bluuebunny/crossref_metadata_2025_split huggingface dataset:
A high-throughput drug combination screen of targeted small molecule inhibitors in cancer cell lines
Authors: Flobak Åsmund , Niederdorfer Barbara , Nakstad Vu To , Thommesen Liv , Klinkenberg Geir , Lægreid Astrid 
Published: October 2019

AbstractWhile there is a high interest in drug combinations in cancer therapy, openly accessible datasets for drug combination responses are sparse. Here we present a dataset comprising 171 pairwise combinations of 19 individual drugs targeting signal transduction mechanisms across eight cancer cell lines, where the effect of each drug and drug combination is reported as cell viability assessed by metabolic activity. Drugs are chosen by their capacity to specifically interfere with well-known signal transduction mechanisms. Signalling processes targeted by the drugs include PI3K/AKT, NFkB, JAK/STAT, CTNNB1/TCF, and MAPK pathways. Drug combinations are classified as synergistic based on the Bliss independence synergy metrics. The data identifies combinations that synergistically reduce cancer cell viability and that can be of interest for further pre-clinical investigations.
Transcriptomic profile of cystic fibrosis airway epithelial cells undergoing repair
Authors: Zoso Alice , Sofoluwe Aderonke , Bacchetta Marc , Chanson Marc 
Published: October 2019

AbstractPathological remodeling of the airway epithelium is commonly observed in Cystic Fibrosis (CF). The different cell types that constitute the airway epithelium are regenerated upon injury to restore integrity and maintenance of the epithelium barrier function. The molecular signature of tissue repair in CF airway epithelial cells has, however, not well been investigated in primary cultures. We therefore collected RNA-seq data from well-differentiated primary cultures of bronchial human airway epithelial cells (HAECs) of CF (F508del/F508del) and non-CF (NCF) origins before and after mechanical wounding, exposed or not to flagellin. We identified the expression changes with time of repair of genes, the products of which are markers of the different cell types that constitute the airway epithelium (basal, suprabasal, intermediate, secretory, goblet and ciliated cells as well as ionocytes). Researchers in the CF field may benefit from this transcriptomic profile, which covers the initial steps of wound repair and revealed differences in this process between CF and NCF cultures.
Noise-free simulation of an FT-IR imaging hyperspectral dataset of pancreatic biopsy core bound by experiment
Authors: Wrobel Tomasz P. , Koziol Paulina , Raczkowska Magda K. , Liberda Danuta , Paluszkiewicz Czeslawa , Kwiatek Wojciech M. 
Published: October 2019

AbstractA noise-free hyperspectral FT-IR imaging dataset of a pancreatic tissue core was simulated based on experimental data that allows to test the performance of various data analysis and processing algorithms. A set of experimental noise levels was also added and used for denoising approaches comparison, which due to the noise-free reference signal enables to truly observe signal distortion caused by different approaches.
Structural and thermodynamic basis for the recognition of the substrate-binding cleft on hen egg lysozyme by a single-domain antibody
Authors: Akiba Hiroki , Tamura Hiroko , Kiyoshi Masato , Yanaka Saeko , Sugase Kenji , Caaveiro Jose M. M. , Tsumoto Kouhei 
Published: October 2019

AbstractSingle-domain antibodies (VHHs or nanobodies), developed from heavy chain-only antibodies of camelids, are gaining attention as next-generation therapeutic agents. Despite their small size, the high affinity and specificity displayed by VHHs for antigen molecules rival those of IgGs. How such small antibodies achieve that level of performance? Structural studies have revealed that VHHs tend to recognize concave surfaces of their antigens with high shape-complementarity. However, the energetic contribution of individual residues located at the binding interface has not been addressed in detail, obscuring the actual mechanism by which VHHs target the concave surfaces of proteins. Herein, we show that a VHH specific for hen egg lysozyme, D3-L11, not only displayed the characteristic binding of VHHs to a concave region of the surface of the antigen, but also exhibited a distribution of energetic hot-spots like those of IgGs and conventional protein-protein complexes. The highly preorganized and energetically compact interface of D3-L11 recognizes the concave epitope with high shape complementarity by the classical lock-and-key mechanism. Our results shed light on the fundamental basis by which a particular VHH accommodate to the concave surface of an antigens with high affinity in a specific manner, enriching the mechanistic landscape of VHHs.
A large intragenic deletion in the CLCN1 gene causes Hereditary Myotonia in pigs
Authors: Araújo C. E. T. , Oliveira C. M. C. , Barbosa J. D. , Oliveira-Filho J. P. , Resende L. A. L. , Badial P. R. , Araujo-Junior J. P. , McCue M. E. , Borges A. S. 
Published: October 2019

AbstractMutations in the CLCN1 gene are the primary cause of non-dystrophic Hereditary Myotonia in several animal species. However, there are no reports of Hereditary Myotonia in pigs to date. Therefore, the objective of the present study was to characterize the clinical and molecular findings of Hereditary Myotonia in an inbred pedigree. The clinical, electromyographic, histopathological, and molecular findings were evaluated. Clinically affected pigs presented non-dystrophic recessive Hereditary Myotonia. Nucleotide sequence analysis of the entire coding region of the CLCN1 gene revealed the absence of the exons 15 and 16 in myotonic animals. Analysis of the genomic region flanking the deletion unveiled a large intragenic deletion of 4,165 nucleotides. Interestingly, non-related, non-myotonic pigs expressed transcriptional levels of an alternate transcript (i.e., X2) that was identical to the deleted X1 transcript of myotonic pigs. All myotonic pigs and their progenitors were homozygous recessive and heterozygous, respectively, for the 4,165-nucleotide deletion. This is the first study reporting Hereditary Myotonia in pigs and characterizing its clinical and molecular findings. Moreover, to the best of our knowledge, Hereditary Myotonia has never been associated with a genomic deletion in the CLCN1 gene in any other species.
Response of Coffee Farms to Hurricane Maria: Resistance and Resilience from an Extreme Climatic Event
Authors: Perfecto Ivette , Hajian-Forooshani Zachary , Iverson Aaron , Irizarry Amarilys D. , Lugo-Perez Javier , Medina Nicholas , Vaidya Chatura , White Alexa , Vandermeer John 
Published: October 2019

AbstractResistance and resilience have become important concepts in the evaluation of disturbance events, providing a framework that is useful in light of the expected increase in frequency and occurrences of hurricanes as a consequence of climate change. Hurricane Maria landed on Puerto Rico as a category 4 storm in September of 2017. Among the affected elements were agricultural systems, including coffee agroecosystems. Historically, coffee has been a major backbone of the island’s agricultural sector. Grown with a range of management styles, the coffee agroecosystem provides an excellent model system to study the resistance/resilience of agroecosystems faced with hurricane disturbance. Sampling 28 farms and comparing pre-hurricane data (2013) with post hurricane data we find that management style had only a small effect on either resistance or resilience, likely due to the especially strong nature of the storm. Rather, the socio-political context of individual farms seems to be a more useful predictor of resilience.
Large and tunable magnetocaloric effect in gadolinium-organic framework: tuning by solvent exchange
Authors: Zeleňák Vladimír , Almáši Miroslav , Zeleňáková Adriána , Hrubovčák Pavol , Tarasenko Róbert , Bourelly Sandrine , Llewellyn Philip 
Published: October 2019

AbstractMagnetic properties of three variants of MOF-76(Gd), {[Gd(BTC)(H2O)]·G}n (BTC = benzene-1,3,5-tricarboxylate, G = guest molecules) were investigated by static susceptibility, isothermal magnetization and specific heat capacity measurements. In the study we used as synthesized MOF-76(Gd)-DMF (1) (G = DMF = dimethylformamide), containing DMF molecules in the cavity system, compound MOF-76(Gd) (2), activated complex without solvents in the cavities and water exchanged sample MOF-76(Gd)-H2O (3). A pronounced change in the magnetic entropy was found near the critical temperature for all three compounds. It was shown, that magnetic entropy change depends on the solvatation of the MOF. The highest value entropy change, ΔSMpk(T) was observed for compound 2 (ΔSMpk(T) = 42 J kg−1 K−1 at 1.8 K for ΔH = 5 T). The ΔSMpk(T) for the compounds 1, 2 and 3 reached 81.8, 88.4 and 100% of the theoretical values, respectively. This suggests that in compound 3 Gd3+···Gd3+ antiferromagnetic interactions are decoupled gradually, and higher fields promote a larger decoupling between the individual spin centers. The observed entropy changes of compounds were comparable with other magnetic refrigerants proposed for low-temperature applications. To study the magnetothermal effect of 2 (the sample with largest −ΔSMpk), the temperature-dependent heat capacities (C) at different fields were measured. The value of magnetic entropy S obtained from heat capacities (39.5 J kg−1 K−1 at 1.8 K for an applied magnetic field change of 5 T) was in good agreement with that derived from the magnetization data (42 J kg−1 K−1 at 1.8 K).
Differential Treatments Based on Drug-induced Gene Expression Signatures and Longitudinal Systemic Lupus Erythematosus Stratification
Authors: Toro-Domínguez Daniel , Lopez-Domínguez Raúl , García Moreno Adrián , Villatoro-García Juan A. , Martorell-Marugán Jordi , Goldman Daniel , Petri Michelle , Wojdyla Daniel , Pons-Estel Bernardo A. , Isenberg David , Morales-Montes de Oca Gabriela , Trejo-Zambrano María Isabel , García González Benjamín , Rosetti Florencia , Gómez-Martín Diana , Romero-Díaz Juanita , Carmona-Sáez Pedro , Alarcón-Riquelme Marta E. 
Published: October 2019

AbstractSystemic lupus erythematosus (SLE) is a heterogeneous disease with unpredictable patterns of activity. Patients with similar activity levels may have different prognosis and molecular abnormalities. In this study, we aimed to measure the main differences in drug-induced gene expression signatures across SLE patients and to evaluate the potential for clinical data to build a machine learning classifier able to predict the SLE subset for individual patients. SLE transcriptomic data from two cohorts were compared with drug-induced gene signatures from the CLUE database to compute a connectivity score that reflects the capability of a drug to revert the patient signatures. Patient stratification based on drug connectivity scores revealed robust clusters of SLE patients identical to the clusters previously obtained through longitudinal gene expression data, implying that differential treatment depends on the cluster to which patients belongs. The best drug candidates found, mTOR inhibitors or those reducing oxidative stress, showed stronger cluster specificity. We report that drug patterns for reverting disease gene expression follow the cell-specificity of the disease clusters. We used 2 cohorts to train and test a logistic regression model that we employed to classify patients from 3 independent cohorts into the SLE subsets and provide a clinically useful model to predict subset assignment and drug efficacy.
A Low Cost and Portable Microwave Imaging System for Breast Tumor Detection Using UWB Directional Antenna array
Authors: Islam M. T. , Mahmud M. Z. , Islam M. Tarikul , Kibria S. , Samsuzzaman M. 
Published: October 2019

AbstractGlobally, breast cancer is a major reason for female mortality. Due to the limitations of current clinical imaging, the researchers are encouraged to explore alternative and complementary tools to available techniques to detect the breast tumor in an earlier stage. This article outlines a new, portable, and low-cost microwave imaging (MWI) system using an iterative enhancing technique for breast imaging. A compact side slotted tapered slot antenna is designed for microwave imaging. The radiating fins of tapered slot antenna are modified by etching nine rectangular side slots. The irregular slots on the radiating fins enhance the electrical length as well as produce strong directive radiation due to the suppression of induced surface currents that radiate vertically at the outer edges of the radiating arms with end-fire direction. It has remarkable effects on efficiency and gain. With the addition of slots, the side-lobe levels are reduced, the gain of the main-lobe is increased and corrects the squint effects simultaneously, thus improving the characteristics of the radiation. For experimental validation, a heterogeneous breast phantom was developed that contains dielectric properties identical to real breast tissues with the inclusion of tumors. An alternative PC controlled and microcontroller-based mechanical MWI system is designed and developed to collect the antenna scattering signal. The radiated backscattered signals from the targeted area of the human body are analyzed to reveal the changes in dielectric properties in tissues. The dielectric constants of tumorous cells are higher than that of normal tissues due to their higher water content. The remarkable deviation of the scattered field is processed by using newly proposed Iteratively Corrected Delay and Sum (IC-DAS) algorithm and the reconstruction of the image of the phantom interior is done. The developed UWB (Ultra-Wideband) antenna based MWI has been able to perform the detection of tumorous cells in breast phantom that can pave the way to saving lives.
Ag-AgCl Nanoparticles Fixation on Electrospun PVA Fibres: Technological Concept and Progress
Authors: Vilamová Zuzana , Konvičková Zuzana , Mikeš Petr , Holišová Veronika , Mančík Pavel , Dobročka Edmund , Kratošová Gabriela , Seidlerová Jana 
Published: October 2019

AbstractPolymer-metal based material with unique 3D structure is an attractive substrate for the development of biomedical applications. A novel preparation of the composite from polymer fibres and silver nanoparticles has been designed through: (1) preparation of silver nanoparticles by phytosynthesis and (2) incorporation of these nanoparticles in a fibrous membrane prepared by electrospinning. The nanoparticle biosynthesis was performed in a pure environmental-friendly, easy, static, bottom-up in vitro regime using Tilia sp. leachate. TEM and XRD depict the formation, stabilisation and encapsulation of crystalline silver (14 ± 9 nm) nanoparticles (NPs) in one simple step with low tendency to aggregate. We achieved successful incorporation in the uniform electrospun 221 ± 24 nm poly(vinylalcohol) fibres, and this confirms the possibility of its use in the biomedical field. Both SEM with EDX and TEM analysis determined fibre uniformity with the presence of silver NPs, and ICP-AES confirmed the relatively similar metal concentration throughout the triplicate measurement of fibre structures on the 2 × 2 cm area in the following manner: 0.303 ± 0.018 wt. %, 0.282 ± 0.017 wt. %, and 0.281 ± 0.017 wt. %. Our hypothesis is based on previously verified preparation of active silver NPs and the easily prepared PVA electrospun fibres which act as a water soluble matrix. The simple methodology of incorporating biosynthetically prepared NPs in the PVA fibers highlights the effectiveness of this material, with simple release from water-soluble PVA and final activation of the prepared NPs.
Empagliflozin and Dulaglutide are Effective against Obesity-induced Airway Hyperresponsiveness and Fibrosis in A Murine Model
Authors: Park Hye Jung , Han Heejae , Oh Eun-Yi , Kim Sung Ryeol , Park Kyung Hee , Lee Jae-Hyun , Park Jung-Won 
Published: October 2019

AbstractPatients with asthma with obesity experience severe symptoms, are unresponsive to conventional asthma treatment, and lack proper pharmacotherapy. Empagliflozin and dulaglutide, developed for diabetes, reduce weight, decrease insulin resistance, and exert additive effects. We evaluated the efficacy of empagliflozin, dulaglutide, and their combination on obesity-induced airway hyperresponsiveness (AHR) and lung fibrosis using a murine model. We assigned C57BL/6J mice to five groups: control, high-fat diet (HFD), and HFD with empagliflozin, dulaglutide, or both. Mice received a 12-week HFD, empagliflozin (5 days/week, oral gavage), and dulaglutide (once weekly, intraperitoneally). Both drugs significantly attenuated HFD-induced weight increase, abnormal glucose metabolism, and abnormal serum levels of leptin and insulin, and co-treatment was more effective. Both drugs significantly alleviated HFD-induced AHR, increased macrophages in bronchoalveolar lavage fluid (BALF), and co-treatment was more effective on AHR. HFD-induced lung fibrosis was decreased by both drugs alone and combined. HFD induced interleukin (IL)-17, transforming growth factor (TGF)-β1, and IL-1β mRNA and protein expression, which was significantly reduced by empagliflozin, dulaglutide, and their combination. Tumour necrosis factor (TNF)-α and IL-6 showed similar patterns without significant differences. HFD-enhanced T helper (Th) 1 and Th17 cell differentiation was improved by both drugs. Empagliflozin and dulaglutide could be a promising therapy for obesity-induced asthma and showed additive effects in combination.
Altered temporal sensitivity in obesity is linked to pro-inflammatory state
Authors: Scarpina Federica , Marzullo Paolo , Mai Stefania , Mauro Alessandro , Scacchi Massimo , Costantini Marcello 
Published: October 2019

AbstractTemporal sensitivity to multisensory stimuli has been shown to be reduced in obesity. We sought to investigate the possible role of the pro-inflammatory state on such alteration, considering the effect of the expression of markers, such as leptin and IL6, which are notably high in obesity. The performance of 15 male individuals affected by obesity and 15 normal-weight males was compared using two audiovisual temporal tasks, namely simultaneity judgment and temporal order judgment. Analyses of serum levels of inflammatory markers of leptin and IL6, and of neurotrophic factors of BDNF and S100SB were quantified. At the behavioral level we confirmed previous evidence showing poorer temporal sensitivity in obesity compared to normal-weight participants. Furthermore, leptin, that is a cytokine overexpressed in obesity, represented the best predictor of behavioral differences between groups in both tasks. The hypothesis we put forward is that the immune system, rather than overall cerebral dysfunction, might contribute to explain the altered temporal sensitivity in obesity. The present finding is discussed within the context of the role of cytokines on the brain mechanisms supporting temporal sensitivity.
Allergic rhinitis is a risk factor of gastro-esophageal reflux disease regardless of the presence of asthma
Authors: Kung Yu-Min , Tsai Pei-Yun , Chang Yu-Han , Wang Yao-Kuang , Hsieh Meng-Shu , Hung Chih-Hsing , Kuo Chao-Hung 
Published: October 2019

AbstractGastroesophageal reflux disease (GERD) can cause several upper airway symptoms and alter the physiology of nasopharyngeal mucosa, while upper airway diseases in turn might also exacerbate GERD symptoms. For a long time, asthma was considered a risk factor of GERD in the literature. Asthma and allergic rhinitis (AR) are usually identified as united airway disease according to similar epidemiology and pathophysiology; however, the association between AR and GERD is less elucidated. We aimed to evaluate whether AR would increase the development of GERD. Patients diagnosed as AR were identified from the National Health Insurance Research Database between January 1, 2000 and December 31, 2005 without prior history of gastroesophageal reflux disease. The outcome of interest was new-onset GERD. Cox regression models were applied to calculate the hazard ratio (HR) of GERD. We analyzed the data of 193,810 AR patients aged 18 years or older and being free of AR at baseline. The AR cohort (n = 96,905) had a significantly increased risk of GERD over a non-AR cohort (n = 96905) (adjusted HR (aHR) 1.94; 95% CI = 1.88–1.99, p < 0.001). AR may have stronger correlation with GERD than does asthma, although asthma might increase GERD risk by means of certain pathways shared with AR.
Mechanisms of soft tissue and protein preservation in Tyrannosaurus rex
Authors: Boatman Elizabeth M. , Goodwin Mark B. , Holman Hoi-Ying N. , Fakra Sirine , Zheng Wenxia , Gronsky Ronald , Schweitzer Mary H. 
Published: October 2019

AbstractThe idea that original soft tissue structures and the native structural proteins comprising them can persist across geological time is controversial, in part because rigorous and testable mechanisms that can occur under natural conditions, resulting in such preservation, have not been well defined. Here, we evaluate two non-enzymatic structural protein crosslinking mechanisms, Fenton chemistry and glycation, for their possible contribution to the preservation of blood vessel structures recovered from the cortical bone of a Tyrannosaurus rex (USNM 555000 [formerly, MOR 555]). We demonstrate the endogeneity of the fossil vessel tissues, as well as the presence of type I collagen in the outermost vessel layers, using imaging, diffraction, spectroscopy, and immunohistochemistry. Then, we use data derived from synchrotron FTIR studies of the T. rex vessels to analyse their crosslink character, with comparison against two non-enzymatic Fenton chemistry- and glycation-treated extant chicken samples. We also provide supporting X-ray microprobe analyses of the chemical state of these fossil tissues to support our conclusion that non-enzymatic crosslinking pathways likely contributed to stabilizing, and thus preserving, these T. rex vessels. Finally, we propose that these stabilizing crosslinks could play a crucial role in the preservation of other microvascular tissues in skeletal elements from the Mesozoic.
Relations of non-motor symptoms and dopamine transporter binding in REM sleep behavior disorder
Authors: Dušek Petr , Ibarburu Veronika Lorenzo y Losada , Bezdicek Ondrej , Dall’antonia Irene , Dostálová Simona , Kovalská Petra , Krupička Radim , Nepožitek Jiří , Nikolai Tomáš , Novotný Michal , Peřinová Pavla , Rusz Jan , Serranová Tereza , Tykalová Tereza , Ulmanová Olga , Mecková Zuzana , Ptáčník Václav , Trnka Jiří , Zogala David , Růžička Evžen , Šonka Karel 
Published: October 2019

AbstractThe aim of this study was to evaluate associations of motor and non-motor symptoms with dopamine transporter binding in prodromal stage of synucleinopathies. We examined 74 patients with idiopathic REM sleep behavior disorder (RBD), which is a prodromal synucleinopathy, and 39 controls using Movement Disorders Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), Montreal Cognitive Assessment, University of Pennsylvania Smell Identification Test (UPSIT), Farnsworth-Munsell 100 hue test, orthostatic test, Scales for Outcomes in PD-Autonomic, Beck depression inventory-II, State-Trait Anxiety Inventory, and video-polysomnography. Electromyographic muscle activity during REM sleep was quantified according to Sleep Innsbruck-Barcelona criteria. In 65 patients, dopamine transporter single-photon emission computed tomography (DAT-SPECT) imaging was performed, putaminal binding ratio was calculated and scans were classified as normal, borderline, or abnormal. Compared to controls, RBD patients had significantly more severe scores in all examined tests. Patients with abnormal DAT-SPECT had higher MDS-UPDRS motor score (p = 0.006) and higher prevalence of orthostatic hypotension (p = 0.008). Putaminal binding ratio was positively associated with UPSIT score (p = 0.03) and negatively associated with tonic (p = 0.003) and phasic (p = 0.01) muscle activity during REM sleep. These associations likely reflect simultaneous advancement of underlying pathology in substantia nigra and susceptible brainstem and olfactory nuclei in prodromal synucleinopathy.