bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pralatrexate in patients with recurrent or refractory peripheral T-cell lymphomas: a multicenter retrospective analysis
Authors: Hong Jung Yong , Yoon Dok Hyun , Yoon Sang Eun , Kim Seok Jin , Lee Ho Sup , Eom Hyeon-Seok , Lee Hye Won , Shin Dong-Yeop , Koh Youngil , Yoon Sung-Soo , Jo Jae-Cheol , Kim Jin Seok , Kim Soo-Jeong , Cho Su-Hee , Lee Won-Sik , Won Jong-Ho , Kim Won Seog , Suh Cheolwon 
Published: December 2019

AbstractPeripheral T-cell lymphomas (PTCL) are a heterogeneous group of non-Hodgkin’s lymphomas with poor clinical outcomes. Pralatrexate showed efficacy and safety in recurrent or refractory PTCLs. The purpose or this study was to investigate the efficacy and safety of pralatrexate in relapsed or refractory PTCLs in real-world practice. This was an observational, multicenter, retrospective analysis. Between December 2012 and December 2016, a total of 38 patients with relapsed or refractory PTCLs were treated with pralatrexate at 10 tertiary hospitals in Korea. Patients received an intravenous infusion of pralatrexate at a dose of 30 mg/m2/week for 6 weeks on a 7-week schedule. Modified dosing and/or scheduling was allowed according to institutional protocols. Median patient age was 58 years (range, 29–80 years) and the most common subtype was peripheral T-cell lymphoma, not otherwise specified (n = 23, 60.5%). The median dosage of pralatrexate per administration was 25.6 mg/m2/wk (range, 15.0–33.0 mg/m2/wk). In intention-to-treat analysis, 3 patients (7.9%) showed a complete response and 5 patients (13.2%) showed a partial response, resulting in an overall response rate (ORR) of 21.1%. The median duration of response was 7.6 months (range, 1.6–24.3 months). The median progression-free survival (PFS) was 1.8 months (95% confidence interval [CI], 1.7–1.8 months) and the median overall survival was 7.7 months (95% CI, 4.4–9.0 months). The most common grade 3/4 adverse events were thrombocytopenia (n = 13, 34.2%), neutropenia (n = 7, 23.7%), and anemia (n = 7, 18.4%). Our study showed relatively lower ORR and shorter PFS in patients with recurrent or refractory PTCLs treated with pralatrexate in real-world practice. The toxicity profile was acceptable and manageable. We also observed significantly lower dose intensity of pralatrexate in real-world practice.
Phenylethylamides derived from bacterial secondary metabolites specifically inhibit an insect serotonin receptor
Authors: Hasan Ariful , Yeom Hyun-Suk , Ryu Jaewook , Bode Helge B. , Kim Yonggyun 
Published: December 2019

AbstractSerotonin (5-hydroxytryptamine: 5-HT) is a biogenic monoamine that mediates immune responses and modulates nerve signal in insects. Se-5HTR, a specific receptor of serotonin, has been identified in the beet armyworm, Spodoptera exigua. It is classified into subtype 7 among known 5HTRs. Se-5HTR was expressed in all developmental stages of S. exigua. It was expressed in all tested tissues of larval stage. Its expression was up-regulated in hemocytes and fat body in response to immune challenge. RNA interference (RNAi) of Se-5HTR exhibited significant immunosuppression by preventing cellular immune responses such as phagocytosis and nodulation. Treatment with an inhibitor (SB-269970) specific to 5HTR subtype 7 resulted in significant immunosuppression. Furthermore, knockout mutant of Se-5HTR by CRISPR-Cas9 led to significant reduction of phagocytotic activity of S. exigua hemocytes. Such immunosuppression was also induced by bacterial secondary metabolites derived from Xenorhabdus and Photorhabdus. To determine specific bacterial metabolites inhibiting Se-5HTR, this study screened 37 bacterial secondary metabolites with respect to cellular immune responses associated with Se-5HTR and selected 10 potent inhibitors. These 10 selected compounds competitively inhibited cellular immune responses against 5-HT and shared phenylethylamide (PEA) chemical skeleton. Subsequently, 46 PEA derivatives were screened and resulting potent chemicals were used to design a compound to be highly inhibitory against Se-5HTR. The designed compound was chemically synthesized. It showed high immunosuppressive activities along with specific and competitive inhibition activity for Se-5HTR. This study reports the first 5HT receptor from S. exigua and provides its specific inhibitor designed from bacterial metabolites and their derivatives.
Concomitant febuxostat enhances methotrexate-induced hepatotoxicity by inhibiting breast cancer resistance protein
Authors: Ikemura Kenji , Hiramatsu Shun-ichi , Shinogi Yuri , Nakatani Yusuke , Tawara Isao , Iwamoto Takuya , Katayama Naoyuki , Okuda Masahiro 
Published: December 2019

AbstractMethotrexate (MTX) is an antifolate agent used for the treatment of various malignancies and is eliminated by breast cancer resistance protein (BCRP). Because febuxostat (FBX) is known to inhibit BCRP activity, FBX might exacerbate MTX-related adverse effects. In this study, we examined the drug-drug interaction between FBX and MTX in BCRP-expressing membrane vesicles. Moreover, we retrospectively investigated the impact of FBX on MTX-related adverse effects in 38 patients (144 cycles) receiving high-dose MTX therapy (HDMTX). The Food and Drug Administration Adverse Event Reporting System (FAERS) database and human hepatocellular carcinoma cell line HepG2 cells were used to evaluate the effects of FBX on MTX-induced hepatotoxicity. In the membrane vesicle study, FBX significantly inhibited BCRP-mediated transport of MTX. Concomitant FBX significantly increased the incidence of hepatotoxicity, but not of nephrotoxicity and hematological toxicity in patients receiving HDMTX. FAERS database analyses revealed that the reporting odds ratio of FBX for MTX-induced hepatotoxicity was 4.16 (95% CI: 2.89–5.98). Co-incubated FBX significantly decreased the cell viability and increased cytotoxicity in MTX-treated HepG2 cells. These findings suggest that concomitant FBX enhances MTX-induced hepatotoxicity by inhibiting hepatic BCRP. These findings provide important information for the safe management of HDMTX therapy in clinical settings.
Nervous system-wide profiling of presynaptic mRNAs reveals regulators of associative memory
Authors: Arey Rachel N. , Kaletsky Rachel , Murphy Coleen T. 
Published: December 2019

AbstractPresynaptic protein synthesis is important in the adult central nervous system; however, the nervous system-wide set of mRNAs localized to presynaptic areas has yet to be identified in any organism. Here we differentially labeled somatic and synaptic compartments in adult C. elegans with fluorescent proteins, and isolated synaptic and somatic regions from the same population of animals. We used this technique to determine the nervous system-wide presynaptic transcriptome by deep sequencing. Analysis of the synaptic transcriptome reveals that synaptic transcripts are predicted to have specialized functions in neurons. Differential expression analysis identified 542 genes enriched in synaptic regions relative to somatic regions, with synaptic functions conserved in higher organisms. We find that mRNAs for pumilio RNA-binding proteins are abundant in synaptic regions, which we confirmed through high-sensitivity in situ hybridization. Presynaptic PUMILIOs regulate associative memory. Our approach enables the identification of new mechanisms that regulate synaptic function and behavior.
Using transfer learning from prior reference knowledge to improve the clustering of single-cell RNA-Seq data
Authors: Mieth Bettina , Hockley James R. F. , Görnitz Nico , Vidovic Marina M.-C. , Müller Klaus-Robert , Gutteridge Alex , Ziemek Daniel 
Published: December 2019

AbstractIn many research areas scientists are interested in clustering objects within small datasets while making use of prior knowledge from large reference datasets. We propose a method to apply the machine learning concept of transfer learning to unsupervised clustering problems and show its effectiveness in the field of single-cell RNA sequencing (scRNA-Seq). The goal of scRNA-Seq experiments is often the definition and cataloguing of cell types from the transcriptional output of individual cells. To improve the clustering of small disease- or tissue-specific datasets, for which the identification of rare cell types is often problematic, we propose a transfer learning method to utilize large and well-annotated reference datasets, such as those produced by the Human Cell Atlas. Our approach modifies the dataset of interest while incorporating key information from the larger reference dataset via Non-negative Matrix Factorization (NMF). The modified dataset is subsequently provided to a clustering algorithm. We empirically evaluate the benefits of our approach on simulated scRNA-Seq data as well as on publicly available datasets. Finally, we present results for the analysis of a recently published small dataset and find improved clustering when transferring knowledge from a large reference dataset. Implementations of the method are available athttps://github.com/nicococo/scRNA.
Modeling Electrical Percolation to optimize the Electromechanical Properties of CNT/Polymer Composites in Highly Stretchable Fiber Strain Sensors
Authors: Jung Sungmin , Choi Hyung Woo , Mocanu Felix Cosmin , Shin Dong-Wook , Chowdhury Mohamed Foysol , Han Soo Deok , Suh Yo-Han , Cho Yuljae , Lee Hanleem , Fan Xiangbing , Bang Sang Yun , Zhan Shijie , Yang Jiajie , Hou Bo , Chun Young Tea , Lee Sanghyo , Occhipinti Luigi Giuseppe , Kim Jong Min 
Published: December 2019

AbstractA simulation model of electrical percolation through a three-dimensional network of curved CNTs is developed in order to analyze the electromechanical properties of a highly stretchable fiber strain sensor made of a CNT/polymer composite. Rigid-body movement of the curved CNTs within the polymer matrix is described analytically. Random arrangements of CNTs within the composite are generated by a Monte-Carlo simulation method and a union-find algorithm is utilized to investigate the network percolation. Consequently, the strain-induced resistance change curves are obtained in a wide strain range of the composite. In order to compare our model with experimental results, two CNT/polymer composite fibers were fabricated and tested as strain sensors. Their effective CNT volume fractions are estimated by comparing the experimental data with our simulation model. The results confirm that the proposed simulation model reproduces well the experimental data and is useful for predicting and optimizing the electromechanical characteristics of highly stretchable fiber strain sensors based on CNT/polymer composites.
Duplication and parallel evolution of the pancreatic ribonuclease gene (RNASE1) in folivorous non-colobine primates, the howler monkeys (Alouatta spp.)
Authors: Janiak Mareike C. , Burrell Andrew S. , Orkin Joseph D. , Disotell Todd R. 
Published: December 2019

AbstractIn foregut-fermenting mammals (e.g., colobine monkeys, artiodactyl ruminants) the enzymes pancreatic ribonuclease (RNASE1) and lysozyme C (LYZ), originally involved in immune defense, have evolved new digestive functions. Howler monkeys are folivorous non-colobine primates that lack the multi-chambered stomachs of colobines and instead digest leaves using fermentation in the caeco-colic region. We present data on the RNASE1 and LYZ genes of four species of howler monkey (Alouatta spp.). We find that howler monkey LYZ is conserved and does not share the substitutions found in colobine and cow sequences, whereas RNASE1 was duplicated in the common ancestor of A. palliata, A. seniculus, A. sara, and A. pigra. While the parent gene (RNASE1) is conserved, the daughter gene (RNASE1B) has multiple amino acid substitutions that are parallel to those found in RNASE1B genes of colobines. The duplicated RNase in Alouatta has biochemical changes similar to those in colobines, suggesting a novel, possibly digestive function. These findings suggest that pancreatic ribonuclease has, in parallel, evolved a new role for digesting the products of microbial fermentation in both foregut- and hindgut-fermenting folivorous primates. This may be a vital digestive enzyme adaptation allowing howler monkeys to survive on leaves during periods of low fruit availability.
Transcriptomic changes during TGF-β-mediated differentiation of airway fibroblasts to myofibroblasts
Authors: Walker Erin Joanne , Heydet Deborah , Veldre Timothy , Ghildyal Reena 
Published: December 2019

AbstractAsthma is the most common chronic lung disease in children and young adults worldwide. Airway remodelling (including increased fibroblasts and myofibroblasts in airway walls due to chronic inflammation) differentiates asthmatic from non-asthmatic airways. The increase in airway fibroblasts and myofibroblasts occurs via epithelial to mesenchymal transition (EMT) where epithelial cells lose their tight junctions and are transdifferentiated to mesenchymal cells, with further increases in myofibroblasts occurring via fibroblast-myofibroblast transition (FMT). Transforming growth factor (TGF)-β is the central EMT- and FMT-inducing cytokine. In this study, we have used next generation sequencing to delineate the changes in the transcriptome induced by TGF-β treatment of WI-38 airway fibroblasts in both the short term and after differentiation into myofibroblasts, to gain an understanding of the contribution of TGF-β induced transdifferentiation to the asthmatic phenotype. The data obtained from RNAseq analysis was confirmed by quantitative PCR (qPCR) and protein expression investigated by western blotting. As expected, we found that genes coding for intermediates in the TGF-β signalling pathways (SMADs) were differentially expressed after TGF-β treatment, SMAD2 being upregulated and SMAD3 being downregulated as expected. Further, genes involved in cytoskeletal pathways (FN1, LAMA, ITGB1) were upregulated in myofibroblasts compared to fibroblasts. Importantly, genes that were previously shown to be changed in asthmatic lungs (ADAMTS1, DSP, TIMPs, MMPs) were similarly differentially expressed in myofibroblasts, strongly suggesting that TGF-β mediated differentiation of fibroblasts to myofibroblasts may underlie important changes in the asthmatic airway. We also identified new intermediates of signalling pathways (PKB, PTEN) that are changed in myofibroblasts compared to fibroblasts. We have found a significant number of genes that are altered after TGF-β induced transdifferentiation of WI-38 fibroblasts into myofibroblasts, many of which were expected or predicted. We also identified novel genes and pathways that were affected after TGF-β treatment, suggesting additional pathways are activated during the transition between fibroblasts and myofibroblasts and may contribute to the asthma phenotype.
Age-related changes of individual macular retinal layers among Asians
Authors: Chua Jacqueline , Tham Yih Chung , Tan Bingyao , Devarajan Kavya , Schwarzhans Florian , Gan Alfred , Wong Damon , Cheung Carol Y. , Majithia Shivani , Thakur Sahil , Fischer Georg , Vass Clemens , Cheng Ching-Yu , Schmetterer Leopold 
Published: December 2019

AbstractWe characterized the age-related changes of the intra-retinal layers measured with spectral-domain optical coherence tomography (SD-OCT; Cirrus high-definition OCT [Carl Zeiss Meditec]. The Singapore Epidemiology of Eye Diseases is a population-based, cross-sectional study of Chinese, Malays and Indians living in Singapore. Iowa Reference Algorithms (Iowa Institute for Biomedical Imaging) were used for intra-retinal layer segmentation and mean thickness of 10 intra-retinal layers rescaled with magnification correction using axial length value. Linear regression models were performed to investigate the association of retinal layers with risk factors. After excluding participants with history of diabetes or ocular diseases, high-quality macular SD-OCT images were available for 2,047 participants (44–89 years old). Most of the retinal layers decreased with age except for foveal retinal nerve fiber layer (RNFL) and the inner/outer segments of photoreceptors where they increased with age. Men generally had thicker retinal layers than women. Chinese have the thickest RNFL and retinal pigment epithelium amongst the ethnic groups. Axial length and refractive error remained correlated with retinal layers in spite of magnification correction. Our data show pronounced age-related changes in retinal morphology. Age, gender, ethnicity and axial length need be considered when establishing OCT imaging biomarkers for ocular or systemic disease.
Microbiology of Cystic Fibrosis Airway Disease
Authors: Blanchard Ana C. , Waters Valerie J. 
Published: December 2019

AbstractAlthough survival of individuals with cystic fibrosis (CF) has been continuously improving for the past 40 years, respiratory failure secondary to recurrent pulmonary infections remains the leading cause of mortality in this patient population. Certain pathogens such as Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus, and species of the Burkholderia cepacia complex continue to be associated with poorer clinical outcomes including accelerated lung function decline and increased mortality. In addition, other organisms such as anaerobes, viruses, and fungi are increasingly recognized as potential contributors to disease progression. Culture-independent molecular methods are also being used for diagnostic purposes and to examine the interaction of microorganisms in the CF airway. Given the importance of CF airway infections, ongoing initiatives to promote understanding of the epidemiology, clinical course, and treatment options for these infections are needed.
High-Content Immunophenotyping and Hierarchical Clustering Reveal Sources of Heterogeneity and New Surface Markers of Human Blood Monocyte Subsets
Authors: Hoffmann Jedrzej , Fišer Karel , Liebetrau Christoph , Staubach Nora , Kost David , Voss Sandra , Heiden Annkathrin zur , Dörr Oliver , Lipps Christoph , Nef Holger M. , Möllmann Helge , Hamm Christian W. , Keller Till , Troidl Christian 
Published: December 2019

Abstract
Objective Blood monocyte subsets are emerging as biomarkers of cardiovascular inflammation. However, our understanding of human monocyte heterogeneity and their immunophenotypic features under healthy and inflammatory conditions is still evolving.
Rationale In this study, we sought to investigate the immunophenome of circulating human monocyte subsets.
Methods Multiplexed, high-throughput flow cytometry screening arrays and computational data analysis were used to analyze the expression and hierarchical relationships of 242 specific surface markers on circulating classical (CD14++CD16−), intermediate (CD14++CD16+), and nonclassical (CD14+CD16++) monocytes in healthy adults.
Results Using generalized linear models and hierarchical cluster analysis, we selected and clustered epitopes that most reliably differentiate between monocyte subsets. We validated existing transcriptional profiling data and revealed potential new surface markers that uniquely define the classical (e.g., BLTR1, CD35, CD38, CD49e, CD89, CD96), intermediate (e.g., CD39, CD275, CD305, CDw328), and nonclassical (e.g., CD29, CD132) subsets. In addition, our analysis revealed phenotypic cell clusters, identified by dendritic markers CMRF-44 and CMRF-56, independent of the traditional monocyte classification.
Conclusion These results reveal an advancement of the clinically applicable multiplexed screening arrays that may facilitate monocyte subset characterization and cytometry-based biomarker selection in various inflammatory disorders.
Organ Transplantation for Cystic Fibrosis
Authors: Morrell Matthew R. , Kiel Sarah C. , Pilewski Joseph M. 
Published: December 2019

AbstractCystic fibrosis (CF) remains the most common indication for lung transplantation in children and the third most common in adults and has the highest median survival posttransplant for all pretransplant diagnoses. Criteria for transplant in patients with CF vary widely among transplant centers and early referral to multiple centers may be needed to maximize opportunities for lung transplantation. Comorbidities unique to CF such as resistant and atypical pathogens like Burkholderia and Mycobacterium abscessus, and cirrhosis require special consideration for lung transplantation but should not be considered as absolute contraindications. For those patients who are listed for lung transplantation, mechanical support with extracorporeal membrane oxygenation and mechanical ventilation can be efficacious as bridges to lung transplantation in experienced centers with adequate resources. Liver and pancreas transplantations are also acceptable options for end-organ disease related to CF and can provide improvements in both quantity and quality of life.
Adult Care in Cystic Fibrosis
Authors: Elborn J. Stuart 
Published: December 2019

AbstractCystic fibrosis (CF) is now more common in adults than children in countries with well-developed health care systems. The number of adults continues to increase and will further increase if the new cystic fibrosis transmembrane conductance regulator (CFTR) modulators are disease modifying. Most of the complex morbidity and almost all the mortality of CF occur in adults and will increasingly follow this pattern even with new effective modulator therapies. Maintaining good quality of life including social functioning and maximizing survival for adults are the key priorities. This requires a highly knowledgeable and adaptable multidisciplinary team, which, though focused on maintaining lung health, requires an increasing range of other disciplines and specialties to maximize well-being. Changes in health care systems will require current models of care to adapt to provide care for the large number of adult patients. With increasing survival and age, many are likely to have both CF morbidities and additional diseases of aging. New models are needed for health care delivery for this expanding population with complex medical conditions.
Aspirin Therapy for Primary Prevention: The Case for Continuing Prescribing to Patients at High Cardiovascular Risk—A Review
Authors: De Caterina Raffaele , Aimo Alberto , Ridker Paul M. 
Published: December 2019

AbstractCurrent evidence supports the use of low-dose aspirin for secondary cardiovascular prevention. By contrast, the benefit-to-risk ratio of aspirin use in primary prevention is debated: three contemporary randomized control trials have been conflicting, and meta-analyses have concluded for an unclear clinical benefit, based on the consideration that the reduction in thromboembolic events is counterbalanced by increased bleeding. The primary prevention setting is, however, a heterogeneous mix of subjects at highly variable cardiovascular risk. One possible explanation for the uncertainty of data interpretation is the progressive reduction in risk of major adverse cardiovascular events (MACEs) in primary prevention that has accompanied global education programs, leading patients to smoke less, exercise more, and increasingly take lipid-lowering therapies. Based on a meta-regression of the benefits and harm of aspirin therapy in primary prevention as a function of the 10-year risk of MACE, we favor a nuanced approach still, however, based on the evaluation of cardiovascular risk, acknowledging differences between patients and emphasizing an individualized assessment of both benefits and harm. After optimal control of cardiovascular risk factors, and when patients are less than 70 years of age, clinicians should assess the risk of MACE and base decision on such stratification, considering the risk of bleeding and patient preferences. Clinicians would then advise the use of aspirin in primary prevention patients at the highest risk of MACE who do not have a prohibitive risk of bleeding, and in the majority of cases after initiation of properly titrated statin therapy.