Here we examine the MIF signaling axis in detail in murine MDSC models, GBM-educated MDSCs and human GBM. We found that the monocytic subset of MDSCs (M-MDSCs) expressed high levels of the MIF cognate receptor CD74 and was localized in the tumor microenvironment. In contrast, granulocytic MDSCs (G-MDSCs) expressed high levels of the MIF non-cognate receptor CXCR2 and showed minimal accumulation in the tumor microenvironment. Furthermore, targeting M-MDSCs with Ibudilast, a brain penetrant MIF-CD74 interaction inhibitor, reduced MDSC function and enhanced CD8 T cell activity in the tumor microenvironment. These findings demonstrate the MDSC subsets differentially express MIF receptors and may be leveraged for specific MDSC targeting. [ABSTRACT FROM AUTHOR]

Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine that has been associated with many diseases. Most studies found in literature describe MIF as a proinflammatory cytokine involved in chronic inflammatory conditions, but evidence from last years suggests that many of its key effects are not directly related to inflammation. In fact, MIF is constitutively expressed in most human tissues and in some cases in high levels, which does not reflect the pattern of expression of a classic proinflammatory cytokine. Moreover, MIF is highly expressed during embryonic development and decreases during adulthood, which point toward a more likely role as growth factor. Accordingly, MIF knockout mice develop age-related spontaneous emphysema, suggesting that MIF presence (e.g., in younger individuals and wild-type animals) is part of a healthy lung. In view of this new line of evidence, we aimed to review data on the role of MIF in the pathogenesis of chronic lung diseases. [ABSTRACT FROM AUTHOR]

Many worldwide live in households with multiple generations of related adults. This paper shows that the number of UK multigenerational households has been increasing but UK multigenerational households have been little studied. The research found that the motivations for multigenerational living are diverse and reflect multiple intersecting structural pressures, including an ageing population, worsening housing affordability and later household formation amongst young people. These intersect with individual circumstances, such as divorce or illness, to make multigenerational living the most practical option for some families. However, forming a multigenerational household is also often an individual and family choice, based on the expectation of mutual benefits brought about by multigenerational living. The research suggests that the extent to which living in a multigenerational household is a positive experience is determined by an individual's degree of agency and choice in the arrangement, rather than an ability to cope with wider structural pressures. [ABSTRACT FROM AUTHOR]