bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterizing the tumor microenvironment in rare renal cancer histological types
Authors: Synnott Naoise C , Poeta Maria Luana , Costantini Manuela , Pfeiffer Ruth M , Li Mengying , Golubeva Yelena , Lawrence Scott , Mutreja Karun , Amoreo Carla , Dabrowska Malgorzata , Simone Giuseppe , Pescarmona Edoardo , Lenz Petra , Olanich Mary , Duggan Maire , Abubakar Mustapha , Fazio Vito Michele , Gallucci Michele , Sentinelli Steno , Landi Maria Teresa 
Published: October 2021

AbstractThe tumor microenvironment (TME), including immune cells, cancer‐associated fibroblasts, endothelial cells, adjacent normal cells, and others, plays a crucial role in influencing tumor behavior and progression. Here, we characterized the TME in 83 primary renal tumors and matched metastatic or recurrence tissue samples (n = 15) from papillary renal cell carcinoma (pRCC) types 1 (n = 20) and 2 (n = 49), collecting duct carcinomas (CDC; n = 14), and high‐grade urothelial carcinomas (HGUC; n = 5). We investigated 10 different markers of immune infiltration, vasculature, cell proliferation, and epithelial‐to‐mesenchymal transition by using machine learning image analysis in conjunction with immunohistochemistry. Marker expression was compared by Mann–Whitney and Kruskal–Wallis tests and correlations across markers using Spearman's rank correlation coefficient. Multivariable Poisson regression analysis was used to compare marker expression between histological types, while accounting for variation in tissue size. Several immune markers showed different rates of expression across histological types of renal carcinoma. Using pRCC1 as reference, the incidence rate ratio (IRR) of CD3+ T cells (IRR [95% confidence interval, CI] = 2.48 [1.53–4.01]) and CD20+ B cells (IRR [95% CI] = 4.38 [1.22–5.58]) was statistically significantly higher in CDC. In contrast, CD68+ macrophages predominated in pRCC1 (IRR [95% CI] = 2.35 [1.42–3.9]). Spatial analysis revealed CD3+ T‐cell and CD20+ B‐cell expressions in CDC to be higher at the proximal (p < 0.0001) and distal (p < 0.0001) tumor periphery than within the central tumor core. In contrast, expression of CD68+ macrophages in pRCC2 was higher in the tumor center compared to the proximal (p = 0.0451) tumor periphery and pRCC1 showed a distance‐dependent reduction, from the central tumor, in CD68+ macrophages with the lowest expression of CD68 marker at the distal tumor periphery (p = 0.004). This study provides novel insights into the TME of rare kidney cancer types, which are often understudied. Our findings of differences in marker expression and localization by histological subtype could have implications for tumor progression and response to immunotherapies or other targeted therapies.
Giant cell tumor of soft tissue: FNA cytopathology of 4 cases, review of the literature, and comparison with giant cell tumor of bone
Authors: Wakely Paul E. 
Published: October 2021

BackgroundThe cytopathology of a giant cell tumor of soft tissue (GCT‐ST), a fibrohistiocytic neoplasm distinct from other giant cell–rich soft tissue tumors, is rarely reported. The authors report their experience with a series of 4 GCT‐ST fine‐needle aspiration (FNA) biopsy cases and compare them with a set from giant cell tumors of bone (GCTBs).MethodsThe authors' cytopathology files were searched for GCT‐ST examples with histopathologic confirmation. FNA biopsy smears were performed and examined with standard techniques.ResultsFour cases of GCT‐ST presenting as a primary soft tissue mass from 4 patients (3 males and 1 female; age range, 28‐75 years, mean age, 53 years) were retrieved. FNA sites included the anterior tibia, buttock, shoulder, and upper back. Three cases were interpreted as suspicious for sarcoma radiographically. The specific diagnoses were atypical giant cell tumor of tendon sheath, suspicious for GCT‐ST, atypical myxoid lesion with giant cells, and benign with osteoclast‐like giant cells (OLGCs). No case was interpreted as malignant. Aspirates consisted of mononuclear polygonal cells, spindled fibroblast cell clusters, and large OLGCs to the near exclusion of other cell types. OLGCs possessed 10 or more nuclei per cell. A comparison with GCTB aspirates and single case reports from the literature showed comparable cytomorphology.ConclusionsGCT‐ST FNA smears mimic those of GCTBs containing a limited population of uniform spindle cell clusters, single dispersed polygonal cells, and cytologically banal OLGCs. GCT‐ST should be considered in the differential diagnosis of aspirates containing numerous osteoclast‐like giant cells.
Smart Two‐Dimensional Membranes for Molecular Separations
Authors: Rouhani Hadi , Ying Yunpan , Zhao Dan 
Published: October 2021

AbstractMembrane‐based separation technologies are gaining prominence in energy‐efficient separation processes. Smart membranes, which change their physical or chemical characteristics in response to environmental stimuli, are attractive membrane candidates. This review summarizes the recent development and applications of smart membranes based on two‐dimensional (2D) materials, mainly focusing on their design, fabrication, and applications in molecular separations. Furthermore, stimuli for triggering smart 2D membranes are classified and explained. Finally, we propose areas for improvement and further development for future studies, such as the issues of complicated fabrication, long term stability in real operating conditions, and responding to different environmental stimuli at the same time.
A new method for textile pattern recognition and recoloring
Authors: Zheng Dejun 
Published: October 2021

AbstractTextile pattern recognition and recoloring separates a fabric image into different color regions and changes colors of the regions in the fabric image. A new method for textile pattern recognition and recoloring is proposed. The proposed method consists of two main steps. First, the binary images are recognized through a series of image enhancement techniques, such as the color‐encoding algorithm, the edge‐based filtering algorithm, and a multiphase image segmentation model. Second, the regions of interest are recolored with different recoloring methods based on intrinsic image decomposition and grayscale image recoloring. Experimental results and comparisons demonstrate that the main disadvantages and difficulties of using palette‐based methods in textile pattern recoloring have been overcome by the proposed method. The proposed method is effective in inhibiting tiny region effects and preserving the geometry structures of textile patterns. It can be applied to recognize and recolor different kinds of fabric images, including the Jacquard, the embroidered, and the printed fabric images.
Semi‐Mechanistic PK/PD Modeling and Simulation of Irreversible BTK Inhibition to Support Dose Selection of Tirabrutinib in Subjects with RA
Authors: Meng Amy , Humeniuk Rita , Jürgensmeier Juliane M. , Hsueh Chia‐Hsiang , Matzkies Franziska , Grant Ethan , Truong Hoa , Billin Andrew N. , Yu Helen , Feng Joy , Kwan Ellen , Tarnowski Thomas , Nelson Cara H. 
Published: October 2021

Tirabrutinib is an irreversible, small‐molecule Bruton’s tyrosine kinase (BTK) inhibitor, which was approved in Japan (VELEXBRU) to treat B‐cell malignancies and is in clinical development for inflammatory diseases. As an application of model‐informed drug development, a semimechanistic pharmacokinetic/pharmacodynamic (PK/PD) model for irreversible BTK inhibition of tirabrutinib was developed to support dose selection in clinical development, based on clinical PK and BTK occupancy data from two phase I studies with a wide range of PK exposures in healthy volunteers and in subjects with rheumatoid arthritis. The developed model adequately described and predicted the PK and PD data. Overall, the model‐based simulation supported a total daily dose of at least 40 mg, either q.d. or b.i.d., with adequate BTK occupancy (> 90%) for further development in inflammatory diseases. Following the PK/PD modeling and simulation, the relationship between model‐predicted BTK occupancy and preliminary clinical efficacy data was also explored and a positive trend was identified between the increasing time above adequate BTK occupancy and better efficacy in treatment for RA by linear regression.
BIA‐ALCL diagnosis on CytoLyt fixed ThinPrep, cell block and immunohistochemistry
Authors: Everest Sedef , Virk Renu , Gonzalez Abel 
Published: October 2021

AbstractBreast implant associated anaplastic large cell lymphoma (BIA‐ALCL) is an emergent rare T cell non‐Hodgkin lymphoma arising in association with a breast implant, particularly textured ones. Recent guidelines list cytopathological examination as the first essential step for diagnosis, routinely followed by CD30 immunohistochemistry (IHC) and flow cytometry (FC) for a T cell clone. The majority of BIA‐ALCL literature regarding cytopathological evaluation describes morphology based on various preparation methods limited to cytospins and smears with the exception of at least one case report detailing cytomorphological and IHC findings on ThinPrep. This case report details initial diagnosis of BIA‐ALCL rendered with CytoLyt prepared ThinPrep and cell block, including the specific antibodies used for IHC. The ThinPrep slide showed numerous singly dispersed large, atypical cells with abundant cytoplasm containing irregular nuclei with dispersed chromatin and prominent nucleoli in a background of macrophages, inflammatory cells and granular debris. TIA‐1 and CD30 along with other T‐cell markers, including specific antibodies, remains immunoreactive in tissue collected in CytoLyt solution. Cell size reduction, artifactual lymphoid cell aggregation and prominent nucleoli in benign and reactive conditions are among other ThinPrep cellular alterations pathologists should bear in mind.
What are the different styles of calcite precipitation within a hyperalkaline leachate? A sedimentological Anthropocene case study
Authors: Bastianini Laura , Rogerson Mike , Mercedes‐Martín Ramon , Prior Timothy J. , Mayes William M. 
Published: October 2021

AbstractThis study aims to compare the fabrics of anthropogenic carbonates downstream of lime and steel disposal sites with models of carbonate precipitation from natural systems to elucidate potential drivers, precipitation mechanisms, morphological similarities, predictability in 3D facies distributions and depositional models of these systems. For this purpose, a combination of sedimentological, mineralogical and geochemical approaches is conducted including the analysis of microfacies (petrographic microscope and electron microscopy), X‐ray diffraction and hydrochemistry. The data show that both anthropogenic and natural systems exhibit clear proximal, middle and distal zones of carbonate precipitation. The main macroscopic differences are the dominance of swamp environments in the proximal zone and the prevalence of tufa‐like barrage‐and‐pool sequences in the middle and distal zones. Microfabrics in anthropogenic sites are comparable to travertines but lack the sub‐surface facies and at extreme pH exhibit sparry crusts without clear equivalents in travertines. This sedimentology of anthropogenic carbonates shows that calcite mineral formation is complex and not homogeneous or purely driven by thermodynamic processes. Considering the sedimentology of these human‐induced systems will help us understand precipitation mechanisms which will aid both efforts to utilise anthropogenic alkaline wastes for carbon capture and manage their environmental impacts.
The new dual gastric inhibitory peptide/glucagon‐like peptide 1 agonist tirzepatide in type 2 diabetes: Is the future bright?
Authors: Papachristou Stella , Popovic Djordje S. , Papanas Nikolaos 
Published: October 2021

AbstractTirzepatide is a dual gastric inhibitory peptide/glucagon‐like peptide 1 (GIP/GLP‐1) receptor agonist formulated as a synthetic linear peptide, based on the native GIP sequence. It has a prolonged half‐life of 5 days, which enables once‐weekly dosing. Studies have hitherto demonstrated its superiority in achieving optimal glycaemic control and body weight management, as compared with various agents used in the treatment of type 2 diabetes mellitus (T2DM), including GLP‐1 receptor agonists. Thus, it is expected to enrich our therapeutic armamentarium in T2DM. However, further experience, notably longer follow‐up data and information on cardiovascular effects, is still needed.
Systematic expression analysis of plasticity‐related genes in mouse brain development brings PRG4 into play
Authors: Gross Isabel , Tschigor Tabea , Salman Angelina L. , Yang Fan , Luo Jiankai , Vonk Danara , Hipp Mark S. , Neidhardt John , Bräuer Anja U. 
Published: October 2021

AbstractBackgroundPlasticity‐related genes (Prgs/PRGs) or lipid phosphate phosphatase‐related proteins (LPPRs) comprise five known members, which have been linked to neuronal differentiation processes, such as neurite outgrowth, axonal branching, or dendritic spine formation. PRGs are highly brain‐specific and belong to the lipid phosphate phosphatases (LPPs) superfamily, which influence lipid metabolism by dephosphorylation of bioactive lipids. PRGs, however, do not possess enzymatic activity, but modify lipid metabolism in a way that is still under investigation.ResultsWe analyzed mRNA expression levels of all Prgs during mouse brain development, in the hippocampus, neocortex, olfactory bulbs, and cerebellum. We found different spatio‐temporal expression patterns for each of the Prgs, and identified a high expression of the uncharacterized Prg4 throughout brain development. Unlike its close family members PRG3 and PRG5, PRG4 did not induce filopodial outgrowth in non‐neuronal cell lines, and does not localize to the plasma membrane of filopodia.ConclusionWe showed PRG4 to be highly expressed in the developing and the adult brain, suggesting that it is of vital importance for normal brain function. Despite its similarities to other family members, it seems not to be involved in changes of cell morphology; instead, it is more likely to be associated with intracellular signaling.
Chemical disturbance cues in aquatic systems: a review and prospectus
Authors: Crane Adam L. , Bairos‐Novak Kevin R. , Goldman Jack A. , Brown Grant E. 
Published: October 2021

AbstractIn the natural environment, animals can face potentially dangerous and often regular exposure to major environmental fluctuations such as flash flooding and drought, or the approach of a predator. For many aquatic species, exposure to these ecological disturbances triggers the release of “disturbance cues” – generally characterized as chemicals released when animals are startled but not injured. While the chemistry of such cues remains largely unexplored, they appear to provide early warning information to nearby individuals, potentially leading to behavioral decisions that increase overall fitness, particularly for social species that may coordinate group defense. In the literature, disturbance cues have received little attention relative to other chemical cues, such as damage‐released alarm cues. However, recent advances in the study of disturbance cue communication have led an uptick in research on the subject. Here, we review the existing literature on responses to disturbance cues in aquatic systems. Although the majority of studies involve behavioral responses to a simulated predator approach, we describe various disturbance types across a broad range of taxa. We discuss the ecological implications of disturbance cues, including their role in risk assessment, signaling, learning, and species specificity. We also address several methodological challenges for this developing field of study, as well as the ethical and conservation implications of this research going forward. Future research on disturbance cues should address a number of key unknowns, including questions regarding disturbance cue chemistry, function, and generality.
Improved inferences about landscape connectivity from spatial capture–recapture by integration of a movement model
Authors: Dupont Gates , Linden Daniel W. , Sutherland Chris 
Published: October 2021

AbstractUnderstanding how broad‐scale patterns in animal populations emerge from individual‐level processes is an enduring challenge in ecology that requires investigation at multiple scales and perspectives. Complementary to this need for diverse approaches is the recent focus on integrated modeling in statistical ecology. Population‐level processes represent the core of spatial capture–recapture (SCR), with many methodological extensions that have been motivated by standing ecological theory and data‐integration opportunities. The extent to which these recent advances offer inferential improvements can be limited by the data requirements for quantifying individual‐level processes. This is especially true for SCR models that use non‐Euclidean distance to relax the restrictive assumption that individual space use is stationary and symmetrical to make inferences about landscape connectivity. To meet the challenges of scale and data quality, we propose integrating an explicit movement model with non‐Euclidean SCR for joint estimation of a shared cost parameter between individual and population processes. Here, we define a movement kernel for step selection that uses “ecological distance” instead of Euclidean distance to quantify availability for each movement step in terms of landscape cost. We compare performance of our integrated model to that of existing SCR models using realistic animal movement simulations and data collected on black bears. We demonstrate that an integrated approach offers improvements both in terms of bias and precision in estimating the shared cost parameter over models fit to spatial encounters alone. Simulations suggest these gains were only realized when step lengths were small relative to home range size, and estimates of density were insensitive to whether or not an integrated approach was used. By combining the fine spatiotemporal scale of individual movement processes with the estimation of population density in SCR, integrated approaches such as the one we develop here have the potential to unify the fields of movement, population, and landscape ecology and improve our understanding of landscape connectivity.
The disruption of a keystone interaction erodes pollination and seed dispersal networks
Authors: Vitali Agustin , Sasal Yamila , Vázquez Diego P. , Miguel M. Florencia , Rodríguez‐Cabal Mariano A. 
Published: October 2021

AbstractUnderstanding the impacts of global change on ecological communities is a major challenge in modern ecology. The gain or loss of particular species and the disruption of key interactions are both consequences and drivers of global change that can lead to the disassembly of ecological networks. We examined whether the disruption of a hummingbird–mistletoe–marsupial mutualism by the invasion of non‐native species can have cascading effects on both pollination and seed dispersal networks in the temperate forest of Patagonia, Argentina. We focused on network motifs, subnetworks composed of a small number of species exhibiting particular patterns of interaction, to examine the structure and diversity of mutualistic networks. We found that the hummingbird–mistletoe–marsupial mutualism plays a critical role in the community by increasing the complexity of pollination and seed dispersal networks through supporting a high diversity of interactions. Moreover, we found that the disruption of this tripartite mutualism by non‐native ungulates resulted in diverse indirect effects that led to less complex pollination and seed dispersal networks. Our results demonstrate that the gains and losses of particular species and the alteration of key interactions can lead to cascading effects in the community through the disassembly of mutualistic networks.
Emergent properties of microbial communities drive accelerated biogeochemical cycling in disturbed temperate forests
Authors: Osburn Ernest D. , Badgley Brian D. , Strahm Brian D. , Aylward Frank O. , Barrett J. E. 
Published: October 2021

AbstractDespite ever‐increasing availability of detailed information about microbial community structure, relationships of microbial diversity with ecosystem functioning remain unclear. We investigated these relationships at the Coweeta Hydrologic Laboratory, where past forest disturbances (e.g., clear‐cut) have altered both ecosystem processes (e.g., increased N export) and microbial communities (e.g., increased bacterial diversity). We sampled soils from disturbed and adjacent reference forests, characterized resident microbial communities, and measured several microbial C‐cycle and N‐cycle process rates. Microbial communities from historically disturbed soils exhibited altered ecosystem functioning, including generally higher rates of C‐ and N‐cycle processes. Disturbed soil microbial communities also exhibited altered ecosystem multifunctionality, a composite variable consisting of all measured process rates as well as extracellular enzyme activities. Although we found few relationships between ecosystem functions and microbial alpha diversity, all functions were correlated with microbial community composition metrics, particularly r:K strategist ratios of bacterial phyla. Additionally, for both ecosystem multifunctionality and specific processes (i.e., C‐ and N‐mineralization), microbial metrics significantly improved models seeking to explain variation in process rates. Our work sheds light on the links between microbial communities and ecosystem functioning and identifies specific microbial metrics important for modeling ecosystem responses to environmental change.
Phylogenetic conservatism explains why plants are more likely to produce fleshy fruits in the tropics
Authors: Wang Gang , Ives Anthony R. , Zhu Hua , Tan Yunhong , Chen Si‐Chong , Yang Jie , Wang Bo 
Published: October 2021

AbstractPlant functional traits often show strong latitudinal trends. To explain these trends, studies have often focused on environmental variables, correlations with other traits that themselves show latitudinal trends, and phylogenetic conservatism. However, few studies have systematically disentangled the relative contributions of these factors. Using a dataset consisting of 9,370 plant species from Southwest China, we investigated factors affecting fruit type (fleshy vs. dry): plant growth form, environmental constraints (summarized by climate region), and phylogenetic conservatism. Growth form and climate region are often cited in the literature as important explanations for the higher proportion of fleshy fruited species in the tropics. Nonetheless, in our analyses using partial R2, growth form and climate region explained only 1.7% and 0.3%, respectively, of the variance in fruit type in a model including phylogeny, while phylogenetic conservatism explained 79.5%. Furthermore, phylogenetic conservatism was evenly distributed along the phylogeny, implying that fruit type reflects both ancient and recent phylogenetic relationships. Our findings illustrate the value of parsing out the contributions of explanatory variables and phylogeny to the variance in species' traits. Methods using phylogenies that calculate partial R2 give a more informative tool than traditional methods to explore the phylogenetic patterns of functional traits.