bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recommendations on RBC Transfusion in Critically Ill Children With Acute Brain Injury From the Pediatric Critical Care Transfusion and Anemia Expertise Initiative
Authors: Tasker Robert C. , Turgeon Alexis F. , Spinella Philip C. 
Published: August 2018

Objectives:
To present the recommendations and supporting literature for RBC transfusions in critically ill children with acute brain injury developed by the Pediatric Critical Care Transfusion and Anemia Expertise Initiative.

Design:
Consensus conference series of international, multidisciplinary experts in RBC transfusion management of critically ill children.

Methods:
The panel of 38 experts developed evidence-based, and when evidence was lacking, expert-based clinical recommendations as well as research priorities for RBC transfusions in critically ill children. The acute brain injury subgroup included three experts. Electronic searches were conducted using PubMed, EMBASE, and Cochrane Library databases from 1980 to May 2017. Agreement was obtained using the Research and Development/UCLA Appropriateness Method. Results were summarized using the Grading of Recommendations Assessment, Development, and Evaluation method.

Results:
Transfusion and Anemia Expertise Initiative Consensus Conference experts developed and agreed upon two clinical and two research recommendations focused on RBC transfusion in the critically ill child with acute brain injury. Recommendations include consideration of RBC transfusion for a hemoglobin concentration between 7 and 10 g/dL in patients with acute brain injury and do not support the use of brain tissue Po
2 monitoring to guide RBC transfusion decisions. Research is needed to better understand transfusion thresholds and brain tissue monitoring for pediatric patients with acute brain injury.

Conclusions:
The Transfusion and Anemia Expertise Initiative Consensus Conference developed pediatric-specific clinical and research recommendations regarding RBC transfusion in the critically ill child with acute brain injury. Although agreement among experts was very strong, the available pediatric evidence was extremely limited with major gaps in the literature.
Ultrasound Combined With Microbubbles Increase the Delivery of Doxorubicin by Reducing the Interstitial Fluid Pressure
Authors: Xiao Nina , Liu Jianhua , Liao Lianlian , Sun Jimei , Jin Wenhui , Shu Xian 
Published: August 2018

Abstract
The aims of this study were to determine the change of interstitial fluid pressure (IFP) after therapy using pulsed low-frequency ultrasound combined with microbubbles and to determine the change of doxorubicin penetration in VX2 tumor. In this study, all 48 tumor-bearing rabbits were divided randomly into 6 groups (n = 8 per group). These 6 groups include doxorubicin therapy together with ultrasound combined with microbubble treatment group (Ad-US-MB treatment group), US-MB treatment group, US treatment group, MB treatment group, doxorubicin treatment group (Ad treatment group), and blank control group. The animals were intravenously injected with doxorubicin hydrochloride, and then the tumors of the animals were disposed by low-intensity ultrasound and mirobubbles for 10 minutes. The IFP of tumor tissues in rabbits was detected before and after intervention. Rabbits in each group were sacrificed immediately after treatment. The concentration and the distribution of doxorubicin were detected. The tumor IFP was significantly lower than that before treatment in the Ad-US-MB treatment and US-MB treatment groups (P = 0.01, P = 0.013). Ultrasound combined with microbubble increased the concentration of doxorubicin in the sample of the Ad-US-MB treatment group compared with the Ad treatment group (P < 0.05). In immunofluorescent staining section, high concentrations of doxorubicin were observed mainly around the blood vessels, and some were even discovered at a farther area in the Ad-US-MB treatment group. The pulsed low-frequency ultrasound combined with the microbubbles enhances the vascular clearance of particles into the tumor interstitium by reducing IFP.
Gray Scale Ultrasound, Color Doppler Ultrasound, and Contrast-Enhanced Ultrasound in Renal Parenchymal Diseases
Authors: Quaia Emilio , Correas Jean Michel , Mehta Maithili , Murchison John T. , Gennari Antonio Giulio , van Beek Edwin J.R. 
Published: August 2018

Abstract
Ultrasound (US), which may be combination of gray scale and spectral Doppler US, color and power Doppler US, with or without microbubble contrast agents, is usually the first imaging modality to be used in renal parenchymal diseases. The most typical appearance of diffuse renal parenchymal diseases on gray scale US is an increased renal cortical echogenicity and increased or reduced corticomedullary differentiation. Spectral Doppler analysis of intrarenal flows may reveal an increase in intrarenal resistive index value greater than 0.70 in native kidneys, and greater than 0.8 in renal transplants. Gray scale US and spectral Doppler US do not exhibit high specificity and sensitivity because different renal parenchymal diseases often display the same US appearance, whereas the same renal parenchymal disease may present different appearances on US according to disease stage. Consequently, correlation of the US pattern with patient's history and clinical background is essential for a correct characterization.
Course Review
Authors: Berner Juan Enrique , Kyriazidis Ioannis 
Published: August 2018

Abstract
Dermoscopy is a physical examination technique that combines the use of illumination and magnification, provided by a handheld device, to scrutinize skin lesions. Its use increases the diagnostic accuracy for the trained operator, providing more information for making better decisions for the management of skin cancer. The “International Dermoscopy Course for Plastic Surgeons” aims to train plastic surgery trainees and consultants in the use of this technique. This 1-day, lecture-based course is held 4 times a year in the city of Oxford, United Kingdom, at a cost of £250 (US $340). This article intends to provide a review of this course.
Molecular dating of the emergence of anaerobic rumen fungi and the impact of laterally acquired genes
Authors: Wang Yan , Youssef Noha , Couger M.B. , Hanafy Radwa , Elshahed Mostafa , Stajich Jason E. 
Published: August 2018

AbstractThe anaerobic gut fungi (AGF) or Neocallimastigomycota inhabit the rumen and alimentary tract of herbivorous mammals, where they play an important role in the degradation of plant fiber. Comparative genomic and phylogenomic analysis of the AGF has long been hampered by their fastidious growth pattern as well as their large and AT-biased genomes. We sequenced 21 AGF transcriptomes and combined them with 5 available genome sequences of AGF taxa to explore their evolutionary relationships, time their divergence, and characterize patterns of gene gain/loss associated with their evolution. We estimate that the most recent common ancestor of the AGF diverged 66 (±10) million years ago, a timeframe that coincides with the evolution of grasses (Poaceae), as well as the mammalian transition from insectivory to herbivory. The concordance of these independently estimated ages of AGF evolution, grasses evolution, and mammalian transition to herbivory suggest that AGF have been important in shaping the success of mammalian herbivory transition by improving the efficiency of energy acquisition from recalcitrant plant materials. Comparative genomics identified multiple lineage-specific genes and protein domains in the AGF, two of which were acquired from an animal host (galectin) and rumen gut bacteria (carbohydrate-binding domain) via horizontal gene transfer (HGT). Four of the bacterial derived “Cthe_2159” genes in AGF genomes also encode eukaryotic Pfam domains (“Atrophin-1”, “eIF-3_zeta”, “Nop14”, and “TPH”) indicating possible gene fusion events after the acquisition of “Cthe_2159” domain. A third AGF domain, plant-like polysaccharide lyase N-terminal domain (“Rhamnogal_lyase”), represents the first report from fungi that potentially aids AGF to degrade pectin. Analysis of genomic and transcriptomic sequences confirmed the presence and expression of these lineage-specific genes in nearly all AGF clades supporting the hypothesis that these laterally acquired and novel genes in fungi are likely functional. These genetic elements may contribute to the exceptional abilities of AGF to degrade plant biomass and enable metabolism of the rumen microbes and animal hosts.
Integrin α6β4 recognition of a linear motif of bullous pemphigoid antigen BP230 controls its recruitment to hemidesmosomes
Authors: Manso José A , Gómez-Hernández Maria , Carabias Arturo , Alonso-García Noelia , García-Rubio Inés , Kreft Maaike , Sonnenberg Arnoud , de Pereda José M 
Published: August 2018

AbstractMechanical stability of epithelia requires firm attachment to the basement membrane via hemidesmosomes. Dysfunction of hemidesmosomal proteins causes severe skin blistering diseases. Two plakins, plectin and BP230 (BPAG1e), link the integrin α6β4 to intermediate filaments in epidermal hemidesmosomes. Here, we show that a linear sequence within the isoform-specific N-terminal region of BP230 binds to the third and fourth FnIII domains of β4. The crystal structure of the complex and mutagenesis analysis revealed that BP230 binds between the two domains of β4. BP230 induces closing of the two FnIII domains that are looked in place by an inter-domain ionic clasp required for binding. Disruption of the BP230-β4 interface prevents the recruitment of BP230 to hemidesmosomes in human keratinocytes, revealing a key role of the BP230-β4 interaction for hemidesmosome assembly. Phosphomimetic substitutions in β4 and BP230 disrupt binding. Our study provides insights into the molecular mechanisms of hemidesmosome architecture and regulation.
What we (don’t) know about global plant diversity
Authors: Cornwell William K. , Pearse William D. , Dalrymple Rhiannon L. , Zanne Amy 
Published: August 2018

SummaryRationaleThe era of big biodiversity data has led to rapid, exciting advances in theoretical and applied biological, ecological and conservation sciences. While large genetic, geographic and trait databases are available, these are neither complete nor random samples of the globe. Biases in species absence in these databases create problems, reducing our inferential and predictive power.MethodsWe performed a comprehensive examination of the taxonomic and spatial sampling in the most complete current databases for plant genes, locations, and traits.ResultsOnly 17.7% of the world’s described land plants feature in all three databases, meaning that more than 82% of plant biodiversity lacks representation in at least one database. Species coverage is highest for location data and lowest for genetic data. Bryophytes and orchids stand out taxonomically and the equatorial region stands out spatially as poorly represented in all databases.ConclusionWe have highlighted a number of clades and regions about which we know little functionally, spatially and genetically, on which we should set research targets. The scientific community should recognize and reward the significant value, both for biodiversity science and conservation, of filling in these gaps in our knowledge of the plant tree of life.
Organization of state transitions in the resting-state human cerebral cortex
Authors: Kang Jiyoung , Pae Chongwon , Park Hae-Jeong 
Published: August 2018

AbstractThe resting-state brain is often considered a nonlinear dynamic system transitioning among multiple coexisting stable states. Despite the increasing number of studies on the multistability of the brain system, the processes of state transitions have rarely been systematically explored. Thus, we investigated the state transition processes of the human cerebral cortex system at rest by introducing a graph-theoretic analysis of the state transition network. The energy landscape analysis of brain state occurrences, estimated using the pairwise maximum entropy model for resting-state fMRI data, identified multiple local minima, some of which mediate multi-step transitions toward the global minimum. The state transition among local minima is clustered into two groups according to state transition rates and most inter-group state transitions were mediated by a hub transition state. The distance to the hub transition state determined the path length of the inter-group transition. The cortical system appeared to have redundancy in inter-group transitions when the hub transition state was removed. Such a hub-like organization of transition processes disappeared when the connectivity of the cortical system was altered from the resting-state configuration. In summary, the resting-state cerebral cortex has a well-organized architecture of state transitions among stable states, when evaluated by nonlinear systematic approach.
Cytotoxic Profiling of Annotated and Diverse Chemical Libraries Using Quantitative High-Throughput Screening
Authors: Lee Olivia W. , Austin Shelley , Gamma Madison , Cheff Dorian M. , Lee Tobie D. , Wilson Kelli M. , Johnson Joseph , Travers Jameson , Braisted John C. , Guha Rajarshi , Klumpp-Thomas Carleen , Shen Min , Hall Matthew D. 
Published: August 2018

AbstractCell-based phenotypic screening is a commonly used approach to discover biological pathways, novel drug targets, chemical probes and high-quality hit-to-lead molecules. Many hits identified from high-throughput screening campaigns are ruled out through a series of follow-up potency, selectivity/specificity, and cytotoxicity assays. Prioritization of molecules with little or no cytotoxicity for downstream evaluation can influence the future direction of projects, so cytotoxicity profiling of screening libraries at an early stage is essential for increasing the likelihood of candidate success. In this study, we assessed cell-based cytotoxicity of nearly 10,000 compounds in NCATS annotated libraries, and over 100,000 compounds in a diversity library, against four ‘normal’ cell lines (HEK 293, NIH 3T3, CRL-7250 and HaCat) and one cancer cell line (KB 3-1, a HeLa subline). This large-scale library profiling was analyzed for overall screening outcomes, hit rates, pan-activity and selectivity. For the annotated library, we also examined the primary targets and mechanistic pathways regularly associated with cell death. To our knowledge, this is the first study to use high-throughput screening to profile a large screening collection (>100,000 compounds) for cytotoxicity in both normal and cancer cell lines. The results generated here constitutes a valuable resource for the scientific community and provides insight on the extent of cytotoxic compounds in screening libraries, identifying and avoiding compounds with cytotoxicity during high-throughput screening campaigns.
A least microenvironmental uncertainty principle (LEUP) as a generative model of collective cell migration mechanisms
Authors: Barua Arnab , Nava-Sedeño Josue M. , Hatzikirou Haralampos 
Published: August 2018

AbstractCollective migration is commonly observed in groups of migrating cells, in the form of swarms or aggregates. Mechanistic models have proven very useful in understanding collective cell migration. Such models, either explicitly consider the forces involved in the interaction and movement of individuals or phenomenologically define rules which mimic the observed behavior of cells. However, mechanisms leading to collective migration are varied and specific to the type of cells involved. Additionally, the precise and complete dynamics of many important chemomechanical factors influencing cell movement, from signalling pathways to substrate sensing, are typically either too complex or largely unknown. The question is how to make quantitative/qualitative predictions of collective behavior without exact mechanistic knowledge. Here we propose the least microenvironmental uncertainty principle (LEUP) that serves as a generative model of collective migration without incorporation of full mechanistic details. Interestingly we show that the famous Vicsek model is a special case of LEUP. Finally, as a proof of concept, we apply the LEUP to quantitatively study ofthe collective behavior of spherical Serratia marcescens bacteria, where the underlying migration mechanisms remain elusive.
Human-like NSG mouse glycoproteins sialylation pattern changes the phenotype of human lymphocytes and sensitivity to HIV-1 infection
Authors: Dagur Raghubendra Singh , Woods Amanda Branch , Mathews Saumi , Joshi Poonam S. , Quadros Rolen M. , Harms Donald W. , Cheng Yan , Miles Shana M , Pirruccello Samuel J. , Gurumurthy Channabasavaiah B. , Gorantla Santhi , Poluektova Larisa Y. 
Published: August 2018

AbstractBackgroundThe use of immunodeficient mice transplanted with human hematopoietic stem cells is an accepted approach to study human-specific infectious diseases, like HIV-1, and to investigate multiple aspects of human immune system development. However, mouse and human are different in sialylation patterns of proteins due to evolutionary mutations of the CMP-N-acetylneuraminic acid hydroxylase (CMAH) gene that prevent formation of N-glycolylneuraminic acid from N-acetylneuraminic acid. How changes of mouse glycoproteins chemistry will affect phenotype and function of transplanted human hematopoietic stem cells and mature human immune cells in the course of HIV-1 infection is not known.ResultsWe mutated mouseCMAHon the most widely human cells transplantation strain NOD/scid-IL2Rγc-/-(NSG) mouse background using the CRISPR/Cas9 system. The new strain provides a better environment for human immune cells. Transplantation of human hematopoietic stem cells leads to broad B cells repertoire, higher sensitivity to HIV-1 infection, and enhanced proliferation of transplanted peripheral blood lymphocytes. The mice showed low effects on the clearance of human immunoglobulins and enhanced transduction efficiency of recombinant adeno-associated viral vector rAAV2/DJ8.ConclusionNSG-cmah-/-mice expand the mouse models suitable for human cells transplantation and this new model has advantages in generating a human B cell repertoire. This strain is suitable to study different aspects of the human immune system development, might provide advantages in patient-derived tissue and cell transplantation, and could allow studies of viral vectors and infectious agents that are sensitive to human-like sialylation of mouse glycoproteins.
Anti-microRNA screen uncovers miR-17 family within miR-17~92 cluster as the primary driver of kidney cyst growth
Authors: Yheskel Matanel , Lakhia Ronak , Flaten Andrea , Patel Vishal 
Published: August 2018

AbstractAutosomal dominant polycystic kidney disease (ADPKD) is the leading genetic cause of renal failure. We have recently shown that inhibiting miR-17~92 is a potential novel therapeutic approach for ADPKD. However, miR-17~92 is a polycistronic cluster that encodes microRNAs (miRNAs) belonging to the miR-17, miR-18, miR-19 and miR-25 families, and the relative pathogenic contribution of these miRNA families to ADPKD progression is unknown. Here we performed an in vivo anti-miR screen to identify the miRNA drug targets within the miR-17~92 miRNA cluster. We designed anti-miRs to individually inhibit miR-17, miR-18, miR-19 or miR-25 families in an orthologous ADPKD model. Treatment with anti-miRs against the miR-17 family reduced cyst proliferation, kidney-weight-to-body-weight ratio and cyst index. In contrast, treatment with anti-miRs against the miR-18, 19, or 25 families did not affect cyst growth. Anti-miR-17 treatment recapitulated the gene expression pattern observed after miR-17~92 genetic deletion and was associated with upregulation of mitochondrial metabolism, suppression of the mTOR pathway, induction of autophagy, and inhibition of cyst-associated inflammation. Our results argue against functional cooperation between the various miR-17~92 cluster families in promoting cyst growth, and instead point to miR-17 family is the primary therapeutic target for ADPKD.
Extreme variation in rates of evolution in the plastid Clp protease complex
Authors: Williams Alissa M. , Friso Giulia , van Wijk Klaas J. , Sloan Daniel B. 
Published: August 2018

AbstractEukaryotic cells represent an intricate collaboration between multiple genomes, even down to the level of multisubunit complexes in mitochondria and plastids. One such complex in plants is the caseinolytic protease (Clp), which plays an essential role in plastid protein turnover. The proteolytic core of Clp comprises subunits from one plastid-encoded gene (clpP1) and multiple nuclear genes. TheclpP1gene is highly conserved across most green plants, but it is by far the fastest evolving plastid-encoded gene in some angiosperms. To better understand these extreme and mysterious patterns of divergence, we investigated the history ofclpP1molecular evolution across green plants by extracting sequences from 988 published plastid genomes. We find thatclpP1has undergone remarkably frequent bouts of accelerated sequence evolution and architectural changes (e.g., loss of introns and RNA-editing sites) within seed plants. AlthoughclpP1is often assumed to be a pseudogene in such cases, multiple lines of evidence suggest that this is rarely the case. We applied comparative native gel electrophoresis of chloroplast protein complexes followed by protein mass spectrometry in two species within the angiosperm genusSilene, which has highly elevated and heterogeneous rates ofclpP1evolution. We confirmed thatclpP1is expressed as a stable protein and forms oligomeric complexes with the nuclear-encoded Clp subunits, even in one of the most divergentSilenespecies. Additionally, there is a tight correlation between amino-acid substitution rates inclpP1and the nuclear-encoded Clp subunits across a broad sampling of angiosperms, suggesting ongoing selection on interactions within this complex.
Wnt/Fgf crosstalk is required for the specification of tracheal basal progenitor cells
Authors: Hou Zhili , Wu Qi , Sun Xin , Chen Huaiyong , Li Yu , Zhang Yongchun , Mori Munemasa , Yang Ying , Jiang Ming , Que Jianwen 
Published: August 2018

AbstractBasal progenitor cells are critical for the establishment and maintenance of the tracheal epithelium. However, it remains unclear how these progenitor cells are specified during foregut development. Here, we found that ablation of the Wnt chaperon protein Gpr177 (also known as Wntless) in the epithelium causes significant reduction in the numbers of basal progenitor cells accompanied by cartilage loss inShh-Cre;Gpr177loxp/loxpmutants. Consistent with the association between cartilage and basal cell development, Nkx2.1+p63+basal cells are co-present with cartilage nodules inShh-Cre;Ctnnb1DM/loxpmutants which keep partial cell-cell adhesion but not the transcription regulation function of ß-catenin. More importantly, deletion ofCtnnb1in the mesenchyme leads to the loss of basal cells and cartilage concomitant with the reduced transcript levels of Fgf10 inDermo1-Cre;Ctnnb1loxp/loxpmutants. Furthermore, deletion ofFgf receptor 2(Fgfr2) in the epithelium also leads to significantly reduced numbers of basal cells, supporting the importance of the Wnt/Fgf crosstalk in early tracheal development.