bluuebunny/crossref_metadata_2025 huggingface dataset:
CD19‐Targeted chimeric antigen receptor‐modified T‐cell immunotherapy for B‐cell malignancies
Authors: Turtle CJ , Riddell SR , Maloney DG
Published: May 2016

Chimeric antigen receptors (CARs) comprise a tumor‐targeting moiety, often in the form of a single chain variable fragment derived from a monoclonal antibody, fused to one or more intracellular T‐cell signaling sequences. Lymphodepletion chemotherapy followed by infusion of T cells that are genetically modified to express a CD19‐specific CAR is a promising therapy for patients with refractory CD19+ B‐cell malignancies, producing rates of complete remission that are remarkably high in acute lymphoblastic leukemia and encouraging in non‐Hodgkin lymphoma and chronic lymphocytic leukemia. Responses are often durable, although additional studies are needed to define the role of CAR‐T cell immunotherapy in the context of other treatments. CAR‐modified T‐cell immunotherapy can be complicated by cytokine release syndrome and neurologic toxicity, which in most cases are manageable and reversible. Here we review recent clinical trial data and discuss issues for the field.
Experimental evolution of the grain of metabolic specialization in yeast
Authors: Samani Pedram , Bell Graham
Published: May 2016

Adaptation to any given environment may be accompanied by a cost in terms of reduced growth in the ancestral or some alternative environment. Ecologists explain the cost of adaptation through the concept of a trade‐off, by which gaining a new trait involves losing another trait. Two mechanisms have been invoked to explain the evolution of trade‐offs in ecological systems, mutational degradation, and functional interference. Mutational degradation occurs when a gene coding a specific trait is not under selection in the resident environment; therefore, it may be degraded through the accumulation of mutations that are neutral in the resident environment but deleterious in an alternative environment. Functional interference evolves if the gene or a set of genes have antagonistic effects in two or more ecologically different traits. Both mechanisms pertain to a situation where the selection and the alternative environments are ecologically different. To test this hypothesis, we conducted an experiment in which 12 experimental populations of wild yeast were each grown in a minimal medium supplemented with a single substrate. We chose 12 different carbon substrates that were metabolized through similar and different pathways in order to represent a wide range of ecological conditions. We found no evidence for trade‐offs between substrates on the same pathway. The indirect response of substrates on other pathways, however, was consistently negative, with little correlation between the direct and indirect responses. We conclude that the grain of specialization in this case is the metabolic pathway and that specialization appears to evolve through mutational degradation.
A Calibration Method for Blink Type Classification
Authors: SATO HIRONOBU , ABE KIYOHIKO , OHI SHOICHI , OHYAMA MINORU
Published: May 2016

Human–computer interaction systems that use eye blinks have been reported. One purpose of these systems is as a communication aid for persons with severe physical disabilities such as amyotrophic lateral sclerosis (ALS). Some of these systems classify the user's voluntary (conscious) blinks. If the voluntary blinks can be distinguished automatically, the usability of the input interface will be improved. We have proposed an eye blink extraction method that utilizes split interlaced images of the eye. These split images are odd‐ and even‐field images and are generated from interlaced images. The proposed method yields a time resolution that is double that of the 1080i Hi‐Vision format. We refer to this approach as a “frame splitting method”. We realized a method for automatic eye blink extraction using the frame splitting method. Based on this extraction method, we also proposed a blink type classification method in which a threshold is set within the duration of an eye blink. Our classification method requires a calibration process before measurement. In this paper, we clarify the required minimum number of eye blinks for calibration. We also discuss the performance of blink type classification using this calibration.
Electrochemical Assessment of Sequence Selective DNA Damage from Myoglogin and Cytochrome P450 Bioactivated Benzo[a]pyrene at TP53 Oligomers
Authors: Trumbo‐White Caitlin M. , Hvastkovs Eli G.
Published: May 2016

Enzymatic bioactivation of an otherwise non‐reactive species into a reactive one can lead to significant health problems in vivo. Bioactivation of benzo[a]pyrene (BP) produces known cancer causing agents, most notably anti‐benzo[a]pyrene‐r‐7,t‐8‐dihydrodiol‐t‐9,10‐epoxide (anti‐BPDE) that has been shown to attack DNA at specific genomic sites termed hotspots. Bioactivation of BP resulting in DNA damage at a specific hotspot codon was determined electrochemically. Gold electrodes were modified with DNA 21‐mer oligomers spanning codons 270–276 of the TP53 gene as well as myoglobin (Mb) that acted as an in vivo bioactivation enzyme mimic. The electrodes were exposed to BP and low concentrations of hydrogen peroxide to activate the enzymes to produce reactive metabolites that could in turn damage the DNA. DNA damage was assayed electrochemically using square wave voltammetry (SWV) to probe a diviologen compound of the form C12H25V2+C6H12V2+C12H25 (V2+=4,4′‐bipyridyl or viologen, C12‐Viologen) that has previously been employed to study DNA damage. DNA damage was dependent on both BP concentration and on the presence of the hotspot 273‐codon guanine. Additionally, cytochrome P450 1A1 and 1A2 isoforms in bicistronic membrane fractions were utilized, and DNA damage from BP exposure followed predicted patterns based on the isoform employed.
Antibody‐mediated neutralization of autocrine Gas6 inhibits the growth of pancreatic ductal adenocarcinoma tumors in vivo
Authors: Moody Gordon , Belmontes Brian , Masterman Stephanie , Wang Wei , King Chadwick , Murawsky Chris , Tsuruda Trace , Liu Shuying , Radinsky Robert , Beltran Pedro J.
Published: May 2016

Gas6 and its receptors Axl, Mer and Tyro‐3 (TAM) are highly expressed in human malignancy suggesting that signaling through this axis may be tumor‐promoting. In pancreatic ductal adenocarcinoma (PDAC), Gas6 and the TAM receptor Axl are frequently co‐expressed and their co‐expression correlates with poor survival. A strategy was devised to generate fully human neutralizing antibodies against Gas6 using XenoMouse® technology. Hybridoma supernatants were selected based on their ability to inhibit Gas6 binding to the receptor Axl and block Gas6‐induced Axl phosphorylation in human cells. Two purified antibodies isolated from the screened hybridomas, GMAB1 and GMAB2, displayed optimal cellular potency which was comparable to that of the soluble extracellular domain of the receptor Axl (Axl‐Fc). In vivo characterization of GMAB1 was conducted using a pharmacodynamic assay that measured inhibition of Gas6‐induced Akt activation in the mouse spleen. Treatment of mice with a single dose (100–1000 µg) of GMAB1 led to greater than 90% inhibition of Gas6‐induced phosphorylated Akt (pAkt) for up to 72 hr. Based on the target coverage observed in the PD assay, the efficacy of GMAB1 was tested against human pancreatic adenocarcinoma xenografts. At doses of 50 µg and 150 µg, twice weekly, GMAB1 was able to inhibit 55% and 76% of tumor growth, respectively (p < 0.001 for both treatments vs. control Ig). When combined with gemcitabine, GMAB1 significantly inhibited tumor growth compared to either agent alone (p < 0.001). Together, the data suggest that Gas6 neutralization may be important as a potential strategy for the treatment of PDAC.
Physical Activity Benefits the Skeleton of Children Genetically Predisposed to Lower Bone Density in Adulthood
Authors: Mitchell Jonathan A , Chesi Alessandra , Elci Okan , McCormack Shana E , Roy Sani M , Kalkwarf Heidi J , Lappe Joan M , Gilsanz Vicente , Oberfield Sharon E , Shepherd John A , Kelly Andrea , Grant Struan FA , Zemel Babette S
Published: May 2016

Both genetics and physical activity (PA) contribute to bone mineral density (BMD), but it is unknown if the benefits of physical activity on childhood bone accretion depend on genetic risk. We, therefore, aimed to determine if PA influenced the effect of bone fragility genetic variants on BMD in childhood. Our sample comprised US children of European ancestry enrolled in the Bone Mineral Density in Childhood Study (N = 918, aged 5 to 19 years, and 52.4% female). We used a questionnaire to estimate hours per day spent in total, high-, and low-impact PA. We calculated a BMD genetic score (% BMD lowering alleles) using adult genome-wide association study (GWAS)-implicated BMD variants. We used dual-energy X-ray absorptiometry to estimate femoral neck, total hip, and spine areal-BMD and total body less head (TBLH) bone mineral content (BMC) Z-scores. The BMD genetic score was negatively associated with each bone Z-score (eg, TBLH-BMC: estimate = –0.03, p = 1.3 × 10−6). Total PA was positively associated with bone Z-scores; these associations were driven by time spent in high-impact PA (eg, TBLH-BMC: estimate = 0.05, p = 4.0 × 10−10) and were observed even for children with lower than average bone Z-scores. We found no evidence of PA-adult genetic score interactions (p interaction > 0.05) at any skeletal site, and there was no evidence of PA-genetic score–Tanner stage interactions at any skeletal site (p interaction > 0.05). However, exploratory analyses at the individual variant level revealed that PA statistically interacted with rs2887571 (ERC1/WNT5B) to influence TBLH-BMC in males (p interaction = 7.1 × 10−5), where PA was associated with higher TBLH-BMC Z-score among the BMD-lowering allele carriers (rs2887571 AA homozygotes: estimate = 0.08 [95% CI 0.06, 0.11], p = 2.7 × 10−9). In conclusion, the beneficial effect of PA on bone, especially high-impact PA, applies to the average child and those genetically predisposed to lower adult BMD (based on GWAS-implicated BMD variants). Independent replication of our exploratory individual variant findings is warranted. © 2016 American Society for Bone and Mineral Research.
The Roche Immunoturbidimetric Albumin Method on Cobas c 501 Gives Higher Values Than the Abbott and Roche BCP Methods When Analyzing Patient Plasma Samples
Authors: Helmersson‐Karlqvist Johanna , Flodin Mats , Havelka Aleksandra Mandic , Xu Xiao Yan , Larsson Anders
Published: May 2016

Background

Serum/plasma albumin is an important and widely used laboratory marker and it is important that we measure albumin correctly without bias. We had indications that the immunoturbidimetric method on Cobas c 501 and the bromocresol purple (BCP) method on Architect 16000 differed, so we decided to study these methods more closely.

Method

A total of 1,951 patient requests with albumin measured with both the Architect BCP and Cobas immunoturbidimetric methods were extracted from the laboratory system. A comparison with fresh plasma samples was also performed that included immunoturbidimetric and BCP methods on Cobas c 501 and analysis of the international protein calibrator ERM‐DA470k/IFCC.

Results

The median difference between the Abbott BCP and Roche immunoturbidimetric methods was 3.3 g/l and the Roche method overestimated ERM‐DA470k/IFCC by 2.2 g/l. The Roche immunoturbidimetric method gave higher values than the Roche BCP method: y = 1.111x – 0.739, R² = 0.971.

Conclusion

The Roche immunoturbidimetric albumin method gives clearly higher values than the Abbott and Roche BCP methods when analyzing fresh patient samples. The differences between the two methods were similar at normal and low albumin levels.
Flavopiridol: An Old Drug With New Perspectives? Implication for Development of New Drugs
Authors: Cimini Annamaria , d'Angelo Michele , Benedetti Elisabetta , D'Angelo Barbara , Laurenti Giulio , Antonosante Andrea , Cristiano Loredana , Di Mambro Antonella , Barbarino Marcella , Castelli Vanessa , Cinque Benedetta , Cifone Maria Grazia , Ippoliti Rodolfo , Pentimalli Francesca , Giordano Antonio
Published: May 2016

Glioblastoma, the most common brain tumor, is characterized by high proliferation rate, invasion, angiogenesis, and chemo‐ and radio‐resistance. One of most remarkable feature of glioblastoma is the switch toward a glycolytic energetic metabolism that leads to high glucose uptake and consumption and a strong production of lactate. Activation of several oncogene pathways like Akt, c‐myc, and ras induces glycolysis and angiogenesis and acts to assure glycolysis prosecution, tumor proliferation, and resistance to therapy. Therefore, the high glycolytic flux depends on the overexpression of glycolysis‐related genes resulting in an overproduction of pyruvate and lactate. Metabolism of glioblastoma thus represents a key issue for cancer research. Flavopiridol is a synthetic flavonoid that inhibits a wide range of Cyclin‐dependent kinase, that has been demonstrate to inactivate glycogen phosphorylase, decreasing glucose availability for glycolysis. In this work the study of glucose metabolism upon flavopiridol treatment in the two different glioblastoma cell lines. The results obtained point towards an effect of flavopiridol in glycolytic cells, thus suggesting a possible new use of this compound or flavopiridol‐derived formulations in combination with anti‐proliferative agents in glioblastoma patients. J. Cell. Physiol. 232: 312–322, 2017. © 2016 Wiley Periodicals, Inc.
Repression of Primitive Erythroid Program Is Critical for the Initiation of Multi‐Lineage Hematopoiesis in Mouse Development
Authors: Yamane Toshiyuki , Ito Chie , Washino Aya , Isono Kana , Yamazaki Hidetoshi
Published: May 2016

Formation of the hematopoietic cells occurs in multiple steps. The first hematopoietic cells observed during ontogeny are primitive erythrocytes, which are produced in the early yolk sac within a limited temporal window. Multi‐lineage hematopoiesis, which supplies almost the entire repertoire of blood cell lineages, lags behind primitive erythropoiesis in the tissue. However, molecular mechanisms regulating sequential generation of primitive erythrocytes and multipotent hematopoietic progenitors in the yolk sac are largely unknown. In this study, the transcription factors involved in the development of hematopoietic cells were examined in purified progenitor cell populations from pluripotent stem cell cultures and from the yolk sac of developing embryos. We found that the earliest committed hematopoietic progenitors highly expressed Gata1, Scl/tal1, and Klf1 genes. Expression of these transcription factors, which is known to form a core erythroid transcriptional network, explained the prompt generation of primitive erythrocytes from these earliest progenitors. Importantly, the multipotent hematopoietic cells, which lack the differentiation potential into primitive erythroid cells, down‐regulated these genes during a transition from the earliest committed progenitors. In addition, we showed that Pu.1 is involved in the multipotent cell differentiation through the suppression of erythroid transcription program. We propose that these molecular mechanisms governed by transcription factors form sequential waves of primitive erythropoiesis and multi‐lineage hematopoiesis in the early yolk sac of developing embryos. J. Cell. Physiol. 232: 323–330, 2017. © 2016 Wiley Periodicals, Inc.
Sex Differences in Estrogen Receptor α and β Levels and Activation Status in LPS‐Stimulated Human Macrophages
Authors: Campesi Ilaria , Marino Maria , Montella Andrea , Pais Sara , Franconi Flavia
Published: May 2016

Immune function, inflammation, and atherosclerosis display sex differences and are influenced by 17β‐estradiol through estrogen receptors subtypes ERα and ERβ. Male tissues express active ERs, but their possible involvement in inflammation in males has never been assessed. Macrophages express both ERα and ERβ and offer the opportunity to evaluate the role of ER levels and activation in inflammation. We assessed the ability of lipopolysaccharide (LPS) to modulate, in a sex‐specific way, the expression and the activation status of ERα and ERβ in blood monocytes‐derived macrophages (MDMs) from men and women. MDMs were incubated with 100 ng/ml LPS for 24 h and used to evaluate ERα, ERβ, P‐ERα, p38, and P‐p38 expression by Western Blotting. In basal conditions, ERα and ERβ were significantly higher in female MDMs than in male MDMs. LPS up‐regulated ERα and ERα phosphorylation in both sexes, with a significantly higher effect observed in male MDMs, and down‐regulated ERβ level only in female MDMs. p38 and P‐p38 proteins, indicative of ERβ activity, did not show sex differences both in basal conditions and after LPS treatment. Finally, ERα/ERβ and P‐ERα/ERα ratios were significantly higher in male MDMs than in female ones. Our data indicate, for the first time, that LPS affects ERα but not ERβ activation status. We identify a significant role of ERα in LPS‐mediated inflammatory responses in MDMs, which represents an initial step in understanding the influence of sex in the relationship between LPS and ERα. J. Cell. Physiol. 232: 340–345, 2017. © 2016 Wiley Periodicals, Inc.
Temporal Expression of the Clock Genes in the Water Flea Daphnia pulex (Crustacea: Cladocera)
Authors: Bernatowicz Piotr P. , Kotwica‐Rolinska Joanna , Joachimiak Ewa , Sikora Anna , Polanska Marta A. , Pijanowska Joanna , Bębas Piotr
Published: May 2016

The timekeeping mechanisms that operate at the core of circadian clocks (oscillators) are based on interacting molecular feedback loops consisting of clock and clock‐associated genes. However, there is a lack of comprehensive studies on the expression of clock genes (particularly those forming its core) in single crustacean species at the mRNA and protein levels, and these studies could serve as a basis for constructing a model of the crustacean molecular oscillator. Studies on Daphnia pulex are well suited to fill this gap because this species is the only representative crustacean whose genome has been sequenced.

We analyzed the abundance of 20 gene transcripts throughout the day in the whole bodies of D. pulex (single clone); we found that 15 of these genes were transcriptionally active, and most had daily expression level changes. According to the functional classification of their homologues in insects, these genes may represent elements of the Daphnia molecular oscillator core and its input and output pathways. Studies of PERIOD (PER) protein, one of the main clock components, revealed its rhythmic expression pattern in the epidermis, gut, and ovaries. Finally, the cycling levels of many of these clock components observed in animals reared in continuous light led to the conclusion that the Daphnia oscillator, even if it is structurally similar to the oscillators of other arthropods, can be considered a particularly important adaptive mechanism for living in environments with extreme photoperiods.
Relative Growth by the Elongated Jaws of Gars: A Perspective on Polyphasic Loglinear Allometry
Authors: Packard Gary C.
Published: May 2016

Nonlinear regression was used to fit power functions with different forms for random error to data for length of the upper jaw versus length of the rest of body in two species of gars. Growth by the jaws of these species was reported earlier to conform to a pattern of polyphasic loglinear allometry indicative of relatively rapid growth by the jaw in small individuals (allometric exponent greater than 1) and relatively slow growth by the jaw in larger ones (allometric exponent less than 1). The new analyses revealed, however, that the pattern of relative growth by jaws of these fishes does not change with body size: the jaws grow more slowly than the rest of the body throughout life. The flaw in earlier investigations was the unrealistic assumption that data comprising a single sample in log domain form two (or more) statistically distinct distributions when expressed in arithmetic domain. The paradigm used in the current study provides a simple way to fit and compare different power functions, with different forms for random error, directly to raw data and thereby obviates the use of logarithmic transformations in allometric research.
The syntheses of [14C]BMS‐823778 for use in a human ADME clinical study and of [13CD313CD2]BMT‐094817, a stable‐isotope labeled standard of a newly detected human metabolite
Authors: Maxwell Brad D. , Tran Scott B. , Lago Michael , Li Jun , Bonacorsi Samuel J.
Published: May 2016

Type 2 diabetes is a significant worldwide health problem. To support the development of BMS‐823778 as an inhibitor of 11β‐hydroxysteroid dehydrogenase type 1 for type 2 diabetes, the synthesis of carbon‐14‐labeled material was required for use in a human adsorption, distribution, metabolism, and excretion (ADME) study. The HCl salt form of [14C]BMS‐823778 was synthesized in two steps from commercially available [2‐14C]acetone. The radiochemical purity of the synthesized [14C]BMS‐823778 after dilution with unlabeled clinical‐grade BMS‐823778 was 99.5% having a specific activity of 7.379 μCi/mg. One result of the human ADME study was the detection of a new human metabolite, BMT‐094817. To support the quantification of BMT‐094817 in clinical samples, it was necessary to synthesize [13CD3 13CD2]BMT‐094817 for use as a liquid chromatography/mass spectrometry standard. [13CD3 13CD2]BMT‐094817 was prepared in five labeled steps from [13CD3]iodomethane.
Literature review of the distribution of hepatitis C virus genotypes across Europe
Authors: Alberti Alfredo , Lacoin Laure , Morais Edith , Lefevre Cinira , Abogunrin Seye , Iheanacho Ike
Published: May 2016

Recent advances in hepatitis C virus (HCV) therapies have transformed the treatment landscape for this disease. However, efficacy of current treatments depends on HCV genotype and individual patient characteristics. This review aimed to appraise observational studies reporting epidemiological outcomes to characterize HCV genotype distribution in Europe, in the general HCV population and various subpopulations of interest. MEDLINE and EMBASE entries published between November 2008 and November 2013 were systematically searched. Studies were grouped according to the patient populations of interest: general HCV population, HCV–HIV co‐infected patients, patients with advanced fibrosis/cirrhosis, and liver transplant recipients. Thirty publications provided estimates of HCV genotype distribution in four distinct patient groups: general HCV population (n = 21), HCV–HIV co‐infected patients (n = 6), liver transplant patients (n = 3), and patients with HCV‐compensated cirrhosis (n = 1). Nationwide estimates of genotype distribution in the general HCV population were available for 10 countries, with genotypes 1 and 3 the most commonly reported. Romanian studies were found to have reported genotype 1 infections almost exclusively (98.0–99.8%). Considerable regional variation was reported in some countries (e.g., Italy), but not others (e.g., France). National and multi‐national estimates for the HCV–HIV co‐infected population suggested a different genotype distribution to that in the general HCV population. No studies reported nationwide genotype distribution in patients with advanced liver disease. Given the clinical importance of genotype in developing optimal HCV eradication strategies, further nationwide European studies are needed to fully characterize genotype distribution in both the general HCV population and in HCV subpopulations. J. Med. Virol. 88:2157–2169, 2016. © 2016 Wiley Periodicals, Inc.
Promising Materials for High Power Laser Isolators
Authors: Stevens Kevin T. , Schlichting Wolfgang , Foundos Gregory , Payne Alexis , Rogers Evan
Published: May 2016

Northrop Grumman Synoptics is developing the growth of large singlecrystal fluoride materials for Faraday rotator / isolator applications. These materials exhibit smaller nonlinear refractive index and thermo‐optic coefficients, while maintaining Verdet constants near those of the commonly used terbium gallium garnet (TGG) crystals. In particular, the cubic potassium terbium fluoride, KTF (KTb3F10) crystal has low absorption and thermo‐optic coefficients. The crystal growth and performance of these single‐crystal fluoride materials will be discussed as well as recent improvements to the performance of TGG crystals.
Dynamics of extracellular superoxide production by Trichodesmium colonies from the Sargasso Sea
Authors: Hansel C. M. , Buchwald C. , Diaz J. M. , Ossolinski J. E. , Dyhrman S. T. , Van Mooy B. A. S. , Polyviou Despo
Published: May 2016

Reactive oxygen species (ROS) are key players in the health and biogeochemistry of the ocean and its inhabitants. The vital contribution of microorganisms to marine ROS levels, particularly superoxide, has only recently come to light, and thus the specific biological sources and pathways involved in ROS production are largely unknown. To better understand the biogenic controls on ROS levels in tropical oligotrophic systems, we determined rates of superoxide production under various conditions by natural populations of the nitrogen‐fixing diazotroph Trichodesmium obtained from various surface waters in the Sargasso Sea. Trichodesmium colonies collected from eight different stations all produced extracellular superoxide at high rates in both the dark and light. Colony density and light had a variable impact on extracellular superoxide production depending on the morphology of the Trichodesmium colonies. Raft morphotypes showed a rapid increase in superoxide production in response to even low levels of light, which was not observed for puff colonies. In contrast, superoxide production rates per colony decreased with increasing colony density for puff morphotypes but not for rafts. These findings point to Trichodesmium as a likely key source of ROS to the surface oligotrophic ocean. The physiological and/or ecological factors underpinning morphology‐dependent controls on superoxide production need to be unveiled to better understand and predict superoxide production by Trichodesmium and ROS dynamics within marine systems.
Consumption and diffusion of oxygen during the thermoxidative ageing process of elastomers
Authors: Herzig A. , Johlitz M. , Lion A.
Published: May 2016

Thermoxidative ageing of elastomers is investigated by having a closer look on the consumption and diffusion of oxygen during the exposure to elevated temperatures. After the introduction of some basic theory an experimental set‐up is described, which enables the measurement of the oxygen amount being absorbed during weathering. Hence the oxygen consumption of natural rubber was detected at elevated temperatures and for varying exposure times. The correlation of changes in the mechanical properties and the oxygen consumption is analysed in order to get new awareness of oxidation affecting the mechanical behaviour. Influences of diffusion effects on the degradation are investigated by the use of micro X‐ray tomography, which detects minor changes in density generated by oxidation. Density profiles over the cross‐section of the samples are created, which illustrate the appearance of diffusion‐limiting oxidation. The results offer a closer look at the thermoxidative ageing of natural rubber and should help to get a better understanding of the degradation during ageing. Finally the findings may improve the life‐time prediction of elastomeric components by providing the basis for the development of advanced material models.
Insight into the quantitative metrics of chemical exchange saturation transfer (CEST) imaging
Authors: Heo Hye‐Young , Lee Dong‐Hoon , Zhang Yi , Zhao Xuna , Jiang Shanshan , Chen Min , Zhou Jinyuan
Published: May 2016

Purpose

To evaluate the reliability of four CEST imaging metrics for brain tumors, at varied saturation power levels and magnetic field strengths (3−9.4 Tesla (T)).

Methods

A five‐pool proton exchange model (free water, semisolid, amide, amine, and NOE‐related protons) was used for the simulations. For the in vivo study, eight glioma‐bearing rats were scanned at 4.7 T. The CEST ratio (CESTR), CESTR normalized with the reference value (CESTRnr), inverse Z‐spectrum‐based (MTRRex), and apparent exchange‐related relaxation (AREX) were compared.

Results

The simulated CEST signal intensities using MTRRex and AREX were substantially increased at relatively high radiofrequency (RF) saturation powers at 3 T and 4.7 T, whereas CESTR and CESTRnr metrics remained relatively stable. There were tremendously high MTRRex and AREX signals around the water frequency at all field strengths because of the small denominators. In the rat tumor study at 4.7 T, both CESTR and CESTRnr showed clear contrasts in the tumor with respect to the normal tissue across all saturation power levels (0.5−3 μT), whereas the AREX showed negligible to negative insignificant contrasts.

Conclusions

CEST metrics must be carefully selected based on the different experimental settings. CESTR and CESTRnr are more reliable at 3 T (a clinical field strength) and 4.7 T. Magn Reson Med 77:1853–1865, 2017. © 2016 International Society for Magnetic Resonance in Medicine
Identification and application of dynamic uncoupling between modifications to vibrating systems
Authors: Wixom Andrew S. , McDaniel J. Gregory
Published: May 2016

This paper develops and demonstrates a strategy for identifying the lack of dynamic interaction, or coupling, between potential design modifications to a vibrating base structure. Such decoupling may be exploited to efficiently compare the performance of competing engineering designs. In particular, it is shown how different design modifications may be represented as the addition or removal of substructures. When these substructures are uncoupled according to the metric developed here, the computational cost of determining the optimal system design can be greatly reduced. For example, if a designer considers seven possible modifications and wishes to examine all possible combinations of the modifications, 128 possible structures must be analyzed. However, if all modifications are dynamically uncoupled, significant computational effort need only be spent on eight of the possible structures in order to generate the responses for all remaining designs. Example problems demonstrate this cost reduction and illustrate cases where dynamic uncoupling occurs. Copyright © 2016 John Wiley & Sons, Ltd.
Increase retention, graduation rates with an academy model
Authors: Hope Joan
Published: May 2016

CHICAGO — Knowing what supports help students persist and graduate is the first step to boosting their success rates. Implementing successful strategies on a large scale is the next challenge.
Controlled synthesis of poly(vinyl acetate) by traditional radical emulsion polymerization
Authors: Guan Yu , Li Jingjing , Shao Leishan , Wang Fei , Dong Dongyu , Wang Yinghan
Published: May 2016

A new redox initiation system, potassium persulfate/N,N‐dimethylethanolamine, was used to initiate traditional radical emulsion polymerization of vinyl acetate at low temperature. Polymers were characterized using gel permeation chromatography, scanning electron microscopy and dynamic light scattering. The results showed that poly(vinyl acetate) with high molar mass and small dispersity (Đ) was successfully synthesized. © 2016 Society of Chemical Industry
Structure of the Escherichia coli ArnA N‐formyltransferase domain in complex with N5‐formyltetrahydrofolate and UDP‐Ara4N
Authors: Genthe Nicholas A. , Thoden James B. , Holden Hazel M.
Published: May 2016

ArnA from Escherichia coli is a key enzyme involved in the formation of 4‐amino‐4‐deoxy‐l‐arabinose. The addition of this sugar to the lipid A moiety of the lipopolysaccharide of pathogenic Gram‐negative bacteria allows these organisms to evade the cationic antimicrobial peptides of the host immune system. Indeed, it is thought that such modifications may be responsible for the repeated infections of cystic fibrosis patients with Pseudomonas aeruginosa. ArnA is a bifunctional enzyme with the N‐ and C‐terminal domains catalyzing formylation and oxidative decarboxylation reactions, respectively. The catalytically competent cofactor for the formylation reaction is N10‐formyltetrahydrofolate. Here we describe the structure of the isolated N‐terminal domain of ArnA in complex with its UDP‐sugar substrate and N5‐formyltetrahydrofolate. The model presented herein may prove valuable in the development of new antimicrobial therapeutics.
Critical assessment of methods of protein structure prediction: Progress and new directions in round XI
Authors: Moult John , Fidelis Krzysztof , Kryshtafovych Andriy , Schwede Torsten , Tramontano Anna
Published: May 2016

Modeling of protein structure from amino acid sequence now plays a major role in structural biology. Here we report new developments and progress from the CASP11 community experiment, assessing the state of the art in structure modeling. Notable points include the following: (1) New methods for predicting three dimensional contacts resulted in a few spectacular template free models in this CASP, whereas models based on sequence homology to proteins with experimental structure continue to be the most accurate. (2) Refinement of initial protein models, primarily using molecular dynamics related approaches, has now advanced to the point where the best methods can consistently (though slightly) improve nearly all models. (3) The use of relatively sparse NMR constraints dramatically improves the accuracy of models, and another type of sparse data, chemical crosslinking, introduced in this CASP, also shows promise for producing better models. (4) A new emphasis on modeling protein complexes, in collaboration with CAPRI, has produced interesting results, but also shows the need for more focus on this area. (5) Methods for estimating the accuracy of models have advanced to the point where they are of considerable practical use. (6) A first assessment demonstrates that models can sometimes successfully address biological questions that motivate experimental structure determination. (7) There is continuing progress in accuracy of modeling regions of structure not directly available by comparative modeling, while there is marginal or no progress in some other areas. Proteins 2016; 84(Suppl 1):4–14. © 2016 Wiley Periodicals, Inc.
Large‐scale extrusion of auxetic polypropylene fibre
Authors: Alderson Kim , Nazaré Shonali , Alderson Andrew
Published: May 2016

Auxetic polyproplyene fibres have been produced on a large‐scale industrial extruder for the first time. A first batch of tests identified a coarse processing window which was then more closely defined by subsequent tests. The effects of barrel temperature, screw speed, take‐up speed and quenching (through the parameters of air gap and bath temperature) on the Poisson's ratio and Young's modulus of the fibres were examined. It was found that a temperature of 200 °C, screw speed of 12.5 rpm and take‐up speed of either 1.5 or 3.5 rpm produced fibres with a high degree of auxeticity up to 5% strain – significantly increasing the auxetic strain range previously reported for lab‐scale extrusions at lower extruder temperatures. Quenching with a water bath reduced the auxeticity, so was not employed as a processing parameter.
Embracing the foreign: Cultural attractiveness and international strategy
Authors: Li Chengguang , Brodbeck Felix C. , Shenkar Oded , Ponzi Leonard J. , Fisch Jan Hendrik
Published: May 2016

Research summary: Prior research focused on cultural differences and their impact on foreign direct investment (FDI), neglecting other potentially relevant variables attesting to the cultural interaction between a multinational enterprise and its host environment. In this article, we draw on interpersonal attraction research to develop a positive approach to cross‐cultural interaction with the cultural attractiveness (CA) construct, whereby members of a focal culture view another culture as desirable. We create a CA measure and establish its predictive validity with country reputation data. Using FDI data for 41 nations from 1985 to 2012 and performance data for 8,519 cross‐border acquisitions (CBA) for 40 nations from 1990 to 2009, we find that CA is a predictor of FDI inflows and CBA outcomes, whose explanatory power is superior to cultural difference measures.

Managerial summary: Practitioners have traditionally emphasized potential difficulties of cross‐cultural interaction when dealing with culturally distant countries. In contrast, our study addresses the positive aspects of cultural differences and suggests that a lot can be gained from dealing with attractive cultures, even when they are different. This insight can be helpful, for example, in contemplating/managing international M&As. Managers of acquiring/merging firms can use our approach to identify whether their employees find the partner's culture desirable, and if they do, proceed with the takeover and then adopt the partner's organizational routines during post‐merger integration. This approach can help avoid conflicts, improve performance of home country expatriates, and ultimately, create value for acquiring firms. Copyright © 2016 John Wiley & Sons, Ltd.
Primary subacute hematogenous osteomyelitis in children: A clearer bacteriological etiology
Authors: Spyropoulou Vasiliki , Dhouib Chargui Amira , Merlini Laura , Samara Eleftheria , Valaikaite Raimonda , Kampouroglou Georgios , Ceroni Dimitri
Published: May 2016

Background

This study aimed to describe the spectrum of pediatric primary subacute hematogenous osteomyelitis (PSAHO) and to investigate its bacterial etiology.

Methods

Sixty-five consecutive cases of PSAHO admitted to our institution over a 16-year period (2000–2015) were retrospectively reviewed to assess their laboratory and radiographic imaging features, as well as their bacteriological etiology.

Results

On evaluation, white blood cell count and C-reactive protein were normal in 53 (81.5 %) and 34 cases (52.3 %), respectively, whereas the erythrocyte sedimentation rate was superior to 20 mm/h in 44 cases (72.1 %). Blood cultures failed to identify the pathogen in all but one patient, and classic bone sample cultures only managed to isolate the pathogen in five cases (11.6 %). Use of polymerase chain reaction (PCR) assays on bone aspirates or blood allowed the causative microorganism to be isolated in a further 22 cases. Using classic cultures and PCR assays together resulted in pathogen detection in 27 cases (62.8 % of the children bacteriologically investigated), with Kingella kingae being the most frequently reported microorganism.

Conclusions

Two distinct forms of PSAHO should be distinguished on the basis of age of patients and bacteriological etiology. The infantile form affects children aged between 6 months and 4 years and is predominantly due to K. kingae. The juvenile form involves children aged >4 years and Staphylococcus aureus appears to be the main bacteriological etiology. Appropriate nucleic amplification assays drastically improve the detection rate of the microorganisms responsible for PSAHO. Level of evidence: Case series, level IV.
Trends of hospitalization for major bipolar II in USA: A Nationwide analysis
Authors: Rathod M. , Mansuri Z. , Shambhu S. , Sutaria A. , Karnik K.
Published: May 2016

Objectives

Bipolar II (B-II) is an important cause of morbidity and mortality in hospitalized patients. While B-II has been extensively studied in the past, the contemporary data for impact of B-II on cost of hospitalization are largely lacking.

Methods

We queried the Healthcare Cost and Utilization Project's Nationwide Inpatient Sample (HCUP-NIS) dataset between 1998–2011 using the ICD-9 codes. Severity of comorbid conditions was defined by Deyo modification of Charlson comorbidity index. Primary outcome was in-hospital mortality and secondary outcome was total charges for hospitalization. Using SAS 9.2, Chi2 test, t-test and Cochran-Armitage test were used to test significance.

Results

A total of 107,152 patients were analyzed; 62.61% were female and 31.39% were male (P < 0.0001); 78.19% were white, 11.44% black and 10.37% of other race (P < 0.0001). Rate of hospitalization increased from 866.87/million to 8156.03/million from 1998–2011. Overall mortality was 0.32% and mean cost of hospitalization was 19,447.89$. The in-hospital mortality increased from 0.00% to 0.07% (P < 0.0001) and mean cost of hospitalization increased from 7565.20$ to 26,511.95$. Total yearly spending on B-II related admissions have increased from $52.24 million/year to $1.6 billion/year.

Conclusions

While mortality has slightly increased from 1998 to 2011, the cost has significantly increased from $52.24 million/year to $1.6 billion/year, which leads to an estimated $1.55 billion/year additional burden to US health care system. In the era of cost conscious care, preventing B-II related hospitalization could save billions of dollars every year. Focused efforts are needed to establish preventive measures for B-II related hospitalization.

Disclosure of interest

The authors have not supplied their declaration of competing interest.
Depression as an interdisciplinary problem
Authors: Vasileva A. , Neznanov N.
Published: May 2016

Traditionally depression was defined as a mental illness. Acknowledgment of biopsychosocial model in modern medicine brought about a number of interdisciplinary studies. In the meantime, a number of correlations in the onset, cause and prognosis between depression and other somatic as well as mental illnesses were discovered. The research results showed that from one hand, depression could be an independent factor of the possible development of heart infarct, on the other hand it can influence the recovery process in cardiological patients. The conducted studies established some common pathways in depression and vascular diseases development. Psychoneuroimmunological research gives the data about the influence of anxiety and depression on the interleukine profile that could be a matter of further investigation of the possible links between depression and cancer diseases. The other dimension is the addiction impact on depression onset. The interrelationship between epilepsy as organic brain disease and depression is also worth of attentional. Hypercortisolemia and low-grade inflammation plays an important role both in depression and dementia. There is also a strong correlation between personality traits and depression itself and as response to unfavorable circumstances and somatic illness as well. We propose to apply to depression the principles of pathological stable circuits with the self-sustained reverbation engram chains mechanisms. All these data calls for consideration of depression as an interdisciplinary phenomena.

Disclosure of interest

The authors have not supplied their declaration of competing interest.
A meta-analysis of gene (5-HTT) × environment interactions in eating pathology using secondary data analyses
Authors: Rozenblat V. , Ng D. , Fuller-Tyszkiewicz M. , Akkermann K. , Collier D. , Engels R. , Fernandez-Aranda F. , Harro J. , Karwautz A. , Homberg J. , Klump K. , Racine S. , Larson C. , Steiger H. , Richardson J. , Stoltenberg S. , van Strien T. , Wagner G. , Treasure J. , Krug I.
Published: May 2016

Background

Gene × environment (G × E) interactions in eating pathology have been increasingly investigated, however studies have been limited by sample size due to the difficulty of obtaining genetic data.

Objective

To synthesize existing G × E research in the eating disorders (ED) field and provide a clear picture of the current state of knowledge with analyses of larger samples.

Method

Complete data from seven studies investigating community (n = 1750, 64.5% female) and clinical (n = 426, 100% female) populations, identified via systematic review, were included. Data were combined to perform five analyses: 5-HTTLPR × Traumatic Life Events (0–17 events) to predict ED status (n = 909), 5-HTTLPR × Sexual and Physical Abuse (n = 1097) to predict bulimic symptoms, 5-HTLPR × Depression to predict bulimic symptoms (n = 1256), and 5-HTTLPR × Impulsivity to predict disordered eating (n = 1149).

Results

The low function (s) allele of 5-HTTLPR interacted with number of traumatic life events (P < .01) and sexual and physical abuse (P < .05) to predict increased likelihood of an ED in females but not males (Fig. 1). No other G × E interactions were significant, possibly due to the medium to low compatibility between datasets (Fig. 1).

Conclusion

Early promising results suggest that increased knowledge of G × E interactions could be achieved if studies increased uniformity of measuring ED and environmental variables, allowing for continued collaboration to overcome the restrictions of obtaining genetic samples.

Disclosure of interest

The authors have not supplied their declaration of competing interest.
Traumatic stress and risk of severe mental illness: A nationwide cohort study
Authors: Okkels N. , Trabjerg B. , Arendt M. , Bøcker Pedersen C.
Published: May 2016

Introduction

A history of traumatic events is prevalent in people with schizophrenia spectrum disorders and mood disorders. However, little is known about their etiological relationship.

Objectives

To explore whether patients with acute or posttraumatic stress disorder are at higher risk of developing a schizophrenia spectrum disorder or mood disorder.

Methods

In this prospective cohort study using registers covering the entire Danish population, we used the Danish Psychiatric Central Research Register to identify patients with ICD-10 diagnoses of acute traumatic stress disorder and/or posttraumatic stress disorder. From inpatient and outpatient mental hospitals, we identified 4371 diagnoses with more than 18 million years of follow-up. Main outcomes and measures were relative risks (RR) with 95% confidence intervals (95% CI) of schizophrenia, schizophrenia spectrum disorder, bipolar disorder and mood disorder.

Results

The incidence of traumatic stress disorder (TSD) has increased steadily from 0.6% in 1996 to 6% in 2012, showed a higher incidence in women and an age distribution with a peak-incidence in early adulthood. We found that diagnoses of TSD increase the risk of schizophrenia (RR 5.85, 95% CI 3.59–8.91), schizophrenia spectrum disorder (RR 3.82, 95% CI 2.38–5.75), bipolar disorder (RR 5.83, 95% CI 3.11–9.83) and mood disorder (RR 4.10, 95% CI 3.15–5.22). Risks were high in the first year after diagnosis of TSD and declined going forward in time.

Conclusions

Our findings indicate that acute and posttraumatic stress disorder are etiological risk factors for schizophrenia spectrum disorders and mood disorders. If replicated, this may underline treatment of traumatized patients in prevention of severe mental disorder.

Disclosure of interest

The authors have not supplied their declaration of competing interest.