bluuebunny/crossref_metadata_2025_split huggingface dataset:
Implementing international law: An avenue for preventing disappearances, resolving cases of missing persons and addressing the needs of their families
Authors: Londoño Ximena , Ortiz Signoret Alexandra 
Published: November 2018

AbstractInternational humanitarian law and international human rights law seek to prevent people from going missing, and to clarify the fate and whereabouts of those who do go missing while upholding the right to know of their relatives. When implementing international law at the domestic level, national authorities should plan carefully before engaging in any policy or legal reform that will address the issue of missing persons and the response to the needs of their families. This article seeks to present a general overview of the provisions of international law that are relevant to understanding the role of national implementation vis-à-vis the clarification of the fate and whereabouts of missing persons and the response to the needs of their relatives. It also presents the role that the ICRC has played in this regard and highlights three challenges that may arise at the national level when working on legal and policy reforms.
Loss of oocyte Rps26 in mice arrests oocyte growth and causes premature ovarian failure
Authors: Liu Xiao-Man , Yan Ming-Qi , Ji Shu-Yan , Sha Qian-Qian , Huang Tao , Zhao Han , Liu Hong-Bin , Fan Heng-Yu , Chen Zi-Jiang 
Published: November 2018

AbstractGlobal transcriptional activity increases as oocytes grow and is silenced in fully grown oocytes. Thus, the chromatin configuration varies during oocyte growth, but the molecular mechanisms regulating these changes remain to be clarified. Here, we studied a susceptibility gene of polycystic ovary syndrome (PCOS), RPS26, which is a ribosomal protein-encoding gene that is highly expressed in the ovary, but the functions of which remain unknown. Specific knockout of Rps26 in mouse oocytes resulted in retarded follicle development from pre-antral follicles to antral follicles, while the chromatin configurations of the oocytes were arrested at the transition from the non-surrounded nucleolus (NSN) to surrounded nucleolus (SN)-type. As a consequence, all oocytes died by postnatal day 84 resulting in premature ovarian failure (POF). Loss of Rps26 in oocytes led to decreased mRNA transcription and low levels of histone trimethylation on H3K4/H3K9 and DNA methylation at 5-cytosine, high levels of which are required for oocytes to transform from NSN to SN-type. Low protein levels of oocyte-derived growth differentiation factor 9, bone morphogenetic protein 15, and the oocyte-granulosa cell gap junction protein connexin 37 inhibited oocyte growth and retarded follicle development. The disruption of the phosphoinositide 3-kinase/protein kinase B/Forkhead box O-3a pathway contributed to oocyte death and follicle atresia. These results provide genetic clues for the clinical diagnosis of POF, especially in PCOS patients without treatment.
Topoisomerase 3β interacts with RNAi machinery to promote heterochromatin formation and transcriptional silencing in Drosophila
Authors: Lee Seung Kyu , Xue Yutong , Shen Weiping , Zhang Yongqing , Joo Yuyoung , Ahmad Muzammil , Chinen Madoka , Ding Yi , Ku Wai Lim , De Supriyo , Lehrmann Elin , Becker Kevin G. , Lei Elissa P. , Zhao Keji , Zou Sige , Sharov Alexei , Wang Weidong 
Published: November 2018

AbstractTopoisomerases solve topological problems during DNA metabolism, but whether they participate in RNA metabolism remains unclear. Top3β represents a family of topoisomerases carrying activities for both DNA and RNA. Here we show that in Drosophila, Top3β interacts biochemically and genetically with the RNAi-induced silencing complex (RISC) containing AGO2, p68 RNA helicase, and FMRP. Top3β and RISC mutants are similarly defective in heterochromatin formation and transcriptional silencing by position-effect variegation assay. Moreover, both Top3β and AGO2 mutants exhibit reduced levels of heterochromatin protein HP1 in heterochromatin. Furthermore, expression of several genes and transposable elements in heterochromatin is increased in the Top3β mutant. Notably, Top3β mutants defective in either RNA binding or catalytic activity are deficient in promoting HP1 recruitment and silencing of transposable elements. Our data suggest that Top3β may act as an RNA topoisomerase in siRNA-guided heterochromatin formation and transcriptional silencing.
Deep learning for universal linear embeddings of nonlinear dynamics
Authors: Lusch Bethany , Kutz J. Nathan , Brunton Steven L. 
Published: November 2018

AbstractIdentifying coordinate transformations that make strongly nonlinear dynamics approximately linear has the potential to enable nonlinear prediction, estimation, and control using linear theory. The Koopman operator is a leading data-driven embedding, and its eigenfunctions provide intrinsic coordinates that globally linearize the dynamics. However, identifying and representing these eigenfunctions has proven challenging. This work leverages deep learning to discover representations of Koopman eigenfunctions from data. Our network is parsimonious and interpretable by construction, embedding the dynamics on a low-dimensional manifold. We identify nonlinear coordinates on which the dynamics are globally linear using a modified auto-encoder. We also generalize Koopman representations to include a ubiquitous class of systems with continuous spectra. Our framework parametrizes the continuous frequency using an auxiliary network, enabling a compact and efficient embedding, while connecting our models to decades of asymptotics. Thus, we benefit from the power of deep learning, while retaining the physical interpretability of Koopman embeddings.
Autophagy is a gatekeeper of hepatic differentiation and carcinogenesis by controlling the degradation of Yap
Authors: Lee Youngmin A. , Noon Luke A. , Akat Kemal M. , Ybanez Maria D. , Lee Ting-Fang , Berres Marie-Luise , Fujiwara Naoto , Goossens Nicolas , Chou Hsin-I , Parvin-Nejad Fatemeh P. , Khambu Bilon , Kramer Elisabeth G. M. , Gordon Ronald , Pfleger Cathie , Germain Doris , John Gareth R. , Campbell Kirk N. , Yue Zhenyu , Yin Xiao-Ming , Cuervo Ana Maria , Czaja Mark J. , Fiel M. Isabel , Hoshida Yujin , Friedman Scott L. 
Published: November 2018

AbstractActivation of the Hippo pathway effector Yap underlies many liver cancers, however no germline or somatic mutations have been identified. Autophagy maintains essential metabolic functions of the liver, and autophagy-deficient murine models develop benign adenomas and hepatomegaly, which have been attributed to activation of the p62/Sqstm1-Nrf2 axis. Here, we show that Yap is an autophagy substrate and mediator of tissue remodeling and hepatocarcinogenesis independent of the p62/Sqstm1-Nrf2 axis. Hepatocyte-specific deletion of Atg7 promotes liver size, fibrosis, progenitor cell expansion, and hepatocarcinogenesis, which is rescued by concurrent deletion of Yap. Our results shed new light on mechanisms of Yap degradation and the sequence of events that follow disruption of autophagy, which is impaired in chronic liver disease.
Entropy production rate is maximized in non-contractile actomyosin
Authors: Seara Daniel S. , Yadav Vikrant , Linsmeier Ian , Tabatabai A. Pasha , Oakes Patrick W. , Tabei S. M. Ali , Banerjee Shiladitya , Murrell Michael P. 
Published: November 2018

AbstractThe actin cytoskeleton is an active semi-flexible polymer network whose non-equilibrium properties coordinate both stable and contractile behaviors to maintain or change cell shape. While myosin motors drive the actin cytoskeleton out-of-equilibrium, the role of myosin-driven active stresses in the accumulation and dissipation of mechanical energy is unclear. To investigate this, we synthesize an actomyosin material in vitro whose active stress content can tune the network from stable to contractile. Each increment in activity determines a characteristic spectrum of actin filament fluctuations which is used to calculate the total mechanical work and the production of entropy in the material. We find that the balance of work and entropy does not increase monotonically and the entropy production rate is maximized in the non-contractile, stable state of actomyosin. Our study provides evidence that the origins of entropy production and activity-dependent dissipation relate to disorder in the molecular interactions between actin and myosin.
Diversity and predictive metabolic pathways of the prokaryotic microbial community along a groundwater salinity gradient of the Pearl River Delta, China
Authors: Sang Shilei , Zhang Xiaoying , Dai Heng , Hu Bill X. , Ou Hao , Sun Liwei 
Published: November 2018

AbstractAlmost half of the groundwater in the Pearl River Delta (PRD) contains salt water originally derived from paleo-seawater due to the Holocene transgression, which then generates intense physicochemical gradients in the mixing zone between freshwater and saltwater. Although some studies have been conducted on the hydrological and geochemical characteristics of groundwater in the PRD to monitor the intrusion of seawater, little attention has been paid to the microbial community of this particular region. In this study, we implemented a high-throughput sequencing analysis to characterize the microbial communities along a salinity gradient in the PRD aquifer, China. Our results indicated that the microbial community composition varied significantly depending on the salinity of the aquifer. The presence of abundant anaerobic microorganisms of the genera Desulfovibrio and Methanococcus in certain saltwater samples may be responsible for the gas generation of H2S and CH4 in the stratum. In saline water samples (TDS > 10 g/L), the linear discriminant analysis effect size (LEfSe) analysis found two biomarkers that usually live in marine environments, and the aquifers of the PRD still contained large quantity of saltwater, indicating that the impact of the paleo-seawater has lasted to this day. The predictive metagenomic analysis revealed that the metabolic pathways present in the groundwater samples studied, included the degradation of pesticides and refractory organics (dichlorodiphenyltrichloroethane (DDT), atrazine and polycyclic aromatic hydrocarbons), matter cycling (methane, nitrogen and sulfur), and inorganic ion and mineral metabolites. This study can help enhance our understanding of the composition of the microbial assemblages and its implications as an environmental indicator in an aquifer affected by saltwater intrusion.
Whole genome amplification of cell-free DNA enables detection of circulating tumor DNA mutations from fingerstick capillary blood
Authors: Gyanchandani Rekha , Kvam Erik , Heller Ryan , Finehout Erin , Smith Nicholas , Kota Karthik , Nelson John R. , Griffin Weston , Puhalla Shannon , Brufsky Adam M. , Davidson Nancy E. , Lee Adrian V. 
Published: November 2018

AbstractThe ability to measure mutations in plasma cell-free DNA (cfDNA) has the potential to revolutionize cancer surveillance and treatment by enabling longitudinal monitoring not possible with solid tumor biopsies. However, obtaining sufficient quantities of cfDNA remains a challenge for assay development and clinical translation; consequently, large volumes of venous blood are typically required. Here, we test proof-of-concept for using smaller volumes via fingerstick collection. Matched venous and fingerstick blood were obtained from seven patients with metastatic breast cancer. Fingerstick blood was separated at point-of-care using a novel paper-based concept to isolate plasma centrifuge-free. Patient cfDNA was then analyzed with or without a new method for whole genome amplification via rolling-circle amplification (WG-RCA). We identified somatic mutations by targeted sequencing and compared the concordance of mutation detection from venous and amplified capillary samples by droplet-digital PCR. Patient mutations were detected with 100% concordance after WG-RCA, although in some samples, allele frequencies showed greater variation likely due to differential amplification or primer inaccessibility. These pilot findings provide physiological evidence that circulating tumor DNA is accessible by fingerstick and sustains presence/absence of mutation detection after whole-genome amplification. Further refinement may enable simpler and less-invasive methods for longitudinal or theranostic surveillance of metastatic cancer.
Feature Ranking in Predictive Models for Hospital-Acquired Acute Kidney Injury
Authors: Wu Lijuan , Hu Yong , Liu Xiaoxiao , Zhang Xiangzhou , Chen Weiqi , Yu Alan S. L. , Kellum John A. , Waitman Lemuel R. , Liu Mei 
Published: November 2018

AbstractAcute Kidney Injury (AKI) is a common complication encountered among hospitalized patients, imposing significantly increased cost, morbidity, and mortality. Early prediction of AKI has profound clinical implications because currently no treatment exists for AKI once it develops. Feature selection (FS) is an essential process for building accurate and interpretable prediction models, but to our best knowledge no study has investigated the robustness and applicability of such selection process for AKI. In this study, we compared eight widely-applied FS methods for AKI prediction using nine-years of electronic medical records (EMR) and examined heterogeneity in feature rankings produced by the methods. FS methods were compared in terms of stability with respect to data sampling variation, similarity between selection results, and AKI prediction performance. Prediction accuracy did not intrinsically guarantee the feature ranking stability. Across different FS methods, the prediction performance did not change significantly, while the importance rankings of features were quite different. A positive correlation was observed between the complexity of suitable FS method and sample size. This study provides several practical implications, including recognizing the importance of feature stability as it is desirable for model reproducibility, identifying important AKI risk factors for further investigation, and facilitating early prediction of AKI.
Host-specific signatures of the cell wall changes induced by the plant parasitic nematode, Meloidogyne incognita
Authors: Bozbuga Refik , Lilley Catherine J. , Knox J. Paul , Urwin Peter E. 
Published: November 2018

AbstractRoot-knot nematodes (Meloidogyne spp.) are an important group of plant parasitic nematodes that induce within host plant roots unique feeding site structures, termed giant cells, which supply nutrient flow to the nematode. A comparative in situ analysis of cell wall polysaccharides in the giant cells of three host species (Arabidopsis, maize and aduki bean) infected with Meloidogyne incognita has been carried out. Features common to giant cell walls of all three species include the presence of high-esterified pectic homogalacturonan, xyloglucan and pectic arabinan. The species-specific presence of xylan and mixed-linkage glucan (MLG) epitopes in giant cell walls of maize reflected that host’s taxonomic group. The LM5 galactan and LM21 mannan epitopes were not detected in the giant cell walls of aduki bean but were detected in Arabidopsis and maize giant cell walls. The LM2 arabinogalactan-protein epitope was notable for its apparent global variations in root cell walls as a response to infection across the three host species. Additionally, a set of Arabidopsis cell wall mutants were used to determine any impacts of altered cell wall structures on M. incognita infection. Disruption of the arabinogalactan-protein 8 gene had the greatest impact and resulted in an increased infection rate.
Cytokine and Chemokine Concentrations as Biomarkers of Feline Mycobacteriosis
Authors: O’Halloran C. , McCulloch L. , Rentoul L. , Alexander J. , Hope J. C. , Gunn-Moore D. A. 
Published: November 2018

AbstractMycobacteriosis is an emerging zoonotic disease of domestic cats and timely, accurate diagnosis is currently challenging. To identify differential cytokine/chemokine concentrations in serum/plasma of cats, which could be diagnostic biomarkers of infection we analysed plasma/serum from 116 mycobacteria-infected cats, 16 healthy controls and six cats hospitalised for unrelated reasons was analysed using the Milliplex MAP Feline Cytokine Magnetic Bead multiplex assay. Three cytokines; sFAS, IL-13 and IL-4 were reduced while seven; GM-CSF, IL-2, PDGF-BB, IL-8, KC, RANTES and TNF-α were elevated in mycobacteria-infected cats compared to healthy controls. However, IL-8 and KC concentrations were not significantly different from cats hospitalised for other reasons. Elevations in TNF-α and PDGF-BB may have potential to identify M. bovis and M. microti infected cats specifically while GM-CSF, IL-2 and FLT3L were increased in MTBC infected cats. This study demonstrates potential use of feline tuberculosis as a spontaneously occurring model of this significant human disease. Cytokine profiling has clear diagnostic potential for mycobacteriosis of cats and could be used discriminate tuberculous from non-tuberculous disease to rapidly inform on zoonotic risk. Future work should focus on the in-field utility of these findings to establish diagnostic sensitivity and specificity of these markers.
L-Proline functionalized magnetic nanoparticles: A novel magnetically reusable nanocatalyst for one-pot synthesis of 2,4,6-triarylpyridines
Authors: Maleki Ali , Firouzi-Haji Razieh 
Published: November 2018

AbstractIn this work, an efficient method for the immobilization of L-proline on magnetic nanoparticles was offered and evaluated as a recoverable magnetic nanocatalyst for synthesis of 2,4,6-triarylpyridines through one-pot three-component reaction of acetophenone, aryl aldehydes and ammonium acetate. This article is the first report of the catalytic application of L-proline functionalized magnetic nanoparticles in organic reactions as a magnetic nanocatalyst. This novel magnetic nanocatalyst proved to be effective and provided the products in high to excellent yield under solvent-free conditions. The structure of obtained nanoparticles was characterized by Fourier transform infrared spectrophotometry (FT-IR), field-emission scanning electron microscopy (FE-SEM), thermogravimetric analysis (TGA) and energy-dispersive X-ray spectroscopy (EDX). TGA result revealed that it is stable up to 200 °C for using as a catalyst in organic reactions. FE-SEM image of the synthesized nanocatalyst showed that it has nearly core-shell spherical shape and uniform size distribution with an average size about 80 nm. Moreover, the catalyst could be easily recovered by facile separation by magnetic forces and recycled for several times without significant loss of its catalytic activity. The benefits of this study are simplicity, nontoxicity, low cost, simple workup, and an environmentally benign nature.
I-BET151 suppresses osteoclast formation and inflammatory cytokines secretion by targetting BRD4 in multiple myeloma
Authors: Guo Ning-Hong , Zheng Ji-Fu , Zi Fu-Ming , Cheng Jing 
Published: November 2018

Abstract
Background: Multiple myeloma (MM) is an incurable hematologic cancer, accompanied by excessive osteoclast formation and inflammatory cytokine secretion. The mechanisms by which bromodomain and extra-terminal domain (BET) protein inhibitor I-BET151 regulates osteoclast differentiation and inflammatory cytokine secretion in MM are largely unknown. Methods: The isolated peripheral blood mononuclear cells from normal or patients with MM were treated with receptor activator of NF-κB ligand (RANKL) and M-CSF to induce osteoclast differentiation. RAW 264.7 cells were treated with RANKL. I-BET151 was applied to investigate the effects of BRD4 inhibition on osteoclast formation and inflammatory cytokine secretion. Osteoclast formation was determined by tartrate-resistant acid phosphatase (TRACP) staining. The expression of osteoclast-specific genes TRACP, matrix metalloproteinase-9 (MMP-9), cathepsin K (Ctsk), and c-Src was tested using quantitative real-time PCR. And the level of inflammatory cytokines TNF-α, IL-1β, and IL-6 was assessed by ELISA. Tumor necrosis factor receptor-associated factor 6 (TRAF6), BRD4, nuclear and cytoplasm p65, IκB-α, nuclear factor of activated T cells cytoplasmic (NFATc1), and osteoprotegerin (OPG) expression were measured by Western blotting. RNAi technology was applied to knock down BET family member BRD4. Results: I-BET151 dose-dependently suppressed osteoclast formation, inhibited the levels of osteoclast-specific genes TRACP, MMP-9, Ctsk, and c-Src and inflammatory cytokines TNF-α, IL-1β, and IL-6 secretion in peripheral blood mononuclear cells and RAW 264.7. I-BET151 inhibited the protein levels of BRD4 and NFATc1, increased OPG expression, and suppressed IκB-α degradation and p65 nuclear translocation. Further, the effects of I-BET151 on osteoclast formation, osteoclast-specific genes expression, inflammatory cytokine secretion, and NF-κB inhibition were promoted by BRD4 knockdown. Conclusion: I-BET151 inhibits osteoclast formation and inflammatory cytokine secretion by targetting BRD4-mediated RANKL-NF-κB signal pathway and BRD4 inhibition might be beneficial for MM treatment.
Long-Term Efficacy of Audiologist-Guided Internet-Based Cognitive Behavior Therapy for Tinnitus
Authors: Beukes Eldré W. , Allen Peter M. , Baguley David M. , Manchaiah Vinaya , Andersson Gerhard 
Published: November 2018

Purpose
The purpose of this study was to investigate the long-term outcomes 1 year after undertaking an audiologist-guided Internet-based cognitive behavioral therapy (iCBT) intervention for tinnitus. Secondary aims were to identify any predictors of outcome and whether there were any unwanted events related to undertaking iCBT for tinnitus.

Method
Participants who had previously undertaken a randomized iCBT efficacy trial for tinnitus were invited to participate. Of the 146 who were initially randomized for the efficacy trial, 104 participants completed the 1-year postintervention assessment measures.
The primary outcome was a change in tinnitus distress as assessed by the Tinnitus Functional Index. Secondary assessment measures were included for insomnia, anxiety, depression, hearing handicap, hyperacusis, cognitive failures, and satisfaction with life. An intention-to-treat analysis using repeated-measures analysis of variance and hierarchical multiple regression was used for statistical analysis. Unwanted effects were categorized according to the unwanted events checklist.

Results
Undertaking iCBT for tinnitus led to significant improvements 1 year postintervention for tinnitus and related difficulties, for example, insomnia, anxiety, depression, hearing handicap, hyperacusis, and life satisfaction. The best predictors of improving tinnitus severity at 1-year postintervention were greater baseline tinnitus severity scores, reading more of the modules, and higher satisfaction with the intervention. Unwanted events were reported by 11% of the participants and were more likely to be reported by women than men. These events were related to worsening of symptoms, the emergence of new symptoms, negative well-being, and prolongation of treatment.

Conclusions
The clinical benefits of audiologist-guided iCBT for tinnitus and tinnitus-related difficulties were sustained 1 year postintervention. Predictors of outcome indicated that the intervention is applicable to a wide range of participants regardless of their demographic backgrounds. Attempts should be made to minimize unwanted events in subsequent trials.