bluuebunny/crossref_metadata_2025 huggingface dataset:
Bone Regeneration of Peri-Implant Defects Using a Collagen Membrane as a Carrier for Recombinant Human Bone Morphogenetic Protein-2
Authors: Sun Yoo-Kyung , Cha Jae-Kook , Thoma Daniel Stefan , Yoon So-Ra , Lee Jung-Seok , Choi Seong-Ho , Jung Ui-Won
Published: June 2018

This study is designed to determine the effect of collagen membrane (CM) soaked with bone morphogenetic protein-2 (rhBMP-2) for the treatment of peri-implant dehiscence defects. Material and Methods. Three treatment groups were allocated at each defect in 5 dogs: (i) collagenated synthetic bone (OC) and CM soaked with rhBMP-2 (BMP group), (ii) OC and CM soaked with saline (nonBMP group), and (iii) no further treatment (control group). Titanium pins were used to stabilize the membranes in two dogs. Radiographic and histomorphometric analyses were performed 4 weeks later. Results. The median augmented volumes were 4.27 mm3, 6.24 mm3, and 2.75 mm3 in the BMP, nonBMP, and control groups, respectively; the corresponding median first bone-to-implant contact (fBIC) distances were 3.25 mm, 3.08 mm, and 2.56 mm (P>0.05). The placement of pins (with the BMP and nonBMP groups pooled) significantly improved bone regeneration: the augmented volumes were 17.60 mm3 with pins and 3.68 mm3 without pins (P=0.024), with corresponding fBIC distances of 2.25 mm and 3.31 mm, respectively (P<0.001). Conclusions. The addition of rhBMP-2 to CM failed to improve bone regeneration of peri-implant dehiscence defects compared to using an unsoaked CM after 4 weeks. However, the stabilization of CMs using pins positively influenced the outcomes.
A Stochastic SIR Epidemic System with a Nonlinear Relapse
Authors: El Myr Ali , Assadouq Abdelaziz , Omari Lahcen , Settati Adel , Lahrouz Aadil
Published: June 2018

We investigate the conditions that control the extinction and the existence of a unique stationary distribution of a nonlinear mathematical spread model with stochastic perturbations in a population of varying size with relapse. Numerical simulations are carried out to illustrate the theoretical results.
Gamisoyo-San Ameliorates Neuroinflammation in the Spinal Cord of hSOD1G93A Transgenic Mice
Authors: Cai MuDan , Yang Eun Jin
Published: June 2018

Amyotrophic lateral sclerosis (ALS), a progressive disorder, causes motor neuron degeneration and neuromuscular synapse denervation. Because this is a complex disease, there are no effective drugs for the treatment of patients with ALS. For example, riluzole is used in many countries but has many side effects and only increases the lifespan of patients by approximately 2-3 months. Therefore, patients with ALS often turn to complementary and alternative medicine, such as acupuncture, homeopathy, and herbal medicine, with the hope and belief of recovery, despite the lack of definite evidence on the efficacy of these methods. Gamisoyo-San (GSS), a herbal medicine known to improve health, has been used for stress-related neuropsychological disorders, including anorexia, in Asian countries, such as China, Korea, and Japan. To evaluate the effects of GSS on the spinal cord, we investigated the expression of neuroinflammatory and metabolic proteins in symptomatic hSOD1G93A mice. We observed that GSS reduces the expression of glial markers, including those for microglia and astrocytes, and prevents neuronal loss. Moreover, we found that GSS inhibits the expression of proteins related to Toll-like receptor 4 signaling and oxidative stress, known to cause neuroinflammation. Notably, GSS also regulates metabolism in the spinal cord of transgenic mice. These results suggest that GSS could be used for improving the immune system and increasing the life quality of patients with ALS.
Survival Outcomes and Factors Associated with Revision Surgery for Metastatic Disease of the Spine
Authors: Alamanda Vignesh K. , Robinson Myra M. , Kneisl Jeffrey S. , Spector Leo R. , Patt Joshua C.
Published: June 2018

Study Design. Retrospective review of a prospective database. Objective. Certain subset of patients undergoing surgical treatment for spinal metastasis will require a revision surgery in their disease course; however, factors predictive of revision surgery and survival outcomes are largely unknown. The goal of this study is to report on survival outcomes as well as factors predictive of revision surgery in this unique patient population. Methods. A total of 55 patients who met the inclusion criteria were included from January 2010 to December 2015. Twelve (22%) of these patients underwent a revision surgery. Patient and tumor characteristics were summarized and survival outcomes were evaluated using Kaplan-Meier methods and Cox proportional hazards regression. Results. Both the revision and the nonrevision groups were similarly matched with respect to spine disease burden, neurological status at time of initial presentation, primary malignancy types, and the use of adjuvant treatment modalities. Tumor progression (66.7%) was the most common reason for necessitating a revision followed by nonunion (16.7%), wound dehiscence (8.3%), and construct failure (8.3%). Following multivariate model selection procedures, smokers were found to have 3.5 times increased odds of undergoing revision compared to nonsmokers (p = 0.05). Analysis of survival curves showed that the median survival in the revision group was 3.0 years (95% CI: 1.5, 4.1), while the median survival in the nonrevision group was 1.5 years (95% CI: 1.1, 2.3; log-rank test, p = 0.105). Conclusion. Despite aggressive treatment, tumor progression is the most common reason for revision surgery. Smoking is an independent risk factor for revision. Revision surgery should be considered in patients when indicated as it does not appear to detrimentally affect survival.
Smilax aristolochiifolia Root Extract and Its Compounds Chlorogenic Acid and Astilbin Inhibit the Activity of α‐Amylase and α‐Glucosidase Enzymes
Authors: Pérez-Nájera Viridiana Candelaria , Gutiérrez-Uribe Janet Alejandra , Antunes-Ricardo Marilena , Hidalgo-Figueroa Sergio , Del-Toro-Sánchez Carmen Lizette , Salazar-Olivo Luis A. , Lugo-Cervantes Eugenia
Published: June 2018

Regulating activities of α‐amylase and α‐glucosidase through the use of specific inhibitors is a main strategy for controlling type 2 diabetes. Smilax aristolochiifolia root decoctions are traditionally used in Mexico as hypoglycemic and for weight loss, but the active principles and mechanisms underlying such putative metabolic effects are yet unknown. Here, we isolated the major bioactive compounds from a hydroethanolic extract of S. aristolochiifolia root by fast centrifugal partition chromatography and evaluated their effects against pancreatic α‐amylase and yeast α‐glucosidase. A chlorogenic acid‐rich fraction (CAF) inhibited α‐amylase activity with an IC50 value of 59.28 μg/mL in an uncompetitive manner and α‐glucosidase activity with an IC50 value of 9.27 μg/mL in a noncompetitive mode. Also, an astilbin‐rich fraction (ABF) inhibited α‐glucosidase activity with an IC50 value of 12.30 μg/mL, in a noncompetitive manner. CAF inhibition α‐amylase was as active as acarbose while both CAF and ABF were 50‐fold more potent inhibitors of α‐glucosidase than acarbose. The molecular docking results of chlorogenic acid and astilbin with α‐amylase and α‐glucosidase enzymes correlated with the inhibition mechanisms suggested by enzymatic assays. Our results prove that S. aristolochiifolia roots contain chlorogenic acid and astilbin, which inhibit carbohydrates‐hydrolyzing enzymes, suggesting a new mechanism for the hypoglycemic effect reported for this plant.
An Effective Watermarking Method Based on Energy Averaging in Audio Signals
Authors: Tsai S. E. , Yang S. M.
Published: June 2018

Methods based on discrete cosine transform (DCT) have been proposed for digital watermarking of audio signals; however, the watermark is often vulnerable to data compression and signal processing. This paper presents an effective audio watermarking method by energy averaging of DCT coefficients such that an audio signal with watermark is robust to data processing. The method is to divide an audio signal into segments by three parameters defining the segment length, the segment sequence of watermark location, and the frequency range of DCT coefficients for watermark location. An error correcting code is also integrated to improve audio signal quality after watermarking. Experimental results show that the method is robust to data compression and many other kinds of signal processing. No original signal is required for decoding the watermark. Comparison of watermarking performance with a recent work validates that the watermarking method has better audio quality and higher robustness.
The GUP Effect on Tunneling of Massive Vector Bosons from The 2+1 Dimensional Black Hole
Authors: Gecim Ganim , Sucu Yusuf
Published: June 2018

In this study, the Generalized Uncertainty Principle (GUP) effect on the Hawking radiation formed by tunneling of a massive vector boson particle from the 2+1 dimensional new-type black hole was investigated. We used modified massive vector boson equation based on the GUP. Then, the Hamilton-Jacobi quantum tunneling approach was used to work out the tunneling probability of the massive vector boson particle and Hawking temperature of the black hole. Due to the GUP effect, the modified Hawking temperature was found to depend on the black hole properties, on the AdS3 radius, and on the energy, mass, and total angular momentum of the tunneling massive vector boson. In the light of these results, we also observed that modified Hawking temperature increases by the total angular momentum of the particle while it decreases by the energy and mass of the particle and the graviton mass. Also, in the context of the GUP, we see that the Hawking temperature due to the tunneling massive vector boson is completely different from both that of the spin-0 scalar and that of the spin-1/2 Dirac particles obtained in the previous study. We also calculate the heat capacity of the black hole using the modified Hawking temperature and then discuss influence of the GUP on the stability of the black hole.
Influence of Microscopic Parameters on the Stress‐Strain Relation in Rocks
Authors: Cheng Yanhui , Yang Weijun
Published: June 2018

Macromaterial properties should correspond to the mesoscopic parameters simulated in practical engineering problems. Discrete element contains a variety of particle models and its corresponding mesoscopic parameters, and the one‐to‐one relationship between the mesoscopic parameters and macroscopic parameters is difficult to establish. This paper studies the influence of microscopical characteristic parameters, such as particle contact stiffness ratio, parallel bond stiffness ratio, particle contact modulus, and parallel bond elastic modulus, on the stress‐strain relation in rocks, which shows that (1) The range of particle contact stiffness ratio kn/ks largely varies, but the stress‐strain relation curve is relatively small. The particle contact stiffness has less influence on the elastic modulus of the simulated specimens than kn/ks. (2) Before the failure of the specimen, the axial strain corresponding to the peak compressive strength increases with the increase in the stiffness ratio / of the parallel bond. (3) The particle contact modulus Ec has a great influence on the elastic modulus of sandstone and is characterized by the increase in the particle contact modulus Ec, corresponding axial strain for the peak compressive strength decreases, and the slope of the stress‐strain relationship curves before damage increases. (4) The elastic modulus of the parallel bond greatly influences the uniaxial compressive strength, and the relationship between them is proportional.
A Study of Coupled Creep Damaged Constitutive Model of Artificial Frozen Soil
Authors: Li Dongwei , Chen Junhao , Zhou Yan
Published: June 2018

Artificial frozen soil is a kind of typical creep material, and the frozen clay under the unloading stress paths of high‐confining pressure conforms to the improved the Zienkiewicz–Pande parabola‐type yield criterion, and the Mohr–Coulomb yield function can describe the shear yield surface of artificial frozen clay under low‐confining pressure. Based on the results of triaxial creep and shear tests for artificial frozen soil, the viscoplastic damage variable and evolution rule of artificial frozen clay were obtained by using the theory of viscoelastic‐plastic mechanics and damage mechanics. An improved Zienkiewicz–Pande parabola‐type yield criterion was used instead of a linear Newton body to obtain a coupled constitutive model of viscoelastic‐plastic damage in the frozen soil under the unloading stress paths and to derive the coupling flexibility matrix for viscoelastic and viscoplastic damage. A finite element program of artificial frozen soil considering creep damage was written in the Visual Fortran 6.6A environment and embedded into the nonlinear finite element software ADINA as a user subroutine. The results of numerical simulation and laboratory testing were identical, with a maximum error of no more than 4.8%. This work shows that it is reasonable to describe the creep constitutive model of frozen soil with the viscoelastic‐plastic‐coupled constitutive model.
Hole Transport Behaviour of Various Polymers and Their Application to Perovskite-Sensitized Solid-State Solar Cells
Authors: Lim Jeongmin , Kong Seong Young , Yun Yong Ju
Published: June 2018

Inorganic-organic mesoscopic solar cells become a promising alternative for conventional solar cells. We describe a CH3NH3PbI3 perovskite-sensitized solid-state solar cells with the use of different polymer hole transport materials such as 2,2′,7,7′-tetrakis-(N,N-di-p-methoxyphenyl-amine)-9,9′-spirobifluorene (spiro-OMeTAD), poly(3-hexylthiophene-2,5-diyl) (P3HT), and poly[[4,8-bis[(2-ethylhexyl)oxy]benzo[1,2-b:4,5-b′]dithiophene-2,6-diyl][3-fluoro-2-[(2-ethylhexyl)carbonyl]thieno[3,4-b]thiophenediyl]] (PTB7). The device with a spiro-OMeTAD-based hole transport layer showed the highest efficiency of 6.9%. Interestingly, the PTB7 polymer, which is considered an electron donor material, showed dominant hole transport behaviors in the perovskite solar cell. A 200 nm thin layer of PTB7 showed comparatively good efficiency (5.5%) value to the conventional spiro-OMeTAD-based device.
Addressing Stem Cell Therapeutic Approaches in Pathobiology of Diabetes and Its Complications
Authors: Peng Bou-Yue , Dubey Navneet Kumar , Mishra Viraj Krishna , Tsai Feng-Chou , Dubey Rajni , Deng Win-Ping , Wei Hong-Jian
Published: June 2018

High morbidity and mortality of diabetes mellitus (DM) throughout the human population is a serious threat which needs to be addressed cautiously. Type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) are most prevalent forms. Disruption in insulin regulation and resistance leads to increased formation and accumulation of advanced end products (AGEs), which further enhance oxidative and nitrosative stress leading to microvascular (retinopathy, neuropathy, and nephropathy) and macrovascular complications. These complications affect the normal function of organ and tissues and may cause life-threatening disorders, if hyperglycemia persists and improperly controlled. Current and traditional treatment procedures are only focused on to regulate the insulin level and do not cure the diabetic complications. Pancreatic transplantation seemed a viable alternative; however, it is limited due to lack of donors. Cell-based therapy such as stem cells is considered as a promising therapeutic agent against DM and diabetic complications owing to their multilineage differentiation and regeneration potential. Previous studies have demonstrated the various impacts of both pluripotent and multipotent stem cells on DM and its micro- and macrovascular complications. Therefore, this review summarizes the potential of stem cells to treat DM and its related complications.
Toward Improving Medication Adherence: The Suppression of Bitter Taste in Edible Taste Films
Authors: Cherian Silvy , Lee Brian Sang , Tucker Robin M. , Lee Kevin , Smutzer Gregory
Published: June 2018

Bitter taste is aversive to humans, and many oral medications exhibit a bitter taste. Bitter taste can be suppressed by the use of inhibitors or by masking agents such as sucralose. Another approach is to encapsulate bitter tasting compounds in order to delay their release. This delayed release can permit the prior release of bitter masking agents. Suppression of bitter taste was accomplished by encapsulating a bitter taste stimulus in erodible stearic acid microspheres, and embedding these 5 µmeter diameter microspheres in pullulan films that contain sucralose and peppermint oil as masking agents, along with an encapsulated masking agent (sucralose). Psychophysical tests demonstrated that films which encapsulated both quinine and sucralose produced a significant and continuous sweet percept when compared to films without sucralose microspheres. Films with both quinine and sucralose microspheres also produced positive hedonic scores that did not differ from control films that contained only sucralose microspheres or only empty (blank) microspheres. The encapsulation of bitter taste stimuli in lipid microspheres, and embedding these microspheres in rapidly dissolving edible taste films that contain masking agents in both the film base and in microspheres, is a promising approach for diminishing the bitter taste of drugs and related compounds.
P-v Criticality of a Specific Black Hole in f(R) Gravity Coupled with Yang-Mills Field
Authors: Övgün Ali
Published: June 2018

We study the P-v criticality of a specific charged AdS type black hole (SBH) in f(R) gravity coupled with Yang-Mills field. In the extended phase space, we treat the cosmological constant as a thermodynamic pressure. After we study the various thermodynamical quantities, we show that the thermodynamic properties of the SBH behave as a Van der Waals liquid-gas system at the critical points and there is a first-order phase transition between small-large SBH.
Variation and Relationships among Agronomic Traits in Durum Wheat [Triticum turgidum(L.) Thell. ssp.turgidumconv.durum(Desf.) MacKey] under South Mediterranean Growth Conditions: Stepwise and Path Analyses
Authors: Mansouri Ali , Oudjehih Bachir , Benbelkacem Abdelkader , Fellahi Zine El Abidine , Bouzerzour Hamenna
Published: June 2018

Relationships among agronomic traits and grain yield were investigated in 56 genotypes of durum wheat (Triticum durumDesf.). The results indicated the presence of sufficient variability nearly for all measured traits. Heritability and expected genetic gain varied among traits. Aboveground biomass, harvest index, and spike number were the most grain yield-influencing traits. Early genotypes showed above-average grain and biological yields, spike number, and lower canopy temperature. Assessed genotypes were clustered into three groups which differed mainly for biological, economical, straw, and grain yields, on the one hand, and plant height, chlorophyll content, and canopy temperature, on the other hand. Selection for direct use from clusters carrying best combinations of yield-related traits and crosses to be made between genotypes belonging to contrasted clusters were suggested to generate more variability. Selection preferentially for spike number, biological yield, harvest index, and canopy temperature to accumulate favorable alleles in the selected entries for future uses is suggested.
Explicit Pricing Formulas for European Option with Asset Exposed to Double Defaults Risk
Authors: He Taoshun
Published: June 2018

We derive analytical formulas for European call and put options on underlying assets that are exposed to double defaults risks which include exogenous counterparty default risk and endogenous default risk. The endogenous default risk leads the asset price to drop to zero and the exogenous counterparty default risk induces a drop in the asset price, but the asset can still be traded after this default time. A novel technique is developed to evaluate the European call and put options by first conditioning on the predefault and the postdefault time and then obtaining the unconditional analytic formulas for their price. We also compare the pricing results of our model with default-free option model and counterparty default risk option model.
Experimental Study and Application of a Novel Foamed Concrete to Yield Airtight Walls in Coal Mines
Authors: Wen Hu , Fan Shixing , Zhang Duo , Wang Weifeng , Guo Jun , Sun Qingfeng
Published: June 2018

Airtight walls are vital to prevent spontaneous combustion of residual coal as caused by air leakage. A new type of foamed concrete (FC) was developed to control air leakage. FC specimens of four densities (250, 450, 650, and 850 kg/m3) were prepared for use in a series of physical and mechanical tests. A thickener was used to control the FC shrinkage and collapse. The permeability of the FC decreased approximately exponentially with an increasing density. On the contrary, the compressive strength (σ) and elastic modulus (E) increased in exponential and linear relationship separately with the increase in density, under uniaxial compression conditions. Under triaxial compression, the compressive strength of the FC increased with an increase in confining pressure and appeared slight plastic. The impact experiment showed that the dynamic compressive strength of the FC appeared to be strain‐rate dependent, and it increased with an increase in the strain rate and pressure under a confining pressure. Without a confining pressure, the variation in compressive strength exhibited a slow decrease. Applied FC resulted in a 5 MPa 28‐day compressive strength of the airtight wall with no remaining fissures and with air leakage suppression to the gob.
An Analysis of the Impact Exerted on Bearing Capacity of Pier and Pile after Increasing Pile Cap Height
Authors: Huang Xianbin , Liu Chenyang , Hou Song , Chen Chunyang , Wangren Yahong , Xu Jialin
Published: June 2018

An analysis was carried out in this paper on the bearing capacity of pier pile and seismic performance rule when the low‐pile cap is increased by 1 meter, 2 meters, and 3 meters. The bottom of the pile cap of pier no. 11 of Minjiang River bridge faces three “lows”: 7.6 meters lower than island, 4.6 meters lower than natural river bed, and 6.5 meters lower than low water level. The numerical simulation method is adopted to input three seismic waves of Wolong, Bajiao, and EL to evaluate the bearing capacity of pier and pile under strong earthquakes. Using the standard formula and numerical simulation method, it is observed that the bending moment and axial force of bridge pier show an insignificant change under different seismic waves when the pile cap is increased by 0–3 meters. With peak ground acceleration increased to 0.35 g, the vertical bearing capacity and flexural capacity of pier and pile gratify the requirements; however, the pile foundation will be subject to compression and bending damage.
Causal Inference in Cancer Epidemiology: What Is the Role of Mendelian Randomization?
Authors: Yarmolinsky James , Wade Kaitlin H. , Richmond Rebecca C. , Langdon Ryan J. , Bull Caroline J. , Tilling Kate M. , Relton Caroline L. , Lewis Sarah J. , Davey Smith George , Martin Richard M.
Published: June 2018

Observational epidemiologic studies are prone to confounding, measurement error, and reverse causation, undermining robust causal inference. Mendelian randomization (MR) uses genetic variants to proxy modifiable exposures to generate more reliable estimates of the causal effects of these exposures on diseases and their outcomes. MR has seen widespread adoption within cardio-metabolic epidemiology, but also holds much promise for identifying possible interventions for cancer prevention and treatment. However, some methodologic challenges in the implementation of MR are particularly pertinent when applying this method to cancer etiology and prognosis, including reverse causation arising from disease latency and selection bias in studies of cancer progression. These issues must be carefully considered to ensure appropriate design, analysis, and interpretation of such studies. In this review, we provide an overview of the key principles and assumptions of MR, focusing on applications of this method to the study of cancer etiology and prognosis. We summarize recent studies in the cancer literature that have adopted a MR framework to highlight strengths of this approach compared with conventional epidemiological studies. Finally, limitations of MR and recent methodologic developments to address them are discussed, along with the translational opportunities they present to inform public health and clinical interventions in cancer. Cancer Epidemiol Biomarkers Prev; 27(9); 995–1010. ©2018 AACR.
Inhibition of BET Bromodomain Proteins with GS-5829 and GS-626510 in Uterine Serous Carcinoma, a Biologically Aggressive Variant of Endometrial Cancer
Authors: Bonazzoli Elena , Predolini Federica , Cocco Emiliano , Bellone Stefania , Altwerger Gary , Menderes Gulden , Zammataro Luca , Bianchi Anna , Pettinella Francesca , Riccio Francesco , Han Chanhee , Yadav Ghanshyam , Lopez Salvatore , Manzano Aranzazu , Manara Paola , Buza Natalia , Hui Pei , Wong Serena , Litkouhi Babak , Ratner Elena , Silasi Dan-Arin , Huang Gloria S. , Azodi Masoud , Schwartz Peter E. , Schlessinger Joseph , Santin Alessandro D.
Published: June 2018

Purpose: Uterine serous carcinoma (USC) is a rare and aggressive variant of endometrial cancer. Whole-exome sequencing (WES) studies have recently reported c-Myc gene amplification in a large number of USCs, suggesting c-Myc as a potential therapeutic target. We investigated the activity of novel BET bromodomain inhibitors (GS-5829 and GS-626510, Gilead Sciences Inc.) and JQ1 against primary USC cultures and USC xenografts.

Experimental Design: We evaluated c-Myc expression by qRT-PCR in a total of 45 USCs including fresh-frozen tumor tissues and primary USC cell lines. We also performed IHC and Western blot experiments in 8 USC tumors. USC cultures were evaluated for sensitivity to GS-5829, GS-626510, and JQ1 in vitro using proliferation, viability, and apoptosis assays. Finally, the in vivo activity of GS-5829, GS-626510, and JQ1 was studied in USC-ARK1 and USC-ARK2 mouse xenografts.

Results: Fresh-frozen USC and primary USC cell lines overexpressed c-Myc when compared with normal tissues (P = 0.0009 and 0.0083, respectively). High c-Myc expression was found in 7 of 8 of primary USC cell lines tested by qRT-PCR and 5 of 8 tested by IHC. In vitro experiments demonstrated high sensitivity of USC cell lines to the exposure to GS-5829, GS-626510, and JQ1 with BET inhibitors causing a dose-dependent decrease in the phosphorylated levels of c-Myc and a dose-dependent increase in caspase activation (apoptosis). In comparative in vivo experiments, GS-5829 and/or GS-626510 were found more effective than JQ1 at the concentrations/doses used in decreasing tumor growth in both USC-ARK1 and USC-ARK2 mouse xenograft models.

Conclusions: GS-5829 and GS-626510 may represent novel, highly effective therapeutics agents against recurrent/chemotherapy-resistant USC-overexpressing c-Myc. Clinical studies with GS-5829 in patients with USC harboring chemotherapy-resistant disease are warranted. Clin Cancer Res; 24(19); 4845–53. ©2018 AACR.
Two Weeks' Notice from Allogeneic Sources
Authors: Anczurowski Mark , Hirano Naoto
Published: June 2018

A novel pipeline for neoantigen-specific T-cell receptor (TCR) identification has been validated in ovarian cancer, making use of HLA-matched allogeneic healthy donor T cells. This workflow allows for the identification of tumor-specific TCRs 2 weeks after antigen-specific stimulation and eliminates problematic patient-to-patient variation in the selection of neoantigen-specific TCRs. Clin Cancer Res; 24(21); 5195–7. ©2018 AACR.

See related article by Matsuda et al., p. 5357
Effectiveness, Costs and Patient Acceptance of a Conventional and a Biological Treatment Approach for Carious Primary Teeth in Children
Authors: BaniHani Alaa , Deery Chris , Toumba Jack , Duggal Monty
Published: June 2018

Background: Over the last years, conventional restorations for the treatment of active carious lesions (CL) in primary teeth have been challenged and a more biological approach has been suggested. This approach involves less invasive techniques that alter the environment of the CL isolating it from the cariogenic biofilm and substrate. Aim: To investigate the cost-effectiveness and patient acceptance of 2 treatment approaches for the treatment of deep CLs in primary teeth in children. Methods: This was a retrospective/prospective cohort study carried out in 2 UK specialist hospital settings. Data on cost-effectiveness was extracted retrospectively from clinical dental records of 246 patients aged 4–9 years. A prospective study design was used to explore patient acceptance of the 2 treatment approaches. One hundred and ten patients aged 4–9 years and their carers completed 2 questionnaires on treatment acceptance. Results: In total, 836 primary teeth that had received treatment with either approach were included. More than 2 thirds (75.7%) of the restorations in the conventional approach were of non-selective removal to hard dentine followed by pulpotomy (24.3%). In the biological approach, most of the restorations were stainless steel crowns placed with the Hall Technique (95%) followed by selective removal to firm dentine (5%). The majority of the primary teeth remained asymptomatic after a follow-up period of up to 77 months; 95.3% in the conventional and 95.8% in the biological arm. When the treatment costs were analysed, a statistically significant difference was found between the mean costs of the 2 approaches with a mean difference of GBP 45.20 (Pound Sterling; p < 0.001), in favour of the biological approach. The majority of the children and carers were happy with the conventional or biological restorations. Conclusion: Although both approaches had similar successful outcomes, the biological approach consisting mainly of Hall Technique was associated with reduced treatment costs. Both approaches were accepted favourably by the children and carers.
A Patient with Ulcerative Colitis Complicated by Systemic Vein Thrombosis
Authors: Meštrović Antonio , Žaja Ivan , Ardalić Žarko , Vrebalov-Cindro Pavle , Šustić Ivan , Puljiz Marko , Bratanić Andre , Bonacin Damir
Published: June 2018

Crohn’s disease and ulcerative colitis (UC) patients have an increased risk for thromboembolic complications, the most common of them are deep venous thrombosis and pulmonary embolism. Other locations and genetic mutations of coagulation factors are not so common in these patients. Here we present a case of a young woman with exacerbation of previously diagnosed mild UC complicated by multiple thrombotic incidents due to MTHFR gene mutation.
Hemolysis and Glucose-6-Phosphate Dehydrogenase Deficiency-Related Neonatal Hyperbilirubinemia
Authors: Kaplan Michael , Wong Ronald J. , Stevenson David K.
Published: June 2018

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common enzyme deficiency affecting more than 300 million individuals worldwide. Extreme neonatal hyperbilirubinemia, with its severe sequelae of bilirubin neurotoxicity and the potential of death, is the most devastating manifestation of G6PD deficiency. In a recent review of Favism, Luzzatto and Arese state that the pathophysiology of jaundice in G6PD-deficient neonates is different from that of favism, as there is little evidence of hemolysis in these infants. Objectives: To explore the role of hemolysis in neonatal hyperbilirubinemia associated with G6PD deficiency. Methods: Previously published works including studies of endogenous production of carbon monoxide (CO), an index of heme catabolism, in hyperbilirubinemic G6PD-deficient neonates were reviewed to determine the role of hemolysis in this condition. Results: Three studies demonstrated that endogenous CO production is elevated in G6PD-deficient neonates with extreme hyperbilirubinemia. Conclusions: Hemolysis is an important pathogenetic factor in G6PD deficiency-associated neonatal hyperbilirubinemia.
Assessing the Surgical Experience to Identify Risk Factors Associated with Severe Retinopathy of Prematurity and Laser Intervention
Authors: Torr Carrie , Yoder Bradley , Beachy Joanna
Published: June 2018

Background: Retinopathy of prematurity (ROP) is a known complication of preterm birth and one of the leading causes of blindness. Known risk factors include low gestational age (GA), birth weight, and oxygen exposure. It is unknown if there are surgical risk factors associated with severe ROP. Objectives: Identify risk factors of a neonatal surgical exposure associated with laser therapy for ROP. Methods: Institutional review of 76 infants with GA ≤27 weeks or birth weight ≤800 g. Infant demographics and details of surgical experience were collected. Infants who underwent a surgical procedure were analyzed to identify risk factors associated with laser treatment for severe ROP. Surgical and nonsurgical infants were compared to assess if the rate of laser intervention differed among institutions/published data. Data were analyzed using the Mann-Whitney U test, unpaired t test, OR and Fischer’s exact test. Result: Out of 49 surgical infants, 11 underwent laser intervention. Infants undergoing laser had surgery at an earlier postmenstrual age (PMA; 31.5 [29.3–39.4] weeks vs. 38.1 [31.3–42.5] weeks, p = 0.01), were more likely to have an exploratory laparotomy (adjusted odds ratio 1.3 [1.04–1.64], p = 0.02), and to undergo more surgical procedures (3 vs. 2, p = 0.04). Conclusion: At our institution, preterm infants who undergo a surgical procedure prior to 32 weeks PMA and those having ≥3 surgeries were at a higher risk for progressing to laser intervention. Additional studies with larger sample sizes are needed to assess if the risk factors we have identified remain significant and to identify other possible risk factors.
Analysis of Genes Involved in Persistent Atrial Fibrillation: Comparisons of ‘Trigger’ and ‘Substrate’ Differences
Authors: Zou Rongjun , Yang Minglei , Shi Wanting , Zheng Chengxi , Zeng Hui , Lin Xifeng , Zhang Dingwen , Yang Songran , Hua Ping
Published: June 2018

Background/Aims: Recent research has improved our understanding of the pulmonary vein and surrounding left atrial (LA-PV) junction and the left atrial appendage (LAA), which are considered the ‘trigger’ and ‘substrate’ in the development of atrial fibrillation (AF), respectively. Herein, with the aim of identifying the underlying potential genetic mechanisms, we compared differences in gene expression between LA-PV junction and LAA specimens via bioinformatic analysis. Methods: Microarray data of AF (GSE41177) were downloaded from the Gene Expression Omnibus database. In addition, linear models for microarray data limma powers differential expression analyses and weighted correlation network analysis (WGCNA) were applied. Results: From the differential expression analyses, 152 differentially expressed genes and hub genes, including LEP, FOS, EDN1, NMU, CALB2, TAC1, and PPBP, were identified. Our analysis revealed that the maps of extracellular matrix (ECM)-receptor interactions, PI3K-Akt and Wnt signaling pathways, and ventricular cardiac muscle tissue morphogenesis were significantly enriched. In addition, the WGCNA results showed high correlations between genes and related genetic clusters to external clinical characteristics. Maps of the ECM-receptor interactions, chemokine signaling pathways, and the cell cycle were significantly enriched in the genes of corresponding modules and closely associated with AF duration, left atrial diameter, and left ventricular ejection function, respectively. Similarly, mapping of the TNF signaling pathway indicated significant association with genetic traits of ischemic heart disease, hypertension, and diabetes comorbidity. Conclusions: The ECM-receptor interaction as a possible central node of comparison between LA-PV and LAA samples reflected the special functional roles of ‘triggers’ and ‘substrates’ and may be closely associated with AF duration. Furthermore, LEP, FOS, EDN1, NMU, CALB2, TAC1, and PPBP genes may be implicated in the occurrence and maintenance of AF through their interactions with each other.
Exosomes: The New Mediator of Peritoneal Membrane Function
Authors: Yu Manshu , Shi Jun , Sheng Meixiao
Published: June 2018

Fibrosis and angiogenesis are the most common processes that result in progressive peritoneal tissue remodeling and, eventually, peritoneal membrane dysfunction. The role of exosomes, which contributes to intercellular communication, in these processes has been neglected. Various biomolecules, including DNA, mRNA, proteins, lipids, and particular certain miRNAs, can be transferred by exosomes to local, neighboring and distal cells. Upon stimulation by cytokines or other microenvironment stimuli, donor cells release a mass of exosomes to peritoneal mesothelial cells, further affecting fibrosis and angiogenesis. This important exosomes-mediated intracellular communication is thought to regulate peritoneal membrane function. Understanding the molecular mechanisms of these processes, targeting changes in exosomes and regulating exosomal miRNAs will advance therapeutic methods for protecting peritoneal membrane function.
A Prospective Cohort Study Showing No Association Between Serum Sclerostin Level and Mortality in Maintenance Hemodialysis Patients
Authors: Sato Madoka , Hanafusa Norio , Kawaguchi Hiroshi , Tsuchiya Ken , Nitta Kosaku
Published: June 2018

Background/Aims: Potential relationships between serum sclerostin levels and the levels of bone metabolic markers in maintenance hemodialysis (MHD) patients have yet to be evaluated. This study sought to determine whether serum sclerostin levels are associated with mortality in MHD patients. Methods: We measured serum sclerostin levels in a Japanese MHD cohort, classified the patients into tertiles according to these levels, and followed their course for a 42-month period. Results: The cohort consisted of 389 MHD patients and there were 75 deaths. Kaplan-Meier analyses showed that the tertile of serum sclerostin was not associated with mortality risk. Cox analyses showed that there were no significant associations between serum sclerostin level and mortality. Conclusion: Serum sclerostin level was not an independent predictor of mortality in MHD patients after adjustment for several confounders. However, whether clinical interventions to modulate serum sclerostin levels in MHD patients would improve their survival remains to be determined.
Multiple Primary Malignancies in Renal Transplant Recipients: a Single Centre Retrospective Cohort Study
Authors: Basic-Jukic Nikolina , Kirincich Jason , Jelakovic Bojan , Kastelan Zeljko
Published: June 2018

Background/Aims: Renal transplant recipients are exposed to immunosuppressive treatment which may increase the risk for developing malignancies. Limited data exists concerning the occurrence of multiple primary malignancies (MPM) in renal transplant patients. Methods: All the patients who received a renal allograft at our institution from 1973 to 2017 were included in this investigation. Data from patients with more MPM were obtained from the charts and medical records. Malignancies were categorized as synchronous if the interval between occurrences was less than or equal to 6 months and metachronous if the interval was more than 6 months. Results: Out of the 1884 patients who received a renal allograft, 164 (8.7%) developed a malignant tumor. Twenty-two patients (13.4%; 6 females, 16 males) developed MPM, 7 synchronous (31.8%) and 15 metachronous types (68.2%). The most common initial primary tumors were skin cancers (8) and kidney cancers (3). Furthermore, skin cancers were the most common second primary malignancies (9). Log-rank analysis revealed significantly better survival in the synchronous group (113.3 months) than in the metachronous group (24.6 months) (p=0.04). Conclusion: MPM are more frequent in renal transplant recipients than in the general population. It is associated with a high mortality rate, especially in the metachronous group. An increased awareness and frequent screening tests are necessary when managing this condition.
Assessment of Peritoneal Membrane Arteriolar Structure in Conjunction with Traditional Cardiovascular System Evaluation in Chronic Kidney Disease (CKD) Stage 5 Patients
Authors: Donderski Rafal , Stróżecki Paweł , Sulikowska Beata , Grajewska Magdalena , Trafny Ryszard , Bodnar Magdalena , Marszałek Andrzej , Stefańska Anna , Siódmiak Joanna , Odrowąż-Sypniewska Grażyna , Manitius Jacek
Published: June 2018

Background/Aims: Cardiovascular complications are responsible for increased mortality and morbidity in chronic kidney disease (CKD) patients. Functional and structural changes of peritoneal membrane are reported in CKD patients both on conservative treatment and on renal replacement therapy (RRT). The aim of the study was to assess the structure of peritoneal membrane small arteries (precapillary arterioles) in diabetic and non-diabetic CKD stage 5 patients before initiation of peritoneal dialysis (PD) and evaluate its relationship with heart and large arteries abnormalities and with selected biochemical parameters. Methods: Evaluation of 42 CKD stage 5 patients before starting PD. Diabetic (n=26) and non-diabetic (n=16) patients were compared. Peritoneal membrane samples were taken during Tenckhoff catheter insertion. Histopathological evaluation of peritoneal precapillary arterioles (arteriolar evaluation) with measurement of wall thickness (WT) and calculation of lumen/vessel (L/V) ratio was performed in each patients. Echocardiography, intima media thickness (IMT), pulse wave velocity (PWV), ambulatory blood pressure monitoring (ABPM) and biochemical parameters assessment: serum albumin (SA), total cholesterol (TCH), hemoglobin (Hgb), parathormone (PTH), serum calcium (Ca), serum phosphorus (P), transferrin saturation (TSAT%), C-reactive protein (CRP) were performed in each participant. Results: There were no statistically significant differences in peritoneal membrane arteriolar indices – wall thickness (WT) and L/V ratio between investigated groups. There was statistically significant higher PWV value in diabetic patients. There were no statistically significant differences in echocardiographic indices, IMT, laboratory data in analyzed groups. There were some linear correlations between: PWV vs IMT (R=0,84; p=0,0006); PWV vs PP (R=0,58; p=0,03) in non-diabetic and linear correlation between: PWV vs age (R=0,75; p=0,02); WT vs DP (R=-0,93; p=0,001); WT vs DBP ( R=0,64; p=0,04) in diabetic group. Conclusion: Peritoneal membrane arteriolar damage seems to be an integrated part of cardiovascular system damage in CKD stage 5 patients.
Gαi Proteins are Indispensable for Hearing
Authors: Beer-Hammer Sandra , Lee Sze Chim , Mauriac Stephanie A. , Leiss Veronika , Groh Isabel A. M. , Novakovic Ana , Piekorz Roland P. , Bucher Kirsten , Chen Chengfang , Ni Kun , Singer Wibke , Harasztosi Csaba , Schimmang Thomas , Zimmermann Ulrike , Pfeffer Klaus , Birnbaumer Lutz , Forge Andrew , Montcouquiol Mireille , Knipper Marlies , Nürnberg Bernd , Rüttiger Lukas
Published: June 2018

Background/Aims: From invertebrates to mammals, Gαi proteins act together with their common binding partner Gpsm2 to govern cell polarization and planar organization in virtually any polarized cell. Recently, we demonstrated that Gαi3-deficiency in pre-hearing murine cochleae pointed to a role of Gαi3 for asymmetric migration of the kinocilium as well as the orientation and shape of the stereociliary (“hair”) bundle, a requirement for the progression of mature hearing. We found that the lack of Gαi3 impairs stereociliary elongation and hair bundle shape in high-frequency cochlear regions, linked to elevated hearing thresholds for high-frequency sound. How these morphological defects translate into hearing phenotypes is not clear. Methods: Here, we studied global and conditional Gnai3 and Gnai2 mouse mutants deficient for either one or both Gαi proteins. Comparative analyses of global versus Foxg1-driven conditional mutants that mainly delete in the inner ear and telencephalon in combination with functional tests were applied to dissect essential and redundant functions of different Gαi isoforms and to assign specific defects to outer or inner hair cells, the auditory nerve, satellite cells or central auditory neurons. Results: Here we report that lack of Gαi3 but not of the ubiquitously expressed Gαi2 elevates hearing threshold, accompanied by impaired hair bundle elongation and shape in high-frequency cochlear regions. During the crucial reprogramming of the immature inner hair cell (IHC) synapse into a functional sensory synapse of the mature IHC deficiency for Gαi2 or Gαi3 had no impact. In contrast, double-deficiency for Gαi2 and Gαi3 isoforms results in abnormalities along the entire tonotopic axis including profound deafness associated with stereocilia defects. In these mice, postnatal IHC synapse maturation is also impaired. In addition, the analysis of conditional versus global Gαi3-deficient mice revealed that the amplitude of ABR wave IV was disproportionally elevated in comparison to ABR wave I indicating that Gαi3 is selectively involved in generation of neural gain during auditory processing. Conclusion: We propose a so far unrecognized complexity of isoform-specific and overlapping Gαi protein functions particular during final differentiation processes.
Insect galls of the Floresta da Cicuta (Volta Redonda, RJ, Brazil)
Authors: Cividini Flor Ismael , Ribeiro Flor Jandira Chacha , Furtado Paulo Sérgio Do Nascimento
Published: June 2018

Abstract. Insect galls of the Floresta da Cicuta (Volta Redonda, RJ, Brazil). Galls are changes in the pattern of growth and development of plant tissues or organs in response to the action of an inducing organism, usually an insect. The goal of the present study was to inventory the insect galls of the Floresta da Cicuta (Volta Redonda, RJ, Brazil). The collections were carried out along all the trails, totaling 16 hours of sampling. Forty-three morphotypes of insect galls were found in 24 plant species (18 genera and 15 families). Sapindaceae and Euphorbiaceae were the most richness host plant families. Six new records of host plant species are presented: Senefeldera verticillata (Vell.) Croizat. (Euphorbiaceae), Inga acuminata (Fabaceae), Ocotea elegans (Lauraceae), Ouratea stipulata (Ochnaceae), Psychotria nuda (Rubiaceae) and Cestrum intermedium (Solanaceae). Most of the galls occurred on leaves (n = 21) and stems (n = 18), followed by buds (n = 2), two gall morphotypes occurred simultaneously on leaves and stems. One-chambered galls were more frequent (n = 31), as well as glabrous galls (n = 33). The gallers belong to three insect orders: Diptera (Cecidomyiidae), Hemiptera, and Lepidoptera. The associated fauna comprised parasitoids (Hymenoptera), inquilines (Hemiptera and Coleoptera) and successors (Isoptera and Acari).
Foto-ostentação: um novo paradigma fotográfico?
Authors: Oliveira Michel de
Published: June 2018

Este exercício conceitual objetiva compreender os usos da fotografia nas dinâmicas da interação em rede. Para isso, traça um histórico da ostentação e apresenta considerações sobre o papel da imagem fotográfica na sociedade do hiperespetáculo. A hipótese levantada é a de que as reconfigurações da fotografia não se encaixam nos paradigmas preestabelecidos, o que torna necessário uma conceituação crítica para descrever o regime que se consolida, voltado à exposição do cotidiano em detrimento do valor de culto atribuído aos registros domésticos.