bluuebunny/crossref_metadata_2025_split huggingface dataset:
Veterinary Fusarioses within the United States
Authors: O'Donnell Kerry , Sutton Deanna A. , Wiederhold Nathan , Robert Vincent A. R. G. , Crous Pedro W. , Geiser David M. 
Published: September 2016

ABSTRACT

Multilocus DNA sequence data were used to assess the genetic diversity and evolutionary relationships of 67
Fusarium
strains from veterinary sources, most of which were from the United States. Molecular phylogenetic analyses revealed that the strains comprised 23 phylogenetically distinct species, all but two of which were previously known to infect humans, distributed among eight species complexes. The majority of the veterinary isolates (47/67 = 70.1%) were nested within the
Fusarium solani
species complex (FSSC), and these included 8 phylospecies and 33 unique 3-locus sequence types (STs). Three of the FSSC species (
Fusarium falciforme
,
Fusarium keratoplasticum
, and
Fusarium
sp. FSSC 12) accounted for four-fifths of the veterinary strains (38/47) and STs (27/33) within this clade. Most of the
F. falciforme
strains (12/15) were recovered from equine keratitis infections; however, strains of
F. keratoplasticum
and
Fusarium
sp. FSSC 12 were mostly (25/27) isolated from marine vertebrates and invertebrates. Our sampling suggests that the
Fusarium incarnatum-equiseti
species complex (FIESC), with eight mycoses-associated species, may represent the second most important clade of veterinary relevance within
Fusarium
. Six of the multilocus STs within the FSSC (3+4-eee, 1-b, 12-a, 12-b, 12-f, and 12-h) and one each within the FIESC (1-a) and the
Fusarium oxysporum
species complex (ST-33) were widespread geographically, including three STs with transoceanic disjunctions. In conclusion, fusaria associated with veterinary mycoses are phylogenetically diverse and typically can only be identified to the species level using DNA sequence data from portions of one or more informative genes.
Cell Adhesion Molecule CD166 Drives Malignant Progression and Osteolytic Disease in Multiple Myeloma
Authors: Xu Linlin , Mohammad Khalid S. , Wu Hao , Crean Colin , Poteat Bradley , Cheng Yinghua , Cardoso Angelo A. , Machal Christophe , Hanenberg Helmut , Abonour Rafat , Kacena Melissa A. , Chirgwin John , Suvannasankha Attaya , Srour Edward F. 
Published: September 2016

Abstract
Multiple myeloma is incurable once osteolytic lesions have seeded at skeletal sites, but factors mediating this deadly pathogenic advance remain poorly understood. Here, we report evidence of a major role for the cell adhesion molecule CD166, which we discovered to be highly expressed in multiple myeloma cell lines and primary bone marrow cells from patients. CD166+ multiple myeloma cells homed more efficiently than CD166− cells to the bone marrow of engrafted immunodeficient NSG mice. CD166 silencing in multiple myeloma cells enabled longer survival, a smaller tumor burden, and less osteolytic lesions, as compared with mice bearing control cells. CD166 deficiency in multiple myeloma cell lines or CD138+ bone marrow cells from multiple myeloma patients compromised their ability to induce bone resorption in an ex vivo organ culture system. Furthermore, CD166 deficiency in multiple myeloma cells also reduced the formation of osteolytic disease in vivo after intratibial engraftment. Mechanistic investigation revealed that CD166 expression in multiple myeloma cells inhibited osteoblastogenesis of bone marrow–derived osteoblast progenitors by suppressing Runx2 gene expression. Conversely, CD166 expression in multiple myeloma cells promoted osteoclastogenesis by activating TRAF6-dependent signaling pathways in osteoclast progenitors. Overall, our results define CD166 as a pivotal director in multiple myeloma cell homing to the bone marrow and multiple myeloma progression, rationalizing its further study as a candidate therapeutic target for multiple myeloma treatment. Cancer Res; 76(23); 6901–10. ©2016 AACR.
Olaparib, Monotherapy or with Ionizing Radiation, Exacerbates DNA Damage in Normal Tissues: Insights from a New p21 Reporter Mouse
Authors: McMahon Michael , Frangova Tania G. , Henderson Colin J. , Wolf C. Roland 
Published: September 2016

Abstract
Many drugs targeting the DNA damage response are being developed as anticancer therapies, either as single agents or in combination with ionizing radiation (IR) or other cytotoxic agents. Numerous clinical trials in this area are either in progress or planned. However, concerns remain about the potential of such treatments to increase toxicity to normal tissues. In order to address this issue, a novel reporter mouse line was created through the simultaneous incorporation of multiple reporters, β-galactosidase, and firefly luciferase, into the DNA damage–inducible p21 (CDKN1A) locus. The data demonstrate that in situ β-galactosidase staining facilitates high fidelity mapping of p21 expression across multiple organs and tissues at single-cell resolution, whereas the luciferase reporter permits noninvasive bioluminescent imaging of p21 expression. This model was used to determine the capacity of a number of DNA-damaging agents, including IR, cisplatin, and etoposide to induce p21 expression in normal tissues. In addition, the PARP inhibitor olaparib was examined alone or in combination with IR as well as cisplatin. A single exposure to olaparib alone caused DNA damage to cells in the mucosal layer lining mouse large intestine. It also exacerbated DNA damage induced in this organ and the kidney by coadministered IR. These studies suggest that olaparib has carcinogenic potential and illustrate the power of this new model to evaluate the safety of new therapeutic regimens involving combination therapies.
Implications: Olaparib causes DNA damage to normal tissues and might be a carcinogen. Mol Cancer Res; 14(12); 1195–203. ©2016 AACR.
Sleep and Breathing … and Cancer?
Authors: Owens Robert L. , Gold Kathryn A. , Gozal David , Peppard Paul E. , Jun Jonathan C. , Dannenberg Andrew J. , Lippman Scott M. , Malhotra Atul 
Published: September 2016

Abstract
Sleep, like eating and breathing, is an essential part of the daily life cycle. Although the science is still emerging, sleep plays an important role in immune, cardiovascular, and neurocognitive function. Despite its great importance, nearly 40% of U.S. adults experience problems with sleep ranging from insufficient total sleep time, trouble initiating or maintaining sleep (Insomnia), circadian rhythm disorders, sleep-related movement disorders, and sleep-related breathing disorders such as obstructive sleep apnea (OSA). Herein, we discuss new evidence that suggests that sleep may also affect carcinogenesis. Specifically, we review recent epidemiologic data suggesting links between cancer and OSA. As OSA is a common, underdiagnosed, and undertreated condition, this has public health implications. Intriguing animal model data support a link between cancer and sleep/OSA, although mechanisms are not yet clear. Leaders in the fields of sleep medicine, pulmonology, and oncology recently met to review and discuss these data, as well as to outline future directions of study. We propose a multidisciplinary, three-pronged approach to studying the associations between cancer and sleep, utilizing mutually interactive epidemiologic studies, preclinical models, and early-phase clinical trials. Cancer Prev Res; 9(11); 821–7. ©2016 AACR.
Systematic Functional Characterization of Resistance to PI3K Inhibition in Breast Cancer
Authors: Le Xiuning , Antony Rajee , Razavi Pedram , Treacy Daniel J. , Luo Flora , Ghandi Mahmoud , Castel Pau , Scaltriti Maurizio , Baselga José , Garraway Levi A. 
Published: September 2016

Abstract
PIK3CA (which encodes the PI3K alpha isoform) is the most frequently mutated oncogene in breast cancer. Small-molecule PI3K inhibitors have shown promise in clinical trials; however, intrinsic and acquired resistance limits their utility. We used a systematic gain-of-function approach to identify genes whose upregulation confers resistance to the PI3K inhibitor BYL719 in breast cancer cells. Among the validated resistance genes, Proviral Insertion site in Murine leukemia virus (PIM) kinases conferred resistance by maintaining downstream PI3K effector activation in an AKT-independent manner. Concurrent pharmacologic inhibition of PIM and PI3K overcame this resistance mechanism. We also observed increased PIM expression and activity in a subset of breast cancer biopsies with clinical resistance to PI3K inhibitors. PIM1 overexpression was mutually exclusive with PIK3CA mutation in treatment-naïve breast cancers, suggesting downstream functional redundancy. Together, these results offer new insights into resistance to PI3K inhibitors and support clinical studies of combined PIM/PI3K inhibition in a subset of PIK3CA-mutant cancers.
Significance: PIM kinase overexpression confers resistance to small-molecule PI3K inhibitors. Combined inhibition of PIM and PI3K may therefore be warranted in a subset of breast cancers. Cancer Discov; 6(10); 1134–47. ©2016 AACR.
This article is highlighted in the In This Issue feature, p. 1069
Missense mutations in the gene encoding prothrombin corresponding to Arg596 cause antithrombin resistance and thrombomodulin resistance
Authors: Takagi Yuki , Murata Moe , Kozuka Toshihiro , Nakata Yukiko , Hasebe Ryo , Tamura Shogo , Takagi Akira , Matsushita Tadashi , Saito Hidehiko , Kojima Tetsuhito 
Published: September 2016

SummaryAntithrombin (AT) and thrombomodulin (TM) play important roles in the process of natural anticoagulation in vivo. Recently, we reported that the prothrombin Yukuhashi mutation (p.Arg596Leu) was associated with AT and TM resistance-related thrombophilia. To assess the AT and TM resistances associated with other missense mutations by single base substitution in the Arg596 codon, we generated recombinant variants (596Gln, 596Trp, 596Gly, and 596Pro) and investigated the effects on AT and TM anticoagulant functions. All variants except 596Pro were secreted in amounts comparable to that of the wild-type but exhibited variable procoagulant activities. After a 30-minute inactivation by AT, the relative residual activity of wild-type thrombin decreased to 15 ± 4.0%, in contrast to values of all variants were maintained at above 80%. The thrombin–AT complex formation, as determined by enzyme-linked immunosorbent assay, was reduced with all tested variants in the presence and absence of heparin. In the presence of soluble TM (sTM), the relative fibrinogen clotting activity of wild-type thrombin decreased to 16 ± 0.12%, whereas that of tested variants was 37%–56%. In a surface plasmon resonance assay, missense Arg596 mutations reduced thrombin–TM affinity to an extent similar to the reduction of fibrinogen clotting inhibition. In the presence of sTM or cultured endothelial-like cells, APC generation was enhanced differently by variant thrombins in a thrombin–TM affinity- dependent manner. These data indicate that prothrombin Arg596 missense mutations lead to AT and TM resistance in the variant thrombins and suggest that prothrombin Arg596 is important for AT- and TM- mediated anticoagulation.
Monocyte subset distribution is associated with mortality in critically ill patients
Authors: Krychtiuk Konstantin A. , Lenz Max , Koller Lorenz , Honeder Maria C. , Wutzlhofer Lisa , Zhang Chao , Chi Lijian , Maurer Gerald , Niessner Alexander , Huber Kurt , Heinz Gottfried , Speidl Walter S. , Wojta Johann 
Published: September 2016

SummaryAlthough patients admitted to an intensive care unit (ICU) suffer from various pathologies, many develop a systemic inflammatory response syndrome (SIRS). As key regulators of innate immunity, monocytes may be crucially involved in SIRS development. Monocytes can be distinguished into three subsets: Classical monocytes (CD14++CD16−; CM), non-classical monocytes (CD14+CD16++CCR2−; NCM) and intermediate monocytes (CD14++CD16+CCR2+; IM). The aim of this prospective, observational study was to analyse whether monocyte subset distribution is associated with 30-day survival in critically ill patients. A total of 195 consecutive patients admitted to a cardiac ICU at a tertiary-care centre were enrolled, blood was taken at admission and after 72 hours and monocyte subset distribution was analysed. Mean APACHE II score was 19.5 ± 8.1 and 30-day mortality was 25.4 %. At admission, NCM were significantly lower in non-survivors as compared to survivors [2.7 (0.4–5.5) vs 4.2 (1.6–7.5)%; p=0.012] whereas CM and IM did not differ according to 30-day survival. In contrast, 72 hours after admission, monocyte subset distribution shifted towards an increased proportion of IM [8.2 (3.9–13.2) vs 4.2 (2.3–7.9)%; p=0.003] with a concomitant decrease of CM [86.9 (78.6–89.2) vs 89.6 (84.9–93.1)%; p=0.02] in non-survivors vs survivors, respectively. NCM at day 3 were not associated with death at 30 days. These results were independent from age, gender, CRP, APACHE II score and primary diagnosis. In conclusion, circulating monocyte subsets are associated with 30-day mortality in critically ill patients. The innate immune system as reflected by monocyte subset distribution may play a major role in ICU outcome despite varying admittance pathologies.Supplementary Material to this article is available online at www.thrombosis-online.com.
Efficacy of indigenous Steinernema abbasi and Heterorhabditis indica isolates as potential biocontrol agent against Holotrichia consanguinea Blanch. (Coleoptera: Scarabaeidae)
Authors: Patil Jagadeesh , Rangasamy Vijayakumar , Verghese Abraham 
Published: September 2016

Holotrichia consanguinea is a serious pest of peanut and sugarcane that attacks other commercial crops in India. The efficacy of two species of entomopathogenic nematodes (EPN), Steinernema abbasi and Heterorhabditis indica, against H. consanguinea was tested under laboratory and field conditions. In a laboratory assay, H. indica caused significantly greater mortality (25-100%) than S. abbasi (20-80%) against second instars and H. indica caused 17.5-82.5% mortality in third-instar grub larvae, while S. abbasi caused (10-60%) mortality. These results revealed that second-instar grubs were more susceptible than third-instar grubs and efficacy of EPN against H. consanguinea varies with nematode species. The penetration and multiplication rate for H. indica was significantly higher than those of S. abbasi. Infective juveniles (IJ) of both nematode species and a commonly used insecticide (phorate) were tested against this insect in a field experiment. Field trail data showed that the percentage reduction in H. consanguinea grub population was significantly higher using H. indica at a dose of 2.5 × 109 IJ ha−1 than S. abbasi and phorate application. Phorate application was more efficient in reducing the grub population than both nematode species at the lower application rate (1.25 × 109 IJ ha−1). Overall, these experiments suggest that H. indica may be a promising biocontrol agent against H. consanguinea.
Quantifying the Uncertainty in Historical and Future Simulations of Northern Hemisphere Spring Snow Cover
Authors: Thackeray Chad W. , Fletcher Christopher G. , Mudryk Lawrence R. , Derksen Chris 
Published: September 2016

AbstractProjections of twenty-first-century Northern Hemisphere (NH) spring snow cover extent (SCE) from two climate model ensembles are analyzed to characterize their uncertainty. Phase 5 of the Coupled Model Intercomparison Project (CMIP5) multimodel ensemble exhibits variability resulting from both model differences and internal climate variability, whereas spread generated from a Canadian Earth System Model–Large Ensemble (CanESM-LE) experiment is solely a result of internal variability. The analysis shows that simulated 1981–2010 spring SCE trends are slightly weaker than observed (using an ensemble of snow products). Spring SCE is projected to decrease by −3.7% ± 1.1% decade−1 within the CMIP5 ensemble over the twenty-first century. SCE loss is projected to accelerate for all spring months over the twenty-first century, with the exception of June (because most snow in this month has melted by the latter half of the twenty-first century). For 30-yr spring SCE trends over the twenty-first century, internal variability estimated from CanESM-LE is substantial, but smaller than intermodel spread from CMIP5. Additionally, internal variability in NH extratropical land warming trends can affect SCE trends in the near future (R2 = 0.45), while variability in winter precipitation can also have a significant (but lesser) impact on SCE trends. On the other hand, a majority of the intermodel spread is driven by differences in simulated warming (dominant in March–May) and snow cover available for melt (dominant in June). The strong temperature–SCE linkage suggests that model uncertainty in projections of SCE could be potentially reduced through improved simulation of spring season warming over land.
Design Strategies of an Hourly Update 3DVAR Data Assimilation System for Improved Convective Forecasting
Authors: Tong Wenxue , Li Gang , Sun Juanzhen , Tang Xiaowen , Zhang Ying 
Published: September 2016

Abstract
This study examines two strategies for improving the analysis of an hourly update three-dimensional variational data assimilation (3DVAR) system and the subsequent quantitative precipitation forecast (QPF). The first strategy is to assimilate synoptic and radar observations in different steps. This strategy aims to extract both large-scale and convective-scale information from observations typically representing different scales. The second strategy is to add a divergence constraint to the momentum variables in the 3DVAR system. This technique aims at improving the dynamic balance and suppressing noise introduced during the assimilation process. A detailed analysis on how the new techniques impact convective-scale QPF was conducted using a severe storm case over Colorado and Kansas during 8 and 9 August 2008. First, it is demonstrated that, without the new strategies, the QPF initialized with an hourly update analysis performs worse than its 3-hourly counterpart. The implementation of the two-step assimilation and divergence constraint in the hourly update system results in improved QPF throughout most of the 12-h forecast period. The diagnoses of the analysis fields show that the two-step assimilation is able to preserve key convective-scale as well as large-scale structures that are consistent with the development of the real weather system. The divergence constraint is effective in improving the balance between the momentum control variables in the analysis, which leads to less spurious convection and improved QPF scores. The improvements of the new techniques were further verified by eight convective cases in 2014 and shown to be statistically significant.
Development of an Innovative 3D Printed Rigid Bronchoscopy Training Model
Authors: AL-Ramahi Jehad , Luo Huiping , Fang Rui , Chou Adriana , Jiang Jack , Kille Tony 
Published: September 2016

Objectives: The objective of this study was to create a 3D printed airway model simulating the size and mechanical properties of various age groups for foreign body removal training. Methods: Three-dimensional printing technology was used to print the anatomically correct airway from rubber-like translucent material, simulating the mechanical properties of human airway tissue. The model’s effectiveness in trainee education was evaluated by otolaryngology residents with varying levels of experience. As part of an Airway Emergencies course, a rigid bronchoscopy procedure was performed on the 3D printed model as well as a porcine model. The participants completed surveys comparing the validity of the 2 models and the effectiveness of the overall training experience. Results: The 3D printed model, which is accurate in terms of anatomy and mechanical properties, was found to be comparable to a porcine model in regards to participant satisfaction as well as face validity. Conclusions: The 3D printed airway model is able to be accurately scaled to various sizes and simulate the mechanical properties of the desired age group. The 3D printed model provides an excellent alternative to animal models in terms of practicality, logistics of use, and anatomical accuracy.
Feasibility Study for Transnasal Endoscopic Repair of Orbital Floor Fracture With Alloplastic Implant
Authors: Engle Robert D. , Chaskes Mark , Wladis Edward , Pinheiro-Neto Carlos D. 
Published: September 2016

Objective: Fractures of the orbital floor are common yet repaired by various techniques, including open periorbital, transantral endoscopic, and endoscopic endonasal approaches. To date, endoscopic endonasal repair of an orbital floor fracture using an alloplastic implant has not been described. We aim to determine the technique and limitations of completely endoscopic endonasal orbital floor repair using an alloplastic implant. Study Design: Cadaveric anatomic study and retrospective case series. Methods: Cadaveric study of 12 sides with endoscopic sinonasal dissection followed by the creation and repair of an isolated orbital floor fracture using an alloplastic implant. Four representative patient cases are presented in which the techniques developed in the cadaveric study were employed. Patients were selected for this technique based on the results of the cadaveric study. Results: Cadaveric study demonstrated feasibility of access and repair for fractures that did not extend lateral to the infraorbital canal or anterior to the nasolacrimal duct. In all cadaveric sides and in all 4 patient cases, successful alloplastic orbital floor reconstruction was achieved. Conclusion: This method of repair is feasible for selected patients and may be considered in cases of favorable fracture anatomy with or without concomitant indication for an ipsilateral sinus procedure.
Change in plasma volume and prognosis in acute decompensated heart failure: an observational cohort study
Authors: Hudson Sarah R , Chan Daniel , Ng Leong L 
Published: September 2016

Objectives This study aimed to develop an inexpensive, readily available prognostic indicator in acute decompensated heart failure patients to guide management and improve outcome. Prognostic biomarkers for heart failure exist but are expensive and not routinely performed. Increasing plasma volume has been associated with worse outcomes. Setting UK University Teaching Hospital. Design Observational Cohort study. Participants 967 patients with acute decompensated heart failure. Methods Haemoglobin and haematocrit were measured at admission and discharge and were used to calculate the plasma volume change using the Strauss-Davis-Rosenbaum formula. Main outcome measures Endpoints were death and the composite of death and/or heart failure hospitalisation. Change in plasma volume was added to ADHERE scoring to determine predictive value. Results During follow-up, 536 died and 626 died or were hospitalised with heart failure. Multivariable Cox models showed change in plasma volume was an independent predictor of mortality (hazard ratio (HR) [95% confidence interval (CI)]: 1.150 [1.031–1.283], p = 0.012) and death or heart failure hospitalisation (HR: 1.138 [1.029–1.259], p = 0.012). Kaplan–Meier analysis of change in plasma volume tertiles for outcome measures showed significant difference for the top tertile compared to the lower two. Multivariable analysis of change in plasma volume with ADHERE scoring showed change in plasma volume change remained an independent predictor of death (HR: 1.138 [1.026–1.261], p = 0.015) and death or heart failure hospitalisation (HR: 1.129 [1.025–1.243], p = 0.014). Conclusions Change in plasma volume over an admission can be used for prognostication and adds value to the ADHERE score. Change in plasma volume can be easily and inexpensively calculated from routine blood tests. Clinically, this may facilitate targeted treatment of acute decompensated heart failure patients at greatest risk.