bluuebunny/crossref_metadata_2025 huggingface dataset:
Thoracic involvement of diffuse lymphangiomatosis successfully treated with sildenafil
Authors: Maurac Arnaud , Debray Marie-Pierre , Crestani Bruno , Taillé Camille
Published: April 2019

General lymphatic anomaly (GLA) is a very rare disorder, characterised by multifocal lymphatic malformations into various tissues that is due to congenital abnormalities of lymphatic development. No treatment has ever proved its efficiency.

We report a 22-year-old man with recurrent bronchial casts due to thoracic involvement of GLA. After a 6-month treatment with sildenafil (20 mg three times a day), a phosphodiesterase 5 inhibitor, chest CT scan showed a complete regression of ground-glass opacities and lung function test results improved substantially and remained stable for 1 year. The treatment was well tolerated.

This observation suggests that sildenafil may be a therapeutic approach to be tested in thoracic involvement of GLA.
Bi-allelic loss of function variants ofTBX6causes a spectrum of malformation of spine and rib including congenital scoliosis and spondylocostal dysostosis
Authors: Otomo Nao , Takeda Kazuki , Kawai Shunsuke , Kou Ikuyo , Guo Long , Osawa Mitsujiro , Alev Cantas , Kawakami Noriaki , Miyake Noriko , Matsumoto Naomichi , Yasuhiko Yukuto , Kotani Toshiaki , Suzuki Teppei , Uno Koki , Sudo Hideki , Inami Satoshi , Taneichi Hiroshi , Shigematsu Hideki , Watanabe Kei , Yonezawa Ikuho , Sugawara Ryo , Taniguchi Yuki , Minami Shohei , Kaneko Kazuo , Nakamura Masaya , Matsumoto Morio , Toguchida Junya , Watanabe Kota , Ikegawa Shiro
Published: April 2019

Background

Congenital scoliosis (CS) is a common vertebral malformation. Spondylocostal dysostosis (SCD) is a rare skeletal dysplasia characterised by multiple vertebral malformations and rib anomalies. In a previous study, a compound heterozygosity for a null mutation and a risk haplotype composed by three single-nucleotide polymorphisms inTBX6have been reported as a disease-causing model of CS. Another study identified bi-allelic missense variants in a SCD patient. The purpose of our study is to identifyTBX6variants in CS and SCD and examine their pathogenicity.

Methods

We recruited 200 patients with CS or SCD and investigatedTBX6variants. We evaluated the pathogenicity of the variants by in silico prediction and in vitro experiments.

Results

We identified five 16p11.2 deletions, one splice-site variant and five missense variants in 10 patients. In vitro functional assays for missense variants identified in the previous and present studies demonstrated that most of the variants caused abnormal localisation of TBX6 proteins. We confirmed mislocalisation of TBX6 proteins in presomitic mesoderm cells induced from SCD patient-derived iPS cells. In induced cells, we found decreased mRNA expressions ofTBX6and its downstream genes were involved in somite formation. All CS patients with missense variants had the risk haplotype in the opposite allele, while a SCD patient with bi-allelic missense variants did not have the haplotype.

Conclusions

Our study suggests that bi-allelic loss of function variants ofTBX6cause a spectrum of phenotypes including CS and SCD, depending on the severity of the loss ofTBX6function.
Empirical analysis of the user reputation and clustering property for user-object bipartite networks
Authors: Liu Xiao-Lu , Jia Shu-Wei , Gu Yan
Published: April 2019

User reputation is of great significance for online rating systems which can be described by user-object bipartite networks, measuring the user ability of rating accurate assessments of various objects. The clustering coefficients have been widely investigated to analyze the local structural properties of complex networks, analyzing the diversity of user interest. In this paper, we empirically analyze the relation of user reputation and clustering property for the user-object bipartite networks. Grouping by user reputation, the results for the MovieLens dataset show that both the average clustering coefficient and the standard deviation of clustering coefficient decrease with the user reputation, which are different from the results that the average clustering coefficient and the standard deviation of clustering coefficient remain stable regardless of user reputation in the null model, suggesting that the user interest tends to be multiple and the diversity of the user interests is centralized for users with high reputation. Furthermore, we divide users into seven groups according to the user degree and investigate the heterogeneity of rating behavior patterns. The results show that the relation of user reputation and clustering coefficient is obvious for small degree users and weak for large degree users, reflecting an important connection between user degree and collective rating behavior patterns. This work provides a further understanding on the intrinsic association between user collective behaviors and user reputation.
Stability and boundedness in AdS/CFT with double trace deformations
Authors: Casper Steven , Cottrell William , Hashimoto Akikazu , Loveridge Andrew , Pettengill Duncan
Published: April 2019

Scalar fields on the bulk side of AdS/CFT correspondence can be assigned unconventional boundary conditions related to the conventional one by Legendre transform. One can further perform double trace deformations which relate the two boundary conditions via renormalization group flow. Thinking of these operators as S and T transformations, respectively, we explore the SL(2, R) family of models which naively emerges from repeatedly applying these operations. Depending on the parameters, the effective masses vary and can render the theory unstable. However, unlike in the SL(2, Z) structure previously seen in the context of vector fields in AdS4, some of the features arising from this exercise, such as the vacuum susceptibility, turns out to be scheme dependent. We explain how scheme independent physical content can be extracted in spite of some degree of scheme dependence in certain quantities.
Effects of halogen substituted on the Mn-O electron transfer of NiMn2O4
Authors: Li Hai-Long , Bian Liang , Dong Fa-Qin , Li Wei-Min , Zou Hao , Song Mian-Xin
Published: April 2019

To observe the effect of halogen-substitution on the Mn-O electron transfer of NiMn2O4, we calculated Mn-mixed-valence configuration (charge-disproportionation) and oxygen vacancy by the density functional theory (DFT). The results indicate that the halogen-p5 state induces the O-2p orbital splitting to create an oxygen vacancy in the VB (valence band: about −5 eV). The oxygen vacancy can capture an electron from Mn[Formula: see text]-3d5 orbital that makes the Mn[Formula: see text]-3d5 change to Mn[Formula: see text]-3d4 states (Mn-charge disproportionate), and providing many effective-hole (40.14 [Formula: see text] 96.72 × 10[Formula: see text] kg). The halogen-p5-O-2p4 hybrid orbitals enhance the O-2p4-Mn-3d5 p-d hybrid orbital (about 19.18 electron). That increases the surface potential in Mn-O octahedron (for Cl-substituted: about 60 meV), the corresponding electron–electron interactions change from complex t[Formula: see text] (O-2p4-Mn[Formula: see text]-3d[Formula: see text] to complete [Formula: see text] (O-2p4-Mn[Formula: see text]-3d[Formula: see text]-e[Formula: see text](O-2p4-halogen-p5) orbital. This study effectively analyzes the microscopic changes of the electron transfer caused by the small amount of doping, provides a theoretical basis for the design of NMO-based semiconductor material.
Some stability results for the complex Ginzburg–Landau equation
Authors: Correia Simão , Figueira Mário
Published: April 2019

Using some classical methods of dynamical systems, stability results and asymptotic decay of strong solutions for the complex Ginzburg–Landau equation (CGL), [Formula: see text] with [Formula: see text], are obtained. Moreover, we show the existence of bound-states under certain conditions on the parameters and on the domain. We conclude with the proof of asymptotic stability of these bound-states when [Formula: see text] and [Formula: see text] large enough.
Optimal Liouville-type theorems for a system of parabolic inequalities
Authors: Duong Anh Tuan , Phan Quoc Hung
Published: April 2019

We establish optimal Liouville-type theorems for the system of parabolic inequalities [Formula: see text] and for the scalar inequality [Formula: see text] in the whole space [Formula: see text] and in [Formula: see text]. Our optimal Liouville-type theorems are proved for two different classes of solutions: the nontrivial nonnegative and the positive.
On periodic boundary value problem for second-order ordinary differential equations
Authors: Lomtatidze Alexander
Published: April 2019

For second-order nonlinear nonautonomous differential equations, new sufficient conditions on the existence of periodic solutions are established.
Quantum spin probabilities at positive temperature are Hölder Gibbs probabilities
Authors: Brasil Jader E. , Lopes Artur O. , Mengue Jairo K. , Moreira Carlos G.
Published: April 2019

We consider the KMS state associated to the Hamiltonian [Formula: see text] over the quantum spin lattice [Formula: see text] For a fixed observable of the form [Formula: see text] where [Formula: see text] is self-adjoint, and for positive temperature [Formula: see text] one can get a naturally defined stationary probability [Formula: see text] on the Bernoulli space [Formula: see text]. The Jacobian of [Formula: see text] can be expressed via a certain continued fraction expansion. We will show that this probability is a Gibbs probability for a Hölder potential. Therefore, this probability is mixing for the shift map. For such probability [Formula: see text] we will show the explicit deviation function for a certain class of functions. When decreasing temperature we will be able to exhibit the explicit transition value [Formula: see text] where the set of values of the Jacobian of the Gibbs probability [Formula: see text] changes from being a Cantor set to being an interval. We also present some properties for quantum spin probabilities at zero temperature (for instance, the explicit value of the entropy).
Crown-ether-substituted asymmetric phthalocyanine derivatives/CdS self-assembled hybrid films with an unprecedented high response toward NO2
Authors: Yang Chaoyi , He Runna , Sun Qiqi , Chen Yanli , Jiang Jianzhuang
Published: April 2019

Two asymmetrical amphiphilic phthalocyanines simultaneously containing hydrophobic alkoxy and hydrophilic 15-crown-5-ether substituents at the phthalocyanine periphery H2{Pc(15C5)3[(OC8H[Formula: see text]]}(Pc-1) and H2{Pc(15C5)[(OC8H[Formula: see text]]}(Pc-2) and their symmetrical analogue H2[Pc(OC8H[Formula: see text]] (Pc-3) have been synthesized and characterized. The Pc-n/CdS ([Formula: see text] 1, 2 and 3, respectively) hybrid films are obtained successfully via a simple quasi-Langmuir–Shäfer (QLS) method using H2S-vapor annealing over the Pc-n/Cd[Formula: see text] self-assembled film formed at the interface of the air/CdCl2 aqueous solution. The film-structure and properties of both the hybrid Pc-n/CdS and pure Pc-n films are comparatively studied by a wide range of methods including UV-vis, polarized UV-vis, XRD, SEM and I–V measurements. Experimental results exhibit a slipped co-facial stacking mode in an “edge-on” conformation ([Formula: see text]-type aggregate) formed for the phthalocyanine molecules in both pure Pc-n films and the corresponding Pc-n/CdS hybrid films, with increasing intermolecular [Formula: see text]–[Formula: see text] interactions in the order of Pc-n <Pc-n/CdS and Pc-3/CdS <Pc-2/CdS <Pc-1/CdS, respectively. Accordingly, film-microstructures, crystallinity and conductivity are effectively improved by introducing CdS nanoparticles into the 15-crown-5-substituented phthalocyanines forming Pc-1/CdS and Pc-2/CdS hybrid films. These render excellent sensing performance towards NO2 in the 0.05–2.5 ppm range within a fast dynamic exposure period of 30 s. Strikingly, Pc-1/CdS hybrid film presents an unprecedented high sensitivity of 157.3%.ppm[Formula: see text] vs. very low NO2 concentration range of 0.05˜0.25 ppm, achieving one of the best room temperature sensing performances in terms of high sensitivity, rapid responsibility and low detection limit among self-assembled film-based NO2 sensors.
CEO TRANSFORMATIONAL LEADERSHIP AND SME INNOVATION: THE MEDIATING ROLE OF SOCIAL CAPITAL AND EMPLOYEE PARTICIPATION
Authors: CORTES ANDRES FELIPE , HERRMANN POL
Published: April 2019

It is widely accepted that CEOs with a transformational leadership style can promote innovation in the organisations they lead, but the specific ways in which they influence followers and shape the organisational context to increase innovation remain largely unexplored. Improvement of our understanding of this relationship requires identifying and explaining the mechanisms that allow transformational CEOs to mobilise employees towards an active support of innovation. We argue that top managers who portray a transformational leadership style have a positive effect on organisational innovation by improving how the firm exchanges and communicates information and knowledge, that is, by increasing employees’ participation and social capital. Data from a sample of 194 executives from 97 Ecuadorian small- and medium-sized firms provide support for our hypotheses.
Octahedral yolk-shell-structured ZnFe2O4/SiO2 formation and Fenton performance
Authors: Huang Xing , Nan Zhaodong
Published: April 2019

Octahedron-shaped ZnFe2O4 was fabricated through a facile process, where the ZnFe2O4 showed yolk-shell-structured. Hollow mesoporous SiO2 spheres were used as template in the process. The SiO2 spheres changed to nanosheets assembled at the surface of the as-formed octahedron-shaped ZnFe2O4. The ZnFe2O4/SiO2 composite exhibits higher surface area (154.03[Formula: see text]m2/g) than those reported. The composite showed excellent catalytic activity in Fenton and photo-Fenton processes, for which the rate constants reached 0.034 and 0.063[Formula: see text][Formula: see text], respectively. And the composite exhibited stable catalytic activity for three cycles. These results demonstrate that the composite shows potential applications in environmental treatment.
Domination When the Stars Are Out
Authors: Hermelin Danny , Mnich Matthias , Leeuwen Erik Jan Van , Woeginger Gerhard
Published: April 2019

We algorithmize the structural characterization for claw-free graphs by Chudnovsky and Seymour. Building on this result, we show that D
ominating
S
et
on claw-free graphs is (i) fixed-parameter tractable and (ii) even possesses a polynomial kernel. To complement these results, we establish that D
ominating
S
et
is unlikely to be fixed-parameter tractable on the slightly larger class of graphs that exclude
K
1,4
as an induced subgraph (
K
1,4
-free graphs). We show that our algorithmization can also be used to show that the related C
onnected
D
ominating
S
et
problem is fixed-parameter tractable on claw-free graphs. To complement that result, we show that C
onnected
D
ominating
S
et
is unlikely to have a polynomial kernel on claw-free graphs and is unlikely to be fixed-parameter tractable on
K
1,4
-free graphs. Combined, our results provide a dichotomy for D
ominating
S
et
and C
onnected
D
ominating
S
et
on
K
1,ℓ
-free graphs and show that the problem is fixed-parameter tractable if and only if ℓ ≤ 3.
Conference reports
Authors: Rovatsos Michael
Published: April 2019

This section features brief reports from recent events sponsored or run in cooperation with ACM SIGAI.
The laws of thought and thinking machines
Authors: Hughes Cameron , Hughes Tracey
Published: April 2019

The ideal value of an AI Cosmology would be to help the general public, researchers, educators, and practitioners to devise the truth of the definition, meaning, applications, and implications of Artificial Intelligence. The pursuit of that truth even if through an arbitrary contrivance would be a noteworthy goal. The fact of the matter is whether any cosmological structure we have hinted at so far tracks the underlying reality, we cannot escape that there is an underlying reality. At some point in time, we (humans) began the endeavor of trying to replicate the human mind with machines. There was first an effort to understand the human mind, describe its inner workings, and then build machines that could essentially duplicate the thinking process. Surely this point in time must mark or at least point to the Cosmological "Big Bang" for AI. Right?
Crosswords
Authors: Botea Adi
Published: April 2019

Across: 1
) One mocking remark
7
) Elite groups
13
) In short supply
14
) __Ahern, Irish politician
15
) The most uninspiring
16
) The most uncovered
17
) Good-quality rock
18
) The most impacted by the cloud
20
) Canadian prov.
21
) Sound in the head
22
) Boolean constant
23
) Baltic state
25
) Wave-amplifying device
26
) Word game
28
) Muscle pain
31
) Cars with flexible protection
35
) Damage
36
) City in Italy
37
) Respond emotionally
38
) Times between
40
) It is shorter
41
) Internet device
42
) Old coin from todays Istanbul
45
) Pressed to serve a side dish
46
) Immediately
47
) Baby birds
48
) Use a coupon
Creative next
Authors: Knemeyer Dirk , Follett Jonathan
Published: April 2019

This forum is dedicated to maximizing the success of HCI practitioners within the frenetic world of product and service design. It focuses on UX strategy approaches, leadership, management techniques, and above all the challenge of bringing HCI to peer-level status with longstanding business disciplines such as marketing and engineering.
--- Daniel Rosenberg, Editor
Repetitive hypoglycemia reduces activation of glucose-responsive neurons in C1 and C3 medullary brain regions to subsequent hypoglycemia
Authors: Kakall Zohra M. , Kavurma Mary M. , Cohen E. Myfanwy , Howe Peter R. , Nedoboy Polina E. , Pilowsky Paul M.
Published: April 2019

The impaired ability of the autonomic nervous system to respond to hypoglycemia is termed “hypoglycemia-associated autonomic failure” (HAAF). This life-threatening phenomenon results from at least two recent episodes of hypoglycemia, but the pathology underpinning HAAF remains largely unknown. Although naloxone appears to improve hypoglycemia counterregulation under controlled conditions, hypoglycemia prevention remains the current mainstay therapy for HAAF. Epinephrine-synthesizing neurons in the rostroventrolateral (C1) and dorsomedial (C3) medulla project to the subset of sympathetic preganglionic neurons that regulate peripheral epinephrine release. Here we determined whether or not C1 and C3 neuronal activation is impaired in HAAF and whether or not 1 wk of hypoglycemia prevention or treatment with naloxone could restore C1 and C3 neuronal activation and improve HAAF. Twenty male Sprague-Dawley rats (250–300 g) were used. Plasma epinephrine levels were significantly increased after a single episode of hypoglycemia ( n = 4; 5,438 ± 783 pg/ml vs. control 193 ± 27 pg/ml, P < 0.05). Repeated hypoglycemia significantly reduced the plasma epinephrine response to subsequent hypoglycemia ( n = 4; 2,179 ± 220 pg/ml vs. 5,438 ± 783 pg/ml, P < 0.05). Activation of medullary C1 ( n = 4; 50 ± 5% vs. control 3 ± 1%, P < 0.05) and C3 ( n = 4; 45 ± 5% vs. control 4 ± 1%, P < 0.05) neurons was significantly increased after a single episode of hypoglycemia. Activation of C1 ( n = 4; 12 ± 3%, P < 0.05) and C3 ( n = 4; 19 ± 5%, P < 0.05) neurons was significantly reduced in the HAAF groups. Hypoglycemia prevention or treatment with naloxone did not restore the plasma epinephrine response or C1 and C3 neuronal activation. Thus repeated hypoglycemia reduced the activation of C1 and C3 neurons mediating adrenal medullary responses to subsequent bouts of hypoglycemia.
Numerical Modeling of Reactive Transport and Self-Sealing Processes in the Fault-Controlled Geothermal System of the Guide Basin, China
Authors: Hou Zhaoyun , Xu Tianfu , Feng Guanhong , Feng Bo , Yuan Yilong , Jiang Zhenjiao
Published: April 2019

Strong chemical reactions in the geothermal systems may cause sealing of fractures, which reduces the permeability in the reservoir and subsequently affects the heat production. However, it is difficult to reveal the sealing range in a deeply buried reservoir based on a limited number of downhole logs. This study recreated the sealing processes of the fault-controlled geothermal system in the Guide Basin, China, by reactive transport modeling. The modeling domain was discretized based on multiple interacting continua (MINC) approach, to address the nonequilibrium heat transport processes between the matrix and conduit in the fractured fault damage zone. Once the model was validated by observations of major ions in spring water and downhole temperature logs in the discharge area, it was used to determine the coupled processes of fluid, heat, and chemical transport in the reservoir and the resultant sealing ranges. It was found that the dissolution of albite and K-feldspar leads to the precipitation of smectite-Ca and illite in the middle and bottom of the fault under the condition of high concentration of Ca2+ and Mg2+ in the recharge water. Calcite veins were formed in discharge zone, because the horizontal fast flow in shallow subsurface zone supplied abundant Ca2+ and HCO3-. As a consequence, the permeability in the discharge zone reduced by 15% when compared to the original permeability of 100 mD. Moreover, another three self-sealing areas were formed near the recharge zone, the deep upgradient zone, and the downgradient area where the fast upward fluid flow occurred. Self-sealing subsequently prevented the deep circulation of the flow and heat absorption, which tends to make the fault-controlled geothermal system inactive.
Dynamic Characteristics of Gas Explosion and Its Mitigation Measures inside Residential Buildings
Authors: Cen Kang , Song Bin , Shen Ruiqing , Zhang Yidong , Yu Wuge , Wang Qingsheng
Published: April 2019

Currently, there is very limited understanding of a gas explosion process inside residential buildings. In this study, a numerical model of gas explosion in a residential building was developed using Computational Fluid Dynamics (CFD). The numerical simulations were performed for different gas cloud filling regions and equivalence ratios to identify the initial scenario, and the simulation results were compared with the real consequences of gas explosion. Additionally, the temporal and spatial evolvement characteristics of explosion overpressure and indoor temperature were analyzed. Furthermore, the effects of vent area ratio and the activation pressure of vent panels in the kitchen were investigated to propose effective mitigation measures for the gas explosions inside residential buildings. The results show that the simulation results reproduced by the CFD model are in good agreement with the real accident consequences. During the explosion process, the overpressure distribution in a room is almost uniform at the same moment and there exists little spatial difference. The maximum temperature can reach up to 1953°C, which can cause secondary fire accidents easily. The maximum flame speed is in the range of 34.3 m/s and 230.9 m/s. It indicates that gas explosion inside residential buildings is a typical deflagration process. When the vent area ratio is less than 0.3, the overpressure peaks decrease rapidly with the increase of the vent area ratio. However, when the vent area ratio is larger than 0.3, the overpressure peaks are almost independent on the vent area ratio. There is a proportional relationship between the overpressure peaks and the activation pressure of vent panels. These achievements provide reliable reference data for the accident investigation of gas explosion and subsequent treatment.
Quantitative Proteomic Analysis Reveals the Deregulation of Nicotinamide Adenine Dinucleotide Metabolism and CD38 in Inflammatory Bowel Disease
Authors: Ning LongGui , Shan Guodong , Sun Zeyu , Zhang Fenming , Xu Chengfu , Lou Xinhe , Li Sha , Du Haojie , Chen Hongtan , Xu Guoqiang
Published: April 2019

Inflammatory bowel disease (IBD) has become a major health challenge worldwide. However, the precise etiological and pathophysiological factors involved in IBD remain unclear. Proteomics can be used for large-scale protein identification analysis. In the current study, using tandem mass tag- (TMT-) based shotgun proteomics, proteomic differences between intestinal tissue from health controls, patients with Crohn’s disease (CD), and patients with ulcerative colitis (UC) were compared. Proteins with fold change >2 or <0.5 and P value < 0.05 between groups were considered differentially expressed. ProteinAtlas was used to analyze the tissue specificity of differentially expressed proteins (DEPs). Reactome pathway analysis was applied to cluster functional pathways. A total of 4786 proteins were identified, with 59 proteins showing higher levels and 43 showing lower levels in patients with IBD than in controls. Seventeen proteins, including angiotensin converting enzyme 2 (ACE2) and angiotensin converting enzyme 1 (ACE), showed higher levels in CD than in UC. Several novel proteins such as CD38, chitinase 3-like 1 (CHI3L1), olfactomedin 4 (OLFM4), and intelectin 1 were screened out between patients with IBD and controls. When proteins with fold change >1.2 or <0.84 and P value < 0.05 between groups were considered differentially expressed, the expression of 10 proteins, including CD38, involved in the nicotinamide adenine dinucleotide (NAD) metabolism and signaling pathway showed significant changes in IBD. Using the NCBI GEO database, we confirmed increased CD38 mRNA expression in patients with UC and in mouse colitis models. Protein CD38 expression was higher in CD and UC than in normal controls. CD38 expression was higher in inflamed tissues than in noninflamed tissues, and CD38 was located in F4/80-positive cells. Our study may provide novel insights into the molecular pathogenesis of IBD. Further studies are required on the role of NAD metabolism and CD38 in intestinal inflammation.
String Theory Explanation of Galactic Rotation Found Using the Geodesic Constraint
Authors: Roberts Mark D.
Published: April 2019

The unique spherically symmetric metric which has vanishing Weyl tensor, is asymptotically de-Sitter, and can model constant galactic rotation curves is presented. Two types of field equations are shown to have this metric as an exact solution. The first is Palatini varied scalar-tensor theory. The second is the low energy limit of string theory modified by inclusion of a contrived potential.
Novel Hybrid Gels Made of High and Low Molecular Weight Hyaluronic Acid Induce Proliferation and Reduce Inflammation in an Osteoarthritis In Vitro Model Based on Human Synoviocytes and Chondrocytes
Authors: Stellavato Antonietta , Vassallo Valentina , La Gatta Annalisa , Pirozzi Anna Virginia Adriana , De Rosa Mario , Balato Giovanni , D’Addona Alessio , Tirino Virginia , Ruosi Carlo , Schiraldi Chiara
Published: April 2019

High molecular weight hyaluronan (H-HA) has a pivotal role in the maintenance of normal functions of synovial fluid and structure of the articular joint, but it has been shown that its concentration is reduced in patients affected by degenerative cartilage diseases, such as osteoarthritis (OA). The aim of this study was to investigate the anti-inflammatory effects and properties of hybrid cooperative complexes based on high and low molecular weight hyaluronan (HCC) compared to H-HA on human primary cells derived by pathological joints. In addition, the rheological behavior of HCC was evaluated in order to define their potential as viscosupplement gel in degenerated joints. The experiments were performed using an in vitro model of OA based on human chondrocytes and synoviocytes isolated from degenerated joints of patients hospitalized for surgical replacement. In order to assess the anti-inflammatory effects of HCC, we evaluated NF-kB, COMP-2, IL-6, and IL-8 as specific markers at the transcriptional and/or protein level. Moreover, the proliferative properties of HCC were assessed using time lapse video microscopy. We showed that chondrocytes and synoviocytes clearly presented an altered cytokine profile compatible with a severe ongoing inflammation status. H-HA and, above all, HCC significantly reduced levels of the specific biomarkers evaluated and improved cartilage healing. The rheological profile indicated HCC suitability for intra-articular injection in joint diseases. HCC viscoelastic properties and the protective/anti-inflammatory effect on human chondrocytes and synoviocytes suggest the novel HCC-based gels as a valid support for OA management.
Preliminary Comparison of the Efficacy and Safety of Needle-Embedding Therapy with Acupuncture for Atopic Dermatitis Patients
Authors: Lee Ho-Chan , Park Soo-Yeon
Published: April 2019

Objectives. Among Traditional Korean Medicine approaches, needle-embedding therapy is used in various fields and consistently studied; however, there have been no clinical studies of the treatment of adult atopic dermatitis (AD) with needle-embedding therapy. Thus, there is a need to investigate the effects of needle-embedding therapy for treatment of AD. This study was performed to identify possible effects of needle-embedding therapy at Quchi acupoint (LI11) on AD and to compare these effects with those of acupuncture therapy. Methods. A total of 14 participants were enrolled in this study. Participants received acupuncture or needle-embedding treatments for 4 weeks and then were followed for an additional 2 weeks because of safety assessment. The participants were divided into 2 groups: the acupuncture group, receiving treatment at Quchi acupoint (LI11) 3 times per week, and the needle-embedding group, receiving treatment at Quchi acupoint (LI11) once per week. The groups were compared on the basis of the SCORing Atopic Dermatitis (SCORAD) index, Transepidermal Water Loss (TEWL), skin hydration, and Dermatology Life Quality Index (DLQI) at baseline and 1 week after treatment was completed (5th week). Results. The SCORAD index, TEWL, Skin hydration, and DLQI at 1 week after treatment were significantly improved in both groups (p<0.05). However, there were no significant differences between the acupuncture and needle-embedding groups in any of the main evaluation indices (p>0.05). The study participants received a total of 84 acupuncture treatments or 28 needle-embedding treatments. No adverse events occurred during the study period. Conclusions. Based on changes in the SCORAD index, TEWL, skin hydration, and DLQI value, we found that both needle-embedding and acupuncture treatments at the Quchi acupoint (LI11) were effective in decreasing the symptoms of AD and exhibited similar therapeutic effects, which suggests that needle-embedding treatment may be more clinically convenient than acupuncture, with longer effects and fewer treatments.
Morphological and Nutritional Properties of Moroccan Capparis spinosa Seeds
Authors: El amri Nidal , Errachidi Faouzi , Bour Abdellatif , Bouhaddaoui Sara , Chabir Rachida
Published: April 2019

Capparis spinosa is one of the few shrub species which has so many qualities with many uses. In this case, the present work aimed to study both some morphological characteristics and biochemical components (proteins, lipids, and carotenoids) of fresh C. spinosa seeds with three different sizes, collected from two Moroccan regions. In this study, C. spinosa seeds present a total of proteins ranging from 23.32 to 28.5% on a dry weight basis. Additionally, the total lipids varied between 2.8 and 3.4%. C. spinosa seeds contained a high level of carotenoids. Besides, the analytical values have been variously affected by both size and location. Further, the preliminary morphological and anatomical characterization of leaves, stems, and morphological properties such as length, width, thickness, geometric mean diameter, sphericity, surface area, and mass of 100 seeds have been determined. Consequently, this present study confirms the importance of Moroccan C. spinosa seeds, which represent a significant nutritional value. Also, its good morphological quality is a significant indicator of commercial criteria.
Incidence of Acute Kidney Injury in Patients with Chronic Renal Insufficiency: Transcatheter versus Surgical Aortic Valve Replacement
Authors: Catalano Michael , Lin Dishen , Cassiere Hugh , Kohn Nina , Rutkin Bruce , Maurer Greg , Berg Jacinda A. , Jahn Jaclyn , Esposito Rick , Hartman Alan , Yu Pey-Jen
Published: April 2019

Objectives. The objective of this study is to determine incidence of acute kidney injury (AKI) associated with transcatheter aortic valve replacement (TAVR) versus surgical aortic valve replacement (SAVR) in patients with preexisting chronic kidney disease. Background. The incidence of AKI in patients with preexisting renal insufficiency undergoing TAVR versus SAVR is not well described. Methods. All patients with preexisting chronic kidney disease who underwent SAVR for aortic stenosis with or without concomitant coronary artery bypass grafting or TAVR from 5/2008 to 6/2017. Patients requiring preoperative hemodialysis were excluded. Chronic kidney disease was defined as an estimated glomerular filtrate rate (eGFR) of < 60 mL/min/1.73 m2. The incidence of postoperative AKI was compared using the RIFLE classification system for acute kidney injury. Results. A total of 406 SAVR patients and 407 TAVR patients were included in this study. TAVR patients were older and had lower preoperative eGFR as compared to SAVR patients. Covariate adjustment using propensity score between the two groups showed that SAVR patients were more likely to have a more severe degree of postoperative AKI as compared to TAVR patients (OR = 4.75; 95% CI: 3.15, 7.17; p <.001). SAVR patients were more likely to require dialysis postoperatively as compared to TAVR patients (OR = 4.55; 95% CI: 1.29, 15.99; p <.018). Conclusion. In patients with preexisting chronic kidney disease, TAVR was associated with significantly less AKI as compared to SAVR.
Comparison of Questionnaire-Based Breast Cancer Prediction Models in the Nurses' Health Study
Authors: Glynn Robert J. , Colditz Graham A. , Tamimi Rulla M. , Chen Wendy Y. , Hankinson Susan E. , Willett Walter W. , Rosner Bernard
Published: April 2019

Background:

The Gail model and the model developed by Tyrer and Cuzick are two questionnaire-based approaches with demonstrated ability to predict development of breast cancer in a general population.

Methods:

We compared calibration, discrimination, and net reclassification of these models, using data from questionnaires sent every 2 years to 76,922 participants in the Nurses' Health Study between 1980 and 2006, with 4,384 incident invasive breast cancers identified by 2008 (median follow-up, 24 years; range, 1–28 years). In a random one third sample of women, we also compared the performance of these models with predictions from the Rosner–Colditz model estimated from the remaining participants.

Results:

Both the Gail and Tyrer–Cuzick models showed evidence of miscalibration (Hosmer–Lemeshow P < 0.001 for each) with notable (P < 0.01) overprediction in higher-risk women (2-year risk above about 1%) and underprediction in lower-risk women (risk below about 0.25%). The Tyrer–Cuzick model had slightly higher C-statistics both overall (P < 0.001) and in age-specific comparisons than the Gail model (overall C, 0.63 for Tyrer–Cuzick vs. 0.61 for the Gail model). Evaluation of net reclassification did not favor either model. In the one third sample, the Rosner–Colditz model had better calibration and discrimination than the other two models. All models had C-statistics <0.60 among women ages ≥70 years.

Conclusions:

Both the Gail and Tyrer–Cuzick models had some ability to discriminate breast cancer cases and noncases, but have limitations in their model fit.

Impact:

Refinements may be needed to questionnaire-based approaches to predict breast cancer in older and higher-risk women.
Predictive Value of HPV Testing in Self-collected and Clinician-Collected Samples Compared with Cytology in Detecting High-grade Cervical Lesions
Authors: El-Zein Mariam , Bouten Sheila , Louvanto Karolina , Gilbert Lucy , Gotlieb Walter H. , Hemmings Robert , Behr Marcel A. , Franco Eduardo L. ,   the CASSIS Study Group*
Published: April 2019

Background:

Self-sampling has become an attractive proposition now that human papillomavirus (HPV) primary testing is being incorporated into cervical cancer screening programs worldwide. We compared predictive values of HPV testing based on self- and physician-collected samples, and cytology, in detecting high-grade cervical intraepithelial neoplasia (CIN).

Methods:

The Cervical And Self-Sample In Screening (CASSIS) study enrolled 1,217 women ages 16–70 years prior to scheduled colposcopies. Vaginal specimens were self-collected using the validated HerSwab device. Cervical specimens were collected by gynecologists. Specimens were tested for presence of high-risk HPV (hrHPV) by the Cobas 4800 HPV test. We estimated positive predictive values (PPV) and negative predictive values (NPV) and 95% confidence intervals (CI) for a subset of women (n = 700) who underwent cervical biopsy and cytology at the actual CASSIS visit.

Results:

hrHPV was detected in 329 women (47%) with HerSwab and in 327 (46.7%) with physician sampling. Respective values for HPV16/18 were 119 (17%) and 121 (17.3%). On histology, 134 women had CIN1, 49 had CIN2, 48 had CIN3, 5 had CIN2/CIN3, and 3 had cancers. PPVs for CIN2+ of any hrHPV were 28% (95% CI, 23.2–33.1) and 29.7% (95% CI, 24.8–34.9) for HerSwab and physician samples, respectively. Corresponding values for HPV16/18 were 43.7% (95% CI, 34.6–53.1) and 43.8% (95% CI, 34.8–53.1). PPV of cytology (ASC-US+) was 26.6% (95% CI, 21.6–32.0). Corresponding NPVs (same order as PPVs) were 96.4% (95% CI, 93.9–98.1), 97.8% (95% CI, 95.6–99), 90.9% (95% CI, 88.2–93.1), 91% (95% CI, 88.4–93.2), and 94.7% (95% CI, 91.8–96.8).

Conclusions:

Our results confirm that HPV self-sampling has comparable performance with a physician-collected sample in detecting cervical lesions.

Impact:

HPV self-sampling has the potential to increase coverage in cervical cancer screening.
OBI-3424, a Novel AKR1C3-Activated Prodrug, Exhibits Potent Efficacy against Preclinical Models of T-ALL
Authors: Evans Kathryn , Duan JianXin , Pritchard Tara , Jones Connor D. , McDermott Lisa , Gu Zhaohui , Toscan Cara E. , El-Zein Narimanne , Mayoh Chelsea , Erickson Stephen W. , Guo Yuelong , Meng Fanying , Jung Donald , Rathi Komal S. , Roberts Kathryn G. , Mullighan Charles G. , Shia Chi-Sheng , Pearce Tillman , Teicher Beverly A. , Smith Malcolm A. , Lock Richard B.
Published: April 2019

Purpose:

OBI-3424 is a highly selective prodrug that is converted by aldo-keto reductase family 1 member C3 (AKR1C3) to a potent DNA-alkylating agent. OBI-3424 has entered clinical testing for hepatocellular carcinoma and castrate-resistant prostate cancer, and it represents a potentially novel treatment for acute lymphoblastic leukemia (ALL).

Experimental Design:

We assessed AKR1C3 expression by RNA-Seq and immunoblotting, and evaluated the in vitro cytotoxicity of OBI-3424. We investigated the pharmacokinetics of OBI-3424 in mice and nonhuman primates, and assessed the in vivo efficacy of OBI-3424 against a large panel of patient-derived xenografts (PDX).

Results:

AKR1C3 mRNA expression was significantly higher in primary T-lineage ALL (T-ALL; n = 264) than B-lineage ALL (B-ALL; n = 1,740; P < 0.0001), and OBI-3424 exerted potent cytotoxicity against T-ALL cell lines and PDXs. In vivo, OBI-3424 significantly prolonged the event-free survival (EFS) of nine of nine ALL PDXs by 17.1–77.8 days (treated/control values 2.5–14.0), and disease regression was observed in eight of nine PDXs. A significant reduction (P < 0.0001) in bone marrow infiltration at day 28 was observed in four of six evaluable T-ALL PDXs. The importance of AKR1C3 in the in vivo response to OBI-3424 was verified using a B-ALL PDX that had been lentivirally transduced to stably overexpress AKR1C3. OBI-3424 combined with nelarabine resulted in prolongation of mouse EFS compared with each single agent alone in two T-ALL PDXs.

Conclusions:

OBI-3424 exerted profound in vivo efficacy against T-ALL PDXs derived predominantly from aggressive and fatal disease, and therefore may represent a novel treatment for aggressive and chemoresistant T-ALL in an AKR1C3 biomarker-driven clinical trial.
A Rationally Designed Peptide Antagonist of the PD-1 Signaling Pathway as an Immunomodulatory Agent for Cancer Therapy
Authors: Sasikumar Pottayil G. , Ramachandra Raghuveer K. , Adurthi Srinivas , Dhudashiya Amit A. , Vadlamani Sureshkumar , Vemula Koteswararao , Vunnum Sriharibabu , Satyam Leena K. , Samiulla Dodderi S. , Subbarao Krishnaprasad , Nair Rashmi , Shrimali Rajeev , Gowda Nagaraj , Ramachandra Murali
Published: April 2019

Pioneering success of antibodies targeting immune checkpoints such as PD-1 and CTLA4 has opened novel avenues for cancer immunotherapy. Along with impressive clinical activity, severe immune-related adverse events (irAE) due to the breaking of immune self-tolerance are becoming increasingly evident in antibody-based approaches. As a strategy to better manage severe adverse effects, we set out to discover an antagonist targeting PD-1 signaling pathway with a shorter pharmacokinetic profile. Herein, we describe a peptide antagonist NP-12 that displays equipotent antagonism toward PD-L1 and PD-L2 in rescue of lymphocyte proliferation and effector functions. In preclinical models of melanoma, colon cancer, and kidney cancers, NP-12 showed significant efficacy comparable with commercially available PD-1–targeting antibodies in inhibiting primary tumor growth and metastasis. Interestingly, antitumor activity of NP-12 in a preestablished CT26 model correlated well with pharmacodynamic effects as indicated by intratumoral recruitment of CD4 and CD8 T cells, and a reduction in PD-1+ T cells (both CD4 and CD8) in tumor and blood. In addition, NP-12 also showed additive antitumor activity in preestablished tumor models when combined with tumor vaccination or a chemotherapeutic agent such as cyclophosphamide known to induce “immunologic cell death.” In summary, NP-12 is the first rationally designed peptide therapeutic targeting PD-1 signaling pathways exhibiting immune activation, excellent antitumor activity, and potential for better management of irAEs.
Chronic Diarrhea Secondary to Newly Diagnosed VIPoma
Authors: Farina Domenico A. , Krogh Katrina M. , Boike Justin R.
Published: April 2019

Vasoactive intestinal polypeptide-secreting tumors (VIPoma) are a rare pancreatic neuroendocrine tumor that can cause chronic diarrhea with 1 case per 10 million people per year. Diagnosis is made based on a combination of laboratory evaluation (serum VIP level), imaging findings (functional positron emission tomography-computed tomography [PET-CT]), and histological analysis (chromogranin A stain). We present a case of a male with 6 months of diarrhea and malaise who was found to have significant kidney injury and hypokalemia requiring admission to the medical intensive care unit. Subsequent laboratory evaluation while admitted eventually showed a low stool osmotic gap (–11 mOsm/kg) consistent with secretory diarrhea, in addition to significantly elevated VIP levels at 940 pg/mL (normal <75). Cross-sectional imaging with functional Gallium-68 dotatate PET-CT confirmed metastatic functional neuroendocrine tumor indicative of a VIPoma. Pathology on subsequent metastatic liver lesion aspiration was consistent with a well-differentiated VIPoma, and symptoms dramatically improved following initiation of octreotide therapy.
Low Serum Levels of HtrA3 at 15 Weeks of Gestation Are Associated with Late-Onset Preeclampsia Development and Small for Gestational Age Birth
Authors: Teoh Sonia Soo Yee , Wang Yao , Li Ying , Leemaqz Shalem Yiner-Lee , Dekker Gus A. , Roberts Claire T. , Nie Guiying
Published: April 2019

Objective: The aim of this study was to investigate the potential utility of serum HtrA1 and HtrA3, serine proteases that are highly expressed in the developing placenta, at 15 and 20 weeks of gestation for predicting later development of adverse pregnancy outcomes of preeclampsia (PE), gestational hypertension (GHT), preterm birth (PTB), and small for gestational age (SGA) birth. Methods: This is a nested case control study of 665 samples (330 controls, 335 cases) from the Adelaide SCOPE cohort. The cases included were 92 PE, 71 GHT, 56 PTB, and 116 SGA. Samples were assessed by ELISA and data adjusted for maternal age, BMI, socioeconomic index, hCG, and smoking status. Multivariate logistic regression was performed with other biochemical and biophysical parameters available for these samples. Results: HtrA1 did not differ between the controls and cases. In contrast, HtrA3 was significantly lower at 15 weeks in pregnancies that later developed late-onset PE (LPE) or resulted in SGA birth, with an area under the ROC curve (AUC) of 0.716 and 0.790, respectively. The combination of HtrA3 with PAPP-A, uterine, and umbilical Doppler improved the AUC to 0.755 for LPE and 0.844 for SGA. Conclusion: HtrA3 at 15 weeks is associated with, and may be useful for, the early detection of LPE development and SGA birth.
A Review of Heuristic Global Optimization Based Artificial Neural Network Training Approahes
Authors: Amali D. Geraldine Bessie , M. Dinakaran
Published: April 2019

Artificial Neural Networks have earned popularity in recent years because of their ability to approximate nonlinear functions. Training a neural network involves minimizing the mean square error between the target and network output. The error surface is nonconvex and highly multimodal. Finding the minimum of a multimodal function is a NP complete problem and cannot be solved completely. Thus application of heuristic global optimization algorithms that computes a good global minimum to neural network training is of interest. This paper reviews the various heuristic global optimization algorithms used for training feedforward neural networks and recurrent neural networks. The training algorithms are compared in terms of the learning rate, convergence speed and accuracy of the output produced by the neural network. The paper concludes by suggesting directions for novel ANN training algorithms based on recent advances in global optimization.
Firefly Algorithm Solution to Improving Threshold Distributed Energy Efficient Clustering Algorithm for Heterogeneous Wireless Sensor Networks
Authors: Mostafa Baghouri , Saad Chakkor , Abderrahmane Hajraoui
Published: April 2019

The improvement of the lifetime of heterogeneous wireless sensor networks is a challenge for many researches. One of the most important protocols to achieve this goal is to divide the network into clusters that run by a single node called cluster head and the others have attached. However, all nodes must form the cluster including the nearest nodes to the base station which should be excluded from the clustering process. Furthermore these nodes consume more energy since each member node communicates directly with their cluster head and not with the base station. To eliminate these notes from cluster process, we need to formulate a new energy total of the network which depends on the number of these nodes. In this paper we propose a new technic to optimize this energy which basing on the firefly algorithm. The developed approach allows the boundary of the excluded nodes efficiently. Computer simulation in MATLAB proves the superiority of this method concerning the increase of the lifetime and the number of the received packet messages compared to the others protocols.