bluuebunny/crossref_metadata_2025 huggingface dataset:
SS‐31 Provides Neuroprotection by Reversing Mitochondrial Dysfunction after Traumatic Brain Injury
Authors: Zhu Yihao , Wang Handong , Fang Jiang , Dai Wei , Zhou Jiang , Wang Xiaoliang , Zhou Mengliang
Published: August 2018

SS‐31, a novel mitochondria‐targeted peptide, has been proven to provide neuroprotection in a variety of neurological diseases. Its role as a mitochondrial reactive oxygen species (ROS) scavenger and the underlying pathophysiological mechanisms in traumatic brain injury (TBI) are still not well understood. The aim of the designed study was to investigate the potential neuroprotective effects of SS‐31 and fulfill our understanding of the process of the mitochondrial change in the modified Marmarou weight‐drop model of TBI. Mice were randomly divided into sham, TBI, TBI + vehicle, and TBI + SS‐31 groups in this study. Peptide SS‐31 (5 mg/kg) or vehicle was intraperitoneally administrated 30 min after TBI with brain samples harvested 24 h later for further analysis. SS‐31 treatment significantly reversed mitochondrial dysfunction and ameliorated secondary brain injury caused by TBI. SS‐31 can directly decrease the ROS content, restore the activity of superoxide dismutase (SOD), and decrease the level of malondialdehyde (MDA) and the release of cytochrome c, thus attenuating neurological deficits, brain water content, DNA damage, and neural apoptosis. Moreover, SS‐31 restored the expression of SIRT1 and upregulated the nuclear translocation of PGC‐1α, which were proved by Western blot and immunohistochemistry. Taken together, these data demonstrate that SS‐31 improves the mitochondrial function and provides neuroprotection in mice after TBI potentially through enhanced mitochondrial rebiogenesis. The present study gives us an implication for further clinical research.
Simultaneous Voltammetric Determination of Ascorbic Acid, Paracetamol, and Caffeine Using Electrochemically Reduced Graphene-Oxide-Modified Electrode
Authors: Phong Nguyen Hai , Toan Tran Thanh Tam , Tinh Mai Xuan , Tuyen Tran Ngoc , Mau Tran Xuan , Khieu Dinh Quang
Published: August 2018

In the present paper, graphene oxide was directly electrodeposited by means of cyclic voltammetric techniques on the glassy-carbon electrode (GCE) to obtain a reduced graphene-oxide-modified electrode (ErGO/GCE). Cyclic voltammetry (CV) and differential pulse anodic stripping voltammetry (DP-ASV) had been utilized to study the electrochemical behavior of ErGO/GCE toward ascorbic acid (AA), paracetamol (PA), and caffeine (CA). Differential pulse voltammetry results show that AA, PA, and CA could be detected selectively and sensitively on ErGO/GCE with peak-to-peak separation of 312 mV and 756 mV for AA–PA and PA–CA, respectively. The factors affecting the voltammetric signals such as pH, scan rate, and interferents were addressed. The results reveal that the ErGO/GCE-modified electrode exhibits excellent electrochemical activity in the oxidation of PA, CA, and AA. The detection limits are 0.36 μM, 0.25 μM, and 0.23 μM for AA, PA and CA, respectively, suggesting that the ErGO/GCE can be utilized with high sensitivity and selectivity for the simultaneous determination of these compounds. Finally, the proposed method was successfully used to determine AA, PA, and CA in pharmaceutical preparations.
A Novel Technique of Spectral Discrimination of Variants of Sickle Cell Anemia
Authors: Masilamani Vadivel , Devanesan Sandanasamy , AlQathani Fatma , AlShebly Mashael , Daban Hebatullah Hassan , Canatan Duran , Farhat Karim , Jabry Mansour , AlSalhi Mohamad S.
Published: August 2018

Sickle cell anemia (SCA) is an inherited blood disorder with worldwide incidence of 15%; out of this, it is found in up to 20% in countries like Kingdom of Saudi Arabia and Bahrain. The standard conventional method of detection is complete blood count (CBC) followed by hemoglobin electrophoresis or high-performance liquid chromatography (HPLC) or both. In this context, spectral detection of variants of sickle cell anemia (SCA) is an innovative technique, which when made accurate and reliable could be an effective alternative, since the instrumentation is compact (5 kg) and hence portable. This makes mass screening even in remote villages possible. In this paper, we give the essential aspects of fluorescent spectral features of sickle cell trait (SCT), sickle cell disease (SCD), beta (β) thalassemia trait (BTT) + SCD, and beta (β) thalassemia disease (BTD) + SCD. All the above four major variants could be discriminated among themselves and also from the normal control blood sample. All these analyses could be carried out with 5 ml of blood, in a time period of 10 minutes. The results of this paper give strong support for an alternative method, a spectral technique, for molecular-level diagnosis of sickle cell anemia and other closely related blood disorders.
Apple Variety Identification Using Near-Infrared Spectroscopy
Authors: Li Caihong , Li Lingling , Wu Yuan , Lu Min , Yang Yi , Li Lian
Published: August 2018

Near-infrared (NIR) spectra of apple samples were submitted in this paper to principal component analysis (PCA) and successive projections algorithm (SPA) to conduct variable selection. Three pattern recognition methods, backpropagation neural network (BPNN), support vector machine (SVM), and extreme learning machine (ELM), were applied to establish models for distinguishing apples of different varieties and geographical origins. Experimental results show that ELM models performed better on identifying apple variety and geographical origin than others. Especially, the SPA-ELM model could reach 98.33% identification accuracy on the calibration set and 96.67% on the prediction set. This study suggests that it is feasible to identify apple variety and cultivation region by using NIR spectroscopy.
Simulating Intraurban Land Use Dynamics under Multiple Scenarios Based on Fuzzy Cellular Automata: A Case Study of Jinzhou District, Dalian
Authors: Yang Jun , Liu Weiling , Li Yonghua , Li Xueming , Ge Quansheng
Published: August 2018

The spatial evolution of land use in Jinzhou area was simulated using fuzzy cellular automata to determine all factors influencing urban land use change. For this purpose, land use data of multiple sources and remote sensing images from 2003 to 2015 were analyzed. The following results were obtained: (1) real land use data and simulation data for 2015 were tested using four indices. Under the 5 m × 5 m scale, the model shows good performance for simulation of areas with various land use types. (2) Among simulations under four scenarios, the effect of traffic guidance on the development of construction land was more distinct under the economic development mode, which clearly showed the phenomenon of “agglomeration” along major traffic lines. (3) Jinshitan Street is adjacent to the sea, and land use changes are significant under the 4th scenario, and thus related departments should pay more attention. (4) Shortcomings of conventional cellular automata model in processing complex systems could be mitigated through the integration of fuzzy sets.
Experimental Study on Explosion Pressure and Rock Breaking Characteristics under Liquid Carbon Dioxide Blasting
Authors: Zhang Yanan , Deng Junren , Ke Bo , Deng Hongwei , Li Jielin
Published: August 2018

A liquid carbon dioxide blasting experiment was carried out under free field conditions, alongside a liquid carbon dioxide rock breaking experiment, to investigate explosion pressure variation and rock breaking characteristics under liquid carbon dioxide blasting. The experimental results show that the internal and external explosion pressures of the liquid carbon dioxide fracturing devices all rapidly increased at first, before attenuating vibrantly after blasting. When the explosion pressure was raised, the internal explosion pressure increased first exponentially and then linearly, while the external explosion pressure increased exponentially throughout. The duration time of the blasting effect stage was about 45 ms. Under the combined effect of jet impingement and a gas wedge of high‐pressure carbon dioxide, the rock is subjected to tensile failure. The impact failure and the “gas wedge effect” of high‐pressure carbon dioxide play a key role in the rock breaking of liquid carbon dioxide blasting technology.
“Diabetes and Metabolism Disorders Medicinal Plants: A Glance at the Past and a Look to the Future 2018”: Antihyperglycemic Activity of Hamelia patens Jacq. Extracts
Authors: Rugerio-Escalona Catalina , Ordaz-Pichardo Cynthia , Becerra-Martinez Elvia , Cruz-López María del Carmen , López-y-López Victor E. , Mendieta-Moctezuma Aarón , Maldonado-Mendoza Ignacio E. , Jiménez-Montejo Fabiola E.
Published: August 2018

Diabetes is one the world’s most widespread diseases, affecting over 327 million people and causing about 300,000 deaths annually. Despite great advances in prevention and therapy, existing treatments for this disorder have serious side effects. Plants used in traditional medicine represent a valuable source in the search for new medicinal compounds. Hamelia patens Jacq. has been used for treating diabetes and, so far, no reports have been made on the in vivo antihyperglycemic activity of this plant. The present study on H. patens aimed to test the antihyperglycemic effect of repeated administrations of the crude and fractional methanolic extracts (CME and FME, respectively) on rats with hyperglycemia induced by streptozotocin. After 10 administrations (20 days), each extract had lowered blood glucose to a normal level. The extracts produced effects similar to metformin. Of the five compounds identified by chromatographic analysis of the extracts, epicatechin and chlorogenic acid demonstrated antihyperglycemic effect. The antioxidant activity of the extracts was evidenced by their IC50 values (51.7 and 50.7 μg/mL, respectively). The LD50≥2000 mg/Kg suggests low toxicity for both CME and FME. Thus, considering that the antihyperglycemic and antioxidant effects of metformin and extracts from H. patens were comparable, the latter may be efficacious for treating diabetes.
Analysis of the Time Series Generated by a New High‐Dimensional Discrete Chaotic System
Authors: Wang Chuanfu , Fan Chunlei , Feng Kai , Huang Xin , Ding Qun
Published: August 2018

The chaotic behavior of low‐dimensional digital chaotic systems is seriously degraded, and the output sequence has a short period. In this study, a digital sequence generator based on a high‐dimensional chaotic system is proposed to ensure performance and security. The proposed generator has low resource consumption, and the digital pseudo‐random output sequence has a large period. To avoid the nonchaotic state, the multistability in the high‐dimensional discrete chaotic system is analyzed. The statistical performance of the output sequence of the proposed digital high‐dimensional chaotic system is evaluated, and the results demonstrate that it is a suitable candidate for a long‐period pseudo‐random sequence generator.
TIP: A Web Server for Resolving Tumor Immunophenotype Profiling
Authors: Xu Liwen , Deng Chunyu , Pang Bo , Zhang Xinxin , Liu Wei , Liao Gaoming , Yuan Huating , Cheng Peng , Li Feng , Long Zhilin , Yan Min , Zhao Tingting , Xiao Yun , Li Xia
Published: August 2018

Systematically tracking the tumor immunophenotype is required to understand the mechanisms of cancer immunity and improve clinical benefit of cancer immunotherapy. However, progress in current research is hindered by the lack of comprehensive immune activity resources and easy-to-use tools for biologists, clinicians, and researchers to conveniently evaluate immune activity during the “cancer-immunity cycle.” We developed a user-friendly one-stop shop web tool called TIP to comprehensively resolve tumor immunophenotype. TIP has the capability to rapidly analyze and intuitively visualize the activity of anticancer immunity and the extent of tumor-infiltrating immune cells across the seven-step cancer-immunity cycle. Also, we precalculated the pan-cancer immunophenotype for 11,373 samples from 33 The Cancer Genome Atlas human cancers that allow users to obtain and compare immunophenotype of pan-cancer samples. We expect TIP to be useful in a large number of emerging cancer immunity studies and development of effective immunotherapy biomarkers. TIP is freely available for use at http://biocc.hrbmu.edu.cn/TIP/.

Significance:

TIP is a one-stop shop platform that can help biologists, clinicians, and researchers conveniently evaluate anticancer immune activity with their own gene expression data.

See related commentary by Hirano, p. 6536
De Novo Fatty Acid Synthesis-Driven Sphingolipid Metabolism Promotes Metastatic Potential of Colorectal Cancer
Authors: Jafari Naser , Drury James , Morris Andrew J. , Onono Fredrick O. , Stevens Payton D. , Gao Tianyan , Liu Jinpeng , Wang Chi , Lee Eun Y. , Weiss Heidi L. , Evers B. Mark , Zaytseva Yekaterina Y.
Published: August 2018

Metastasis is the most common cause of death in colorectal cancer patients. Fatty acid synthase (FASN) and sphingosine kinase-1 and -2 (SPHK1 and 2) are overexpressed in many cancers, including colorectal cancer. However, the contribution of FASN-mediated upregulation of sphingolipid metabolism to colorectal cancer metastasis and the potential of these pathways as targets for therapeutic intervention remain unknown. This study determined that sphingosine kinases (SPHK) are overexpressed in colorectal cancer as compared with normal mucosa. FASN expression significantly correlated with SPHK2 expression in data sets from The Cancer Genome Atlas (TCGA) and a colorectal cancer tumor microarray. FASN, SPHK1, and SPHK2 colocalized within invadopodia of primary colorectal cancer cells. Moreover, FASN inhibition decreased SPHK2 expression and the levels of dihydrosphingosine 1-phosphate (DH-S1P) and sphingosine 1-phosphate (S1P) in colorectal cancer cells and tumor tissues. Inhibition of FASN using TVB-3664 and sphingolipid metabolism using FTY-720 significantly inhibited the ability of primary colorectal cancer cells to proliferate, migrate, form focal adhesions, and degrade gelatin. Inhibition of the FASN/SPHK/S1P axis was accompanied by decreased activation of p-MET, p-FAK, and p-PAX. S1P treatment rescued FASN-mediated inhibition of these proteins, suggesting that FASN promotes metastatic properties of colorectal cancer cells, in part, through an increased sphingolipid metabolism. These data demonstrate that upregulation of the FASN/SPHK/S1P axis promotes colorectal cancer progression by enhancing proliferation, adhesion, and migration.

Implications:

This study provides a strong rationale for further investigation of the interconnection of de novo lipogenesis and sphingolipid metabolism that could potentially lead to the identification of new therapeutic targets and strategies for colorectal cancer.
Epidemiology of Transthyretin Familial Amyloid Polyneuropathy in Portugal: A Nationwide Study
Authors: Inês Mónica , Coelho Teresa , Conceição Isabel , Duarte-Ramos Filipa , de Carvalho Mamede , Costa João
Published: August 2018

Background: Transthyretin-associated familial amyloid polyneuropathy (TTR-FAP) is a rare, hereditary, progressive and neurodegenerative disease. We aimed to study ­TTR-FAP epidemiology in Portugal. Methods: National, observational, prospective and retrospective, case identification of adults with TTR-FAP. Countrywide patient multiple identification sources included reference centers registries and centralized medical electronic prescription database. Crude rates were reported per 100,000 adult inhabitants. Results: Over 2010–2016 period, mean incidence rates was 0.87/100,000 (95% CI 0.68–1.10) corresponding to 71 new patients yearly, that has decreased 31% in the last 7 years. The proportion of late-onset cases (age ≥50 years) among incident cases was 28.7%. Estimated crude 2016 prevalence was 22.93/100,000 adult inhabitants (95% CI 21.90–23.99) corresponding to 1,865 TTR-FAP individuals in Portugal (45.8% male; mean age: 52.3 ± 15.4 years). In 2016, the Portuguese region with the highest TTR-FAP prevalence shows a 16% prevalence increase over the last 25 years. Conclusions: In Portugal, TTR-FAP affects both genders and mainly young adults. TTR-FAP incidence appears to be decreasing while prevalence is increasing. In comparison to previous studies, there is an increased representativeness of late-onset patients. This epidemiological setting poses future and complex challenges for the social and healthcare system, strengthening the relevance of regular epidemiologic surveillance.
Risk of Hemorrhagic Stroke in Patients Exposed to Nonsteroidal Anti-Inflammatory Drugs: A Meta-Analysis of Observational Studies
Authors: Islam Md. Mohaimenul , Poly Tahmina Nasrin , Walther Bruno Andreas , Yang Hsuan-Chia , Lin Ming-Chin , Li Yu-Chuan
Published: August 2018

Background and Aim: Nonsteroidal anti-inflammatory drugs (NSAIDs) are one of the most common pain relief medications, but the risk of hemorrhagic stroke in patients taking these medications is unclear. In this study, our aim was to systematically review, synthesize, and critique the epidemiological studies that evaluate the association between NSAIDs and hemorrhagic stroke risk. We therefore assessed the current state of knowledge, filling the gaps in our existing concern, and make a recommendation for future research. Methods: We searched for articles in PubMed, EMBASE, Scopus, and Web of Science between January 1, 1990, and July 30, 2017, which reported on the association between the use of NSAIDs and hemorrhagic stroke. The search was limited to studies published in English. The quality of the included studies was assessed in accordance with the Cochrane guidelines and the Newcastle-Ottawa criteria. Summary risk ratios (RRs) with 95% CI were pooled using a random-effects model. Subgroup and sensitivity analyses were also conducted. Results: We selected 15 out of the 785 unique abstracts for full-text review using our selection criteria, and 13 out of these 15 studies met all of our inclusion criteria. The overall pooled RR of hemorrhagic stroke was 1.332 (95% CI 1.105–1.605, p = 0.003) for the random effect model. In the subgroup analysis, a significant risk was observed among meloxicam, diclofenac, and indomethacin users (RR 1.48; 95% CI 1.149–1.912, RR 1.392; 95% CI 1.107–1.751, and RR 1.363; 95% CI 1.088–1.706). In addition, a greater risk was found in studies from Asia (RR 1.490, 95% CI 1.226–1.811) followed by Europe (RR 1.393, 95% CI 1.104–1.757) and Australia (RR 1.361, 95% CI 0.755–2.452). Conclusion: Our results indicated that the use of NSAIDs is significantly associated with a higher risk of developing hemorrhagic stroke. These results should be interpreted with caution because they may be confounded owing to the observational design of the individual studies. Nevertheless, we recommend that NSAIDs should be used judiciously, and their efficacy and safety should be monitored proactively.
Increased Mortality Rate after Hospitalization Among Chronic Hemodialysis Patients: A Prospective Cohort Study
Authors: Shimizu Sayaka , Fukuma Shingo , Ikenoue Tatsuyoshi , Akizawa Tadao , Fukuhara Shunichi
Published: August 2018

Background/Aims: Hemodialysis patients are at high risk of hospitalization and their condition may worsen with repeated hospitalization. The aim of this study was to evaluate the impact of the cumulative number of hospitalizations on post-discharge mortality. Methods: This study was a prospective cohort study. We examined 3,359 adult patients on hemodialysis for at least 90 days who participated in the Japanese Dialysis Outcomes and Practice Patterns Study phases 3 and 4 (2005–2012). The patients hospitalized within 3 months before enrollment were excluded. The main exposure was the time-varying cumulative number of hospitalizations during the follow-up period. Hazard ratios (HRs) for all-cause mortality rate after discharge were estimated by time-dependent Cox regressions after adjusting for potential confounders. Results: The median follow-up time was 2.7 years, and 873 (26%) patients experienced at least 1 hospitalization during follow-up. The hospitalization rate was 0.23 per person-year and the mortality rate was 0.036 per person-year. The HR and 95% CI for post-discharge mortality increased as the cumulative number of hospitalizations increased: once, 1.41 (0.99–2.00); and twice or more, 2.27 (1.59–3.23). The cause-specific hospitalization categories, “infectious disease” and “cancer,” affected post-discharge mortality HRs in a similar manner: 2.41(1.32–4.41) and 2.70 (1.23–5.93), respectively. Conclusion: A higher cumulative number of hospitalizations is associated with increased post-discharge mortality in chronic hemodialysis patients. The cause-specific hospitalizations category of “infectious disease” showed an impact on mortality similar to that of hospitalization for “cancer.” Therefore, physicians should pay more attention to reducing preventable hospitalizations.
Neurocognitive Functioning in Alcohol Use Disorder: Cognitive Test Results Do not Tell the Whole Story
Authors: Moritz Steffen , Irshaid Schaimaa , Lüdtke Thies , Schäfer Ingo , Hauschildt Marit , Lipp Michael
Published: August 2018

Objectives: It is textbook knowledge that individuals with alcohol use disorder (AUD) show large neurocognitive deficits. However, these patients display a number of additional impairments (e.g., lack of drive and motivation) that may contribute to poor test results. The impact of these secondary mediators has not been explored systematically. Based on prior findings that low performance motivation, a negative attitude toward cognitive assessment, and momentary symptoms compromise neuropsychological test results in depression, schizophrenia, and obsessive-compulsive disorder, we examined the possibility that impaired test results in AUD partially represent an epiphenomenon. Methods: Fifteen patients with AUD and 20 matched nonclinical individuals underwent a comprehensive neuropsychological test battery. The neurocognitive assessment was flanked by the Momentary Influences, Attitudes and Motivation Impact on Cognitive Performance Scale (MIAMI), which captures momentary influences affecting performance. Results: Patients with AUD performed worse than nonclinical controls on most test parameters. Group differences achieved a very large effect size for parameters tapping speed and accuracy. Patients with AUD showed deviant scores, particularly on the post version of the MIAMI (retrospective assessment of symptoms and influences during testing) and the total scores. For accuracy, the MIAMI scores represented a partial mediator. For speed, significant group effect sizes were rendered nonsignificant when the MIAMI was taken into account. Conclusion: Like other psychiatric patients, patients with AUD show marked neurocognitive impairments that seem to be aggravated by, for example, distraction and lack of effort. This tentatively suggests that performance only partly reflects cortical impairments in areas hosting neurocognitive faculties. Contextual factors deserve greater attention in patients with addiction. The cross-sectional design of our study limits conclusions relating to causality.
A Case of Primary Cutaneous Basal Cell Carcinosarcoma
Authors: Suzuki Hiromi , Hashimoto Akira , Saito Ryoko , Izumi Miki , Aiba Setsuya
Published: August 2018

A 94-year-old man consulted our hospital due to a rapidly growing tumor on the left cheek. The histological diagnosis of the tumor was basal cell carcinosarcoma, which was composed of intermingled epithelial and mesenchymal components. The former was basal cell carcinoma, while the latter was spindle cell sarcoma. The tumor was completely resected with a 3-mm margin and the patient remained free of local recurrence or distinct metastasis for 2 years. We report here a case of cutaneous basal cell carcinosarcoma and a review of the literature.
TGFβ Is Specifically Upregulated on Circulating CD14++ CD16+ and CD14+ CD16++ Monocytes in Patients with Atrial Fibrillation and Severe Atrial Fibrosis
Authors: Heinzmann David , Fuß Stefan , Ungern-Sternberg Saskia v. , Schreieck Jürgen , Gawaz Meinrad , Gramlich Michael , Seizer Peter 
Published: August 2018

Background/Aims: Fibrotic remodeling of the atria plays a key role in the pathogenesis of atrial fibrillation (AF). As little is known about the contribution of circulating monocytes in atrial remodeling and the pathophysiology of AF, we investigated profibrotic factors in different subsets of circulating monocytes obtained from patients with atrial fibrillation undergoing catheter ablation. Methods: A 3D high density voltage mapping was performed in sinus rhythm to evaluate the extent of low-voltage areas (LVAs) in the atria of 71 patients with persistent AF. Low-voltage was defined as signals of < 0.5mV during sinus rhythm. Prior to ablation, blood was drawn and monocytes were analyzed by FACS. Based on the expression of CD14 and CD16, three subgroups including CD14++ CD16- (‘classical’), CD14++ CD16+ (‘intermediate’), and CD14+ CD16++ (‘non-classical’) were analyzed for the expression of TGFb, CD147, and MMP-9, representing pivotal profibrotic pathways in myocardial remodeling. Results: Expression of TGFb was increased in CD14+ monocytes of patients with extensive LVAs compared to patients with a low extend of LVAs. While CD14++ CD16- monocytes showed no difference, CD14++ CD16+ and CD14+ CD16++ monocytes showed a strong increase of TGFb abundance. Although CD147 and MMP-9 are strongly associated with myocardial fibrosis, we found no difference in expression between the two groups in any monocyte subsets. Conclusion: TGFb is specifically upregulated on CD14++ CD16+ and CD14+ CD16++ monocytes in patients with extensive LVAs undergoing catheter ablation.
tRNA-Derived Fragments as Novel Predictive Biomarkers for Trastuzumab-Resistant Breast Cancer
Authors: Sun Chunxiao , Yang Fan , Zhang Yanhong , Chu Jiahui , Wang Jian , Wang Yifan , Zhang Yanqiu , Li Jun , Li Yongfei , Fan Ruihua , Li Wei , Huang Xiang , Wu Hao , Fu Ziyi , Jiang Zefei , Yin Yongmei
Published: August 2018

Background/Aims: Resistance to trastuzumab remains a common challenge to HER-2 positive breast cancer. Up until now, the underlying mechanism of trastuzumab resistance is still unclear. tRNA-derived small non-coding RNAs, a new class of small non-coding RNA (sncRNAs), have been observed to play an important role in cancer progression. However, the relationship between tRNA-derived fragments and trastuzumab resistance is still unknown. Methods: We detected the levels of tRNA-derived fragments expression in normal breast epithelial cell lines, trastuzumab-sensitive and -resistant breast cancer cell lines using high-throughput sequencing. qRT-PCR was conducted to validate the differentially expressed fragments in serums from trastuzumab-sensitive and -resistant patients. A receiver operating characteristic (ROC) curve analysis was performed to evaluate the power of specific tRNA-derived fragments. Progression-free survival (PFS) was analyzed using Cox-regression. Results: Our sequence results showed that tRNA-derived fragments were differentially expressed in the HBL-100, SKBR3, and JIMT-1 cell lines. tRF-30-JZOYJE22RR33 and tRF-27-ZDXPHO53KSN were found significantly upregulated in trastuzumab-resistant patients compared to sensitive individuals, and the ROC analysis showed that tRF-30-JZOYJE22RR33 and tRF-27-ZDXPHO53KSN were correlated with trastuzumab resistance. In a multivariate analysis, higher levels of tRF-30-JZOYJE22RR33 and tRF-27-ZDXPHO53KSN expression were associated with significantly shorter PFS in patients with metastatic HER-2 positive breast cancer. Conclusion: Our results suggest that tRF-30-JZOYJE22RR33 and tRF-27-ZDXPHO53KSN play important roles in trastuzumab resistance. Patients with high levels of tRF-30-JZOYJE22RR33 and tRF-27-ZDXPHO53KSN expression benefitted less from trastuzumab-based therapy than those that express lower-levels of these molecules. tRF-30-JZOYJE22RR33 and tRF-27-ZDXPHO53KSN may be potential biomarkers and intervention targets in the clinical treatment of trastuzumab-resistant breast cancer.
Long Noncoding RNA Lnc-SEMT Modulates IGF2 Expression by Sponging miR-125b to Promote Sheep Muscle Development and Growth
Authors: Wei Caihong , Wu Mingming , Wang Chuduan , Liu Ruizao , Zhao Huijing , Yang Li , Liu Jiafan , Wang Yayu , Zhang Shuzhen , Yuan Zehu , Liu Zhen , Hu Shijin , Chu Mingxing , Wang Xiaogang , Du Lixin 
Published: August 2018

Background/Aims: Long noncoding RNAs (lncRNAs) are RNA transcripts that are more than 200 nt long but have little protein-coding potential. Within the last few years, thousands of lncRNAs have been identified and their functions in biological processes have begun to be understood. Although many studies havebegun to examine the functions of many noncoding RNAs, very little is known about the functions of long noncoding (lncRNA) function of livestock production and molecular mechanisms of their functions are still lackingrelated to livestock production. Methods: Expression of sheep enhanced muscularityTranscript lncRNA (lnc-SEMT) and miR-125b were examined in sheep using quantitative reverse-transcription polymerase chain reaction. Expression of Myod (myogenic determination factor), Myog (myoglobin) and Insulin-like growth factor 2 (IGF2)were examined by Western Blot.Luciferase reporter assays were performedto confirm the relationship between lnc-SEMT and miR-125b. Results: Here, we identified a novel lnc-SEMT that promote sheep myoblast differentiation in vitro and enhanced sheep muscularity in vivo. Functional analyses showed that lnc-SEMT accelerates sheep myoblast differentiation in vitro. lnc-SEMT transgenic sheep exhibit a muscle hypertrophy phenotype characterized by increased body weight, and increased the number of muscle fibers indicating that lnc-SEMT play an important role in the regulation of skeletal muscle differentiation in vivo. Our results show that lnc-SEMT acts as a molecular sponge by antagonizing miR-125b to control IGF2 protein labundance in vitro and in vivo. Conclusion: In brief, lnc-SEMT is the first example of a lncRNA could be a useful candidate for improving biological growth traits such as skeletal muscle production in sheep.
Evaluation of Clinical Prognostic Factors and Further Delineation of the Effect of Mesenteric Fibrosis on Survival in Advanced Midgut Neuroendocrine Tumours
Authors: Laskaratos Faidon-Marios , Walker Martin , Wilkins Dominic , Tuck Alexander , Ramakrishnan Shashank , Phillips Edward , Gertner Julian , Megapanou Maria , Papantoniou Dimitrios , Shah Ruchir , Banks Jamie , Vlachou Erasmia , Garcia-Hernandez Jorge , Woodbridge Lorna , Papadopoulou Anthie , Grant Lee , Theocharidou Eleni , Watkins Jennifer , Luong Tu Vinh , Mandair Dalvinder , Caplin Martyn , Toumpanakis Christos
Published: August 2018

Background: Small intestinal neuroendocrine tumours (SI NETs) represent 30–50% of small bowel neoplasms and often present at an advanced stage. To date, there is relatively limited literature regarding prognostic factors affecting overall survival (OS) in stage IV disease. In addition, the prevalence of mesenteric fibrosis (MF) in SI NETs and its effect on OS have not been sufficiently explored in the literature. Aim: The primary aim of this study was to perform a large-scale survival analysis in an institutional cohort of 387 patients with metastatic (stage IV) SI NETs. The secondary aim was to provide epidemiological information regarding the prevalence of MF and to evaluate its effect on OS. Results: The median OS was 101 months (95% CI 84, 118). Age > 65 years, mesenteric metastases with and without desmoplasia, liver metastases, carcinoid heart disease (CHD) and bone metastases were associated with a significantly shorter OS, while primary tumour resection was predictive of a longer OS. The benefit of surgical resection was limited to symptomatic patients. MF was present in approximately 50% of patients with mesenteric lymphadenopathy. Elevated urinary 5-HIAA levels correlated strongly with the presence of CHD (p < 0.001) and to a lesser extent (p = 0.02) with MF. MF and CHD did not usually co-exist, suggesting that different mechanisms are likely to be involved in the development of these fibrotic complications. Conclusions: This study has identified specific prognostic factors in a large cohort of 387 patients with advanced SI NETs and has provided useful epidemiological data regarding carcinoid-related fibrotic complications.
Unmet Medical Needs in Metastatic Lung and Digestive Neuroendocrine Neoplasms
Authors: Capdevila Jaume , Bodei Lisa , Davies Philippa , Gorbounova Vera , Jensen Robert T. , Knigge Ulrich P. , Krejs Guenter J. , Krenning Eric , O’Connor Juan Manuel , Peeters Marc , Rindi Guido , Salazar Ramon , Vullierme Marie-Pierre , Pavel Marianne E. ,   the ENETS 2016 Munich Advisory Board Participants
Published: August 2018

Unmet medical needs are not infrequent in oncology, and these needs are usually of higher magnitude in rare cancers. The field of neuroendocrine neoplasms (NENs) has evolved rapidly during the last decade, and, currently, a new WHO classification is being implemented and several treatment options are available in the metastatic setting after the results of prospective phase III clinical trials. However, several questions are still unanswered, and decisions in our daily clinical practice should be made with limited evidence. In the 2016 meeting of the advisory board of the European Neuroendocrine Tumor Society (ENETS), the main unmet medical needs in the metastatic NENs setting were deeply discussed, and several proposals to try to solve them are presented in this article, including biomarkers, imaging, and therapy.
Por que as empresas realizam aquisições com frequência?
Authors: Pimenta Daiana Paula , Porto Rafael Barreiros
Published: August 2018

Apesar da relevância das aquisições frequentes como um programa estratégico corporativo, sabe-se pouco sobre os motivos de sua ocorrência. Os estudos focam na identificação dos fatores que determinam a primeira aquisição, desconsiderando que as empresas podem se envolver em sucessivos eventos. Para preencher essa lacuna, este estudo identifica os motivos que levam as empresas a se tornarem adquirentes frequentes, comparando com o que já se sabe sobre as motivações para realização da primeira aquisição. Por meio de Regressões Logísticas e de Poisson, identificamos que os preditores da primeira aquisição contribuem para explicar a frequência desses eventos. Ainda, a frequência de aquisições pode ser vista como uma estratégia para manter a competitividade da empresa, cujo principal propulsor é o auto interesse dos principais executivos.
Salerno’s Lombard Prince: Johannes ‘Abbas de Curte’ as Medical Practitioner
Authors: Glaze Florence Eliza
Published: August 2018

This paper examines the state of medical learning and practitioner identity at the time Constantine the African arrived in Salerno, Italy. The author utilizes surviving early manuscripts of medical texts, documentary evidence, regional chronicles, and early Salernitan antidotaria to frame the identity and activity of a renowned practitioner, a member of the Lombard princely family, who continued after the Norman conquest to work as a practitioner and health administrator, and to serve both the region and the Norman-Lombard leadership. The author concludes that pharmacy, particularly interests in exotic substances from the East, was one of the driving forces behind the transformation of medicine in the late eleventh and early twelfth centuries.
How to Accurately Account for Astrology’s Marginalization in the History of Science and Culture: The Central Importance of an Interpretive Framework
Authors: Rutkin H. Darrel
Published: August 2018

Astrology is a complex, multifold and long-lived subject that has been approached from many different perspectives in a broad range of scholarly disciplines. In order to understand its many roles within the history of science, theology, and culture, one needs a well-articulated historically and conceptually sound interpretive framework. In this article, a framework is proposed based on the curricular structures at medieval universities by which fundamental conceptual patterns and practices were passed down from generation to generation. It is argued that this will be helpful both for framing answerable questions, and for approaching their solutions. This goes particularly for the complex long-term patterns of astrology’s marginalization from the domain of legitimate knowledge and practice during the Scientific Revolution and the Enlightenment.
New taxa and notes on spine-headed katydids (Orthoptera: Conocephalinae: Agraeciini) from the Philippines
Authors: TAN MING KAI , INGRISCH SIGFRID , ROBILLARD TONY , BAROGA-BARBECHO JESSICA B. , YAP SHERYL A.
Published: August 2018

The diversity of the Agraeciini spine-headed katydids (Orthoptera: Tettigonioidea: Conocephalinae) in Southeast Asia remains poorly known, with species still awaiting discovery. Recent field collections in the Philippines resulted in the discovery of three novel species and redescription of two known species of Agraeciini, namely, (1) Anthracites furvuseques sp. nov. from Siargao in Mindanao, a species close to A. major Hebard, 1922; (2) Axylus mabinii sp. nov. from Luzon: (3) a new variant in Axylus c.f. philippinus (Hebard, 1922); (4) Salomona lumadae sp. nov. from Siargao in Mindanao; and (5) Salomona brevicollis Stål, 1877 comb. resurr. is a valid species distinct from Salomona maculifrons Stål, 1877.
Every Pixel of GOES-17 Imagery at Your Fingertips
Authors: Micke Kevin
Published: August 2018

The GOES-16, GOES-17, and Himawari-8 satellites bring with them rich datasets that can help protect life and property from extreme weather events, but these data are too immense for conventional ways of viewing satellite imagery over the web. New visualization tools are needed to facilitate their exploration, and to that end, the Satellite Loop Interactive Data Explorer in Real-Time (SLIDER) web application was recently developed and an experimental version was launched for public use. This new web application allows users to easily explore many terabytes of satellite imagery at full resolution, including a multiweek archive and cases of interest. Diverse user groups, from National Weather Service forecast offices to the general public, use SLIDER’s basic and advanced features to help get the most out of these new datasets.
On Different Microphysical Pathways to Convective Rainfall
Authors: Lasher-Trapp Sonia , Kumar Shailendra , Moser Daniel H. , Blyth Alan M. , French Jeffrey R. , Jackson Robert C. , Leon David C. , Plummer David M.
Published: August 2018

The Convective Precipitation Experiment (COPE) documented the dynamical and microphysical evolution of convection in southwestern England for testing and improving quantitative precipitation forecasting. A strong warm rain process was hypothesized to produce graupel quickly, initiating ice production by rime splintering earlier to increase graupel production and, ultimately, produce heavy rainfall. Here, convection observed on two subsequent days (2 and 3 August 2013) is used to test this hypothesis and illustrate how environmental factors may alter the microphysical progression. The vertical wind shear and cloud droplet number concentrations on 2 August were 2 times those observed on 3 August. Convection on both days produced comparable maximum radar-estimated rain rates, but in situ microphysical measurements indicated much less ice in the clouds on 2 August, despite having maximum cloud tops that were nearly 2 km higher than on 3 August. Idealized 3D numerical simulations of the convection in their respective environments suggest that the relative importance of particular microphysical processes differed. Higher (lower) cloud droplet number concentrations slow (accelerate) the warm rain process as expected, which in turn slows (accelerates) graupel formation. Rime splintering can explain the abundance of ice observed on 3 August, but it was hampered by strong vertical wind shear on 2 August. In the model, the additional ice produced by rime splintering was ineffective in enhancing surface rainfall; strong updrafts on both days lofted supercooled raindrops well above the 0°C level where they froze to become graupel. The results illustrate the complexity of dynamical–microphysical interactions in producing convective rainfall and highlight unresolved issues in understanding and modeling the competing microphysical processes.
Adaptive backstepping sliding mode control for wheel slip tracking of vehicle with uncertainty observer
Authors: Zhang Jiaxu , Li Jing
Published: August 2018

The wheel slip tracking control is the basis of automatic braking control systems, and the accurate tracking for the desired wheel slip in the presence of lumped uncertainty is a vital guarantee of automatic braking control systems reliable operation. Therefore, an adaptive backstepping sliding mode control approach with radial basis function neural network is proposed to design the nonlinear robust wheel slip controller based on a quarter-vehicle model with lumped uncertainty. The radial basis function neural network as the uncertainty observer can effectively reduce the chattering of sliding mode by estimating the lumped uncertainty, and the adaptive law for the unknown weight vector of radial basis function neural network is derived by Lyapunov-based method. The influence of changes in tire sideslip angle and camber angle on the tire -road friction coefficient acts as an unknown scaling factor, and the adaptive law for the unknown scaling factor is derived via Lyapunov-based method. Then, the performance of the proposed controller is verified through simulations of various maneuvers on a full-vehicle dynamics simulation software.
Monitoring deformation mechanism of foam cells in polyethylene foams via optical microscopy: Effect of density and microstructure
Authors: Zakaria Zunaida , Mohamad Ariff Zulkifli , Abu Bakar Azhar
Published: August 2018

The effect of cellular microstructure and density of low-density polyethylene (LDPE) foam during the compressive deformation were evaluated. Progressive foam cell structure deformation at crosshead speed of 10 mm/min was closely monitored and captured using a portable digital microscope with the assistance of a proposed coating technique to enhance contrast of the foam cells. Results revealed that higher density foam, LDPE1.0, experienced higher compressive stress than the LDPE0.5 foam. It was believed that thicker cell walls in the LDPE1.0 foam contributed to the foam stiffness and higher stress was required to impose cell bending, buckling, and collapse. It was also discovered that the existence of larger cells within a group or cluster of small cells in the LDPE1.0 foam acted as stress concentration points and initiated the formation of shear bands in the foam cells deformation mechanism. The extent of compressive strain on the foam cells were also investigated, and results showed that cells undergo lower compressive strain compared to the actual deformation level given directly by the machine crosshead. Cells located in the middle section of the foam recorded a strain of about 13% when the bulk foam was deformed at 20% strain. The success in capturing the actual cell strain using the proposed coating technique proved that with the right improvisation, the micromechanical deformation of optically challenged white polyethylene foam samples can be monitored effectively using optical microscopy.
Mechanical behavior of laminated functionally graded carbon nanotube reinforced composite plates resting on elastic foundations in thermal environments
Authors: Fu Tao , Chen Zhaobo , Yu Hongying , Wang Zhonglong , Liu Xiaoxiang
Published: August 2018

The present study is concerned with static and free vibration analyses of laminated functionally graded carbon nanotube reinforced composite rectangular plates on elastic foundation based on nth-order shear deformation theory. Four types of carbon nanotubes distributions along the plate thickness are considered, which include uniformly distributed and three other functionally graded distributions. Governing differential equations are derived by means of Hamilton’s principle. The differential quadrature method is developed to formulate the problem, and rapid convergence is observed in this study. A numerical comparison with available results in the literature is carried out to show the validity of the proposed theory. Furthermore, effects of the carbon nanotubes volume fraction, thickness side ratio, aspect ratio, foundation parameters, different thermal environments, the number of layers, lamination angle, boundary condition, and carbon nanotubes distribution types on the static response of laminated functionally graded carbon nanotube reinforced composite plates are also investigated.
The Rose and the Lotus: Bulgarian Electronic Entanglements in India, 1967–89
Authors: Petrov Victor
Published: August 2018

This article examines Bulgaria's electronic trade with India between 1967 and 1990. The developing world became a formative learning experience for the computer industry, as it came up against both a highly protectionist state trying to foster its own industry, and competition from Western companies playing to different rules than COMECON rivals. In order to gain a place in this lucrative market, Bulgarian computer enterprises developed their technical services, advertising and negotiating capacities, learning how to be capitalists in a socialist world. This ‘learning through competition and copying’ was a feedback channel that changed the way that the company operated in other parts of the world, diversifying its marketing and user services within the socialist world too, standing out from the other socialist industries. As such, this global operation was a formative experience for many executives and technicians, making them a group that was plugged into international expertise networks. Thus the computer became a channel for being part of the emerging information economy, and the Global South became a place to meet the First World without restriction. The article thus shows India's importance to Bulgaria as a space to learn from and profit in, rather than an object of socialist development.
A retrospective cohort study describing the characteristics of patients under 18 years old in one section 136 suite
Authors: Eswaravel Abiramy , O’Brien Aileen
Published: August 2018

Section 136 of the Mental Health Act 1983 is an authority allowing police officers to remove a person ‘who appears to him to be suffering from mental disorder’ from a public area. There has been much media coverage regarding the inappropriate detention of minors under section 136 and the suggestion that many were taken to police cells, as there were no suitable places of safety. Although previous studies describe characteristics of a typical individual detained under section 136, few distinguish the differences between adults and adolescents. Profiling these adolescents can help to identify adolescents at risk, allowing for earlier intervention and prevent the inappropriate detention of individuals. Data were collected retrospectively for all patients under 18 years of age who were brought to a section 136 suite in south-west London over a five-year period. The typical profile of an adolescent presenting to this suite was a 16-year-old female of white ethnicity who was sectioned in a public area due to attempted suicide or deliberate self-harm. The individual is more likely to have mental or behavioural difficulties, a history of abuse, be under the care of local authorities and have had previous convictions compared to adolescents in the general population.
The Editor’s Note
Authors: Heller Rafael
Published: August 2018

This year, the PDK poll turns 50 and Kappan magazine turns 100. Age has its virtue, says Kappan’s editor. Within the poll and the magazine are public education’s collective memory, which can help to ground our current and ongoing conversations about teaching, learning, and the purposes and priorities of the nation’s schools.