bluuebunny/crossref_metadata_2025 huggingface dataset:
Temporal analysis of determinants for respiratory emergency department visits in a large German hospital
Authors: Krefis Anne Caroline , Fischereit Jana , Hoffmann Peter , Pinnschmidt Hans , Sorbe Christina , Augustin Matthias , Augustin Jobst
Published: November 2018

Introduction

Associations between air pollutants, meteorological conditions and respiratory diseases have been extensively shown. The aim of this study was to investigate associations between daily meteorological data, data on air pollution and emergency department (ED) visits depending on the day of the week, season and year (study period from 2013 to 2015).

Methods

Highly correlated environmental data entered a categorical principal components analysis (CATPCA). We analysed cross-correlation functions between the time series of the respective daily environmental factors and daily ED visits. Time lags with peak correlations of environmental variables obtained by the CATPCA on ED visits together with day of the week, year, running day (linear, quadratic and cubic), season and interaction terms entered the univariate analysis of variance (UNIANOVA) model.

Results

The analyses demonstrated main effects on ED visits for the day of the week with highest admission rates on Mondays (B=10.69; ƞ2=0.333; p<0.001). A significant time trend could be observed showing increasing numbers of ED visits per each year (p<0.001). The variable ‘running day’ (linear, quadratic and cubic) indicated a significant non-linear effect over time. The variable season showed significant results with winter, spring and summer recording fewer ED visits compared with the reference season autumn. Environmental variables showed no direct associations with respiratory ED visits.

Discussion

ED visits were significantly associated with temporal variables. Our data did not show direct associations between environmental variables and ED visits.

In times of rapid urbanisation, increases in respiratory diseases, temperature and air pollution, our analyses can help focus future studies and enhance strategies to reduce increasing numbers of respiratory diseases and ED visits. Because the potential costs of medical care in hospitals can be high compared with physicians, public health recommendations for reducing the increasing ED visits should be promoted and evaluated.
Early diagnosis of progressive multifocal leucoencephalopathy: longitudinal lesion evolution
Authors: Scarpazza Cristina , Signori Alessio , Prosperini Luca , Sormani Maria Pia , Cosottini Mirco , Capra Ruggero , Gerevini Simonetta
Published: November 2018

Objective

Early diagnosis of natalizumab-related progressive multifocal leucoencephalopathy (NTZ-PML) in multiple sclerosis has been deemed a major priority by the regulatory agencies but has yet to become a reality. The current paper aims to: (1) investigate whether patients with NTZ-PML pass through a prolonged presymptomatic phase with MRI abnormalities, (2) estimate the longitudinal PML lesion volume increase during the presymptomatic phase and (3) estimate the presymptomatic phase length and its impact on therapy duration as a risk stratification parameter.

Methods

All Italian patients who developed NTZ-PML between 2009 and 2018 were included. The data of patients with available prediagnostic MRI were analysed (n=41). Detailed clinical and neuroradiological information was available for each participant.

Results

(1) PML lesions were detectable in the presymptomatic phase in 32/41 (78%) patients; (ii) the lesion volume increased by 62.8 % for each month spent in the prediagnostic phase; (3) the prediagnostic phase length was 150.8±74.9 days; (4) PML MRI features were detectable before the 24th month of therapy in 31.7 % of patients in our cohort.

Conclusions

Considering the latency of PML clinical manifestation, the presymptomatic phase length supports the usefulness of MRI surveillance every 3–4  months. Early diagnosis could prompt a better outcome for patients due to the relationship between lesion volume and JC virus infection. The insight from this study might also have an impact on risk stratification algorithms, as therapy duration as a parameter of stratification appears to need reassessment.
More than three passes of stent retriever is an independent predictor of parenchymal hematoma in acute ischemic stroke
Authors: Bourcier Romain , Saleme Suzana , Labreuche Julien , Mazighi Mikael , Fahed Robert , Blanc Raphael , Gory Benjamin , Kyheng Maeva , Marnat Gaultier , Bracard Serge , Desal Hubert , Consoli Arturo , Piotin Michel , Lapergue Bertrand
Published: November 2018

Introduction

Despite successful recanalization with mechanical thrombectomy (MT) for acute anterior ischemic stroke (AAIS), the number of passes may impact clinical outcome.

We analyzed the impact of more than three MT passes (>3) in a trial that evaluated contact aspiration (CA) versus stent retriever (SR) as the first-line technique in AAIS.

Methods

We included patients with mTICI 2b/3 recanalization after MT for isolated intracranial occlusions. The primary outcome was the percentage of patients with a 90-day modified Rankin Scale (mRS)≤2. Secondary outcomes included overall distribution of 90-day mRS, parenchymal hematoma on 24 hours' brain imaging (PH), and 90-day mortality.

Results

Among the 281 patients included and even after adjustment on time to recanalization, significantly more patients with >3 passes had PH than patients with ≤3 passes in multivariate analysis (adjusted OR, 3.62; 95% CI, 1.55 to 8.44). When the analyses were stratified according to CA vs. SR, patients with >3 passes had a stronger risk of PH than patients with ≤3 passes, only in the SR first-line-treated group (adjusted OR, 9.24; 95% CI, 2.65 to 32.13) and not in the CA first-line-treated group (adjusted RR, 1.73; 95% CI, 0.57 to 5.19). A negative association of borderline significance (P=0.07) between >3 passes and favorable outcome was observed only in SR first-line-treated patients (adjusted OR, 0.33; 95% CI, 0.09 to 1.11).

Conclusions

After three passes of SR and unlike for three passes of CA, there is an increased risk of PH and a trend toward a worse clinical outcome.
Pre-test characteristics of unstable angina patients with obstructive coronary artery disease confirmed by coronary angiography
Authors: Fladseth Kristina , Kristensen Andreas , Mannsverk Jan , Trovik Thor , Schirmer Henrik
Published: November 2018

Objective

Patients referred for acute coronary angiography (CAG) with unstable angina (UA) have low mortality and low rate of obstructive coronary artery disease (CAD). Better pre-test selection criteria are warranted. We aimed to assess the current guidelines against other clinical variables as predictors of obstructive CAD in patients with UA referred for acute CAG.

Methods

From 2005 to 2012, all CAGs performed at the University Hospital of North Norway, the sole provider of CAG in the region, were recorded in a registry. We included 979 admissions of UA and retrospectively collected data regarding presenting clinical parameters from patient hospital records. Obstructive CAD was defined as ≥50% stenosis and considered prognostically significant if found in the left main stem, proximal LAD or all three main coronary arteries. Characteristics were analysed by logistic regression analysis. A score was developed using ORs from significant factors in a multivariable model.

Results

The overall rate of obstructive CAD was 45%, and the rate of prognostically significant CAD was 11%. The risk criteria recommended in American College of Cardiology/American Heart Association and European Society of Cardiology guidelines had an area under the curve (AUC) of 0.58. Adding clinical information increased the AUC to 0.77 (95% CI 0.74 to 0.80). Applying the derived score, we found that 56% (n=546) of patients had a score of <13, which was associated with a negative predictive value of 95% for prognostic significant CAD.

Conclusions

The current results suggest that CAG may be postponed or cancelled in more than half of patients with UA by improving pre-test selection criteria with the addition of clinical parameters to current guidelines.
Obesity paradox on outcome in atrial fibrillation maintained even considering the prognostic influence of biomarkers: insights from the ARISTOTLE trial
Authors: Sandhu Roopinder K , Ezekowitz Justin A , Hijazi Ziad , Westerbergh Johan , Aulin Julia , Alexander John H , Granger Christopher B , Halvorsen Sigrun , Hanna Michael S , Lopes Renato D , Siegbahn Agneta , Wallentin Lars
Published: November 2018

Objective

We investigated the association between obesity and biomarkers indicating cardiac or renal dysfunction or inflammation and their interaction with obesity and outcomes.

Methods

A total of 14 753 patients in the Apixaban for Reduction In STroke and Other ThromboemboLic Events in Atrial Fibrillation (ARISTOTLE) trial provided plasma samples at randomisation to apixaban or warfarin. Median follow-up was 1.9 years. Body Mass Index (BMI) was measured at baseline and categorised as normal, 18.5–25  kg/m2; overweight, >25 to <30 kg/m2; and obese, ≥30 kg/m2. We analysed the biomarkers high-sensitivity C reactive protein (hs-CRP), interleukin 6 (IL-6), growth differentiation factor-15 (GDF-15), troponin T and N-terminal B-type natriuretic peptide (NT-pro-BNP). Outcomes included stroke/systemic embolism (SE), myocardial infarction (MI), composite (stroke/SE, MI, or all-cause mortality), all-cause and cardiac mortality, and major bleeding.

Results

Compared with normal BMI, obese patients had significantly higher levels of hs-CRP and IL-6 and lower levels of GDF-15, troponin T and NT-pro-BNP. In multivariable analyses, higher compared with normal BMI was associated with a lower risk of all-cause mortality (overweight: HR 0.73 (95% CI 0.63 to 0.86); obese: 0.67 (0.56 to 0.80), p<0.0001), cardiac death (overweight: HR 0.74 (95% CI 0.60 to 0.93); obese: 0.71 (0.56 to 0.92), p=0.01) and composite endpoint (overweight: 0.80 (0.70 to 0.92); obese: 0.72 (0.62 to 0.84), p<0.0001).

Conclusions

Regardless of biomarkers indicating inflammation or cardiac or renal dysfunction, obesity was independently associated with an improved survival in anticoagulated patients with AF.

Trial registration number

NCT00412984.
Multiple biomarker panel to screen for severe aortic stenosis: results from the CASABLANCA study
Authors: Elmariah Sammy , McCarthy Cian , Ibrahim Nasrien , Furman Deborah , Mukai Renata , Magaret Craig , Rhyne Rhonda , Barnes Grady , van Kimmenade Roland R J , Januzzi James L
Published: November 2018

Objective

Severe aortic valve stenosis (AS) develops via insidious processes and can be challenging to correctly diagnose. We sought to develop a circulating biomarker panel to identify patients with severe AS.

Methods

We enrolled study participants undergoing coronary or peripheral angiography for a variety of cardiovascular diseases at a single academic medical centre. A panel of 109 proteins were measured in blood obtained at the time of the procedure. Statistical learning methods were used to identify biomarkers and clinical parameters that associate with severe AS. A diagnostic model incorporating clinical and biomarker results was developed and evaluated using Monte Carlo cross-validation.

Results

Of 1244 subjects (age 66.4±11.5  years, 28.7% female), 80 (6.4%) had severe AS (defined as aortic valve area (AVA) <1.0  cm2). A final model included age, N-terminal pro-B-type natriuretic peptide, von Willebrand factor and fetuin-A. The model had good discrimination for severe AS (OR=5.9, 95% CI 3.5 to 10.1, p<0.001) with an area under the curve of 0.76 insample and 0.74 with cross-validation. A diagnostic score was generated. Higher prevalence of severe AS was noted in those with higher scores, such that 1.6% of those with a score of 1 had severe AS compared with 15.3% with a score of 5 (p<0.001), and score values were inversely correlated with AVA (r=−0.35; p<0.001). At optimal model cut-off, we found 76% sensitivity, 65% specificity, 13% positive predictive value and 98% negative predictive value.

Conclusions

We describe a novel, multiple biomarker approach for diagnostic evaluation of severe AS.

Trial registration number

NCT00842868.
Modification of gene expression in rat cardiomyocytes by linoleic and docosahexaenoic acids
Authors: Cheema Sukhinder K. , Tappia Paramjit S. , Dhalla Naranjan S.
Published: November 2018

Regulation of cardiac fatty acid metabolism is central to the development of cardiac hypertrophy and heart failure. We investigated the effects of select fatty acids on the expression of genes involved in immediate early as well as inflammatory and hypertrophic responses in adult rat cardiomyocytes. Cardiac remodeling begins with upregulation of immediate early genes for c-fos and c-jun, followed by upregulation of inflammatory genes for nuclear factor kappa B (NF-κB) and nuclear factor of activated T-cells (NFAT). At later stages, genes involved in hypertrophic responses, such as atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), are upregulated. Adult rat cardiomyocytes were treated with palmitic acid, a saturated fatty acid; oleic acid, a monounsaturated fatty acid; linoleic acid, a polyunsaturated fatty acid belonging to the n-6 class; and docosahexaenoic acid, a polyunsaturated fatty acid belonging to the n-3 class. Linoleic acid produced a greater increase in the mRNA expression of c-fos, c-jun, NF-κB, NFAT3, ANP, and BNP relative to palmitic acid and oleic acid. In contrast, docosahexaenoic acid caused a decrease in the expression of genes involved in cardiac hypertrophy. Our findings suggest that linoleic acid may be a potent inducer of genes involved in cardiac hypertrophy, whereas docosahexaenoic acid may be protective against the cardiomyocyte hypertrophic response.
Novel molecular therapeutic targets in cardiac fibrosis: a brief overview
Authors: Wang Ryan , Lin Justin , Bagchi Rushita A.
Published: November 2018

Cardiac fibrosis, characterized by excessive accumulation of extracellular matrix, abolishes cardiac contractility, impairs cardiac function, and ultimately leads to heart failure. In recent years, significant evidence has emerged that supports the highly dynamic and responsive nature of the cardiac extracellular matrix. Although our knowledge of cardiac fibrosis has advanced tremendously over the past decade, there is still a lack of specific therapies owing to an incomplete understanding of the disease etiology and process. In this review, we attempt to highlight some of the recently investigated molecular determinants of ischemic and non-ischemic fibrotic remodeling of the myocardium that present as promising avenues for development of anti-fibrotic therapies.
An extended continuum model with consideration of the self-anticipative effect
Authors: Zhai Cong , Wu Wei-Tiao
Published: November 2018

Drivers would adjust the speeds in response to not only the external environment, but also the anticipated traffic condition. In this paper, we propose a new continuum model considering the driver’s self-anticipative effect. Such effect is mainly reflected by the difference between the current speed and optimal speed within the anticipation time step. By applying the linear stability theory, the stability condition of the new model is obtained. Through the nonlinear analysis method, the KdV–Burgers equation of the model is provided. The solution describes the evolution of density waves near the neutral stability region. The simulation example verifies that the self-anticipative effect of the driver contributes to suppressing traffic congestion and reducing exhaust emissions effectively. We thus suggest that the traffic flow stability could be improved in an ad hoc manner.
Astrophysics inspired multi-objective approach for automatic clustering and feature selection in real-life environment
Authors: Dhiman Gaurav , Kumar Vijay
Published: November 2018

In this paper, a novel astrophysics-based approach is proposed for automatically finding the clusters and features simultaneously. A novel agent encoding scheme is used to encode both the number of clusters and features. A novel dynamic threshold technique is proposed for an efficient searching. The validation of proposed technique is tested on eight real-life data sets. The statistical significance of proposed technique is attributed by statistical tests. It is also applied on solving image segmentation and microarray data analysis problems. Experimental results reveal that the proposed technique outperforms the other competitive approaches.
Modes simulation and numerical optimization of encapsulated connecting-layer grating for high efficiency
Authors: Gao Chenhao , Wang Bo , Li Hongtao , Wen Kunhua , Meng Ziming , Wang Qu , Xing Xiangjun , Chen Li , Lei Liang , Zhou Jinyun
Published: November 2018

We propose and investigate a polarization-independent high-efficiency encapsulated subwavelength grating with a connecting layer in this paper. Numerical simulated method of rigorous coupled-wave analysis is adopted for optimization. Based on the simulated precise results, a simplified modal method is used to give perspicuous physical propagating fundamentals and explain wideband performance in the grating, where the coupled efficiencies by means of the simplified modal method are to be in conformity with the calculated values of the rigorous coupled-wave analysis for TE and TM polarizations. Compared with the researched surface-relief polarization-independent single-port grating, efficiencies are improved with 98.1% for TE polarization and 98.2% for TM polarization. Hence, the novel gratings with some superiorities are suitable for promising photonic devices.
Lump solutions and interaction behaviors to the (2+1)-dimensional extended shallow water wave equation
Authors: Cheng Wenguang , Xu Tianzhou
Published: November 2018

In this paper, the exact solutions to the (2[Formula: see text]+[Formula: see text]1)-dimensional extended shallow water wave (SWW) equation are investigated by using its bilinear form and ansatz techniques. Following the method given by Ma [Phys. Lett. A 379 (2015) 1975–1978], two classes of lump solutions are constructed by searching for positive quadratic function solutions to the associated bilinear equation. Furthermore, two kinds of interaction solutions between a lump and solitary waves are presented by taking the solution of the associated bilinear equation as a linear combination function of a quadratic function and the double exponential function, one of which is the interaction solution between a lump and an exponentially decayed soliton, and the other one is the interaction solution between a lump and an exponentially decayed twin soliton. Finally, some figures are given to illustrate the dynamic properties of these obtained solutions.
MASH DDSM with Negative Feedback
Authors: Liao Yilong , Fan Xiangning , Hua Zaijun
Published: November 2018

This paper proposes a Multi-stAge noise SHaping (MASH) digital delta-sigma modulator (DDSM) with negative feedback to acquire the maximum sequence length. The mathematical analysis shows that the sequence length is [Formula: see text], which is not affected by the input values and initial conditions, where [Formula: see text] is the smallest prime number above the quantization interval [Formula: see text], and [Formula: see text] is the order of the MASH DDSM. Moreover, the influence of the negative feedback on the input range is analyzed. Finally, the simulations and experiments are performed to verify the theoretical analysis.
The Loewy series of principal indecomposable modules in the regular nilpotent representations of 𝔰𝔩(3,k)
Authors: Li Yi-Yang , Yao Yu-Feng
Published: November 2018

Let [Formula: see text] be a simple Lie algebra of type [Formula: see text] over an algebraically closed field [Formula: see text] of prime characteristic [Formula: see text] and [Formula: see text] be the reduced enveloping algebra of [Formula: see text]. In this paper, when the [Formula: see text]-character [Formula: see text] is regular nilpotent and has standard Levi form, we precisely determine the Lowey series of principal indecomposable [Formula: see text]-modules and the dimensions for the self-extension of irreducible [Formula: see text]-modules.
2D Coordination Polymer Derived Co3O4Nanocrystals as High Performance Anode Material of Lithium-Ion Batteries
Authors: Wen Hao , Shi Changdong , Gao Yuanrui , Rong Hongren , Sha Yanyong , Liu Hongjiang , Liu Qi
Published: November 2018

Co3O4 nanocrystals have been synthesized via an ordinary one-step calcination of a cobalt-based 2D coordination polymer [Co(tfbdc)(4,4[Formula: see text]-bpy)(H2O)2]. As an anode material for lithium-ion batteries, the obtained Co3O4 nanocrystals exhibit high reversible capacity, excellent cyclic stability and better rate capability. The reversible capacity of the Co3O4 nanocrystals maintains 713[Formula: see text]mA[Formula: see text]h[Formula: see text]g[Formula: see text] after 50 cycles at a current density of 50[Formula: see text]mA[Formula: see text]g[Formula: see text]. Our results confirm that searching for metal oxides nanomaterials used as anode materials of lithium ion batteries via the calcinations of 2D coordination polymer is a new route.
Ion-Imprinted Polymers Modified Sensor for Electrochemical Detection of Cu2+
Authors: An Zhuolin , Liu Weifeng , Liang Qi , Yan Guang , Qin Lei , Chen Lin , Wang Meiling , Yang Yongzhen , Liu Xuguang
Published: November 2018

An electrochemical sensor (Cu[Formula: see text]-IIPs/GCE) was developed for detection of Cu[Formula: see text] in water. Cu[Formula: see text]-IIPs/GCE was prepared by dispersing Cu[Formula: see text] imprinted polymers (Cu[Formula: see text]-IIPs) on a preprocessed glassy carbon electrode. Cu[Formula: see text]-IIPs were synthesized on the surface of modified carbon spheres by ion imprinting technology. The electrochemical performance of Cu[Formula: see text]-IIPs/GCE was evaluated by differential pulse voltammetry method. The response of Cu[Formula: see text]-IIPs/GCE to Cu[Formula: see text] was linear in [Formula: see text][Formula: see text]mol/L to [Formula: see text][Formula: see text]mol/L. The detection limit was [Formula: see text][Formula: see text]mol/L ([Formula: see text]). The current response value of Cu[Formula: see text]-IIPs/GCE was 2.14 times that of the nonimprinted electrode. These results suggest that Cu[Formula: see text]-IIPs/GCE can detect the concentration of Cu[Formula: see text] in water, providing a new way for heavy metal ions adsorption and testing.
Dielectric properties and temperature dependency of automotive catalyst coatings and substrate materials: Experimental results, influences and approximation approach
Authors: Dietrich Markus , Hagen Gunter , Moos Ralf
Published: November 2018

For the radio frequency-based catalyst state monitoring of SCR catalysts, the dielectric properties of the used SCR catalyst materials are essential to design the measurement system and to adjust it to the given conditions. This work focuses on the experimental determination of the effective complex dielectric properties of zeolite coatings on cordierite substrates and the approximation of the latter to describe and transfer these systems in an easier manner. Therefore, different influences were investigated to approximate the real and the imaginary part of the complex permittivity of zeolite coatings on cordierite substrates.
The reciprocal Mahler ensembles of random polynomials
Authors: Sinclair Christopher D. , Yattselev Maxim L.
Published: November 2018

We consider the roots of uniformly chosen complex and real reciprocal polynomials of degree [Formula: see text] whose Mahler measure is bounded by a constant. After a change of variables, this reduces to a generalization of Ginibre’s complex and real ensembles of random matrices where the weight function (on the eigenvalues of the matrices) is replaced by the exponentiated equilibrium potential of the interval [Formula: see text] on the real axis in the complex plane. In the complex (real) case, the random roots form a determinantal (Pfaffian) point process, and in both cases, the empirical measure on roots converges weakly to the arcsine distribution supported on [Formula: see text]. Outside this region, the kernels converge without scaling, implying among other things that there is a positive expected number of outliers away from [Formula: see text]. These kernels as well as the scaling limits for the kernels in the bulk [Formula: see text] and at the endpoints [Formula: see text] are presented. These kernels appear to be new, and we compare their behavior with related kernels which arise from the (non-reciprocal) Mahler measure ensemble of random polynomials as well as the classical Sine and Bessel kernels.
The Geikie Archive at Haslemere Museum: family and professional material
Authors: Betterton John
Published: November 2018

The family history of Sir Archibald Geikie (1835–1924) is examined with reference to his immediate family and descendants, including much previously unpublished documentary archival material preserved at the Haslemere Educational Museum. The lives of Archibald's children are also examined. This account includes previously unpublished images of the Geikie family and gives new insights into aspects of Archibald Geikie's character through the memories of his grandson, Derick Jacob Behrens (1917–2004). Geikie's continued academic life after his retirement from the Geological Survey is discussed in relation to that institution.
Botulinum and Tetanus Neurotoxins
Authors: Dong Min , Masuyer Geoffrey , Stenmark Pål
Published: November 2018

Botulinum neurotoxins (BoNTs) and tetanus neurotoxin (TeNT) are the most potent toxins known and cause botulism and tetanus, respectively. BoNTs are also widely utilized as therapeutic toxins. They contain three functional domains responsible for receptor-binding, membrane translocation, and proteolytic cleavage of host proteins required for synaptic vesicle exocytosis. These toxins also have distinct features: BoNTs exist within a progenitor toxin complex (PTC), which protects the toxin and facilitates its absorption in the gastrointestinal tract, whereas TeNT is uniquely transported retrogradely within motor neurons. Our increasing knowledge of these toxins has allowed the development of engineered toxins for medical uses. The discovery of new BoNTs and BoNT-like proteins provides additional tools to understand the evolution of the toxins and to engineer toxin-based therapeutics. This review summarizes the progress on our understanding of BoNTs and TeNT, focusing on the PTC, receptor recognition, new BoNT-like toxins, and therapeutic toxin engineering.
Zika Virus Vaccine Development: Progress in the Face of New Challenges
Authors: Diamond Michael S. , Ledgerwood Julie E. , Pierson Theodore C.
Published: November 2018

Zika virus (ZIKV) emerged at a global level when it spread to the Americas and began causing congenital malformations and microcephaly in 2015. A rapid response by academia, government, public health infrastructure, and industry has enabled the expedited development and testing of a suite of vaccine platforms aiming to control and eliminate ZIKV-induced disease. Analysis of key immunization and pathogenesis studies in multiple animal models, including during pregnancy, has begun to define immune correlates of protection. Nonetheless, the deployment of ZIKV vaccines, along with the confirmation of their safety and efficacy, still has major challenges, one of which is related to the waning of the epidemic. In this review, we discuss the measures that enabled rapid progress and highlight the path forward for successful deployment of ZIKV vaccines.
Women in (neuro)science: report of a meeting held at the University of Valencia, Spain, in February 2018
Authors: Mello-Carpes Pâmela B. , Lloret Ana
Published: November 2018

February 11th is the International Day of Women and Girls in Science. To mark this day, research centers and universities were invited by the Spanish Neuroscience Association to organize a symposium. Twenty-five centers in Spain participated in the event, with the intent of giving visibility to the existing problem of the scarcity of women compared with men in (neuro)science in positions of responsibility and command. Fourteen neuroscientists, all staff members of the University of Valencia, arranged the meeting. The morning included lectures by women neuroscientists in different phases of their career: a PhD student, a junior and a senior postdoctoral investigator, and a well-established investigator. In the evening, a roundtable composed of expert women philosophists, STEM (Science, Technology, Engineering, and Mathematics) scientists, and social experts discussed why the gap exists. At the end of the meeting, the exhibition entitled, “Women in Science” commenced: pictures and a brief biography of women who made significant contributions to science were presented. More than 200 people attended the meeting, including the general public, scientists, and secondary school and university students.
Exercise-induced calf muscle hyperemia: quantitative mapping with low-dose dynamic contrast enhanced magnetic resonance imaging
Authors: Zhang Jeff L. , Layec Gwenael , Hanrahan Christopher , Conlin Christopher C. , Hart Corey , Hu Nan , Khor Lillian , Mueller Michelle , Lee Vivian S.
Published: November 2018

Peripheral artery disease (PAD) in the lower extremities often leads to intermittent claudication. In the present study, we proposed a low-dose DCE MRI protocol for quantifying calf muscle perfusion stimulated with plantar flexion and multiple new metrics for interpreting perfusion maps, including the ratio of gastrocnemius over soleus perfusion (G/S; for assessing the vascular redistribution between the two muscles) and muscle perfusion normalized by whole body perfusion (for quantifying the muscle’s active hyperemia). Twenty-eight human subjects participated in this Institutional Review Board-approved study, with 10 healthy subjects ( group A) for assessing interday reproducibility and 8 healthy subjects ( group B) for exploring the relationship between plantar-flexion load and induced muscle perfusion. In a pilot group of five elderly healthy subjects and five patients with PAD ( group C), we proposed a protocol that measured perfusion for a low-intensity exercise and for an exhaustion exercise in a single MRI session. In group A, perfusion estimates for calf muscles were highly reproducible, with correlation coefficients of 0.90–0.93. In group B, gastrocnemius perfusion increased linearly with the exercise workload ( P < 0.05). With the low-intensity exercise, patients with PAD in group C showed substantially lower gastrocnemius perfusion compared with elderly healthy subjects [43.4 (SD 23.5) vs. 106.7 (SD 73.2) ml·min−1·100 g−1]. With exhaustion exercise, G/S [1.0 (SD 0.4)] for patients with PAD was lower than both its low-intensity level [1.9 (SD 1.3)] and the level in elderly healthy subjects [2.7 (SD 2.1)]. In conclusion, the proposed MRI protocol and the new metrics are feasible for quantifying exercise-induced muscle hyperemia, a promising functional test of PAD.

NEW & NOTEWORTHY To quantitatively map exercise-induced hyperemia in calf muscles, we proposed a high-resolution MRI method shown to be highly reproducible and sensitive to exercise load. With the use of low contrast, it is feasible to measure calf muscle hyperemia for both low-intensity and exhaustion exercises in a single MRI session. The newly proposed metrics for interpreting perfusion maps are promising for quantifying intermuscle vascular redistribution or a muscle’s active hyperemia.
T-cell–Secreted TNFα Induces Emergency Myelopoiesis and Myeloid-Derived Suppressor Cell Differentiation in Cancer
Authors: Al Sayed Mohamad F. , Amrein Michael A. , Bührer Elias D. , Huguenin Anne-Laure , Radpour Ramin , Riether Carsten , Ochsenbein Adrian F.
Published: November 2018

Hematopoiesis in patients with cancer is characterized by reduced production of red blood cells and an increase in myelopoiesis, which contributes to the immunosuppressive environment in cancer. Some tumors produce growth factors that directly stimulate myelopoiesis such as G-CSF or GM-CSF. However, for a majority of tumors that do not directly secrete hematopoietic growth factors, the mechanisms involved in the activation of myelopoiesis are poorly characterized. In this study, we document in different murine tumor models activated hematopoiesis with increased proliferation of long-term and short-term hematopoietic stem cells and myeloid progenitor cells. As a consequence, the frequency of myeloid-derived suppressor cells and its ratio to CD8+ T cells increased in tumor-bearing mice. Activation of hematopoiesis and myeloid differentiation in tumor-bearing mice was induced by TNFα, which was mainly secreted by activated CD4+ T cells. Therefore, the activated adaptive immune system in cancer induces emergency myelopoiesis and immunosuppression.

Significance:

These findings characterize a regulatory circuit linking activated T cells to suppression of tumor-specific immune responses, providing a conceptual advance in the understanding of emergency-hematopoiesis in cancer and opening new targets for therapeutic approaches.
Loss of TRIM29 Alters Keratin Distribution to Promote Cell Invasion in Squamous Cell Carcinoma
Authors: Yanagi Teruki , Watanabe Masashi , Hata Hiroo , Kitamura Shinya , Imafuku Keisuke , Yanagi Hiroko , Homma Akihiro , Wang Lei , Takahashi Hidehisa , Shimizu Hiroshi , Hatakeyama Shigetsugu
Published: November 2018

TRIM29 (tripartite motif-containing protein 29) is a TRIM family protein that has been implicated in breast, colorectal, and pancreatic cancers. However, its role in stratified squamous epithelial cells and tumors has not been elucidated. Here, we investigate the expression of TRIM29 in cutaneous head and neck squamous cell carcinomas (SCC) and its functions in the tumorigenesis of such cancers. TRIM29 expression was lower in malignant SCC lesions than in adjacent normal epithelial tissue or benign tumors. Lower expression of TRIM29 was associated with higher SCC invasiveness. Primary tumors of cutaneous SCC showed aberrant hypermethylation of TRIM29. Depletion of TRIM29 increased cancer cell migration and invasion; conversely, overexpression of TRIM29 suppressed these. Comprehensive proteomics and immunoprecipitation analyses identified keratins and keratin-interacting protein FAM83H as TRIM29 interactors. Knockdown of TRIM29 led to ectopic keratin localization of keratinocytes. In primary tumors, lower TRIM29 expression correlated with the altered expression of keratins. Our findings reveal an unexpected role for TRIM29 in regulating the distribution of keratins, as well as in the migration and invasion of SCC. They also suggest that the TRIM29–keratin axis could serve as a diagnostic and prognostic marker in stratified epithelial tumors and may provide a target for SCC therapeutics.

Significance:

These findings identify TRIM29 as a novel diagnostic and prognostic marker in stratified epithelial tissues.
Adipokines Deregulate Cellular Communication via Epigenetic Repression of Gap Junction Loci in Obese Endometrial Cancer
Authors: Polusani Srikanth R. , Huang Yi-Wen , Huang Guangcun , Chen Chun-Wei , Wang Chiou-Miin , Lin Li-Ling , Osmulski Pawel , Lucio Nicholas D. , Liu Lu , Hsu Ya-Ting , Zhou Yufan , Lin Chun-Lin , Aguilera-Barrantes Irene , Valente Philip T. , Kost Edward R. , Chen Chun-Liang , Shim Eun Yong , Lee Sang Eun , Ruan Jianhua , Gaczynska Maria E. , Yan Pearlly , Goodfellow Paul J. , Mutch David G. , Jin Victor X. , Nicholson Bruce J. , Huang Tim H.-M. , Kirma Nameer B.
Published: November 2018

Emerging evidence indicates that adipose stromal cells (ASC) are recruited to enhance cancer development. In this study, we examined the role these adipocyte progenitors play relating to intercellular communication in obesity-associated endometrial cancer. This is particularly relevant given that gap junctions have been implicated in tumor suppression. Examining the effects of ASCs on the transcriptome of endometrial epithelial cells (EEC) in an in vitro coculture system revealed transcriptional repression of GJA1 (encoding the gap junction protein Cx43) and other genes related to intercellular communication. This repression was recapitulated in an obesity mouse model of endometrial cancer. Furthermore, inhibition of plasminogen activator inhibitor 1 (PAI-1), which was the most abundant ASC adipokine, led to reversal of cellular distribution associated with the GJA1 repression profile, suggesting that PAI-1 may mediate actions of ASC on transcriptional regulation in EEC. In an endometrial cancer cohort (n = 141), DNA hypermethylation of GJA1 and related loci TJP2 and PRKCA was observed in primary endometrial endometrioid tumors and was associated with obesity. Pharmacologic reversal of DNA methylation enhanced gap-junction intercellular communication and cell–cell interactions in vitro. Restoring Cx43 expression in endometrial cancer cells reduced cellular migration; conversely, depletion of Cx43 increased cell migration in immortalized normal EEC. Our data suggest that persistent repression by ASC adipokines leads to promoter hypermethylation of GJA1 and related genes in the endometrium, triggering long-term silencing of these loci in endometrial tumors of obese patients.

Significance:

Studies reveal that adipose-derived stem cells in endometrial cancer pathogenesis influence epigenetic repression of gap junction loci, which suggests targeting of gap junction activity as a preventive strategy for obesity-associated endometrial cancer.
VCAM-1–targeted MRI Enables Detection of Brain Micrometastases from Different Primary Tumors
Authors: Cheng Vinton W.T. , Soto Manuel Sarmiento , Khrapitchev Alexandre A. , Perez-Balderas Francisco , Zakaria Rasheed , Jenkinson Michael D. , Middleton Mark R. , Sibson Nicola R.
Published: November 2018

Purpose:

A major issue for the effective treatment of brain metastasis is the late stage of diagnosis with existing clinical tools. The aim of this study was to evaluate the potential of vascular cell adhesion molecule 1 (VCAM-1)-targeted MRI for early detection of brain micrometastases in mouse models across multiple primary tumor types.

Experimental Design: Xenograft models of brain micrometastasis for human breast carcinoma (MDA231Br-GFP), lung adenocarcinoma (SEBTA-001), and melanoma (H1_DL2) were established via intracardiac injection in mice. Animals (n = 5–6/group) were injected intravenously with VCAM-1–targeted microparticles of iron oxide (VCAM-MPIO) and, subsequently, underwent T2*-weighted MRI. Control groups of naïve mice injected with VCAM-MPIO and tumor-bearing mice injected with nontargeting IgG-MPIO were included.

Results:

All models showed disseminated micrometastases in the brain, together with endothelial VCAM-1 upregulation across the time course. T2*-weighted MRI of all tumor-bearing mice injected with VCAM-MPIO showed significantly more signal hypointensities (P < 0.001; two-sided) than control cohorts, despite a lack of blood–brain barrier (BBB) impairment. Specific MPIO binding to VCAM-1–positive tumor-associated vessels was confirmed histologically. VCAM-1 expression was demonstrated in human brain metastasis samples, across all three primary tumor types.

Conclusions:

VCAM-1–targeted MRI enables the detection of brain micrometastases from the three primary tumor types known to cause the majority of clinical cases. These findings represent an important step forward in the development of a broadly applicable and clinically relevant imaging technique for early diagnosis of brain metastasis, with significant implications for improved patient survival.
Posterior Vitreous Detachment and the Associated Risk of Retinal Toxicity with Intravitreal Melphalan Treatment for Retinoblastoma
Authors: Berry Jesse L. , Lee Ramon , Patel Luv , Le Bao Han A. , O’Fee John , Jubran Rima , Kim Jonathan W.
Published: November 2018

Background/Aims: The presence of a posterior vitreous detachment (PVD) may play a role in the development of severe retinal toxicity following intravitreal melphalan (IVM) injection for vitreous seeding. We aimed to evaluate the incidence of PVD in retinoblastoma eyes and its association with retinal toxicity after IVM. Methods: We reviewed 112 eyes of 81 retinoblastoma patients with B-scan images available for review from 2010 to 2017. A cohort with vitreous seeding treated with IVM was compared to a cohort that did not undergo injection. The primary outcome measure was the presence of PVD at diagnosis and after treatment. Secondary measures included IVM-associated retinal toxicity and other ocular complications. Results: The incidence of PVD was 20% at diagnosis, and in eyes with B-scans available both at diagnosis and after treatment 18% of eyes developed a PVD over the course of therapy, more frequently after IVM (p = 0.05). Of 34 eyes receiving IVM treatment, the incidences of posterior segment toxicity and globe salvage were similar between eyes with and without PVD (p = 0.4015 and 0.52, respectively). Conclusion: In this cohort of patients, there did not appear to be an association with the presence of PVD during IVM and the development of retinal toxicity.
NFAT5 Has a Job in the Brain
Authors: Yang Xing-Liang , Wang Xin , Peng Bi-Wen
Published: November 2018

Nuclear factor of activated T cells 5 (NFAT5) has recently been classified as a new member of the Rel family. In addition, there are 5 more well-defined members (NF-κB and NFAT1–4) in the Rel family, which participate in regulating the expression of immune and inflammatory response-related genes. NFAT5 was initially identified in renal medullary cells where it regulated the expression of osmoprotective-related genes during the osmotic response. Many studies have demonstrated that NFAT5 is highly expressed in the nuclei of neurons in fetal and adult brains. Additionally, its expression is approximately 10-fold higher in fetal brains. With the development of detection technologies (laser scanning confocal microscopy, transgene technology, etc.), recent studies suggest that NFAT5 is also expressed in glial cells and plays a more diverse functional role. This article aims to summarize the current knowledge regarding the expression of NFAT5, its regulation of activation, and varied biological functions in the brain.
Patient Satisfaction and Clinical Outcomes with Budesonide plus Formoterol Spiromax for Asthma and Chronic Obstructive Pulmonary Disease: A Real-World, Observational Trial
Authors: Gillissen Adrian , Gessner Christian , Hechenbichler Klaus , Herth Felix J.F. , Juenemann Ralf , Kanniess Frank , Kardos Peter , Lommatzsch Marek , Schneidereit Regina , Windisch Wolfram
Published: November 2018

Background: The fixed-dose combination of budesonide/formoterol (B/F) has been available in the Spiromax® dry powder inhaler since 2014. Objectives: To assess patient satisfaction, inhaler use errors, and disease control in patients with asthma or chronic obstructive pulmonary disease (COPD) treated with B/F Spiromax. Methods: This non-interventional, prospective, 12-week study enrolled consecutive asthma or COPD patients who had recently begun treatment with B/F Spiromax or were switched from another inhaled corticosteroid/long-acting β2-agonist combination to B/F Spiromax in routine clinical practice. Patients recruited from 243 specialist respiratory clinics or general practices in Germany were assessed for patient satisfaction (Satisfaction with Inhalers and Preference questionnaire), inhaler application errors (modified Easy Low Instruction over Time checklist), disease control, and safety. Results: The population included 3,943 patients: asthma n = 2,707 (68.7%); COPD n = 1,236 (31.3%). At baseline, 60.1% of patients were “satisfied” or “very satisfied” with their previous inhaler, and this increased to 88.8% at week 12 of B/F Spiromax use. Overall, 62.1% of pre-treated patients preferred B/F Spiromax to their old inhaler. The frequency of any handling error observed with B/F Spiromax at week 12 was lower than at baseline (11.9 vs. 25.5% of patients, respectively). After 12 weeks, 77.4% were assessed as having improved (minimally, much, or very much) overall health status versus baseline. Guideline-defined disease severity (as rated by physicians) and patient-reported symptom severity improved during the study in both asthma and COPD patients. B/F Spiromax was well tolerated. Conclusion: B/F Spiromax was associated with high patient satisfaction, low device handling error rate, and improvements in clinical outcomes in real-world clinical practice.
Gonaphodioides zempoaltepetlensis (Coleoptera: Scarabaeidae: Aphodiinae), a new species from Oaxaca, Mexico
Authors: DELLACASA MARCO , DELLACASA GIOVANNI , ARRIAGA-JIMÉNEZ ALFONSINA
Published: November 2018

The genus Gonaphodioides Dellacasa, Dellacasa, & Gordon, 2012 (Coleoptera: Scarabaeidae: Aphodiinae: Aphodiini) was created for seven species distributed in Mesoamerica and South America. Subsequently, G. cartwrighti Dellacasa, Dellacasa, & Gordon, 2013 was described from El Salvador (Dellacasa et al. 2013).
Combined Use of Multiple Drought Indices for Global Assessment of Dry Gets Drier and Wet Gets Wetter Paradigm
Authors: Yang Tao , Ding Jinzhi , Liu Dan , Wang Xiaoyi , Wang Tao
Published: November 2018

Global warming is expected to enhance the global hydrological cycle, leading dry regions to become drier and wet regions to become wetter (the DDWW paradigm). However, this hypothesis has been challenged by both observational and modeling studies. One major source of these disagreements originates from the choice of the drought indices used. Hydrological processes are complex, but drought indices are often based on a relatively simple calculation. A single index may, therefore, place undue emphasis on particular processes while ignoring others, with the result that it would not capture the holistic picture of hydrological changes and may even lead to an incorrect interpretation. Six common drought indices were calculated for the global vegetated land areas for the period from 1982 to 2012 and different indices tend to create apparently contradictory results for many regions. To overcome the single-index problem, the six drought indices were integrated into a composite map of global land moisture trends. By using this integrated approach, the majority (55%) of vegetated land areas experienced wetting or drying trends. For the regions with significant changes, supporting evidence was identified for the DDWW paradigm in one-fifth of the area. The opposite pattern to DDWW (dry areas becoming wetter and wet areas drier) occurred over 29% of the area. We also find an asymmetrical pattern with a larger proportion of wet areas getting wetter (12%) than dry areas getting drier (8%). The DDWW theory is more useful when the pure precipitation-driven drought metrics are considered but when evapotranspiration and soil conditions are integrated, the DDWW is not conclusive.
It’s Only Wrong If It’s Transactional: Moral Perceptions of Obfuscated Exchange
Authors: Schilke Oliver , Rossman Gabriel
Published: November 2018

A wide class of economic exchanges, such as bribery and compensated adoption, are considered morally disreputable precisely because they are seen as economic exchanges. However, parties to these exchanges can structurally obfuscate them by arranging the transfers so as to obscure that a disreputable exchange is occurring at all. In this article, we propose that four obfuscation structures—bundling, brokerage, gift exchange, and pawning—will decrease the moral opprobrium of external audiences by (1) masking intentionality, (2) reducing the explicitness of the reciprocity, and (3) making the exchange appear to be a type of common practice. We report the results from four experiments assessing participants’ moral reactions to scenarios that describe either an appropriate exchange, a quid pro quo disreputable exchange, or various forms of obfuscated exchange. In support of our hypotheses, results show that structural obfuscation effectively mitigates audiences’ moral offense at disreputable exchanges and that the effects are substantially mediated by perceived attributional opacity, transactionalism, and collective validity.