bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumour‐associated macrophages as a novel target of VEGI‐251 in cancer therapy
Authors: Dong Xinhuai , Huang Xuan , Yao Zhicheng , Wu Yun , Chen Delin , Tan Chahui , Lin Jiajie , Zhang Danrui , Hu Yiwen , Wu Jueheng , Wei Guohong , Zhu Xun 
Published: May 2020

AbstractTumour‐associated macrophages (TAMs), which possess M2‐like characters and are derived from immature monocytes in the circulatory system, represent a predominant population of inflammatory cells in solid tumours. TAM infiltration in tumour microenvironment can be used as an important prognostic marker in many cancer types and is a potential target for cancer prevention or treatment. VEGI‐251 not only is involved in the inhibition of tumour angiogenesis, but also participates in the regulation of host immunity. This work aimed to investigate the involvement of VEGI‐251 in the regulation of specific antitumour immunity. We found that recombinant human VEGI‐251(rhVEGI‐251) efficiently mediated the elimination of TAMs in tumour tissue in mice, and induced apoptosis of purified TAMs in vitro. During this process, caspase‐8 and caspase‐3 were activated, leading to PARP cleavage and apoptosis. Most importantly, we further elucidated the mechanism underlying VEGI‐251‐triggered TAM apoptosis, which suggests that ASK1, an intermediate component of the VEGI‐251, activates the JNK pathway via TRAF2 in a potentially DR3‐dependent manner in the process of TAM apoptosis. Collectively, our findings provide new insights into the basic mechanisms underlying the actions of VEGI‐251 that might lead to future development of antitumour therapeutic strategies using VEGI‐251 to target TAMs.
Validation of a Patient Global Assessment for extent, severity and impact to define the severity strata for the Self Assessment Vitiligo Extent Score (SA‐VES)
Authors: van Geel N. , Uitentuis S.E. , Zuidgeest M. , Wolkerstorfer A. , Bekkenk M.W. , Moock C. , Van Goethem C. , Verlaeckt E. , Smet C. , Grine L. , Speeckaert R. 
Published: May 2020

AbstractBackgroundThe Self Assessment Vitiligo Extent Score (SA‐VES) is a validated, patient‐reported outcome measure to assess the body surface area affected with vitiligo. Information on how to translate the obtained score into extent, severity and impact strata (mild–moderate–severe) is still lacking. Stratification is helpful to define inclusion criteria for trials, enables comparison and pooling of trial results and can be used for epidemiological research.ObjectivesThe aim was to develop extent, severity and impact strata for the SA‐VES based on validated anchor‐based questions.MethodsIn total, 315 patients with vitiligo (non‐segmental; age ≥ 16) recruited at the Ghent University Hospital (Belgium) completed a questionnaire that was conducted in cooperation with the Dutch Society for vitiligo patients to ensure content validity. First three anchor questions included in the questionnaire [Patient Global Assessment (PtGA) for vitiligo extent, severity and impact] were assessed for content validity, construct validity and intrarater reliability. Subsequently, the PtGAs were used to stratify the SA‐VES based on ROC analysis.ResultsFor all PtGAs (PtGA extent, PtGA severity, PtGA impact), at least 75% of hypotheses evaluated for construct validity were confirmed. Intrarater reliability of all PtGAs was good to excellent (ICCs PtGA extent: 0.623; PtGA severity: 0.828; PtGA impact: 0.851). The optimal cut‐off values of the SA‐VES between the three global categories (mild/limited – moderate – severe/extensive) were 1.05% and 6.45% based on PtGA extent, 2.07% and 4.8% based on PtGA severity and 2% and 3.35% based on PtGA impact.ConclusionThis study provides the first guide for the interpretation of the numerical output obtained by the SA‐VES (vitiligo extent) and enables the translation into a global vitiligo grading for extent, severity and impact. As patients’ interpretation of vitiligo extent, severity and impact may vary amongst patients worldwide, future international studies will be required.
Impact of modern systemic therapies and clinical markers on treatment outcome for metastatic melanoma in a real‐world setting
Authors: Krakowski I. , Bottai M. , Häbel H. , Masucci G. , Girnita A. , Smedby K.E. , Eriksson H. 
Published: May 2020

AbstractBackgroundThe survival in metastatic melanoma has dramatically improved after the introduction of immune checkpoint‐ (ICIs) and MAPKinase inhibitors (MAPKis).ObjectiveOur aim was to describe therapy response and survival in a real‐world population as well as to assess the associations between clinical variables and therapy outcome for patients with metastatic melanoma receiving first‐line ICIs or MAPKis.MethodsA total of 252 patients with metastatic (stage IV) melanoma were prospectively followed between 1 January 2010 and 3 December 2017 with follow‐up until 31 March 2019, at the Karolinska University Hospital, Sweden. Hazard ratios (HRs) for progression‐free survival (PFS) and overall survival (OS) were analysed with Cox regression, and logistic regression was used to estimate odds ratios (ORs) for therapy response.ResultsPatients receiving ICIs (n = 138) experienced longer PFS compared to patients that received MAPKis (n = 114; median PFS for ICIs was 6.8 months, and median PFS for MAPKis was 5.3 months). In the multivariable analyses of clinical markers, increasing M‐stage (OR 0.65; 95% CI 0.45–0.94; P = 0.022) and male sex (OR 0.41; 95% CI 0.19–0.90; P = 0.027) were significantly associated with lower response to ICIs. Lower baseline albumin levels (OR 0.90; 95% CI 0.83–0.98; P = 0.019) and male sex (OR 0.33; 95% CI 0.12–0.93; P = 0.036) were related with lower response to MAPKis. For ICIs, increasing M‐stage (HR 1.34; 95% CI 1.07–1.68; P = 0.010), increasing LDH (HR 1.73; 95% CI 1.19–2.50; P = 0.004) and decreasing albumin (HR 1.06; 95% CI 1.01–1.10; P = 0.011) were significantly associated lower PFS in the adjusted model. The corresponding markers for MAPKis were increasing LDH (HR 1.44; 95% CI 1.08–1.92; P = 0.013) and decreasing albumin (HR 1.05; 95% CI 1.02–1.09; P = 0.005) for PFS.ConclusionICIs and MAPKis were effective in this real‐world population, and we could confirm the importance of previously reported clinical prognostic markers. Albumin values may be associated with therapy outcome but need further validation.
Does Formation of Multicellular Colonies by Choanoflagellates Affect Their Susceptibility to Capture by Passive Protozoan Predators?
Authors: Kumler William E. , Jorge Justin , Kim Paul M. , Iftekhar Noama , Koehl M. A. R. 
Published: May 2020

AbstractMicrobial eukaryotes, critical links in aquatic food webs, are unicellular, but some, such as choanoflagellates, form multicellular colonies. Are there consequences to predator avoidance of being unicellular vs. forming larger colonies? Choanoflagellates share a common ancestor with animals and are used as model organisms to study the evolution of multicellularity. Escape in size from protozoan predators is suggested as a selective factor favoring evolution of multicellularity. Heterotrophic protozoans are categorized as suspension feeders, motile raptors, or passive predators that eat swimming prey which bump into them. We focused on passive predation and measured the mechanisms responsible for the susceptibility of unicellular vs. multicellular choanoflagellates, Salpingoeca helianthica, to capture by passive heliozoan predators, Actinosphaerium nucleofilum, which trap prey on axopodia radiating from the cell body. Microvideography showed that unicellular and colonial choanoflagellates entered the predator's capture zone at similar frequencies, but a greater proportion of colonies contacted axopodia. However, more colonies than single cells were lost during transport by axopodia to the cell body. Thus, feeding efficiency (proportion of prey entering the capture zone that were engulfed in phagosomes) was the same for unicellular and multicellular prey, suggesting that colony formation is not an effective defense against such passive predators.
Design of low impact development in the urban context considering hydrological performance and life‐cycle cost
Authors: Li Yu , Huang Jeanne J. , Hu Maochuan , Yang Hong , Tanaka Kenji 
Published: May 2020

AbstractThe pressures on water system are increasing in cities. Rapid urbanisation caused by booming population leads to more impervious area and less infiltration, with the consequence of larger runoff volume and higher flood risk. Launched in 2014, the low impact development (LID), an important part of Sponge City in China initiative, invests in projects that aim to restore the water cycle in the urban area. A comprehensive understanding of the performance of LID measures at watershed scale under different rainfall scenarios and life cycle costs is necessary. The objectives of this study are to assess the hydrological performance and to identify the optimal LID design by using SWMM model and life cycle cost (LCC) method. This study found that LID practices, including bioretention, grass swale, and permeable pavement, showed good performance on urban storm mitigation at watershed scale under different rainfall scenarios. Furthermore, the rates of surface runoff reduction were largely insusceptible to the change of rainfall volume and duration. Regarding the cost‐effectiveness, the priority was grass swale > bioretention > permeable pavement in the study area. The optimal LID scenario was the combination of these three types of LID. The proposed approach can help the decision‐makers to determine the preferable LID plan suitable for the local communities.
Heterogeneity of fibrillin‐rich microfibrils extracted from human skin of diverse ethnicity
Authors: Langton Abigail K , Hann Mark , Costello Patrick , Halai Poonam , Sisto Alessi César Sabrina , Lien‐Lun Chien Anna , Kang Sewon , Griffiths Christopher E.M. , Sherratt Michael J. , Watson Rachel E.B. 
Published: May 2020

AbstractThe dermal elastic fibre network is the primary effector of skin elasticity, enabling it to extend and recoil many times over the lifetime of the individual. Fibrillin‐rich microfibrils (FRMs) constitute integral components of the elastic fibre network, with their distribution showing differential deposition in the papillary dermis across individuals of diverse skin ethnicity. Despite these differential findings in histological presentation, it is not known if skin ethnicity influences FRM ultrastructure. FRMs are evolutionarily highly conserved from jellyfish to man and, regardless of tissue type or species, isolated FRMs have a characteristic ‘beads‐on‐a‐string’ ultrastructural appearance, with an average inter‐bead distance (or periodicity) of 56 nm. Here, skin biopsies were obtained from the photoprotected buttock of healthy volunteers (18‐27 years; African: n = 5; European: n = 5), and FRMs were isolated from the superficial papillary dermis and deeper reticular dermis and imaged by atomic force microscopy. In the reticular dermis, there was no significant difference in FRM ultrastructure between European and African participants. In contrast, in the more superficial papillary dermis, inter‐bead periodicity was significantly larger for FRMs extracted from European participants than from African participants by 2.20 nm (p < .001). We next assessed whether these differences in FRM ultrastructure were present during early postnatal development by characterizing FRMs from full‐thickness neonatal foreskin. Analysis of FRM periodicity identified no significant difference between neonatal cohorts (p = .865). These data suggest that at birth, FRMs are developmentally invariant. However, in adults of diverse skin ethnicity, there is a deviation in ultrastructure for the papillary dermal FRMs that may be acquired during the passage of time from child to adulthood. Understanding the mechanism by which this difference in papillary dermal FRMs arises warrants further study.
National survey of confirmed thromboembolism related to female hormones in Japan
Authors: Sugiura Kazuko , Kobayashi Takao , Ojima Toshiyuki 
Published: May 2020

AbstractAimThe aim of this study was to determine the number of thromboembolism patients among Japanese users of female hormones.MethodsA survey of confirmed thromboembolism patients among Japanese users of female hormones was conducted at randomly selected hospitals from across Japan. The survey examined six types of venous thromboembolism (VTE) and arterial thromboembolism (ATE) in all users of female hormones, including women and men: pulmonary embolism (PE), deep vein thrombosis (DVT), other venous thrombosis (other VTE), cerebral infarction (stroke), myocardial infarction (MI) and other arterial thrombosis (other ATE). The survey covered 5 years from 2009 to 2013. This study was approved in an ethical review by the Hamamatsu University School of Medicine.ResultsThe overall number of thromboembolism patients over the 5 years was estimated to be about 3211. They included 452 patients with PE, 795 with DVT, 157 with other VTE, 1228 with stroke, 478 with MI and 101 with other ATE. Among the abovementioned conditions, detailed information was available for 750 thromboembolism patients (645 women and 105 men), including 63 PE, 203 DVT, 159 PE + DVT, 65 other VTE, 189 stroke, 35 MI, 21 other ATE and 15 other cases. Thromboembolism increased year by year. The number of VTE was larger than that of ATE in younger people who used female hormones, while the number of ATE was larger than that of VTE in older people who used female hormones.ConclusionThe number and characteristics of thromboembolism patients among Japanese female hormone users were revealed in this national survey.
Abundance and Extracellular Release of Phytohormones in Aero‐terrestrial Microalgae (Trebouxiophyceae, Chlorophyta) As a Potential Chemical Signaling Source1
Authors: Pichler Gregor , Stöggl Wolfgang , Candotto Carniel Fabio , Muggia Lucia , Ametrano Claudio Gennaro , Holzinger Andreas , Tretiach Mauro , Kranner Ilse 
Published: May 2020

Phytohormones are pivotal signaling compounds in higher plants, in which they exert their roles intracellularly, but are also released for cell‐to‐cell communication. In unicellular organisms, extracellularly released phytohormones can be involved in chemical crosstalk with other organisms. However, compared to higher plants, hardly any knowledge is available on the roles of phytohormones in green algae. Here, we studied phytohormone composition and extracellular release in aero‐terrestrial Trebouxiophyceae. We investigated (a) which phytohormones are produced and if they are released extracellularly, and if extracellular phytohormone levels are (b) affected by environmental stimuli, and (c) differ between lichen‐forming and non‐lichen‐forming species. Three free‐living microalgae (Apatococcus lobatus, Chloroidium ellipsoideum, and Myrmecia bisecta) and three lichen‐forming microalgae (Asterochloris glomerata, Trebouxia decolorans, and Trebouxia sp.) were studied. Algae were grown on solid media and the following cellular phytohormones were identified by ultra‐high‐performance liquid chromatography coupled with tandem mass spectrometry (UHPLC‐MS/MS): indole‐3‐acetic acid (IAA), indole‐3‐butyric acid (IBA), abscisic acid (ABA), gibberellin A4 (GA4), and zeatin (ZT). Furthermore, IAA, IBA, ABA, jasmonic acid (JA), gibberellin A3 (GA3), and GA4 were found to be released extracellularly. IAA and ABA were released by all six species, and IAA was the most concentrated. Phytohormone release was affected by light and water availability, especially IAA in A. glomerata, Trebouxia sp., and C. ellipsoideum. No clear patterns were observed between lichen‐forming and non‐lichen‐forming species. The results are envisaged to contribute valuable baseline information for further studies into the roles of phytohormones in microalgae.
Genome‐wide SNP analysis reveals an increase in adaptive genetic variation through selective breeding of coral
Authors: Quigley Kate M. , Bay Line K. , van Oppen Madeleine J. H. 
Published: May 2020

AbstractMarine heat waves are increasing in magnitude, duration, and frequency as a result of climate change and are the principal global driver of mortality in reef‐building corals. Resilience‐based genetic management may increase coral heat tolerance, but it is unclear how temperature responses are regulated at the genome level and thus how corals may adapt to warming naturally or through selective breeding. Here we combine phenotypic, pedigree, and genomic marker data from colonies sourced from a warm reef on the Great Barrier Reef reproductively crossed with conspecific colonies from a cooler reef to produce combinations of warm purebreds and warm‐cool hybrid larvae and juveniles. Interpopulation breeding created significantly greater genetic diversity across the coral genome compared to breeding between populations and maintained diversity in key regions associated with heat tolerance and fitness. High‐density genome‐wide scans of single nucleotide polymorphisms (SNPs) identified alleles significantly associated with larval families reared at 27.5°C (87–2,224 loci), including loci putatively associated with proteins involved in responses to heat stress (cell membrane formation, metabolism, and immune responses). Underlying genetics of these families explained 43% of PCoA multilocus variation in survival, growth, and bleaching responses at 27.5°C and 31°C at the juvenile stage. Genetic marker contribution to total variation in fitness traits (narrow‐sense heritability) was high for survival but not for growth and bleaching in juveniles, with heritability of these traits being higher at 31°C relative to 27.5°C. While based on only a limited number of crosses, the mechanistic understanding presented here demonstrates that allele frequencies are affected by one generation of selective breeding, key information for the assessments of genetic intervention feasibility and modelling of reef futures.
Environmental DNA surveys detect distinct metazoan communities across abyssal plains and seamounts in the western Clarion Clipperton Zone
Authors: Laroche Olivier , Kersten Oliver , Smith Craig R. , Goetze Erica 
Published: May 2020

AbstractThe deep seafloor serves as a reservoir of biodiversity in the global ocean, with >80% of invertebrates at abyssal depths still undescribed. These diverse and remote deep‐sea communities are critically under‐sampled and increasingly threatened by anthropogenic impacts, including future polymetallic nodule mining. Using a multigene environmental DNA (eDNA) metabarcoding approach, we characterized metazoan communities sampled from sediments, polymetallic nodules and seawater in the western Clarion Clipperton Zone (CCZ) to test the hypotheses that deep seamounts (a) are species richness hotspots in the abyss, (b) have structurally distinct communities in comparison to other deep‐sea habitats, and (c) that seafloor particulate organic carbon (POC) flux and polymetallic nodule density are positively correlated with metazoan diversity. eDNA metabarcoding was effective at characterizing distinct biotas known to occur in association with different abyssal substrate types (e.g., nodule‐ and sediment‐specific fauna), with distinct community composition and few taxa shared across substrates. Seamount faunas had higher overall taxonomic richness, and different community composition and biogeography than adjacent abyssal plains, with seamount communities displaying less connectivity between regions than comparable assemblages on the abyssal plains. Across an estimated gradient of low to moderate POC flux, we find lowest taxon richness at the lowest POC flux, as well as an effect of nodule size on community composition. Our results suggest that while abyssal seamounts are important reservoirs of metazoan diversity in the CCZ, given limited taxonomic overlap between seamount and plains fauna, conservation of seamount assemblages will be insufficient to protect biodiversity and ecosystem function in regions targeted for mining.
Internal force monitoring and estimation of a long‐span ring beam using long‐gauge strain sensing
Authors: Zhang Qingqing , Zhang Jian 
Published: May 2020

AbstractThe internal force information of curved beam members is important evidence for the stress state evaluation and design verification of long‐span space structure during construction. Many structural analysis methods for curved beams have been proposed, but most are used to handle the complex geometric shapes. For stress state evaluation of long‐span steel‐concrete composite (SCC) ring beam, this article presents a method that employs a sectional strain distribution model (SSDM) and a fiber model to estimate the internal force distribution depending on the long‐gauge strain. The SSDM of the ring beam used in the article is based on a mechanical model of two‐dimensional (2‐D) plane bending deformation and a three‐dimensional (3‐D) solid finite element model of curved beam members. The application range of the SSDM is defined by the divided different stress areas of ring beam based on the 3‐D solid finite element model. Combined with the established SSDM and the different stress areas, the axial force and bending moment along the span are then identified separately based on the fiber model. In consideration of field monitoring, the influence of different sensor layout on the establishment of SSDM and the result of internal force identification is discussed. The results of the numerical studies show that the proposed methodology can identify the internal force distribution accurately. Internal force of long‐span ring beam from Jiangsu Grand Theater during construction is also identified through the proposed method by using the strain monitoring data.
Evidence summaries and recommendations from the international evidence‐based guideline for the assessment and management of polycystic ovary syndrome: Lifestyle management
Authors: Moran Lisa J. , Tassone Eliza C. , Boyle Jacqueline , Brennan Leah , Harrison Cheryce L. , Hirschberg Angelica Lindén , Lim Siew , Marsh Kate , Misso Marie L. , Redman Leanne , Thondan Mala , Wijeyaratne Chandrika , Garad Rhonda , Stepto Nigel K. , Teede Helena J. 
Published: May 2020

SummaryLifestyle is fundamental in chronic disease prevention and management, and it has been recommended as a first‐line treatment in the Australian polycystic ovary syndrome (PCOS) guideline 2011. The first international evidence‐based guideline on PCOS was developed in 2018, which expanded the scope and evidence in the Australian guideline. This paper summarizes the lifestyle recommendations and evidence summaries from the guideline. International multidisciplinary guideline development groups delivered the International Evidence‐based Guideline for the Assessment and Management of Polycystic Ovary Syndrome 2018. The process followed the Appraisal of Guidelines for Research and Evaluation II and The Grading of Recommendations, Assessment, Development and Evaluation framework. Extensive communication and meetings addressed six prioritized clinical questions through five reviews. Evidence‐based recommendations were formulated before consensus voting within the panel. Evidence shows the benefits of multicomponent lifestyle intervention, efficacy of exercise and weight gain prevention with no specific diet recommended. Lifestyle management is the first‐line management in the intervention hierarchy in PCOS. Multicomponent lifestyle intervention including diet, exercise and behavioural strategies is central to PCOS management with a focus on weight and healthy lifestyle behaviours. The translation programme optimizes reach and dissemination for health professionals and consumers.