bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of a Structural Element in HIV-1 Gag Required for Virus Particle Assembly and Maturation
Authors: Novikova Mariia , Adams Lucas J. , Fontana Juan , Gres Anna T. , Balasubramaniam Muthukumar , Winkler Dennis C. , Kudchodkar Sagar B. , Soheilian Ferri , Sarafianos Stefan G. , Steven Alasdair C. , Freed Eric O.
Published: October 2018

Capsid (CA) plays multiple roles in the HIV-1 replication cycle. CA-CA domain interactions are responsible for multimerization of the Gag polyprotein at virus assembly sites, and in the mature virion, CA monomers assemble into a conical core that encapsidates the viral RNA genome. Multiple CA regions that contribute to the assembly and release of HIV-1 particles have been mapped and investigated. Here, we identified and characterized a Pro-rich loop in CA that is important for the formation of the immature Gag lattice. Changes in this region disrupt viral production and abrogate the formation of infectious, mature virions. Propagation of the mutants in culture led to the selection of second-site compensatory mutations within CA. These results expand our knowledge of the assembly and maturation steps in the viral replication cycle and may be relevant for development of antiviral drugs targeting CA.
Newly diagnosed type 2 diabetes in an ethnic minority population: clinical presentation and comparison to other populations
Authors: Morkos Michael , Tahsin Bettina , Fogg Louis , Fogelfeld Leon
Published: October 2018

Objective

To characterize the clinical presentation of newly diagnosed type 2 diabetes of ethnic minority adults in Chicago and compare with other populations.

Research design and methods

Cross-sectional study examining the data of 2280 patients newly diagnosed with type 2 diabetes treated between 2003 and 2013 in a large Chicago public healthcare system.

Results

Mean age of the patients was 49±11.3 years, men 54.4%, African-Americans 48.1%, Hispanics 32.5%, unemployed 69.9%, uninsured 82.2%, English-speaking 75.1%, and body mass index was 32.8±7.4 kg/m2. Microvascular complications were present in 50.1% and macrovascular complications in 13.4%. There was a presence of either macrovascular or microvascular complications correlated with older age, hypertension, dyslipidemia, inactivity, speaking English, and being insured (p<0.01). Glycosylated hemoglobin A1c(HbA1c) at presentation did not correlate with diabetes complications. In our cohort, when compared with a diverse population in the UK and insured population in the USA, HbA1cat presentation was 10.0% (86 mmol/mol), 6.6% (49 mmol/mol), and 8.2% (66 mmol/mol); nephropathy was 22.2%, 16.7%, and 5.7%; retinopathy was 10.7%, 7.9%, and 1.4%; and neuropathy was 27.7%, and 6.7% in the UK (p<0.001). There were no significant differences between groups in the prevalence of macrovascular complications.

Conclusion

These results show the vulnerability of underserved and underinsured patients for developing diabetes complications possibly related to a delayed diagnosis.
Does extending the duration of legislated paid maternity leave improve breastfeeding practices? Evidence from 38 low-income and middle-income countries
Authors: Chai Yan , Nandi Arijit , Heymann Jody
Published: October 2018

Introduction

Among all barriers to breastfeeding, the need to work has been cited as one of the top reasons for not breastfeeding overall and for early weaning among mothers who seek to breastfeed. We aimed to examine whether extending the duration of paid maternity leave available to new mothers affected early initiation of breastfeeding, exclusive breastfeeding under 6  months and breastfeeding duration in low-income and middle-income countries (LMICs).

Methods

We merged longitudinal data measuring national maternity leave policies with information on breastfeeding related to 992 419 live births occurring between 1996 and 2014 in 38 LMICs that participated in the Demographic and Health Surveys. We used a difference-in-differences approach to compare changes in the prevalence of early initiation and exclusive breastfeeding, as well as the duration of breastfeeding, among treated countries that lengthened their paid maternity leave policy between 1995 and 2013 versus control countries that did not. Regression models included country and year fixed effects, as well as measured individual-level, household-level and country-level covariates. All models incorporated robust SEs and respondent-level sampling weights.

Results

A 1-month increase in the legislated duration of paid maternity leave was associated with a 7.4 percentage point increase (95%  CI 3.2 to 11.7) in the prevalence of early initiation of breastfeeding, a 5.9 percentage point increase (95%  CI 2.0 to 9.8) in the prevalence of exclusive breastfeeding and a 2.2- month increase (95%  CI 1.1 to 3.4) in breastfeeding duration.

Conclusion

Extending the duration of legislated paid maternity leave appears to promote breastfeeding practices in LMICs. Our findings suggest a potential mechanism to reduce barriers to breastfeeding for working mothers.
Familial clustering of bicuspid aortic valve and its relationship with aortic dilation in first-degree relatives
Authors: Galian-Gay Laura , Carro Hevia Amelia , Teixido-Turà Gisela , Rodríguez Palomares José , Gutiérrez-Moreno Laura , Maldonado Giuliana , Gonzàlez-Alujas María Teresa , Sao-Aviles Augusto , Gallego Pastora , Calvo-Iglesias Francisco , Bermejo Javier , Robledo-Carmona Juan , Sánchez Violeta , Saura Daniel , Sevilla Teresa , Burillo-Sanz Sergio , Guala Andrea , Garcia-Dorado David , Evangelista Arturo
Published: October 2018

Objective

Bicuspid aortic valve (BAV) is the most common congenital heart disease. This study aimed to determine the prevalence rate of BAV in first-degree relatives (FDR) and the inheritance pattern according to different morphotypes and aortic dilation.

Methods

BAV probands were consecutively studied at eight tertiary referral centres. After sequential screening, FDR were included in the study. The BAV morphotype, aortic dilation and aortic phenotype were assessed by transthoracic echocardiography.

Results

Seven hundred and twenty-four FDR of 256 BAV probands agreed to undergo family screening. The prevalence of BAV was 6.4% in FDR (9.2% in men, 3.5% in women, p=0.002). Aortic dilation was diagnosed in 9.6% of FRD with tricuspid aortic valves (TAV), with a root phenotype in 2.7% and tubular in 6.9% and more frequently in the presence of arterial hypertension (OR 4.48; CI 95% 2.51 to 7.99; p=0.0001) and valvular regurgitation (OR 5.87, CI 95% 1.37 to 25.16; p=0.025). The heritability (h2) of BAV was highly significant (0.47; p=0.002); however, no concordance was observed among valve morphotypes. Aortic dilation heritability was not significant.

Conclusions

The BAV prevalence rate in FDR was low (6.4%) but aortic dilation was observed in 9.6% of FDR with TAV. The heritability of BAV was high without concordance in valve morphotypes, and aortic dilation heritability was not observed. Patients with BAV should be made aware of its familial pattern.
Challenges for assessing vertebrate diversity in turbid Saharan water-bodies using environmental DNA
Authors: Egeter Bastian , Peixoto Sara , Brito José C. , Jarman Simon , Puppo Pamela , Velo-Antón Guillermo
Published: October 2018

The Sahara desert is the largest warm desert in the world and a poorly explored area. Small water-bodies occur across the desert and are crucial habitats for vertebrate biodiversity. Environmental DNA (eDNA) is a powerful tool for species detection and is being increasingly used to conduct biodiversity assessments. However, there are a number of difficulties with sampling eDNA from such turbid water-bodies and it is often not feasible to rely on electrical tools in remote desert environments. We trialled a manually powered filtering method in Mauritania, using pre-filtration to circumvent problems posed by turbid water in remote arid areas. From nine vertebrate species expected in the water-bodies, four were detected visually, two via metabarcoding, and one via both methods. Difficulties filtering turbid water led to severe constraints, limiting the sampling protocol to only one sampling point per study site, which alone may largely explain why many of the expected vertebrate species were not detected. The amplification of human DNA using general vertebrate primers is also likely to have contributed to the low number of taxa identified. Here we highlight a number of challenges that need to be overcome to successfully conduct metabarcoding eDNA studies for vertebrates in desert environments in Africa.
Complexity and fractal dimensions for infinite sequences with positive entropy
Authors: Mauduit Christian , Moreira Carlos Gustavo
Published: October 2018

The complexity function of an infinite word [Formula: see text] on a finite alphabet [Formula: see text] is the sequence counting, for each non-negative [Formula: see text], the number of words of length [Formula: see text] on the alphabet [Formula: see text] that are factors of the infinite word [Formula: see text]. The goal of this work is to estimate the number of words of length [Formula: see text] on the alphabet [Formula: see text] that are factors of an infinite word [Formula: see text] with a complexity function bounded by a given function [Formula: see text] with exponential growth and to describe the combinatorial structure of such sets of infinite words. We introduce a real parameter, the word entropy [Formula: see text] associated to a given function [Formula: see text] and we determine the fractal dimensions of sets of infinite sequences with complexity function bounded by [Formula: see text] in terms of its word entropy. We present a combinatorial proof of the fact that [Formula: see text] is equal to the topological entropy of the subshift of infinite words whose complexity is bounded by [Formula: see text] and we give several examples showing that even under strong conditions on [Formula: see text], the word entropy [Formula: see text] can be strictly smaller than the limiting lower exponential growth rate of [Formula: see text].
A generalized pseudorelativistic Schrödinger equation with supercritical growth
Authors: Secchi Simone
Published: October 2018

We prove that the generalized pseudorelativistic equation [Formula: see text] can be solved for large values of the “light speed” [Formula: see text] even when [Formula: see text] crosses the critical value for the fractional Sobolev embedding.
Combining Losing Games into a Winning Game
Authors: Rémillard Bruno , Vaillancourt Jean
Published: October 2018

Parrondo’s paradox is extended to regime switching random walks in random environments. The paradoxical behavior of the resulting random walk is explained by the effect of the random environment. Full characterization of the asymptotic behavior is achieved in terms of the dimensions of some random subspaces occurring in Oseledec’s theorem. The regime switching mechanism gives our models a richer and more complex asymptotic behavior than the simple random walks in random environments appearing in the literature, in terms of transience and recurrence.
On the structure of modules defined by subinjectivity
Authors: Altinay Ferhat , Büyükaşık Engı̇n , Durg̃un Yılmaz
Published: October 2018

The aim of this paper is to present new results and generalize some results about indigent modules. The commutative rings whose simple modules are indigent or injective are fully determined. The rings whose cyclic right modules are indigent are shown to be semisimple Artinian. We give a complete characterization of indigent modules over commutative hereditary Noetherian rings. We show that a reduced module is indigent if and only if it is a Whitehead test module for injectivity over commutative hereditary noetherian rings. Furthermore, Dedekind domains are characterized by test modules for injectivity by subinjectivity.
Micromechanical Studies of Strain Rate Dependent Compressive Strength in Brittle Polycrystalline Materials
Authors: Jiang Hao , Fan Zongyue , Lu Jian , Li Bo
Published: October 2018

We propose a novel computational model for the high fidelity prediction of failure mechanisms in brittle polycrystalline materials. A three-dimensional finite element model of the polycrystalline structure is reconstructed to explicitly account for the micro-features such as grain sizes, grain orientations, and grain boundary misorientations. Grain boundaries are explicitly represented by a thin layer of elements with non-zero misorientation angles. In addition, the Eigen-fracture algorithm is employed to predict the crack nucleation and propagation in the grain structure. In the framework of variational fracture mechanics, an equivalent energy release rate is defined at each finite element to evaluate the local failure state by comparing to the critical energy release rate, which varies at the grain boundaries and the interior of grains. Moreover, constitutive models are considered as functions of the local microstructure features. As a result, a direct mesoscale simulation model is developed to resolve the anisotropic response, intergranular and transgranular fractures during the microstructure evolution of brittle materials under general loading conditions. A micromechanics-based interpretation for the rate dependent strength of brittle materials is derived and verified in examples of dynamic compression tests. In specific, the compressive dynamic response of hexagonal SiC with equiaxed grain structures is studied under different strain rates.
Holographic dark energy model in unimodular f(T) gravity
Authors: Godonou A. E. , Houndjo M. J. S. , Tossa J.
Published: October 2018

This work deals with holographic dark energy in the context of unimodular [Formula: see text] gravity, which is a modification of teleparallel gravity. We develop the general reconstruction procedure of the [Formula: see text] form that can yield the holographic feature of the dark energy. We fit the reconstructed model with the [Formula: see text] data and our results show a perfect agreement with the WMAP9 cosmological observational data, at least for the range [Formula: see text]. We investigate the consistency of the reconstructed model by studying its stability against linear gravitational and matter perturbations, fixing [Formula: see text] to [Formula: see text]. The model presents stability for both de Sitter and power-law solutions and we conclude that it is a good candidate as alternative viable model for characterizing holographic dark energy.
Callias-type operators in C∗-algebras and positive scalar curvature on noncompact manifolds
Authors: Cecchini Simone
Published: October 2018

A Dirac-type operator on a complete Riemannian manifold is of Callias-type if its square is a Schrödinger-type operator with a potential uniformly positive outside of a compact set. We develop the theory of Callias-type operators twisted with Hilbert [Formula: see text]-module bundles and prove an index theorem for such operators. As an application, we derive an obstruction to the existence of complete Riemannian metrics of positive scalar curvature on noncompact spin manifolds in terms of closed submanifolds of codimension one. In particular, when [Formula: see text] is a closed spin manifold, we show that if the cylinder [Formula: see text] carries a complete metric of positive scalar curvature, then the (complex) Rosenberg index on [Formula: see text] must vanish.
GPlace3.0
Authors: Abuowaimer Ziad , Maarouf Dani , Martin Timothy , Foxcroft Jeremy , Gréwal Gary , Areibi Shawki , Vannelli Anthony
Published: October 2018

Optimizing for routability during FPGA placement is becoming increasingly important, as failure to spread and resolve congestion hotspots throughout the chip, especially in the case of large designs, may result in placements that either cannot be routed or that require the router to work excessively hard to obtain success. In this article, we introduce a new, analytic routability-aware placement algorithm for Xilinx UltraScale FPGA architectures. The proposed algorithm, called GPlace3.0, seeks to optimize both wirelength and routability. Our work contains several unique features including a novel window-based procedure for satisfying legality constraints in lieu of packing, an accurate congestion estimation method based on modifications to the pathfinder global router, and a novel detailed placement algorithm that optimizes both wirelength and external pin count. Experimental results show that compared to the top three winners at the recent ISPD’16 FPGA placement contest, GPlace3.0 is able to achieve (on average) a 7.53%, 15.15%, and 33.50% reduction in routed wirelength, respectively, while requiring less overall runtime. As well, an additional 360 benchmarks were provided directly from Xilinx Inc. These benchmarks were used to compare GPlace3.0 to the most recently improved versions of the first- and second-place contest winners. Subsequent experimental results show that GPlace3.0 is able to outperform the improved placers in a variety of areas including number of best solutions found, fewest number of benchmarks that cannot be routed, runtime required to perform placement, and runtime required to perform routing.
Adaptive information distribution for dynamic sets using multicast push and pull
Authors: Prellwitz Matthias , Parzyjegla Helge , Mühl Gero
Published: October 2018

When developing applications in the area of ubiquitous computing, the developer often does not know at design time which and how many devices will be available at runtime when the user deploys the application in his personal environment. To tackle this problem, we proposed a new programming abstraction called
dynamic sets
in previous work. A dynamic set allows an application to interact transparently with a set of remote objects in the same way it interacts with a single object. The developer programs against a proxy that replicates the calls to the objects and aggregates the return values. While dynamic sets make application development easier and more flexible, efficiency problems can arise when an application is calling proxy methods with high frequency as if the object was local (since the calls are replicated to all members of the dynamic set).

In this paper, we propose adaptive heuristics that tackle this problem for getter methods returning information about the objects' state. The heuristics use unicast and multicast communication and dynamically switch between pull (application requests update from object) and push (object sends update to application) depending on the getter rates of applications and the setter rates of objects to optimize communication costs. After describing the basic interaction patterns and presenting the details of our heuristics, we present the results of a comprehensive evaluation based on discrete event simulations. The results show that our heuristics effectively reduce communication costs although they operate on the application layer and, thus, have no detailed knowledge about the physical network topology.
Role of the Soluble Receptor for Advanced Glycation End Products (sRAGE) as a Prognostic Factor for Mortality in Hemodialysis and Peritoneal Dialysis Patients
Authors: Dozio Elena , Ambrogi Federico , de Cal Massimo , Vianello Elena , Ronco Claudio , Corsi Romanelli Massimiliano M.
Published: October 2018

End-stage renal disease patients on dialysis (CKD-G5D) have a high mortality rate due to cardiovascular diseases (CVD). In these patients, inflammation, oxidative stress, and uremia increase the production of glycation products (AGEs) which in turn accelerate CVD onset and progression. Recently, attention has been given to the soluble receptor for AGEs (sRAGE) as a marker of inflammation, oxidative stress, atherosclerosis, and heart failure in CKD-G5D. However, its association with patient outcomes is still under debate. Our aim is to explore whether sRAGE may be a predictor of mortality in CKD-G5D. We studied 123 CKD-G5D for 24 months. Of these patients, 56 were on hemodialysis (HD) and 67 on peritoneal dialysis (PD). Demographic, anthropometric, biochemical, and clinical data were recorded. sRAGE was quantified by enzyme-linked immunosorbent assay. sRAGE was a predictor of mortality at 2-year follow-up. Each increase of 100 pg/mL in sRAGE levels was associated with an approximately 7% increased risk of mortality. Furthermore, in the entire study group, as well as in PD and HD patient subgroups, sRAGE was positively correlated with brain natriuretic peptide (BNP) levels. Mortality rates as well as sRAGE levels in patients who died did not differ between PD and HD patients. In conclusion, the positive association observed with BNP levels suggests a role for sRAGE as a prognostic factor for mortality in CKD-G5D patients displaying an active process of cardiac remodeling.
A Data Dissemination Method Based on Region Type Correlations for Mobile Opportunistic Networks
Authors: Liu Linfeng , Chen Daoliang
Published: October 2018

In Mobile Opportunistic Networks (MONs), due to the node movements and the uncontrollable on/off switches of the carried communication devices, the contacts between nodes may be scarce and momentary, and thus a data packet should be transferred through some discrete hops. To avoid the costly flooding of data packets, the data packets are typically disseminated to some relay nodes selected by data holders. However, the mobility patterns of nodes will become different in different types of regions (such as residential regions, commercial regions, scenery regions, or industrial regions); i.e., the movement directions and movement ranges of nodes are frequently varied when the nodes move among various regions. At present, the issues regarding the region types and region type correlations have not been investigated for the data dissemination in existing works. To this end, we propose a Region Type based Data Dissemination Method (RTDDM) for MONs, which exploits the region type correlations and selects the proper relay nodes through a Markov decision model. To verify the performance of RTDDM, we give some theoretical analysis as well as an elaborated simulation study, the results of which show that RTDDM can improve the delivery ratio and reduce the delivery delay, especially in the applications with various region types.
Theoretical and Experimental Investigation of Direct Detection Optical OFDM Systems with Clipping and Normalization
Authors: Wu Jiang , Wang Zhongpeng
Published: October 2018

A data clipping and normalization technique is employed to improve the performance of the overall direct detection optical orthogonal frequency division multiplexing (DCO-OFDM) system. A detailed analysis of clipping distortion introduced by digital clipping and normalization is provided. The normalization operation amplifies the clipped data signal to the maximum input amplitude of a digital-to-analog converter (DAC). Based on the analysis, a BER formula of the proposed scheme is derived over the AWGN channel and single fiber channel. Performance of an optical clipped OFDM with normalization is assessed through numerical simulations and Monte Claro simulation over the AWGN channel. Theoretical analysis and simulation results both show that the clipping and normalization scheme can greatly improve the BER of an optical OFDM. In particular, BER performance of the proposed transmission scheme was measured in a practical OFDM transmission platform. The measured experimental results show that the clipped and amplified OFDM signal exhibits superior performance in comparison with the conventional OFDM signal. The received sensitivity at a BER of 10−3 for a 4 Gsamples/s (2.6667 Gbits/s) clipped and normalized OFDM signal with clipping ratio of 4 after 100 km standard single-mode fiber (SMF) transmission was improved by 4.3 dB when compared with the conventional OFDM system. The measured results also showed that the clipped OFDM signal exhibits superior performance in comparison with the conventional OFDM signal. Therefore, a clipping and normalization at the transmitter is most effective, and a substantial performance improvement can be obtained by a simple normalization after clipping.
Fuzzy Logic Tool to Forecast Soil Fertility in Nigeria
Authors: Ogunleye G. O. , Fashoto S. G. , Mashwama Petros , Arekete S. A. , Olaniyan O. M. , Omodunbi B. A.
Published: October 2018

The soil is composed of several nutrients which are important for the effective growth of plants. Nitrogen, phosphorus, and potassium are micronutrients which are very important for plant growth. There have been several methods and soil tests developed to test the compositions of these nutrients in the soil. Interpreting the results gotten from such tests has been a herculean task for farmers. Employing the use of a soft computing method to interpret such result would be a noble idea. In this paper, we describe the use of fuzzy logic to interpret the values of nitrogen, phosphorus, and potassium (NPK) gotten from conventional soil test to know their levels in the soil and predict possible NPK inputs.
Changes and Diurnal Variation of Visual Quality after Orthokeratology in Myopic Children
Authors: Guo Hao-Chen , Jin Wan-Qing , Pan An-Peng , Wang Qin-Mei , Qu Jia , Yu A-Yong
Published: October 2018

Purpose. To assess the changes and the diurnal variation of visual quality after orthokeratology in myopic children.Methods.Forty-four eyes of 22 subjects with a mean age of 10.55 ± 1.53 years (8 to 14 years) were enrolled in this prospective study. Their spherical equivalent ranged from −1.25 to −4.25 diopters (D) and astigmatism was less than 1.00 D. Parameters including corneal curvature, ocular objective scatter index (OSI), the modulation transfer function (MTF), root mean square of ocular and corneal wavefront aberrations, and contrast sensitivity function (CSF) were measured before and at two time points during the same day after 1 month of orthokeratology.Results. After orthokeratology, uncorrected visual acuity (UCVA) and spherical equivalent were significantly improved from baseline (P<0.001), and their diurnal variation was not significant (P=0.083,0.568). OSI increased from 0.29 ± 0.15 to 0.65 ± 0.31 (P<0.001). MTF decreased significantly (P<0.01). Corneal curvature and ocular total aberration decreased (P<0.001), while the ocular and corneal higher-order aberration increased significantly (P<0.01). The CSF under photopic condition decreased at 3 cpd (P=0.006) and increased at 18 cpd (P=0.012). The diurnal variation of CSF at 18 cpd under mesopic and high glare conditions and at 12 cpd under photopic condition was significant (P=0.002,0.01,0.017).Conclusions. Orthokeratology can effectively improve UCVA and high spatial frequency CSF by decreasing the low-order aberrations. However, MTF and CSF at low spatial frequency decreased because of the increase of intraocular scattering and high-order aberrations. Meanwhile, CSF at high spatial frequency fluctuates significantly at two times during the same day after 1 month orthokeratology.
A Comparison between the Implant Stability Quotient and the Fractal Dimension of Alveolar Bone at the Implant Site
Authors: Kulczyk Tomasz , Czajka-Jakubowska Agata , Przystańska Agnieszka
Published: October 2018

Objectives. Fractal analysis of the radiographic pattern of bone has been used to evaluate its quantitative properties. However, the relation between initial implant stability and quality of bone remains unclear. The objective of this study was to evaluate RFA values in relation to the fractal dimension of bone where the implant was inserted. Material and Methods. A total of 50 two-stage dental implants were placed in the maxilla and mandible of 32 patients. After implant placement, an implant stability quotient (ISQ) was measured in two perpendicular planes. On intraoral digital periapical radiographs, three 35x35 pixels’ regions of interest (ROIs) were chosen covering the bone adjacent to the neck (ROI 1), middle (ROI 2), and apical (ROI 3) part of the implant, respectively. For every ROI, a fractal dimension (FD) was calculated. A linear correlation, as well as a logistic regression analysis, was used to identify a possible relation between the ISQ and FD values for every ROI in the maxilla and mandible. Results. The ISQ and FD values were found to be correlated at ROI 1 for the maxilla. There was no linear correlation between ISQ and FD values in any of the three ROIs in the mandible. However, logistic regression analysis showed that in ROI 1 and ROI 3 the values of FD and ISQ are statistically important and may be used to express the difference between maxilla and mandible. Conclusion. The fractal dimension of alveolar bone measured from intraoral digital radiographs alone may be an insufficient parameter to determine initial implant stability.
Hyperkalemia Induced by the Sequential Administration of Metoprolol and Carvedilol
Authors: Barold S. Serge , Upton Scott
Published: October 2018

This report describes the occurrence of asymptomatic hyperkalemia induced by the sequential administration of metoprolol and carvedilol in an 81-year-old man with type II diabetes and stable stage III renal insufficiency. The potassium level rose to 5.6–5.7 mEq/L with metoprolol and normalized when the agent was discontinued. However, the potassium level rose again to 5.6 mEq/L after the administration of carvedilol but the level normalized by halving the dose. The observations of hyperkalemia induced by two different β-blocker drugs in the same patient confirm that this side effect is common to all β-blocker drugs.
Impact of Sleeve Gastrectomy on Psychiatric Medication Use and Symptoms
Authors: Monte Scott V. , Russo Kristen M. , Mustafa Esra , Caruana Joseph A.
Published: October 2018

Background. Sleeve gastrectomy (SG) has become the primary bariatric surgery procedure in the U.S. Over 50% of people presenting for surgery have psychiatric diagnoses. The study purpose was to evaluate change in anxiety and depression symptoms and medication use after SG. Methods. Subjects completing SG with a diagnosis of anxiety and/or depression treated with medication were retrospectively identified from the electronic medical record (EMR) of Synergy Bariatrics, a department of the Erie County Medical Center. Phone outreach was made to complete seven-point global impression of change scale classifying symptom improvement or worsening in the 3- to 6-month postoperative period. Improvement or worsening was defined as either all reported symptoms improving or worsening or ≥1 improving or worsening while remaining unchanged. If ≥1 symptom improved and worsened, it was classified as mixed. No change required the same profile before and after surgery. Medication, dose, and changes were identified by EMR, verified during interview and classified as no change, discontinued, decreased, or increased. Results. 59 subjects completed the interview. 21 subjects were diagnosed with anxiety. 13 (62%) had no change in therapy and 5 (24%) decreased. Symptoms improved in 12 (57%), worsened in 3 (14%), and mixed in 5 (24%). When symptoms improved, the same dose was present in 7/12 (58%) and dose decreased in 3 (25%). 51 subjects were diagnosed with depression. 32 (63%) had no change in therapy, 11 (21%) discontinued, and 4 (8%) decreased. Symptoms improved in 34 (67%), mixed in 10 (20%), worsened in 4 (8%), and unchanged in 3 (6%). When symptoms improved, the same regimen and dose was present in 21/34 cases (62%) and discontinued in 9 (26%). Conclusion. Anxiety symptoms improved in >50% of subjects at predominantly the same or reduced dosage. Depression symptoms improved in 67% and commonly without therapy change. These data suggest evidence that patients undergoing SG while on medication for anxiety or depression may have early symptom improvement on the same or lessened dosage.
Differences between Transdermal Fentanyl and Buprenorphine in the Elderly Hospice Patients
Authors: Golčić Marin , Dobrila-Dintinjana Renata , Golčić Goran , Gović-Golčić Lidija
Published: October 2018

Introduction. Opioids are the most important drugs in treating pain in palliative care patients. Transdermal formulations are especially useful due to their noninvasive nature and minimal interference in daily life. However, studies have shown a controversial relationship of opioids to survival and a rise in deaths associated with the use of transdermal opioids. Although applying precise doses is paramount, we have no clear recommendations for the exact equianalgesic ratio for buprenorphine patch and no recommendation for the type of transdermal opioid to use in hospice. Methods. We analyzed the differences between the transdermal fentanyl and buprenorphine group by analyzing patient characteristics and evaluating the differences in survival in hospice patients over the age of 65, from 2013 to 2017. Results. A total of 292 patients (75.8%) used fentanyl patch and 93 (24.1%) were on buprenorphine patch. Patients had virtually the same characteristics in both groups. However, when using a 1:100 buprenorphine equianalgesic ratio, there were significant differences in initial and final doses, and it seems that a 1:80 conversion rate is more accurate for elderly hospice patients. Finally, there was no difference in survival between the two groups using transdermal opioids, with or without adjuvant analgesics. Discussion. There were no differences in survival between the group using transdermal fentanyl and the group using buprenorphine in the elderly hospice population. Although adjuvant NSAIDs could be useful in the treatment of pain in terminal cancer, they do not affect survival or reduce the opioid doses, while a 1:80 equianalgesic ratio of buprenorphine might be the most appropriate in this population.
Circulating Glioma Cells Exhibit Stem Cell-like Properties
Authors: Liu Tianrun , Xu Haineng , Huang Menggui , Ma Wenjuan , Saxena Deeksha , Lustig Robert A. , Alonso-Basanta Michelle , Zhang Zhenfeng , O'Rourke Donald M. , Zhang Lin , Gong Yanqing , Kao Gary D. , Dorsey Jay F. , Fan Yi
Published: October 2018

Circulating tumor cells (CTC) are known to be present in the blood of patients with glioblastoma (GBM). Here we report that GBM-derived CTC possess a cancer stem cell (CSC)-like phenotype and contribute to local tumorigenesis and recurrence by the process of self-seeding. Genetic probes showed that mouse GBM-derived CTC exhibited Sox2/ETn transcriptional activation and expressed glioma CSC markers, consistent with robust expression of stemness-associated genes including SOX2, OCT4, and NANOG in human GBM patient-derived samples containing CTC. A transgenic mouse model demonstrated that CTC returned to the primary tumor and generated new tumors with enhanced tumorigenic capacity. These CTCs were resistant to radiotherapy and chemotherapy and to circulation stress-induced cell apoptosis. Single-cell RNA-seq analysis revealed that Wnt activation induced stemness and chemoresistance in CTC. Collectively, these findings identify GBM-derived CTC as CSC-like cells and suggest that targeting Wnt may offer therapeutic opportunities for eliminating these treatment-refractory cells in GBM.

Significance:

These findings identify CTCs as an alternative source for in situ tumor invasion and recurrence through local micrometastasis, warranting eradication of systemic "out-of-tumor" CTCs as a promising new therapeutic opportunity for GBM.
Monte Carlo Simulation of the Treatment of Uveal Melanoma Using Measured Heterogeneous 106Ru Plaques
Authors: Zaragoza Francisco J. , Eichmann Marion , Flühs Dirk , Wittig Andrea , Sauerwein Wolfgang , Brualla Lorenzo
Published: October 2018

Background/Aims: Ruthenium plaques are used for the treatment of ocular tumors. The aim of this work is the comparison between simulated absorbed dose distributions tallied in an anthropomorphic phantom, obtained from ideal homogeneous plaques, and real eye plaques in which the actual heterogeneous distribution of 106Ru was measured. The placement of the plaques with respect to the tumor location was taken into consideration to optimize the effectiveness of the treatment. Methods: The generic CCA and CCB, and the specific CCA1364 and CCB1256 106Ru eye plaques were modeled with the Monte Carlo code PENELOPE. To compare the suitability of each treatment for an anterior, equatorial and posterior tumor location, cumulative dose-volume histograms for the tumors and structures at risk were calculated. Results: Eccentric placements of the plaques, taking into account the inhomogeneities of the emitter map, can substantially reduce the dose delivered to structures at risk while maintaining the prescribed dose at the tumor apex. Conclusions: The emitter map distribution of the plaque and the computerized tomography of the patient used in a Monte Carlo simulation allow an accurate determination of the plaque position with respect to the tumor with the potential to reduce the dose to sensitive structures.
Comparison of Renal Function after Radical Surgery for Upper Tract Urothelial Carcinoma versus Renal Cell Carcinoma: Propensity Score Matching
Authors: Tae Bum Sik , Ku Ja Hyeon , Kwak Cheol , Kim Hyeon Hoe , Jeong Chang Wook
Published: October 2018

Objectives: To compare renal function after radical nephrectomy for renal cell carcinoma (RCC) and for upper tract urothelial carcinoma (UTUC). Method: Data from 1,236 patients with RCC or UTUC treated surgically from 2000 to 2013 were enrolled. The estimated glomerular filtration rate (eGFR) was calculated preoperatively and postoperatively at 12, 24, 36, 48, and 60 months. A multivariate logistic regression was used to determine independent factors for a decrease in eGFR to < 60 mL/min/1.73 m2 and end-stage renal disease. Result: After propensity score matching, a total of 554 patients were included. During follow-up for 5 years, there was statistically significant difference in eGFR between 2 groups. And there was a statistically significant difference in the number of patients developing impaired renal function between the 2 groups (UTUC 73.3 vs. RCC 66.1%, p = 0.039). Multivariate analysis showed that old age (OR 3.957, p < 0.001), UTUC (OR 1.838, p = 0.006), BMI (OR 2.463, p = 0.001) and a baseline eGFR (OR 0.976, p = 0.001) were independent risk factors for postoperative impaired renal function. Conclusion: Patients with UTUC had worse baseline eGFR, old age, comorbidities than RCC patients. Even after adjusting by PS matching, UTUC patients had lower postoperative eGFR and higher rates of CKD development than RCC patients.
Uterine Leiomyosarcoma
Authors: Juhasz-Böss Ingolf , Gabriel Lena , Bohle Rainer M. , Horn Lars C. , Solomayer Erich-Franz , Breitbach Georg-Peter
Published: October 2018

Uterine leiomyosarcoma (uLMS) is a rare entity among malignant gynecologic tumors with a very unfavorable prognosis and the highest prevalence in the pre- and peri-menopause. Only early-stage tumors have an acceptable prognosis, provided the patient has been treated without injuring the uterus. uLMS is often diagnosed accidentally and the correct diagnosis ishampered by equivocal features similar to the far more frequent benign uterine fibroids. Surgery is the basis of therapy, and it should be done in order to remove the uterus intact. As vaginal, abdominal, and endoscopic surgery - possibly including morcellation - are the methods of choice for the treatment of uterine fibroids, pre-operatively undiagnosed leiomyosarcoma detected by pathologic examination will have a worsened prognosis. Systemic treatment and radiotherapy are of no proven value in the adjuvant setting. Thus, there is strong need for a reliable pre-operative risk score for leiomyosarcoma in order to justify diagnostic means beyond clinical routine and to choose the correct surgical pathway. The clinical problems in the diagnosis of leiomyosarcoma and treatment are exemplified by a case report of a 30-year-old childless patient. Diagnostic tools as well as treatment options in adjuvant and palliative situations are reviewed.
Glutathione S-Transferases and Cytochrome P450 Enzyme Expression in Patients with Intracranial Tumors: Preliminary Report of 55 Patients
Authors: Kural Cahit , Kaya Kocdogan Arzu , Şimşek Gulcin Güler , Oğuztüzün Serpil , Kaygın Pınar , Yılmaz Irmak , Bayram Tugbag , Izci Yusuf
Published: October 2018

Objective: Intracranial tumors are one of the most frightening and difficult-to-treat tumor types. In addition to surgery, protocols such as chemotherapy and radiotherapy also take place in the treatment. Glutathione S-transferase (GST) and cytochrome P450 (CYP) enzymes are prominent drug-metabolizing enzymes in the human body. The aim of this study is to show the expression of GSTP1, GSTM1, CYP1A1, and CYP1B1 in different types of brain tumors and compare our results with those in the literature. Subjects and Methods: The expression of GSTP1, GSTM1, CYP1A1, and CYP1B1 was analyzed using immunostaining in 55 patients with intracranial tumors in 2016–2017. For GST and CYP expression in normal brain tissue, samples of a portion of surrounding normal brain tissue as well as a matched far neighbor of tumor tissue were used. The demographic features of the patients were documented and the expression results compared. Results: The mean age of the patients was 46.72 years; 29 patients were female and 26 were male. Fifty-seven specimens were obtained from 55 patients. Among them, meningioma was diagnosed in 12, metastases in 12, glioblastoma in 9, and pituitary adenoma in 5. The highest GSTP1, GSTM1, and CYP­1A1 expressions were observed in pituitary adenomas. The lowest GSTP1 expression was detected in glioblastomas and the lowest CYP1B1 expression in pituitary adenomas. Conclusion: GSTP1 and CYP expression is increased in intracranial tumors. These results should be confirmed with a larger series and different enzyme subtypes.
Differential Gene Expression in Macrophages From Human Atherosclerotic Plaques Shows Convergence on Pathways Implicated by Genome-Wide Association Study Risk Variants
Authors: Chai Joshua T. , Ruparelia Neil , Goel Anuj , Kyriakou Theodosios , Biasiolli Luca , Edgar Laurienne , Handa Ashok , Farrall Martin , Watkins Hugh , Choudhury Robin P.
Published: October 2018

Objective—

Plaque macrophages are intricately involved in atherogenesis and plaque destabilization. We sought to identify functional pathways in human plaque macrophages that are differentially regulated in respect of (1) plaque stability and (2) lipid content. We hypothesized that differentially regulated macrophage gene sets would relate to genome-wide association study variants associated with risk of acute complications of atherosclerosis.

Approach and Results—

Forty patients underwent carotid magnetic resonance imaging for lipid quantification before endarterectomy. Carotid plaque macrophages were procured by laser capture microdissection from (1) lipid core and (2) cap region, in 12 recently symptomatic and 12 asymptomatic carotid plaques. Applying gene set enrichment analysis, a number of gene sets were found to selectively upregulate in symptomatic plaque macrophages, which corresponded to 7 functional pathways: inflammation, lipid metabolism, hypoxic response, cell proliferation, apoptosis, antigen presentation, and cellular energetics. Predicted upstream regulators included
IL-1β
,
TNF-α
, and
NF-κB
. In vivo lipid quantification by magnetic resonance imaging correlated most strongly with the upregulation of genes of the
IFN
/
STAT1
pathways. Cross-interrogation of gene set enrichment analysis and meta-analysis gene set enrichment of variant associations showed lipid metabolism pathways, driven by genes coding for
APOE
and
ABCA1/G1
coincided with known risk-associated SNPs (single nucleotide polymorphisms) from genome-wide association studies.

Conclusions—

Macrophages from recently symptomatic carotid plaques show differential regulation of functional gene pathways. There were additional quantitative relationships between plaque lipid content and key gene sets. The data show a plausible mechanism by which known genome-wide association study risk variants for atherosclerotic complications could be linked to (1) a relevant cellular process, in (2) the key cell type of atherosclerosis, in (3) a human disease-relevant setting.
Endothelial Mitochondrial Preprotein Translocase Tomm7-Rac1 Signaling Axis Dominates Cerebrovascular Network Homeostasis
Authors: Shi Dan , Qi Man , Zhou Liping , Li Xiang , Ni Le , Li Changming , Yuan Tianyou , Wang Yunqian , Chen Yongli , Hu Chaoyue , Liang Dandan , Li Li , Liu Yi , Li Jun , Chen Yi-Han
Published: October 2018

Objective—

Mitochondria are the important yet most underutilized target for cardio-cerebrovascular function integrity and disorders. The Tom (translocases of outer membrane) complex are the critical determinant of mitochondrial homeostasis for making organs acclimate physiological and pathological insults; however, their roles in the vascular system remain unknown.

Approach and Results—

A combination of studies in the vascular-specific transgenic zebrafish and genetically engineered mice was conducted. Vascular casting and imaging, endothelial angiogenesis, and mitochondrial protein import were performed to dissect potential mechanisms. A loss-of-function genetic screening in zebrafish identified that selective inactivation of the
tomm7
(translocase of outer mitochondrial membrane 7) gene, which encodes a small subunit of the Tom complex, specially impaired cerebrovascular network formation. Ablation of the ortholog
Tomm7
in mice recapitulated cerebrovascular abnormalities. Restoration of the cerebrovascular anomaly by an endothelial-specific transgenesis of
tomm7
further indicated a defect in endothelial function. Mechanistically, Tomm7 deficit in endothelial cells induced an increased import of Rac1 (Ras-related C3 botulinum toxin substrate 1) protein into mitochondria and facilitated the mitochondrial Rac1-coupled redox signaling, which incurred angiogenic impairment that underlies cerebrovascular network malformation.

Conclusions—

Tomm7 drives brain angiogenesis and cerebrovascular network formation through modulating mitochondrial Rac1 signaling within the endothelium.
SR-BI (Scavenger Receptor Class B Type 1) Is Critical in Maintaining Normal T-Cell Development and Enhancing Thymic Regeneration
Authors: Zheng Zhong , Ai Junting , Guo Ling , Ye Xiang , Bondada Subbarao , Howatt Deborah , Daugherty Alan , Li Xiang-An
Published: October 2018

Objective—

Continuous T-cell production from thymus is essential in replenishing naïve T-cell pool and maintaining optimal T-cell functions. However, the underlying mechanisms regulating the T-cell development in thymus remains largely unknown.

Approach and Results—

We identified SR-BI (scavenger receptor class B type 1), an HDL (high-density lipoprotein) receptor, as a novel modulator in T-cell development. We found that SR-BI deficiency in mice led to reduced thymus size and decreased T-cell production, which was accompanied by narrowed peripheral naïve T-cell pool. Further investigation revealed that SR-BI deficiency impaired progenitor thymic homing, causing a dramatic reduction in the percentage of earliest thymic progenitors, but did not affect other downstream T-cell developmental steps inside the thymus. As a result of the impaired progenitor thymic homing, SR-BI-deficient mice displayed delayed thymic regeneration postirradiation. Using a variety of experimental approaches, we revealed that the impaired T-cell development in SR-BI-deficient mice was not caused by hematopoietic SR-BI deficiency or SR-BI deficiency-induced hypercholesterolemia, but mainly attributed to the SR-BI deficiency in adrenal glands, as adrenal-specific SR-BI-deficient mice exhibited similar defects in T-cell development and thymic regeneration with SR-BI-deficient mice.

Conclusions—

This study demonstrates that SR-BI deficiency impaired T-cell development and delayed thymic regeneration by affecting progenitor thymic homing in mice, elucidating a previously unrecognized link between SR-BI and adaptive immunity.