bluuebunny/crossref_metadata_2025 huggingface dataset:
Socio-Economic Factors Responsible For Adoption of Alien Fish Species by Fish Farmers in Bangladesh
Authors: Sakib Md. Hashmi , Reza Arif , Islam Afrad Md. Safiul , Lee Sang-Go
Published: March 2019

Adoption of alien fish species for aquaculture has become a common practice in Bangladesh. In this study, the socio-economic factors responsible for alien species adoption by fish farmers in Bogra District of Bangladesh were investigated. Data on adoption and socio-economic factors were collected from randomly selected 110 fish farmers. A multiple regression model was used to determine the factors influencing the adoption of alien fish species. The majority of the respondents (62.7%) belong to the moderate adoption category. The results showed that socio-economic factors such as commercialization, social participation, innovativeness, knowledge significantly affected fish farmers decision to adopt alien species. A stepwise regression analysis reveals that farmers knowledge on aquaculture is the deterministic factor regarding adoption. The trend of adopting alien fish species is not a concern limited to the study area, rather it reflects the general scenario of the aquaculture industry in Bangladesh. Therefore, socio-economic studies on alien fish species adoption could be helpful in forecasting future trends and formulating management strategies.
Assessment of risk factors and clinical characteristics of elderly patients with hypertensive encephalopathy against the background of hypertension
Authors: Jaworski V. V.
Published: March 2019

The article presents the results of clinical and neurological examination of 105 elderly and middle- aged hipertenzivnoyu encephalopathy of II degree on a background of hypertension. The urgency of a detailed analysis of the patients to determine risk factors for cerebrovascular disease and basic research cognitive functions of patients.
Analysis of the frequency of vascular comorbidity in patients with recurrent acute stroke
Authors: Mikitey O. N. , Svyrydova N. K. , Pavliuk N. P.
Published: March 2019

Stroke is an important medical and social problem, which occupies the second place in the population figures for mortality and one of the first rate for disability. Given the magnitude of the incidence, severity, effects, high incidence of recurrence great importance becomes its primary and secondary prevention that provides impact on the risk factors: high blood pressure, diabetes, high cholesterol, atrial fibrillation, sickle-cell anemia, open oval window, alcoholism. Prognosis depends on many factors, primarily on the amount and location of lesions of the brain, the severity of comorbidity and the patient’s age.
PENGARUH PEMBELAJARAN CONCEPT ATTAINMENT MODEL (CAM) TERHADAP KEMAMPUAN BERPIKIR KRITIS SISWA DI SMA NAHDATUL ULAMA (NU) PALEMBANG
Authors: Munir Munir , Afriyansyah Dini , Sundari Dewi
Published: March 2019

This study aims to determine whether the learning model Concept Attainment Model (CAM) affect the Critical Thinking Ability of Students in SMA Nahdatul Ulama (NU) Palembang. This research uses a quasi-experimental method (Quasi-Experimental) with pretest-posttest control group design research design. Sampling is done by saturated sampling technique. The sample of this research is class X IPA 1 and class X IPA 2 in SMA Nahdatul Ulama (NU) Palembang. The results showed that there are differences in critical thinking ability of Animalia subject matter. Improvement Critical thinking ability can be seen on the result before using learning model that is Interpreter indicator, Analysis, Evaluation, Inference (Conclusion), Explanation (Explanation), Self-regulation is 36%, 36%, 37%, 41% 45%, and 46%. Whereas after using Learning Model on interpretation indicator, analysis, evaluation, inference (Conclusion), Explanation (Self Explanation), Self-regulation is 80%, 84%, 85%, 85%, 83%, and 84%. The results showed that this learning model can improve students' critical thinking ability. The results of statistical calculations obtained count = 3.474 and t table of 1.666 with DK (degrees of freedom) of 73 with a significant level of 5% so that tcount> t table is 3.474> 1.666 and significance value 0.001> 0.05. Based on the hypothesis test, it can be concluded that the influence of the learning model Concept Attainment Model to the critical thinking ability of students in SMA Nahdatul Ulama Palembang.
WAKTU TUMBUH MATA TUNAS DAUN Mangifera indica L. PADA BERBAGAI TINGKATAN
Authors: Fajar Dede , Cahyanto Tri , Fadillah Afriansyah
Published: March 2019

Fenology including one of scientific that study about development phases such as flowering character or development of leaf. One of leaf’s development M.indica leaf has a very high diversity such as shape size even the color is often different according to its development as well as the buds that appear in the plan. The observation of buds’s growth period in the M.indica plan has ever done before, but the levels and the time is still not clear. This research aimed to know the buds’s time grows on various levels of M. indica so obtained the good appearance time and the level of M.indica species for further research material. The collecting data uses exploration method by exploring the area of sub-district Cibiru, district Bandung, West Java and an act of determine a level. The act of determine of the length and the diameter of each stand which is found at the three regions. The result of observation shows 7 of the 12 specimen that has been observed experiencing the growth of leaf buds. The average growth time of the buds in the specimen that experienced a growth is 13 days which dominate with pole, as for the existence of the variation of shape and bud color appearance enable to the existence of growth to the next phase from that buds.
PENGEMBANGAN MODUL PRAKTIKUM GENETIKA BERBASIS KETERAMPILAN PROSES SAINS UNTUK MAHASISWA PROGRAM STUDI PENDIDIKAN BIOLOGI
Authors: Fadillah Etty Nurmala , Angraini Erni
Published: March 2019

The development of this practicum module is based on overcoming student difficulties in practicum implementation and final report making. Skills-based modules of the scientific process to practice the skills of the process of science are observing, grouping, interpreting, predicting, formulating hypotheses, planning experiments, and communicating. This module is expected to lead the students to be actively involved in carrying out practicum activities independently related to the concept of the material to be studied. The purpose of this research is to produce teaching material product in the form of practical genetic module based on the skill of science process that is feasible and practical used by students in genetic lecturing. The procedure of development in this research with the 4-D model proposed by Thiagarajan that is define (definition), design (design), develop (development), and disseminate (dissemination). Data collection instruments used in the form of interviews and assessment questionnaire. Data analysis techniques used qualitative analysis by calculating the average score of each component of the module assessment and calculating practicality data on the use of the practicum module. The science-based genetic module of the science process module is appropriate for use by professors of materials experts, media experts, and linguists. Second, module practicum based on science skill based on students' responses have practicality in practicum practice that is 76,05% module contents, 76,26% presentation, and 76,10% from the language.
PENINGKATAN KEAKTIFAN SISWA DALAM PERMAINAN FUTSAL MELALUI METODE TGT PADA SISWA KELAS X DI SMA SELAMAT PAGI INDONESIA KOTA BATU
Authors: Wibowo Pandu Adi
Published: March 2019

Pendidikan jasmani sebagai bagian integral dari pendidikan dari sistem pendidikan secara keseluruhan.  Pendidikan jasmani harus diarahkan pada pencapaian tujuan pendidikan tersebut. Tujuan pendidikan jasmani bukan aktivitas jasmani, tetapi bagaimana mengembangkan seluruh potensi siswa melalui aktivitas jasmani. Penelitian ini menggunakan penelitian tindakan kelas. Penelitian ini bertujuan untuk meningkatkan keaktifan siswa melalui metode TGT dalam permainan futsal. Subjek penelitian adalah siswa Kelas X SMA Selamat Pagi Indonesia Kota Batu yang terdiri dari25orang siswa. Dalam pelaksanaan TGT pembagian kelompok dilakukan dengan dua cara: cara pertama kelompok berdasarkan gender, cara kedua kelompok dicampur antara putra dan putri. Penelitian ini telah dilaksanakan dalam dua siklus. Siklus pertama menunjukkan bahwa aspek afektif tentang keaktifan masih diperlukan perbaikan, sehingga perlu dilakukan perbaikan pada siklus 2. Pada siklus 2 sudah menunjukkan hasil yang optimal sehinggatidak diperlukan lagi siklus berikutnya. Karena pada siklus 2 sudah meningkat. Dari hasil penelitian menunjukkan bahwa metode TGT dapatmeningkatkan keaktifan siswa SMA Selamat Pagi Indonesia Kota Batu. Meningkatnya keaktifan siswa juga akan mempengaruhi pola belajar siswa dalam mencapai tujuan baik secara kognitif, afektif maupun psikomotor
PENERAPAN MEDIA LACTORA UNTUK MENINGKATKAN HASIL BELAJAR MAHASISWA PADA MATA KULIAH ANATOMI MAHASISWA PENDIDIKAN JASMANI KESEHATAN DAN REKREASI IKIP BUDI UTOMO MALANG
Authors: Afandi Achmad , Andriani Ira
Published: March 2019

This research is a study that aims to improve student learning outcomes in anatomy courses at IkIIP in favor of Utomo Malang. class action research (PTK) which involves repeated reflection consisting of four stages (4 D), namely: planning, action, observation and reflection. Each cycle was conducted two meetings. The results of the study showed that there was an increase in learning outcomes with the use of media Lactora in the subject of motion systems in humans in senior high school VI-A 2017/2018 school year. This can be seen from the average value of the test class I cycle (74.48) with learning completeness (83.87%), indicating an increase compared to before the action with the class average value (60.8) and the learning completeness (38, 71%). Then in the second cycle, the average score of the class increased (83.29) with learning completeness (100%) compared to the results of the first cycle test (74.48%). In the results of this second cycle test all students have completed their study by achieving the specified SKM. The learning process has been proven to improve student learning outcomes.
PENGEMBANGAN MEDIA PEMBELAJARAN BERBASIS MOBILE LEARNING TEKNIK DASAR DAN PERATURAN PERMAINAN FUTSAL
Authors: Yuniarto Andryas , Supriyadi Supriyadi , Sudjana I Nengah
Published: March 2019

The purpose of this research and development is to develop a learning media for futsal games based on mobile learning (digital books) so that participants learn to acquire new teaching media and be more enthusiastic in learning futsal games. The data analysis technique used in this development research is a descriptive analysis technique with percentages. This technique is used to analyze data obtained from the results of questionnaires / questionnaires. Based on the results of the data analysis of small group trials obtained an average percentage of 85.28% and in the large group trials obtained an average percentage of 91.05% so that it meets the valid criteria with the content of the material which includes basic techniques of futsal games and the rules of official futsal games from FIFA in Indonesian. The product specifications are in the form of a 37.5MB .epub file that can be accessed through an application (. Reader reader) on a smartphone that can be accessed anytime and anywhere
PENINGKATAN KEMAMPUAN MENULIS DAN MEMBACA BERITA MELALUI BAHAN MATERI MASALAH SOSIAL SISWA KELAS VIII SMP NEGERI 3 PATI
Authors: Nyamat Nyamat
Published: March 2019

ENGLISHAs the educational institution, schools should improve continuously to create the high-quality education. The purpose of this study was to describe the initial condition and the improvement of student’s news writing and reading skills regarding social issues. This study used classroom-action research design, namely self-reflection method. It involved 25 students of the first semester at 8th grade, SMP 3 Pati. The study was conducted in the pre-cycle used the printed textbooks and two cycles : the cycle 1 used printed and electronics (television) news sources, while the cycle 2 used the materials produced by the students by exploring the surround social issues. The results of the study were: (1) In the pre-cycle, the student acquired on average 81.48 for the writing skill and 79.42 for the news-reading skill. (2) In the cycle 1, the students acquired 89.9 and 82.62 for news writing and reading skills respectively. Meanwhile, in cycle 2, their news writing improved to 90.7 and their reading skill improved to 90.78 INDONESIASebagai lembaga pendidikan, sekolah secara terus menerus harus mengadakan pembenahan diri dalam rangka meningkatkan mutu pendidikan. Tujuan penelitian adalah untuk mengetahui kondisi awal dan peningkatan kemampuan menulis dan membaca berita melalui bahan materi masalah sosial. Penelitian ini merupakan penelitian tindakan kelas melalui metode refleksi diri. Penelitian dilakukan terhadap 25 siswa kelas VIII SMP Negeri 3 Pati semester 1. Analisis data dilakukan yaitu pra siklus dengan teks dari buku cetak dan 2 siklus : (1); siklus 1 menggunakan bahan dari media cetak dan elektronik (televisi); sedangkan siklus 2 bahan materi yang dihasilkan peserta didik dengan menggali masalah-masalah sosial di lingkungannya. Hasil penelitian adalah (1) pada kondisi awal, nilai siswa rata-rata 81,48 untuk kemampuan menulis and 79,42 untuk kemampuan membaca berita. (2) Siklus 1, nilai siswa rata-rata 89,8 dan 82,62 untuk kemampuan menulis dan membaca berita. Sementara, pada siklus 2, kemampuan menulis berita meningkat menjadi 90,70 dan membaca berita meningkat menjadi 90,78.
Heterogeneous Distributed Big Data Clustering on Sparse Grids
Authors: Pfander David , Daiß Gregor , Pflüger Dirk
Published: March 2019

Clustering is an important task in data mining that has become more challenging due to the ever-increasing size of available datasets. To cope with these big data scenarios, a high-performance clustering approach is required. Sparse grid clustering is a density-based clustering method that uses a sparse grid density estimation as its central building block. The underlying density estimation approach enables the detection of clusters with non-convex shapes and without a predetermined number of clusters. In this work, we introduce a new distributed and performance-portable variant of the sparse grid clustering algorithm that is suited for big data settings. Our computed kernels were implemented in OpenCL to enable portability across a wide range of architectures. For distributed environments, we added a manager–worker scheme that was implemented using MPI. In experiments on two supercomputers, Piz Daint and Hazel Hen, with up to 100 million data points in a ten-dimensional dataset, we show the performance and scalability of our approach. The dataset with 100 million data points was clustered in 1198 s using 128 nodes of Piz Daint. This translates to an overall performance of 352 TFLOPS . On the node-level, we provide results for two GPUs, Nvidia’s Tesla P100 and the AMD FirePro W8100, and one processor-based platform that uses Intel Xeon E5-2680v3 processors. In these experiments, we achieved between 43% and 66% of the peak performance across all computed kernels and devices, demonstrating the performance portability of our approach.
Seasonal and Interannual Variation Characteristics of Low-Cloud Fraction in Different North Pacific Regions
Authors: Wang Qian , Xu Haiming , Zhang Leying , Deng Jiechun
Published: March 2019

In this study, we use the long-term satellite data to investigate seasonal and interannual variation of low-cloud fraction (LCF) and the associated controlling factors over the eastern and western North Pacific. On the seasonal time scale, the enhanced LCF over the eastern North Pacific in summer is actively coupled with strong estimated inversion strength (EIS) and 700-hPa relative humidity, and the LCF over the western North Pacific in winter is large and mainly caused by increased sensible heat flux and tropospheric low-level cold advection. On the interannual time scale, the increased LCF over the eastern North Pacific in summer is associated with increased EIS and decreased sea surface temperatures, in which the El Niño plays an important role; the enhanced LCF over the western North Pacific in spring and winter has a positive correlation with enhanced sensible heat flux (SHF) and tropospheric low-level cold advection, which can be partly explained by the subpolar frontal zone (SPFZ) intensity.
Efficacy of the Localized Aviation MOS Program in Ceiling Flight Category Forecasts
Authors: Boyd Douglas , Guinn Thomas
Published: March 2019

(1) Background: Flying in instrument meteorological conditions (IMC) carries an elevated risk of fatal outcome for general aviation (GA) pilots. For the typical GA flight, aerodrome-specific forecasts (Terminal Aerodrome Forecast (TAF), Localized Aviation Model Output Statistics Program (LAMP)) assist the airman in pre-determining whether a flight can be safely undertaken. While LAMP forecasts are more prevalent at GA-frequented aerodromes, the Federal Aviation Administration (FAA) recommends that this tool be used as supplementary to the TAF only. Herein, the predictive accuracy of LAMP for ceiling flight categories of visual flight rules (VFR) and instrument flight rules (IFR) was determined. (2) Methods: LAMP accuracy was evaluated for the period of July–December 2018 using aviation-specific probability of detection (PODA), false alarm ratio (FARA) and critical success scores (CSSA). Statistical differences were determined using Chi-Square tests. (3) Results: LAMP forecasts (n = 823) across 39 states were accrued. LAMP PODA for VFR (0.67) and IFR (0.78) exceeded (p < 0.031) the corresponding TAF scores (0.57 and 0.56). For VFR, the LAMP showed a non-significant (p = 0.243) higher FARA (0.25) than the TAF (0.19). For IFR forecasts, the LAMP FARA was lower (p < 0.001) (0.48 and 0.81, respectively). LAMP CSSA scores exceeded the TAF for VFR (p = 0.012) and IFR forecasts (p < 0.001). (4) Conclusion: These findings support the greater integration of LAMP into pre-flight weather briefings.
SST-Forced and Internal Variability of a Winter Wave Train over the Tropical Indo–Western Pacific and East Asia
Authors: Zheng Jian , Liu Qinyu , Chen Zesheng , Wang Faming
Published: March 2019

Previous studies have indicated that a high-level wave train from the tropical Indo–Western Pacific to East Asia (IWP-EA, expressed as geopotential height at 200 hPa) is triggered by dipolar convective activity anomalies over the IWP during the boreal winter. The current study highlights the relative importance of sea surface temperature forcing versus atmospheric internal variability on the IWP-EA pattern, based on an Atmospheric Model Intercomparison Project (AMIP) experiment with 30 integrations. It was found that the SST-forcing component can reproduce the observed IWP–EA pattern and the related rainfall dipole well, for both the spatial features and temporal evolutions. The internal variability of the rainfall dipole is strong in the southern and eastern Indian Ocean and region north of Australia, while the internal variability of height generally increases with latitude. The signal-to-noise ratios are just over 1 over the northernmost lobe of the IWP-EA (Japan and the region to its east), while ratios over the other centers reach values greater than 3. An inter-member EOF analysis of the rainfall dipole indicates that the variability associated with the first two modes can explain more than 70% of the total spread over most regions with large spread for both rainfall dipole and IWP-EA, including the region over Japan. Thus, some parts of internal variability of rainfall dipole and IWP-EA are connected.
Alcohol Interaction with Cocaine, Methamphetamine, Opioids, Nicotine, Cannabis, and γ-Hydroxybutyric Acid
Authors: Singh Ashok K.
Published: March 2019

Millions of people around the world drink alcoholic beverages to cope with the stress of modern lifestyle. Although moderate alcohol drinking may have some relaxing and euphoric effects, uncontrolled drinking exacerbates the problems associated with alcohol abuse that are exploding in quantity and intensity in the United States and around the world. Recently, mixing of alcohol with other drugs of abuse (such as opioids, cocaine, methamphetamine, nicotine, cannabis, and γ-hydroxybutyric acid) and medications has become an emerging trend, exacerbating the public health concerns. Mixing of alcohol with other drugs may additively or synergistically augment the seriousness of the adverse effects such as the withdrawal symptoms, cardiovascular disorders, liver damage, reproductive abnormalities, and behavioral abnormalities. Despite the seriousness of the situation, possible mechanisms underlying the interactions is not yet understood. This has been one of the key hindrances in developing effective treatments. Therefore, the aim of this article is to review the consequences of alcohol’s interaction with other drugs and decipher the underlying mechanisms.
The Enigmatic HOX Genes: Can We Crack Their Code?
Authors: Luo Zhifei , Rhie Suhn K. , Farnham Peggy J.
Published: March 2019

Homeobox genes (HOX) are a large family of transcription factors that direct the formation of many body structures during early embryonic development. There are 39 genes in the subgroup of homeobox genes that constitute the human HOX gene family. Correct embryonic development of flies and vertebrates is, in part, mediated by the unique and highly regulated expression pattern of the HOX genes. Disruptions in these fine-tuned regulatory mechanisms can lead to developmental problems and to human diseases such as cancer. Unfortunately, the molecular mechanisms of action of the HOX family of transcription factors are severely under-studied, likely due to idiosyncratic details of their structure, expression, and function. We suggest that a concerted and collaborative effort to identify interacting protein partners, produce genome-wide binding profiles, and develop HOX network inhibitors in a variety of human cell types will lead to a deeper understanding of human development and disease. Within, we review the technological challenges and possible approaches needed to achieve this goal.
Breast Cancer Prognosis Using a Machine Learning Approach
Authors: Ferroni Patrizia , Zanzotto Fabio M. , Riondino Silvia , Scarpato Noemi , Guadagni Fiorella , Roselli Mario
Published: March 2019

Machine learning (ML) has been recently introduced to develop prognostic classification models that can be used to predict outcomes in individual cancer patients. Here, we report the significance of an ML-based decision support system (DSS), combined with random optimization (RO), to extract prognostic information from routinely collected demographic, clinical and biochemical data of breast cancer (BC) patients. A DSS model was developed in a training set (n = 318), whose performance analysis in the testing set (n = 136) resulted in a C-index for progression-free survival of 0.84, with an accuracy of 86%. Furthermore, the model was capable of stratifying the testing set into two groups of patients with low- or high-risk of progression with a hazard ratio (HR) of 10.9 (p < 0.0001). Validation in multicenter prospective studies and appropriate management of privacy issues in relation to digital electronic health records (EHR) data are presently needed. Nonetheless, we may conclude that the implementation of ML algorithms and RO models into EHR data might help to achieve prognostic information, and has the potential to revolutionize the practice of personalized medicine.
CAFs and TGF-β Signaling Activation by Mast Cells Contribute to Resistance to Gemcitabine/Nabpaclitaxel in Pancreatic Cancer
Authors: Porcelli Letizia , Iacobazzi Rosa Maria , Di Fonte Roberta , Serratì Simona , Intini Angelica , Solimando Antonio Giovanni , Brunetti Oronzo , Calabrese Angela , Leonetti Francesco , Azzariti Amalia , Silvestris Nicola
Published: March 2019

Tumor–stroma interactions are of key importance for pancreatic ductal adenocarcinoma (PDAC) progression. Our aim was to investigate whether cancer associated fibroblasts (CAFs) and mast cells (MC) affected the sensitivity of PDAC cells to gemcitabine/nabpaclitaxel (GEM/NAB). For this purpose, the combination cytotoxicity and the effect on tumor invasion and angiogenesis were evaluated with or without a conditioned medium from the mast cell line HMC-1 (human mast cell line-1 cells) and CAFs. Beside the clinical outcome of a homogenous population of PDAC patients, receiving GEM/NAB, was correlated to the circulating levels of mast cell tryptase and to a panel of inflammatory and immunosuppressive cytokines. CAFs neither affected drugs’ cytotoxicity nor the inhibition of angiogenesis, but promoted tumor cell invasion. The MC instead, caused resistance to drugs by reducing apoptosis, by activating the TGF-β signalling and by promoting tumor invasion. Indeed, the inhibition of TβRI serine/threonine kinase activity by galunisertib restored drugs cytotoxicity. Moreover, MC induced the release of TGF-β1, and increased expression of PAR-2, ERK1/2 and Akt activation. Accordingly, TGF-β1, tryptase and other pro-inflammatory and immunosuppressive cytokines increased in the unresponsive patients. In conclusion, MC play a pivotal role in the resistance to GEM/NAB. A correlation between high level of circulating pro-inflammatory/ immunosuppressive cytokines and unresponsiveness was found in PDAC patients.
Liquid Biopsies in Lung Cancer: Four Emerging Technologies and Potential Clinical Applications
Authors: Chudasama Dimple , Katopodis Periklis , Stone Nick , Haskell Jennifer , Sheridan Hannah , Gardner Benjamin , Urnovitz Howard , Schuetz Ekkehard , Beck Julia , Hall Marcia , Barr James , Sisu Cristina , Rice Alexandra , Polychronis Andreas , Anikin Vladimir , Karteris Emmanouil
Published: March 2019

Background: Liquid biopsies offer a promising alternative to tissue samples, providing non-invasive diagnostic approaches or serial monitoring of disease evolution. However, certain challenges remain, and the full potential of liquid biopsies has yet to be reached. Here we report several methodological approaches to interrogate liquid biopsies using circulating tumour cell (CTC) enumeration and characterisation, transcriptomics, Raman spectroscopy, and copy number instability (CNI) scores using blood samples of lung cancer (LC) patients. Methods: We choose LC; since it still is the most common cause of cancer-related mortality worldwide, and therefore there is a need for development of new non-invasive diagnostic/prognostic technologies. Changes in gene expression were assessed using RNA-seq, and in CTCs using ImageStream, an imaging flow-cytometer. CNI scores, from paired tissue/ctDNA were also explored. Raman spectroscopy was used to provide chemical fingerprints of plasma samples. Results: CTCs were detected in all LC patients (n = 10). We observed a significant increase in CTC levels in LC patients (n = 10) compared to controls (n = 21). A similar CNI was noted in the tissue and plasma of 2 patients, where higher CNI scores corresponded with poorer outcome. Significant changes in Raman spectra (carotenoid concentrations) were noted in LC patients (n = 20) compared to controls (n = 10). RNA-seq revealed differential expression of 21 genes between LC cases and controls in both LC tissue and blood samples. Conclusions: Liquid biopsies can potentially provide a more comprehensive picture of the disease compared to a single tissue biopsy. CTC enumeration is feasible and sensitive for LC patients. Molecular profiling of CTCs is also possible from total blood. CNI scores and Raman spectra require further investigation. Further work is being undertaken to explore these methods of detection in a larger LC cohort.
Therapeutic Targeting of Stat3 Using Lipopolyplex Nanoparticle-Formulated siRNA in a Syngeneic Orthotopic Mouse Glioma Model
Authors: Linder Benedikt , Weirauch Ulrike , Ewe Alexander , Uhmann Anja , Seifert Volker , Mittelbronn Michel , Harter Patrick N. , Aigner Achim , Kögel Donat
Published: March 2019

Glioblastoma (GBM), WHO grade IV, is the most aggressive primary brain tumor in adults. The median survival time using standard therapy is only 12–15 months with a 5-year survival rate of around 5%. Thus, new and effective treatment modalities are of significant importance. Signal transducer and activator of transcription 3 (Stat3) is a key signaling protein driving major hallmarks of cancer and represents a promising target for the development of targeted glioblastoma therapies. Here we present data showing that the therapeutic application of siRNAs, formulated in nanoscale lipopolyplexes (LPP) based on polyethylenimine (PEI) and the phospholipid 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC), represents a promising new approach to target Stat3 in glioma. We demonstrate that the LPP-mediated delivery of siRNA mediates efficient knockdown of Stat3, suppresses Stat3 activity and limits cell growth in murine (Tu2449) and human (U87, Mz18) glioma cells in vitro. In a therapeutic setting, intracranial application of the siRNA-containing LPP leads to knockdown of STAT3 target gene expression, decreased tumor growth and significantly prolonged survival in Tu2449 glioma-bearing mice compared to negative control-treated animals. This is a proof-of-concept study introducing PEI-based lipopolyplexes as an efficient strategy for therapeutically targeting oncoproteins with otherwise limited druggability.
Heterogeneous Nuclear Ribonucleoproteins A1 and A2 Function in Telomerase-Dependent Maintenance of Telomeres
Authors: Wang Tong-Hong , Chen Chin-Chuan , Hsiao Yuan-Chao , Lin Yu-Han , Pi Wen-Chieh , Huang Pei-Rong , Wang Tzu-Chien V. , Chen Chi-Yuan
Published: March 2019

The A/B subfamily of heterogeneous nuclear ribonucleoproteins (hnRNPs A/B), which includes hnRNP A1, A2/B1, and A3, plays an important role in cell proliferation. The simultaneous suppression of hnRNP A1/A2, but not the suppression of hnRNP A1 or A2 alone, has been shown to inhibit cell proliferation and induce apoptosis in cancer cells, but not in mortal normal cells. However, the molecular basis for such a differential inhibition of cell proliferation remains unknown. Here, we show that the simultaneous suppression of hnRNP A1 and hnRNP A2 resulted in dysfunctional telomeres and induced DNA damage responses in cancer cells. The inhibition of apoptosis did not alleviate the inhibition of cell proliferation nor the formation of dysfunctional telomeres in cancer cells depleted of hnRNP A1/A2. Moreover, while proliferation of mortal normal fibroblasts was not sensitive to the depletion of hnRNP A1/A2, the ectopic expression of hTERT in normal fibroblasts rendered these cells sensitive to proliferation inhibition, which was associated with the production of dysfunctional telomeres. Our study demonstrates that hnRNP A1 and A2 function to maintain telomeres in telomerase-expressing cells only, suggesting that the maintenance of functional telomeres in telomerase-expressing cancer cells employs factors that differ from those used in the telomerase-negative normal cells.
Glioblastoma in Elderly Patients: Current Management and Future Perspectives
Authors: Minniti Giuseppe , Lombardi Giuseppe , Paolini Sergio
Published: March 2019

The incidence of glioblastoma (GBM) in the elderly population is slowly increasing in Western countries. Current management includes surgery, radiation therapy (RT) and chemotherapy; however, survival is significantly worse than that observed in younger patients and the optimal treatment in terms of efficacy and safety remains a matter of debate. Surgical resection is often employed as initial treatment for elderly patients with GBM, although the survival benefit is modest. Better survival has been reported in elderly patients treated with RT compared with those receiving supportive care alone, with similar survival outcome for patients undergoing standard RT (60 Gy over 6 weeks) and hypofractionated RT (25–40 Gy in 5–15 daily fractions). Temozolomide, an alkylating agent, may represent an effective and safe therapy in patients with promoter methylation of O6-methylguanine-DNA-methyltransferase (MGMT) gene which is predictor of responsiveness to alkylating agents. An abbreviated course of RT, 40 Gy in 15 daily fractions in combination with adjuvant and concomitant temozolomide has emerged as an effective treatment for patients aged 65 years old or over with GBM. Results of the National Cancer Institute of Canada Clinical Trials Group (NCIC CTG CE6) and European Organization for Research and Treatment of Cancer (EORTC 26062/22061) randomized study of short-course RT with or without concurrent and adjuvant temozolomide have demonstrated a significant improvement in progression-free survival and overall survival for patients receiving RT and temozolomide over RT alone, without impairing either quality of life or functional status. Although combined chemoradiation has become the recommended treatment in fit elderly patients with GBM, several questions remain unanswered, including the survival impact of chemoradiation in patients with impaired neurological status, advanced age (>75–80 years old), or for those with severe comorbidities. In addition, the efficacy and safety of alternative therapeutic approaches according to the methylation status of the O6-methylguanine-DNA methyl-transferase (MGMT) gene promoter need to be explored in future trials.
Prognostic and Clinicopathological Significance of SERTAD1 in Various Types of Cancer Risk: A Systematic Review and Retrospective Analysis
Authors: Mongre Raj Kumar , Jung Samil , Mishra Chandra Bhushan , Lee Beom Suk , Kumari Shikha , Lee Myeong-Sok
Published: March 2019

SERTAD/TRIP-Br genes are considered as a key nuclear transcriptional player in diverse mechanisms of cell including carcinogenesis. The Oncomine™-Online Platform was used for differential expression and biological insights. Kaplan-Meier survival estimated by KM-plotter/cBioPortal/PrognoScan with 95% CI. SERTAD1 was found significantly elevated levels in most of tumor samples. Kaplan-Meier Plotter results distinctly showed the SERTAD1 over-expression significantly reduced median overall-survival (OS) of patients in liver (n = 364/Logrank-test p = 0.0015), ovarian (n = 655/Logrank-test p = 0.00011) and gastric (n = 631/Logrank-test p = 0.1866). Increased level of SERTAD1 has a significantly higher survival rate in the initial time period, but after 100 months slightly reduced OS (n = 26/Logrank-test p = 0.34) and RFS in HER2 positive breast cancer patients. In meta-analysis, cancer patients with higher SERTAD1 mRNA fold resulted worse overall survival than those with lower SERTAD1 levels. Heterogeneity was observed in the fixed effect model analysis DFS [Tau2 = 0.0.073, Q (df = 4) = 15.536 (p = 0.004), I2 = 74.253], DSS [Tau2 = 1.015, Q (df = 2) = 33.214, (p = 0.000), I2 = 93.973], RFS [Tau2 = 0.492, Q (df = 7) = 71.133 (p = 0.000), I2 = 90.159] (Figure 5). OS [Tau2 = 0.480, Q (df = 17) = 222.344 (p = 0.000), I2 = 92.354]. Lastly, SERTAD1 involved in several signaling cascades through interaction and correlation with many candidate factors as well as miRNAs. This meta-analysis demonstrates a robust evidence of an association between higher or lower SERTAD1, alteration and without alteration of SERTAD1 in cancers in terms of survival and cancer invasiveness.
Connexin 43 Loss Triggers Cell Cycle Entry and Invasion in Non-Neoplastic Breast Epithelium: A Role for Noncanonical Wnt Signaling
Authors: Fostok Sabreen , El-Sibai Mirvat , Bazzoun Dana , Lelièvre Sophie , Talhouk Rabih
Published: March 2019

(1) Background: The expression of connexin 43 (Cx43) is disrupted in breast cancer, and re-expression of this protein in human breast cancer cell lines leads to decreased proliferation and invasiveness, suggesting a tumor suppressive role. This study aims to investigate the role of Cx43 in proliferation and invasion starting from non-neoplastic breast epithelium. (2) Methods: Nontumorigenic human mammary epithelial HMT-3522 S1 cells and Cx43 shRNA-transfected counterparts were cultured under 2-dimensional (2-D) and 3-D conditions. (3) Results: Silencing Cx43 induced mislocalization of β-catenin and Scrib from apicolateral membrane domains in glandular structures or acini formed in 3-D culture, suggesting the loss of apical polarity. Cell cycle entry and proliferation were enhanced, concomitantly with c-Myc and cyclin D1 upregulation, while no detectable activation of Wnt/β-catenin signaling was observed. Motility and invasion were also triggered and were associated with altered acinar morphology and activation of ERK1/2 and Rho GTPase signaling, which acts downstream of the noncanonical Wnt pathway. The invasion of Cx43-shRNA S1 cells was observed only under permissive stiffness of the extracellular matrix (ECM). (4) Conclusion: Our results suggest that Cx43 controls proliferation and invasion in the normal mammary epithelium in part by regulating noncanonical Wnt signaling.
Rab7a and Mitophagosome Formation
Authors: Tan Esther Hui Na , Tang Bor Luen
Published: March 2019

The small GTPase, Rab7a, and the regulators of its GDP/GTP-binding status were shown to have roles in both endocytic membrane traffic and autophagy. Classically known to regulate endosomal retrograde transport and late endosome-lysosome fusion, earlier work has indicated a role for Rab7a in autophagosome-lysosome fusion as well as autolysosome maturation. However, as suggested by recent findings on PTEN-induced kinase 1 (PINK1)-Parkin-mediated mitophagy, Rab7a and its regulators are critical for the correct targeting of Atg9a-bearing vesicles to effect autophagosome formation around damaged mitochondria. This mitophagosome formation role for Rab7a is dependent on an intact Rab cycling process mediated by the Rab7a-specific guanine nucleotide exchange factor (GEF) and GTPase activating proteins (GAPs). Rab7a activity in this regard is also dependent on the retromer complex, as well as phosphorylation by the TRAF family-associated NF-κB activator binding kinase 1 (TBK1). Here, we discuss these recent findings and broadened perspectives on the role of the Rab7a network in PINK1-Parkin mediated mitophagy.
Excessive Reactive Iron Impairs Hematopoiesis by Affecting Both Immature Hematopoietic Cells and Stromal Cells
Authors: Tanaka Hirokazu , Espinoza J. Luis , Fujiwara Ryosuke , Rai Shinya , Morita Yasuyoshi , Ashida Takashi , Kanakura Yuzuru , Matsumura Itaru
Published: March 2019

Iron overload is the accumulation of excess iron in the body that may occur as a result of various genetic disorders or as a consequence of repeated blood transfusions. The surplus iron is then stored in the liver, pancreas, heart and other organs, which may lead to chronic liver disease or cirrhosis, diabetes and heart disease, respectively. In addition, excessive iron may impair hematopoiesis, although the mechanisms of this deleterious effect is not entirely known. In this study, we found that ferrous ammonium sulfate (FeAS), induced growth arrest and apoptosis in immature hematopoietic cells, which was mediated via reactive oxygen species (ROS) activation of p38MAPK and JNK pathways. In in vitro hematopoiesis derived from embryonic stem cells (ES cells), FeAS enhanced the development of dysplastic erythroblasts but inhibited their terminal differentiation; in contrast, it had little effect on the development of granulocytes, megakaryocytes, and B lymphocytes. In addition to its directs effects on hematopoietic cells, iron overload altered the expression of several adhesion molecules on stromal cells and impaired the cytokine production profile of these cells. Therefore, excessive iron would affect whole hematopoiesis by inflicting vicious effects on both immature hematopoietic cells and stromal cells.
Bees in the D: A Message of Conservation from an Urban Environment
Authors: Peterson Roest Brian
Published: March 2019

Examples of urban restoration and rewilding are critical in promoting grass roots efforts to restore ecosystems diversity in built environments. Honey bees are a vital part of many ecosystems, and urban beekeeping is a growing initiative with multiple benefits, spanning from ecological revitalization, to community cooperation, education, and cohesion. Here, we provide our own experience establishing an extensive system of roof top apiaries as cooperative effort between residents, schools, organizations, and businesses in the city of Detroit, Michigan. Our goal was to contribute to both the health of honey bee colonies and the education of their importance to our urban environment, through wide community engagement including interactive children’s educational events. Honey produced from this not-for-profit initiative is donated to local charities and small businesses, for fundraising, and also used for food and beverages in hospitality around the city. Research collaborations with scientists studying honey bee colony health, including the microbiome of honey bees, will explore possible solutions to help protect from pathogens and diseases. Most of all, we hope that this example will be of inspiration to others to take steps towards ecological solutions, in any and every form, within their own communities.
Tradeoffs with Growth and Behavior for Captive Box Turtles Head-Started with Environmental Enrichment
Authors: Tetzlaff Sasha J. , Sperry Jinelle H. , DeGregorio Brett A.
Published: March 2019

Head-starting is a conservation strategy that entails releasing captive-reared animals into nature at sizes large enough to better resist post-release predation. However, efforts to maximize growth in captivity may jeopardize development of beneficial behaviors. Environmental enrichment can encourage natural behaviors before release but potentially comes with a tradeoff of reduced growth in complex enclosures. We compared growth and behavior of enriched and unenriched captive-born juvenile box turtles (Terrapene carolina). Enriched turtles grew slower than unenriched turtles during the first eight months in captivity, although growth rates did not differ between treatments from 9–20 months old. After five months post-hatching, unenriched turtles became and remained larger overall than enriched turtles. During two foraging tasks, unenriched turtles consumed more novel prey than enriched turtles. In a predator recognition test, eight-month-old enriched turtles avoided raccoon (Procyon lotor) urine more than unenriched turtles of the same age, but this difference was not apparent one year later. The odds of turtles emerging from a shelter did not differ between treatments regardless of age. Although our results suggest turtles raised in unenriched environments initially grew faster and obtained larger overall sizes than those in enriched conditions, tradeoffs with ecologically-relevant behaviors were either absent or conditional.
Regeneration of the Periodontal Apparatus in Aggressive Periodontitis Patients
Authors: Artzi Zvi , Sudri Shiran , Platner Ori , Kozlovsky Avital
Published: March 2019

The purpose of this study is to evaluate and compare, retrospectively, the outcome of two different periodontal regeneration procedures in patients suffering from aggressive periodontitis (AgP). Twenty-eight patients were diagnosed with AgP, suffering from several intra-bony defects (IBD); that were treated by one of two periodontal regeneration techniques randomly assigned to each patient: a. guided tissue regeneration (GTR) or b. an application of extracted enamel matrix derivatives (EMD) combined with demineralized bone xenograft particles (DBX). Probing pocket depth (PPD), clinical attachment level (CAL), and gingival recession were recorded. Pre-treatment and follow-up (up to 10 years from the surgery) recordings were analyzed statistically within and between groups. A significant reduction was shown at time on PPD and CAL values, however, not between subject groups. CAL values decreased in all sites. At the EMD group (44 sites), CAL gain was 1.92 mm (±1.68) from pre-treatment to follow-up (p < 0.001) and at the GTR group (12 sites) CAL gain of 2.27 (±1.82) mm. In conclusion, 1–10 years observations have shown that surgical treatment of AgP patients by either GTR or by application of EMD/DBX results in similar successful clinical results.
Investigation of the Pressure Gain Characteristics and Cycle Performance in Gas Turbines Based on Interstage Bleeding Rotating Detonation Combustion
Authors: Qi Lei , Wang Zhitao , Zhao Ningbo , Dai Yongqiang , Zheng Hongtao , Meng Qingyang
Published: March 2019

To further improve the cycle performance of gas turbines, a gas turbine cycle model based on interstage bleeding rotating detonation combustion was established using methane as fuel. Combined with a series of two-dimensional numerical simulations of a rotating detonation combustor (RDC) and calculations of cycle parameters, the pressure gain characteristics and cycle performance were investigated at different compressor pressure ratios in the study. The results showed that pressure gain characteristic of interstage bleeding RDC contributed to an obvious performance improvement in the rotating detonation gas turbine cycle compared with the conventional gas turbine cycle. The decrease of compressor pressure ratio had a positive influence on the performance improvement in the rotating detonation gas turbine cycle. With the decrease of compressor pressure ratio, the pressurization ratio of the RDC increased and finally made the power generation and cycle efficiency enhancement rates display uptrends. Under the calculated conditions, the pressurization ratios of RDC were all higher than 1.77, the decreases of turbine inlet total temperature were all more than 19 K, the power generation enhancements were all beyond 400 kW and the cycle efficiency enhancement rates were all greater than 6.72%.