bluuebunny/crossref_metadata_2025 huggingface dataset:
Implication of Nonalcoholic Fatty Liver Disease, Metabolic Syndrome, and Subclinical Inflammation on Mild Renal Insufficiency
Authors: Nam Ga Eun , Hwang Soon Young , Chung Hye Soo , Choi Ju Hee , Lee Hyun Jung , Kim Nam Hoon , Yoo Hye Jin , Seo Ji-A , Kim Sin Gon , Kim Nan Hee , Baik Sei Hyun , Choi Kyung Mook
Published: April 2018

Background. Limited information exists about the impact of nonalcoholic fatty liver disease (NAFLD) on mild renal insufficiency. We compared the relative influence of NAFLD, metabolic syndrome (MetS), and subclinical inflammation, alone or in combination, on mild renal insufficiency. Methods. This study included 1174 Korean adults. NAFLD was diagnosed using ultrasonography. Mild renal insufficiency was defined as an estimated glomerular filtration rate (eGFR) ≥ 60 and <90 mL/min/1.73 m2. Results. In partial correlation analysis, several components of MetS and liver aminotransferase levels, but not high-sensitivity C-reactive protein (hsCRP), were associated with eGFR. Multivariate logistic regression analysis demonstrated the independent association of NAFLD (P=0.034) and MetS (P=0.018) with mild renal insufficiency, but not elevated hsCRP (P=0.885). Furthermore, NAFLD without the MetS group (odds ratio (95% confidence interval) = 1.56 (1.05–2.34)) or MetS without the NAFLD group (1.82 (1.11–3.00)) was associated with mild renal insufficiency after adjusting for confounding variables. However, individuals with high hsCRP showed no relationship with mild renal insufficiency, irrespective of the existence of NAFLD. Conclusions. This study demonstrated that NAFLD and MetS are independently associated with mild renal insufficiency, whereas subclinical inflammation did not affect the risk for mild renal insufficiency in Korean adults.
1D TiO2 Nanostructures Prepared from Seeds Presenting Tailored TiO2 Crystalline Phases and Their Photocatalytic Activity for Escherichia coli in Water
Authors: Cabrera Julieta , Acosta Dwight , López Alcides , Candal Roberto J. , Marchi Claudia , García Pilar , Ríos Dante , Rodriguez Juan M.
Published: April 2018

TiO2 nanotubes were synthesized by alkaline hydrothermal treatment of TiO2 nanoparticles with a controlled proportion of anatase and rutile. Tailoring of TiO2 phases was achieved by adjusting the pH and type of acid used in the hydrolysis of titanium isopropoxide (first step in the sol-gel synthesis). The anatase proportion in the precursor nanoparticles was in the 3–100% range. Tube-like nanostructures were obtained with an anatase percentage of 18 or higher while flake-like shapes were obtained when rutile was dominant in the seed. After annealing at 400°C for 2 h, a fraction of nanotubes was conserved in all the samples but, depending on the anatase/rutile ratio in the starting material, spherical and rod-shaped structures were also observed. The photocatalytic activity of 1D nanostructures was evaluated by measuring the deactivation of E. coli in stirred water in the dark and under UV-A/B irradiation. Results show that in addition to the bactericidal activity of TiO2 under UV-A illumination, under dark conditions, the decrease in bacteria viability is ascribed to mechanical stress due to stirring.
Role of “Second Look” Lymph Node Search in Harvesting Optimal Number of Lymph Nodes for Staging of Colorectal Carcinoma
Authors: Hamza Ameer , Sakhi Ramen , Khawar Sidrah , Alrajjal Ahmed , Edens Jacob , Khurram Muhammad Siddique , Khan Uqba , Szpunar Susanna , Mazzara Paul
Published: April 2018

As with other malignancies, lymph node metastasis is an important staging element and prognostic factor in colorectal carcinomas. The number of involved lymph nodes is directly related to decreased 5-year overall survival for all pT stages according to United States Surveillance, Epidemiology, and End Results (SEER) cancer registry database. The National Quality Forum specifies that the presence of at least 12 lymph nodes in a surgical resection is one of the key quality measures for the evaluation of colorectal cancer. Therefore, the harvesting of a minimum of twelve lymph nodes is the most widely accepted standard for evaluating colorectal cancer. Since this is an accepted quality standard, a second attempt at lymph node dissection in the gross specimen is often performed when the initial lymph node count is less than 12, incurring a delay in reporting and additional expense. However, this is an arbitrary number and not based on any hard scientific evidence. We decided to investigate whether the additional effort and expense of submitting additional lymph nodes had any effect on pathologic lymph node staging (pN). We identified a total of 99 colectomies for colorectal cancer in which the prosector subsequently submitted additional lymph nodes following initial review. The mean lymph node count increased from 8.3 ± 7.5 on initial search to 14.6 ± 8.0 following submission of additional sections. The number of cases meeting the target of 12 lymph nodes increased from 14 to 69. Examination of the additional lymph nodes resulted in pathologic upstaging (pN) of five cases. Gross reexamination and submission of additional lymph nodes may provide more accurate staging in a limited number of cases. Whether exhaustive submission of mesenteric fat or fat-clearing methods is justified will need to be further investigated.
lncRNA-MEG3 Suppresses the Proliferation and Invasion of Melanoma by Regulating CYLD Expression Mediated by Sponging miR-499-5p
Authors: Long Jianwen , Pi Xianming
Published: April 2018

The abnormal expression of long noncoding RNA- (lncRNA-) MEG3 was clearly identified in a number of malignant tumors, but the specific function of MEG3 remains unknown in malignant melanoma until now. The research attempts to explore the effects of MEG3 on the growth and metastasis of malignant melanoma. MEG3 and miR-499-5p expression were determined by qRT-PCR method. Western blotting assay was applied to detect protein expression. Luciferase reporter assay was used to assess the correlation between MEG3 and miR-499-5p and between CYLD and miR-499-5p. Cell growth, cell cycle, and cell apoptosis were examined by CCK-8 assay, EdU assay, and flow cytometry assay, respectively. The invasion ability of melanoma cells was investigated by wound-healing and Transwell assays. The effect of MEG3 on growth of melanoma in vivo and cell chemosensitivity was detected by xenograft animal model and CCK-8 assay. As a result, the expression of MEG3 was decreased in melanoma tissues and cell lines. The level of MEG3 was significantly associated with poor prognosis. MEG3 could bind to miR-499-5p and CYLD mRNA contained a binding site of miR-499-5p. The expression of CYLD was reduced and the level of miR-499-5p was elevated in melanoma tissues and cell lines. Luciferase reporter assay and western blot assay confirmed that MEG3 regulated the expression of CYLD by sponging miR-499-5p. Functionally, upregulation of MEG3 inhibited melanoma cell proliferation, invasion, and migration, enhanced melanoma cell apoptosis, arrested melanoma cell cycle, and regulated the expression of E-cadherin, N-cadherin, and cyclin D1 by regulating CYLD expression mediated by sponging miR-499-5p. Importantly, overexpression of MEG3 suppressed the growth of xenograft tumor and improved chemotherapy sensitivity of A375 cells to cisplatin and 5-FU treatment. In conclusion, MEG3 has a crucial function in the tumorigenesis of melanoma, and MEG3 may be a potential therapeutic target in the treatment of melanoma.
BRAF1799T>A Mutation Frequency in Mexican Mestizo Patients with Papillary Thyroid Cancer
Authors: Fernández-Ramírez Fernando , Hurtado-López Luis M. , López Mario A. , Martínez-Peñafiel Eva , Herrera-González Norma E. , Kameyama Luis , Sepúlveda-Robles Omar
Published: April 2018

Thyroid cancer is the most frequent endocrine malignancy, and its incidence and prevalence are increasing worldwide. Despite its generally good prognosis, the observed mortality rates are higher in the less-developed regions. This indicates that timely diagnosis and appropriate initial management of this disease are important to achieve a positive outcome. We performed an observational study in order to describe the frequency of theBRAF1799T>A mutation in Mexican mestizo patients with thyroid nodules, a scarcely studied ethnic group with large populations. Competitive allele-specific Taqman PCR was performed in 147 samples of thyroid tissue DNA obtained from patients histologically diagnosed with papillary thyroid cancer (PTC), colloid goiters, and follicular adenomas. TheBRAF1799T>A mutation frequency was 61.1% in PTC samples (p= 4.99 × 10−11). Potential diagnostic values were as follows: sensitivity, 61.1%; specificity, 96%; PPV, 94.2%; NPV, 69.5%; accuracy, 77.9%. Taking into account the fact that this mutation is not frequently found in cytologically indeterminate nodules, we suggest that theBRAFmutational analysis should be implemented in the clinical setting along with other diagnostic criteria such as USG, in order to contribute to diagnosis and to surgical decision-making during the initial management of thyroid nodules in Mexican public hospitals.
The Hepatoprotection by Oleanolic Acid Preconditioning: Focusing on PPARαActivation
Authors: Wang Wenwen , Chen Kan , Xia Yujing , Mo Wenhui , Wang Fan , Dai Weiqi , Niu Peiqin
Published: April 2018

Objective. Previous studies have characterized the hepatoprotective and anti-inflammatory properties of oleanolic acid (OA). This study aimed to investigate the molecular mechanisms of OA hepatoprotection in concanavalin A- (ConA-) induced acute liver injury.Materials and Methods. ConA (20 mg/kg) was intravenously injected to induce acute liver injury in Balb/C mice. OA pretreatment (20, 40, and 80 mg/kg) was administered subcutaneously once daily for 3 consecutive days prior to treatment with ConA; 2, 8, and 24 h after ConA injection, the levels of serum liver enzymes and the histopathology of major factors and inflammatory cytokines were determined.Results. OA reduced the release of serum liver enzymes and inflammatory factors and prevented ConA mediated damage to the liver. OA elevated the expression levels of peroxisome proliferator-activated receptor alpha (PPARα) and decreased the phosphorylation of c-Jun NH2-terminal kinase (JNK).Conclusion. OA exhibits anti-inflammatory properties during ConA-induced acute liver injury by attenuating apoptosis and autophagy through activation of PPARαand downregulation of JNK signaling.
A Rare Case of Metastasis to the Thyroid Gland from Renal Clear Cell Carcinoma 11 Years after Nephrectomy and Concurrent Primary Esophageal Carcinoma
Authors: Khan Mohammad Saud , Iyer Veena Balakrishnan , Varshney Neha
Published: April 2018

Renal cell carcinoma is known to cause metastasis to unusual sites, which can be both synchronous or metachronous. Thyroid gland is a rare site for metastasis, but when it occurs, renal cell carcinoma is the most common primary neoplasm. We report the case of a 81-year-old female patient who had a significant medical history of right clear cell renal carcinoma with adrenal metastasis. She underwent right radical nephrectomy and adrenalectomy followed by radiofrequency ablation of left adrenal metastasis and systemic chemotherapy with sunitinib. Eleven years later, she presented with dysphagia and was found to have distal esophageal adenocarcinoma. On imaging, there was incidental detection of a left renal mass lesion and a right thyroid nodule, which on histopathology and immunohistochemistry were confirmed to be clear cell carcinoma of renal origin.
Investigation on the Deterioration Mechanism of Recycled Plaster
Authors: Li Zhixin , Xu Kaidong , Peng Jiahui , Wang Jina , Ma Xianwei , Niu Jishou
Published: April 2018

The deterioration mechanism of recycled plaster (R‐P) was studied. The large specific surface area (SSA), improper preparation temperature, increased water requirement of R‐P, and microstructure of its hardened body were analyzed by particle size distribution (PSD), Blaine method, differential scanning calorimetry (DSC), scanning electron microscopy (SEM), and nitrogen adsorption porosimetry. The results indicated that the properties of R‐P were deteriorated, but its strength decreases from 50% at the same manufacturing process to 30%–40% at similar specific surface area. The analysis shows that the large SSA, poor morphology, narrow PSD, and increased internal detects give rise to increase of water requirement. In addition, the deterioration properties are caused by unsuitable temperature of preparation, loose structure, and large average pore diameter in hardened R‐P as well.
Subdural Hemorrhage after Scoliosis and Detethering of Cord Surgery
Authors: Bhimani Rohan , Bhimani Fardeen , Singh Preeti
Published: April 2018

Introduction. Intracranial hypotension may occur when CSF leaks from the subarachnoid space. Formation of intracranial, subdural, and subarachnoid hemorrhage has been observed after significant CSF leak as seen in lumbar puncture or ventricular shunt placement. However, very few cases, referring to these remote complications following spine surgery, have been described in literature. We present a case of a 10-year-old male child operated for idiopathic scoliosis with low-lying conus medullaris who postoperatively developed subdural hemorrhage. Case Report. A case of a 10-year-old male operated for idiopathic scoliosis with low-lying conus medullaris is presented. To correct this, detethering was done at the L3 level, laminectomy was done from L2 to L3 with pedicular screw fixation from T3 to L2, and bone grafting with right costoplasty was done from the 3rd to the 6th ribs. On the 5th day postoperatively, the patient developed convulsions and drowsiness and recovered subsequently by postoperative day 7. Conclusion. We report a rare case of an acute intracranial subdural hemorrhage caused by intracranial hypotension following scoliosis and detethering of cord surgery. This report highlights the potential morbidity associated with CSF leak occurring after this surgery.
Solid‐Gas Coupling Model for Coal‐Rock Mass Deformation and Pressure Relief Gas Flow in Protection Layer Mining
Authors: Zhu Zhuohui , Feng Tao , Yuan Zhigang , Xie Donghai , Chen Wei
Published: April 2018

The solid‐gas coupling model for mining coal‐rock mass deformation and pressure relief gas flow in protection layer mining is the key to determine deformation of coal‐rock mass and migration law of pressure relief gas of protection layer mining in outburst coal seams. Based on the physical coupling process between coal‐rock mass deformation and pressure‐relief gas migration, the coupling variable of mining coal‐rock mass, a part of governing equations of gas seepage field and deformation field in mining coal‐rock mass, is introduced. Then, a new solid‐gas coupling mathematical model reflecting the coupling effects of gas adsorption/desorption, gas pressure, and coal‐rock mass deformation on the mining coal‐rock mass deformation and pressure relief gas flow is established combined with the corresponding definite conditions. It lays a theoretical foundation for the numerical calculation of the deformation of mining coal‐rock mass and the migration law of gas under pressure relief in the outburst coal seam group.
Parabolic Equation Accumulated Split Error and Its Correction Method for Tropospheric Radio Propagation
Authors: Wei Peipei , Du Xiaoyan , Hu Xinwei , Jiang Changyin
Published: April 2018

An increasingly popular approach of modeling electromagnetic wave propagation in the troposphere is to use the slip-step Fourier transform (SSFT) numerical algorithm to solve a parabolic equation (PE). However, available SSFT does not provide perfect solutions by introducing accumulated split error (ASE) for its step-by-step iteration process with a fixed propagation range step. The common analysis on one step split error is only a simple discussion on the split error of PE. Therefore, the main motivation of this study is to provide improvement on the accuracy of the PE by proposing an error correction method for the first time in the literature for PE. This method is on the basis of defining and deriving the accumulated split error. Its performance is then demonstrated with measured radar sea clutter data from Huanghai Sea, China.
Design of the Variable Inclination Continuous Transverse Stub Antenna Based on Rectangular Grating Slow-Wave Structure
Authors: Gao Jun , Lei Xue , Chen Guo-Hu , Zhang Yi , Wu Jun-Mo
Published: April 2018

In order to solve difficulty in designing nonlinear slow-wave structure (SWS) of the variable inclination continuous transverse stub (VICTS) antenna, we combine the study of the semiopen rectangular grating SWS in the PPW with equivalent circuit theory of leaky-wave antenna to propose a theoretical model for SWS of VICTS element. The computations that the propagation characteristics of VICTS element are calculated by the theoretical model. The results are consistent with the full-wave simulation, which prove the validity and accuracy of the theoretical model. Lastly, by using the theoretical model, an approach for nonlinearly designing SWS is introduced and carried out. The approach improves the gain of the VICTS antenna 0.4 dB.
Research and Implementation of Rateless Spinal Codes Based Massive MIMO System
Authors: Wang Liangliang , Chen Xiang , Tan Hongzhou
Published: April 2018

The potential performance gains promised by massive multi‐input and multioutput (MIMO) rely heavily on the access to accurate channel state information (CSI), which is difficult to obtain in practice when channel coherence time is short and the number of mobile users is huge. To make the system with imperfect CSI perform well, we propose a rateless codes‐aided massive MIMO scheme, with the aim of approaching the maximum achievable rate (MAR) as well as improving the achieved rate over that based on the fixed‐rate codes. More explicitly, a recently proposed family of rateless codes, called spinal codes, are applied to massive MIMO systems, where the spinal codes bring the benefit of approximately achieving the MAR with sufficiently large encoding block size. In addition, the multilevel puncturing and dynamic block‐size allocation (MPDBA) scheme is proposed, where the block sizes are determined by user MAR to curb the average retransmission delay for successfully decoding the messages, which further enhances the system retransmission efficiency. Multilevel puncturing, which is MAR dependent, narrows the gap between the system MAR and the related achieved rate. Theoretical analysis is provided to demonstrate that spinal codes with the MPDBA can guarantee the system retransmission efficiency as well as achieved rate, which are also verified by numerical simulations. Finally, a simplified but comparable MIMO testbed with 2 transmit antennas and 2 single‐antenna users, based on NI Universal Software Radio Peripheral (USRP) and LabVIEW communication toolkits, is built up to demonstrate the effectiveness of our proposal in realistic wireless channels, which is easy to be extended to massive MIMO scenarios in future.
Mechanical Behavior Analysis of Y‐Type S‐SRC Column in a Large‐Space Vertical Hybrid Structure Using Local Fine Numerical Simulation Method
Authors: Yue Jianguang
Published: April 2018

In a large spatial structure, normally the important members are of special type and are the safety key for the global structure. In order to study the mechanical behavior details of the local member, it is difficult for the common test method to realize the complex spatial loading state of the local member. Therefore, a local‐fine finite element model was proposed and a large‐space vertical hybrid structure was numerically simulated. The seismic responses of the global structure and the Y‐type S‐SRC column were analyzed under El Centro seismic motions with the peak acceleration of 35 gal and 220 gal. The numerical model was verified with the results of the seismic shaking table test of the structure model. The failure mechanism and stiffness damage evolution of the Y‐type S‐SRC column were analyzed. The calculated results agreed well with the test results. It indicates that the local‐fine FEM could reflect the mechanical details of the local members in a large spatial structure.
Attitude and Vaccination Status of Healthcare Workers against Hepatitis B Infection in a Teaching Hospital, Ethiopia
Authors: Akibu Mohammed , Nurgi Sodere , Tadese Mesfin , Tsega Wendwesen Dibekulu
Published: April 2018

Background. World Health Organization and Centers for Disease Control and Prevention recommend all health professionals to get vaccinated against hepatitis B virus before they start the clinical attachments during their stay in the medical school. However, only 18–39% of healthcare workers in low- and middle-income countries received the vaccine. Therefore, this study aims to determine the attitude and vaccination status of health professionals working at Adama General Hospital and Medical College.Methods. An institution-based cross-sectional study was conducted from December 2016 to February 2017 with 403 health professionals working at Adama General Hospital and Medical College. Data were collected using self-administered questionnaire distributed at the participant’s work unit and analyzed using SPSS version 20. Multiple logistic regression analysis was conducted to identify factors that affect the complete vaccination status andpvalue < 0.05 was considered statistically significant.Result. The prevalence of complete vaccination against hepatitis B virus was 25.6%. The most frequently mentioned reasons for not being vaccinated were high cost of the vaccine (41%) and unavailability of the vaccine (36%). More than three-fourths (77.8%) of study participants strongly agreed that hepatitis B is a major public health threat and there was tendency among participants to believe that their profession will put them at increased risk of acquiring the disease (strongly agreed: 75.9%). Attending infection-prevention training [AOR = 2.3; 95% CI, 1.24–6.31], history of exposure to risky behavior [AOR = 5.5; 95% CI, 2.86–9.29], and long years of work experience [AOR = 3.1; 95% CI, 1.98–5.24] were statistically significant with complete vaccination status.Conclusion. Only one-quarter of health professionals received the recommended full dose of the vaccine. Sustained hepatitis B vaccination programs for healthcare workers need to be established by collaboration of different stakeholders to optimize health professionals’ safety against this contagious infection.
Chemical Changes of Enamel Produced by Sodium Fluoride, Hydroxyapatite, Er:YAG Laser, and Combined Treatments
Authors: Ceballos-Jiménez Alma Yadira , Rodríguez-Vilchis Laura Emma , Contreras-Bulnes Rosalía , Alatorre Jesús Arenas , Scougall-Vilchis Rogelio José , Velazquez-Enriquez Ulises , de los Angeles Moyaho-Bernal María
Published: April 2018

Occlusal pits and fissures of permanent molars are considered to have higher risk of developing caries. Enamel demineralization can be prevented by applying remineralizing agents, and their absorption increases with prior irradiation. This work evaluates the chemical changes produced by treating occlusal surfaces with sodium fluoride (NaF), hydroxyapatite-NaF-xylitol (HA-NaF-X), Er:YAG laser irradiation (L), and combinations thereof. Fifty enamel samples were randomly assigned to five groups (n=10): NaF, HA-NaF-X, L, L + NaF, and L + HA-NaF-X. The chemical composition of human enamel was evaluated before (BT) and after (AT) treatment using energy-dispersive X-ray spectroscopy (EDS) and expressed in atomic percentages (at%). For combined treatment groups, the products were applied after laser irradiation. The statistical analyses included a pairedt-test and ANOVA (p≤0.05). After treatment, a significant increase in F at% was observed in the NaF group (2.71 ± 1.41). The irradiated groups showed significant increases in Ca and P at% and the Ca/P ratio. The highest values occurred for L + NaF (30.44 ± 4.28 Ca at%, 11.97 ± 1.45 P at%, and 2.55 ± 0.22 Ca/P ratio). Er:YAG laser irradiation alone or in combined protocols increased the Ca and P content of dental enamel, in vitro.
The Correction and Evaluation of Cavitation Model considering the Thermodynamic Effect
Authors: Li Wei , Yang Yongfei , Shi Wei-dong , Zhao Xiaofan , Li Weiqiang
Published: April 2018

Two cavitation models with thermodynamic effects were established based on the Rayleigh-Plesset equation to predict accurately the cavitation characteristics in the high-temperature fluid. The evaporation and the condensation coefficient of the cavitation model were corrected. The cavitation flow of NACA0015 airfoil was calculated using the modified cavitation model, where the influence of the thermodynamic effects of airfoil cavitation was analyzed. The result showed that the pressure coefficient distribution and the bubble volume fraction simulated have the same tendency of Zwart-Gerber-Belamri model’s result. According to the experimental data, the two models provide more accurate results. At the room temperature, the values ofdpv/dTobtained by the two improved models are approximately equal. The difference between the two models’ results increases gradually with the temperature increasing, but it is still small. The simulation results are consistent with the experimental data when the evaporation coefficient is 10 and 1. When the evaporation coefficient is 1, the bubble growth is inhibited, the volume fraction becomes lower, and the cavitation area becomes flat. As the temperature increases, the cavitation area and the bubble volume fraction at airfoil front edge become larger, showing that the temperature plays a “catalytic” role in the cavitation process.
A Novel Data Collection Method with Recharge Plan for Rechargeable Wireless Sensor Networks
Authors: Chen Chi-Chang
Published: April 2018

Because of recent advances in wireless power transfer technologies, several key topics of wireless sensor networks (WSNs) need to be revisited. Traditional data collection methods for WSNs typically consider the balance of power consumption among sensors as a critical design criterion for avoiding uneven power depletion in the networks. I propose a solution for the uneven power consumption problem of data collection over WSNs. I designed a node‐Gosper island‐based scalable hierarchical cluster transmission method in conjunction with a wireless recharge plan for data collection over rechargeable WSNs. For the recharge plan, I used mobile wireless chargers to visit and recharge the batteries of sensors located on different levels of node‐Gosper curves with various frequencies. The duration of each recharging process for each layer of sensors was calculated to verify the feasibility of the proposed recharge plan. The simulation results indicate that my proposed data collection method outperforms several well‐known data collection methods in terms of energy consumption and that my proposed recharge plan is more efficient than previous approaches in terms of charge path length, number of alive nodes, and traveling efficiency.
h-Adic Polynomials and Partial Fraction Decomposition of Proper Rational Functions over R or C
Authors: Kim Kwang Hyun , Zhang Xin
Published: April 2018

The partial fraction decomposition technique is very useful in many areas including mathematics and engineering. In this paper we present a new and simple method on the partial fraction decomposition of proper rational functions which have completely factored denominators over R or C. The method is based on a recursive computation of the h-adic polynomial in commutative algebra which is a generalization of the Taylor polynomial. Since its computation requires only simple algebraic operations, it does not require a computer algebra system to be programmed.
Spermatogenesis Abnormalities following Hormonal Therapy in Transwomen
Authors: Jindarak Sirachai , Nilprapha Kasama , Atikankul Taywin , Angspatt Apichai , Pungrasmi Pornthep , Iamphongsai Seree , Promniyom Pasu , Suwajo Poonpissamai , Selvaggi Gennaro , Tiewtranon Preecha
Published: April 2018

Objective. To measure spermatogenesis abnormalities in transwomen at the time of sex reassignment surgery (SRS) and to analyze the association between hormonal therapy duration and infertility severity.Design. Retrospective study.Setting. University hospital.Patients. One-hundred seventy-three transwomen who underwent SRS from January 2000 to December 2015.Interventions. All orchidectomy specimens were retrospectively reviewed and classified. History of hormonal therapy duration was retrieved from medical records.Main Outcome Measures. Histological examinations of orchidectomy specimens were performed to assess spermatogenesis.Results. One-hundred seventy-three orchidectomy specimens were evaluated. Histological examinations showed maturation arrest in 36.4%, hypospermatogenesis in 26%, Sertoli cell-only syndrome in 20.2%, normal spermatogenesis in 11%, and seminiferous tubule hyalinization in 6.4% of the specimens. Spermatogenesis abnormality severity was not associated with the total therapy duration (P=0.81) or patient age at the time of surgery (P=0.88). Testicular volumes and sizes were associated with spermatogenesis abnormality severity (P=0.001andP=0.026, right testicle and left testicle, resp.).Conclusion(s). Feminizing hormonal treatment leads to reductions in testicular germ cell levels. All transwomen should be warned about this consequence, and gamete preservation should be offered before starting hormonal treatment.
Bioactivity and Toxicity of Senna cana and Senna pendula Extracts
Authors: Monteiro J. A. , Ferreira Júnior J. M. , Oliveira I. R. , Batista F. L. A. , Pinto C. C. C. , Silva A. A. S. , Morais S. M. , Silva M. G. V.
Published: April 2018

This work investigated the content of total polyphenolic compounds and flavonoids as well as their toxicity and larvicidal and acetylcholinesterase inhibitory activities. The antioxidant activities of two medicinal Senna species extracts (Senna cana and Senna pendula) were also investigated. The ethanol extract of the leaves of S. cana and the ethanol extract of the branches of S. pendula presented the best performance in the DPPH/FRAP and ABTS/ORAC assays, respectively. For the inhibition of acetylcholinesterase, the hexane extract of the flowers of S. pendula presented the lowest IC50 value among the ethanol extracts of the leaves of S. cana and showed the best performance in some assays. The hexane extract of the leaves of S. pendula and the hexane extract of the branches of S. cana were moderate to Artemia salina Leach. In the quantification of phenols and flavonoids, the ethanol extract of the leaves of S. cana presented the best results. The ethanol extracts of the leaves of S. cana were found to be rich in antioxidants, phenolic compounds, and flavonoids. These results indicate the antioxidant potential of the extracts of Senna species and can be responsible for some of the therapeutic uses of these plants.
Saliva Dysfunction and Oral Microbial Changes among Systemic Lupus Erythematosus Patients with Dental Caries
Authors: Yang Lijie , Wang Jing , Xiao Yan , Wang Xi , Sun Qiang , Shang Junlan , Zhao Yulin
Published: April 2018

Systemic lupus erythematosus (SLE) is a chronic autoimmune and inflammatory disease affecting multiorgans of human body. Independent studies show that SLE patients had higher caries prevalence compared to non-SLE individuals. However, the underlying mechanisms remain unclear. In present study, we enrolled SLE patients to explore potential factors contributing to the susceptibility of SLE patients to dental caries (such as oral hygiene, salivary function, and oral microbial community). Dental examination confirmed SLE patients were more vulnerable to caries. Although subjects in both groups announced similar oral hygiene habits, more dental plaque was found on tooth surfaces of SLE patents as revealed by plaque index. In addition, the salivary function was impaired in SLE group as salivary flow rate, buffering capacity, and pH were lower among SLE subjects compared to healthy controls. Importantly, disturbed microbial community with lower richness and diversity was observed in SLE group, as well as disequilibrium between acidogenic/aciduric pathogens and alkali-generating commensal bacteria. Our data suggest that SLE increases patients’ sensitivity to dental caries through imposing stress to both host and oral microbes.
Influences of Environmental Conditions on the Cracking Tendency of Dry‐Mixed Plastering Mortar
Authors: Tongyuan Ni , Yang Yang , Dandan Wu , Chenhui Jiang
Published: April 2018

Cracking tendency is one of the important performances of dry‐mixed plastering mortar (DMPM). Environmental condition is a key factor to affect the cracking tendency of DMPM. For the purpose of evaluating the cracking resistance of DMPM and revealing the influence of environmental conditions on the cracking tendency of DMPM, a series of experiments were performed on restriction‐induced cracking behaviors as well as free shrinkage, water loss, and mechanical properties of DMPM. The restricted shrinkage tests were based on ring tests and plate experiments. The results showed that the initial drying age exhibits significant influence on the cracking tendency of DMPM, and there was a stress balance period when the initial drying age was 2 days. But, the phenomena cannot be observed when the initial age was 3 d, 5 d, and 7 d. In order to eliminate the cracking tendency of DMPM, it should avoid water loss from the plaster layer during construction in practical engineering, especially, before initial drying ages.
Physical and Mechanical Properties of Cemented Ash‐Based Lightweight Building Materials with and without Pumice
Authors: Doğan-Sağlamtimur Neslihan , Güven Adnan , Bilgil Ahmet
Published: April 2018

Pumice, cements (CEM I‐ and CEM II‐type), waste fly and bottom ashes (IFA, GBA, and BBA) supplied from international companies were used to produce lightweight building materials, and physical‐mechanical properties of these materials were determined. Axial compressive strength (ACS) values were found above the standards of 4 and 8 MPa (Bims Concrete (BC) 40 and 80 kgf/cm2 class) for cemented (CEM I) pumice‐based samples. On the contrary, the ACS values of the pumice‐based cemented (CEM II) samples could not be reached to these standards. Best ACS results (compatible with BC80) from these cemented lightweight material samples produced with the ashes were found in 50% mixing ratio as 10.6, 13.2, and 20.5 MPa for BBA + CEM I, GBA + CEM II, and IFA + CEM I, respectively, and produced with pumice were found as 8.4 MPa (same value) for GBA + pumice + CEM II (in 25% mixing ratio), BBA + pumice + CEM I (in 100% mixing ratio), and pumice + IFA + CEM I (in 100% mixing ratio), respectively. According to the results, cemented ash‐based lightweight building material produced with and without pumice could widely be used for constructive purposes. As a result of this study, an important input to the ecosystem has been provided using waste ashes, whose storage constitutes a problem.
Development of Steel Fiber‐Reinforced Expanded‐Shale Lightweight Concrete with High Freeze‐Thaw Resistance
Authors: Zhao Mingshuang , Zhang Xiaoyan , Song Wenhui , Li Changyong , Zhao Shunbo
Published: April 2018

For the popularized structural application, steel fiber‐reinforced expanded‐shale lightweight concrete (SFRELC) with high freeze‐thaw resistance was developed. The experimental study of this paper figured out the effects of air‐entraining content, volume fraction of steel fibers, and fine aggregate type. Results showed that while the less change of mass loss rate was taken place for SFRELC after 300 freeze‐thaw cycles, the relative dynamic modulus of elasticity and the relative flexural strength presented clear trends of freeze‐thaw resistance of SFRELC. The compound effect of the air‐entraining agent and the steel fibers was found to support the SFRELC with high freeze‐thaw resistance, and the mechanisms were explored with the aid of the test results of water penetration of SFRELC. The beneficial effect was appeared from the replacement of lightweight sand with manufactured sand. Based on the test results, suggestions are given out for the optimal mix proportion of SFRELC to satisfy the durability requirement of freeze‐thaw resistance.
CD163 Is Required for Protumoral Activation of Macrophages in Human and Murine Sarcoma
Authors: Shiraishi Daisuke , Fujiwara Yukio , Horlad Hasita , Saito Yoichi , Iriki Toyohisa , Tsuboki Junko , Cheng Pan , Nakagata Naomi , Mizuta Hiroshi , Bekki Hirofumi , Nakashima Yasuharu , Oda Yoshinao , Takeya Motohiro , Komohara Yoshihiro
Published: April 2018

Recent findings have shown the significance of CD163-positive macrophages in tumor progression, yet there have been few studies on the function of CD163 in macrophages. Here, we uncover the role of CD163 in macrophage activation using CD163-deficient mice and human samples. We detected CD163 in 62 undifferentiated pleomorphic sarcoma samples, in which a high percentage of CD163-positive macrophages was associated with decreased overall survival and higher histologic grade. We observed macrophage-induced tumor cell proliferation in cocultures of human monocyte-derived macrophages and leiomyosarcoma (TYLMS-1) and myxofibrosarcoma (NMFH-1) cell lines, which was abrogated by silencing of CD163. Tumor development of sarcoma (MCA205 and LM8) cells in CD163-deficient mice was significantly abrogated in comparison with wild-type (WT) mice. Coculture with WT peritoneal macrophages significantly increased proliferation of MCA205 cells but decreased in the presence of CD163-deficient macrophages. Production of IL6 and CXCL2 in CD163-deficient macrophages was suppressed in comparison with WT macrophages, and overexpression of CD163 in CD163-deficient macrophages induced production of IL6 and CXCL2. Silencing of IL6 but not CXCL2 abrogated macrophage-induced proliferation of MCA205 cells. Taken together, our results show that CD163 is involved in protumoral activation of macrophages and subsequent development and progression of tumors in mice and humans.

Significance: Macrophage CD163-mediated induction of IL6 promotes tumor development and progression in murine and human malignant tumors. Cancer Res; 78(12); 3255–66. ©2018 AACR.
Renin–Angiotensin System Inhibitors to Mitigate Cancer Treatment–Related Adverse Events
Authors: Pinter Matthias , Kwanten Wilhelmus J. , Jain Rakesh K.
Published: April 2018

Treatment-related side effects are a major clinical problem in cancer treatment. They lead to reduced compliance to therapy as well as increased morbidity and mortality. Well-known are the sequelae of chemotherapy on the heart, especially in childhood cancer survivors. Therefore, measures to mitigate the adverse events of cancer therapy may improve health and quality of life in patients with cancer, both in the short and long term. The renin–angiotensin system (RAS) affects all hallmarks of cancer, and blockage of the RAS is associated with an improved outcome in several cancer types. There is also increasing evidence that inhibition of the RAS might be able to alleviate or even prevent certain types of cancer treatment–related adverse effects. In this review, we summarize the potential of RAS inhibitors to mitigate cancer treatment–related adverse events, with a special emphasis on chemotherapy-induced cardiotoxicity, radiation injury, and arterial hypertension. Clin Cancer Res; 24(16); 3803–12. ©2018 AACR.
Adaptive Resistance to Chemotherapy, A Multi–FAK-torial Linkage
Authors: Taylor Kristin N. , Schlaepfer David D.
Published: April 2018

Oncogenes provide tumor cells with a growth and survival advantage. Directed therapies targeted to oncogenic mutations (such as BRAF V600E) are part of effective late-stage melanoma treatment. However, tumors with BRAF V600E mutations, in approximately 10% of colorectal cancer, are generally treatment-insensitive. Research has identified various “feedback” mechanisms that result in BRAF signal pathway reactivation in response to BRAF inhibition. Herein, we highlight key findings from Chen and colleagues (this issue) showing that integrin-associated focal adhesion kinase (FAK) activation selectively occurs in BRAF V600E-mutant colorectal cancer cells in response to pharmacological BRAF inhibition. FAK activation results in elevated β-catenin protein levels, β-catenin nuclear localization, and increased gene transcription. Small-molecule inhibitors of β-catenin or FAK synergize with vemurafenib BRAF inhibitor to prevent BRAF V600E colorectal cancer cell proliferation in vitro and xenograft tumor growth in mice. This study complements findings linking FAK to β-catenin in intestinal tumorigenesis, resistance to radiotherapy, and cancer stem cell survival. Thus, FAK activation may occur as a frequent tumor cell “adaptive resistance” mechanism. Although FAK (PTK2) is not mutated in most cancers, targeting FAK activity in combinational approaches may limit tumor cell escape mechanisms and enhance durable responses to treatment. Mol Cancer Ther; 17(4); 719–23. ©2018 AACR.
E-Cadherin/ROS1 Inhibitor Synthetic Lethality in Breast Cancer
Authors: Bajrami Ilirjana , Marlow Rebecca , van de Ven Marieke , Brough Rachel , Pemberton Helen N. , Frankum Jessica , Song Feifei , Rafiq Rumana , Konde Asha , Krastev Dragomir B. , Menon Malini , Campbell James , Gulati Aditi , Kumar Rahul , Pettitt Stephen J. , Gurden Mark D. , Cardenosa Marta Llorca , Chong Irene , Gazinska Patrycja , Wallberg Fredrik , Sawyer Elinor J. , Martin Lesley-Ann , Dowsett Mitch , Linardopoulos Spiros , Natrajan Rachael , Ryan Colm J. , Derksen Patrick W.B. , Jonkers Jos , Tutt Andrew N.J. , Ashworth Alan , Lord Christopher J.
Published: April 2018

The cell adhesion glycoprotein E-cadherin (CDH1) is commonly inactivated in breast tumors. Precision medicine approaches that exploit this characteristic are not available. Using perturbation screens in breast tumor cells with CRISPR/Cas9-engineered CDH1 mutations, we identified synthetic lethality between E-cadherin deficiency and inhibition of the tyrosine kinase ROS1. Data from large-scale genetic screens in molecularly diverse breast tumor cell lines established that the E-cadherin/ROS1 synthetic lethality was not only robust in the face of considerable molecular heterogeneity but was also elicited with clinical ROS1 inhibitors, including foretinib and crizotinib. ROS1 inhibitors induced mitotic abnormalities and multinucleation in E-cadherin–defective cells, phenotypes associated with a defect in cytokinesis and aberrant p120 catenin phosphorylation and localization. In vivo, ROS1 inhibitors produced profound antitumor effects in multiple models of E-cadherin–defective breast cancer. These data therefore provide the preclinical rationale for assessing ROS1 inhibitors, such as the licensed drug crizotinib, in appropriately stratified patients.

Significance: E-cadherin defects are common in breast cancer but are currently not targeted with a precision medicine approach. Our preclinical data indicate that licensed ROS1 inhibitors, including crizotinib, should be repurposed to target E-cadherin–defective breast cancers, thus providing the rationale for the assessment of these agents in molecularly stratified phase II clinical trials. Cancer Discov; 8(4); 498–515. ©2018 AACR.

This article is highlighted in the In This Issue feature, p. 371
Response to ERBB3-Directed Targeted Therapy in NRG1-Rearranged Cancers
Authors: Drilon Alexander , Somwar Romel , Mangatt Biju P. , Edgren Henrik , Desmeules Patrice , Ruusulehto Anja , Smith Roger S. , Delasos Lukas , Vojnic Morana , Plodkowski Andrew J. , Sabari Joshua , Ng Kenneth , Montecalvo Joseph , Chang Jason , Tai Huichun , Lockwood William W. , Martinez Victor , Riely Gregory J. , Rudin Charles M. , Kris Mark G. , Arcila Maria E. , Matheny Christopher , Benayed Ryma , Rekhtman Natasha , Ladanyi Marc , Ganji Gopinath
Published: April 2018

NRG1 rearrangements are oncogenic drivers that are enriched in invasive mucinous adenocarcinomas (IMA) of the lung. The oncoprotein binds ERBB3–ERBB2 heterodimers and activates downstream signaling, supporting a therapeutic paradigm of ERBB3/ERBB2 inhibition. As proof of concept, a durable response was achieved with anti-ERBB3 mAb therapy (GSK2849330) in an exceptional responder with an NRG1-rearranged IMA on a phase I trial (NCT01966445). In contrast, response was not achieved with anti-ERBB2 therapy (afatinib) in four patients with NRG1-rearranged IMA (including the index patient post-GSK2849330). Although in vitro data supported the use of either ERBB3 or ERBB2 inhibition, these clinical results were consistent with more profound antitumor activity and downstream signaling inhibition with anti-ERBB3 versus anti-ERBB2 therapy in an NRG1-rearranged patient-derived xenograft model. Analysis of 8,984 and 17,485 tumors in The Cancer Genome Atlas and MSK-IMPACT datasets, respectively, identified NRG1 rearrangements with novel fusion partners in multiple histologies, including breast, head and neck, renal, lung, ovarian, pancreatic, prostate, and uterine cancers.

Significance: This series highlights the utility of ERBB3 inhibition as a novel treatment paradigm for NRG1-rearranged cancers. In addition, it provides preliminary evidence that ERBB3 inhibition may be more optimal than ERBB2 inhibition. The identification of NRG1 rearrangements across various solid tumors supports a basket trial approach to drug development. Cancer Discov; 8(6); 686–95. ©2018 AACR.

See related commentary by Wilson and Politi, p. 676.

This article is highlighted in the In This Issue feature, p. 663
Long-Term Risk of Cardiovascular Disease in Women Who Have Had Infants With Heart Defects
Authors: Auger Nathalie , Potter Brian J. , Bilodeau-Bertrand Marianne , Paradis Gilles
Published: April 2018

Background:

The possibility that congenital heart defects signal a familial predisposition to cardiovascular disease has not been investigated. We aimed to determine whether the risk of cardiovascular disorders later in life was higher for women who have had newborns with congenital heart defects.

Methods:

We studied a cohort of 1 084 251 women who had delivered infants between 1989 and 2013 in Quebec, Canada. We identified women whose infants had critical, noncritical, or no heart defects, and tracked the women over time for future hospitalizations for cardiovascular disease, with follow-up extending up to 25 years past pregnancy. We calculated the incidence of cardiovascular hospitalization per 1000 person-years, and used Cox proportional hazards regression to estimate hazard ratios and 95% confidence intervals (CIs) for the association between infant heart defects and risk of maternal cardiovascular hospitalization. Models were adjusted for age, parity, preeclampsia, comorbidity, material deprivation, and time period.

Results:

Women whose infants had heart defects had a higher overall incidence of cardiovascular hospitalization. There were 3.38 cardiovascular hospitalizations per 1000 person-years for those with critical defects (95% CI, 2.67–4.27), 3.19 for noncritical defects (95% CI, 2.96–3.45), and 2.42 for no heart defects (95% CI, 2.39–2.44). In comparison with no heart defects, women whose infants had critical defects had a hazard ratio of 1.43 (95% CI, 1.13–1.82) for any cardiovascular hospitalization, and women whose infants had noncritical defects had a hazard ratio of 1.24 (95% CI, 1.15–1.34), in adjusted models. Risks of specific causes of cardiovascular hospitalization, including myocardial infarction, heart failure, and other atherosclerotic disorders, were also greater for mothers of infants with congenital heart defects than with no defects.

Conclusions:

Women whose infants have congenital heart defects have a greater risk of cardiovascular hospitalization later in life. Congenital heart defects in offspring may be an early marker of predisposition to cardiovascular disease.