bluuebunny/crossref_metadata_2025_split huggingface dataset:
PCA-PAM50 improves consistency between breast cancer intrinsic and clinical subtyping reclassifying a subset of luminal A tumors as luminal B
Authors: Raj-Kumar Praveen-Kumar , Liu Jianfang , Hooke Jeffrey A. , Kovatich Albert J. , Kvecher Leonid , Shriver Craig D. , Hu Hai 
Published: May 2019

AbstractThe PAM50 classifier is widely used for breast tumor intrinsic subtyping based on gene expression. Clinical subtyping, however, is based on immunohistochemistry assays of 3–4 biomarkers. Subtype calls by these two methods do not completely match even on comparable subtypes. Nevertheless, the estrogen receptor (ER)-balanced subset for gene-centering in PAM50 subtyping, is selected based on clinical ER status. Here we present a new method called Principle Component Analysis-based iterative PAM50 subtyping (PCA-PAM50) to perform intrinsic subtyping in ER status unbalanced cohorts. This method leverages PCA and iterative PAM50 calls to derive the gene expression-based ER status and a subsequent ER-balanced subset for gene centering. Applying PCA-PAM50 to three different breast cancer study cohorts, we observed improved consistency (by 6–9.3%) between intrinsic and clinical subtyping for all three cohorts. Particularly, a more aggressive subset of luminal A (LA) tumors as evidenced by higher MKI67 gene expression and worse patient survival outcomes, were reclassified as luminal B (LB) increasing the LB subtype consistency with IHC by 25–49%. In conclusion, we show that PCA-PAM50 enhances the consistency of breast cancer intrinsic and clinical subtyping by reclassifying an aggressive subset of LA tumors into LB. PCA-PAM50 code is available at ftp://ftp.wriwindber.org/.
Theoretical Stable Hydraulic Section based on the Principle of Least Action
Authors: Ohara Noriaki , Yamatani Katsu 
Published: May 2019

AbstractDespite decades of effort, stable hydraulic geometry for an open channel water flow has hardly been established because of too many unknown variables for too few rational relationships. This article derives the most efficient channel cross section using calculus of variations for the given flow area at the minimum wetting perimeter length, which is equivalent to the principle of least action. Analysis indicates that water can most efficiently flow in a semi-ellipse section channel with minimum friction and erosion. Anisotropy in channel erodibility was found to be necessary in the natural stable channel characterization because gravitation force and channel bank consolidation cannot be ignored in earth surface material. This channel cross section, based on the principle of least action, may be regarded as the theoretical stable hydraulic section for erodible bed, which was comparable to the observed river cross-sections during high flow periods.
Low frequency Raman Spectroscopy for micron-scale and in vivo characterization of elemental sulfur in microbial samples
Authors: Nims Christine , Cron Brandi , Wetherington Maxwell , Macalady Jennifer , Cosmidis Julie 
Published: May 2019

AbstractElemental sulfur (S(0)) is an important intermediate of the sulfur cycle and is generated by chemical and biological sulfide oxidation. Raman spectromicroscopy can be applied to environmental samples for the detection of S(0), as a practical non-destructive micron-scale method for use on wet material and living cells. Technical advances in filter materials enable the acquisition of ultra-low frequency (ULF) Raman measurements in the 10–100 cm−1 range using a single-stage spectrometer. Here we demonstrate the potency of ULF Raman spectromicroscopy to harness the external vibrational modes of previously unrecognized S(0) structures present in environmental samples. We investigate the chemical and structural nature of intracellular S(0) granules stored within environmental mats of sulfur-oxidizing γ-Proteobacteria (Thiothrix). In vivo intracellular ULF scans indicate the presence of amorphous cyclooctasulfur (S8), clarifying enduring uncertainties regarding the content of microbial sulfur storage globules. Raman scattering of extracellular sulfur clusters in Thiothrix mats furthermore reveals an unexpected abundance of metastable β-S8 and γ-S8, in addition to the stable α-S8 allotrope. We propose ULF Raman spectroscopy as a powerful method for the micron-scale determination of S(0) structure in natural and laboratory systems, with a promising potential to shine new light on environmental microbial and chemical sulfur cycling mechanisms.
Breast-lesions characterization using Quantitative Ultrasound features of peritumoral tissue
Authors: Klimonda Ziemowit , Karwat Piotr , Dobruch-Sobczak Katarzyna , Piotrzkowska-Wróblewska Hanna , Litniewski Jerzy 
Published: May 2019

AbstractThe presented studies evaluate for the first time the efficiency of tumour classification based on the quantitative analysis of ultrasound data originating from the tissue surrounding the tumour. 116 patients took part in the study after qualifying for biopsy due to suspicious breast changes. The RF signals collected from the tumour and tumour-surroundings were processed to determine quantitative measures consisting of Nakagami distribution shape parameter, entropy, and texture parameters. The utility of parameters for the classification of benign and malignant lesions was assessed in relation to the results of histopathology. The best multi-parametric classifier reached an AUC of 0.92 and of 0.83 for outer and intra-tumour data, respectively. A classifier composed of two types of parameters, parameters based on signals scattered in the tumour and in the surrounding tissue, allowed the classification of breast changes with sensitivity of 93%, specificity of 88%, and AUC of 0.94. Among the 4095 multi-parameter classifiers tested, only in eight cases the result of classification based on data from the surrounding tumour tissue was worse than when using tumour data. The presented results indicate the high usefulness of QUS analysis of echoes from the tissue surrounding the tumour in the classification of breast lesions.
Long-Term Aspirin Administration Has No Effect on Erectile Function: Evidence from Adult Rats and Ageing Rat Model
Authors: Li Tao , Wu Changjing , Fu Fudong , Xiong Wenfeng , Qin Feng , Yuan Jiuhong 
Published: May 2019

AbstractAs the broad spectrum pharmacological action, aspirin has been one of the most widely used medicines since its initial synthesis; however, the association between aspirin and erectile function is still controversial. We aim to explore whether long-term aspirin administration deteriorates or preserves erectile function from adult rats and ageing rat model. Twenty adult rats (10 weeks of age) and twenty ageing rats (80 weeks of age) were randomly divided into four groups as follows: Adult-Control (normal saline [NS]), Adult-Aspirin (aspirin, 10 mg/kg/d), Ageing-Control (NS), and Ageing-Aspirin (aspirin, 10 mg/kg/d) groups (n = 10 per group). For all rats, erectile function was assessed by maximum intracavernous pressure (ICP), total area under ICP curve (AUC), ICP/mean arterial pressure (MAP) ratio, and MAP. The total treatment duration was one month. Protein expression levels of cyclooxygenase-1 (COX-1), COX-2, endothelial nitric oxide synthase (eNOS), and nNOS of the corpus cavernosum were detected by Western blot. ELISA kits were used to determine 6-keto PGF1a, PGE2, TXB2, cyclic adenosine monophosphate (cAMP), and cyclic guanosine monophosphate (cGMP) levels. Total nitric oxide (NO) concentration was measured using a fluorometric assay kit. As a result, Ageing-Control rats revealed significantly decreased ICP, AUC, and ICP/MAP ratios compared to Adult-Control rats, and these effects were accompanied by reduced eNOS protein expression and lower total NO and cGMP levels; however, no difference was found in nNOS protein expression. For adult rat groups, aspirin significantly inhibited the production of 6-keto PGF1a, PGE2, and TXB2; however, it neither changed the ICP, AUC, or ICP/ MAP ratios nor altered the protein expression of eNOS, nNOS, COX-1, and COX-2. Meanwhile, aspirin did not influence the concentrations of total NO, cAMP, or cGMP. The same tendency was also found in the ageing rat model, which confirmed that aspirin did not alter erectile function. Our data suggested that long-term aspirin administration did not strengthen or weaken erectile function in adult rats or ageing rat model. Thus, it had no impact on erectile function.
Aptamer-based Targeted Delivery of a G-quadruplex Ligand in Cervical Cancer Cells
Authors: Carvalho Josué , Paiva Artur , Cabral Campello Maria Paula , Paulo António , Mergny Jean-Louis , Salgado Gilmar F. , Queiroz João A. , Cruz Carla 
Published: May 2019

AbstractAS1411 is a G-rich DNA oligonucleotide that functions as an aptamer of the protein nucleolin, found at high levels on the surface of cancer cells but not on the surface of normal cells. Herein, we have studied AS1411 as a supramolecular carrier for the delivery of an acridine-based G-quadruplex ligand, C8, to HeLa cancer cells. Two AS1411 derivatives, LNA-AS1411 and U-AS1411, were also tested, in an attempt to compare AS1411 pharmacological properties. The results showed that AS1411-C8 complexation was made with great binding strength and that it lowered the ligand’s cytotoxicity towards non-malignant cells. This effect was suggested to be due to a decreased internalization of the complexed versus free C8 as shown by flow cytometry. The AS1411 derivatives, despite forming a stable complex with C8, lacked the necessary tumour-selective behaviour. The binding of C8 to AS1411 G-quadruplex structure did not negatively affect the recognition of nucleolin by the aptamer. The AS1411-C8 repressed c-MYC expression at the transcriptional level, possibly due to C8 ability to stabilize the c-MYC promoter G-quadruplexes. Overall, this study demonstrates the usefulness of AS1411 as a supramolecular carrier of the G-quadruplex binder C8 and the potential of using its tumour-selective properties for the delivery of ligands for cancer therapy.
Permutation Statistics for Connectivity Analysis between Regions of Interest in EEG and MEG Data
Authors: Mamashli Fahimeh , Hämäläinen Matti , Ahveninen Jyrki , Kenet Tal , Khan Sheraz 
Published: May 2019

AbstractConnectivity estimates based on electroencephalography (EEG) and magnetoencephalography (MEG) are unique in their ability to provide neurophysiologically meaningful spectral and temporal information non-invasively. This multi-dimensional aspect of the MEG/EEG based connectivity increases the challenges of the analysis and interpretation of the data. Many MEG/EEG studies address this complexity by using a hypothesis-driven approach, which focuses on particular regions of interest (ROI). However, if an effect is distributed unevenly over a large ROI and variable across subjects, it may not be detectable using conventional methods. Here, we propose a novel approach, which enhances the statistical power for weak and spatially discontinuous effects. This results in the ability to identify statistically significant connectivity patterns with spectral, temporal, and spatial specificity while correcting for multiple comparisons using nonparametric permutation methods. We call this new approach the Permutation Statistics for Connectivity Analysis between ROI (PeSCAR). We demonstrate the processing steps with simulated and real human data. The open-source Matlab code implementing PeSCAR are provided online.
Circulating Tumor Cell cluster phenotype allows monitoring response to treatment and predicts survival
Authors: Balakrishnan Ajay , Koppaka Deepak , Anand Abhishek , Deb Barnali , Grenci Gianluca , Viasnoff Virgile , Thompson Erik W. , Gowda Harsha , Bhat Ramray , Rangarajan Annapoorni , Thiery Jean Paul , Govind Babu K. , Kumar Prashant 
Published: May 2019

AbstractCirculating tumor cells (CTCs) are putative markers of tumor prognosis and may serve to evaluate patient’s response to chemotherapy. CTCs are often detected as single cells but infrequently as clusters and are indicative of worse prognosis. In this study, we developed a short-term culture of nucleated blood cells which was applied to blood samples from breast, lung, esophageal and bladder cancer patients. Clusters of different degrees of compactness, classified as very tight, tight and loose were observed across various cancer types. These clusters show variable expression of cytokeratins. Cluster formation from blood samples obtained during the course of chemotherapy was found to be associated with disease progression and shorter overall survival. The short-term cultures offer a robust and highly reliable method for early prediction of treatment response in different cancer types.
Effect of ovariectomy on the progression of chronic kidney disease-mineral bone disorder (CKD-MBD) in female Cy/+ rats
Authors: Vorland Colby J. , Lachcik Pamela J. , Swallow Elizabeth A. , Metzger Corinne E. , Allen Matthew R. , Chen Neal X. , Moe Sharon M. , Hill Gallant Kathleen M. 
Published: May 2019

AbstractMale Cy/+ rats have shown a relatively consistent pattern of progressive kidney disease development that displays multiple key features of late stage chronic kidney disease-mineral bone disorder (CKD-MBD), specifically the development of cortical bone porosity. However, progression of disease in female Cy/+ rats, assessed in limited studies, is more heterogeneous and to date has failed to show development of the CKD-MBD phenotype, thus limiting their use as a practical model of progressive CKD-MBD. Animal and human studies suggest that estrogen may be protective against kidney disease in addition to its established protective effect on bone. Therefore, in this study, we aimed to determine the effect of ovariectomy (OVX) on the biochemical and skeletal manifestations of CKD-MBD in Cy/+ female rats. We hypothesized that OVX would accelerate development of the biochemical and skeletal features of CKD-MBD in female Cy/+ rats, similar to those seen in male Cy/+ rats. Female Cy/+ rats underwent OVX (n = 8) or Sham (n = 8) surgery at 15 weeks of age. Blood was collected every 5 weeks post-surgery until 35 weeks of age, when the rats underwent a 4-day metabolic balance, and the tibia and final blood were collected at the time of sacrifice. OVX produced the expected changes in trabecular and cortical parameters consistent with post-menopausal disease, and negative phosphorus balance compared with Sham. However, indicators of CKD-MBD were similar between OVX and Sham (similar kidney weight, plasma blood urea nitrogen, creatinine, creatinine clearance, phosphorus, calcium, parathyroid hormone, and no cortical porosity). Contrary to our hypothesis, OVX did not produce evidence of development of the CKD-MBD phenotype in female Cy/+ rats.
Dynamically Stable Topological Phase of Arsenene
Authors: Rahman Gul , Mahmood Asad , García-Suárez Víctor M. 
Published: May 2019

AbstractFirst-principles calculations based on density functional theory (DFT) are used to investigate the electronic structures and topological phase transition of arsenene under tensile and compressive strains. Buckling in arsenene strongly depends on compressive/tensile strain. The phonons band structures reveal that arsenene is dynamically stable up to 18% tensile strain and the frequency gap between the optical and acoustic branches decreases with strain. The electronic band structures show the direct bandgap decreases with tensile strain and then closes at 13% strain followed by band inversion. With spin-orbit coupling (SOC), the 14% strain-assisted topological insulator phase of arsenene is mainly governed by the p-orbitals. The SOC calculated bandgap is about 43 meV. No imaginary frequency in the phonons is observed in the topological phase of arsenene. The dynamically stable topological phase is accessed through Z2 topological invariant ν using the analysis of the parity of the wave functions at the time-reversal invariant momentum points. The calculated ν is shown to be 1, implying that arsenene is a topological insulator which can be a candidate material for nanoelectronic devices.
Internalization, distribution, and activity of peptide H2 against the intracellular multidrug-resistant bovine mastitis-causing bacterium Staphylococcus aureus
Authors: Wang Xiao , Teng Da , Wang Xiumin , Hao Ya , Chen Huixian , Mao Ruoyu , Wang Jianhua 
Published: May 2019

AbstractBovine mastitis is mainly caused by Staphylococcus aureus, which is difficult to eliminate, prone to escape from antibacterial agents, and may cause recurring infections due to the intracellular nature of its infection and multidrug resistance. In this study, the intracellular activities of the NZ2114 derivative peptide H18R (H2) against methicillin-resistant S. aureus (MRSA) and multidrug-resistant bovine S. aureus strains were investigated in bovine mammary epithelial MAC-T cells and mouse mammary glands. The minimum inhibitory concentrations of H2 against S. aureus were 0.5‒1 μg/ml; H2 displayed a lower cytotoxicity than its parental peptide NZ2114 (survival rates of MAC-T cells: 100% [H2 treatment] vs 60.7% [NZ2114 (256 μg/ml) treatment]). H2 was internalized into MAC-T cells mainly via clathrin-mediated endocytosis, and distributed in the cytoplasm. The intracellular inhibition rates against MRSA ATCC43300, the mastitis isolates S. aureus CVCC 3051 and E48 were above 99%, 99%, and 94%, respectively; these were higher than those in case of vancomycin (23–47%). In the mouse model of S. aureus E48-induced mastitis, after treatment with 100 μg of H2 and vancomycin, bacterial numbers in each mammary gland were reduced by 3.96- and 1.59-log CFU, respectively. Additionally, similar to NZ2114 and vancomycin, H2 alleviated the histopathological damage of the mammary tissue and polymorphonuclear neutrophil infiltration in the alveoli. These results suggest that H2 can be used as a safe and effective candidate for treating S. aureus-induced mastitis.
Free Flap Outcomes of Microvascular Reconstruction after Repeated Segmental Mandibulectomy in Head and Neck Cancer Patients
Authors: Lin Jennifer An-Jou , Loh Charles Yuen Yung , Tsai Chia-Hsuan , Chang Kai-Ping , Wu John Chung-Han , Kao Huang-Kai 
Published: May 2019

AbstractThis is the first study to investigate the impact of a second fibula flap or a soft tissue flap combined with bridging plate for a repeated segmental mandibulectomy reconstruction on flap outcomes in head and neck cancer patients. A retrospective comparative analysis (2007–2016) of 61 patients who underwent a second segmental mandibulectomy was performed. 20 patients underwent a fibula flap reconstruction whereas 41 had a soft tissue flap and plate reconstruction. No significant difference was seen in the operative time, total hospital stay, flap loss, re-exploration rates, plate exposure rate, or recipient site infection rate. On multivariate analysis, patients reconstructed with a soft tissue flap and bridging plate (odds ratio (OR) 3.997; 95% confidence interval (CI), 1.046–15.280, p = 0.043) and complications developed in previous surgery (OR 4.792; 95% CI, 1.120–20.493, p = 0.035) were shown to be independent predictors of a prolonged nasogastric tube dependence. The utilization of a soft tissue flap with plate is associated with comparative results of acute complication rate within 1 week, recipient site infection rate, and plate exposure rate to free fibula flaps alone. Free fibula flaps may result in a decreased risk for prolonged tube dependence compared to free soft tissue flap reconstructions.
Osmotic tolerance of avian erythrocytes to complete hemolysis in solute free water
Authors: Singh Snigdha , Ponnappan Nisha , Verma Anand , Mittal Aditya 
Published: May 2019

AbstractOsmotic behavior of erythrocytes is not only important clinically, but is also significant in understanding of material transport across biological membranes. It is most commonly studied through fragiligrams – plots of the degree of hemolysis as a function of extracellular osmolarity. A fundamental assumption in experimental and theoretical studies on osmolarity driven transport of water across the plasma membranes of all cells is the sigmoidal nature of their osmotic behavior. Sigmoidal data is mathematically monotonic showing either a decreasing only or an increasing only trend, but not both, within certain thresholds; beyond these thresholds the data is asymptotic or flat. Fragiligrams of erythrocytes are usually sigmoidal, with maximal hemolysis in plain solute-free water and often up to a certain extracellular hypotonic environment. In this work, we report a new discovery of non-monotonic osmotic behavior of avian erythrocytes. In contrast to the expected monotonic fragiligrams obtained for mammalian erythrocytes, fragiligrams of avian erythrocytes show non-monotonic curves. Maximal hemolysis of avian erythrocytes was not observed at the most hypotonic conditions – instead, maximal hemolysis was observed at mild hypotonic conditions. Hemolysis of avian erythrocytes first increases then decreases with increasing extracellular osmolarity. We also report that the non-monotonic fragiligrams of chicken erythrocytes are converted to the expected monotonic sigmoids subsequent to controlled extracellular trypsinization. While possibly having profound evolutionary implications for vertebrates, the findings reported in this work have a direct impact on understanding of avian physiology. Our results also compel revisiting of experimental and theoretical models for understanding material transport across biological membranes under different osmotic conditions.
MR-Guided Focused Ultrasound in Fibroid Treatment – Results of the 4th Radiological-Gynecological Expert Meeting
Authors: Kröncke Thomas , David Matthias 
Published: May 2019

Magnetic Resonance-guided focused ultrasound (MRgFUS; Syn.: HIFU = high intensity focused ultrasound) is a safe and effective thermoablative technique to treat fibroid-related symptoms. The evidence is limited due to a lack of randomized trials. The indication for treatment by MRgFUS are symptomatic uterine fibroids. This consensus paper covers criteria to measure success, contraindications, side effects and complications of MRgFUS treatment. The role of MRgFUS in the setting of family planning is part of this publication.
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Persönlichkeitsstörungen und Werteorientierungen als Prädiktoren männlicher Depression bei militärischen und zivilen Patienten
Authors: Hohl-Radke Felix , Leutheußer Gregor , Groh Maria , Reimann Irina , Koch Milena , Zimmermann Peter 
Published: May 2019

ZusammenfassungZiel der Studie war es, Unterschiede zwischen einer militärischen und einer zivilen Stichprobe von Patienten mit Depressionen im Hinblick auf das Konstrukt der männlichen Depression, auf weitere depressive Symptome, Persönlichkeitsakzentuierungen und Werteorientierung zu identifizieren. Dazu wurden je 50 zivile und militärische Patienten untersucht. Unterschiede hinsichtlich des Vorkommens der männlichen Depression fanden sich nicht, es zeigten sich aber Zusammenhänge mit einzelnen Persönlichkeitsakzenten und Werteorientierungen.