bluuebunny/crossref_metadata_2025 huggingface dataset:
Inflammatory but not mitogenic contexts prime synovial fibroblasts for compensatory signaling responses to p38 inhibition
Authors: Jones Douglas S. , Jenney Anne P. , Joughin Brian A. , Sorger Peter K. , Lauffenburger Douglas A.
Published: March 2018

Context-dependent kinase pathway cross-talk explains why p38 MAPK inhibitors are ineffective in patients with rheumatoid arthritis.
Heavy Metal Resistance Genes Are Associated with
bla
NDM-1
- and
bla
CTX-M-15
-Carrying Enterobacteriaceae
Authors: Yang Qiu E. , Agouri Siham Rajab , Tyrrell Jonathan Mark , Walsh Timothy Rutland
Published: March 2018

The occurrence of heavy metal resistance genes in multiresistant
Enterobacteriaceae
possessing
bla
NDM-1
or
bla
CTX-M-15
genes was examined by PCR and pulsed-field gel electrophoresis with S1 nuclease. Compared with clinical susceptible isolates (10.0% to 30.0%), the
pcoA
,
merA
,
silC
, and
arsA
genes occurred with higher frequencies in
bla
NDM-1
-positive (48.8% to 71.8%) and
bla
CTX-M-15
-positive (19.4% to 52.8%) isolates, and they were mostly located on plasmids. Given the high association of metal resistance genes with multidrug-resistant
Enterobacteriaceae
, increased vigilance needs to be taken with the use of heavy metals in hospitals and the environment.
Chemotaxis Allows Bacteria To Overcome Host-Generated Reactive Oxygen Species That Constrain Gland Colonization
Authors: Collins Kieran D. , Hu Shuai , Grasberger Helmut , Kao John Y. , Ottemann Karen M.
Published: March 2018

The epithelial layer of the gastrointestinal tract contains invaginations, called glands or crypts, which are colonized by symbiotic and pathogenic microorganisms and may function as designated niches for certain species. Factors that control gland colonization are poorly understood, but bacterial chemotaxis aids occupation of these sites. We report here that a
Helicobacter pylori
cytoplasmic chemoreceptor, TlpD, is required for gland colonization in the stomach.
tlpD
mutants demonstrate gland colonization defects characterized by a reduction in the percentage of glands colonized but not in the number of bacteria per gland. Consistent with TlpD's reported role in reactive oxygen species (ROS) avoidance,
tlpD
mutants showed hallmarks of exposure to high ROS. To assess the role of host-generated ROS in TlpD-dependent gland colonization, we utilized mice that lack either the ability to generate epithelial hydrogen peroxide or immune cell superoxide.
tlpD
gland colonization defects were rescued to wild-type
H. pylori
levels in both of these mutants. These results suggest that multiple types of innate immune-generated ROS production limit gland colonization and that bacteria have evolved specific mechanisms to sense and direct their motility in response to this signal and thus spread throughout tissue.
Iron and Zinc Regulate Expression of a Putative ABC Metal Transporter in Corynebacterium diphtheriae
Authors: Peng Eric D. , Oram Diana M. , Battistel Marcos D. , Lyman Lindsey R. , Freedberg Darón I. , Schmitt Michael P.
Published: March 2018

Corynebacterium diphtheriae
, a Gram-positive, aerobic bacterium, is the causative agent of diphtheria and cutaneous infections. While mechanisms required for heme iron acquisition are well known in
C. diphtheriae
, systems involved in the acquisition of other metals such as zinc and manganese remain poorly characterized. In this study, we identified a genetic region that encodes an ABC-type transporter (
iutBCD
) and that is flanked by two genes (
iutA
and
iutE
) encoding putative substrate binding proteins of the cluster 9 family, a related group of transporters associated primarily with the import of Mn and Zn. We showed that IutA and IutE are both membrane proteins with comparable Mn and Zn binding abilities. We demonstrated that the
iutABCD
genes are cotranscribed and repressed in response to iron by the iron-responsive repressor DtxR. Transcription of
iutE
was positively regulated in response to iron availability in a DtxR-dependent manner and was repressed in response to Zn by the Zn-dependent repressor Zur. Electrophoretic mobility shift assays showed that DtxR does not bind to the
iutE
upstream region, which indicates that DtxR regulation of
iutE
is indirect and that other regulatory factors controlled by DtxR are likely responsible for the iron-responsive regulation. Analysis of the
iutE
promoter region identified a 50-bp sequence at the 3′ end of the
iutD
gene that is required for the DtxR-dependent and iron-responsive activation of the
iutE
gene. These findings indicate that transcription of
iutE
is controlled by a complex mechanism that involves multiple regulatory factors whose activity is impacted by both Zn and Fe.

IMPORTANCE
Vaccination against diphtheria prevents toxin-related symptoms but does not inhibit bacterial colonization of the human host by the bacterium. Thus,
Corynebacterium diphtheriae
remains an important human pathogen that poses a significant health risk to unvaccinated individuals. The ability to acquire iron, zinc, and manganese is critical to the pathogenesis of many disease-causing organisms. Here, we describe a gene cluster in
C. diphtheriae
that encodes a metal importer that is homologous to broadly distributed metal transport systems, some with important roles in virulence in other bacterial pathogens. Two metal binding components of the gene cluster encode surface exposed proteins, and studies of such proteins may guide the development of second-generation vaccines for
C. diphtheriae
.
Visual Impairment Screening Assessment (VISA) tool: pilot validation
Authors: Rowe Fiona J , Hepworth Lauren R , Hanna Kerry L , Howard Claire
Published: March 2018

Objective

To report and evaluate a new Vision Impairment Screening Assessment (VISA) tool intended for use by the stroke team to improve identification of visual impairment in stroke survivors.

Design

Prospective case cohort comparative study.

Setting

Stroke units at two secondary care hospitals and one tertiary centre.

Participants

116 stroke survivors were screened, 62 by naïve and 54 by non-naïve screeners.

Main outcome measures

Both the VISA screening tool and the comprehensive specialist vision assessment measured case history, visual acuity, eye alignment, eye movements, visual field and visual inattention.

Results

Full completion of VISA tool and specialist vision assessment was achieved for 89 stroke survivors. Missing data for one or more sections typically related to patient’s inability to complete the assessment. Sensitivity and specificity of the VISA screening tool were 90.24% and 85.29%, respectively; the positive and negative predictive values were 93.67% and 78.36%, respectively. Overall agreement was significant; k=0.736. Lowest agreement was found for screening of eye movement and visual inattention deficits.

Conclusions

This early validation of the VISA screening tool shows promise in improving detection accuracy for clinicians involved in stroke care who are not specialists in vision problems and lack formal eye training, with potential to lead to more prompt referral with fewer false positives and negatives. Pilot validation indicates acceptability of the VISA tool for screening of visual impairment in stroke survivors. Sensitivity and specificity were high indicating the potential accuracy of the VISA tool for screening purposes. Results of this study have guided the revision of the VISA screening tool ahead of full clinical validation.
The ConCom Safety Management Scale: developing and testing a measurement instrument for control-based and commitment-based safety management approaches in hospitals
Authors: Alingh Carien W , Strating Mathilde M H , van Wijngaarden Jeroen D H , Paauwe Jaap , Huijsman Robbert
Published: March 2018

Background

Nursing management is considered important for patient safety. Prior research has predominantly focused on charismatic leadership styles, although it is questionable whether these best characterise the role of nurse managers. Managerial control is also relevant. Therefore, we aimed to develop and test a measurement instrument for control-based and commitment-based safety management of nurse managers in clinical hospital departments.

Methods

A cross-sectional survey design was used to test the newly developed questionnaire in a sample of 2378 nurses working in clinical departments. The nurses were asked about their perceptions of the leadership behaviour and management practices of their direct supervisors. Psychometric properties were evaluated using confirmatory factor analysis and reliability estimates.

Results

The final 33-item questionnaire showed acceptable goodness-of-fit indices and internal consistency (Cronbach’s α of the subscales range: 0.59–0.90). The factor structure revealed three subdimensions for control-based safety management: (1) stressing the importance of safety rules and regulations; (2) monitoring compliance; and (3) providing employees with feedback. Commitment-based management consisted of four subdimensions: (1) showing role modelling behaviour; (2) creating safety awareness; (3) showing safety commitment; and (4) encouraging participation. Construct validity of the scale was supported by high factor loadings and provided preliminary evidence that control-based and commitment-based safety management are two distinct yet related constructs. The findings were reconfirmed in a cross-validation procedure.

Conclusion

The results provide initial support for the construct validity and reliability of our ConCom Safety Management Scale. Both management approaches were found to be relevant for managing patient safety in clinical hospital departments. The scale can be used to deepen our understanding of the influence of patient safety management on healthcare professionals’ safety behaviour as well as patient safety outcomes.
Evidence for cannabis and cannabinoids for epilepsy: a systematic review of controlled and observational evidence
Authors: Stockings Emily , Zagic Dino , Campbell Gabrielle , Weier Megan , Hall Wayne D , Nielsen Suzanne , Herkes Geoffrey K , Farrell Michael , Degenhardt Louisa
Published: March 2018

Review evidence for cannabinoids as adjunctive treatments for treatment-resistant epilepsy. Systematic search of Medline, Embase and PsycINFO was conducted in October 2017. Outcomes were: 50%+ seizure reduction, complete seizure freedom; improved quality of life (QoL). Tolerability/safety were assessed by study withdrawals, adverse events (AEs) and serious adverse events (SAEs). Analyses were conducted in Stata V.15.0. 36 studies were identified: 6 randomised controlled trials (RCTs), 30 observational studies. Mean age of participants was 16.1 years (range 0.5–55 years). Cannabidiol (CBD) 20 mg/kg/day was more effective than placebo at reducing seizure frequency by 50%+(relative risk (RR) 1.74, 95% CI 1.24 to 2.43, 2 RCTs, 291 patients, low Grades of Recommendation, Assessment, Development and Evaluation (GRADE) rating). The number needed to treat for one person using CBD to experience 50%+ seizure reduction was 8 (95% CI 6 to 17). CBD was more effective than placebo at achieving complete seizure freedom (RR 6.17, 95% CI 1.50 to 25.32, 3 RCTs, 306 patients, low GRADE rating), and improving QoL (RR 1.73, 95% CI 1.33 to 2.26), however increased risk of AEs (RR 1.24, 95% CI 1.13 to 1.36) and SAEs (RR 2.55, 95% CI 1.48 to 4.38). Pooled across 17 observational studies, 48.5% (95% CI 39.0% to 58.1%) of patients reported 50%+ reductions in seizures; in 14 observational studies 8.5% (95% CI 3.8% to 14.5%) were seizure-free. Twelve observational studies reported improved QoL (55.8%, 95% CI 40.5 to 70.6); 50.6% (95% CI 31.7 to 69.4) AEs and 2.2% (95% CI 0 to 7.9) SAEs. Pharmaceutical-grade CBD as adjuvant treatment in paediatric-onset drug-resistant epilepsy may reduce seizure frequency. Existing RCT evidence is mostly in paediatric samples with rare and severe epilepsy syndromes; RCTs examining other syndromes and cannabinoids are needed.

PROSPERO registration number

CRD42017055412.
Is previous azithromycin treatment associated with azithromycin resistance in Neisseria gonorrhoeae? A cross-sectional study using national surveillance data in England
Authors: Clifton Soazig , Town Katy , Furegato Martina , Cole Michelle , Mohammed Hamish , Woodhall Sarah C , Kevin Dunbar J , Fifer Helen , Hughes Gwenda
Published: March 2018

Objectives

It has been suggested that treatment of STIs with azithromycin may facilitate development of azithromycin resistance in Neisseria gonorrhoeae (NG) by exposing the organism to suboptimal doses. We investigated whether treatment history for non-rectal Chlamydia trachomatis (CT), non-gonococcal urethritis (NGU) or NG (proxies for azithromycin exposure) in sexual health (GUM) services was associated with susceptibility of NG to azithromycin.

Methods

Azithromycin susceptibility data from the Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP 2013–2015, n=4606) and additional high-level azithromycin-resistant isolates (HL-AziR) identified by the Public Health England reference laboratory (2013–2016, n=54) were matched to electronic patient records in the national GUMCAD STI surveillance dataset (2012–2016). Descriptive and regression analyses were conducted to examine associations between history of previous CT/NGU/NG and subsequent susceptibility of NG to azithromycin.

Results

Modal azithromycin minimum inhibitory concentration (MIC) was 0.25 mg/L (one dilution below the resistance breakpoint) in those with and without history of previous CT/NGU/NG (previous 1 month/6 months). There were no differences in MIC distribution by history of CT/NGU (P=0.98) or NG (P=0.85) in the previous 1 month/6 months or in the odds of having an elevated azithromycin MIC (>0.25 mg/L) (Adjusted OR for CT/NGU 0.97 (95% CI 0.76 to 1.25); adjusted OR for NG 0.82 (95% CI: 0.65 to 1.04)) compared with those with no CT/NGU/NG in the previous 6 months. Among patients with HL-AziR NG, 3 (4%) were treated for CT/NGU and 2 (3%) for NG in the previous 6 months, compared with 6% and 8%, respectively for all GRASP patients.

Conclusions

We found no evidence of an association between previous treatment for CT/NGU or NG in GUM services and subsequent presentation with an azithromycin-resistant strain. As many CT diagnoses occur in non-GUM settings, further research is needed to determine whether azithromycin-resistant NG is associated with azithromycin exposure in other settings and for other conditions.
Geographical variations in the use of cancer treatments are associated with survival of lung cancer patients
Authors: Møller Henrik , Coupland Victoria H , Tataru Daniela , Peake Michael D , Mellemgaard Anders , Round Thomas , Baldwin David R , Callister Matthew E J , Jakobsen Erik , Vedsted Peter , Sullivan Richard , Spicer James
Published: March 2018

Introduction

Lung cancer outcomes in England are inferior to comparable countries. Patient or disease characteristics, healthcare-seeking behaviour, diagnostic pathways, and oncology service provision may contribute. We aimed to quantify associations between geographic variations in treatment and survival of patients in England.

Methods

We retrieved detailed cancer registration data to analyse the variation in survival of 176,225 lung cancer patients, diagnosed 2010-2014. We used Kaplan-Meier analysis and Cox proportional hazards regression to investigate survival in the two-year period following diagnosis.

Results

Survival improved over the period studied. The use of active treatment varied between geographical areas, with inter-quintile ranges of 9%–17% for surgical resection, 4%–13% for radical radiotherapy, and 22%–35% for chemotherapy. At 2 years, there were 188 potentially avoidable deaths annually for surgical resection, and 373 for radical radiotherapy, if all treated proportions were the same as in the highest quintiles. At the 6 month time-point, 318 deaths per year could be postponed if chemotherapy use for all patients was as in the highest quintile. The results were robust to statistical adjustments for age, sex, socio-economic status, performance status and co-morbidity.

Conclusion

The extent of use of different treatment modalities varies between geographical areas in England. These variations are not attributable to measurable patient and tumour characteristics, and more likely reflect differences in clinical management between local multi-disciplinary teams. The data suggest improvement over time, but there is potential for further survival gains if the use of active treatments in all areas could be increased towards the highest current regional rates.
The expansive library of jadomycins
Authors: MacLeod Jeanna M. , Forget Stephanie M. , Jakeman David L.
Published: March 2018

The jadomycin family of natural products was discovered from Streptomyces venezuelae ISP5230 in the 1990s. Subsequent identification of the biosynthetic gene cluster along with synthetic efforts established that incorporation of an amino acid into the polyaromatic angucycline core occurs non-enzymatically. Over two decades, the precursor-directed biosynthetic potential of the jadomycins has been heavily exploited, generating a library exceeding 70 compounds. This review compiles the jadomycins that have been isolated and characterized to date; these include jadomycins incorporating proteinogenic and non-proteinogenic amino acids, semi-synthetic derivatives, biosynthetic shunt products, compounds isolated in structural gene deletion studies, and deoxysugar sugar variant jadomycins produced by deletion or heterologous expression of sugar biosynthetic genes.
China and Lusophonia: A Compatible Alliance Network?
Authors: Vogt William J.
Published: March 2018

A significant phenomenon of the international system over the past decade is the empowerment of emerging economies, particularly the BRICS (Brazil, Russia, India, China, and South Africa), in diplomatic and trade relations. Thus, alliances between China, the world’s largest developing country, and newly efficacious powers in the global South have become salient topics in foreign policy research. This article focuses on the relations China maintains with Portuguese-speaking countries, or Lusophonia, which are notable for their geographic and cultural heft in the global South. As a nation removed from foreign imperial influence only a few decades ago, China shares a series of cultural commonalities with a Brazil-dominated Lusophonia that represents key political influences in middle-income countries. As a result, Lusophone countries are core targets in an overall international policy strategy that serves to benefit China for continued trade and economic growth, an orientation well aligned to enhance Sino-Lusophone cooperation in the short to medium term.
Credit Risk Contagion in an Evolving Network Model Integrating Spillover Effects and Behavioral Interventions
Authors: Chen Tingqiang , Xiao Binqing , Liu Haifei
Published: March 2018

We introduce an evolving network model of credit risk contagion in the credit risk transfer (CRT) market. The model considers the spillover effects of infected investors, behaviors of investors and regulators, emotional disturbance of investors, market noise, and CRT network structure on credit risk contagion. We use theoretical analysis and numerical simulation to describe the influence and active mechanism of the same spillover effects in the CRT market. We also assess the reciprocal effects of market noises, risk preference of investors, and supervisor strength of financial market regulators on credit risk contagion. This model contributes to the explicit investigation of the connection between the factors of market behavior and network structure. It also provides a theoretical framework for considering credit risk contagion in an evolving network context, which is greatly relevant for credit risk management.
Experimental Verification of Optimized Multiscroll Chaotic Oscillators Based on Irregular Saturated Functions
Authors: Muñoz-Pacheco J. M. , Guevara-Flores D. K. , Félix-Beltrán O. G. , Tlelo-Cuautle E. , Barradas-Guevara J. E. , Volos C. K.
Published: March 2018

Multiscroll chaotic attractors generated by irregular saturated nonlinear functions with optimized positive Lyapunov exponent are designed and implemented. The saturated nonlinear functions are designed in an irregular way by modifying their parameters such as slopes, delays between slopes, and breakpoints. Then, the positive Lyapunov exponent is optimized using the differential evolution algorithm to obtain chaotic attractors with 2 to 5 scrolls. We observed that the resulting chaotic attractors present more complex dynamics when different patterns of irregular saturated nonlinear functions are considered. After that, the optimized chaotic oscillators are physically implemented with an analog discrete circuit to validate the use of proposed irregular saturated functions. Experimental results are consistent with MATLAB™ and SPICE circuit simulator. Finally, the synchronization between optimized and nonoptimized chaotic oscillators is demonstrated.
Intrusion Detection System Based on Decision Tree over Big Data in Fog Environment
Authors: Peng Kai , Leung Victor C. M. , Zheng Lixin , Wang Shangguang , Huang Chao , Lin Tao
Published: March 2018

Fog computing, as the supplement of cloud computing, can provide low‐latency services between mobile users and the cloud. However, fog devices may encounter security challenges as a result of the fog nodes being close to the end users and having limited computing ability. Traditional network attacks may destroy the system of fog nodes. Intrusion detection system (IDS) is a proactive security protection technology and can be used in the fog environment. Although IDS in tradition network has been well investigated, unfortunately directly using them in the fog environment may be inappropriate. Fog nodes produce massive amounts of data at all times, and, thus, enabling an IDS system over big data in the fog environment is of paramount importance. In this study, we propose an IDS system based on decision tree. Firstly, we propose a preprocessing algorithm to digitize the strings in the given dataset and then normalize the whole data, to ensure the quality of the input data so as to improve the efficiency of detection. Secondly, we use decision tree method for our IDS system, and then we compare this method with Naïve Bayesian method as well as KNN method. Both the 10% dataset and the full dataset are tested. Our proposed method not only completely detects four kinds of attacks but also enables the detection of twenty‐two kinds of attacks. The experimental results show that our IDS system is effective and precise. Above all, our IDS system can be used in fog computing environment over big data.
Emblic Leafflower (Phyllanthus emblica L.) Fruits Ameliorate Vascular Smooth Muscle Cell Dysfunction in Hyperglycemia: An Underlying Mechanism Involved in Ellagitannin Metabolite Urolithin A
Authors: Zhou Junxuan , Zhang Cong , Zheng Guo-Hua , Qiu Zhenpeng
Published: March 2018

Ellagitannins in Phyllanthus emblica L. (emblic leafflower fruits) have been thought of as the beneficial constituents for ameliorating endocrinal and metabolic diseases including diabetes. However, the effect of emblic leafflower fruits on diabetic vascular complications involved in ellagitannin‐derived urolithin metabolites is still rare. In this study, acetylcholine‐induced endothelium‐independent relaxation in aortas was facilitated upon emblic leafflower fruit consumption in the single dose streptozotocin‐induced hyperglycemic rats. Emblic leafflower fruit consumption also suppressed the phosphorylation of Akt (Thr308) in the hyperglycemic aortas. More importantly, urolithin A (UroA) and its derived phase II metabolites were identified as the metabolites upon emblic leafflower fruit consumption by HPLC‐ESI‐Q‐TOF‐MS. Moreover, UroA reduced the protein expressions of phosphor‐Akt (Thr308) and β‐catenin in a high glucose‐induced A7r5 vascular smooth muscle cell proliferation model. Furthermore, accumulation of β‐catenin protein and activation of Wnt signaling in LiCl‐triggered A7r5 cells were also ameliorated by UroA treatment. In conclusion, our data demonstrate that emblic leafflower fruit consumption facilitates the vascular function in hyperglycemic rats by regulating Akt/β‐catenin signaling, and the effects are potentially mediated by the ellagitannin metabolite urolithin A.
Research on Monitoring and Prewarning System of Accident in the Coal Mine Based on Big Data
Authors: Xia Xu , Chen Zhigang , Wei Wei
Published: March 2018

More and more big data come from sensor nodes. There are many sensor nodes placed in the monitoring and prewarning system of the coal mine in China for the purpose of monitoring the state of the environment. It works every day and forms the coal mine big data. Traditional coal mine monitoring and prewarning systems are mainly based on mine communication cable, but they are difficult to place at coal working face tunnels. We use WSN to replace mine communication cable and build the monitoring and prewarning system. The sensor nodes in WSN are energy limited and the sensor data are complicated so it is very difficult to use these data directly to prewarn the accident. To solve these problems, in this paper, a new data aggregation strategy and fuzzy comprehensive assessment model are proposed. Simulations compared the energy consumption, delay time, cooperation cost, and prewarning time with our previous work. The result shows our method is reasonable.
An Epidemic Model of Computer Worms with Time Delay and Variable Infection Rate
Authors: Yao Yu , Fu Qiang , Yang Wei , Wang Ying , Sheng Chuan
Published: March 2018

With rapid development of Internet, network security issues become increasingly serious. Temporary patches have been put on the infectious hosts, which may lose efficacy on occasions. This leads to a time delay when vaccinated hosts change to susceptible hosts. On the other hand, the worm infection is usually a nonlinear process. Considering the actual situation, a variable infection rate is introduced to describe the spread process of worms. According to above aspects, we propose a time-delayed worm propagation model with variable infection rate. Then the existence condition and the stability of the positive equilibrium are derived. Due to the existence of time delay, the worm propagation system may be unstable and out of control. Moreover, the threshold τ0 of Hopf bifurcation is obtained. The worm propagation system is stable if time delay is less than τ0. When time delay is over τ0, the system will be unstable. In addition, numerical experiments have been performed, which can match the conclusions we deduce. The numerical experiments also show that there exists a threshold in the parameter a, which implies that we should choose appropriate infection rate β(t) to constrain worm prevalence. Finally, simulation experiments are carried out to prove the validity of our conclusions.
Tissue Tranglutaminase Regulates Interactions between Ovarian Cancer Stem Cells and the Tumor Niche
Authors: Condello Salvatore , Sima Livia , Ivan Cristina , Cardenas Horacio , Schiltz Gary , Mishra Rama K. , Matei Daniela
Published: March 2018

Cancer progression and recurrence are linked to a rare population of cancer stem cells (CSC). Here, we hypothesized that interactions with the extracellular matrix drive CSC proliferation and tumor-initiating capacity and investigated the functions of scaffold protein tissue transglutaminase (TG2) in ovarian CSC. Complexes formed by TG2, fibronectin (FN), and integrin β1 were enriched in ovarian CSC and detectable in tumors. A function-inhibiting antibody against the TG2 FN-binding domain suppressed complex formation, CSC proliferation as spheroids, tumor-initiating capacity, and stemness-associated Wnt/β-catenin signaling. Disruption of the interaction between TG2 and FN also blocked spheroid formation and the response to Wnt ligands. TG2 and the Wnt receptor Frizzled 7 (Fzd7) form a complex in cancer cells and tumors, leading to Wnt pathway activation. Protein docking and peptide inhibition demonstrate that the interaction between TG2 and Fzd7 overlaps with the FN-binding domain of TG2. These results support a new function of TG2 in ovarian CSC, linked to spheroid proliferation and tumor-initiating capacity and mediated through direct interactions with Fzd7. We propose this complex as a new stem cell target.

Significance: These findings reveal a new mechanism by which ovarian CSCs interact with the tumor microenvironment, promoting cell proliferation and tumor initiation. Cancer Res; 78(11); 2990–3001. ©2018 AACR.
Telatinib Is an Effective Targeted Therapy for Pseudomyogenic Hemangioendothelioma
Authors: van IJzendoorn David G.P. , Sleijfer Stefan , Gelderblom Hans , Eskens Ferry A.L.M. , van Leenders Geert J.L.H. , Szuhai Karoly , Bovée Judith V.M.G.
Published: March 2018

Purpose: Pseudomyogenic hemangioendothelioma (PHE) is an extremely rare locally aggressive neoplasm with endothelial differentiation, which often presents with multiple lesions. These tumors have characteristic SERPINE1–FOSB fusions. We report a 17 years old patient with advanced unresectable PHE with a durable complete remission to the multi-tyrosine kinase inhibitor telatinib. The aim of this study was to generate an in vitro model for PHE, to study the functional consequences of SERPINE1–FOSB in endothelial cells, and its interaction with telatinib, to biologically substantiate the complete response to telatinib.

Experimental Design: As the fusion results in overexpression of a truncated form of FOSB, we overexpressed truncated FOSB in normal endothelial cells.

Results: Truncated FOSB significantly affected tumor growth in three-dimensional (3D) on matrigel with increased and sustained sprouting. Moreover, truncated FOSB acted as an active transcription factor capable to regulate its own transcription, as well as to upregulate PDGFRA and FLT1 expression (four-fold). Telatinib decreased proliferation and tumor growth in 3D and induced apoptosis. As expected, telatinib blocked VEGF signaling as phosphorylation of ERK was abolished. Interestingly, in FOSB overexpressing cells, telatinib specifically affected PDGFRA, FLT1, and FLT4 signaling and downregulated SERPINE1, thereby affecting the self-regulation of the fusion gene.

Conclusions: We provide a biological substantiation of a complete clinical remission that was seen in a patient with PHE, showing that telatinib indirectly interferes with the self-regulated expression of the fusion product. Thus, telatinib or any other currently available VEGFR1-4/PDGFRA inhibitor could be a highly specific treatment option for patients with multifocal unresectable PHE. Clin Cancer Res; 24(11); 2678–87. ©2018 AACR.
Unmatched Type O RhD+ Red Blood Cells in Multiple Injured Patients
Authors: Flommersfeld Sabine , Mand Carsten , Kühne Christian A. , Bein Gregor , Ruchholtz Steffen , Sachs Ulrich J.
Published: March 2018

Background: Immediate supply of red blood cell (RBC) concentrates is crucial in the initial treatment of exsanguinating patients in the emergency room. General shortage of RhD- RBCs has led to protocols in which patients with unknown blood groups are initially transfused with group O, RhD+ RBCs. Limited data are available regarding the safety of such an approach. Methods: Transfusion protocols for all multiple injured patients from the regional polytrauma database were retrospectively analyzed over a period of 5 years. Data on side effects were retrieved from the local safety update registry. Follow-up data were obtained from patients with identified RhD-incompatible transfusions. Results: In total, 823 patients were registered as multiple injured in the database. An immediate transfusion of 259 units (mean number of units 4, range 1-6) group O, RhD+ RBCs was initiated in 62 of them. 14 of these patients were RhD- and received 60 units of RhD-incompatible RBCs in the emergency room. In the later course RhD- patients received additional 185 incompatible transfusions (13; 1-31). The overall seroconversion rate was 50%. No adverse outcome due to incompatible transfusion was observed. Conclusions: Initial supply with group O, RhD+ RBCs in multiple injured patients appears to be safe. Significant numbers of RhD- units can be saved for use in other patients.
Congenital Posterior Urethral Fistulae: Literature Review and Case Report
Authors: Perez Jaime F. , Díaz B. Ana María , Ramos Gustavo U. , Peralta Sara R.
Published: March 2018

Congenital posterior urethral-perineal fistula is an abnormal communication extending from the posterior urethra to the perineal skin. We present the case of an 11-year-old boy who had recurrent febrile urinary tract infections and abnormal dribbling of urine from the perineum. Fistulogram showed a paraescrotal fistula tract, which was then surgically excised. During the 10 months of follow-up, the patient remained asymptomatic without recurrence of urinary pathology.
Cytokine Production by Mononuclear Cells from Patients with Familial Infantile Bilateral Striatal Necrosis
Authors: Ganelin Cohen Esther , Bessler Hanna , Djaldetti Meir , Straussberg Rachel
Published: March 2018

Prompted by findings suggesting immune instability in infantile bilateral striatal necrosis (IBSN), we evaluated levels of proinflammatory (tumor necrosis factor α, interleukin [IL]-1β, IL-6, interferon [IFN]γ) and anti-inflammatory (IL-10 and IL-1ra) cytokines produced by peripheral blood mononuclear cells (PBMC) from 6 children with IBSN and 11 age-matched controls. Compared to controls, non-stimulated PBMC from the IBSN group produced a significantly lower level of IL-1ra (by 38%; p < 0.001) and significantly lower levels of TNFα, IL-1β, and IFNγ (by 36% [p < 0.001], 25% [p = 0.06], and 32% [p < 0.02]) under PBMC stimulation. The severe cachexia manifesting shortly after IBSN onset may impair the immunological state, placing patients at risk of death from hyperpyrexia and sepsis.
Body Mass Index as a Risk Factor for Toxicities in Patients with Advanced Soft-Tissue Sarcoma Treated with Trabectedin
Authors: Vincenzi Bruno , Badalamenti Giuseppe , Armento Grazia , Silletta Marianna , Spalato Ceruso Mariella , Catania Giovanna , Napolitano Andrea , Maltese Giuseppa , Valeri Sergio , Incorvaia Lorena , Santini Daniele , Tonini Giuseppe
Published: March 2018

Objectives: Low body mass index (BMI) and/or low lean body mass have been shown to be risk factors for chemotherapy-related toxicities in a number of different cancers. However, no data are available regarding the role of BMI as a risk factor for developing toxicities related to the novel anticancer agent, trabectedin, in patients with soft-tissue sarcoma (STS). We evaluated the role of BMI as a risk factor for trabectedin-related toxicity in patients with STS. Methods: Data from 51 patients with metastatic/advanced STS treated with trabectedin after progression on ≥1 anthracycline ± ifosfamide regimen were retrospectively reviewed. Results: Eighteen patients (35.3%) were underweight, and the remainder were of normal bodyweight (45.1%) or overweight (19.6%). Neutropenia of any grade (77.8 vs. 33.3%) and grade 3–4 neutropenia (50.0 vs. 18.2%) occurred more frequently in the underweight versus normal/overweight patients (p = 0.025). Febrile neutropenia also occurred more frequently in underweight patients. Differences remained statistically significant after adjusting for other predictors of toxicity. There were no significant differences in other hematological and nonhematological toxicities between the groups. Conclusions: The data suggest for the first time that BMI should be considered a risk factor for neutropenia in patients with STS treated with trabectedin.
International Consensus Statement on Screening, Diagnosis and Treatment of Substance Use Disorder Patients with Comorbid Attention Deficit/Hyperactivity Disorder
Authors: Crunelle Cleo L. , van den Brink Wim , Moggi Franz , Konstenius Maija , Franck Johan , Levin Frances R. , van de Glind Geurt , Demetrovics Zsolt , Coetzee Corné , Luderer Mathias , Schellekens Arnt ,   ICASA consensus group, Matthys Frieda
Published: March 2018

Adult attention deficit/hyperactivity disorder (ADHD) often co-occurs with substance use disorders (SUD) and is associated with early onset and more severe development of SUD and with reduced treatment effectiveness. Screening tools allow for a good recognition of possible ADHD in adults with SUD and should be used routinely, followed by an ADHD diagnostic process initiated as soon as possible. Simultaneous and integrated treatment of ADHD and SUD, using a combination of pharmaco- and psychotherapy, is recommended. Long-acting methylphenidate, extended-release amphetamines, and atomoxetine with up-titration to higher dosages may be considered in patients unresponsive to standard doses. This paper includes evidence- and consensus-based recommendations developed to provide guidance in the screening, diagnosis and treatment of patients with ADHD-SUD comorbidity.
Suppression of Non-Small Cell Lung Cancer Growth and Metastasis by a Novel Small Molecular Activator of RECK
Authors: Shen Jia , Wang Banghua , Zhang Tao , Zhu Ni , Wang Zexia , Jin Jing , He Yi , Hu Meichun
Published: March 2018

Background/Aims: Reversion-inducing cysteine-rich protein with kazal motifs (RECK) is a novel tumor suppressor gene that is critical for regulating tumor cell invasion and metastasis. The expression of RECK is dramatically down-regulated in human cancers. Harmine, a tricyclic compound from Peganum harmala, has been shown to have potential anti-cancer activity. Methods: Cell proliferation assay (CCK-8 cell viability assay), cell cycle analysis (detection by flow cytometry), apoptosis staining assay (TUNEL staining), cell migration assay and invasion assay (transwell assay) were carried out to investigate the Harmine’s efficacy on non-small cell lung cancer (NSCLC) cells in vitro. A549-luciferase cell orthotropic transplantation xenograft mouse model was used to determine the effect of Harmine treatment on NSCLC in vivo. Western blotting analysis of cell growth and metastasis related signal pathways was conducted to investigate the molecular mechanism of Harmine’s inhibitory effect on NSCLC. Results: Harmine treatment effectively inhibited cell proliferation and induced the G1/S cell cycle arrest of NSCLC cells. Further study proved that Harmine treatment led to apoptosis induction. Furthermore, treatment with NSCLC cells with Hamine resulted in decreased cell migration and cell invasion in vitro. More importantly, Harmine treatment significantly suppressed the NSCLC tumor growth and metastasis in mouse xenograft model in vivo. Mechanistically, in Harmine-treated NSCLC cells, RECK expression and its downstream signaling cascade were dramatically activated. As a consequence, the expression level of MMP-9 and E-cadherin were significantly decreased. Conclusion: These findings identify Harmine as a promising activator of RECK signaling for metastatic NSCLC treatment.
The Biopolitics of International Exchange: International Educational Exchange Programs – Facilitator or Victim in the Battle for Biopolitical Normativity?
Authors: Erbsen Heidi
Published: March 2018

This article addresses how international educational exchange programs are increasingly used as political, and particularly bio-political, tools to promote ideologies of biological normativity. Such programs have historically been promoted by national and international institutions as means to increase participants (and therefore the sending institution’s) knowledge of the world and transfer favorable values through individuals. us and eu exchange programs with Russia in particular have been focused on achieving a ‘mutual understanding’ or promoting ‘common’ or ‘shared values’ across countries; however, a tendency of educational institutions to select like-minded individuals and countries for participation has arguably complicated rather than mended global divides. The difference in values associated with biological practices in Russia, the us, and the eu related to traditional gender roles, marriage, nuclear families, birth control, etc. have become more apparent with the spread of information and globalization.

The main argument of this work supports that attention to the promotion or cancelation of certain exchange programs can be used to better understand larger patterns in international relations and the modern system of global governance. An investigation into the founding ideologies behind programs such as flex and Fulbright (by the us) and Erasmus + (by the European Commission) and their politicization exemplifies how educational programs can become ‘battlefields’ for ideologies of biological normativity. The example of the cancelation of the flex program by the Russian Federation is used to understand key relationships between biopolitics and geopolitics, modern and post-modern, and value transfer and human capital.
2. The Emergence of the Concept of Consciousness
Authors: Gamez David
Published: March 2018

In daily life we treat colour, sound and smell as objective properties of the world. Over the last three hundred years science has developed a series of interpretations of the world that have stripped objects of their sensory properties. Apples used to be red and tasty; now physical apples are colourless collections of jigging atoms, probability distributions of wave-particles. The physical world has become invisible. When science eliminated sensory properties from the physical world it was necessary to find a way of grouping, describing and explaining the colours, sounds and smells that we continued to encounter in daily life. We solved this problem by inventing the modern concept of consciousness. ‘Consciousness’ is a name for the sensory properties that were removed from the physical world by modern science.
12. Conclusion
Authors: Gamez David
Published: March 2018

The conclusion summarises the framework, highlights some of its limitations and suggests future directions of research.
Observational Constraint for Precipitation in Extratropical Cyclones: Sensitivity to Data Sources
Authors: Naud Catherine M. , Booth James F. , Lebsock Matthew , Grecu Mircea
Published: March 2018

Using cyclone-centered compositing and a database of extratropical-cyclone locations, the distribution of precipitation frequency and rate in oceanic extratropical cyclones is analyzed using satellite-derived datasets. The distribution of precipitation rates retrieved using two new datasets, the Global Precipitation Measurement radar–microwave radiometer combined product (GPM-CMB) and the Integrated Multisatellite Retrievals for GPM product (IMERG), is compared with CloudSat, and the differences are discussed. For reference, the composites of AMSR-E, GPCP, and two reanalyses are also examined. Cyclone-centered precipitation rates are found to be the largest with the IMERG and CloudSat datasets and lowest with GPM-CMB. A series of tests is conducted to determine the roles of swath width, swath location, sampling frequency, season, and epoch. In all cases, these effects are less than ~0.14 mm h−1 at 50-km resolution. Larger differences in the composites are related to retrieval biases, such as ground-clutter contamination in GPM-CMB and radar saturation in CloudSat. Overall the IMERG product reports precipitation more often, with larger precipitation rates at the center of the cyclones, in conditions of high precipitable water (PW). The CloudSat product tends to report more precipitation in conditions of dry or moderate PW. The GPM-CMB product tends to systematically report lower precipitation rates than the other two datasets. This intercomparison provides 1) modelers with an observational uncertainty and range (0.21–0.36 mm h−1 near the cyclone centers) when using composites of precipitation for model evaluation and 2) retrieval-algorithm developers with a categorical analysis of the sensitivity of the products to PW.
Quantitative Identification of the Annealing Degree of Apatite Fission Tracks Using Terahertz Time Domain Spectroscopy (THz-TDS)
Authors: Wu Hang , Wu Shixiang , Qiu Nansheng , Chang Jian , Bao Rima , Zhang Xin , Liu Nian , Liu Shuai
Published: March 2018

Apatite fission-track (AFT) analysis, a widely used low-temperature thermochronology method, can provide details of the hydrocarbon generation history of source rocks for use in hydrocarbon exploration. The AFT method is based on the annealing behavior of fission tracks generated by 238U fission in apatite particles during geological history. Due to the cumbersome experimental steps and high expense, it is imperative to find an efficient and inexpensive technique to determinate the annealing degree of AFT. In this study, on the basis of the ellipsoid configuration of tracks, the track volume fraction model (TVFM) is established and the fission-track volume index is proposed. Furthermore, terahertz time domain spectroscopy (THz-TDS) is used for the first time to identify the variation of the AFT annealing degree of Durango apatite particles heated at 20, 275, 300, 325, 450, and 500 ℃ for 10 h. The THz absorbance of the sample increases with the degree of annealing. In addition, the THz absorption index is exponentially related to annealing temperature and can be used to characterize the fission-track volume index. Terahertz time domain spectroscopy can be an ancillary technique for AFT thermochronological research. More work is urgently needed to extrapolate experimental data to geological conditions.
National evaluation of policies governing funding for wheelchairs and scooters in Canada
Authors: Smith Emma M. , Roberts Lynn , McColl Mary Ann , Martin Ginis Kathleen A. , Miller William C.
Published: March 2018

Background.

Wheelchairs, scooters, and related equipment are essential for the well-being of individuals with limited mobility and impact participation, health, and quality of life.

Purpose.

Our objective was to identify and evaluate policies governing equipment funding for Canadian adults. We reviewed funding legislation and program documentation for adult Canadians (≥18 years of age) covered by their provincial, territorial, or federal health care plan. Documents were obtained online or through administrative staff. Policy evaluation was guided by the Disability Policy Lens from the Canadian Disability Policy Alliance.

Key Issues.

Coverage ranges from full funding for all individuals within the jurisdiction to programs limited by strict eligibility criteria. Each jurisdiction defines “disability” or “basic/essential need” differently, contributing to further funding disparities.

Implications.

Funding policies differ substantially across Canada, resulting in unequal access to equipment dependent on province or territory. We identified eligibility, funding, definitions of mobility, repair and replacement, and prescriber requirement benchmarks that represent policy targets for improved access.
College students’ experiences of hedonia and eudaimonia in their everyday activities
Authors: Atler Karen E. , Eakman Aaron M. , Orsi Rebecca
Published: March 2018

Background.

Experiences of hedonia (i.e., seeking pleasure) and eudaimonia (i.e., actualizing human potential in pursuit of meaningful goals) are central to the study of human well-being.

Purpose.

This study sought to examine levels of hedonia (pleasure) and eudaimonia (productivity) in a convenience sample of college (university) students’ ( n = 264) daily activities, controlling for levels of perceived stress.

Method.

Data were gathered using a 24-hr time-use recall diary designed to assess objective and subjective information about everyday activities. Descriptions of self-reported everyday activities were coded into 20 activity types.

Findings.

Activities reported high in pleasure were eating, listening to music/watching movies, and exercise. Activities reported as high in productivity were studying and working. Activities reported as high in both pleasure and productivity were reported less frequently and often had a recognizable outcome or provided social connection.

Implications.

Developing a greater understanding of how college students experience their daily activities could strengthen programs designed to enable students to manage stress and sustain their well-being.