bluuebunny/crossref_metadata_2025 huggingface dataset:
A generalized method for controlling end-tidal respiratory gases during nonsteady physiological conditions
Authors: O'Connor Shawn M. , Wong Jeremy D. , Donelan J. Maxwell
Published: September 2016

While forcing of end-tidal gases by regulating inspired gas concentrations is a common technique for studying cardiorespiratory physiology, independently controlling end-tidal gases is technically challenging. Feedforward control methods are challenging because end-tidal values vary as a dynamic function of both inspired gases and other nonregulated physiological parameters. Conventional feedback control is limited by delays within the lungs and body tissues and within the end-tidal forcing system itself. Consequently, modern end-tidal forcing studies have generally restricted their analysis to simple time courses of end-tidal gases and to resting steady-state conditions. To overcome these limitations, we have designed and validated a more generalized end-tidal forcing system that removes the need for manual tuning and rule-of-thumb based control heuristics, while allowing for accurate control of gases along spontaneous and complicated time courses and under nonsteady physiological conditions. On average during resting, steady walking, and walking with time varying speed, our system achieved step changes in PetCO2 within 3.0 ± 0.9 (mean ± SD) breaths and PetO2 within 4.4 ± 0.9 breaths, while also maintaining small steady-state errors of 0.1 ± 0.2 mmHg for PetCO2 and 0.3 ± 0.8 mmHg for PetO2. The system also accurately tracked more complicated changes in end-tidal values through a bandwidth of 1/10 the respiratory (sampling) frequency, a practical limit of feedback control systems. The primary mechanism enabling this controller performance is a generic mathematical model of the cardiopulmonary system that captures the breath-by-breath relationship between inspired and end-tidal gas concentrations, with secondary contributions from reduced delays in controlled air delivery.
Endoscopic Closure for EUS and ERCP Related Duodenal Perforation by Endoclips
Authors: Liu Yaping , Wang Dong , Li Zhaoshen
Published: September 2016

Objective. To investigate the therapeutic safety, feasibility, and efficacy of endoclips for closing the endoscopic ultrasound (EUS) and endoscopic retrograde cholangiopancreatography (ERCP) related duodenal perforation in a retrospective study from a single center.Methods. Patients who developed EUS and ERCP related duodenal perforation between January 2012 and January 2015 were included in the study. All the cases underwent endoscopic closure by endoclips, and the efficacy, feasibility, and safety of this technique were evaluated.Results. During the study period, a total of 17,406 patients were treated by EUS and/or ERCP. EUS and ERCP related duodenal perforation occurred in 9 cases (0.05%): 2 males and 7 females. The mean age was 69 years (range: 59–79 years). The success rate of endoscopic closure by endoclips was 100%. The mean procedure time was45±12.5 min. The mean number of endoclips placed for the closure of the duodenal perforation was7±3.2. All the patients recovered completely without any severe complications.Conclusion. The endoscopic closure by using endoclips is recommended as the first-line treatment for duodenal perforation associated with EUS and ERCP.
Development and Application of the Downhole Drilling String Shock-Absorption and Hydraulic Supercharging Device
Authors: Liu Yongwang , Guan Zhichuan , Zhang Hongning , Zhang Bo
Published: September 2016

It is a hot topic for deep/ultradeep wells to improve rock-breaking efficiency and drilling speed by available downhole energy. Based on different downhole energies and working conditions, specialized plunger pump is proposed to convert longitudinal vibration of drilling string into rock-breaking energy. Technical design is developed to generate high-pressure water jet. And then a simulation model is built to verify feasibility of the technical design. Through simulation, the influence law of key factors is obtained. On this basis, this device is tested in several wells. The result indicates this device can increase drilling speed as much as 136%. Meanwhile the harmful vibration can be absorbed. The energy from drilling string vibration is of high frequency and increases as well depth and formation anisotropy increase. By reducing adverse vibration, this device is able to increase the drilling speed and the service life also meets the demand of field application. The longest working time lasts for more than 130 hours. The performance of this device demonstrates great application prospect in deep/ultradeep resources exploration. To provide more equipment support for deep/ultradeep wells, more effort should be put into fundamental study on downhole drill string vibration and related equipment.
SOCS1 Mimetic Peptide Suppresses Chronic Intraocular Inflammatory Disease (Uveitis)
Authors: He Chang , Yu Cheng-Rong , Mattapallil Mary J. , Sun Lin , Larkin III Joseph , Egwuagu Charles E.
Published: September 2016

Uveitis is a potentially sight-threatening disease characterized by repeated cycles of remission and recurrent inflammation. The JAK/STAT pathway regulates the differentiation of pathogenic Th1 and Th17 cells that mediate uveitis. A SOCS1 mimetic peptide (SOCS1-KIR) that inhibits JAK2/STAT1 pathways has recently been shown to suppress experimental autoimmune uveitis (EAU). However, it is not clear whether SOCS1-KIR ameliorated uveitis by targeting JAK/STAT pathways of pathogenic lymphocytes or via inhibition of macrophages and antigen-presenting cells that also enter the retina during EAU. To further investigate mechanisms that mediate SOCS1-KIR effects and evaluate the efficacy of SOCS1-KIR as an investigational drug for chronic uveitis, we induced EAU in rats by adoptive transfer of uveitogenic T-cells and monitored disease progression and severity by slit-lamp microscopy, histology, and optical coherence tomography. Topical administration of SOCS1-KIR ameliorated acute and chronic posterior uveitis by inhibiting Th17 cells and the recruitment of inflammatory cells into retina while promoting expansion of IL-10-producing Tregs. We further show that SOCS1-KIR conferred protection of resident retinal cells that play critical role in vision from cytotoxic effects of inflammatory cytokines by downregulating proapoptotic genes. Thus, SOCS1-KIR suppresses uveitis and confers neuroprotective effects and might be exploited as a noninvasive treatment for chronic uveitis.
A Fetal Electrocardiogram Signal Extraction Algorithm Based on Fast One-Unit Independent Component Analysis with Reference
Authors: Jia Yanfei , Yang Xiaodong
Published: September 2016

Fetal electrocardiogram (FECG) extraction is very important procedure for fetal health assessment. In this article, we propose a fast one-unit independent component analysis with reference (ICA-R) that is suitable to extract the FECG. Most previous ICA-R algorithms only focused on how to optimize the cost function of the ICA-R and payed little attention to the improvement of cost function. They did not fully take advantage of the prior information about the desired signal to improve the ICA-R. In this paper, we first use the kurtosis information of the desired FECG signal to simplify the non-Gaussian measurement function and then construct a new cost function by directly using a nonquadratic function of the extracted signal to measure its non-Gaussianity. The new cost function does not involve the computation of the difference between the function of the Gaussian random vector and that of the extracted signal, which is time consuming. Centering and whitening are also used to preprocess the observed signal to further reduce the computation complexity. While the proposed method has the same error performance as other improved one-unit ICA-R methods, it actually has lower computation complexity than those other methods. Simulations are performed separately on artificial and real-world electrocardiogram signals.
Use of NeuroEyeCoach™ to Improve Eye Movement Efficacy in Patients with Homonymous Visual Field Loss
Authors: Sahraie Arash , Smania Nicola , Zihl Josef
Published: September 2016

Visual field deficits are common in patients with damaged retinogeniculostriate pathways. The patient’s eye movements are often affected leading to inefficient visual search. Systematic eye movement training also called compensatory therapy is needed to allow patients to develop effective coping strategies. There is a lack of evidence-based, clinical gold-standard registered medical device accessible to patients at home or in clinical settings and NeuroEyeCoach (NEC) is developed to address this need. In three experiments, we report on performance of patients on NEC compared to the data obtained previously on the earlier versions of the search task (n=32); we assessed whether the self-administered computerised tasks can be used to monitor the progress (n=24) and compared the findings in a subgroup of patients to a healthy control group. Performance on cancellation tasks, simple visual search, and self-reported responses on activities of daily living was compared, before and after training. Patients performed similarly well on NEC as on previous versions of the therapy; the inbuilt functionality for pre- and postevaluation functions was sensitive to allowing assessment of improvements; and improvements in patients were significantly greater than those in a group of healthy adults. In conclusion, NeuroEyeCoach can be used as an effective rehabilitation tool to develop compensatory strategies in patients with visual field deficits after brain injury.
Anti‐Inflammatory Effects of Traditional Chinese Medicines against Ischemic Injury in In Vivo Models of Cerebral Ischemia
Authors: Cheng Chin-Yi , Lee Yu-Chen
Published: September 2016

Inflammation plays a crucial role in the pathophysiology of acute ischemic stroke. In the ischemic cascade, resident microglia are rapidly activated in the brain parenchyma and subsequently trigger inflammatory mediator release, which facilitates leukocyte‐endothelial cell interactions in inflammation. Activated leukocytes invade the endothelial cell junctions and destroy the blood‐brain barrier integrity, leading to brain edema. Toll‐like receptors (TLRs) stimulation in microglia/macrophages through the activation of intercellular signaling pathways secretes various proinflammatory cytokines and enzymes and then aggravates cerebral ischemic injury. The secreted cytokines activate the proinflammatory transcription factors, which subsequently regulate cytokine expression, leading to the amplification of the inflammatory response and exacerbation of the secondary brain injury. Traditional Chinese medicines (TCMs), including TCM‐derived active compounds, Chinese herbs, and TCM formulations, exert neuroprotective effects against inflammatory responses by downregulating the following: ischemia‐induced microglial activation, microglia/macrophage‐mediated cytokine production, proinflammatory enzyme production, intercellular adhesion molecule‐1, matrix metalloproteinases, TLR expression, and deleterious transcription factor activation. TCMs also aid in upregulating anti‐inflammatory cytokine expression and neuroprotective transcription factor activation in the ischemic lesion in the inflammatory cascade during the acute phase of cerebral ischemia. Thus, TCMs exert potent anti‐inflammatory properties in ischemic stroke and warrant further investigation.
Molecular Cloning and Characterization of Full-Length cDNA of Calmodulin Gene from Pacific OysterCrassostrea gigas
Authors: Li Xing-Xia , Yu Wen-Chao , Cai Zhong-Qiang , He Cheng , Wei Na , Wang Xiao-Tong , Yue Xi-Qing
Published: September 2016

The shell of the pearl oyster (Pinctada fucata) mainly comprises aragonite whereas that of the Pacific oyster (Crassostrea gigas) is mainly calcite, thereby suggesting the different mechanisms of shell formation between above two mollusks. Calmodulin (CaM) is an important gene for regulating the uptake, transport, and secretion of calcium during the process of shell formation in pearl oyster. It is interesting to characterize the CaM in oysters, which could facilitate the understanding of the different shell formation mechanisms among mollusks. We cloned the full-length cDNA of Pacific oyster CaM (cgCaM) and found that the cgCaM ORF encoded a peptide of 113 amino acids containing three EF-hand calcium-binding domains, its expression level was highest in the mantle, hinting that the cgCaM gene is probably involved in shell formation of Pacific oyster, and the common ancestor of Gastropoda and Bivalvia may possess at least three CaM genes. We also found that the numbers of some EF hand family members in highly calcified species were higher than those in lowly calcified species and the numbers of these motifs in oyster genome were the highest among the mollusk species with whole genome sequence, further hinting the correlation between CaM and biomineralization.
Positioning Error Analysis of Ranging-Mode Using AIS Signals in China
Authors: Zheng Kai , Hu Qing , Zhang Jingbo
Published: September 2016

In order to provide resilient position, navigation, and time (PNT) information forE-Navigation, the ranging-mode (R-Mode) positioning using automatic identification system (AIS) signals is encouraged. As the accuracy is the key for the positioning system, this paper investigates the position error of the R-Mode positioning based on AIS shore-based station in China. The measurement errors of Gaussian filtered minimum shift keying (GMSK) demodulation based on carrier phase locking loop are investigated in theory. The dilution of precision (DOP) for time of arrival (TOA) and time difference of arrival (TDOA) used in R-Mode positioning of AIS is discussed in two measurement mechanisms. The positioning error distributions in the North, East, and South Sea regions of China based on the existing AIS shore-based stations are evaluated. The positioning accuracy is at the meter level in the most traffic dense areas to meet the requirements for vessel navigation.
A Meta-Path-Based Prediction Method for Human miRNA-Target Association
Authors: Luo Jiawei , Huang Cong , Ding Pingjian
Published: September 2016

MicroRNAs (miRNAs) are short noncoding RNAs that play important roles in regulating gene expressing, and the perturbed miRNAs are often associated with development and tumorigenesis as they have effects on their target mRNA. Predicting potential miRNA-target associations from multiple types of genomic data is a considerable problem in the bioinformatics research. However, most of the existing methods did not fully use the experimentally validated miRNA-mRNA interactions. Here, we developed RMLM and RMLMSe to predict the relationship between miRNAs and their targets. RMLM and RMLMSe are global approaches as they can reconstruct the missing associations for all the miRNA-target simultaneously and RMLMSe demonstrates that the integration of sequence information can improve the performance of RMLM. In RMLM, we use RM measure to evaluate different relatedness between miRNA and its target based on different meta-paths; logistic regression and MLE method are employed to estimate the weight of different meta-paths. In RMLMSe, sequence information is utilized to improve the performance of RMLM. Here, we carry on fivefold cross validation and pathway enrichment analysis to prove the performance of our methods. The fivefold experiments show that our methods have higher AUC scores compared with other methods and the integration of sequence information can improve the performance of miRNA-target association prediction.
A Prospective Observational Cohort Study on Orthopaedic and Anaesthetic Registrars Performing Femoral Nerve Block on Patients with an Acute Hip Fracture
Authors: Thelaus Åsa , Pettersson Tobias , Gordon Max , Krupic Ferid , Sköldenberg Olof
Published: September 2016

We investigated if a femoral nerve block (FNB) for patients with a proximal femoral fracture (PFF) and administered by an orthopaedic registrar (OR) instead of an anaesthesiology registrar (AR) lowers the lead time to block and reduces the total amount of rescue analgesics during the preoperative phase. 205 patients were included in a prospective observational cohort study. The main outcome variable was rescue analgesics as total intravenous morphine prior to surgery. All results were adjusted for confounding using age, sex, cognitive dysfunction, and ASA classification. The OR group (n=135) was over 2 hours faster in performing the block compared to the AR group (n=70) but was nonetheless correlated with an increased amount of rescue analgesics during the study, 2.4 mg morphine (95% CI 0.0–4.9) more compared to the AR group. We found no difference between the groups in the risk of adverse events. We conclude that, for patients with an acute PFF and with morphine consumption as end point, how soon from arrival to hospital the patients receive a FNB is of lesser importance than who is administering it. Based on our results we recommend that emergency hospitals should have routines for anaesthesiologists performing FNB on this frail patient group.
Relativistic Energy Analysis of Five-Dimensionalq-Deformed Radial Rosen-Morse Potential Combined withq-Deformed Trigonometric Scarf Noncentral Potential Using Asymptotic Iteration Method
Authors: Pramono Subur , Suparmi A. , Cari Cari
Published: September 2016

We study the exact solution of Dirac equation in the hyperspherical coordinate under influence of separableq-deformed quantum potentials. Theq-deformed hyperbolic Rosen-Morse potential is perturbed byq-deformed noncentral trigonometric Scarf potentials, where all of them can be solved by using Asymptotic Iteration Method (AIM). This work is limited to spin symmetry case. The relativistic energy equation and orbital quantum number equationlD-1have been obtained using Asymptotic Iteration Method. The upper radial wave function equations and angular wave function equations are also obtained by using this method. The relativistic energy levels are numerically calculated using Matlab, and the increase of radial quantum numberncauses the increase of bound state relativistic energy level in both dimensionsD=5andD=3. The bound state relativistic energy level decreases with increasing of both deformation parameterqand orbital quantum numbernl.
Holographic Schwinger Effect in a Confining D3-Brane Background with Chemical Potential
Authors: Zhang Zi-qiang , Hou De-fu , Wu Yan , Chen Gang
Published: September 2016

Using the AdS/CFT correspondence, we investigate the Schwinger effect in a confining D3-brane background with chemical potential. The potential between a test particle pair on the D3-brane in an external electric field is obtained. The critical fieldEcin this case is calculated. Also, we apply numerical method to evaluate the production rate for various cases. The results imply that the presence of chemical potential tends to suppress the pair production effect.
Efficacy and Safety of a Permethrin-Fipronil Spot-On Solution (Effitix®) in Dogs Naturally Infested by Ticks in Europe
Authors: Navarro Christelle , Reymond Nadège , Crastes Nolwenn , Bonneau Stéphane
Published: September 2016

Effitix is a new broad spectrum product based on the combination of fipronil 6.1% and permethrin 54.5% in a solution for spot-on application. It has been shown to be safe and efficacious in dogs in controlling tick, flea, sandfly, and mosquito infestations in laboratory conditions. The aim of this controlled, randomised study was to assess its safety and efficacy against natural tick infestations in field conditions. One hundred eighty-two privately owned dogs were included in France and Germany: 123 dogs were treated on day 0 with the permethrin-fipronil combination (Effitix) and 59 with a permethrin-imidacloprid combination (Advantix®). Tick counts were conducted on days 0 (before treatment), 7, 14, 21, and 28. The percentages of efficacy on days 7, 14, 21, and 28 were, respectively, 91.2%, 97%, 98.3%, and 96.7% with Effitix and were 94.8%, 96.9%, 95.7%, and 94.6% with Advantix. Very few adverse events were reported. Most were not serious and/or not related to the treatment with pruritus being the most common. One administration of Effitix was highly effective and safe to treat and control tick infestations for four weeks in field conditions and had a similar efficacy as the permethrin-imidacloprid combination for all visits.
Regulation of IL-33 by Oncostatin M in Mouse Lung Epithelial Cells
Authors: Richards Carl D. , Izakelian Laura , Dubey Anisha , Zhang Grace , Wong Steven , Kwofie Karen , Qureshi Aatif , Botelho Fernando
Published: September 2016

IL-33 modulates both innate and adaptive immune responses at tissue sites including lung and may play critical roles in inflammatory lung disease. Although IL-33 expression can be altered upon NF-Kappa B activation, here we examine regulation by Oncostatin M, a gp130 cytokine family member, in mouse lung tissue. Responses were assessed in BALB/c mouse lung at day 7 of transient overexpression using endotracheally administered adenovirus encoding OSM (AdOSM) or empty vector (AdDel70). Whole lung extracts showed induction of IL-33 mRNA (>20-fold) and protein (10-fold increase in immunoblots) by AdOSM relative to AdDel70. Immunohistochemistry for IL-33 indicated a marked induction of nuclear staining in alveolar epithelial cellsin vivo. Oncostatin M stimulated IL-33 mRNA and IL-33 full length protein in C10 mouse type 2 alveolar epithelial cells in culture in time-dependent and dose-dependent fashion, whereas IL-6, LIF, IL-31, IL-4, or IL-13 did not, and TGFβrepressed IL-33. IL-33 induction was associated with activation of STAT3, and pharmacological inhibition of STAT3 ameliorated IL-33 levels. These results indicate Oncostatin M as a potent inducer of IL-33 in mouse lung epithelial cells and suggest that an OSM/IL-33 axis may participate in innate immunity and inflammatory conditions in lung.
Nowcasting Mobile Games Ranking Using Web Search Query Data
Authors: Sekhavat Yoones A.
Published: September 2016

In recent years, the Internet has become embedded into the purchasing decision of consumers. The purpose of this paper is to study whether the Internet behavior of users correlates with their actual behavior in computer games market. Rather than proposing the most accurate model for computer game sales, we aim to investigate to what extent web search query data can be exploited to nowcast (contraction of “now” and “forecasting” referring to techniques used to make short-term forecasts) (predict the present status of) the ranking of mobile games in the world. Google search query data is used for this purpose, since this data can provide a real-time view on the topics of interest. Various statistical techniques are used to show the effectiveness of using web search query data to nowcast mobile games ranking.
Endosialin-Expressing Pericytes Promote Metastatic Dissemination
Authors: Viski Carmen , König Courtney , Kijewska Magdalena , Mogler Carolin , Isacke Clare M. , Augustin Hellmut G.
Published: September 2016

Metastasis is a multistep process that is critically dependent on the interaction of metastasizing tumor cells with cells in the local microenvironment. Within this tumor stroma, vessel-associated pericytes and myofibroblasts share a number of traits, including the upregulated expression of the transmembrane receptor endosialin (CD248). Comparative experiments in wild-type and endosialin-deficient mice revealed that stromal endosialin does not affect primary tumor growth but strongly promotes spontaneous metastasis. Mechanistically, endosialin-expressing pericytes in the primary tumor facilitate distant site metastasis by promoting tumor cell intravasation in a cell contact–dependent manner, resulting in elevated numbers of circulating tumor cells. Corresponding to these preclinical experiments, in independent cohorts of primary human breast cancers, upregulated endosialin expression significantly correlates with increased metastasis and poorer patient survival. Together, the data demonstrate a critical role for endosialin-expressing primary tumor pericytes in mediating metastatic dissemination and identify endosialin as a promising therapeutic target in breast cancer. Cancer Res; 76(18); 5313–25. ©2016 AACR.
p21(WAF1) Mediates Cell-Cycle Inhibition, Relevant to Cancer Suppression and Therapy
Authors: El-Deiry Wafik S.
Published: September 2016

p21 (WAF1/CIP1; CDKN1a) is a universal cell-cycle inhibitor directly controlled by p53 and p53-independent pathways. Knowledge of the regulation and function of p21 in normal and cancer cells has opened up several areas of investigation and has led to novel therapeutic strategies. The discovery in 1993 and subsequent work on p21 has illuminated basic cellular growth control, stem cell phenotypes, the physiology of differentiation, as well as how cells respond to stress. There remain open questions in the signaling networks, the ultimate role of p21 in the p53-deficiency phenotype in the context of other p53 target defects, and therapeutic strategies continue to be a work in progress. Cancer Res; 76(18); 5189–91. ©2016 AACR.

See related article by El-Deiry et al., Cancer Res 1994;54:1169–74.

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Chronic Myelogenous Leukemia– Initiating Cells Require Polycomb Group Protein EZH2
Authors: Xie Huafeng , Peng Cong , Huang Jialiang , Li Bin E. , Kim Woojin , Smith Elenoe C. , Fujiwara Yuko , Qi Jun , Cheloni Giulia , Das Partha P. , Nguyen Minh , Li Shaoguang , Bradner James E. , Orkin Stuart H.
Published: September 2016

Tyrosine kinase inhibitors (TKI) have revolutionized chronic myelogenous leukemia (CML) management. Disease eradication, however, is hampered by innate resistance of leukemia-initiating cells (LIC) to TKI-induced killing, which also provides the basis for subsequent emergence of TKI-resistant mutants. We report that EZH2, the catalytic subunit of Polycomb Repressive Complex 2 (PRC2), is overexpressed in CML LICs and required for colony formation and survival and cell-cycle progression of CML cell lines. A critical role for EZH2 is supported by genetic studies in a mouse CML model. Inactivation of Ezh2 in conventional conditional mice and through CRISPR/Cas9-mediated gene editing prevents initiation and maintenance of disease and survival of LICs, irrespective of BCR–ABL1 mutational status, and extends survival. Expression of the EZH2 homolog EZH1 is reduced in EZH2-deficient CML LICs, creating a scenario resembling complete loss of PRC2. EZH2 dependence of CML LICs raises prospects for improved therapy of TKI-resistant CML and/or eradication of disease by addition of EZH2 inhibitors.

Significance: This work defines EZH2 as a selective vulnerability for CML cells and their LICs, regardless of BCR–ABL1 mutational status. Our findings provide an experimental rationale for improving disease eradication through judicious use of EZH2 inhibitors within the context of standard-of-care TKI therapy. Cancer Discov; 6(11); 1237–47. ©2016 AACR.

See related article by Scott et al., p. 1248.

This article is highlighted in the In This Issue feature, p. 1197
Epigenetic Reprogramming Sensitizes CML Stem Cells to Combined EZH2 and Tyrosine Kinase Inhibition
Authors: Scott Mary T. , Korfi Koorosh , Saffrey Peter , Hopcroft Lisa E.M. , Kinstrie Ross , Pellicano Francesca , Guenther Carla , Gallipoli Paolo , Cruz Michelle , Dunn Karen , Jorgensen Heather G. , Cassels Jennifer E. , Hamilton Ashley , Crossan Andrew , Sinclair Amy , Holyoake Tessa L. , Vetrie David
Published: September 2016

A major obstacle to curing chronic myeloid leukemia (CML) is residual disease maintained by tyrosine kinase inhibitor (TKI)–persistent leukemic stem cells (LSC). These are BCR–ABL1 kinase independent, refractory to apoptosis, and serve as a reservoir to drive relapse or TKI resistance. We demonstrate that Polycomb Repressive Complex 2 is misregulated in chronic phase CML LSCs. This is associated with extensive reprogramming of H3K27me3 targets in LSCs, thus sensitizing them to apoptosis upon treatment with an EZH2-specific inhibitor (EZH2i). EZH2i does not impair normal hematopoietic stem cell survival. Strikingly, treatment of primary CML cells with either EZH2i or TKI alone caused significant upregulation of H3K27me3 targets, and combined treatment further potentiated these effects and resulted in significant loss of LSCs compared to TKI alone, in vitro, and in long-term bone marrow murine xenografts. Our findings point to a promising epigenetic-based therapeutic strategy to more effectively target LSCs in patients with CML receiving TKIs.

Significance: In CML, TKI-persistent LSCs remain an obstacle to cure, and approaches to eradicate them remain a significant unmet clinical need. We demonstrate that EZH2 and H3K27me3 reprogramming is important for LSC survival, but renders LSCs sensitive to the combined effects of EZH2i and TKI. This represents a novel approach to more effectively target LSCs in patients receiving TKI treatment. Cancer Discov; 6(11); 1248–57. ©2016 AACR.

See related article by Xie et al., p. 1237.

This article is highlighted in the In This Issue feature, p. 1197
Proteomic Analyses Uncover the Mechanisms Underlying Antibiotic Resistance Differences among Three Acinetobacter baumannii Isolates
Authors: Wang Junrui , Zhang Junli , Fu Quan , Guo Sufang , Ta La , Sun Peng
Published: September 2016

This study aimed to investigate the molecular mechanisms underlying the antibiotic resistance difference among three Acinetobacter baumannii isolates. Fifty A. baumannii isolates were first subjected to an antimicrobial susceptibility test, then three isolates differing in antibiotic resistance were selected and subjected to iTRAQ (isobaric tags for relative and absolute quantification)-based proteomics analysis. Differential proteins among the three A. baumannii isolates were further identified and subjected to gene ontology functional enrichment analysis. A resistant isolate (A1), a less resistant one (A8) and a susceptible one (A9) were selected. In total, there were 424 differentially expressed proteins (DEPs) between the A1 and A8 isolates, 1,992 DEPs between the A9 and A1 isolates, and 1,956 DEPs between the A8 and A9 isolates. The upregulation of I6TUC8 and Q0GA83 in the A1 and A8 isolates may be responsible for their higher resistance to ceftriaxone. The higher gentamicin resistance of A. baumannii isolates A1 and A8 when compared to A9 may be related to the higher expression levels of O05286 and D0CCK1, while the higher Q2FCY1 expression level may contribute more to strong gentamicin resistance in A1. The higher levels of L9LWL7, L9MDB0, K9C9W3, E2IGU7, B6E129, G8HYR7, D2XTB0 and D2XTB0 may be responsible for the higher carbapenem resistance of isolate A1 as compared to A8.
In vivo anti-Trichophyton Activities of Seed Oil Obtained from Caraganakorshinskii Kom.
Authors: Zhou Wenna , Xu Heng , Luan Guangxiang , Wang HongLun , Wang Xiaoyan , Ji Mingkai
Published: September 2016

Aim: The objective of this study was to evaluate the effects of seed oil of Caragana korshinskii Kom. against Trichophyton mentagrophytes on an in vivo guinea pig model of dermatophytosis. Methods: The skin of albino guinea pigs was infected with T. mentagrophytes, and the animals were divided into five groups: negative control (NC group), positive control (PC group), vehicle control, CK50% group (received topical 50% seed oil of C.korshinskii), and CK100% group (received topical 100% seed oil of C.korshinskii). Evaluation of clinical efficacy was performed 72 h after the completion of a 10-day treatment regimen. Skin biopsy samples were processed for histopathological examination. Results: The infected untreated control guinea pigs showed patches of hair loss and ulcerated or scaly skin. Lower clinical scores indicate improved efficacy compared with NC. The lesion scores significantly declined in the CK50%, CK100%, and PC groups in comparison with the NC group. The CK50% group (45.31%) and the CK100% group (75%) showed clinical efficacy compared with the PC group (78.13%). In addition, no fungal elements, inflammation, or tissue destruction was observed in any of the PAS-stained sections of the infected skin in the groups treated with CK100% or 1% terbinafine. Conclusion: Seed oil of C.korshinskii demonstrated high antifungal efficacy in experimental dermatophytosis.
Evidence of Interruption of the comM Gene in a Large Series of Clinical Isolates of Multidrug-Resistant Acinetobacter baumannii
Authors: Douraghi Masoumeh , Jasemi Seyedesomaye , Kodori Mansoor , Rahbar Mohammad , Boroumand Mohammad Ali
Published: September 2016

Recent studies have recognized the ATPase-encoding comM gene as a hot spot for the integration of Acinetobacter baumannii resistance islands (RIs). Despite the circulation of high numbers of multidrug-resistant A. baumannii (MDR-AB) isolates in Middle East countries, no information is available about the interruption of comM and subsequent transposition into comM in isolates belonging to the global clones (GC) GC1, GC2, or GC3. In this study 401 A. baumannii isolates from hospitals in Tehran, Iran, were included. The resistance profile was determined by disc diffusion against 22 antibiotics. PCR was used to assess the GC type, presence of the comM gene, and the boundary junctions (J1 and J2) of RIs. Most of the MDR-AB isolates (384 of 388; 98%) and more than half of the susceptible A. baumannii isolates (9 of 13; 69%) had interrupted comM gene-carrying integrative elements. Among the isolates tested, 57 belonged to GC1, 86 to GC2, and 8 to GC3. A set of 250 isolates showed distinct patterns of allele-specific PCR for ompA, csuE, and blaOXA-51-like genes. All but 2 of the GC1 isolates and 2 of the GC2 isolates contained interrupted comM genes. Four A. baumannii isolates harbored intact comM, but were multiply resistant to antibiotics. This study demonstrated that the comM gene is targeted by transposons in Iranian MDR-AB isolates belonging to different GCs. The data also showed that the carriage of interrupted comM is not exclusive to MDR isolates of A. baumannii.
Efficacy of Vitrectomy Combined with Subretinal Recombinant Tissue Plasminogen Activator for Subretinal versus Subpigment Epithelial versus Combined Hemorrhages
Authors: Waizel Maria , Todorova Margarita G. , Kazerounian Sara , Rickmann Annekatrin , Blanke Björn R. , Szurman Peter
Published: September 2016

Background: The aim of this study was to compare the outcomes after subretinal recombinant tissue plasminogen activator (rtPA) treatment for subretinal hemorrhages (SRH), subpigment epithelial hemorrhages (SPH), and combined subretinal and subpigment epithelial hemorrhages (CH). Methods: An observational analysis of patients treated with subretinal rtPA was performed. The primary endpoint was the assessment of visual improvement (best-corrected visual acuity, BCVA) after surgery. Secondary endpoints were evaluation of the maximal hemorrhage diameter (MHD) and central macular thickness (CMT) measured by spectral domain optical coherence tomography. Results: From a total of 83 eyes included in the study, 19 eyes showed SRH, 11 eyes SPH, and 53 eyes CH. For SRH and CH, the mean BCVA, MHD, and CMT improved significantly (p < 0.05). For patients with SPH, both the mean MHD and CMT decreased significantly (p < 0.05), whereas the mean BCVA improved only slightly after surgery (p = 0.28). Conclusion: Vitrectomy combined with subretinal rtPA injection and gas or air tamponade has a strong functional and anatomical effect on both SRH and CH and also seems to slightly improve the anatomical outcome in SPH.
Myxedema Coma Secondary to Central Hypothyroidism: A Rare but Real Cause of Altered Mental Status in Pediatrics
Authors: Thompson Michael D. , Henry Rohan K.
Published: September 2016

Background: Myxedema coma (MC), a medical emergency defined as severe hypothyroidism leading to altered mental status, is more common in older women with hypothyroidism. Methods/Results: A 7-year-old Caucasian male with chromosome 1q deletion presented with altered mental status preceded by milestone regression. His presenting labs results were: thyroid-stimulating hormone (TSH) 0.501 μIU/ml and free thyroxine (T4) <0.5 ng/dl. His morning cortisol level was 8.1 μg/dl with repeat testing, while TSH was 1.119 μIU/ml and free T4 was 0.5 ng/dl. Low-dose cosyntropin test showed baseline and peak cortisol levels of 1.9 and 16 μg/dl, respectively. Aside from altered mental status, heart block was present in addition to hypothermia and hypercarbia. Diffuse cerebral cortical and corpus callosum atrophy were seen on MRI. An intravenous (i.v.) stress dose of hydrocortisone was administered for 24 h prior to an i.v. loading dose of levothyroxine. His activity level subsequently returned to baseline within 48 h after treatment had been initiated. Conclusion: Though MC is rare, occurring mainly with noncompliance in primary hypothyroidism, it may occur at the diagnosis of secondary hypothyroidism. Based on features like hypothermia, hypoventilation, and cardiovascular instability occurring in the setting of central hypothyroidism, it should be suspected and managed urgently in order to avert the associated high mortality resulting from treatment delays.
Ditos acadêmicos do ontem e do hoje acerca do papel da enfermagem no processo e rotina da desinstitucionalização
Authors: Duarte Viviane Freitas , Lavorato Neto Gabriel , Rodrigues Larissa , Campos Claudinei José Gomes
Published: September 2016

Esta Revisão Integrativa objetiva explorar a produção científica nacional de enfermagem psiquiátrica sobre a reabilitação psicossocial no período de 1992 a 2014. A análise dos artigos levantados, resulta cinco categorias temáticas: enfermagem e a Reforma Psiquiátrica, ferramentas e estratégias que possibilitam a reabilitação psicossocial, o contexto familiar na reabilitação psicossocial, CAPS e outros espaços como facilitadores da reabilitação psicossocial e saúde mental na atenção básica. Nossas conclusões consideram a necessidade de um investimento maior na capacitação profissional do enfermeiro para compatibilizar com as demandas de cuidados aos doentes mentais apresentadas pela Reforma Psiquiátrica, que vem se consolidando paulatinamente com estratégias de inclusão que parecem adequadas, porém ainda insuficientes.
Impactos legais e no trabalho na vida do dependente químico
Authors: Nimtz Miriam Aparecida , Tavares Anna Maria Fornalski , Maftum Mariluci Alves , Ferreira Aline Cristina Zerwes , Capistrano Fernanda Carolina
Published: September 2016

O objetivo desse estudo é identificar o impacto do uso de drogas na vida do dependente químico em situações de criminalidade e de trabalho. Trata-se de uma pesquisa qualitativa exploratória, cujos dados foram coletados entre agosto e setembro de 2012 , em uma unidade de reabilitação para dependentes químicos do Paraná. Foram entrevistados 20 dependentes químicos. Os dados foram tratados com a análise categorial temática. Dos resultados encontrados, ressalta-se a vulnerabilidade laboral e social dos entrevistados. Conclui-se que o uso de substâncias químicas ilícitas leva o usuário a prejuízos da vida funcional de trabalho, além de sujeitá-lo à penalidades na esfera criminal.
Ruídos do processo de trabalho e o acolhimento da família na atenção psicossocial em álcool e outras drogas
Authors: Lisbôa Gabrielle Leite Pacheco , Brêda Mércia Zeviani , Albuquerque Maria Cícera dos Santos de
Published: September 2016

Pesquisa qualitativa, exploratória, objetivando apresentar ruídos encontrados no processo de trabalho de um Centro de Atenção Psicossocial em Álcool e outras Drogas, e possibilidades para o acolhimento efetivo da família neste serviço. A coleta dos dados foi realizada através de entrevista semiestruturada com oito profissionais. A análise dos dados foi realizada através da Análise de Conteúdo na perspectiva de Bardin e a discussão foi fundamentada na perspectiva teórica de Merhy. Os resultados evidenciaram ruídos produzidos no processo de trabalho e suas interfaces com o acolhimento aos familiares. Mais especificamente, revelaram demanda excessiva de atendimento, despreparo dos profissionais, acolhimento focado na dependência, dificuldades para o trabalho interdisciplinar e ausência de uma rede efetiva. Este estudo concluiu que ampliação dos vínculos, territorialização, articulação com grupos de apoio e flexibilidade dos grupos familiares , são possíveis caminhos para o acolhimento das famílias.
Associação entre o estado nutricional e padrões de uso de drogas em pacientes atendidos em Centros de Atenção Psicossocial Álcool e Drogas
Authors: Ribeiro Daniele Do Rocio , Carvalho Denise Siqueira de
Published: September 2016

O objetivo deste estudo foi avaliar o estado nutricional de pacientes em início e no terceiro mês de tratamento nos Centros de Atenção Psicossocial Álcool e Drogas de Curitiba-PR e verificar a sua relação com os aspectos socioeconômicos, demográficos e padrões de uso de drogas nesses dois grupos. Foram avaliados 254 adultos, 175 do grupo de início de tratamento e 79 de terceiro mês. Ambos apresentaram alterações no estado nutricional, tanto baixo peso como excesso de peso. O baixo peso associou-se ao sexo feminino e uso recente de crack, e o excesso de peso ao tempo de uso de álcool e ao uso frequente de maconha. O estudo demonstrou a grande vulnerabilidade dessa população em relação ao aspecto nutricional.
O Ensino de Enfermagem Psiquiátrica /Saúde Mental: avanços, limites e desafios
Authors: Souza Maria Conceição Bernardo de Mello e
Published: September 2016

O estudo teve como objetivos analisar como ocorre o ensino de Enfermagem Psiquiátrica/ Saúde Mental nos cursos públicos de enfermagem existentes no estado de São Paulo e investigar e analisar a prática pedagógica de professores responsáveis por disciplinas da área. Foram realizadas entrevistas com 12 professores, cuja verificação deu-se através da análise temática. Trata-se de pesquisa qualitativa. Resultados evidenciaram que os professores, em sua maioria, desconhecem o Projeto Político Pedagógico dos cursos de graduação em que estão inseridos; método de ensino predominante tradicional, com desejo de mudanças para uso de metodologias ativas; conteúdos de ensino prioritariamente com enfoque biologicista; apontam também desvalorização da profissão de professor. Apesar de se perceber desejo de avanços por parte desses profissionais nota-se pouco investimento na formação pedagógica dos mesmos
Trainspotting: uma perspectiva psicanalítica da toxicomania na contemporaneidade
Authors: Verceze Flávia Angelo , Cordeiro Sílvia Nogueira
Published: September 2016

O uso de substâncias consideradas tóxicas consiste em uma prática milenar presente em diferentes povos e culturas. Todavia, em cada civilização ou época, a droga apresenta uma finalidade diferente. Na contemporaneidade o uso de drogas está relacionado ao modo de vida e aos ideais vigentes no contexto social, caracterizado fundamentalmente por uma cultura do narcisismo e do espetáculo. Partindo dessa concepção de droga presente na atualidade e do pressuposto de que a subjetividade humana e as patologias são construídas a partir de articulações das relações culturais com a história individual do sujeito, o presente artigo tem como objetivo discutir o fenômeno da toxicomania na contemporaneidade através de vinhetas do filme Trainspotting. Para fundamentar essa discussão, utilizará o referencial teórico psicanalítico
Reinserção social de dependentes químicos residentes em comunidades terapêuticas
Authors: Souza Kévin Da Silva , Silva Iuri Fernando Coutinho e , Batista Sonis Henrique Rezende , Almeida Rogério José de
Published: September 2016

O estudo teve por objetivo caracterizar as ações e atividades voltadas para a reinserção social de dependentes químicos residentes em comunidades terapêuticas. Foram avaliadas 43 comunidades, localizadas no estado de Goiás, com a utilização de um questionário semiestruturado. Os dados foram analisados por meio de estatística descritiva e os resultados apontaram que essas comunidades apresentam mecanismos de preparo do residente para a alta terapêutica e encaminhamento ao mercado de trabalho. Entretanto, desenvolvem poucas atividades para a inserção no mercado de trabalho. O envolvimento da família no tratamento dos residentes é estimulado com visitas e atividades conjuntas. Conclui-se que embora o trabalho das comunidades seja relevante, ainda carece de ajuda de políticas públicas de assistência social que contribuam com a reinserção desses indivíduos na sociedade
Outcomes of Transvenous Lead Extraction for Cardiovascular Implantable Electronic Device Infections in Patients With Prosthetic Heart Valves
Authors: Huang Xin-miao , Fu Hai-xia , Zhong Li , Cao Jiang , Asirvatham Samuel J. , Baddour Larry M. , Sohail M. Rizwan , Nkomo Vuyisile T. , Nishimura Rick A. , Greason Kevin L. , Suri Rakesh M. , Friedman Paul A. , Cha Yong-Mei
Published: September 2016

Background—

Lead-related or valve-related endocarditis can complicate cardiovascular implantable electronic device (CIED) infection in patients with both CIED and prosthetic valves. The objective of this study was to determine the outcomes of transvenous lead extraction for CIED infection in patients with prosthetic valves.

Methods and Results—

We retrospectively screened 794 transvenous lead extraction procedures, between September 1, 2001 and August 31, 2012, at Mayo Clinic to identify patients with prosthetic valves who underwent lead extraction for infection. Demographic, clinical, and follow-up characteristics were analyzed. In total, 51 patients (6%) met the study inclusion criteria, of whom 20 had pocket infection and 31 had lead-related or valve-related, or both, endocarditis or bloodstream infection (mean age, 67 [18] years). Staphylococcal species were the most common pathogens, including
Staphylococcus aureus
in 20 cases (39%) and coagulase-negative staphylococci in 19 cases (37%). Overall, 127 transvenous leads (median lead age, 52 months) were extracted. Of these leads, 123 (97%) were removed completely. The in-hospital mortality rate was 9.8%; no deaths were attributable to the extraction procedure. Ninety-five percent of patients who survived had no evidence of recurrent device-related or valve-related infection.

Conclusions—

Transvenous lead extraction seems safe and curative in patients with CIED infection and prosthetic valves. Cure of infection can be achieved in the majority of patients with complete CIED removal and antimicrobial therapy and without valve surgery.