bluuebunny/crossref_metadata_2025_split huggingface dataset:
A curated collection of tissue microarray images and clinical outcome data of prostate cancer patients
Authors: Zhong Qing , Guo Tiannan , Rechsteiner Markus , Rüschoff Jan H. , Rupp Niels , Fankhauser Christian , Saba Karim , Mortezavi Ashkan , Poyet Cédric , Hermanns Thomas , Zhu Yi , Moch Holger , Aebersold Ruedi , Wild Peter J. 
Published: March 2017

AbstractMicroscopy image data of human cancers provide detailed phenotypes of spatially and morphologically intact tissues at single-cell resolution, thus complementing large-scale molecular analyses, e.g., next generation sequencing or proteomic profiling. Here we describe a high-resolution tissue microarray (TMA) image dataset from a cohort of 71 prostate tissue samples, which was hybridized with bright-field dual colour chromogenic and silver in situ hybridization probes for the tumour suppressor gene PTEN. These tissue samples were digitized and supplemented with expert annotations, clinical information, statistical models of PTEN genetic status, and computer source codes. For validation, we constructed an additional TMA dataset for 424 prostate tissues, hybridized with FISH probes for PTEN, and performed survival analysis on a subset of 339 radical prostatectomy specimens with overall, disease-specific and recurrence-free survival (maximum 167 months). For application, we further produced 6,036 image patches derived from two whole slides. Our curated collection of prostate cancer data sets provides reuse potential for both biomedical and computational studies.
Loss of Centromere Cohesion in Aneuploid Human Oocytes Correlates with Decreased Kinetochore Localization of the Sac Proteins Bub1 and Bubr1
Authors: Lagirand-Cantaloube Julie , Ciabrini Cendrine , Charrasse Sophie , Ferrieres Alice , Castro Anna , Anahory Tal , Lorca Thierry 
Published: March 2017

AbstractIn human eggs, aneuploidy increases with age and can result in infertility and genetic diseases. Studies in mouse oocytes suggest that reduced centromere cohesion and spindle assembly checkpoint (SAC) activity could be at the origin of chromosome missegregation. Little is known about these two features in humans. Here, we show that in human eggs, inter-kinetochore distances of bivalent chromosomes strongly increase with age. This results in the formation of univalent chromosomes during metaphase I (MI) and of single chromatids in metaphase II (MII). We also investigated SAC activity by checking the localization of BUB1 and BUBR1. We found that they localize at the kinetochore with a similar temporal timing than in mitotic cells and in a MPS1-dependent manner, suggesting that the SAC signalling pathway is active in human oocytes. Moreover, our data also suggest that this checkpoint is inactivated when centromere cohesion is lost in MI and consequently cannot inhibit premature sister chromatid separation. Finally, we show that the kinetochore localization of BUB1 and BUBR1 decreases with the age of the oocyte donors. This could contribute to oocyte aneuploidy.
Blockade of vascular endothelial growth factor receptors by tivozanib has potential anti-tumour effects on human glioblastoma cells
Authors: Momeny Majid , Moghaddaskho Farima , Gortany Narges K. , Yousefi Hassan , Sabourinejad Zahra , Zarrinrad Ghazaleh , Mirshahvaladi Shahab , Eyvani Haniyeh , Barghi Farinaz , Ahmadinia Leila , Ghazi-Khansari Mahmoud , Dehpour Ahmad R. , Amanpour Saeid , Tavangar Seyyed M. , Dardaei Leila , Emami Amir H. , Alimoghaddam Kamran , Ghavamzadeh Ardeshir , Ghaffari Seyed H. 
Published: March 2017

AbstractGlioblastoma (GBM) remains one of the most fatal human malignancies due to its high angiogenic and infiltrative capacities. Even with optimal therapy including surgery, radiotherapy and temozolomide, it is essentially incurable. GBM is among the most neovascularised neoplasms and its malignant progression associates with striking neovascularisation, evidenced by vasoproliferation and endothelial cell hyperplasia. Targeting the pro-angiogenic pathways is therefore a promising anti-glioma strategy. Here we show that tivozanib, a pan-inhibitor of vascular endothelial growth factor (VEGF) receptors, inhibited proliferation of GBM cells through a G2/M cell cycle arrest via inhibition of polo-like kinase 1 (PLK1) signalling pathway and down-modulation of Aurora kinases A and B, cyclin B1 and CDC25C. Moreover, tivozanib decreased adhesive potential of these cells through reduction of intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Tivozanib diminished GBM cell invasion through impairing the proteolytic cascade of cathepsin B/urokinase-type plasminogen activator (uPA)/matrix metalloproteinase-2 (MMP-2). Combination of tivozanib with EGFR small molecule inhibitor gefitinib synergistically increased sensitivity to gefitinib. Altogether, these findings suggest that VEGFR blockade by tivozanib has potential anti-glioma effects in vitro. Further in vivo studies are warranted to explore the anti-tumour activity of tivozanib in combinatorial approaches in GBM.
Novel enhancement mechanism of tyrosine hydroxylase enzymatic activity by nitric oxide through S-nitrosylation
Authors: Wang Yuanyuan , Sung Chun Chau , Chung Kenny K. K. 
Published: March 2017

AbstractTyrosine hydroxylase (TH) is a rate-limiting step enzyme in the synthesis of catecholamines. Catecholamines function both as hormone and neurotransmitters in the peripheral and central nervous systems, therefore TH’s expression and enzymatic activity is tightly regulated by various mechanisms. Several post-translational modifications have been shown to regulate TH’s enzymatic activity such as phosphorylation, nitration and S-glutathionylation. While phosphorylation at N-terminal of TH can activate its enzymatic activity, nitration and S-glutathionylation can inactivate TH. In this study, we found that TH can also be S-nitrosylated by nitric oxide (NO). S-nitrosylation is a reversible modification of cysteine (cys) residue in protein and is known to be an emerging signaling mechanism mediated by NO. We found that TH can be S-nitrosylated at cys 279 and TH S-nitrosylation enhances its enzymatic activity both in vitro and in vivo. These results provide a novel mechanism of how NO can modulate TH’s enzymatic activity through S-nitrosylation.
Physiological Mechanisms Only Tell Half Story: Multiple Biological Processes are involved in Regulating Freezing Tolerance of Imbibed Lactuca sativa Seeds
Authors: Jaganathan Ganesh K. , Han Yingying , Li Weijie , Song Danping , Song Xiaoyan , Shen Mengqi , Zhou Qiang , Zhang Chenxue , Liu Baolin 
Published: March 2017

AbstractThe physiological mechanisms by which imbibed seeds survive freezing temperatures in their natural environment have been categorized as freezing avoidance by supercooling and freezing tolerance by extracellular freeze-desiccation, but the biochemical and molecular mechanisms conferring seed freezing tolerance is unexplored. In this study, using imbibed Lactuca sativa seeds we show that fast cooled seeds (60 °C h−1) suffered significantly higher membrane damage at temperature between −20 °C and −10 °C than slow cooled (3 °Ch−1) seeds (P < 0.05), presumably explaining viability loss during fast cooling when temperature approaches −20 °C. Total soluble sugars increase in low temperature environment, but did not differ significantly between two cooling rates (P > 0.05). However, both SOD activity and accumulation of free proline were induced significantly after slow cooling to −20 °C compared with fast cooling. RNA-seq demonstrated that multiple pathways were differentially regulated between slow and fast cooling. Real-time verification of some differentially expressed genes (DEGs) revealed that fast cooling caused mRNA level changes of plant hormone and ubiquitionation pathways at higher sub-zero temperature, whilst slow cooling caused mRNA level change of those pathways at lower sub-zero ttemperatures. Thus, we conclude that imbibed seed tolerate low temperature not only by physiological mechanisms but also by biochemical and molecular changes.
Self-Assembled Array of Tethered Manganese Oxide Nanoparticles for the Next Generation of Energy Storage
Authors: Stevens Tyler E. , Pearce Charles J. , Whitten Caleah N. , Grant Richard P. , Monson Todd C. 
Published: March 2017

AbstractMany challenges must be overcome in order to create reliable electrochemical energy storage devices with not only high energy but also high power densities. Gaps exist in both battery and supercapacitor technologies, with neither one satisfying the need for both large power and energy densities in a single device. To begin addressing these challenges (and others), we report a process to create a self-assembled array of electrochemically active nanoparticles bound directly to a current collector using extremely short (2 nm or less) conductive tethers. The tethered array of nanoparticles, MnO in this case, bound directly to a gold current collector via short conducting linkages eliminates the need for fillers, resulting in a material which achieves 99.9% active material by mass (excluding the current collector). This strategy is expected to be both scalable as well as effective for alternative tethers and metal oxide nanoparticles.
Near-field terahertz probes with room-temperature nanodetectors for subwavelength resolution imaging
Authors: Mitrofanov Oleg , Viti Leonardo , Dardanis Enrico , Giordano Maria Caterina , Ercolani Daniele , Politano Antonio , Sorba Lucia , Vitiello Miriam S. 
Published: March 2017

AbstractNear-field imaging with terahertz (THz) waves is emerging as a powerful technique for fundamental research in photonics and across physical and life sciences. Spatial resolution beyond the diffraction limit can be achieved by collecting THz waves from an object through a small aperture placed in the near-field. However, light transmission through a sub-wavelength size aperture is fundamentally limited by the wave nature of light. Here, we conceive a novel architecture that exploits inherently strong evanescent THz field arising within the aperture to mitigate the problem of vanishing transmission. The sub-wavelength aperture is originally coupled to asymmetric electrodes, which activate the thermo-electric THz detection mechanism in a transistor channel made of flakes of black-phosphorus or InAs nanowires. The proposed novel THz near-field probes enable room-temperature sub-wavelength resolution coherent imaging with a 3.4 THz quantum cascade laser, paving the way to compact and versatile THz imaging systems and promising to bridge the gap in spatial resolution from the nanoscale to the diffraction limit.
Separation of nuclear isomers for cancer therapeutic radionuclides based on nuclear decay after-effects
Authors: Bhardwaj R. , van der Meer A. , Das S. K. , de Bruin M. , Gascon J. , Wolterbeek H. T. , Denkova A. G. , Serra-Crespo P. 
Published: March 2017

Abstract177Lu has sprung as a promising radionuclide for targeted therapy. The low soft tissue penetration of its β− emission results in very efficient energy deposition in small-size tumours. Because of this, 177Lu is used in the treatment of neuroendocrine tumours and is also clinically approved for prostate cancer therapy. In this work, we report a separation method that achieves the challenging separation of the physically and chemically identical nuclear isomers, 177mLu and 177Lu. The separation method combines the nuclear after-effects of the nuclear decay, the use of a very stable chemical complex and a chromatographic separation. Based on this separation concept, a new type of radionuclide generator has been devised, in which the parent and the daughter radionuclides are the same elements. The 177mLu/177Lu radionuclide generator provides a new production route for the therapeutic radionuclide 177Lu and can bring significant growth in the research and development of 177Lu based pharmaceuticals.
Prognostic and clinicopathological role of high Ki-67 expression in patients with renal cell carcinoma: a systematic review and meta-analysis
Authors: Xie Yongpeng , Chen Luyao , Ma Xin , Li Hongzhao , Gu Liangyou , Gao Yu , Fan Yang , Zhang Yu , Zhang Xu 
Published: March 2017

AbstractPrevious studies have elevated the prognostic value of Ki-67 in renal cell carcinoma (RCC), but the reports are controversial and inconsistent. We conducted a systematic review and meta-analysis to clarify the significance of Ki-67 in RCC prognosis. We systematically searched PubMed, Web of Science, and Embase to identify relevant studies until April 2016. Based on the inclusion and exclusion criteria, 20 studies, including 5,398 patients, were eligible for further analysis. Results showed that high Ki-67 expression in RCC was associated with poor OS (HR = 1.95, 95% CI: 1.44–2.64), CSS (HR = 1.67, 95% CI: 1.47–1.89), and DFS (HR = 2.56, 95% CI: 1.79–3.67). In addition, high Ki-67 expression was significantly associated with TNM stage (III/IV vs. I/II: RR = 2.03, 95% CI: 1.68–2.44), pathological T stage (T3/T4 vs. T1/T2: RR = 1.67, 95% CI: 1.35–2.06), metastasis (yes vs. no: RR = 2.15, 95% CI: 1.77–2.62), and Fuhrman grade (III/IV vs. I/II: RR = 1.77, 95% CI: 1.20–2.60). Our study suggested that Ki-67 was a prognostic marker in RCC. High Ki-67 expression was correlated with poor prognosis and advanced clinicopathological features, and it could serve as a biomarker for disease management.
Neurovascular microcirculatory vasodilation mediated by C-fibers and Transient receptor potential vanilloid-type-1 channels (TRPV 1) is impaired in type 1 diabetes
Authors: Marche P. , Dubois S. , Abraham P. , Parot-Schinkel E. , Gascoin L. , Humeau-Heurtier A. , Ducluzeau PH. , Mahe G. 
Published: March 2017

AbstractMicrovascular dysfunction may have an early onset in type 1 diabetes (T1D) and can precede major complications. Our objectives were to assess the endothelial-dependent (acetylcholine, ACh; and post-occlusive hyperemia, PORH), non-endothelial-dependent (sodium nitroprusside, SNP) and neurovascular-dependent (local heating, LH and current induced vasodilation, CIV) microcirculatory vasodilation in T1D patients compared with matched control subjects using a laser speckle contrast imager. Seventeen T1D patients - matched with 17 subjects according to age, gender, Body-Mass-Index, and smoking status - underwent macro- and microvascular investigations. The LH early peak assessed the transient receptor potential vanilloid type 1 channels (TRPV1) mediated vasodilation, whereas the plateau assessed the Nitirc-Oxyde (NO) and endothelium-derived hyperpolarizing factor (EDHF) pathways. PORH explored sensory nerves and (EDHF), while CIV assessed sensory nerves (C-fibers) and prostaglandin-mediated vasodilation. Using neurological investigations, we observed that C-fiber and A-delta fiber functions in T1D patients were similar to control subjects. PORH, CIV, LH peak and plateau vasodilations were significantly decreased in T1D patients compared to controls, whereas there was no difference between the two groups for ACh and SNP vasodilations. Neurovascular microcirculatory vasodilations (C-fibers and TRPV 1-mediated vasodilations) are impaired in TD1 patients whereas no abnormalities were found using clinical neurological investigations. Clinicaltrials: No. NCT02538120.
Characterization of long and stable de novo single alpha-helix domains provides novel insight into their stability
Authors: Wolny Marcin , Batchelor Matthew , Bartlett Gail J. , Baker Emily G. , Kurzawa Marta , Knight Peter J. , Dougan Lorna , Woolfson Derek N. , Paci Emanuele , Peckham Michelle 
Published: March 2017

AbstractNaturally-occurring single α-helices (SAHs), are rich in Arg (R), Glu (E) and Lys (K) residues, and stabilized by multiple salt bridges. Understanding how salt bridges promote their stability is challenging as SAHs are long and their sequences highly variable. Thus, we designed and tested simple de novo 98-residue polypeptides containing 7-residue repeats (AEEEXXX, where X is K or R) expected to promote salt-bridge formation between Glu and Lys/Arg. Lys-rich sequences (EK3 (AEEEKKK) and EK2R1 (AEEEKRK)) both form SAHs, of which EK2R1 is more helical and thermo-stable suggesting Arg increases stability. Substituting Lys with Arg (or vice versa) in the naturally-occurring myosin-6 SAH similarly increased (or decreased) its stability. However, Arg-rich de novo sequences (ER3 (AEEERRR) and EK1R2 (AEEEKRR)) aggregated. Combining a PDB analysis with molecular modelling provides a rational explanation, demonstrating that Glu and Arg form salt bridges more commonly, utilize a wider range of rotamer conformations, and are more dynamic than Glu–Lys. This promiscuous nature of Arg helps explain the increased propensity of de novo Arg-rich SAHs to aggregate. Importantly, the specific K:R ratio is likely to be important in determining helical stability in de novo and naturally-occurring polypeptides, giving new insight into how single α-helices are stabilized.
Single-mode interface states in heterostructure waveguides with Bragg and non-Bragg gaps
Authors: Fan Ya-Xian , Sang Tang-Qing , Liu Ting , Xu Lan-Lan , Tao Zhi-Yong 
Published: March 2017

AbstractInterface states can always arise in heterostructures that consist of two or more (artificial) materials with topologically different energy bands. The gapped band structure can be classified by the Chern number (a topological invariant) generally or the Zak phase in one-dimensional periodic systems. Recently, topological properties have been employed to investigate the interface states occurring at the connecting regions of the heterostructures of mechanical isostatic lattices and acoustical waveguides. Here, we study this heterostructure phenomenon by carefully connecting two corrugated stainless steel waveguides with Bragg and non-Bragg gaps at approximately the same frequency. These two waveguide structures can be achieved by continuously varying their geometry parameters when a topological transition exists in the forbidden bands, in which the reflection impedance changes the sign. Furthermore, a localized single high-order mode has been observed at the interface because of the transverse mode interactions, which relate to the non-Bragg gaps created by the different transverse mode resonances. Such a localized acoustic single mode with very large enhanced intensity could find its applications in sound detection, biomedical imaging, and underwater sound control, and could also enrich our means of wave front manipulations in various engineering fields.
A novel strategy for clustering major depression individuals using whole-genome sequencing variant data
Authors: Yu Chenglong , Baune Bernhard T. , Licinio Julio , Wong Ma-Li 
Published: March 2017

AbstractMajor depressive disorder (MDD) is highly prevalent, resulting in an exceedingly high disease burden. The identification of generic risk factors could lead to advance prevention and therapeutics. Current approaches examine genotyping data to identify specific variations between cases and controls. Compared to genotyping, whole-genome sequencing (WGS) allows for the detection of private mutations. In this proof-of-concept study, we establish a conceptually novel computational approach that clusters subjects based on the entirety of their WGS. Those clusters predicted MDD diagnosis. This strategy yielded encouraging results, showing that depressed Mexican-American participants were grouped closer; in contrast ethnically-matched controls grouped away from MDD patients. This implies that within the same ancestry, the WGS data of an individual can be used to check whether this individual is within or closer to MDD subjects or to controls. We propose a novel strategy to apply WGS data to clinical medicine by facilitating diagnosis through genetic clustering. Further studies utilising our method should examine larger WGS datasets on other ethnical groups.
Monitoring and Modeling the Tibetan Plateau’s climate system and its impact on East Asia
Authors: Ma Yaoming , Ma Weiqiang , Zhong Lei , Hu Zeyong , Li Maoshan , Zhu Zhikun , Han Cunbo , Wang Binbin , Liu Xin 
Published: March 2017

AbstractThe Tibetan Plateau is an important water source in Asia. As the “Third Pole” of the Earth, the Tibetan Plateau has significant dynamic and thermal effects on East Asian climate patterns, the Asian monsoon process and atmospheric circulation in the Northern Hemisphere. However, little systematic knowledge is available regarding the changing climate system of the Tibetan Plateau and the mechanisms underlying its impact on East Asia. This study was based on “water-cryosphere-atmosphere-biology” multi-sphere interactions, primarily considering global climate change in relation to the Tibetan Plateau -East Asia climate system and its mechanisms. This study also analyzed the Tibetan Plateau to clarify global climate change by considering multi-sphere energy and water processes. Additionally, the impacts of climate change in East Asia and the associated impact mechanisms were revealed, and changes in water cycle processes and water conversion mechanisms were studied. The changes in surface thermal anomalies, vegetation, local circulation and the atmospheric heat source on the Tibetan Plateau were studied, specifically, their effects on the East Asian monsoon and energy balance mechanisms. Additionally, the relationships between heating mechanisms and monsoon changes were explored.
Endoscopic ultrasound-guided tissue sampling of small subepithelial tumors of the upper gastrointestinal tract with a 22-gauge core biopsy needle
Authors: Schlag Christoph , Menzel Christoph , Götzberger Manuela , Nennstiel Simon , Klare Peter , Wagenpfeil Stefan , Schmid Roland , Weirich Gregor , von Delius Stefan 
Published: March 2017

Abstract
Background and study aims The optimal approach to small subepithelial tumors (SETs) of the upper gastrointestinal tract remains inconclusive. The aim of this study was to evaluate endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) for less invasive tissue sampling of small SETs of the upper gastrointestinal tract.
Patients and methods In this prospective observational study patients with small ( ≤ 3 cm) SETs of the upper gastrointestinal tract were eligible and underwent EUS-FNB with a 22-gauge core biopsy needle. The main outcome measure was the diagnostic yield. The number of obtained core biopsies was also assessed.
Results Twenty patients were included. The mean SET size was 16 mm (range 10 – 27 mm). EUS-FNB was technically feasible in all cases and no complications were observed. The diagnostic yield was 75 %. Core biopsy specimens were obtained in only 25 % of cases.
Conclusion EUS-FNB with a 22-gauge core biopsy needle of small SETs can achieve a definite diagnosis in the majority of cases. However, because core samples cannot regularly be obtained, EUS-FNB seems not to be convincingly superior to standard EUS-FNA in this setting