bluuebunny/crossref_metadata_2025 huggingface dataset:
Frontline Science: High fat diet and leptin promote tumor progression by inducing myeloid-derived suppressor cells
Authors: Clements Virginia K , Long Tiha , Long Ramses , Figley Chas , Smith Daniel M C , Ostrand-Rosenberg Suzanne
Published: January 2018

Obesity is a risk factor for cancer incidence and cancer mortality. The association of obesity and cancer is attributed to multiple factors, but the tightest linkage is with the chronic, low-grade inflammation that accompanies obesity. Myeloid-derived suppressor cells (MDSC) are known facilitators of cancer progression that act by suppressing the activation and function of tumor-reactive T cells. Because MDSC quantity and function are driven by chronic inflammation, we hypothesized that MDSC may accumulate in obese individuals and facilitate tumor growth by suppressing antitumor immunity. To test this hypothesis, tumor-bearing mice on a high fat or low fat diet (HFD or LFD) were assessed for tumor progression and the metabolic dysfunction associated with obesity. HFD enhanced the accumulation of MDSC, and the resulting MDSC had both beneficial and detrimental effects. HFD-induced MDSC protected mice against diet-induced metabolic dysfunction and reduced HFD-associated inflammation, but also increased the accumulation of fat, enhanced tumor progression, and spontaneous metastasis and reduced survival time. HFD-induced MDSC facilitated tumor growth by limiting the activation of tumor-reactive CD8+ T cells. Leptin, an adipokine that regulates appetite satiety and is overexpressed in obesity, undergoes crosstalk with MDSC in which leptin drives the accumulation of MDSC while MDSC down-regulate the production of leptin. Collectively, these studies demonstrate that although MDSC protect against some metabolic dysfunction associated with HFD they enhance tumor growth in HFD mice and that leptin is a key regulator linking HFD, chronic inflammation, immune suppression, and tumor progression.
Early events in TNF signaling: a story of associations and dissociations
Authors: Darnay Bryant G , Aggarwal Bharat B
Published: January 2018

At the cellular level, the multifunctional cytokine tumor necrosis factor (TNF) modulates growth and activates genes through various intermediates, including protein kinases, protein phosphatases, reactive oxygen intermediates, phospholipases, proteases, sphingomyelinases, and transcription factors. Unlike many cytokine receptors, however, the cytoplasmic domain (CD) of the TNF receptors lacks an intrinsic protein kinase activity and yet on interaction with ligand it phosphorylates various proteins. Although the kinetics of most of these activities differ, their interactions are coordinated through the selective interplay between the CD of the receptors and the associated proteins. A unique pathway has been identified by the ability of the TNF receptors to associate with a novel family of proteins. Two distinct families of proteins have emerged, the TNF receptor-associated factors (TRAFs) and the death domain homologues. The cloning of members of these gene families and the identification of the protein-interaction motifs found within their gene products has initiated the molecular identity of factors (TRADD, FADD/MORT, RIP, FLICE/ MACH, and TRAFs) associated with both of the p60 and p80 forms of the TNF receptor and with other members of the TNF receptor superfamily. In this review, we summarize these and other TNF receptor-associated proteins and their potential roles in regulating the activation of nuclear factor-κB and apoptosis, two major responses activated by engagement of TNF receptors by the ligand.
Enhanced cytokine production by milk macrophages following infection with respiratory syncytial virus
Authors: Sone Shigemi , Tsutsumi Hiroyuki , Takeuchi Ryoh , Matsuda Kazuko , Lmai Shosuke , Ogra Pearay L , Chiba Shunzo
Published: January 2018

Paired samples of milk and serum collected 3 days postpartum from 20 women were tested for the presence and level of interleukin (IL)-1β, IL-6, IL-12, tumor necrosis factor α (TNF-α), and interferon-γ (IFN-γ) by enzyme immunoassay. The expression of these cytokine mRNAs in milk macrophages from eight donors were semiquantitatively analyzed by reverse transcriptase-polymerase chain reaction. The effects of respiratory syncytial virus (RSV) infection on cytokine production were determined in five samples of milk macrophages. Over 90% of the milk samples tested exhibited detectable levels of IL-1β, IL-6, and TNF-α. No IL-12 or IFN-γ activity was detected in the milk. IL-6 activity was weakly detected in about 45%, and TNF-α activity in about 10% of the serum samples tested. However, no IL-1β, IL-12, or IFN-γ activity was demonstrated in any of the serum samples. Milk macrophages from eight subjects all exhibited mRNA for IL-1β, TNF-α, and IL-6, and IFN-γ mRNA in six of eight subjects, although no IFN-γ was detected in any of the 20 samples of milk tested. RSV exposure resulted in a 2- to 100-fold increase in the expression of IL-1β, IL-6, and TNF-α mRNA as well as cytokine protein. Although RSV infection enhanced the expression of IFN-γ mRNA, no detectable IFN-γ was produced by the milk macrophages. These observations suggest that the milk macrophages are actively engaged in the physiological production of IL-1β, IL-6, TNF-α, and IFN-γ in the mammary gland and continue to possess the capacity to increase production of these cytokines in response to RSV and possibly other viral infections.
Leukocyte contribution to parenchymal cell death in an experimental model of inflammation
Authors: Tung David K-L , Bjursten Lars M , Zweifach Benjamin W , Schmid-Schönbein Geert W
Published: January 2018

The relationship between leukocyte migration and parenchymal cell death in vivo remains poorly documented. Accordingly, cell killing in the rat mesentery, as recorded by propidium iodide staining, was investigated with an intravital approach. Superfusion of platelet-activating factor (PAF, 10–8 M) or N-formyl-methionyl-leucyl-phenylalanine (fMLP, 10–8 M) led to extensive leukocyte extravasation but no significant cell death. In contrast, pretreatment with 10–8 M PAF or fMLP for 1 h, followed by superfusion of PAF in combination with fMLP (both at 10–8 M) led to an increase in cell death. Mesenteric parenchymal cells but no endothelial cells were killed. Some of the dead cells were identified as granulocytes/monocytes that were already in the tissue at the start of the experiment. The incidence of cell death was lower but not eliminated when leukocyte migration was blocked with a monoclonal antibody against CD18. A xanthine oxidase inhibitor, BOF-4272, failed to diminish cell death, whereas a hydroxyl radical scavenger, dimethylthiourea, attenuated cell killing without an effect on the number of adhering and migrating leukocytes. These observations demonstrate that leukocytes serve as a factor in the killing of extravascular cells only after the development of a level of stimulation that differs from that required to induce a migratory stimulus into the extravascular space.
Porcine bone marrow myeloid cells: phenotype and adhesion molecule expression
Authors: Summerfield Artur , McCullough Kenneth C
Published: January 2018

The purpose of this study was the discrimination of porcine bone marrow hematopoietic cell (BMHC) subpopulations and cell maturation stages by using cluster of differentiation (CD) and Swine Workshop Cluster (SWC) molecules, combined with cell size, granularity, and the capacity to generate an oxidative burst. SWC3 was the earliest myeloid marker identified in the differentiation pathways. Through SWC3/SWC8 double labeling, three populations committed to the myeloid lineage were discriminated: early myeloid progenitors, which were SWC3lowSWC8–; cells committed to the granulocytic lineage, which were SWC3+SWC8+; monocytic cells, which were SWC3+-SWC8–. The SWC3lowSWC8– myeloid progenitors expressed high levels of CD44 and CD49d, but no CD14. Among the SWC3+SWC8+ granulocytic cells, the most immature were CD14– CD11a/18– CD44low, an intermediate stage was CD14+CD11a/18lowCD44–, and the most mature were CD14+CD11a/18high–CD44high. Only the latter could generate a rapid oxidative burst. Moreover, during granulocytic maturation, a constant decrease in CD49d/29 expression was observed. In contrast, the SWC3+SWC8– monocytic cells were mainly CD14+ and expressed high levels of the adhesion molecules. These results define porcine hematopoietic differentiation and maturation stages. Similarities in human and porcine adhesion molecule expression have been identified, suggesting common functionalities in the regulation of hematopoiesis and the potential of the pig as a model for hematopoietic studies.
Activation-associated changes in blood and bone marrow neutrophils
Authors: Klut Maria E , Whalen Beth A , Hogg James C
Published: January 2018

Accelerated granulocytopoiesis and polymorphonuclear leukocyte (PMN) activation via the complement system are important events in the inflammatory response. This study tests the hypothesis that PMN of the peripheral blood and the bone marrow behave differently when stimulated with zymosan-activated plasma (ZAP). PMN were treated with ZAP and processed to determine the content and distribution of F-actin, the expression of CD18 integrins, and the cell area/shape with the use of a combination of flow cytometry, fluorescence, and light microscopy. The results show that untreated bone marrow PMN display similar F-actin content and cell area but express less CD18 than peripheral blood PMN. ZAP-activated peripheral blood PMN show a marked increase in the F-actin content, CD18 expression, cell area, and length. Highly elongated PMN develop a polar shape in which microfilaments are redistributed in cell protrusions and CD18 is located in the uropod and the lamellipodium. In comparision, activated bone marrow PMN show a lower and more transient increase in the F-actin content, express less CD18, show a reduced increase in the cell area, and display reduced polarity and microfilament redistribution. We conclude that bone marrow PMN show lower complement-activation response than peripheral blood PMN and suggest that the lower expression of surface membrane integrins and related cytoskeletal filaments may account for their reduced ability to develop the polar shape required for diapedesis and migration.
Mast cell granules potentiate endotoxin-induced interleukin-6 production by endothelial cells
Authors: Li Yuai , Stechschulte Ann C , Smith Donald D , Lindsley Herbert B , Stechschulte Daniel J , Dileepan Kottarappat N
Published: January 2018

Mast cells are constituent cells of vascular tissue and their numbers are increased in atherosclerotic vessels. To gain insight into the role of mast cells in vascular inflammation, the effect of mast cell granules (MCG) on endothelial cell production of interleukin-6 (IL-6) was examined. Human umbilical vein endothelial cells (HUVEC) were cultured with lipopolysaccharide (LPS) in the presence or absence of rat peritoneal MCG and IL-6 production was assayed by enzymelinked immunosorbent assay. The interaction of MCG with HUVEC in culture was examined by electron microscopy (EM). The EM studies revealed that MCG are internalized by HUVEC and appear intact even after 24 h in culture. Unactivated HUVEC produced little or no IL-6 either in the presence or absence of MCG. Treatment of HUVEC with LPS stimulated IL-6 production in a dose- and time-dependent fashion. Addition of MCG to LPS-activated HUVEC resulted in the potentiation of IL-6 production at all LPS doses. MCG-induced enhancement of IL-6 production was evident even at a mast cell-to-endothelial cell ratio of 1:32. The enhancement of IL-6 production by MCG was also seen when tumor necrosis factor α was used as an activator. Although potentiation was evident when MCG were added 6 h before or after LPS stimulation, the maximum effect was noted when MCG and LPS were added simultaneously. MCG-mediated enhancement of IL-6 production was abrogated by pretreating MCG with protease inhibitors. Although MCG proteases potentiate IL-6 production by HUVEC, they do not degrade secreted IL-6. These results demonstrate that MCG interact with endothelial cells and modulate the production of an important inflammatory cytokine.
Characterization of a culture-derived CD15+CD11b- promyelocytic population from CD34+ peripheral blood cells
Authors: Unverzagt Kristen L , Bender James G , Loudovaris Maureen , Martinson Jeffrey A , Hazelton Bonnie , Weavert Charles
Published: January 2018

Selected CD34+ cells from mobilized apheresis products were cultured in serum-free or serum-containing media supplemented with granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor (GM-CSF), interleukin-3 (IL-3), and stem cell factor (SCF; c-kit ligand). We examined the emergence of a CD15+ CD11b- population, which appeared morphologically to be promyelocytes. This CD15+CD11b- population can be further expanded in culture into morphologically mature granulocytes. In an attempt to characterize this culture-derived CD15+CD11b- promyelocytic population, single cells were clone sorted into wells of a Terasaki plate containing various growth factors. We compared the growth factor requirements and kinetics of this apheresis culture-derived CD15+ CD11b- population to the CD15+CD11b- population from fresh bone marrow samples. Our studies indicate that the CD15+CD11b- promyelocytic population from bone marrow and blood are equivalent in their ability to proliferate and in their requirements for growth factors. The CD15+CD11b- population in vitro shows a high proliferative capacity when compared with the other CD15/CD11b populations (CD15-CD11b-, CD15+CD11b+, CD15-CD11b+). Thus, we can manipulate CD34+ cells in vitro to proliferate and differentiate toward a mature neutrophil lineage. The CD15+ CDllb- promyelocytic population derived from this culture may represent the most effective cultured cell population for therapeutic reduction of neutropenia in vivo based on both its stage of differentiation and its proliferative potential.
Enhanced mobilization of hematopoietic progenitor cells by mouse MIP-2 and granulocyte colony-stimulating factor in mice
Authors: Wang Jian-bin , Mukaida Naofumi , Zhang Yi , Lto Takaaki , Nakao Shinji , Matsushima Kouji
Published: January 2018

Human interleukin-8 (IL-8) induces a rapid mobilization of hematopoietic progenitor cells (HPCs) into peripheral blood in mice and primates. Because an exact homologue of human IL-8 does not exist in mice, a chemokine, macrophage inflammatory protein-2 (MIP-2), is supposed to substitute the function of IL-8 in mice. Hence, we investigated the capacity of mouse MIP-2 to induce HPC mobilization in mice. Mouse MIP-2 induced, in either untreated or splenectomized mice, a rapid HPC mobilization, as evidenced by increased numbers of colony-forming unit granulocyte-macrophage (CFU-GM) and lineage marker (Lin)- c-kit+Sca-1 + cells. Although release of elastase from activated neutrophils was proposed to be involved in IL-8-induced HPC mobilization, mouse MIP-2 induced similar levels of HPC mobilization in elastase-deficient beige mice at a similar level to normal ones. This HPC mobilization by MIP-2 was markedly enhanced by pretreatment with granulocyte-colony-stimulating factor (G-CSF). Moreover, the combination of G-CSF and MIP-2 apparently down-regulated L-selectin expression on Lin- Sca-1 + cells in peripheral blood as well as bone marrow. Thus, MIP-2 may down-modulate the interaction between HPCs and bone marrow stroma by reducing L-selectin expression on HPCs and cause rapid mobilization of HPCs into peripheral blood.
Suppression of TNF-α gene expression by hemin: implications for the role of iron homeostasis in host inflammatory responses
Authors: Silver Bernard J , Hamilton Beverly D , Toossit Zahra
Published: January 2018

Tumor necrosis factor α (TNF-α) has multiple effects on iron homeostasis and erythropoiesis and has been implicated in the pathogenesis of the anemia of inflammation. We postulated that intracellular iron in turn may regulate the expression of TNF-α. In the human monocytic leukemia cell line, THP-1, low basal TNF-α message levels were stimulated (sevenfold) when serum was excluded from the culture medium. Addition of hemin completely suppressed TNF-α expression. Similarly, hemin suppressed lipopolysaccharide-induced expression of TNF-α. Snprotoporphyrin, an inhibitor of heme oxygenase (which releases iron from hemin), prevented hemin-induced suppression of TNF-α expression. Conversely, the intracellular iron chelator, desferrioxamine, stimulated TNF-α expression. Thus, the expression of TNF-α, itself a physiological regulator of iron homeostasis, appears to be controlled by intracellular levels of iron. J.
The role of CXC chemokines in the regulation of angiogenesis in non-small cell lung cancer
Authors: Arenberg Douglas A , Polverini Peter J , Kunkel Steven L , Shanafelt Armen , Hesselgesser Joseph , Horuk Richard , Strieter Robert M
Published: January 2018

Angiogenesis is a critical component of tumor biology. In recent years newer techniques of cell and molecular biology have led to important advances in our understanding of this process. The regulation of angiogenesis depends on a balance between the activity of local factors that promote (angiogenic factors) or inhibit (angiostatic factors) neovascularization. Nowhere is this paradigm of a balance more apparent than in the study of tumor-associated angiogenesis. Tumors promote angiogenesis through a combination of overexpression of angiogenic factors and local inhibition of angiostatic factors. This strategy leads to an angiogenic environment that promotes tumor growth and metastases. Our laboratory has focused studies on the role of the CXC chemokine family in the regulation of angiogenesis by non-small cell lung cancer (NSCLC). In this article, we review our findings that the CXC chemokine family is composed of members that are either angiogenic or angiostatic. We have found that in NSCLC an imbalance exists in the expression of these factors that favors tumor-derived angiogenesis, and therefore tumor growth and metastases. Furthermore, when this imbalance is corrected to reduce the presence of angiogenic factors or increase the presence of angiostatic factors, tumor growth and metastases are reduced.
Regulation of CCR2 chemokine receptor mRNA stability
Authors: Xu L , Rahimpour R , Ran L , Kong C , Biragyn A , Andrews J , Devries M , Wang J-M , Kelvin D J
Published: January 2018

During inflammatory and immunological responses, leukocytes respond to external stimuli by altering the stability of cytokine and cytokine receptor messages. Change in message stability is an effective mechanism for rapidly regulating steady state levels of mRNA. Cytokine messages containing A-U-rich elements located in the 3′ untranslated region (ARE) are the best studied examples of this process. AREs have been shown to act as targeting motifs for degradation of cytokine and transcription factor messages. We have recently observed that the interleukin-8 (IL-8) receptor messages, IL-8RA and B (CXCR1 and CXCR2), also undergo changes in stability in response to the inflammatory stimulator lipopolysaccharide (LPS). To determine whether regulation of message stability is a common mechanism for modulation of chemokine receptor mRNA we explored whether the stability of the CC chemokine receptor message for CCR2 (monocyte chemotactic protein-1 receptor) is also regulated by LPS. We found that LPS induces a rapid loss of steady state levels of CCR2 message through message degradation. Furthermore, LPS stimulated the decay of Poly(A) CCR2 mRNA faster than total CCR2 RNA, indicating that deadenylation is the first step in LPS-induced CCR2 RNA degradation. We conclude from these experiments that LPS stimulates the rapid degradation of CCR2 messages through a two-step process, deadenylation followed by degradation of the message body. In contrast to the results obtained for CCR2 mRNA, macrophage inflammatory protein-1α messages, which contain an ARE motif, were stabilized by LPS stimulation, indicating that chemokine and chemokine receptor mRNA stability are regulated by different and opposing mechanisms.
Obstetric and Gynecologic Ultrasound Curriculum and Competency Assessment in Residency Training Programs: Consensus Report
Authors: Abuhamad Alfred , Minton Katherine K. , Benson Carol B. , Chudleigh Trish , Crites Lori , Doubilet Peter M. , Driggers Rita , Lee Wesley , Mann Karen V. , Perez James J. , Rose Nancy C. , Simpson Lynn L. , Tabor Ann , Benacerraf Beryl R.
Published: January 2018

Ultrasound imaging has become integral to the practice of obstetrics and gynecology. With increasing educational demands and limited hours in residency programs, dedicated time for training and achieving competency in ultrasound has diminished substantially. The American Institute of Ultrasound in Medicine assembled a multisociety task force to develop a consensus‐based, standardized curriculum and competency assessment tools for obstetric and gynecologic ultrasound training in residency programs. The curriculum and competency assessment tools were developed based on existing national and international guidelines for the performance of obstetric and gynecologic ultrasound examinations and thus are intended to represent the minimum requirement for such training. By expert consensus, the curriculum was developed for each year of training, criteria for each competency assessment image were generated, the pass score was established at, or close to, 75% for each, and obtaining a set of 5 ultrasound images with pass score in each was deemed necessary for attaining each competency. Given the current lack of substantial data on competency assessment in ultrasound training, the task force expects that the criteria set forth in this document will evolve with time. The task force also encourages use of ultrasound simulation in residency training and expects that simulation will play a significant part in the curriculum and the competency assessment process. Incorporating this training curriculum and the competency assessment tools may promote consistency in training and competency assessment, thus enhancing the performance and diagnostic accuracy of ultrasound examination in obstetrics and gynecology.
The fast signal diffusion limit in a chemotaxis system with strong signal sensitivity
Authors: Mizukami Masaaki
Published: January 2018

This paper gives an insight into making a mathematical bridge between the parabolic‐parabolic signal‐dependent chemotaxis system and its parabolic‐elliptic version. To be more precise, this paper deals with convergence of a solution for the parabolic‐parabolic chemotaxis system with strong signal sensitivity
urn:x-wiley:0025584X:media:mana201700270:mana201700270-math-0001to that for the parabolic‐elliptic chemotaxis system
urn:x-wiley:0025584X:media:mana201700270:mana201700270-math-0002where Ω is a bounded domain in () with smooth boundary, is a constant and χ is a function generalizing
urn:x-wiley:0025584X:media:mana201700270:mana201700270-math-0006In chemotaxis systems parabolic‐elliptic systems often gave some guide to methods and results for parabolic‐parabolic systems. However, the relation between parabolic‐elliptic systems and parabolic‐parabolic systems has not been studied except for the case that . Namely, in the case that Ω is a bounded domain, it still remains to analyze on the following question: Does a solution of the parabolic‐parabolic system converge to that of the parabolic‐elliptic system as ?
This paper gives some positive answer in the chemotaxis system with strong signal sensitivity.
Sensor kinase KinB and its pathway‐associated key factors sense the signal of nutrition starvation in sporulation of Bacillus subtilis
Authors: Liu Weipeng , He Zeying , Gao Feng , Yan Jinyuan , Huang Xiaowei
Published: January 2018

Bacillus subtilis responds to environmental stress cues and develops endospores for survival. In the process of endospore formation, sporulation initiation is a vital stage and this stage is governed by autophosphorylation of the sensor histidine kinases. The second major sensor kinase KinB perceives the intracellular changes of GTP and ATP during sporulation. However, determination of the environmental signals as well as its related signaling pathway of KinB requires further elucidation. Our current study found that, contrary to the sporulation failure induced by ΔkinA in the nutrient‐rich 2× SG medium, the sensor kinase KinB sensed the environmental cues in the nutrient‐poor MM medium. Two other membrane proteins, KapB and KbaA, also responded similarly to the same external signal as KinB. Both KapB and KbaA acted upstream of KinB, but they exerted their regulation upon KinB independently. Furthermore, we demonstrated that both the SH3 domain and the α‐helix structure in KapB are required for sensing or transducing the signal of sporulation initiation. Collectively, our work here supplied the direct evidences that KinB and its pathway sense the external signal of nutrient starvation in MM medium, and further analyzes the interrelationship among KinB, KbaA, and KapB.
Well‐being and moral identity
Authors: Garcia Danilo , Moradi Saleh , Amato Clara , Granjard Alexandre , Cloninger Kevin
Published: January 2018

The good life is the result of flourishing and resilience, but also of being a morally good person. We found that moral identity was associated with engagement, meaning, the identification and acceptance of others (i.e., cooperativeness), and the sense of being part of something bigger than the self (i.e., self‐transcendence).
Membranal and Blood‐Soluble HLA Class II Peptidome Analyses Using Data‐Dependent and Independent Acquisition
Authors: Ritz Danilo , Sani Emiliano , Debiec Hanna , Ronco Pierre , Neri Dario , Fugmann Tim
Published: January 2018

The interaction between HLA class II peptide complexes on antigen‐presenting cells and CD4+ T cells is of fundamental importance for anticancer and antipathogen immunity as well as for the maintenance of immunological tolerance. To study CD4+ T cell reactivities, detailed knowledge of the presented peptides is necessary. In recent years, dramatic advances in the characterization of membranal and soluble HLA class I peptidomes could be observed. However, the same is not true for HLA class II peptidomes, where only few studies identify more than hundred peptides. Here we describe a MS‐based workflow for the characterization of membranal and soluble HLA class II DR and DQ peptidomes. Using this workflow, we identify a total of 8595 and 3727 HLA class II peptides from Maver‐1 and DOHH2 cells, respectively. Based on this data, a motif‐based binding predictor is developed and compared to NetMHCIIpan 3.1. We then apply the workflow to human plasma, resulting in the identification of between 34 and 152 HLA‐DR and between 100 and 180 HLA‐DQ peptides, respectively. Finally, we implement a data‐independent acquisition workflow to increase reproducibility and sensitivity of HLA class II peptidome characterizations.
Semiochemicals to enhance herbivory by Diorhabda carinulata aggregations in saltcedar (Tamarix spp.) infestations
Authors: Gaffke Alexander M , Sing Sharlene E , Dudley Tom L , Bean Daniel W , Russak Justin A , Mafra‐Neto Agenor , Grieco Paul A , Peterson Robert KD , Weaver David K
Published: January 2018

BACKGROUND

Semiochemicals for monitoring, attracting or repelling pest and beneficial organisms are increasingly deployed in agricultural and forest systems for pest management. However, the use of aggregation pheromones and host‐plant attractants for the express purpose of increasing the efficacy of classical biological control agents of weeds has not been widely reported. Therefore, we conducted field‐based assays to determine if a specialized wax‐based matrix impregnated with an aggregation pheromone of the northern tamarisk beetle Diorhabda carinulata (Desbrochers) or host‐plant volatiles could increase the efficacy of D. carinulata.

RESULTS

The aggregation pheromone and host‐plant volatiles were formulated for field application using a wax‐based matrix. Reported release rates suggest that this matrix is a viable formulation for enhancing D. carinulata aggregations under field conditions. Pheromone‐treated saltcedar plants (Tamarix spp.) not only had higher densities of adult and larval D. carinulata, but also sustained greater levels of foliar damage than control plants. Increased damage from the focused feeding of D. carinulata caused an increase in foliar dieback and decrease in live canopy volume of semiochemical‐treated plants.

CONCLUSION

Field deployment of these semiochemical formulations could be useful in directing populations of D. carinulata for increased impact on Tamarix spp. © 2018 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
Development of predictive signatures for treatment selection in precision medicine with survival outcomes
Authors: Chen Yu‐Chuan , Lee Un Jung , Tsai Chen‐An , Chen James J.
Published: January 2018

For survival endpoints in subgroup selection, a score conversion model is often used to convert the set of biomarkers for each patient into a univariate score and using the median of the univariate scores to divide the patients into biomarker‐positive and biomarker‐negative subgroups. However, this may lead to bias in patient subgroup identification regarding the 2 issues: (1) treatment is equally effective for all patients and/or there is no subgroup difference; (2) the median value of the univariate scores as a cutoff may be inappropriate if the sizes of the 2 subgroups are differ substantially. We utilize a univariate composite score method to convert the set of patient's candidate biomarkers to a univariate response score. We propose applying the likelihood ratio test (LRT) to assess homogeneity of the sampled patients to address the first issue. In the context of identification of the subgroup of responders in adaptive design to demonstrate improvement of treatment efficacy (adaptive power), we suggest that subgroup selection is carried out if the LRT is significant. For the second issue, we utilize a likelihood‐based change‐point algorithm to find an optimal cutoff. Our simulation study shows that type I error generally is controlled, while the overall adaptive power to detect treatment effects sacrifices approximately 4.5% for the simulation designs considered by performing the LRT; furthermore, the change‐point algorithm outperforms the median cutoff considerably when the subgroup sizes differ substantially.
Clinically Relevant Radioactive Dose Formulation of 177Lu‐Labeled Cetuximab‐Fab Fragment for Potential Use in Cancer Theranostics
Authors: Chakravarty Rubel , Rohra Nanda , Chakraborty Sudipta , Jain Ratnesh , Sarma Haladhar Dev , Dash Ashutosh
Published: January 2018

The goal of this study is to generate Fab fragment of cetuximab, a chimeric monoclonal antibody targeting epidermal growth factor receptor (EGFR) on the surface of cancer cells, and radiolabel it with 177Lu for potential use in cancer theranostics. Cetuximab‐Fab was produced with high purity through papain digestion of cetuximab, and used for formulation of clinically relevant radioactive dose (∼ 1.3 GBq) of 177Lu‐labeled cetuximab‐Fab after conjugation with a suitable bifunctional chelator, N‐[(R)‐2‐amino‐3‐(para‐isothiocyanato‐phenyl) propyl]‐trans‐(S,S)‐cyclohexane‐1,2‐diamine‐N,N,N′,N′′,N′′‐pentaacetic acid (CHX−A′′‐DTPA). The radiolabeled agent could be prepared with adequate specific activity (50.2 ± 0.6 GBq/μmol), high radiochemical purity (95.3 ± 0.5%) and appreciable in vitro stability under physiological conditions. Biodistribution studies with 177Lu‐CHX−A′′‐DTPA‐cetuximab‐Fab carried out in Swiss mice bearing fibrosarcoma tumors demonstrated significant tumor uptake (10.7 ± 2.2 %ID/g) within 4 h post‐injection (p.i.) with good tumor‐to‐background contrast. While rapid clearance of the radiolabeled agent from non‐target organs/tissues through hepatobiliary and renal routes was observed, tumor uptake remained consistently high up to 7 d p.i. (13.3 ± 3.6 %ID/g). Blocking studies with unlabeled cetuximab confirmed EGFR specificity of the radiotracer in vivo. This study might aid toward future clinical translation of radiolabeled antibody‐fragments in cancer theranostics.
Modifying the Acidity of Charged Droplets
Authors: Ojakivi Mari , Liigand Jaanus , Kruve Anneli
Published: January 2018

The concept of acidity in confined spaces is up to date poorly understood; especially, in case of media violating electroneutrality. Here, we describe the acidity of charged droplets via their ability to protonate simple nitrogen bases and we propose ways to modify the protonation efficiency with the help of additives. We observed that the protonation of compounds in charged water droplets is independent of solution‐phase acidity; instead, it can be adjusted with the help of additive type. On the other hand, the extent of protonation in charged methanol droplets can be adjusted with the conventional approach of changing the pH.
Production of Toluene by Decomposition of 2‐Hydroxy‐6‐methylbenzaldehyde: A DFT Study
Authors: Verma Anand Mohan , Agrawal Kushagra , Kawale Harshal D. , Kishore Nanda
Published: January 2018

The fast pyrolysis of lignocellulosic biomass produces raw bio‐oil that comprises of several oxygenated organic compounds which are disadvantageous and lower the quality of bio‐oil as a fuel. In this numerical study, 2‐hydroxy‐6‐methylbenzaldehyde (HMB) component, one such oxygenated compound which represents aromatic aldehyde category of bio‐oil, is considered as model compound for its decomposition within the framework of density functional theory. The bond dissociation analysis of HMB component suggests that the dehydrogenation of methyl group is the least energy demanding amongst all nine possible bond scissions. Further, eight reaction pathways are investigated for the conversion of HMB into toluene as end product along with the analyses of their corresponding potential energy surfaces. Briefly, results indicate that the optimum reaction progress for the production of toluene from HMB requires an activation energy of 12.26 kcal/mol. It is further observed that the production of toluene from HMB includes m‐cresol as an intermediate instead of 2‐formyltoulene; and, the production of 2‐hydroxybenzaldehyde is not favourable. Furthermore, the thermochemistry analyses for the production of toluene using optimum reaction pathway and for the production of 2‐hydroxybenzaldehyde using reaction pathway 9 are performed over a wide range of temperature, i. e., 473–873 K at an interval of 100 K. The thermochemistry also suggests higher favourability for the production of toluene compared to the production of 2‐hydroxybenzaldehdye by decomposing HMB.
Chloronium Cations in Dichloromethane Solutions as Catalysts for the Conversion of CH2Cl2 to CHCl3/CCl4 and CH3Cl/CH4
Authors: Stoyanov Evgenii S. , Stoyanova Irina V.
Published: January 2018

The mechanism of homogeneous acidic catalytic conversion of CH2Cl2 to CHCl3 and CCl4 and simultaneously to CH3Cl and CH4 in solutions of the H(CHB11Cl11) superacid in dichloromethane was identified. The role of the catalysts is played by the chloronium cations formed in the solutions. The processes proceed through the exchange of the Cl atoms of the CH2Cl‐ group of cations CH2Cl‐Cl+‐CH2Cl and CH2Cl‐Cl+‐CH3 for the H atoms of the CH2Cl2 molecules, transforming them initially to CHCl3 and then to CCl4. Simultaneously, the CH3‐group of cations CH3‐Cl+‐CH2Cl and CH3‐Cl+‐CH3 exchanges its H atom for the Cl atom of CH2Cl2 molecules, transforming them to CH3Cl and further to CH4. The processes of chlorination and dechlorination lead to cyclic reproduction of chloronium cations.
Study on lifetime prediction considering fatigue accumulative effect for die‐attach solder layer in an IGBT module
Authors: Lai Wei , Chen Minyou , Ran Li , Xu Shengyou , Pan Liang‐ming , Alatise Olayiwola , Mawby Philip
Published: January 2018

An accurate lifetime model is needed in power electronic systems as a cost‐effective means of improving reliability and performance assessment, which have long been highly desired to reduce the maintenance cost and to make the product more competitive in the market. Die‐attach solder layer fatigue has been identified as one of the root causes of failure of power electronic modules. This paper presents “physics‐of‐failure lifetime model”, which takes fatigue accumulative effect into consideration and can quantify the effect of long‐term small‐temperature cycling to device fatigue life cycle to estimate the lifetime of the power module. First, small ΔTj power cycling tests were designed to obtain the effects of ΔTj on aged and un‐aged modules. They indicated that the traditional lifetime models were not accurate in predicting the lifetime of power modules. Therefore, a new time‐domain crack propagation model based on the cumulative damage in the die‐attach solder layer is proposed, which includes time‐dependent material properties and temperature profiles. Moreover, power cycling experiments and simulations are conducted to demonstrate the method by comparing the number of cycles to failure. © 2018 Institute of Electrical Engineers of Japan. Published by John Wiley & Sons, Inc.
Ultrasound and hematological changes during early luteal phase in women at high risk for developing ovarian hyperstimulation syndrome
Authors: Lainas G. T. , Lainas T. G. , Venetis C. A. , Sfontouris I. A. , Zorzovilis I. Z. , Alexopoulou E. , Tarlatzis B. C. , Kolibianakis E. M.
Published: January 2018

Objective

To assess ultrasound and hematological changes during the early luteal phase following triggering of final oocyte maturation with human chorionic gonadotropin (hCG) in women at high risk for developing ovarian hyperstimulation syndrome (OHSS).

Methods

This was a retrospective cohort study of 319 women undergoing in‐vitro fertilization who were at high risk for OHSS following administration of hCG for the triggering of final oocyte maturation. Patients were treated with a gonadotropin‐releasing hormone agonist or antagonist protocol and were monitored for 5 days post‐oocyte retrieval (early luteal phase). Severe OHSS was diagnosed in the presence of at least moderate ascites and two or more of the following: maximum ovarian diameter (MOD) > 100 mm, hematocrit (Ht) > 45%, white blood cell count (WBC) > 15 000/mm3, hydrothorax, dyspnea and oliguria. Outcome measures included change in Ht, ascites grade, WBC and MOD, as well as the association between these changes during the early luteal phase.

Results

Ascites grade, Ht and WBC increased significantly (P ≤ 0.001) during the early luteal phase, both in patients who developed and in those who did not develop severe early OHSS. MOD increased significantly (P = 0.001) only in patients who developed severe early OHSS. On multivariable analysis, both time following oocyte retrieval and whether severe early OHSS developed were significantly associated with ascites grade, Ht, WBC and MOD; furthermore, there was also a significant interaction between time and development of severe early OHSS for all four variables (P ≤ 0.001).

Conclusions

In women at high risk of OHSS, ascites grade, Ht and WBC significantly increased with time over the 5‐day observation period, in line with the pathophysiology of the syndrome. Our data support the use of MOD in the diagnosis of severe early OHSS, and provide novel evidence for the role of change in Ht as a patient‐specific hemoconcentration marker during development of OHSS. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.
Re: Fetal cardiac remodeling in twin pregnancy conceived by assisted reproductive technology. B. Valenzuela‐Alcaraz, M. Cruz‐Lemini, M. Rodriguez‐Lopez, A. Gonce, L. Garcia‐Otero, H. Ayuso, M. Sitges, B. Bijnens, J. Balasch, E. Gratacos and F. Crispi. Ultrasound Obstet Gynecol 2018; 51: 94–100.
Authors: Moon‐Grady A. J.
Published: January 2018

Linked Comment: Ultrasound Obstet Gynecol 2018; 51: 94–100
Description of a new approach for great auricular and auriculotemporal nerve blocks: A cadaveric study in foxes and dogs
Authors: Stathopoulou Thaleia‐ Rengina , Pinelas Rui , Haar Gert Ter , Cornelis Ine , Viscasillas Jaime
Published: January 2018

Otitis externa is a painful condition that may require surgical intervention in dogs. A balanced analgesia protocol should combine systemic analgesic agents and local anaesthesia techniques. The aim of the study was to find anatomical landmarks for the great auricular and the auriculotemporal nerves that transmit nociceptive information from the ear pinna and to develop the optimal technique for a nerve block. The study consisted of two phases. In phase I, one fox cadaver was used for dissection and anatomical localization of the auricular nerves to derive landmarks for needle insertion. Eight fox cadavers were subsequently used to evaluate the accuracy of the technique by injecting methylene blue bilaterally. In phaseIIfindings from phase I were applied in four Beagle canine cadavers. A block was deemed successful if more than 0.6 cm of the nerve's length was stained. Successful great auricular nerve block was achieved by inserting the needle superficially along the wing of the atlas with the needle pointing towards the jugular groove. For the auriculotemporal nerve block the needle was inserted perpendicular to the skin at the caudal lateral border of the zygomatic arch, close to the temporal process. The overall success rate was 24 out of 24 (100%) and 22 out of 24 (91%) for the great auricular and the auriculotemporal nerves, respectively, while the facial nerve was stained on three occasions. Our results suggest that it is feasible to achieve a block of the auricular nerves, based on anatomical landmarks, without concurrently affecting the facial nerve.
Breast and Tumour Volume Measurements in Breast Cancer Patients Using 3‐D Automated Breast Volume Scanner Images
Authors: Lagendijk M. , Vos E. L. , Ramlakhan K. P. , Verhoef C. , Koning A. H. J. , van Lankeren W. , Koppert L. B.
Published: January 2018

Background

The resection volume in relation to the breast volume is known to influence cosmetic outcome following breast‐conserving therapy. It was hypothesised that three‐dimensional ultrasonography (3‐D US) could be used to preoperatively assess breast and tumour volume and show high association with histopathological measurements.

Methods

Breast volume by the 3D‐US was compared to the water displacement method (WDM), mastectomy specimen weight, 3‐D MRI and three different calculations for breast volume on mammography. Tumour volume by the 3‐D US was compared to the histopathological tumour volume and 3‐D MRI. Relatedness was based on the intraclass correlation coefficient (ICC) with corresponding 95% confidence interval (95% CI). Bland–Altman plots were used to graphically display the agreement for the different assessment techniques. All measurements were performed by one observer.

Results

A total of 36 patients were included, 20 and 23 for the evaluation of breast and tumour volume (ductal invasive carcinomas), respectively. 3‐D US breast volume showed ‘excellent’ association with WDM, ICC 0.92 [95% CI (0.80–0.97)]. 3‐D US tumour volume showed a ‘excellent’ association with histopathological tumour volume, ICC 0.78 [95% CI (0.55–0.91)]. Bland–Altman plots showed an increased overestimation in lager tumour volumes measured by 3‐D MRI compared to histopathological volume.

Conclusions

3‐D US showed a high association with gold standard WDM for the preoperative assessment of breast volume and the histopathological measurement of tumour volume. 3‐D US is an patient‐friendly preoperative available technique to calculate both breast volume and tumour volume. Volume measurements are promising in outcome prediction of intended breast‐conserving treatment.
The Surgical Strategy in Massive Corrosive Injury in Digestive Tract: Is the Extensive Surgery Appropriate?
Authors: Chang Yung‐Hung , Chien Chih‐Ying , Chen Chih‐Chi , Fu Chih‐Yuan , Hsieh Chi‐Hsun , Liao Chien‐Hung
Published: January 2018

Background

Corrosive ingestion results in necrosis of the digestive tract, spillage of intraluminal fluid, and spread of bacteria that threatens the lives of patients. Some authors advise extensive surgery, although others recommend conservative operation. This study presents the outcomes of the patients of corrosive injury who undergo emergent surgery.

Methods

We conducted a retrospective review including patients with corrosive injury from Jan 2007 to Dec 2013. We retrieved and analyzed the demographic characteristics, injury location and extent, endoscopic grade, presence of surgery, surgical timing and procedure, and mortality.

Results

The cohort consisted of 112 patients; 23 of the patients underwent an emergent operation. Patients who needed emergent surgery had the worse endoscopic severity and a higher mortality rate of 47.8% (12/23). Perforation of the digestive tract [odds ratio (OR) 13.5, p = 0.011] and unscheduled reoperation (OR 13.2, p = 0.033) were factors that predict mortality.

Conclusion

Corrosive injury resulted in a dismal prognosis, especially when patients required an operation. The mortality is related to digestive tract perforation and unscheduled reoperation. Inadequate resection might lead to unscheduled reoperations, which lead to a dismal prognosis.
Surgical Management of Intrahepatic Cholangiocarcinoma in Patients with Cirrhosis: Impact of Lymphadenectomy on Peri‐Operative Outcomes
Authors: Bagante Fabio , Spolverato Gaya , Weiss Matthew , Alexandrescu Sorin , Marques Hugo P. , Aldrighetti Luca , Maithel Shishir K. , Pulitano Carlo , Bauer Todd W. , Shen Feng , Poultsides George A. , Soubrane Olivier , Martel Guillaume , Groot Koerkamp B. , Guglielmi Alfredo , Itaru Endo , Ruzzenente Andrea , Pawlik Timothy M.
Published: January 2018

Background

The consequences of lymphadenectomy (LND) on cirrhotic patients undergoing hepatectomy for intrahepatic cholangiocarcinoma (ICC) have not been investigated. We sought to analyze the impact of LND on morbidity among patients undergoing resection for ICC.

Methods

A total of 1005 patients who underwent hepatectomy for ICC at one of the 14 participating institutions between 1990 and 2015 were identified. A propensity score match analysis was performed to reduce confounding biases between cirrhosis and non‐cirrhosis groups.

Results

Cirrhosis was diagnosed in 118 (11.7%) patients. Among non‐cirrhotic patients, 63% underwent major liver resection versus only 20% among patients with cirrhosis (p < 0.001). LND was also less common among cirrhotic versus non‐cirrhotic patients (19 vs. 50%, p < 0.001). The incidence of complications was 41 and 30% among patients who did not and did have cirrhosis, respectively (p = 0.022). The propensity‐matched cohort included 150 patients. The incidence of complications was 71% among patients who underwent lymphadenectomy versus 23% among patients who did not undergo lymphadenectomy (OR 8.39) (p < 0.001). In the propensity‐matched analysis, the median HLN was comparable among patients independent of cirrhosis status (median HLN: non‐cirrhosis, 2.5 vs. cirrhosis, 2) (p = 0.95). While lymphadenectomy was associated with a higher risk of infections (non‐cirrhosis, 0% vs. cirrhosis, 21%, p < 0.001) among patients with cirrhosis, infections were not associated with lymphadenectomy among non‐cirrhotic patients (p = 0.19).

Conclusion

Lymphadenectomy was associated with an increased risk of complications among patients with cirrhosis undergoing surgery for ICC. The benefit of lymphadenectomy in cirrhotic patients should be considered in light of the higher risk of postoperative complications compared with non‐cirrhotic patients.