bluuebunny/crossref_metadata_2025 huggingface dataset:
Prediction of Epileptic Seizure by Analysing Time Series EEG Signal Using k-NN Classifier
Authors: Hasan Md. Kamrul , Ahamed Md. Asif , Ahmad Mohiuddin , Rashid M. A.
Published: August 2017

Electroencephalographic signal is a representative signal that contains information about brain activity, which is used for the detection of epilepsy since epileptic seizures are caused by a disturbance in the electrophysiological activity of the brain. The prediction of epileptic seizure usually requires a detailed and experienced analysis of EEG. In this paper, we have introduced a statistical analysis of EEG signal that is capable of recognizing epileptic seizure with a high degree of accuracy and helps to provide automatic detection of epileptic seizure for different ages of epilepsy. To accomplish the target research, we extract various epileptic features namely approximate entropy (ApEn), standard deviation (SD), standard error (SE), modified mean absolute value (MMAV), roll-off (R), and zero crossing (ZC) from the epileptic signal. The k-nearest neighbours (k-NN) algorithm is used for the classification of epilepsy then regression analysis is used for the prediction of the epilepsy level at different ages of the patients. Using the statistical parameters and regression analysis, a prototype mathematical model is proposed which helps to find the epileptic randomness with respect to the age of different subjects. The accuracy of this prototype equation depends on proper analysis of the dynamic information from the epileptic EEG.
Rosmarinic Acid Alleviates the Endothelial Dysfunction Induced by Hydrogen Peroxide in Rat Aortic Rings via Activation of AMPK
Authors: Zhou Hui , Fu Baocai , Xu Bo , Mi Xiangquan , Li Gang , Ma Chengjun , Xie Jianxin , Li Ji , Wang Zhenhua
Published: August 2017

Endothelial dysfunction is the key player in the development and progression of vascular events. Oxidative stress is involved in endothelial injury. Rosmarinic acid (RA) is a natural polyphenol with antioxidative, antiapoptotic, and anti‐inflammatory properties. The present study investigates the protective effect of RA on endothelial dysfunction induced by hydrogen peroxide (H2O2). Compared with endothelium‐denuded aortic rings, the endothelium significantly alleviated the decrease of vasoconstrictive reactivity to PE and KCl induced by H2O2. H2O2 pretreatment significantly injured the vasodilative reactivity to ACh in endothelium‐intact aortic rings in a concentration‐dependent manner. RA individual pretreatment had no obvious effect on the vasoconstrictive reaction to PE and KCl, while its cotreatment obviously mitigated the endothelium‐dependent relaxation impairments and the oxidative stress induced by H2O2. The RA cotreatment reversed the downregulation of AMPK and eNOS phosphorylation induced by H2O2 in HAEC cells. The pretreatment with the inhibitors of AMPK (compound C) and eNOS (L‐NAME) wiped off RA’s beneficial effects. All these results demonstrated that RA attenuated the endothelial dysfunction induced by oxidative stress by activating the AMPK/eNOS pathway.
Antioxidant and Anti‐Inflammatory Effects of Shungite against Ultraviolet B Irradiation‐Induced Skin Damage in Hairless Mice
Authors: Sajo Ma. Easter Joy , Kim Cheol-Su , Kim Soo-Ki , Shim Kwang Yong , Kang Tae-Young , Lee Kyu-Jae
Published: August 2017

As fullerene‐based compound applications have been rapidly increasing in the health industry, the need of biomedical research is urgently in demand. While shungite is regarded as a natural source of fullerene, it remains poorly documented. Here, we explored the in vivo effects of shungite against ultraviolet B‐ (UVB‐) induced skin damage by investigating the physiological skin parameters, immune‐redox profiling, and oxidative stress molecular signaling. Toward this, mice were UVB‐irradiated with 0.75 mW/cm2 for two consecutive days. Consecutively, shungite was topically applied on the dorsal side of the mice for 7 days. First, we found significant improvements in the skin parameters of the shungite‐treated groups revealed by the reduction in roughness, pigmentation, and wrinkle measurement. Second, the immunokine profiling in mouse serum and skin lysates showed a reduction in the proinflammatory response in the shungite‐treated groups. Accordingly, the redox profile of shungite‐treated groups showed counterbalance of ROS/RNS and superoxide levels in serum and skin lysates. Last, we have confirmed the involvement of Nrf2‐ and MAPK‐mediated oxidative stress pathways in the antioxidant mechanism of shungite. Collectively, the results clearly show that shungite has an antioxidant and anti‐inflammatory action against UVB‐induced skin damage in hairless mice.
Cognitive Impairment in Relapsing-Remitting Multiple Sclerosis Patients with Very Mild Clinical Disability
Authors: Migliore S. , Ghazaryan A. , Simonelli I. , Pasqualetti P. , Squitieri F. , Curcio G. , Landi D. , Palmieri M. G. , Moffa F. , Filippi M. M. , Vernieri F.
Published: August 2017

Cognitive dysfunction affects 40–65% of multiple sclerosis (MS) patients and can occur in the early stages of the disease. This study aimed to explore cognitive functions by means of the Italian version of the minimal assessment of cognitive function in MS (MACFIMS) in relapsing-remitting MS (RRMS) patients with very mild clinical disability to identify the primarily involved cognitive functions. Ninety-two consecutive RRMS patients with Expanded Disability Status Scale (EDSS) scores ≤ 2.5 and forty-two healthy controls (HC) were investigated. Our results show that 51.1% of MS patients have cognitive dysfunction compared to HC. An impairment of verbal and visual memory, working memory, and executive functions was found in the RRMS group. After subgrouping RRMS by EDSS, group 1 (EDSS ≤ 1.5) showed involvement of verbal memory and executive functions; moreover, group 2 (2 ≤ EDSS ≤ 2.5) patients were also impaired in information processing speed and visual memory. Our results show that utilizing a comprehensive neuropsychological assessment, approximately half of MS patients with very mild physical disability exhibit cognitive impairment with a primary involvement of prefrontal cognitive functions. Detecting impairment of executive functions at an early clinical stage of disease could be useful to promptly enroll MS patients in targeted rehabilitation.
Effective Heart Disease Detection Based on Quantitative Computerized Traditional Chinese Medicine Using Representation Based Classifiers
Authors: Shu Ting , Zhang Bob , Tang Yuan Yan
Published: August 2017

At present, heart disease is the number one cause of death worldwide. Traditionally, heart disease is commonly detected using blood tests, electrocardiogram, cardiac computerized tomography scan, cardiac magnetic resonance imaging, and so on. However, these traditional diagnostic methods are time consuming and/or invasive. In this paper, we propose an effective noninvasive computerized method based on facial images to quantitatively detect heart disease. Specifically, facial key block color features are extracted from facial images and analyzed using the Probabilistic Collaborative Representation Based Classifier. The idea of facial key block color analysis is founded in Traditional Chinese Medicine. A new dataset consisting of 581 heart disease and 581 healthy samples was experimented by the proposed method. In order to optimize the Probabilistic Collaborative Representation Based Classifier, an analysis of its parameters was performed. According to the experimental results, the proposed method obtains the highest accuracy compared with other classifiers and is proven to be effective at heart disease detection.
Natural Modulators of Endosomal Toll-Like Receptor-Mediated Psoriatic Skin Inflammation
Authors: Lai Chao-Yang , Su Yu-Wen , Lin Kuo-I , Hsu Li-Chung , Chuang Tsung-Hsien
Published: August 2017

Psoriasis is a chronic inflammatory autoimmune disease that can be initiated by excessive activation of endosomal toll-like receptors (TLRs), particularly TLR7, TLR8, and TLR9. Therefore, inhibitors of endosomal TLR activation are being investigated for their ability to treat this disease. The currently approved biological drugs adalimumab, etanercept, infliximab, ustekinumab, ixekizumab, and secukizumab are antibodies against effector cytokines that participate in the initiation and development of psoriasis. Several immune modulatory oligonucleotides and small molecular weight compounds, including IMO-3100, IMO-8400, and CPG-52364, that block the interaction between endosomal TLRs and their ligands are under clinical investigation for their effectiveness in the treatment of psoriasis. In addition, several chemical compounds, including AS-2444697, PF-05387252, PF-05388169, PF-06650833, ML120B, and PHA-408, can inhibit TLR signaling. Although these compounds have demonstrated anti-inflammatory activity in animal models, their therapeutic potential for the treatment of psoriasis has not yet been tested. Recent studies demonstrated that natural compounds derived from plants, fungi, and bacteria, including mustard seed,Antrodia cinnamomeaextract, curcumin, resveratrol, thiostrepton, azithromycin, and andrographolide, inhibited psoriasis-like inflammation induced by the TLR7 agonist imiquimod in animal models. These natural modulators employ different mechanisms to inhibit endosomal TLR activation and are administered via different routes. Therefore, they represent candidate psoriasis drugs and might lead to the development of new treatment options.
Candidemia in the Neonatal Intensive Care Unit: A Retrospective, Observational Survey and Analysis of Literature Data
Authors: Caggiano Giuseppina , Lovero Grazia , De Giglio Osvalda , Barbuti Giovanna , Montagna Osvaldo , Laforgia Nicola , Montagna Maria Teresa
Published: August 2017

We evaluated the epidemiology ofCandidabloodstream infections in the neonatal intensive care unit (NICU) of an Italian university hospital during a 9-year period as a means of quantifying the burden of infection and identifying emerging trends. Clinical data were searched for in the microbiological laboratory database. For comparative purposes, we performed a review of NICU candidemia. Forty-one candidemia cases were reviewed (overall incidence, 3.0 per 100 admissions).Candida parapsilosis sensu stricto(58.5%) andC. albicans(34.1%) were the most common species recovered. A variable drift through years was observed; in 2015, 75% of the cases were caused by non-albicansspecies. The duration of NICU hospitalization of patients with non-albicanswas significantly longer than in those withC. albicans(median days, 10 versus 12). Patients with non-albicansspecies were more likely to have parenteral nutrition than those withC. albicans(96.3% versus 71.4%).Candida albicanswas the dominant species in Europe and America (median, 55% and 60%; resp.); non-albicansspecies predominate in Asia (75%). Significant geographic variation is evident among cases of candidemia in different parts of the world, recognizing the importance of epidemiological data to facilitate the treatment.
The Role of miRNAs as Biomarkers for Pregnancy Outcomes: A Comprehensive Review
Authors: Barchitta Martina , Maugeri Andrea , Quattrocchi Annalisa , Agrifoglio Ottavia , Agodi Antonella
Published: August 2017

Several studies showed that altered expression of the miRNA-ome in maternal circulation or in placental tissue may reflect not only gestational disorders, such as preeclampsia, spontaneous abortion, preterm birth, low birth weight, or macrosomia, but also prenatal exposure to environmental pollutants. Generally, the relationships between environmental exposure, changes in miRNA expression, and gestational disorders are explored separately, producing conflicting findings. However, validation of tissue-accessible biomarkers for the monitoring of adverse pregnancy outcomes needs a systematic methodological approach that takes also into account early-life environmental exposure. To achieve this goal, exposure to xenochemicals, endogenous agents, and diet should be assessed. This study has the aim to provide a comprehensive review on the role of miRNAs as potential biomarkers for adverse pregnancy outcomes and prenatal environmental exposure.
Synergistic Antitumor Effects of Berbamine and Paclitaxel through ROS/Akt Pathway in Glioma Cells
Authors: Jia Feng , Ruan Shu , Liu Ning , Fu Linshan
Published: August 2017

In our preliminary study, Berbamine (BA), one of the most commonly used traditional Chinese medicines, was effective in inducing the intracellular ROS levels. Since the regulation of cellular antioxidant capacity is crucial to the sensitivity of Ptx, it is feasible to propose that sensitizing cells to Ptx can be achieved through increasing the antioxidant capacity by codelivering BA. Cytotoxicity test demonstrates that either single or combinational treatment of BA and Ptx dose‐dependently inhibits the proliferation of U‐87 cells. Median‐effect analysis clearly proves the synergistic anticancer effect between BA and Ptx. Combinational treatment of both drugs induced more intracellular ROS generation than either of the drugs did. Cotreatment of NAC could partially reverse the ROS generation and ameliorate the cytotoxicity induced by BA plus Ptx. Moreover, sequential activation of ROS‐dependent phosphor‐Akt expression was dose‐dependently inhibited by the combinational application of BA and Ptx, which was more significantly effective than the single treatment of either BA or Ptx. Additionally, the coadministration of BA and Ptx shows the strongest tumor delaying effect in a U87 xenograft model, demonstrating the synergism between two drugs. Therefore, BA is a promising adjuvant to traditional chemotherapy, especially in combination with Ptx, to treat malignant glioma.
Determination of Optical Properties of Thin Films from Ketteler-Helmholtz Dispersion Relations: Application to the Case of Ultraviolet Irradiated Zirconium Oxide
Authors: Desforges Jean , Robichaud Luc , Gauvin Serge
Published: August 2017

A new method based on the Ketteler-Helmholtz dispersion relations is described. This method allows accurately determining the optical properties of thin films from a single transmittance curve. The case of zirconium oxide thin film postdeposition irradiated with ultraviolet light is analysed. The effect of ultraviolet irradiation is compared with low temperature postdeposition heating. It is shown that both processes have a comparable effect on the optical properties of the films. However, as our analysis leads to inferring that ultraviolet irradiation produces smoother film surfaces, the use of ultraviolet irradiation is an interesting alternative to the heating process. Accordingly, the reduction of light scattering from the interface with air provides films of better optical quality, which is especially valuable in case of multilayer systems.
The Influence of the Activation Temperature on the Structural Properties of the Activated Carbon Xerogels and Their Electrochemical Performance
Authors: Quach Nguyen Khanh Nguyen , Yang Wein-Duo , Chung Zen-Ja , Tran Hoai Lam
Published: August 2017

The effect of activation temperature on the structural properties and the electrochemical performance of KOH-activated carbon xerogel was investigated in range of 700 to 1000°C. At a high temperature (1000°C), the chemical activation regenerated a more crystalline network structure of activated carbon xerogels, which was observed by Raman, XRD, and TEM images. Additionally, SEM images, BET, BJH, and t-plot were used to study the structural properties of carbon xerogels. The carbon xerogel sample activated at 900°C was found with the most appropriate structure, which has the high micropore area and a more-balanced porosity between the micropores and mesopores, for using as an electrode material. The highest obtained specific capacitance value was 270 Fg−1 in 6 M KOH electrolyte at scan rate of 5 mVs−1 from the cyclic voltammetry.
A Liquid Chromatography-Tandem Mass Spectrometry Method for Evaluation of Two Brands of Enalapril 20 mg Tablets in Healthy Human Volunteers
Authors: Dayyih Wael Abu , Hamad Mohammed , Awwad Ahmad Abu , Mallah Eyad , Zakarya Zainab , Dayyih Alice Abu , Arafat Tawfiq
Published: August 2017

Enalapril is an angiotensin-converting enzyme inhibitor used for treatment of hypertension and chronic heart disease. Enalaprilat is its active metabolite responsible for the activity. This study aimed to develop and validate a method for enalapril and enalaprilat analysis and to determine the bioequivalence of two tablet formulae of enalapril. LC-MS/MS bioanalytical method was developed and validated and then applied to evaluate the bioavailability of two enalapril formulae. Antihyperglycemic sitagliptin was used as internal standard (IS). The method was accurate for the within- and between-days analysis, and precise CV% was <5%, being linear over the calibration range 1.0–200.0 ng/ml. Stability was >85% and the LOD was 0.907 and 0.910 ng/ml for enalapril and enalaprilat, respectively, and LLOQ was 1 ng/ml. The pharmacokinetic parameters Cmax, tmax, AUC0–72, and AUC0–∞ values of enalapril and enalaprilat of the two formulae were calculated and nonsignificant differences were found. A linearity, specific, accurate, and precise method was developed and applied for the analysis of enalapril and enalaprilat in human plasma after oral administration of two formulae of enalapril 20 mg tablets in healthy volunteers. Depending on the statistical analysis it was concluded that the two enalapril formulae were bioequivalent.
BMI Modulates the Effect of Thyroid Hormone on Lipid Profile in Euthyroid Adults
Authors: Wang Yanqiu , Yin Qinglei , Xu Min , Ni Qicheng , Wang Weiqing , Wang Qidi
Published: August 2017

The impacts of thyroid hormones (TH) on lipid profile in euthyroid adults have gained much attention. It is currently unknown whether BMI influences such interaction. In the present study, we investigate the role of BMI in modulating the association between TH and lipid parameters in 1372 euthyroid healthy adults. Our results show that thyroid parameters are differentially associated with lipid profile. FT3 is positively correlated with total cholesterol (β=0.176±0.046, P<0.001) and LDL cholesterol levels (β=0.161±0.040, P<0.001). FT4 is negatively correlated with TG (β=−0.087±0.029, P<0.01) while positively correlated with HDL cholesterol levels (β=0.013±0.005, P<0.01). TSH is positively associated with TG (β=0.145±0.056, P<0.05) and total cholesterol levels (β=0.094±0.030, P<0.01). Importantly, BMI modulates the effect of TH on lipid profile: the interaction of FT4 and BMI and the interaction of FT3 and BMI reach statistical significance in predicting TG and HDL cholesterol levels, respectively. Stratified according to BMI levels, most associations between TH and lipid profile are significant only in normal-weight group. In conclusion, in euthyroid adults, high normal FT3, TSH levels, and low normal FT4 levels are associated with unfavorable lipid profile. BMI mediates the effect of thyroid function on lipid profile in euthyroid adults.
MiR-219-5p Inhibits the Growth and Metastasis of Malignant Melanoma by Targeting BCL-2
Authors: Long Jianwen , Menggen Qiqige , Wuren Qimige , Shi Quan , Pi Xianming
Published: August 2017

Malignant melanoma is a very dangerous tumor which is resistant to conventional therapy. MicroRNA exerts a vital function in promoting or inhibiting tumor development. The research has investigated the expression and function of miR-219-5p in melanoma. As a result, miR-219-5p expression was distinctly reduced in melanoma tissues and cell lines and was negatively correlated with Bcl-2 protein level in melanoma. Patients with low miR-219-5p level represented obviously a low overall survival in comparison with patients with high miR-219-5p level. The upregulation of miR-219-5p inhibited melanoma growth and metastasis and strengthened melanoma cells chemosensitivity by targeting Bcl-2. Therefore, the modulation of miR-219-5p expression may be a novel treatment strategy in melanoma.
Cereblon: A Protein Crucial to the Multiple Functions of Immunomodulatory Drugs as well as Cell Metabolism and Disease Generation
Authors: Shi Qinglin , Chen Lijuan
Published: August 2017

It is well known that cereblon is a key protein in autosomal recessive nonsyndromic mental retardation. Studies have reported that it has an intermediary role in helping immunomodulatory drugs perform their immunomodulatory and tumoricidal effects. In addition, cereblon also regulates the expression, assembly, and activities of other special proteins related to cell proliferation and metabolism, resulting in the occurrence and development of metabolic diseases. This review details the multiple functions of cereblon and the underlying mechanisms. We also put forward some unsolved problems, including the intrinsic mechanism of cereblon function and the possible regulatory mechanisms of its expression.
Renal Function Improvement by Telbivudine in Liver Transplant Recipients with Chronic Kidney Disease
Authors: Lee Wei-Chen , Wu Tsung-Han , Wang Yu-Chao , Cheng Chih-Hsien , Lee Chen-Fang , Wu Ting-Jung , Chou Hong-Shiue , Chan Kun-Ming , Lee Ching-Song
Published: August 2017

Chronic renal failure is a frequent complication in liver transplantation. Telbivudine, anti-hepatitis B virus (HBV) nucleoside, can improve renal function. It is interesting if using telbivudine for prophylaxis of HBV recurrence has additional value on renal function improvement. 120 liver transplant recipients with lamivudine prophylaxis for HBV recurrence were 1 : 1 randomized into lamivudine-continuous (n=60) and telbivudine-replacement (n=60) groups. Fifty-eight patients in lamivudine-continuous group and 54 in telbivudine-replacement group completed the study. In telbivudine-replacement group, the estimated glomerular filtration rate (eGRF) was improved from 63.0 ± 16.3 ml/min to 72.8 ± 21.1 ml/min at 12 months after telbivudine administration (p = 0.003). Stratifying the patients according to renal function staging, the eGRF was improved from 74.7 ± 6.9 ml/min to 84.2 ± 16.6 ml/min (p = 0.002) in 32 stage II patients and from 48.2 ± 7.3 ml/min to 59.7 ± 11.8 ml/min in 20 stage III patients after 12 months of telbivudine administration (p<0.001). Eleven (18.3%) patients with telbivudine developed polyneuritis during the trial and post hoc following-up. In conclusion, renal function was improved by telbivudine in liver transplant recipients with long-term chronic kidney disease. However, the high incidence of polyneuritis induced by telbivudine has to be closely monitored. This trial is registered with ClinicalTrials NCT02447705.
Plastic Zone Analysis of Deep‐Buried, Noncircular Tunnel and Application on the High‐Speed Railway in the Karst Area
Authors: Shi Hai , Bai Mingzhou
Published: August 2017

With the conformal mapping function provided by Verruijt, the outland of a noncircular tunnel can be mapped to a circular unit in the complex plane and then spread the analytic function into a Laurent series. The stress unified solution of oval and horseshoe cross section can be determined using Muskhelishvili’s complex variables function method. Subsequently, the solution can be taken into the Griffith strength failure criterion and determine the scale and shape of plastic zone in the tunnel surrounding rock. Aiming at the critical safety thickness between a concealed cave and tunnel in the karst area and determining whether the plastic zone of tunnel surrounding rock is connected with the plastic zone of cave as a judgment standard, the model of critical safety thickness among the concealed caves and tunnels is established. The numerical model is established in comparison with the computing method of rock plate critical safety thickness in actual engineering based on the Doumo tunnel engineering of Shanghai‐Kunming (Guizhou segment) high‐speed railway. The following conclusions can be drawn: the analytical approximation method has less indexes, and the output of this method is approximately close to actual engineering and numerical analysis, in which it is reliable and rational.
Evaluation of Epigallocatechin-3-gallate Modified Collagen Membrane and Concerns on Schwann Cells
Authors: Chu Chenyu , Deng Jia , Cao Cong , Man Yi , Qu Yili
Published: August 2017

Collagen is an essential component of the extracellular matrix (ECM) and is a suitable material for nerve repair during tissue remodeling for fracture repair. Epigallocatechin-3-gallate (EGCG), an extract of green tea, shows various biological activities that are beneficial to nerve repair. Here, we developed modified collagen containing different concentrations of EGCG (0.0064%, 0.064%, and 0.64%, resp.) to induce Schwann cell proliferation and differentiation. Cell Counting Kit-8 test, live/dead assay, and SEM showed that collagen cross-linked by EGCG induced Schwann cell proliferation. Real-time polymerase chain reaction, enzyme-linked immunosorbent assay, and Western blotting revealed that EGCG-modified collagen induced Schwann cell differentiation and downregulated reactive oxygen species (ROS) levels by downregulating the MAPK P38 signaling pathway. Our results indicate that collagen cross-linked with an appropriate concentration of EGCG induces the proliferation and differentiation of Schwann cells. The EGCG-modified collagen membrane may be applicable for nerve repair and guided tissue regeneration applications.
Bone Marrow Metastasis Is an Early Stage of Bone Metastasis in Breast Cancer Detected Clinically by F18-FDG-PET/CT Imaging
Authors: Al-Muqbel Kusai M.
Published: August 2017

Objective. To determine the value of 18F-FDG PET/CT in detection of bone marrow (BM) metastasis in breast cancer which is considered an early stage of bone metastasis. Patients and Methods. Retrospectively, breast cancer patients with bone metastasis were included. BM metastasis was considered if the lesion was PET positive/CT occult while bone metastasis was considered if the lesion was PET positive/ CT positive. BM metastases were observed sequentially on F18-FDG PET/CT. Results. We included 35 patients. Eighteen patients (51%) had BM metastases in addition to other bone metastases. BM metastases comprised 24% of all lesions. Posttreatment scan was performed on 26/35 patients. Twenty-three percent of BM metastases had resolved completely without causing bone destruction after treatment. Sixty-five percent of BM metastases had converted into bone metastases after treatment. Twelve percent of BM metastases had persisted after treatment. Conclusion. This retrospective study showed clinically by 18F-FDG PET/CT imaging that BM metastasis is an early stage of bone metastasis in breast cancer. Interestingly, 18F-FDG-PET/CT showed that early eradication of individual BM metastasis by systemic treatment precluded development of bone metastasis. However, more research is needed to study the impact of an early diagnosis of BM metastases on treatment outcome.
Chromatin-Associated Protein SIN3B Prevents Prostate Cancer Progression by Inducing Senescence
Authors: Bainor Anthony J. , Deng Fang-Ming , Wang Yu , Lee Peng , Cantor David J. , Logan Susan K. , David Gregory
Published: August 2017

Distinguishing between indolent and aggressive prostate adenocarcinoma remains a priority to accurately identify patients who need therapeutic intervention. SIN3B has been implicated in the initiation of senescence in vitro. Here we show that in a mouse model of prostate cancer, SIN3B provides a barrier to malignant progression. SIN3B was required for PTEN-induced cellular senescence and prevented progression to invasive prostate adenocarcinoma. Furthermore, SIN3B was downregulated in human prostate adenocarcinoma correlating with upregulation of its target genes. Our results suggest a tumor suppressor function for SIN3B that limits prostate adenocarcinoma progression, with potential implications for the use of SIN3B and its target genes as candidate diagnostic markers to distinguish indolent from aggressive disease. Cancer Res; 77(19); 5339–48. ©2017 AACR.
Genomic Alterations in Circulating Tumor DNA from Diverse Cancer Patients Identified by Next-Generation Sequencing
Authors: Schwaederle Maria , Chattopadhyay Ranajoy , Kato Shumei , Fanta Paul T. , Banks Kimberly C. , Choi In Sil , Piccioni David E. , Ikeda Sadakatsu , Talasaz AmirAli , Lanman Richard B. , Bazhenova Lyudmila , Kurzrock Razelle
Published: August 2017

Noninvasive genomic profiling of tumors may be possible with next-generation sequencing (NGS) of blood-derived circulating tumor DNA (ctDNA), but proof of concept in a large cohort of patients with diverse cancers has yet to be reported. Here we report the results of an analysis of plasma-derived ctDNA from 670 patients with diverse cancers. The tumors represented in the patient cohort were mainly gastrointestinal (31.8%), brain (22.7%), or lung (20.7%). ctDNA obtained from most patients [N = 423 (63%)] displayed at least one alteration. The most frequent alterations seen, as characterized mutations or variants of unknown significance, occurred in TP53 (32.5% of patients), EGFR (13%), KRAS (12.5%), and PIK3CA (9.1%); for characterized alterations, 30.7% (TP53), 7.6% (EGFR), 12.2% (KRAS), and 7.7% (PIK3CA). We found that 32% of brain tumors had at least one ctDNA alteration. Head and neck tumors were independently associated with a higher number of alterations in a multivariable analysis (P = 0.019). Notably, 320/670 (48%) of patients displayed potentially actionable alterations, with 241 patients possible candidates for on-label or off-label treatment with an FDA-approved drug. Several illustrations of the clinical utility of the information obtained for improving treatment of specific patients is provided. Our findings demonstrate the feasibility and impact of genomic profiling of tumors by ctDNA NGS, greatly encouraging broader investigations of the application of this technology for precision medicine in cancer management. Cancer Res; 77(19); 5419–27. ©2017 AACR.
The Rac GTPase in Cancer: From Old Concepts to New Paradigms
Authors: Kazanietz Marcelo G. , Caloca Maria J.
Published: August 2017

Rho family GTPases are critical regulators of cellular functions that play important roles in cancer progression. Aberrant activity of Rho small G-proteins, particularly Rac1 and their regulators, is a hallmark of cancer and contributes to the tumorigenic and metastatic phenotypes of cancer cells. This review examines the multiple mechanisms leading to Rac1 hyperactivation, particularly focusing on emerging paradigms that involve gain-of-function mutations in Rac and guanine nucleotide exchange factors, defects in Rac1 degradation, and mislocalization of Rac signaling components. The unexpected pro-oncogenic functions of Rac GTPase-activating proteins also challenged the dogma that these negative Rac regulators solely act as tumor suppressors. The potential contribution of Rac hyperactivation to resistance to anticancer agents, including targeted therapies, as well as to the suppression of antitumor immune response, highlights the critical need to develop therapeutic strategies to target the Rac pathway in a clinical setting. Cancer Res; 77(20); 5445–51. ©2017 AACR.
Use of Antihypertensive Medications and Risk of Adverse Breast Cancer Outcomes in a SEER–Medicare Population
Authors: Chen Lu , Chubak Jessica , Boudreau Denise M. , Barlow William E. , Weiss Noel S. , Li Christopher I.
Published: August 2017

Background: It is unclear if use of common antihypertensive medications influences the risk of adverse breast cancer outcomes.

Methods: Using the linked Surveillance, Epidemiology and End-Results (SEER)–Medicare database, we identified 14,766 women between ages 66 and 80 years diagnosed with incident stage I/II breast cancer between 2007 and 2011. Medicare Part D data were obtained to characterize women's post-cancer use of various antihypertensive medications. Outcomes included a second breast cancer event (SBCE; a composite outcome defined as the first of a recurrence or a second contralateral primary breast cancer), breast cancer recurrence, and breast cancer–specific mortality. Time-varying Cox proportional hazard models were used to estimate hazard ratios (HR) and their associated 95% confidence intervals (CI).

Results: There were 791 SBCEs, 627 breast cancer recurrences, and 237 breast cancer deaths identified over a median follow-up of 3 years. Use of diuretics (n = 8,517) after breast cancer diagnosis was associated with 29% (95% CI, 1.10–1.51), 36% (95% CI, 1.14–1.63) and 51% (95% CI, 1.11–2.04) higher risks of a SBCE, recurrence, and breast cancer death, respectively. Compared with nonusers, β-blockers users (n = 7,145) had a 41% (95% CI, 1.07–1.84) higher risk of breast cancer death. Use of angiotensin II receptor blockers, calcium channel blockers and angiotensin-converting enzyme inhibitors were not associated with risks of breast cancer outcomes.

Conclusions: Use of diuretics and β-blockers may be associated with increased risk of breast cancer outcomes among older women.

Impact: Most antihypertensive medications are safe with respect to breast cancer outcomes, but more research is needed for diuretics and β-blockers. Cancer Epidemiol Biomarkers Prev; 26(11); 1603–10. ©2017 AACR.
Increasing Haemodialytic Clearances as Residual Renal Function Declines: An Incremental Approach
Authors: Tangvoraphonkchai Kamonwan , Davenport Andrew
Published: August 2017

Many patients with chronic kidney disease start undergoing thrice-weekly haemodialysis (HD), aiming for an HD sessional dialyzer urea clearance target, irrespective of whether they have residual renal function (RRF). While increasing sessional dialyzer urea clearance above a target of 1.2 has not been shown to improve patient survival, it has been shown that the preservation of RRF improves patient self-reported outcomes and survival. Observational studies have suggested that initiating twice-weekly HD schedules leads to greater preservation of RRF. This has led to the concept of following an incremental approach to initiating HD, steadily increasing the amount of weekly dialyzer clearance as RRF decreases. Incremental dialysis practice requires the regular assessment of RRF to prevent inadequate delivery of dialysis treatment. Once RRF is lost, then the dialysis schedule and modality need to be adjusted to try to increase the middle-sized solute clearance and protein-bound toxins.
Obesity as a Conditioning Factor for High-Altitude Diseases
Authors: San Martin Rocío , Brito Julio , Siques Patricia , León-Velarde Fabiola
Published: August 2017

Obesity, a worldwide epidemic, has become a major health burden because it is usually accompanied by an increased risk for insulin resistance, diabetes, hypertension, cardiovascular diseases, and even some kinds of cancer. It also results in associated increases in healthcare expenditures and labor and economic consequences. There are also other fields of medicine and biology where obesity or being overweight play a major role, such as high-altitude illnesses (acute mountain sickness, hypoxic pulmonary hypertension, and chronic mountain sickness), where an increasing relationship among these two morbid statuses has been demonstrated. This association could be rooted in the interactions between obesity-related metabolic alterations and critical ventilation impairments due to obesity, which would aggravate hypobaric hypoxia at high altitudes, leading to hypoxemia, which is a trigger for developing high-altitude diseases. This review examines the current literature to support the idea that obesity or overweight could be major conditioning factors at high altitude.
Cytoplasmic Lipid Accumulation Characteristic of the Cribriform Variant of Papillary Thyroid Carcinoma
Authors: Takada Nami , Hirokawa Mitsuyoshi , Ito Aki , Suzuki Ayana , Higuchi Miyoko , Kuma Seiji , Hayashi Toshitetsu , Daa Tsutomu , Miyauchi Akira
Published: August 2017

Objective: The purpose of this study was to clarify the diagnostic significance of cytoplasmic lipid accumulation (CLIA) in the cribriform variant of papillary thyroid carcinoma (CV-PTC). Methods: We performed a histological, immunohistochemical, and cytological examination of 35 CV-PTC cases at the Kuma Hospital. CLIA was defined as bubble-like multivacuolation in cytoplasm with distinct cell border. We also examined 100 conventional PTC (con-PTC) cases as controls. Results: Histological analysis showed the presence of carcinoma cells with CLIA in 60.0% of CV-PTC and 5.0% of con-PTC cases. The vacuoles tended to distribute in the subnuclear portion of carcinoma cells showing papillary growth. They were positive for oil red O staining and adipophilin. The carcinoma cells without the vacuoles showed a subnuclear dot-like expression for adipophilin in CV-PTC cases, but not in the con-PTC cases. Cytological analysis showed CLIA in 17 (54.8%) of the 31 CV-PTC cases, but not in the con-PTC cases. Conclusion: This is the first study to report the presence of carcinoma cells with CLIA in CV-PTC. The subnuclear dot-like expression of adipophilin may be characteristic of CV-PTC. These findings might be related to degenerative changes occurring in CV-PTC.
Long-Term Weight Maintenance Strategies Are Experienced as a Burden by Persons Who Have Lost Weight Compared to Persons with a lifetime Normal, Stable Weight
Authors: Kruseman Maaike , Schmutz Noémi , Carrard Isabelle
Published: August 2017

Objective: To assess dietary intake, eating patterns, physical activity and eating behaviors, and to explore strategies and perceptions of the experience of weight maintenance in weight loss maintainers (weight loss maintenance (WLM) ≥ 10% weight loss maintained for ≥1 year) and in matched controls with a lifetime stable normal weight. Methods: Volunteers (32) were recruited by a snowball procedure in this cross-sectional, mixed-methods study. Diet, physical activity, and eating behaviors were assessed with validated questionnaires. Strategies and experiences were investigated during interviews. Descriptive coding, thematic analysis (qualitative data) as well as descriptive analysis and t-tests (quantitative data) were performed. Results: Both groups had similar energy and macronutrient consumption. Those in the WLM group reported higher levels of exercise and scored higher on several dimensions of eating disorders. Four themes - ‘food choices,' ‘quantities and portion control,' ‘physical activity', and ‘burden' - emerged from the qualitative data. Both groups used similar weight maintenance strategies, but those in the WLM group experienced a higher burden, expressing effortful control which contrasted with the control group's confidence in their internal cues. Conclusion: Our results show an additional burden related with maintaining weight loss compared to keeping a stable normal weight. They provide evidence to devise interventions that will address the difficulty of regulating intake.
Karyotypes and Distribution of Tandem Repeat Sequences in Brassica nigra Determined by Fluorescence in situ Hybridization
Authors: Wang Gui-xiang , He Qun-yan , Macas Jiri , Novák Petr , Neumann Pavel , Meng De-xuan , Zhao Hong , Guo Ning , Han Shuo , Zong Mei , Jin Wei-wei , Liu Fan
Published: August 2017

Whole-genome shotgun reads were analyzed to determine the repeat sequence composition in the genome of black mustard, Brassica nigra (L.) Koch. The analysis showed that satellite DNA sequences are very abundant in the black mustard genome. The distribution pattern of 7 new tandem repeats (BnSAT13, BnSAT28, BnSAT68, BnSAT76, BnSAT114, BnSAT180, and BnSAT200) on black mustard chromosomes was visualized using fluorescence in situ hybridization (FISH). The FISH signals of BnSAT13 and BnSAT76 provided useful cytogenetic markers; their position and fluorescence intensity allowed for unambiguous identification of all 8 somatic metaphase chromosomes. A karyotype showing the location and fluorescence intensity of these tandem repeat sequences together with the position of rDNAs and centromeric retrotransposons of Brassica (CRB) was constructed. The establishment of the FISH-based karyotype in B. nigra provides valuable information that can be used in detailed analyses of B. nigra accessions and derived allopolyploid Brassica species containing the B genome.
The Etiology of Hoarding Disorder: A Review
Authors: Dozier Mary E. , Ayers Catherine R.
Published: August 2017

This article will review the evidence of various proposed factors that contribute to the onset and maintenance of hoarding disorder (HD). Data suggests that hoarding is a chronic condition that starts early in life and does not remit if left untreated. There is emerging evidence that a number of factors contribute to the expression of HD symptoms, including genetics, neurocognitive functioning, attachments to possessions, beliefs, avoidance, personality factors, and life events. The extent to which each etiological factor uniquely contributes to hoarding is still unknown. Other demographic factors, such as socioeconomic status, age, and gender, may impact hoarding severity. Research on the causes and characteristics of hoarding has recently started making progress into understanding this newly recognized disorder, yet we still have a ways to go in understanding the biological and environmental causes. This paper will synthesize available literature on the etiology of HD.
Conditional Cash Transfers and Nutrition: An Evaluation of the Bolsa Familia Program in rural and urban areas of Brazil
Authors: Pinho Neto Valdemar Rodrigues de , Berriel Cecilia Machado
Published: August 2017

Este trabalho investiga o efeito do Programa Bolsa Família (PBF) sobre o estado nutricional das crianças e adolescentes beneficiadas. Para tanto, foram utilizados os dados da Pesquisa de Orçamentos Familiares (POF- 2008/2009), conjuntamente com o método Propensity Score Matching. A caracterização nutricional foi realizada com base em recentes recomenda- ções da Organização Mundial da Saúde. A amostra estudada inclui crianças e adolescentes menores de 19 anos de idade, permitindo-se efeitos heterogêneos do programa entre as áreas urbanas e rurais do país. Os resultados indicam que o PBF melhorou os indicadores nutricionais daqueles que pertenciam ao grupo de tratamento. Além da transferência de renda, acredita-se que as condicionalidades nas áreas da saúde e educação possam explicar parte desse resultado.
Education spending: more resources without management?
Authors: Castro Carlos Renato De Melo , Souza Geraldo Da Silva e , Tannuri-Pianto Maria Eduarda
Published: August 2017

Neste trabalho, modela-se uma função custo para o ensino fundamental brasileiro. Metodologicamente, destaca-se a utilização da Forma Flexí- vel de Fourier para transpor os vieses normalmente apresentados na utilização das formas flexíveis locais. Os resultados indicam que, tudo mais constante, mesmo gastos da ordem de 10% do PIB não seriam suficientes para alcançar a proficiência mínima para 100% dos alunos. Observou-se que municípios com mais renda, menos urbanos, com menos desigualdade de renda e com maiores taxas de analfabetismo apresentam maiores exigências de gastos e maiores níveis de ineficiência. Quanto às variáveis que estão sob a gestão educacional do município, destaca-se a importância do número de alunos por turma e da carga horária diária. Por fim, obteve-se ineficiência média de 14,7%.
As vice-rainhas e o exercício do poder na Nova Espanha (sec. XVI e XVII)
Authors: Zapatero Alberto Baena
Published: August 2017

Este artigo trata da corte vice-reinal mexicana ao longo dos séculos XVI e XVII, refletindo sobre um dos aspectos menos trabalhados pela historiografia especializada: o papel das vice-rainhas e seus cortejos. A investigação aprofunda o estudo do significado de suas relações com a sociedade local e sua participação no exercício quotidiano da autoridade. O trabalho não se centrará exclusivamente na figura das vice-rainhas, ocupando-se também de todas as mulheres que formaram seu cortejo e participaram das dinâmicas sociais e políticas da corte mexicana. Essas damas, que poderiam ser de origem peninsular ou criollas (mulheres de origem espanhola nascidas na América), permaneceram anônimas para os historiadores, e seu papel é fundamental para entendermos as estratégias políticas e sociais desenvolvidas na corte.
Temporal Relationship Between Hyperuricemia and Insulin Resistance and Its Impact on Future Risk of Hypertension
Authors: Han Tianshu , Lan Li , Qu Rongge , Xu Qian , Jiang Ruyue , Na Lixin , Sun Changhao
Published: August 2017

Although hyperuricemia and insulin resistance significantly correlated, their temporal sequence and how the sequence influence on future risk of hypertension are largely unknown. This study assessed temporal relationship between uric acid and insulin resistance and its impact on future risk of hypertension by examining a longitudinal cohort including 8543 subjects aged 20 to 74 years from China, with an average follow-up of 5.3 years. Measurements of fasting uric acid, as well as fasting and 2-hour serum glucose and insulin, were obtained at baseline and follow-up. Indicators of hepatic and peripheral insulin resistance were calculated. Cross-lagged panel and mediation analysis were used to examine the temporal relationship between uric acid and insulin resistance and its impact on follow-up hypertension. After adjusting for covariates, the cross-lagged path coefficients (
β
1
values) from baseline uric acid to follow-up insulin resistance indices were significantly greater than path coefficients (
β
2
values) from baseline insulin resistance indices to follow-up uric acid (
β
1
=0.110 versus
β
2
=0.017;
P
<0.001, for hepatic insulin resistance;
β
1
=−0.208 versus
β
2
=−0.021;
P
<0.001, for peripheral insulin resistance). The path coefficients from baseline uric acid to follow-up insulin resistance indices in the hypertensive group were significantly greater than that in the normotensive group (
P
<0.001 for the difference of
β
1
values in the 2 groups). Insulin resistance partially mediated the effect of uric acid on subsequent hypertension, and the mediation effect of peripheral insulin resistance was significantly greater than that of hepatic insulin resistance (31.3% versus 13.2%;
P
<0.001, for the difference of mediation effects). These findings provide evidence that higher uric acid levels probably precede insulin resistance, and peripheral insulin resistance likely plays a more important role in the development of hypertension than hepatic insulin resistance does.
Resource Extraction Technologies: Is a More Responsible Path of Development Possible?
Authors: David Martin , Wallkamm Magdalena , Bleicher Alena
Published: August 2017

Technologies impact societies in manifold and often unforeseen ways. In several fields of technology (e.g. nanotechnology, biotechnology) it has been argued that reflexive modes of technology development are appropriate to deal with this challenge. A central aim of reflexive modes is the integration of broader societal perspectives early in technology development processes in order to achieve a more (societal) responsible way of technology development. Whereas social scientific accounts on mining and resource extraction emphasize topics like corporate social responsibility, occupational safety, or distributive justice, little light is shed on the possibility of more reflexive modes that integrate societal perspectives early on in the development of resource extraction technologies. These technologies decisively influence social life worlds. Within this article we will shed light on mining technologies, and discuss the relevance of early integration of societal concerns into their development. We argue that an early integration of these concerns can help to shape new technologies in societally responsible ways, and by so doing, to deal with globally increasing opposition to resource extraction operations. To underline this argument, the article delineates four major challenges connected to technology development and application in the domain of resource extraction: the identification of the problems’ locus, knowledge integration, the consideration of non-knowledge, and the reflection of manifold roles that actors have in technology development contexts. The article concludes with future research challenges for technology development in the domain of resource extraction.