bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nano-Biphasic Calcium Phosphate Ceramic for the Repair of Bone Defects
Authors: Rezaei Majid , Farhadian Mohammad , Rashidi Ali Mohammad , Saeidipour Mahshid , Manshaei Maziar , Rezaee Masih 
Published: March 2018

AbstractCalcium phosphate bioceramics has recently experienced increased interest in bone reconstruction. Mimicking of natural structure of bone, like the use of nanomaterials, is an attractive approach for generating scaffolds for bone regeneration. The aim of present study was to evaluate the effect of nanonization on the biphasic calcium phosphate (BCP) ceramic in the repair of bone cavities in the canine mandible. A commercial BCP was dry-milled in a high energy planetary ball mill with zirconia balls and container. Three holes (8 mm in diameter) were outlined to the depth of cortical bone of mandibular angle of 5 dogs bilaterally. The first hole (positive control group A, n = 10) was filled in with commercial BCP material. The second hole was loaded with the nanonized BCP (experimental group C, n = 10) and the third one was left untreated (negative control group B, n = 10). The defects were allowed to regenerate for 8 weeks. New bone formation was greater in groups A and C than in B. No difference was seen between group A and group C (P = 0.676). The residual bone material in group C (19.34 ± 8.03) was as much as one-half of that in group A (38.69 ± 7.90%) (P = 0.000). The negative control group B presented the highest amount of soft tissue within the bone defects. The least percentage of marrow space was found in the positive control group (13.23 ± 13.52). Our results depicted that the rate of resorption increased significantly after nanonization even though the nano-sized BCP failed to make a superior regeneration than the ordinary BCP.
The evolution of pediatric transfusion practice during combat operations 2001-2013
Authors: Cannon Jeremy W. , Neff Lucas P. , Pidcoke Heather F. , Aden James K. , Spinella Philip C. , Johnson Michael A. , Cap Andrew P. , Borgman Matthew A. 
Published: March 2018

BACKGROUND
Hemostatic resuscitation principles have significantly changed adult trauma resuscitation over the past decade. Practice patterns in pediatric resuscitation likely have changed as well; however, this evolution has not been quantified. We evaluated pediatric resuscitation practices over time within a combat trauma system.

METHODS
The Department of Defense Trauma Registry was queried from 2001 to 2013 for pediatric patients (<18 years). Patients with burns, drowning, and missing injury severity score were excluded. Volumes of crystalloid, packed red blood cells (PRBC), whole blood, plasma, and platelets (PLT) given in the first 24 hours were calculated per kilogram body weight. Tranexamic acid use was also determined. Patients were divided into Early (2001–2005) and Late (2006–2013) cohorts, and subgroups of transfused (TX+) and massively transfused (MT+) patients were created. Intensive care unit and hospital length of stay and 24-hour and in-hospital mortality rates were compared.

RESULTS
A total of 4,358 patients met inclusion criteria. Comparing Early versus Late, injuries from explosions, isolated or predominant head injuries, and injury severity score all increased. The proportion of TX+ patients also increased significantly (13.6% vs 37.4%, p < 0.001) as did the number of MT+ patients (2.1% vs 15.5%, p < 0.001). Transfusion of high plasma:RBC and PLT:RBC ratios increased in both the TX+ and MT+ subgroups, although overall, PLT and whole blood use was low. After adjusting for differences between groups, the odds of death was no different Early versus Late but decreased significantly in the MT+ patients with time as a continuous variable.

CONCLUSION
Transfusion practice in pediatric combat casualty care shifted toward a more hemostatic approach over time. All-cause mortality was low and remained stable overall and even decreased in MT+ patients despite more injuries due to explosions, more head injuries, and greater injury severity. However, further study is required to determine the optimal resuscitation practices in critically injured children.

LEVEL OF EVIDENCE
Epidemiologic study, level IV.
Systemic hyperfibrinolysis after trauma: a pilot study of targeted proteomic analysis of superposed mechanisms in patient plasma
Authors: Banerjee Anirban , Silliman Christopher C. , Moore Ernest E. , Dzieciatkowska Monika , Kelher Marguerite , Sauaia Angela , Jones Kenneth , Chapman Michael P. , Gonzalez Eduardo , Moore Hunter B. , D’Alessandro Angelo , Peltz Erik , Huebner Benjamin E. , Einerson Peter , Chandler James , Ghasabayan Arsen , Hansen Kirk 
Published: March 2018

BACKGROUND
Viscoelastic measurements of hemostasis indicate that 20% of seriously injured patients exhibit systemic hyperfibrinolysis, with increased early mortality. These patients have normal clot formation with rapid clot lysis. Targeted proteomics was applied to quantify plasma proteins from hyperfibrinolytic (HF) patients to elucidate potential pathophysiology.

METHODS
Blood samples were collected in the field or at emergency department arrival and thrombelastography (TEG) was used to characterize in vitro clot formation under native and tissue plasminogen activator (tPA)-stimulated conditions. Ten samples were taken from injured patients exhibiting normal lysis time at 30 min (Ly30), “eufibrinolytic” (EF), 10 from HF patients, defined as tPA-stimulated TEG Ly30 >50%, and 10 from healthy controls. Trauma patient samples were analyzed by targeted proteomics and ELISA assays for specific coagulation proteins.

RESULTS
HF patients exhibited increased plasminogen activation. Thirty-three proteins from the HF patients were significantly decreased compared with healthy controls and EF patients; 17 were coagulation proteins with anti-protease consumption (p < 0.005). The other 16 decreased proteins indicate activation of the alternate complement pathway, depletion of carrier proteins, and four glycoproteins. CXC7 was elevated in all injured patients versus healthy controls (p < 0.005), and 35 proteins were unchanged across all groups (p > 0.1 and fold change of concentrations of 0.75–1.3).

CONCLUSION
HF patients had significant decreases in specific proteins and support mechanisms known in trauma-induced hyperfibrinolysis and also unexpected decreases in coagulation factors, factors II, X, and XIII, without changes in clot formation (SP, R times, or angle). Decreased clot stability in HF patients was corroborated with tPA-stimulated TEGs.

LEVEL OF EVIDENCE
Prognostic, level III.
Programmed death 1/programmed cell death-ligand 1 pathway participates in gastric surgery-induced imbalance of T-helper 17/regulatory T cells in mice
Authors: Dong Linlin , Zheng Xiaoyu , Wang Kun , Wang Guonian , Zou Huichao 
Published: March 2018

BACKGROUND
The T-helper 17 (Th17)/regulatory T (Treg) cell balance is essential for immune homeostasis. However, the effects of gastric surgery on this balance remain unclear. The aim of present study is to identify the influence of gastric surgery on Th17/Treg cell balance and the role of programmed death 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) pathway in this process.

METHODS
Mice were divided into control, sham, and surgery group randomly. Animals in surgery group accepted partial gastrectomy. Mice in sham group only received laparotomy without partial gastrectomy. Then, we detected the percentages of Treg and Th17 cells, the expression of fork-head/winged helix transcription factor (Foxp3) and retinoic acid-related orphan receptor γt (RORγt) in splenocytes, as well as plasma levels of transforming growth factor (TGF)-β1 and interleukin (IL)-17 on Days 1, 3, 5, 7 after surgery. We also analyzed the expression of PD-1 and PD-L1. The roles of PD-1/PD-L1 on the Th17/Treg balance were evaluated by the induction of Th17 or Treg cells in the presence or absence of PD-1 antibody and recombinant PD-L1 immunoglobulin (Ig) in vitro.

RESULTS
The percentage of Treg cells increased, accompanied with elevated expression of Foxp3 and TGF-β1 (p < 0.05), whereas the percentage of Th17 cells and the expression of RORγt and IL-17 decreased in mice that underwent partial gastrectomy (p < 0.05). The levels of PD-1 and PD-L1 were higher in surgery group than those in control and sham groups (p < 0.05). In vitro, the polarization of Th17 cells was enhanced, and the polarization of Treg cells was inhibited in anti–PD-1 treatment group compared with that in isotype group (p < 0.05).

CONCLUSION
Partial gastrectomy resulted in Th17/Treg imbalance, and increased the expression of PD-1 and PD-L1. blockade of PD-1/PD-L1 pathway alleviated gastric surgery-induced imbalance of Th17/Treg cells.
Adaptive and platform trials in remote damage control resuscitation
Authors: Tolles Juliana , Lewis Roger J. 
Published: March 2018

ABSTRACT
The traditional approach to clinical trial design requires assuming precise values for multiple unknown parameters, resulting in a trial design that is unlikely to perform well if one or more of those assumptions turn out to be incorrect. During conduct of the trial, trial characteristics are often held fixed, even if incoming data suggest that one or more design assumptions were incorrect. This leads to an increased risk of a failed trial. In contrast, an adaptive clinical trial is designed to take advantage of partial, incoming data during the conduct of the trial, modifying key clinical trial characteristics according to prespecified rules, in order to avoid a failed or inconclusive trial, improve statistical efficacy, better treat patients within the trial, or achieve other scientific or ethical goals. The concept of an adaptive trial can be expanded to a platform trial, a clinical trial that is intended to evaluate multiple treatments or combinations of treatments, often for patients with any of a group of related diseases, and to continue beyond the evaluation of any particular treatment. Platform trial design strategies can be applied to the problem of finding the best treatment strategy for patients suffering from posttraumatic hemorrhagic shock. We present the rationale and considerations surrounding adaptive and platform trial design and apply these concepts to the problem of investigating strategies for remote damage control resuscitation.
Cerebrospinal Fluid Pressure Reduction Results in Dynamic Changes in Optic Nerve Angle on Magnetic Resonance Imaging
Authors: Hu Ranliang , Holbrook John , Newman Nancy J. , Biousse Valerie , Bruce Beau B. , Qiu Deqiang , Oshinski John , Saindane Amit M. 
Published: March 2018

Background:
Optic nerve sheath tortuosity is a previously reported, but incompletely characterized, finding in idiopathic intracranial hypertension (IIH). We hypothesized that optic nerve angle (ONA), as a quantitative measure of tortuosity, would change dynamically with cerebrospinal fluid (CSF) pressure status of patients with IIH immediately before and after lumbar puncture (LP).

Methods:
Consecutive patients with suspected IIH referred for MRI and diagnostic LP were prospectively enrolled in this single institution, institutional review board–approved study. Each patient underwent a pre-LP MRI, diagnostic LP with opening pressure (OP) and closing pressure (CP), and then post-LP MRI all within 1 session. Sagittal and axial ONAs were measured on multiplanar T2 SPACE images by 2 neuroradiologists on pre- and post-LP MRI. Effects of measured pressure and CSF volume removal on changes in ONA were analyzed as was interrater reliability for ONA measurement.

Results:
Ten patients with IIH were included {all female, median age 29 (interquartile range [IQR] 25–32)}. All patients had elevated OP (median 37, IQR 34–41 cm H2O), and significantly reduced CP (median 18, IQR 16–19 cm H2O, P < 0.001) after CSF removal (IQR 13–16 mL). Within patients, mean ONAs (sagittal and axial) were significantly lower before (162 ± 9°, 163 ± 10°) than after (168 ± 7°, 169 ± 5°) LP (P = 0.001, 0.008, respectively). Interrater reliability was higher with sagittal ONA measurements (0.89) than axial (0.72).

Conclusions:
ONA changes with short-term CSF pressure reduction in patients with IIH, establishing optic nerve tortuosity as a dynamic process related to CSF status.
PI3Kδ hyper-activation promotes the development of B cells that exacerbateStreptococcus pneumoniaeinfection in an antibody-independent manner
Authors: Stark Anne-Katrien , Chandra Anita , Chakraborty Krishnendu , Alam Rafeah , Carbonaro Valentina , Clark Jonathan , Sriskantharajah Srividya , Bradley Glyn , Richter Alex G. , Banham-Hall Edward , Clatworthy Menna R. , Nejentsev Sergey , Nicole Hamblin J. , Hessel Edith M. , Condliffe Alison M. , Okkenhaug Klaus 
Published: March 2018

AbstractStreptococcus pneumoniaeis a major cause of pneumonia and a leading cause of death world-wide. Antibody-mediated immune responses can offer protection against repeated exposure toS. pneumoniae, yet vaccines only offer partial protection. Patients with Activated PI3Kδ Syndrome (APDS) are highly susceptible toS. pneumoniae. We generated a conditional knockin mouse model of this disease and identified a CD19+B220−B cell subset that is induced by PI3Kδ signaling, is resident in the lungs, and which promotes increased susceptibility toS. pneumoniaeduring the early phase of infection via an antibody-independent mechanism. We show that an inhaled PI3Kδ inhibitor improves survival rates followingS. pneumoniaeinfection in wild-type mice and in mice with activated PI3Kδ. These results suggest that a subset of B cells in the lung can promote the severity ofS. pneumoniaeinfection, representing a novel therapeutic target.
Genome-wide features of introns are evolutionary decoupled among themselves and from genome size throughout Eukarya
Authors: Lozada-Chávez Irma , Stadler Peter F. , Prohaska Sonja J. 
Published: March 2018

AbstractThe impact of spliceosomal introns on genome and organismal evolution remains puzzling. Here, we investigated the correlative associations among genome-wide features of introns from protein-coding genes (e.g., size, density, genome-content, repeats), genome size and multicellular complexity on 461 eukaryotes. Thus, we formally distinguished simple from complex multicellular organisms (CMOs), and developed the program GenomeContent to systematically estimate genomic traits. We performed robust phylogenetic controlled analyses, by taking into account significant uncertainties in the tree of eukaryotes and variation in genome size estimates. We found that changes in the variation of some intron features (such as size and repeat composition) are only weakly, while other features measuring intron abundance (within and across genes) are not, scaling with changes in genome size at the broadest phylogenetic scale. Accordingly, the strength of these associations fluctuates at the lineage-specific level, and changes in the length and abundance of introns within a genome are found to be largely evolving independently throughout Eukarya. Thereby, our findings are in disagreement with previous estimations claiming a concerted evolution between genome size and introns across eukaryotes. We also observe that intron features vary homogeneously (with low repetitive composition) within fungi, plants and stramenophiles; but they vary dramatically (with higher repetitive composition) within holozoans, chlorophytes, alveolates and amoebozoans. We also found that CMOs and their closest ancestral relatives are characterized by high intron-richness, regardless their genome size. These patterns contrast the narrow distribution of exon features found across eukaryotes. Collectively, our findings unveil spliceosomal introns as a dynamically evolving non-coding DNA class and strongly argue against both, a particular intron feature as key determinant of eukaryotic gene architecture, as well as a major mechanism (adaptive or non-adaptive) behind the evolutionary dynamics of introns over a large phylogenetic scale. We hypothesize that intron-richness is a pre-condition to evolve complex multicellularity.
State-Unspecific Modes of Whole-Brain Functional Connectivity Predict Intelligence and Life Outcomes
Authors: Takagi Yu , Hirayama Jun-ichiro , Tanaka Saori C 
Published: March 2018

AbstractRecent functional magnetic resonance imaging (fMRI) studies have increasingly revealed potential neural substrates of individual differences in diverse types of brain function and dysfunction. Although most previous studies have been inherently limited to state-specific characterizations of related brain networks and their functions, several recent studies have examined the potential state-unspecific nature of functional brain networks, such as their global similarities across different experimental conditions (i.e., states) including both task and rest. However, no previous studies have carried out direct, systematic characterizations of state-unspecific brain networks, or their functional implications. Here, we quantitatively identified several modes of state-unspecific individual variation in whole-brain functional connectivity patterns, called “Common Neural Modes (CNMs)”, from a large fMRI dataset including eight task/rest states, obtained from the Human Connectome Project. Furthermore, we tested how CNMs account for variability in individual behavioral measures. The results revealed that three CNMs were robustly extracted under various different preprocessing conditions. Each of these CNMs was significantly correlated with different aspects of behavioral measures of both fluid and crystalized intelligence. The three CNMs were also able to predict several life outcomes, such as income and life satisfaction, achieving the highest performance when combined with behavioral intelligence measures as inputs. Our findings highlight the importance of state-unspecific brain networks to characterize fundamental individual variation.
Selection signatures underlying dramatic male inflorescence transformation during modern hybrid maize breeding
Authors: Gage Joseph L. , White Michael R. , Edwards Jode W. , Kaeppler Shawn , de Leon Natalia 
Published: March 2018

AbstractInflorescence capacity plays a crucial role in reproductive fitness in plants, and in production of hybrid crops. Maize is a monoecious species bearing separate male and female flowers (tassel and ear, respectively). The switch from open-pollinated populations of maize to hybrid-based breeding schemes in the early 20thcentury was accompanied by a dramatic reduction in tassel size, and the trend has continued with modern breeding over the recent decades. The goal of this study was to identify selection signatures in genes that may underlie this dramatic transformation. Using a population of 942 diverse inbred maize accessions and a nested association mapping population comprised of three 200-line biparental populations, we measured 15 tassel morphological characteristics by manual and image-based methods. Genome-wide association studies identified 242 single nucleotide polymorphisms significantly associated with measured traits. We compared 41 unselected lines from the Iowa Stiff Stalk Synthetic (BSSS) population to 21 highly selected lines developed by modern commercial breeding programs and show that tassel size and weight were reduced significantly. We assayed genetic differences between the two groups using selection statistics XP-EHH, XP-CLR, and FST. All three selection statistics show evidence of selection at genomic regions associated with tassel morphology relative to genome-wide null distributions. These results support the tremendous effect, both phenotypic and genotypic, that selection has had on maize male inflorescence morphology.
Extensive horizontal exchange of transposable elements in theDrosophila pseudoobscuragroup
Authors: Hill Tom , Betancourt Andrea J. 
Published: March 2018

AbstractWhile the horizontal transfer of a parasitic element can be a potentially catastrophic, it is increasingly recognized as a common occurrence. The horizontal exchange, or lack of exchange, of TE content between species results in different levels of divergence among a species group in the mobile component of their genomes. Here, we examine differences in the TE content of theDrosophila pseudoobscuraspecies group. We identify several putative horizontal transfer events, and examine the role that horizontal transfer plays in the spread of TE families to new species and the homogenization of TE content in these species. Despite rampant exchange of TE families between species, we find that both TE content differs hugely across the group, likely due to differing activity of each TE family and differing suppression of TEs due to divergence in Y chromosome size, and its resulting effects of TE regulation. Overall, we show that TE content is highly dynamic in this species group, and that it plays a large role in shaping the differences seen between species.Data availabilityAll data used in this study (summarized in table S1) is freely available online through the NCBI short read archive (NCBI SRA: ERR127385, SRR330416, SRR330418, SRR1925723, SRR330426, SRR330420, SRR330423, SRR617430-74). All genomes used are either available throughflybase.orgorpopoolation.at.
Altered Bile Acid Profile in Mild Cognitive Impairment and Alzheimer’s Disease: Relationship to Neuroimaging and CSF Biomarkers
Authors: Nho Kwangsik , Kueider-Paisley Alexandra , MahmoudianDehkordi Siamak , Arnold Matthias , Risacher Shannon L. , Louie Gregory , Blach Colette , Baillie Rebecca , Han Xianlin , Kastenmüller Gabi , Jia Wei , Xie Guoxiang , Ahmad Shahzad , Hankemeier Thomas , van Duijn Cornelia M. , Trojanowski John Q. , Shaw Leslie M. , Weiner Michael W. , Doraiswamy P. Murali , Saykin Andrew J. , Kaddurah-Daouk Rima ,   for the Alzheimer’s Disease Neuroimaging Initiative and the Alzheimer Disease Metabolomics Consortium
Published: March 2018

AbstractIntroductionBile acids (BAs) are the end products of cholesterol metabolism produced by human and gut microbiome co-metabolism. Recent evidence suggests gut microbiota influence pathological features of Alzheimer’s disease (AD) including neuroinflammation and amyloid-β deposition.MethodSerum levels of 20 primary and secondary BA metabolites from the AD Neuroimaging Initiative (n=1562) were measured using targeted metabolomic profiling. We assessed the association of BAs with the “A/T/N” (Amyloid, Tau and Neurodegeneration) biomarkers for AD: CSF biomarkers, atrophy (MRI), and brain glucose metabolism ([18F]FDG-PET).ResultsOf 23 BA and relevant calculated ratios, three BA signatures were associated with CSF Aβ1-42 (“A”) and three with CSF p-tau181 (“T”) (correctedp<0.05). Furthermore, three, twelve, and fourteen BA signatures were associated with CSF t-tau, glucose metabolism, and atrophy (“N”), respectively (correctedp<0.05).ConclusionThis is the first study to show serum-based BA metabolites are associated with “A/T/N” AD biomarkers, providing further support for a role of BA pathways in AD pathophysiology. Prospective clinical observations and validation in model systems are needed to assess causality and specific mechanisms underlying this association.