bluuebunny/crossref_metadata_2025_split huggingface dataset:
A 2-oxa-spiro[5.4]decane scaffold displays neurotrophic, neurogenic and anti-neuroinflammatory activities with high potential for development as a versatile CNS therapeutic
Authors: Joshi Pranav Chintamani , Samineni Ramesh , Bhattacharya Dwaipayan , Reddy Bommana Raghunath , Veeraval Lenin , Das Tapatee , Maitra Swati , Wahul Abhipradnya Bipin , Karri Shailaja , Pabbaraja Srihari , Mehta Goverdhan , Kumar Arvind , Chakravarty Sumana 
Published: April 2017

AbstractFollowing our recent discovery of a new scaffold exhibiting significant neurotrophic and neurogenic activities, a structurally tweaked analogue, embodying a 2-oxa-spiro [5.4]decane framework, has been conceptualised and found to be more potent and versatile. It exhibits enhanced neurotrophic and neurogenic action in in vitro, ex vivo and in vivo models and also shows robust neuroprotection in mouse acute cerebral stroke model. The observed attributes are traceable to the predominant activation of the TrkB-PI3K-AKT-CREB pathway. In addition, it also exhibits remarkable anti-neuroinflammatory activity by concurrently down-regulating pro-inflammatory cytokines IL-1α and IL-6, thereby providing a unique molecule with a trinity of neuroactivities, i.e. neurotrophic, neurogenic and anti-inflammatory. The new chemical entity disclosed here has the potential to be advanced as a versatile therapeutic molecule to treat stroke, depression, and possibly other neuropsychiatric disorders associated with attenuated neurotrophic/ neurogenic activity, together with heightened neuroinflammation.
Safety and tolerance of propranolol in neonates with severe infantile hemangiomas: a prospective study
Authors: Ji Yi , Chen Siyuan , Xiang Bo , Yang Yang , Qiu Liqing 
Published: April 2017

AbstractAlthough the efficacy of propranolol for the treatment of infantile hemangiomas (IHs) has been well documented, there is a paucity of clinical data regarding the safety and tolerance of propranolol in neonates. A prospective study of 51 patients less than 30 days of age with severe IH was conducted. All patients were admitted to the hospital for monitoring during initial propranolol treatment at day 0 with dose adjustments at days 7 and 28. Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), blood glucose (BG) levels and potential side effects were evaluated during treatment. There were significant decreases in mean heart rate and SBP after the initiation of propranolol therapy (P < 0.05). In contrast, no significant differences in mean DBP and BG levels were observed after each dose during hospitalization (P > 0.05). Bradycardia and hypotension were noted in at least 1 recorded instance in 11.8% and 5.9% of patients, respectively. These hemodynamic changes were not persistent and were asymptomatic. Two patients who had a history of neonatal pneumonia reported severe bronchial hyperreactivity during treatment. This study demonstrated that propranolol administered to properly selected young infants was safe and well tolerated. However, close monitoring should be considered in high-risk young patients.
Highly sensitive and specific protein detection via combined capillary isoelectric focusing and proximity ligation
Authors: Padhan Narendra , Yan Junhong , Boge Annegret , Scrivener Elaine , Birgisson Helgi , Zieba Agata , Gullberg Mats , Kamali-Moghaddam Masood , Claesson-Welsh Lena , Landegren Ulf 
Published: April 2017

AbstractDetection and quantification of proteins and their post-translational modifications are crucial to decipher functions of complex protein networks in cell biology and medicine. Capillary isoelectric focusing together with antibody-based detection can resolve and identify proteins and their isoforms with modest sample input. However, insufficient sensitivity prevents detection of proteins present at low concentrations and antibody cross-reactivity results in unspecific detection that cannot be distinguished from bona fide protein isoforms. By using DNA-conjugated antibodies enhanced signals can be obtained via rolling circle amplification (RCA). Both sensitivity and specificity can be greatly improved in assays dependent on target recognition by pairs of antibodies using in situ proximity ligation assays (PLA). Here we applied these DNA-assisted RCA techniques in capillary isoelectric focusing to resolve endogenous signaling transducers and isoforms along vascular endothelial growth factor (VEGF) signaling pathways at concentrations too low to be detected in standard assays. We also demonstrate background rejection and enhanced specificity when protein detection depended on binding by pairs of antibodies using in situ PLA, compared to assays where each antibody preparation was used on its own.
A New Strategy for Deleting Animal drugs from Traditional Chinese Medicines based on Modified Yimusake Formula
Authors: Wang Jinghui , Li Yan , Yang Yinfeng , Chen Xuetong , Du Jian , Zheng Qiusheng , Liang Zongsuo , Wang Yonghua 
Published: April 2017

AbstractTraditional Chinese medicine (TCM), such as Uyghur Medicine (UM) has been used in clinical treatment for many years. TCM is featured as multiple targets and complex mechanisms of action, which is normally a combination of medicinal herbs and sometimes even contains certain rare animal medicinal ingredients. A question arises as to whether these animal materials can be removed replaced from TCM applications due to their valuable rare resources or animal ethics. Here, we select a classical UM Yimusake formula, which contains 3 animal drugs and other 8 herbs, and has got wealthy experience and remarkable achievements in treating erectile dysfunction (ED) in China. The active components, drug targets and therapeutic mechanisms have been comprehensively analyzed by systems-pharmacology methods. Additionally, to validate the inhibitory effects of all candidate compounds on their related targets, in vitro experiments, computational analysis and molecular dynamics simulations were performed. The results show that the modified, original and three animal materials display very similar mechanisms for an effective treatment of ED, indicating that it is quite possible to remove these three animal drugs from the original formula while still keep its efficiency. This work provides a new attempt for deleting animal materials from TCM, which should be important for optimization of traditional medicines.
High-Resolution Morphological Approach to Analyse Elastic Laminae Injuries of the Ascending Aorta in a Murine Model of Marfan Syndrome
Authors: López-Guimet Júlia , Andilla Jordi , Loza-Alvarez Pablo , Egea Gustavo 
Published: April 2017

AbstractIn Marfan syndrome, the tunica media is disrupted, which leads to the formation of ascending aortic aneurysms. Marfan aortic samples are histologically characterized by the fragmentation of elastic laminae. However, conventional histological techniques using transverse sections provide limited information about the precise location, progression and 3D extension of the microstructural changes that occur in each lamina. We implemented a method using multiphoton excitation fluorescence microscopy and computational image processing, which provides high-resolution en-face images of segmented individual laminae from unstained whole aortic samples. We showed that internal elastic laminae and successive 2nd laminae are injured to a different extent in murine Marfan aortae; in particular, the density and size of fenestrae changed. Moreover, microstructural injuries were concentrated in the aortic proximal and convex anatomical regions. Other parameters such as the waviness and thickness of each lamina remained unaltered. In conclusion, the method reported here is a useful, unique tool for en-face laminae microstructure assessment that can obtain quantitative three-dimensional information about vascular tissue. The application of this method to murine Marfan aortae clearly shows that the microstructural damage in elastic laminae is not equal throughout the thickness of the tunica media and in the different anatomical regions of the ascending aorta.
CancerPDF: A repository of cancer-associated peptidome found in human biofluids
Authors: Bhalla Sherry , Verma Ruchi , Kaur Harpreet , Kumar Rajesh , Usmani Salman Sadullah , Sharma Suresh , Raghava Gajendra P. S. 
Published: April 2017

AbstractCancerPDF (Cancer Peptidome Database of bioFluids) is a comprehensive database of endogenous peptides detected in the human biofluids. The peptidome patterns reflect the synthesis, processing and degradation of proteins in the tissue environment and therefore can act as a gold mine to probe the peptide-based cancer biomarkers. Although an extensive data on cancer peptidome has been generated in the recent years, lack of a comprehensive resource restrains the facility to query the growing community knowledge. We have developed the cancer peptidome resource named CancerPDF, to collect and compile all the endogenous peptides isolated from human biofluids in various cancer profiling studies. CancerPDF has 14,367 entries with 9,692 unique peptide sequences corresponding to 2,230 unique precursor proteins from 56 high-throughput studies for ~27 cancer conditions. We have provided an interactive interface to query the endogenous peptides along with the primary information such as m/z, precursor protein, the type of cancer and its regulation status in cancer. To add-on, many web-based tools have been incorporated, which comprise of search, browse and similarity identification modules. We consider that the CancerPDF will be an invaluable resource to unwind the potential of peptidome-based cancer biomarkers. The CancerPDF is available at the web addresshttp://crdd.osdd.net/raghava/cancerpdf/.
Engineered HSV vector achieves safe long-term transgene expression in the central nervous system
Authors: Verlengia Gianluca , Miyagawa Yoshitaka , Ingusci Selene , Cohen Justus B. , Simonato Michele , Glorioso Joseph C. 
Published: April 2017

AbstractPreviously we reported a new series of highly defective herpes simplex virus type 1 (HSV-1) vectors that were functionally devoid of all viral immediately early (IE) genes, resulting in virtual absence of viral gene expression. Nevertheless, a reporter gene cassette inserted into the vector flanked by boundary elements from the viral latency locus showed high, persistent reporter gene activity in non-neuronal cells while an independent expression cassette inserted into a deleted ICP4 locus remained almost silent. In contrast to non-neuronal cells, we show here that the ICP4 locus cassette permitted robust reporter gene expression in a diversity of neurons following stereotactic injection of different rat brain regions; transgene expression in the hippocampus lasted up to 6 months and was essentially restricted to neurons. No evidence of neuronal cell toxicity or induction of inflammatory cell infiltrates was observed. An independent reporter gene cassette located in an intergenic region remained silent, indicating that the transgene promoter and/or insertion site are critical for sustained expression. These findings suggest the suitability of this vector for therapeutic intervention into diseases of the central nervous system that require the expression of large and/or multiple therapeutic transgenes.
Assessment of neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio and platelet count as predictors of long-term outcome after R0 resection for colorectal cancer
Authors: Pedrazzani Corrado , Mantovani Guido , Fernandes Eduardo , Bagante Fabio , Luca Salvagno Gian , Surci Niccolò , Campagnaro Tommaso , Ruzzenente Andrea , Danese Elisa , Lippi Giuseppe , Guglielmi Alfredo 
Published: April 2017

AbstractNeutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and platelet count (PC) were shown to be prognostic in several solid malignancies. We analysed 603 R0 resected patients to assess whether NLR, PLR and PC correlate with other well-known prognostic factors and survival of patients with colorectal cancer (CRC). Receiver operating characteristic (ROC) curve analysis was performed to define cut-off values for high and low ratios of these indices. Univariate and multivariate analysis were used to determine the prognostic value of NLR, PLR and PC for overall and cancer-related survival. The distribution of NLR, PLR and PC in CRC patients was compared with 5270 healthy blood donors. The distribution of NLR, PLR and PC was significantly different between CRC patients and controls (all p < 0.05). A significant but heterogeneous association was found between the main CRC prognostic factors and high values of NLR, PLR and PC. Survival appeared to be worse in patients with high NLR with cancers in AJCC/UICC TNM Stages I-IV; nonetheless its prognostic value was not confirmed for cancer-related survival in multivariate analysis. After stratification of patients according to AJCC/UICC TNM stages, high PC value was significantly correlated with overall and cancer-related survival in TNM stage IV patients.
Comparison of the Left Main Coronary Bifurcating Angle among Patients with Normal, Non-significantly and Significantly Stenosed Left Coronary Arteries
Authors: Juan Yu-Hsiang , Tsay Pei-Kwei , Shen Wei-Chih , Yeh Chih-Seng , Wen Ming-Shien , Wan Yung-Liang 
Published: April 2017

AbstractWe evaluated the correlation of the left main coronary bifurcating angle (LCBA) with the severity of coronary atherosclerosis, risk factors of coronary artery disease (CAD) and the feasibility of measuring the LBCA using the axial plane. Coronary Computed tomography angiographies (CTAs) of 313 patients between Nov. 2006 and Oct. 2013 were reviewed and separated into three groups. Group I (211 patients) had significant stenosis (≥50%) of the left anterior descending coronary artery (LAD) and/or left circumflex coronary artery (LCX). Group II (62 subjects) had atherosclerosis without significant stenosis. Group III (40 subjects) had unremarkable coronary CTAs. Both Group I and II patients received conventional catheter angiography to confirm the severities of coronary stenoses. Significant differences were found among the groups with respect to risk factors, such as male gender, hypertension and body mass index. Axial plane measurement was feasible in most patients (82.1%), without significant differences among the groups. The mean LCBA was 84.7° among all patients, and significantly differed among groups I, II and III (87.34°, 81.16° and 75.53°, P < 0.001). The LCBA of group I was significantly higher than group III (P < 0.001) in univariate analysis, but insignificant in multivariate analysis (P = 0.064).
Fully transparent high performance thin film transistors with bilayer ITO/Al-Sn-Zn-O channel structures fabricated on glass substrate
Authors: Cong Yingying , Han Dedong , Dong Junchen , Zhang Shengdong , Zhang Xing , Wang Yi 
Published: April 2017

AbstractIn this work, fully transparent high performance double-channel indium-tin-oxide/Al–Sn–Zn–O thin-film transistors (ITO/ATZO TFTs) are successfully fabricated on glass by radio frequency (RF) magnetron sputtering. The ITO layer acts as the bottom channel layer to increase the channel carrier concentration. The top ATZO channel layer, which is deposited via high oxygen partial pressure in the sputtering process, is useful to control the minimum off-state current. After annealing, the ITO/ATZO TFT demonstrates outstanding electrical performances, including a high ON/OFF current ratio (Ion/Ioff) of 3.5 × 108, a steep threshold swing (SS) of 142.2 mV/decade, a superior saturation mobility (μsat) of 246.0 cm2/Vs, and a threshold voltage VT of 0.5 V. The operation mechanisms for double-channel structures are also clarified.
A short artificial antimicrobial peptide shows potential to prevent or treat bone infections
Authors: Bormann N. , Koliszak A. , Kasper S. , Schoen L. , Hilpert K. , Volkmer R. , Kikhney J. , Wildemann B. 
Published: April 2017

AbstractInfection of bone is a severe complication due to the variety of bacteria causing it, their resistance against classical antibiotics, the formation of a biofilm and the difficulty to eradicate it. Antimicrobial peptides (AMPs) are naturally occurring peptides and promising candidates for treatment of joint infections. This study aimed to analyze the effect of short artificial peptides derived from an optimized library regarding (1) antimicrobial effect on different bacterial species, (2) efficacy on biofilms, and (3) effect on osteoblast‑like cells. Culturing the AMP-modifications with Escherichia coli, Enterococcus faecalis, Pseudomonas aeruginosa, Staphylococcus aureus (including clinical isolates of MRSA and MSSA) and Staphylococcus epidermidis identified one candidate that was most effective against all bacteria. This AMP was also able to reduce biofilm as demonstrated by FISH and microcalorimetry. Osteoblast viability and differentiation were not negatively affected by the AMP. A cation concentration comparable to that physiologically occurring in blood had almost no negative effect on AMP activity and even with 10% serum bacterial growth was inhibited. Bacteria internalized into osteoblasts were reduced by the AMP. Taken together the results demonstrate a high antimicrobial activity of the AMP even against bacteria incorporated in a biofilm or internalized into cells without harming human osteoblasts.
Prognostic significance of huntingtin interacting protein 1 expression on patients with acute myeloid leukemia
Authors: Wang Jinghan , Yu Mengxia , Guo Qi , Ma Qiuling , Hu Chao , Ma Zhixin , Yin Xiufeng , Li Xia , Wang Yungui , Pan Hanzhang , Wang Dongmei , Huang Jiansong , Meng Haitao , Tong Hongyan , Qian Wenbin , Jin Jie 
Published: April 2017

AbstractHuntingtin interacting protein 1 (HIP1) is an endocytic protein which is overexpressed in a variety of human cancers and involved in cancer-causing translocation in leukemia. However, the prognostic impact of HIP1 expression on AML remains unclear. In this study, quantification of HIP1 transcript by real-time quantitative PCR in bone marrow blasts was performed in 270 AML patients. As a result, high HIP1 expression was seen more frequently in older patients, M4/M5 morphology and genes of NPM1 and DNMT3A mutations, and underrepresented in favorable karyotype subgroups and CEBPA double allele mutations in our AML patients. We also found high HIP1 expressers showed lower levels of hemoglobin. In addition, overexpression of HIP1 was associated with an inferior overall survival. The prognostic value of HIP1 expression was validated in patients from an independent TCGA cohort. Notably, up-regulation of miR-16, miR-15a, miR-28 and miR-660 were seen in high HIP1 expressers from the two independent cohorts. In vitro, interfereing of HIP1 expression by siRNA suppressed the proliferation of leukemic cells, and downregulation of these miRNAs were seen in THP-1 and Kasumi cell lines after silencing HIP1 expression. In conclusion, the HIP1 gene expression might serve as a reliable predictor for overall survival in AML patients.
Method and Mechanisms of Soil Stabilization Using Electric Arc Furnace Dust
Authors: Al-Amoudi Omar S. Baghabra , Al-Homidy Abdullah A. , Maslehuddin Mohammed , Saleh Tawfik A. 
Published: April 2017

AbstractThis paper reports the method and mechanism for improving the strength of marl and desert sand utilizing electric arc furnace dust (EAFD), an industrial by-product, in lieu of cement or lime. EAFD was used in conjunction with a small quantity (2%) of cement. The mechanical properties and durability characteristics of marl and sand mixed with 2% cement plus 5-, 10-, 20- or 30%-EAFD, by weight of the soil, were evaluated. The soil-cement-EAFD mixtures were used to determine their unconfined compressive strength (UCS), soaked California Bearing Ratio (CBR) and durability. The risk of leaching of toxic heavy metals, such as lead and cadmium, from the stabilized soils to the groundwater was also investigated. The mechanisms of stabilization of the selected soils due to the use of EAFD along with a small quantity of cement are also elucidated. The usage of 20 to 30% EAFD with 2% cement was noted to considerably improve the mechanical properties and durability of both marl and sand.
Power theft localisation using voltage measurements from distribution feeder nodes
Authors: Dasgupta Kalyan , Padmanaban Manikandan , Hazra Jagabondhu 
Published: April 2017

In this study, a novel algorithm to locate regions in a distribution feeder, where power is being illegally tapped, is proposed. The basic requirements of the algorithm are voltage measuring devices located at distribution feeder nodes or transformers that can communicate data to the distribution substation. Initially, how voltage magnitude difference between successive nodes in a feeder can help identify possible locations of illegal tapping is shown. The technique is further refined by a normalised voltage double difference method, to pin‐point the exact location of power theft. The algorithm does not require network parameters. Simulations are performed on the IEEE 34 node test feeder, to demonstrate the efficacy of this method.
Adenomatous Tumors of the Middle Ear: A Literature Review
Authors: Cardoso Flavia , Monteiro Eduardo Machado , Lopes Livia , Avila Marianna , Scarioli Bernardo 
Published: April 2017

Introduction Neuroendocrine adenomas of the middle ear (NAME) are uncommon causes of middle ear masses. Mostly limited to case reports and small series, the literature is poor in providing an overall assessment of these tumors.
Objective To review the current literature about all aspects of the disease, including its etiology, clinical manifestations, diagnosis, and treatment.
Data Synthesis The pathogenesis of adenomatous tumors of the middle ear is not clear yet. One potential explanation is that an undifferentiated pluripotent endodermal stem cell may still be present in the middle ear mucosal surface, and may be the origin of the tumors. It typically appears as a nonspecific retrotympanic mass. The average age of onset for the disease is the fifth decade, and the most common clinical symptom is conductive hearing loss. Malign behavior is rare. There are numerous differential diagnoses of NAME. The final diagnosis depends on microscopic findings. The preoperative evaluation should include the use of computed tomography and magnetic resonance imaging. The adjunctive therapy of middle ear adenomatous tumors with radiotherapy, chemotherapy or somatostatin analogs is generally not recommended.
Conclusion There is still much debate on pathogenesis and classification of NAME. Saliba's classification is currently the most complete and preferable one. Aggressive surgical procedure with ossicular chain excision is the gold standard treatment. Follow-up with physical and radiological exams is mandatory, particularly if the first procedure was conservative, without the removal of the encased ossicles.