bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disruption of podocyte cytoskeletal biomechanics by dasatinib leads to nephrotoxicity
Authors: Calizo Rhodora C. , Bhattacharya Smiti , van Hasselt J. G. Coen , Wei Chengguo , Wong Jenny S. , Wiener Robert J. , Ge Xuhua , Wong Nicholas J. , Lee Jia-Jye , Cuttitta Christina M. , Jayaraman Gomathi , Au Vivienne H. , Janssen William , Liu Tong , Li Hong , Salem Fadi , Jaimes Edgar A. , Murphy Barbara , Campbell Kirk N. , Azeloglu Evren U. 
Published: May 2019

AbstractNephrotoxicity is a critical adverse event that leads to discontinuation of kinase inhibitor (KI) treatment. Here we show, through meta-analyses of FDA Adverse Event Reporting System, that dasatinib is associated with high risk for glomerular toxicity that is uncoupled from hypertension, suggesting a direct link between dasatinib and podocytes. We further investigate the cellular effects of dasatinib and other comparable KIs with varying risks of nephrotoxicity. Dasatinib treated podocytes show significant changes in focal adhesions, actin cytoskeleton, and morphology that are not observed with other KIs. We use phosphoproteomics and kinome profiling to identify the molecular mechanisms of dasatinib-induced injury to the actin cytoskeleton, and atomic force microscopy to quantify impairment to cellular biomechanics. Furthermore, chronic administration of dasatinib in mice causes reversible glomerular dysfunction, loss of stress fibers, and foot process effacement. We conclude that dasatinib induces nephrotoxicity through altered podocyte actin cytoskeleton, leading to injurious cellular biomechanics.
Social-ecological alignment and ecological conditions in coral reefs
Authors: Barnes Michele L. , Bodin Örjan , McClanahan Tim R. , Kittinger John N. , Hoey Andrew S. , Gaoue Orou G. , Graham Nicholas A. J. 
Published: May 2019

AbstractComplex social-ecological interactions underpin many environmental problems. To help capture this complexity, we advance an interdisciplinary network modeling framework to identify important relationships between people and nature that can influence environmental conditions. Drawing on comprehensive social and ecological data from five coral reef fishing communities in Kenya; including interviews with 648 fishers, underwater visual census data of reef ecosystem condition, and time-series landings data; we show that positive ecological conditions are associated with ‘social-ecological network closure’ – i.e., fully linked and thus closed network structures between social actors and ecological resources. Our results suggest that when fishers facing common dilemmas form cooperative communication ties with direct resource competitors, they may achieve positive gains in reef fish biomass and functional richness. Our work provides key empirical insight to a growing body of research on social-ecological alignment, and helps to advance an integrative framework that can be applied empirically in different social-ecological contexts.
Integrating Hi-C and FISH data for modeling of the 3D organization of chromosomes
Authors: Abbas Ahmed , He Xuan , Niu Jing , Zhou Bin , Zhu Guangxiang , Ma Tszshan , Song Jiangpeikun , Gao Juntao , Zhang Michael Q. , Zeng Jianyang 
Published: May 2019

AbstractThe new advances in various experimental techniques that provide complementary information about the spatial conformations of chromosomes have inspired researchers to develop computational methods to fully exploit the merits of individual data sources and combine them to improve the modeling of chromosome structure. Here we propose GEM-FISH, a method for reconstructing the 3D models of chromosomes through systematically integrating both Hi-C and FISH data with the prior biophysical knowledge of a polymer model. Comprehensive tests on a set of chromosomes, for which both Hi-C and FISH data are available, demonstrate that GEM-FISH can outperform previous chromosome structure modeling methods and accurately capture the higher order spatial features of chromosome conformations. Moreover, our reconstructed 3D models of chromosomes revealed interesting patterns of spatial distributions of super-enhancers which can provide useful insights into understanding the functional roles of these super-enhancers in gene regulation.
Lnc-TALC promotes O6-methylguanine-DNA methyltransferase expression via regulating the c-Met pathway by competitively binding with miR-20b-3p
Authors: Wu Pengfei , Cai Jinquan , Chen Qun , Han Bo , Meng Xiangqi , Li Yansheng , Li Ziwei , Wang Ruijia , Lin Lin , Duan Chunbin , Kang Chunsheng , Jiang Chuanlu 
Published: May 2019

AbstractLong noncoding RNAs (lncRNAs) have emerged as new regulatory molecules implicated in diverse biological processes, including therapeutic resistance. However, the mechanisms underlying lncRNA-mediated temozolomide (TMZ) resistance in glioblastoma (GBM) remain largely unknown. To illustrate the role of lncRNA in TMZ resistance, we induce TMZ-resistant GBM cells, perform a lncRNA microarray of the parental and TMZ-resistant cells, and find an unreported lncRNA in GBM, lnc-TALC (temozolomide-associated lncRNA in glioblastoma recurrence), correlated with TMZ resistance via competitively binding miR-20b-3p to facilitate c-Met expression. A phosphorylated AKT/FOXO3 axis regulated lnc-TALC expression in TMZ-resistant GBM cells. Furthermore, lnc-TALC increased MGMT expression by mediating the acetylation of H3K9, H3K27 and H3K36 in MGMT promoter regions through the c-Met/Stat3/p300 axis. In clinical patients, lnc-TALC is required for TMZ resistance and GBM recurrence. Our results reveal that lnc-TALC in GBM could serve as a therapeutic target to overcome TMZ resistance, enhancing the clinical benefits of TMZ chemotherapy.
Coral carbon isotope sensitivity to growth rate and water depth with paleo-sea level implications
Authors: Linsley Braddock K. , Dunbar Robert B. , Dassié Emilie P. , Tangri Neil , Wu Henry C. , Brenner Logan D. , Wellington Gerard M. 
Published: May 2019

AbstractAlthough reef coral skeletal carbon isotopes (δ13C) are routinely measured, interpretation remains controversial. Here we show results of a consistent inverse relationship between coral δ13C and skeletal extension rate over the last several centuries in Porites corals at Fiji, Tonga, Rarotonga and American Samoa in the southwest Pacific. Beginning in the 1950s, this relationship breaks down as the atmospheric 13C Suess effect shifts skeletal δ13C > 1.0‰ lower. We also compiled coral δ13C from a global array of sites and find that mean coral δ13C decreases by −1.4‰ for every 5 m increase in water depth (R = 0.68, p < 0.01). This highlights the fundamental sensitivity of coral δ13C to endosymbiotic photosynthesis. Collectively, these results suggest that photosynthetic rate largely determines mean coral δ13C while changes in extension rate and metabolic effects over time modulate skeletal δ13C around this mean value. The newly quantified coral δ13C-water depth relationship may be an effective tool for improving the precision of paleo-sea level reconstruction using corals.
Microclot array elastometry for integrated measurement of thrombus formation and clot biomechanics under fluid shear
Authors: Chen Zhaowei , Lu Jiankai , Zhang Changjie , Hsia Isaac , Yu Xinheng , Marecki Leo , Marecki Eric , Asmani Mohammadnabi , Jain Shilpa , Neelamegham Sriram , Zhao Ruogang 
Published: May 2019

AbstractBlood clotting at the vascular injury site is a complex process that involves platelet adhesion and clot stiffening/contraction in the milieu of fluid flow. An integrated understanding of the hemodynamics and tissue mechanics regulating this process is currently lacking due to the absence of an experimental system that can simultaneously model clot formation and measure clot mechanics under shear flow. Here we develop a microfluidic-integrated microclot-array-elastometry system (clotMAT) that recapitulates dynamic changes in clot mechanics under physiological shear. Treatments with procoagulants and platelet antagonists and studies with diseased patient plasma demonstrate the ability of the system to assay clot biomechanics associated with common antiplatelet treatments and bleeding disorders. The changes of clot mechanics under biochemical treatments and shear flow demonstrate independent yet equally strong effects of these two stimulants on clot stiffening. This microtissue force sensing system may have future research and diagnostic potential for various bleeding disorders.
Bacteroidetes use thousands of enzyme combinations to break down glycans
Authors: Lapébie Pascal , Lombard Vincent , Drula Elodie , Terrapon Nicolas , Henrissat Bernard 
Published: May 2019

AbstractUnlike proteins, glycan chains are not directly encoded by DNA, but by the specificity of the enzymes that assemble them. Theoretical calculations have proposed an astronomical number of possible isomers (> 1012 hexasaccharides) but the actual diversity of glycan structures in nature is not known. Bacteria of the Bacteroidetes phylum are considered primary degraders of polysaccharides and they are found in all ecosystems investigated. In Bacteroidetes genomes, carbohydrate-degrading enzymes (CAZymes) are arranged in gene clusters termed polysaccharide utilization loci (PULs). The depolymerization of a given complex glycan by Bacteroidetes PULs requires bespoke enzymes; conversely, the enzyme composition in PULs can provide information on the structure of the targeted glycans. Here we group the 13,537 PULs encoded by 964 Bacteroidetes genomes according to their CAZyme composition. We find that collectively Bacteroidetes have elaborated a few thousand enzyme combinations for glycan breakdown, suggesting a global estimate of diversity of glycan structures much smaller than the theoretical one.
Coordination-driven self-assembly of a molecular figure-eight knot and other topologically complex architectures
Authors: Dang Li-Long , Sun Zhen-Bo , Shan Wei-Long , Lin Yue-Jian , Li Zhen-Hua , Jin Guo-Xin 
Published: May 2019

AbstractOver the past decades, molecular knots and links have captivated the chemical community due to their promising mimicry properties in molecular machines and biomolecules and are being realized with increasing frequency with small molecules. Herein, we describe how to utilize stacking interactions and hydrogen-bonding patterns to form trefoil knots, figure-eight knots and [2]catenanes. A transformation can occur between the unique trefoil knot and its isomeric boat-shaped tetranuclear macrocycle by the complementary concentration effect. Remarkably, the realization and authentication of the molecular figure-eight knot with four crossings fills the blank about 41knot in knot tables. The [2]catenane topology is obtained because the selective naphthalenediimide (NDI)-based ligand, which can engender favorable aromatic donor-acceptor π interactions due to its planar, electron-deficient aromatic surface. The stacking interactions and hydrogen-bond interactions play important roles in these self-assembly processes. The advantages provide an avenue for the generation of structurally and topologically complex supramolecular architectures.
Cortical thinning in patients with REM sleep behavior disorder is associated with clinical progression
Authors: Pereira Joana B. , Weintraub Daniel , Chahine Lana , Aarsland Dag , Hansson Oskar , Westman Eric 
Published: May 2019

AbstractThe aim of this study is to determine whether structural MRI measures are associated with clinical impairment and progression to a Lewy body disease in patients with idiopathic REM sleep behavior disorder (iRBD). Twenty-seven patients with iRBD in addition to patients with de novo PD and healthy controls were included from the Parkinson’s Progression Markers Initiative. Patients with iRBD were followed for up to 3 years. Clinical and MRI measures were compared across groups and the association between clinical features and structural MRI was assessed in iRBD patients. Cox regression analyses were applied to identify risk factors for progressing to a Lewy body disease in iRBD. Our results showed that, at baseline, iRBD patients showed parietal and occipital cortical thinning, compared to controls. They also showed worse motor and non-motor abilities, some of which correlated with motor, frontal or temporal cortical thinning. At follow-up, six (22%) iRBD patients were diagnosed with a Lewy body disorder. These patients showed cortical thinning in frontal, occipital and parietal areas compared to iRBD non-converters. Cortical thinning was a significant predictor for future development of a Lewy body disorder (HR: 0.784; 95% CI: 0.640–0.960; p = 0.02). We conclude that cortical thinning is associated with worse motor and non-motor abilities, and predicts conversion to a Lewy body disorder in iRBD, suggesting it could be used to select candidates for clinical trials to delay the onset of neurodegenerative disease.
Asthma care based on Chronic Care Model in an aging Asian community
Authors: Zheng L. F. , Koh Y. L. E. , Sankari U. , Tan N. C. 
Published: May 2019

AbstractTo cope with the higher prevalence of asthma and other non-communicable diseases without compromising on quality of care, a Singapore public primary care institution has adopted the Chronic Care Model (CCM). This retrospective cohort study aimed to describe the proportion of patients with well-controlled asthma (based on Asthma Control Test score ≥20) between 2010 and 2016 in association with their management based on the CCM (which covers the polyclinic clinical information system, self-management measures, system re-design and decision support). Data were retrieved from the Singapore National Asthma Programme (SNAP) and institutional clinical quality databases of eight local polyclinics in eastern and southern Singapore. The data were aggregated, analysed and presented in proportions against monthly polyclinic attendances for asthma. From 2010 to 2016, the total asthma attendances increased by 31% from 27,345 to 35,731, with the highest rise among patients aged ≥60 years. The proportion of patients with good asthma control rose from 71.4% to 80.9%; those who received rescue therapy for acute exacerbations fell from 15.8% to 11.7% and those referred to emergency departments after failed rescue therapy decreased from 0.7% to 0.6%. The proportion of patients with updated asthma action plans increased from 66.7% to 73.4% (proxy for self-management). The overall health and process outcomes of asthma seemed to have improved with multiplex of system-based interventions relating to the introduction of CCM in a public primary healthcare institution in Singapore.
Differences in respiratory consultations in primary care between underweight, normal-weight, and overweight children
Authors: van Leeuwen Janneke , El Jaouhari Zoubeir , Paulis Winifred D. , Bindels Patrick J. E. , Koes Bart W. , van Middelkoop Marienke 
Published: May 2019

AbstractThis prospective cohort study investigates whether the suggested association between weight status and respiratory complaints in open populations is also reflected in the frequency of consultations for respiratory complaints at the general practice. Children aged 2–18 years presenting at one of the participating general practices in the Netherlands could be included. Electronic medical files were used to extract data on consultations. Logistic regression analyses and negative binomial regression analyses were used to assess the associations between weight status and the presence, and frequency of respiratory consultations, respectively, during 2-year follow-up. Subgroup analyses were performed in children aged 2–6, 6–12, and 12–18 years old. Of the 617 children, 115 (18.6%) were underweight, 391 (63.4%) were normal-weight, and 111 (18%) were overweight. Respiratory consultations were not more prevalent in underweight children compared to normal-weight children (odds ratio (OR) 0.87, 95% confidence inteval (CI) 0.64–1.10), and in overweight children compared to normal-weight children (OR 1.33, 95% CI 0.99–1.77). Overweight children aged 12–18 years had more respiratory consultations (OR 2.14, 95% CI 1.14–4.01), more asthma-like consultations (OR 3.94, 95%CI 1.20–12.88), and more respiratory allergy-related consultations (OR 3.14, 95% CI 1.25–7.86) than normal-weight children. General practitioners should pay attention to weight loss as part of the treatment of respiratory complaints in overweight and obese children.
Elementary excitation in the spin-stripe phase in quantum chains
Authors: Pregelj Matej , Zorko Andrej , Gomilšek Matjaž , Klanjšek Martin , Zaharko Oksana , White Jonathan S. , Luetkens Hubertus , Coomer Fiona , Ivek Tomislav , Rivas Góngora David , Berger Helmuth , Arčon Denis 
Published: May 2019

AbstractElementary excitations in condensed matter capture the complex many-body dynamics of interacting basic entities in a simple quasiparticle picture. In magnetic systems the most established quasiparticles are magnons, collective excitations that reside in ordered spin structures, and spinons, their fractional counterparts that emerge in disordered, yet correlated spin states. Here we report on the discovery of elementary excitation inherent to spin-stripe order that represents a bound state of two phason quasiparticles, resulting in a wiggling-like motion of the magnetic moments. We observe these excitations, which we dub “wigglons”, in the frustrated zigzag spin-1/2 chain compound β-TeVO4, where they give rise to unusual low-frequency spin dynamics in the spin-stripe phase. This result provides insights into the stripe physics of strongly-correlated electron systems.
Gelatin methacryloyl and its hydrogels with an exceptional degree of controllability and batch-to-batch consistency
Authors: Zhu Mengxiang , Wang Yingying , Ferracci Gaia , Zheng Jing , Cho Nam-Joon , Lee Bae Hoon 
Published: May 2019

AbstractGelatin methacryloyl (GelMA) is a versatile material for a wide range of bioapplications. There is an intense interest in developing effective chemical strategies to prepare GelMA with a high degree of batch-to-batch consistency and controllability in terms of methacryloyl functionalization and physiochemical properties. Herein, we systematically investigated the batch-to-batch reproducibility and controllability of producing GelMA (target highly and lowly substituted versions) via a one-pot strategy. To assess the GelMA product, several parameters were evaluated, including the degree of methacryloylation, secondary structure, and enzymatic degradation, along with the mechanical properties and cell viability of GelMA hydrogels. The results showed that two types of target GelMA with five batches exhibited a high degree of controllability and reproducibility in compositional, structural, and functional properties owing to the highly controllable one-pot strategy.
Development and Validation of a Pathology Image Analysis-based Predictive Model for Lung Adenocarcinoma Prognosis - A Multi-cohort Study
Authors: Luo Xin , Yin Shen , Yang Lin , Fujimoto Junya , Yang Yikun , Moran Cesar , Kalhor Neda , Weissferdt Annikka , Xie Yang , Gazdar Adi , Minna John , Wistuba Ignacio Ivan , Mao Yousheng , Xiao Guanghua 
Published: May 2019

AbstractPrediction of disease prognosis is essential for improving cancer patient care. Previously, we have demonstrated the feasibility of using quantitative morphological features of tumor pathology images to predict the prognosis of lung cancer patients in a single cohort. In this study, we developed and validated a pathology image-based predictive model for the prognosis of lung adenocarcinoma (ADC) patients across multiple independent cohorts. Using quantitative pathology image analysis, we extracted morphological features from H&E stained sections of formalin fixed paraffin embedded (FFPE) tumor tissues. A prediction model for patient prognosis was developed using tumor tissue pathology images from a cohort of 91 stage I lung ADC patients from the Chinese Academy of Medical Sciences (CAMS), and validated in ADC patients from the National Lung Screening Trial (NLST), and the UT Special Program of Research Excellence (SPORE) cohort. The morphological features that are associated with patient survival in the training dataset from the CAMS cohort were used to develop a prognostic model, which was independently validated in both the NLST (n = 185) and the SPORE (n = 111) cohorts. The association between predicted risk and overall survival was significant for both the NLST (Hazard Ratio (HR) = 2.20, pv = 0.01) and the SPORE cohorts (HR = 2.15 and pv = 0.044), respectively, after adjusting for key clinical variables. Furthermore, the model also predicted the prognosis of patients with stage I ADC in both the NLST (n = 123, pv = 0.0089) and SPORE (n = 68, pv = 0.032) cohorts. The results indicate that the pathology image-based model predicts the prognosis of ADC patients across independent cohorts.
Long-term evaluation of coronary artery calcifications in kidney transplanted patients: a follow up of 5 years
Authors: Alfieri C. , Forzenigo L. , Tripodi F. , Meneghini M. , Regalia A. , Cresseri D. , Messa P. 
Published: May 2019

AbstractCoronary artery calcifications(CACs), are related to the increased cardiovascular mortality during kidney transplantation(KTx). Using coronary-CT performed at 1 month(T0) and 5 years(T5) after KTx we evaluated: (1) the prevalence of CACs; (2) the clinical and biochemical factors related to CACs; 3) the factors implicated with CACs progression. We evaluated 67-pts selected from the 103-pts transplanted in our unit between 2007 and 2008. Clinical and biochemical parameters were recorded at the time of pre-KTx evaluation and for five years after KTx. Coronary-CT for the Agatson score (AS) evaluation was performed at T0 and at T5, and CACs progression was determined. At baseline AS was 45 [0–233]. At T5 AS was 119 [1–413]. At T0, 69% of patients had CACs. Age and dialytic vintage were the main independent variables related to CACs. At T5, CACs were present in 76% of patients. Age was the only independent factor in determining CACs. A progression of CACs was observed in 74% of patients. They were older, had higher CACs-T0 and higher SBP throughout the 5-years. The presence of CACs at T0 and age were the only independent factors in determining the CACs-progression. CACs-T0 had the best discriminative power for CACs progression. CACs prevalence is quite high in KTx patients; Age is strictly related to CACs; Age and the presence of CACs at baseline were the two major factors associated with the progression of CACs during the five years of follow up. CACs-T0 had the best discriminative power for progression of CACs.