bluuebunny/crossref_metadata_2025 huggingface dataset:
Modeling and forecasting the oil volatility index
Authors: Mazzeu João H. Gonçalves , Veiga Helena , Mariti Massimo B.
Published: April 2019

The increase in oil price volatility in recent years has raised the importance of forecasting it accurately for valuing and hedging investments. The paper models and forecasts the crude oil exchange‐traded funds (ETF) volatility index, which has been used in the last years as an important alternative measure to track and analyze the volatility of future oil prices. Analysis of the oil volatility index suggests that it presents features similar to those of the daily market volatility index, such as long memory, which is modeled using well‐known heterogeneous autoregressive (HAR) specifications and new extensions that are based on net and scaled measures of oil price changes. The aim is to improve the forecasting performance of the traditional HAR models by including predictors that capture the impact of oil price changes on the economy. The performance of the new proposals and benchmarks is evaluated with the model confidence set (MCS) and the Generalized‐AutoContouR (G‐ACR) tests in terms of point forecasts and density forecasting, respectively. We find that including the leverage in the conditional mean or variance of the basic HAR model increases its predictive ability. Furthermore, when considering density forecasting, the best models are a conditional heteroskedastic HAR model that includes a scaled measure of oil price changes, and a HAR model with errors following an exponential generalized autoregressive conditional heteroskedasticity specification. In both cases, we consider a flexible distribution for the errors of the conditional heteroskedastic process.
Extraction optimization, antioxidant activity, and tyrosinase inhibitory capacity of polyphenols from Lonicera japonica
Authors: Fan ZiLuan , Li Lu , Bai XiaoLin , Zhang Hua , Liu QiRui , Zhang He , Fu YuJie , Moyo Rumbani
Published: April 2019

The objective of this research was twofold: first, to optimize the extraction process of Lonicera japonica polyphenols using a response surface methodology, and second, to study the antioxidant activity and tyrosinase inhibitory capacity of the polyphenols of different purities. High‐speed shearing homogenization extraction was used to extract the polyphenols from L. japonica. The antioxidant activity and the effect of polyphenols on tyrosinase activity were studied using free radical scavenging assay and the tyrosinase method, respectively. The optimal extraction conditions with an extraction yield of 6.96% for polyphenols were determined as follows: ethanol volume fraction 57%, shearing time 3.30 min, and solid–liquid ratio 1:58. Lonicera japonica polyphenols exhibited potent scavenging activity on 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH) and 2, 2'‐azino‐bis(3‐ethylbenzothiazoline‐6‐sulfonic acid) (ABTS), and inhibitory capacity on tyrosinase. The results suggested that L. japonica polyphenols could be explored as a natural antioxidant and tyrosinase inhibitor.
Controlling Measles through Politics and Policy
Authors: Silverman Ross D.
Published: April 2019

Vaccination is one of history's most successful public health interventions. Since 2000, vaccination campaigns against measles, which is highly contagious but preventable through the measles‐mumps‐rubella (MMR) vaccine, have reduced both the global incidence of the disease and measles deaths by 80 percent. However, progress toward measles elimination has slid backward in several previously well‐protected global regions. With more communities below or at risk of falling below the 95 percent immunization rates required for herd immunity—due more and more to vaccine skepticism and declination rather than lack of access—many U.S. states and countries must reappraise their vaccination policies and programs.
Liver Macrophages: Old Dogmas and New Insights
Authors: Guillot Adrien , Tacke Frank
Published: April 2019

Inflammation is a hallmark of virtually all liver diseases, such as liver cancer, fibrosis, nonalcoholic steatohepatitis, alcoholic liver disease, and cholangiopathies. Liver macrophages have been thoroughly studied in human disease and mouse models, unravelling that the hepatic mononuclear phagocyte system is more versatile and complex than previously believed. Liver macrophages mainly consist of liver‐resident phagocytes, or Kupffer cells (KCs), and bone marrow‐derived recruited monocytes. Although both cell populations in the liver demonstrate principal functions of macrophages, such as phagocytosis, danger signal recognition, cytokine release, antigen processing, and the ability to orchestrate immune responses, KCs and recruited monocytes retain characteristic ontogeny markers and remain remarkably distinct on several functional aspects. While KCs dominate the hepatic macrophage pool in homeostasis (“sentinel function”), monocyte‐derived macrophages prevail in acute or chronic injury (“emergency response team”), making them an interesting target for novel therapeutic approaches in liver disease. In addition, recent data acquired by unbiased large‐scale techniques, such as single‐cell RNA sequencing, unraveled a previously unrecognized complexity of human and murine macrophage polarization abilities, far beyond the old dogma of inflammatory (M1) and anti‐inflammatory (M2) macrophages. Despite tremendous progress, numerous challenges remain in deciphering the full spectrum of macrophage activation and its implication in either promoting liver disease progression or repairing injured liver tissue. Being aware of such heterogeneity in cell origin and function is of crucial importance when studying liver diseases, developing novel therapeutic interventions, defining macrophage‐based prognostic biomarkers, or designing clinical trials. Growing knowledge in gene expression modulation and emerging technologies in drug delivery may soon allow shaping macrophage populations toward orchestrating beneficial rather than detrimental inflammatory responses.
Immune Determinants in the Acquisition and Maintenance of Antibody to Hepatitis B Surface Antigen in Adults After First‐Time Hepatitis B Vaccination
Authors: Doi Hiroyoshi , Yoshio Sachiyo , Yoneyama Keiichiro , Kawai Hironari , Sakamoto Yuzuru , Shimagaki Tomonari , Aoki Yoshihiko , Osawa Yosuke , Yoshida Hitoshi , Kanto Tatsuya
Published: April 2019

Global implementation of a birth‐dose hepatitis B (HB) vaccine has significantly reduced the prevalence of hepatitis B virus (HBV) carriers. Durable and sufficient titers of antibodies to hepatitis B surface antigen (anti‐HBs) are desirable for vaccinees to gain resistance to HBV exposure. However, the existence of primary nonresponders and vaccinees who lost anti‐HBs over time remains a challenge for the strategy of HBV elimination. We thus aim to clarify the mechanisms of acquisition and maintenance of vaccine‐induced anti‐HBs in healthy adults. We retrospectively analyzed the vaccination records of 3,755 first‐time HB‐vaccinated students and also traced the acquired antibody transition of 392 first‐time vaccinees for 10 consecutive years. To understand the cellular and humoral immune response, we prospectively examined peripheral blood from 47 healthy first‐time HB‐vaccinated students, 62 booster‐vaccinated health care workers, and 20 individuals who maintained their anti‐HBs. In responders, a significant increase of follicular helper T (Tfh) cells, activated plasmablasts, and plasma cells was observed in first‐time‐vaccinated but not booster‐vaccinated persons. We also discovered memory B cells and antibody‐secreting cells were more abundant in individuals who maintained anti‐HBs. According to vaccination records, higher anti‐HBs antibody titer acquisition was related to the longer term maintenance of anti‐HBs, the level of which was positively correlated with prevaccination levels of serum interferon‐γ and related chemokines. The second series of vaccination as a booster provided significantly higher anti‐HBs antibody titers compared to the initial series. Conclusion: Coordinated activation of Tfh and B‐cell lineages after HB vaccination is involved in the acquisition and maintenance of anti‐HBs. Our findings support the rationale of preconditioning the immune status of recipients to ensure durable vaccine responses.
Emricasan Ameliorates Portal Hypertension and Liver Fibrosis in Cirrhotic Rats Through a Hepatocyte‐Mediated Paracrine Mechanism
Authors: Gracia‐Sancho Jordi , Manicardi Nicolò , Ortega‐Ribera Martí , Maeso‐Díaz Raquel , Guixé‐Muntet Sergi , Fernández‐Iglesias Anabel , Hide Diana , García‐Calderó Héctor , Boyer‐Díaz Zoe , Contreras Patricia C. , Spada Alfred , Bosch Jaime
Published: April 2019

In cirrhosis, liver microvascular dysfunction is a key factor increasing hepatic vascular resistance to portal blood flow, which leads to portal hypertension. De‐regulated inflammatory and pro‐apoptotic processes due to chronic injury play important roles in the dysfunction of liver sinusoidal cells. The present study aimed at characterizing the effects of the pan‐caspase inhibitor emricasan on systemic and hepatic hemodynamics, hepatic cells phenotype, and underlying mechanisms in preclinical models of advanced chronic liver disease. We investigated the effects of 7‐day emricasan on hepatic and systemic hemodynamics, liver function, hepatic microcirculatory function, inflammation, fibrosis, hepatic cells phenotype, and paracrine interactions in rats with advanced cirrhosis due to chronic CCl4 administration. The hepato‐protective effects of emricasan were additionally investigated in cells isolated from human cirrhotic livers. Cirrhotic rats receiving emricasan showed significantly lower portal pressure than vehicle‐treated animals with no changes in portal blood flow, indicating improved vascular resistance. Hemodynamic improvement was associated with significantly better liver function, reduced hepatic inflammation, improved phenotype of hepatocytes, liver sinusoidal endothelial cells, hepatic stellate cells and macrophages, and reduced fibrosis. In vitro experiments demonstrated that emricasan exerted its benefits directly improving hepatocytes’ expression of specific markers and synthetic capacity, and ameliorated nonparenchymal cells through a paracrine mechanism mediated by small extracellular vesicles released by hepatocytes. Conclusion: This study demonstrates that emricasan improves liver sinusoidal microvascular dysfunction in cirrhosis, which leads to marked amelioration in fibrosis, portal hypertension and liver function, and therefore encourages its clinical evaluation in the treatment of advanced chronic liver disease.
Variant classification in precision oncology
Authors: Leichsenring Jonas , Horak Peter , Kreutzfeldt Simon , Heining Christoph , Christopoulos Petros , Volckmar Anna‐Lena , Neumann Olaf , Kirchner Martina , Ploeger Carolin , Budczies Jan , Heilig Christoph E. , Hutter Barbara , Fröhlich Martina , Uhrig Sebastian , Kazdal Daniel , Allgäuer Michael , Harms Alexander , Rempel Eugen , Lehmann Ulrich , Thomas Michael , Pfarr Nicole , Azoitei Ninel , Bonzheim Irina , Marienfeld Ralf , Möller Peter , Werner Martin , Fend Falko , Boerries Melanie , von Bubnoff Nikolas , Lassmann Silke , Longerich Thomas , Bitzer Michael , Seufferlein Thomas , Malek Nisar , Weichert Wilko , Schirmacher Peter , Penzel Roland , Endris Volker , Brors Benedikt , Klauschen Frederick , Glimm Hanno , Fröhling Stefan , Stenzinger Albrecht
Published: April 2019

Next‐generation sequencing has become a cornerstone of therapy guidance in cancer precision medicine and an indispensable research tool in translational oncology. Its rapidly increasing use during the last decade has expanded the options for targeted tumor therapies, and molecular tumor boards have grown accordingly. However, with increasing detection of genetic alterations, their interpretation has become more complex and error‐prone, potentially introducing biases and reducing benefits in clinical practice. To facilitate interdisciplinary discussions of genetic alterations for treatment stratification between pathologists, oncologists, bioinformaticians, genetic counselors and medical scientists in specialized molecular tumor boards, several systems for the classification of variants detected by large‐scale sequencing have been proposed. We review three recent and commonly applied classifications and discuss their individual strengths and weaknesses. Comparison of the classifications underlines the need for a clinically useful and universally applicable variant reporting system, which will be instrumental for efficient decision making based on sequencing analysis in oncology. Integrating these data, we propose a generalizable classification concept featuring a conservative and a more progressive scheme, which can be readily applied in a clinical setting.
Integrin α9 depletion promotes β‐catenin degradation to suppress triple‐negative breast cancer tumor growth and metastasis
Authors: Wang Zhishan , Li Yunfei , Xiao Yajuan , Lin Hsuan‐Pei , Yang Ping , Humphries Brock , Gao Tianyan , Yang Chengfeng
Published: April 2019

Although integrin α9 (ITGA9) is known to be involved in cell adhesion and motility, its expression in cancer and its role in tumor growth and metastasis remain largely unknown. Our study was designed to investigate the role of ITGA9 in triple‐negative breast cancer (TNBC). ITGA9 expression in TNBC cells was knocked out (KO) using CRISPR/Cas9 technology. Four orthotopic mouse mammary xenograft tumor models coupled with cell culture studies were performed to determine the effect of ITGA9 depletion on TNBC tumor growth and metastasis and the underlying mechanism. Bioinformatics analysis showed that ITGA9 level is significantly higher in TNBC than other breast cancer subtypes, and higher ITGA9 level is associated with significantly worse distant metastasis‐free survival and recurrence‐free survival in TNBC patients. Experimentally, ITGA9 KO significantly reduced TNBC cell cancer stem cell (CSC)‐like property, tumor angiogenesis, tumor growth and metastasis by promoting β‐catenin degradation. Further mechanistic studies revealed that ITGA9 KO causes integrin‐linked kinase (ILK) relocation from the membrane region to the cytoplasm, where it interacts with protein kinase A (PKA) and inhibits PKA activity leading to increased activity of glycogen synthase kinase 3 (GSK3) and subsequent β‐catenin degradation. Overexpressing β‐catenin in ITGA9 KO cells reversed the inhibitory effect of ITGA9 KO on tumor growth and metastasis. Furthermore, ITGA9 downregulation in TNBC tumors by nanoparticle‐mediated delivery of ITGA9 siRNA drastically decreased tumor angiogenesis, tumor growth and metastasis. These findings indicate that ITGA9 depletion suppresses TNBC tumor growth and metastasis by promoting β‐catenin degradation through the ILK/PKA/GSK3 pathway.
Polycomb complex mediated epigenetic reprogramming alters TGF‐β signaling via a novel EZH2/miR‐490/TGIF2 axis thereby inducing migration and EMT potential in glioblastomas
Authors: Vinchure Omkar S. , Sharma Vikas , Tabasum Saba , Ghosh Sourabh , Singh Rana P. , Sarkar Chitra , Kulshreshtha Ritu
Published: April 2019

Recent advancement in understanding cancer etiology has highlighted epigenetic deregulation as an important phenomenon leading to poor prognosis in glioblastoma (GBM). Polycomb repressive complex 2 (PRC2) is one such important epigenetic modifier reportedly altered in GBM. However, its defined mechanism in tumorigenesis still remains elusive. In present study, we analyzed our in‐house ChIPseq data for H3k27me3 modified miRNAs and identified miR‐490‐3p to be the most common target in GBM with significantly downregulated expression in glioma patients in both TCGA and GBM patient cohort. Our functional analysis delineates for the first time, a central role of PRC2 catalytic unit EZH2 in directly regulating expression of this miRNA and its host gene CHRM2 in GBM. In accordance, cell line treatment with EZH2 siRNA and 5‐azacytidine also confirmed its coregulation by CpG and histone methylation based epigenetic mechanisms. Furthermore, induced overexpression of miR‐490‐3p in GBM cell lines significantly inhibited key hallmarks including cellular proliferation, colony formation and spheroid formation, as well as epithelial‐to‐mesenchymal transition (EMT), with downregulation of multiple EMT transcription factors and promigratory genes (MMP9, CCL5, PIK3R1, ICAM1, ADAM17 and NOTCH1). We also for the first time report TGFBR1 and TGIF2 as two direct downstream effector targets of miR‐490‐3p that are also deregulated in GBM. TGIF2, a novel target, was shown to promote migration and EMT that could partially be rescued by miR‐490‐3p overexpression. Overall, this stands as a first study that provides a direct link between epigenetic modulator EZH2 and oncogenic TGF‐β signaling involving novel miR‐490‐3p/TGIF2/TGFBR1 axis, that being targetable might be promising in developing new therapeutic intervention strategies for GBM.
Three‐dimensional static optical coherence elastography based on inverse compositional Gauss‐Newton digital volume correlation
Authors: Meng Fanchao , Chen Cheng , Hui Shun , Wang Jingbo , Feng Yvlong , Sun Cuiru
Published: April 2019

The three‐dimensional (3D) mechanical properties characterization of tissue is essential for physiological and pathological studies, as biological tissue is mostly heterogeneous and anisotropic. A digital volume correlation (DVC)‐based 3D optical coherence elastography (OCE) method is developed to measure the 3D displacement and strain tensors. The DVC algorithm includes a zero‐mean normalized cross‐correlation criterion‐based coarse search regime, an inverse compositional Gauss‐Newton fine search algorithm and a local ternary quadratic polynomial fitting strain calculation method. A 3D optical coherence tomography (OCT) scanning protocol is proposed through theoretical analysis and experimental verification. Measurement errors of the DVC‐based 3D OCE method are evaluated to be less than 2.0 μm for displacements and 0.30% for strains by rigid body motion experiments. The 3D displacements and strains of a phantom and a specimen of chicken breast tissue under compression are measured. Results of the phantom show a good agreement with theoretical analysis and tensile testing. The strains of the chicken breast tissue indicate anisotropic biomechanical properties. This study provides an effective method for 3D biomechanical property studies of soft tissue and improves the development of 3D OCE techniques.
Dendrimer mediated targeting of siRNA against polo‐like kinase for the treatment of triple negative breast cancer
Authors: Jain Anjali , Mahira Shaheen , Majoral Jean‐Pierre , Bryszewska Maria , Khan Wahid , Ionov Maksim
Published: April 2019

Irresponsiveness of triple negative breast cancer (TNBC) toward conventional therapies has drawn attention toward siRNA therapeutics. In gene delivery, dendrimers are gaining significant attention due to their characteristic features and polo‐like kinase (PLK1) is reported as a potential target for TNBC. In this work, phosphorus and polyamidoamine dendrimer (generation 3 and 4 of each type) are explored to address delivery challenges of PLK1 siRNA (siPLK1). Dendriplexes were formed and complexation was found at 3:1 N/P ratio for all dendrimers by gel electrophoresis. Complexation was also supported by zeta potential, circular dichroism and intercalation assay. Dendriplexes were found to be stable in presence of ribonuclease and serum. Dendriplexes resulted in enhanced cell uptake of siPLK1 compared to siPLK1 solution in MDA‐MB‐231 and MCF‐7 cells. Dendriplexes caused increased cell arrest in sub‐G1 phase compared to solution. These observations suggested phosphorus and polyamidoamine dendrimers as potential carriers for siPLK1 delivery to treat TNBC.
Hypoxia inducible factor‐1 promotes liver fibrosis in nonalcoholic fatty liver disease by activating PTEN/p65 signaling pathway
Authors: Han Jie , He Yaping , Zhao Hui , Xu Xiaowei
Published: April 2019

Obesity is a major contributor to the development of steatohepatitis and fibrosis from nonalcoholic fatty liver disease (NAFLD). Hypoxia aggravates progression of NAFLD. In mice on high‐fat diet (HFD), hepatic steatosis leads to liver tissue hypoxia, evidenced by accumulation of hypoxia inducible factor‐1‐alpha (HIF‐1α), which is a central regulator of the global response to hypoxia. Hepatocyte cell signaling is an important factor in hepatic fibrogenesis. We here hypothesize that HIF‐1α knockout in hepatocyte may protect against liver fibrosis. We first found that HFD led to 80% more hepatic collagen deposition than Hif1a−/−hep mice, which was confirmed by a‐SMA staining of liver tissue. Body weight and liver weight were similar between groups. We then found the increasing HIF1a expression and decreasing PTEN expression in the mice on HFD and in PA‐treated HepG2 cells. Finally, we found that HIF1 mediated PTEN/nfkb‐p65 pathway plays an important role in the development of NAFLD to liver fibrosis. Collectively, these results identify a novel HIF1a/PTEN/NF‐κ Bp65 signaling pathway in NAFLD, which could be targeted for the therapy.
miR‐188‐5p emerges as an oncomiRNA to promote gastric cancer cell proliferation and migration via upregulation of SALL4
Authors: Wang Mei , Qiu Rong , Gong Zheng , Zhao Xinxin , Wang Tingting , Zhou Lulu , Lu Weiwei , Shen Bo , Zhu Wei , Xu Wenrong
Published: April 2019

MicroRNAs (miRNAs) play pivotal roles in modulating key biological processes in gastric cancer (GC). As a newly identified miRNA, the function and potential mechanism of miR‐188‐5p in GC has not been thoroughly elucidated. Here, quantitative real‐time polymerase chain reaction detection showed abnormally higher expression of miR‐188‐5p in GC cells and tissues. Gain‐of‐function analysis in vitro showed that miR‐188‐5p promoted GC cell proliferation and migration, while loss‐of‐function studies showed the reverse. Targetscan has predicted that phosphatase and tensin homolog (PTEN) was a potential target gene of miR‐188‐5p. miR‐188‐5p suppressed PTEN messenger RNA and protein expression and activated downstream AKT/mTOR signaling in GC cells, but luciferase reporter analysis showed that PTEN was not regulated by miR‐188‐5p via the 3′ untranslated region. Furthermore, we observed that miR‐188‐5p overexpression promoted Sal‐like protein 4 (SALL4) protein expression, cellular nuclear translocation, and transcription. Knockdown of SALL4 eliminated the effect of miR‐188‐5p in GC cells as well as suppression of PTEN. Taken together, our results demonstrate that miR‐188‐5p promotes GC cell proliferation and migration while suppressing tumor suppressor gene PTEN expression via transcriptional upregulation of oncogene SALL4. We conclude that miR‐188‐5p acts as an oncomiRNA in GC and may be a promising therapeutic target for GC.
Apical cell protrusions cause vertical deformation of the soft cancer nucleus
Authors: Kent Ian A. , Zhang Qiao , Katiyar Aditya , Li Yuan , Pathak Shreya , Dickinson Richard B. , Lele Tanmay P.
Published: April 2019

Breast cancer nuclei have highly irregular shapes, which are diagnostic and prognostic markers of breast cancer progression. The mechanisms by which irregular cancer nuclear shapes develop are not well understood. Here we report the existence of vertical, apical cell protrusions in cultured MDA‐MB‐231 breast cancer cells. Once formed, these protrusions persist over time scales of hours and are associated with vertically upward nuclear deformations. They are absent in normal mammary epithelial cells (MCF‐10A cells). Microtubule disruption enriched these protrusions preferentially in MDA‐MB‐231 cells compared with MCF‐10A cells, whereas inhibition of nonmuscle myosin II (NMMII) abolished this enrichment. Dynamic confocal imaging of the vertical cell and nuclear shape revealed that the apical cell protrusions form first, and in response, the nucleus deforms and/or subsequently gets vertically extruded into the apical protrusion. Overexpression of lamin A/C in MDA‐MB‐231 cells reduced nuclear deformation in apical protrusions. These data highlight the role of mechanical stresses generated by moving boundaries, as well as abnormal nuclear mechanics in the development of abnormal nuclear shapes in breast cancer cells.
Pyrazole‐4‐carboxylic Acids from Vanadium‐catalyzed Chemical Transformation of Pyrazole‐4‐carbaldehydes
Authors: Bala Renu , Kumari Poonam , Sood Sumit , Phougat Harshita , Kumar Anil , Singh Karan
Published: April 2019

The conversion of aldehydes into carboxylic acids using oxidizing agents is a common protocol in transformation chemistry. An efficient oxidation strategy of transformation of pyrazole‐4‐aldehydes to the corresponding acids using vanadium catalysts in the presence of 30% H2O2 as an oxidant is described. The catalytic technology was successfully applied to a range of various 4‐formylpyrazoles, and plausible mechanism is also discussed.
Synthesis and Screening of Phosphodiesterase 5 Inhibitory Activity of Fused and Isolated Triazoles Based on Thieno[2,3‐d]pyrimidines
Authors: Ameen Mohamed A. , Ahmed Essam Kh. , Mahmoud Hemdan I. , Ramadan Mohamed
Published: April 2019

Novel fused and isolated triazoles based on thieno[2,3‐d]pyrimidines were synthesized starting from 2‐aminothiophene ester and structurally confirmed by spectral and analytical data. The synthesized triazolo compounds were screened for their phosphodiesterase 5 inhibitory activity and showed encouraging activity than did sildenafil as a reference drug.
Locomotory adaptations in entoptychine gophers (Rodentia: Geomyidae) and the mosaic evolution of fossoriality
Authors: Calede Jonathan J.M. , Samuels Joshua X. , Chen Meng
Published: April 2019

Pocket gophers (family Geomyidae) are the dominant burrowing rodents in North America today. Their fossil record is also incredibly rich; in particular, entoptychine gophers, a diverse extinct subfamily of the Geomyidae, are known from countless teeth and jaws from Oligocene and Miocene‐aged deposits of the western United States and Mexico. Their postcranial remains, however, are much rarer and little studied. Yet, they offer the opportunity to investigate the locomotion of fossil gophers, shed light on the evolution of fossoriality, and enable ecomorphological comparisons with contemporaneous rodents. We present herein a quantitative study of the cranial and postcranial remains of eight different species of entoptychine gophers as well as many contemporary rodent species. We find a range of burrowing capabilities within Entoptychinae, including semifossorial scratch‐digging animals and fossorial taxa with cranial adaptations to burrowing. Our results suggest the repeated evolution of chisel‐tooth digging across genera. Comparisons between entoptychine gophers and contemporaneous rodent taxa show little ecomorphological overlap and suggest that the succession of burrowing rodent taxa on the landscape may have had more to do with habitat partitioning than competition.
Flipper bone distribution reveals flexible trailing edge in underwater flying marine tetrapods
Authors: DeBlois Mark C. , Motani Ryosuke
Published: April 2019

Hydrofoil‐shaped limbs (flipper‐hydrofoils) have evolved independently several times in secondarily marine tetrapods and generally fall into two functional categories: (1) those that produce the majority of thrust during locomotion (propulsive flipper‐hydrofoils); (2) those used primarily to steer and resist destabilizing movements such as yaw, pitch, and roll (controller flipper‐hydrofoils). The morphological differences between these two types have been poorly understood. Theoretical and experimental studies on engineered hydrofoils suggest that flapping hydrofoils with a flexible trailing edge are more efficient at producing thrust whereas hydrofoils used in steering and stabilization benefit from a more rigid one. To investigate whether the trailing edge is generally more flexible in propulsive flipper‐hydrofoils, we compared the bone distribution along the chord in both flipper types. The propulsive flipper‐hydrofoil group consists of the forelimbs of Chelonioidea, Spheniscidae, and Otariidae. The controller flipper‐hydrofoil group consists of the forelimbs of Cetacea. We quantified bone distribution from radiographs of species representing more than 50% of all extant genera for each clade. Our results show that the proportion of bone in both groups is similar along the leading edge (0–40% of the chord) but is significantly less along the trailing edge for propulsive flipper‐hydrofoils (40–80% of the chord). Both flipper‐hydrofoil types have little to no bony tissue along the very edge of the trailing edge (80–100% of the chord). This suggests a relatively flexible trailing edge for propulsive flipper‐hydrofoils compared to controller flipper‐hydrofoils in line with findings from prior studies. This study presents a morphological correlate for inferring flipper‐hydrofoil function in extinct taxa and highlights the importance of a flexible trailing edge in the evolution of propulsive flipper‐hydrofoils in marine tetrapods.
Neuroimaging in alcohol use disorder: From mouse to man
Authors: Fritz Michael , Klawonn Anna M. , Zahr Natalie M.
Published: April 2019

This article provides an overview of recent advances in understanding the effects of alcohol use disorders (AUD) on the brain from the perspective of magnetic resonance imaging (MRI) research in preclinical models and clinical studies. As a noninvasive investigational tool permitting assessment of morphological, metabolic, and hemodynamic changes over time, MRI offers insight into the dynamic course of alcoholism beginning with initial exposure through periods of binge drinking and escalation, sobriety, and relapse and has been useful in differential diagnosis of neurological diseases associated with AUD. Structural MRI has revealed acute and chronic effects of alcohol on both white and gray matter volumes. MR Spectroscopy, able to quantify brain metabolites in vivo, has shed light on biochemical alterations associated with alcoholism. Diffusion tensor imaging permits microstructural characterization of white matter fiber tracts. Functional MRI has allowed for elucidation of hemodynamic responses at rest and during task engagement. Positron emission tomography, a non‐MRI imaging tool, has led to a deeper understanding of alcohol‐induced receptor and neurotransmitter changes during various stages of drinking and abstinence. Together, such in vivo imaging tools have expanded our understanding of the dynamic course of alcoholism including evidence for regional specificity of the effects of AUD, hints at mechanisms underlying the shift from casual to compulsive use of alcohol, and profound recovery with sustained abstinence.
Nutrition During Targeted Temperature Management After Cardiac Arrest: Observational Study of Neurological Outcomes and Nutrition Tolerance
Authors: Martin Maelle , Reignier Jean , Le Thuaut Aurélie , Lacherade Jean Claude , Martin‐Lefèvre Laurent , Fiancette Maud , Vinatier Isabelle , Lebert Christine , Bachoumas Konstantinos , Yehia Aihem , Henry Lagarrigue Matthieu , Colin Gwenhael , Lascarrou Jean Baptiste
Published: April 2019

Background

Whether providing nutrition support is beneficial or deleterious during targeted temperature management (TTM) after cardiac arrest is unclear. We therefore performed a retrospective observational study to determine whether early nutrition was beneficial or deleterious during TTM.

Methods

We retrospectively studied patients admitted to our intensive care unit (ICU) between 2008 and 2014 after successfully resuscitated cardiac arrest. We compared the group given nutrition within 48 hours after ICU admission (E+ group) to the group given nutrition later on or not at all (E‐ group).

Results

Of the 203 included patients, 143 were in the E+ group and 60 in the E‐ group. The E+ group had a significantly higher proportion of patients with a good 3‐month neurological outcome (42.7% vs 16.7%, P < 0.001). The difference remained significant after adjustment on a propensity score (odds ratio, 3.47; 95% confidence interval, 1.48–8.14; P = 0.004). The cumulative energy deficit for an energy goal of 20 kcal/kg/d from admission to day 7 was significantly lower in the E+ group (3304 ± 2863 kcal vs 5017 ± 2655 kcal, P < 0.001). Within the E+ group, the subgroups with nutrition initiation when body temperature was <36°C vs ≥36°C were not significantly different regarding the frequencies of early‐onset pneumonia, ventilator‐associated pneumonia, vomiting, and prokinetic drug use (all P‐values > 0.05).

Conclusions

Early nutrition after cardiac arrest during TTM appears safe and may be associated with better neurological outcomes. These findings warrant a randomized controlled trial to resolve the remaining issues.
Self‐Assembly of Polyethylene Glycol Ether Surfactants in Aqueous Solutions: The Effect of Linker between Alkyl and Ethoxylate
Authors: Bodratti Andrew M. , Cheng Junce , Kong Stephanie M. , Chow Matthew R. , Tsianou Marina , Alexandridis Paschalis
Published: April 2019

The aqueous self‐assembly behavior of two homologous series of poly(ethylene oxide) (PEO)‐containing nonionic surfactants based on a C10‐Guerbet hydrophobe is reported. The two families of surfactants, alkyl ethoxylates and alkyl alkoxylates, are commercially available from BASF under the trade name Lutensol® XP‐series and XL‐series, respectively. The latter incorporate propylene oxide (PO) units in the surfactant chain. Dye solubilization was used to determine the critical micellization concentration (CMC) of each surfactant at 22 and 50 °C. The PO‐containing alkyl alkoxylates displayed lower CMC values, which were also more sensitive to temperature. The Gibbs free energy, enthalpy, and entropy of micellization were computed from the CMC data and used to identify the contribution of each surfactant moiety (alkyl chain, PO unit, and PEO block) in controlling the CMC. The micellization properties are compared with compositionally similar surfactants with linear alkyl chains, yielding information about the effects of the Guerbet alkyl chain on micellization. Isothermal titration calorimetry was also used to characterize the CMC and enthalpy of micellization which generally compare well with the dye solubilization results. Cloud point data reveal nonmonotonic relationships for the Lutensol® surfactants with respect to composition, unlike linear alkyl chain surfactants. Finally, dilute solution viscosity measurements performed on some Lutensol® surfactants show a change in the slope, suggesting a structural change that tends to be more pronounced for surfactants with longer PEO blocks. The data presented herein enhance the understanding of surfactant structure–property relationships required for industrial formulation.
Associations Between Trauma‐Related Rumination and Symptoms of Posttraumatic Stress and Depression in Treatment‐Seeking Female Veterans
Authors: Arditte Hall Kimberly A. , Davison Eve H. , Galovski Tara E. , Vasterling Jennifer J. , Pineles Suzanne L.
Published: April 2019

Trauma‐related rumination is a cognitive style characterized by repetitive negative thinking about the causes, consequences, and implications of a traumatic experience. Frequent trauma‐related rumination has been linked to posttraumatic stress disorder (PTSD) and depression in civilian samples but has yet to be examined among military veterans. This study extended previous research by examining trauma‐related rumination in female veterans who presented to a Veterans Affairs women's trauma recovery clinic (N = 91). The study had two main aims: (a) to examine associations between trauma‐related rumination and specific PTSD symptoms, adjusting for the overlap between trauma‐related rumination and other relevant cognitive factors, such as intrusive trauma memories and self‐blame cognitions; and (b) to assess associations between trauma‐related rumination, PTSD, and depression, adjusting for symptom comorbidity. At intake, patients completed a semistructured interview and self‐report questionnaires. Primary diagnoses were confirmed via medical record review. Trauma‐related rumination was common, with more than 80% of patients reporting at least sometimes engaging in this cognitive style in the past week. After adjusting for other relevant cognitive factors, trauma‐related rumination was significantly associated with several specific PTSD symptoms, rps = .33–.48. Additionally, the severity of trauma‐related rumination was associated with overall PTSD symptom severity, even after adjusting for comorbid depression symptoms, rp2 = .35. In contrast, the association between trauma‐related rumination and depressive symptom severity was not significant after adjusting for comorbid PTSD symptoms, rp2 = .008. These results highlight trauma‐related rumination as a unique contributing factor to the complex clinical presentation for a subset of trauma‐exposed veterans.
Validation of an Electronic Medical Record–Based Algorithm for Identifying Posttraumatic Stress Disorder in U.S. Veterans
Authors: Harrington Kelly M. , Quaden Rachel , Stein Murray B. , Honerlaw Jacqueline P. , Cissell Shadha , Pietrzak Robert H. , Zhao Hongyu , Radhakrishnan Krishnan , Aslan Mihaela , Gaziano John Michael , Concato John , Gagnon David R. , Gelernter Joel , Cho Kelly ,   on behalf of the VA Million Veteran Program and Cooperative Studies Program
Published: April 2019

We developed an algorithm for identifying U.S. veterans with a history of posttraumatic stress disorder (PTSD), using the Department of Veterans Affairs (VA) electronic medical record (EMR) system. This work was motivated by the need to create a valid EMR‐based phenotype to identify thousands of cases and controls for a genome‐wide association study of PTSD in veterans. We used manual chart review (n = 500) as the gold standard. For both the algorithm and chart review, three classifications were possible: likely PTSD, possible PTSD, and likely not PTSD. We used Lasso regression with cross‐validation to select statistically significant predictors of PTSD from the EMR and then generate a predicted probability score of being a PTSD case for every participant in the study population (range: 0–1.00). Comparing the performance of our probabilistic approach (Lasso algorithm) to a rule‐based approach (International Classification of Diseases [ICD] algorithm), the Lasso algorithm showed modestly higher overall percent agreement with chart review than the ICD algorithm (80% vs. 75%), higher sensitivity (0.95 vs. 0.84), and higher accuracy (AUC = 0.95 vs. 0.90). We applied a 0.7 probability cut‐point to the Lasso results to determine final PTSD case‐control status for the VA population. The final algorithm had a 0.99 sensitivity, 0.99 specificity, 0.95 positive predictive value, and 1.00 negative predictive value for PTSD classification (grouping possible PTSD and likely not PTSD) as determined by chart review. This algorithm may be useful for other research and quality improvement endeavors within the VA.
Multifactorial positive influence of cochlear implantation on patients with single‐sided deafness
Authors: Häußler Sophia M. , Köpke Vanessa , Knopke Steffen , Gräbel Stefan , Olze Heidi
Published: April 2019

Objectives

Single‐sided deafness (SSD) is an extreme case with profound unilateral hearing loss in the poorer ear and regular hearing in the other ear. The aim of this study is to investigate the impairment in the daily life of SSD patients and the influence of cochlear implants (CI) on their health‐related quality of life (HRQoL), the impact on existing tinnitus distress and psychological comorbidities, and audiometric parameters.

Methods

In total, 21 patients (8 male and 13 female) were included, and the Charité Test Battery was applied for all patients. Data on HRQoL were collected with the Nijmegen Cochlear Implant Questionnaire and the Medical Outcome Study Short Form 36 (SF‐36) Survey. Tinnitus distress was assessed with the Tinnitus Questionnaire (TQ). Data with regard to psychological comorbidities were collected using four validated questionnaires. Speech perception was assessed with the Freiburg Monosyllable Test (FMS), the Oldenburg Sentence Test (OLSA), and the Oldenburg Inventory (OI).

Results

HRQoL improved in the subdomain social interactions. Tinnitus distress dropped significantly 6 months postoperatively. SSD patients preoperatively showed elevated levels of stress, depressive symptoms, and anxiety. Postoperatively, these psychological symptoms improved with regard to stress, tension, and demands.

The audiometry tools revealed a significant improvement in directional hearing (OI), speech perception in silence, and in the speech intelligibility threshold (OLSA).

Conclusion

There was an improvement in HRQoL and a reduction of tinnitus and cognitive distress. The preoperatively elevated stress level decreased significantly, and psychological comorbidities such as depressive symptoms and anxiety all improved postimplantation.

Level of Evidence

II‐2 Laryngoscope, 130:500–506, 2020
Anemia and neutrophil‐to‐lymphocyte ratio in laryngeal cancer treated with induction chemotherapy
Authors: Gorphe Philippe , Bouhir Samia , Garcia Gabriel C. T. E. , Alali Abeer , Even Caroline , Breuskin Ingrid , Tao Yungan , Janot François , Bidault François , Temam Stéphane
Published: April 2019

Objectives/Hypothesis

We studied the influence of the neutrophil‐to‐lymphocyte ratio (NLR) and anemia on the response to induction chemotherapy (IC) and survival outcomes in laryngeal cancer patients treated with a preservation protocol.

Study Design

Retrospective single‐center case series.

Methods

We analyzed patients with T3 laryngeal cancer treated with IC using a preservation protocol. The NLR and hemoglobin levels were assessed before treatment and after IC. The response to chemotherapy was assessed using Response Evaluation Criteria in Solid Tumours 1.1 and World Heath Organization standards. The oncological endpoints were overall survival (OS) and disease‐free survival (DFS).

Results

Sixty‐eight patients were analyzed. The median NLR and hemoglobin levels before and after IC were 2.76 and 14.5 g/dL, and 2.01 and 11.6 g/dL, respectively. The NLR and anemia before treatment were not correlated, and they were not associated with the response to chemotherapy. However, an NLR > 5 and anemia before treatment were both associated with shorter OS and DFS. Notably, they were the only factors found to be significantly associated with survival outcomes.

Conclusions

In laryngeal cancer, patients treated with a preservation protocol, a high NLR ratio, and anemia before IC were associated with shorter survival, independently of the response to chemotherapy.

Level of Evidence

4 Laryngoscope, 130:E144–E150, 2020
Tropical Vegetable Oils Do Not Alter Growth Performance in African Catfish through a High n‐6 Polyunsaturated Fatty Acids Biosynthesis Capacity
Authors: Sourabié Aboubacar , Mandiki Syaghalirwa N. M. , Geay Florian , Ahoulé Ange G. , Naert Nathan , Toguyeni Aboubacar , Kestemont Patrick
Published: April 2019

The main objective of this study was to determine the best vegetable oils (VO) for nutrition of African catfish by assessing the effects of a complete replacement of fish oil (FO) by different VO sources on its growth performance, fatty acid composition, and elongase‐desaturase gene expression levels. Fish (16.2 g of initial body weight) were fed with five experimental isonitrogenous, isolipidic, and isoenergetic diets in which FO was totally replaced by cottonseed oil (CO), palm oil (PO), desert date oil (DO), or Shea butter (SB). Complete replacement of FO with VO did not affect growth performance except for low values in fish fed SB diet. Muscle n‐3 LC‐polyunsaturated fatty acids (PUFA) were significantly reduced in fish fed VO‐based diets when compared with FO fed fish. However, the muscle arachidinic acid (ARA) levels in phospholipid class were 1.4 to 1.6 times higher in fish fed CO and DO diets than FO fed fish despite the lower ARA suppliers from these VO‐based diets, suggesting endogenous LC‐PUFA biosynthesis from PUFA precursors in fish fed these VO. The fads2 and elovl5 gene expression levels in liver of fish fed DO were also higher compared to FO controls. Therefore, all the results support the hypothesis that African catfish has higher biosynthesis capacity to convert vegetable n‐6 PUFA precursors like linoleic acid (LNA, 18:2n‐6) into n‐6 LC‐PUFA of the ARA type, compared to the conversion of vegetable α‐linolenic acid (ALA, 18:3n‐3) into n‐3 LC‐PUFA of the eicosapentanoic acid (EPA) or docosahexanoic acid (DHA) type. The results also indicate that DO can be recommended as the best alternative to FO replacement in African catfish nutrition.
Prey taxonomy rather than size determines salp diets
Authors: Dadon‐Pilosof Ayelet , Lombard Fabien , Genin Amatzia , Sutherland Kelly R. , Yahel Gitai
Published: April 2019

Salps are gelatinous planktonic suspension feeders that filter large volumes of water in the food‐dilute open ocean. Their life cycle allows periodic exponential growth and population blooms. Dense swarms of salps have a high grazing impact that can deplete the photic zone of phytoplankton and export huge quantities of organic matter to the deep sea. Previous studies described their feeding manner as mostly nonselective, with larger particles retained at higher efficiencies than small particles. To examine salp diets, we used direct in situ sampling (InEx method) of undisturbed solitarySalpa maxima. Aggregates (“chains”) ofSalpa fusiformisandThalia democraticawere studied using in situ incubations. Our findings suggest that in situ feeding rates are higher than previously reported and that cell removal is size independent with ∼ 1μm picoeukaryotes preferentially removed over both larger eukaryotes and smaller bacteria. The prey : predator size ratios we measured (1 : 104–1 : 105) are an order of magnitude smaller than previously reported values and to the best of our knowledge, are the smallest values reported so far for any planktonic suspension feeders. Despite differences among the three species studied, they had similar prey preferences with no correlation between salp body length and prey size. Our findings shed new light on prey : predator relationships in planktonic systems—in particular, that factors other than size influence filtration efficiency—and suggest that in situ techniques should be devised and applied for the study of suspension feeding in the ocean.
Engaging High School Students as Collaborators in Ecological Investigation of the Columbia River Estuary: Lessons from a Transdisciplinary University–High School Partnership
Authors: Rollwagen‐Bollens Gretchen , Holmlund Tamara , Bollens Stephen , Wait Jude , Zimmerman Julie , Connelly Kristin , Bargmann Lucas
Published: April 2019

The Columbia River Estuary Science Education and Outreach (CRESCENDO) project was a university–high school partnership between Washington State University (WSU) researchers and science teachers and students from five high schools located in southwest Washington, adjacent to the Columbia River Estuary (CRE). The CRESCENDO project explicitly integrated ecological research with science education research that assessed how high school students' participation in university‐sponsored research impacted their knowledge of CRE ecology and their attitudes about science and stewardship. From October 2016 to September 2018, CRESCENDO teachers and students measured water quality and conducted plankton tows from a dock near each of their schools every month. Each May, the CRESCENDO participants (WSU scientists, science educators, high school teachers, and students from each school) convened a Research Symposium to interpret the results. Here, we describe the project design and outcomes to illustrate the lessons learned from CRESCENDO and provide recommendations for developing future university–high school partnerships focused on locally relevant environmental problems.