bluuebunny/crossref_metadata_2025_split huggingface dataset:
Metabolomics of sebum reveals lipid dysregulation in Parkinson’s disease
Authors: Sinclair Eleanor , Trivedi Drupad K. , Sarkar Depanjan , Walton-Doyle Caitlin , Milne Joy , Kunath Tilo , Rijs Anouk M. , de Bie Rob M. A. , Goodacre Royston , Silverdale Monty , Barran Perdita 
Published: March 2021

AbstractParkinson’s disease (PD) is a progressive neurodegenerative disorder, which is characterised by degeneration of distinct neuronal populations, including dopaminergic neurons of the substantia nigra. Here, we use a metabolomics profiling approach to identify changes to lipids in PD observed in sebum, a non-invasively available biofluid. We used liquid chromatography-mass spectrometry (LC-MS) to analyse 274 samples from participants (80 drug naïve PD, 138 medicated PD and 56 well matched control subjects) and detected metabolites that could predict PD phenotype. Pathway enrichment analysis shows alterations in lipid metabolism related to the carnitine shuttle, sphingolipid metabolism, arachidonic acid metabolism and fatty acid biosynthesis. This study shows sebum can be used to identify potential biomarkers for PD.
Biofilm formation in the lung contributes to virulence and drug tolerance of Mycobacterium tuberculosis
Authors: Chakraborty Poushali , Bajeli Sapna , Kaushal Deepak , Radotra Bishan Dass , Kumar Ashwani 
Published: March 2021

AbstractTuberculosis is a chronic disease that displays several features commonly associated with biofilm-associated infections: immune system evasion, antibiotic treatment failures, and recurrence of infection. However, although Mycobacterium tuberculosis (Mtb) can form cellulose-containing biofilms in vitro, it remains unclear whether biofilms are formed during infection in vivo. Here, we demonstrate the formation of Mtb biofilms in animal models of infection and in patients, and that biofilm formation can contribute to drug tolerance. First, we show that cellulose is also a structural component of the extracellular matrix of in vitro biofilms of fast and slow-growing nontuberculous mycobacteria. Then, we use cellulose as a biomarker to detect Mtb biofilms in the lungs of experimentally infected mice and non-human primates, as well as in lung tissue sections obtained from patients with tuberculosis. Mtb strains defective in biofilm formation are attenuated for survival in mice, suggesting that biofilms protect bacilli from the host immune system. Furthermore, the administration of nebulized cellulase enhances the antimycobacterial activity of isoniazid and rifampicin in infected mice, supporting a role for biofilms in phenotypic drug tolerance. Our findings thus indicate that Mtb biofilms are relevant to human tuberculosis.
Spin-state-dependent electrical conductivity in single-walled carbon nanotubes encapsulating spin-crossover molecules
Authors: Villalva Julia , Develioglu Aysegul , Montenegro-Pohlhammer Nicolas , Sánchez-de-Armas Rocío , Gamonal Arturo , Rial Eduardo , García-Hernández Mar , Ruiz-Gonzalez Luisa , Costa José Sánchez , Calzado Carmen J. , Pérez Emilio M. , Burzurí Enrique 
Published: March 2021

AbstractSpin crossover (SCO) molecules are promising nanoscale magnetic switches due to their ability to modify their spin state under several stimuli. However, SCO systems face several bottlenecks when downscaling into nanoscale spintronic devices: their instability at the nanoscale, their insulating character and the lack of control when positioning nanocrystals in nanodevices. Here we show the encapsulation of robust Fe-based SCO molecules within the 1D cavities of single-walled carbon nanotubes (SWCNT). We find that the SCO mechanism endures encapsulation and positioning of individual heterostructures in nanoscale transistors. The SCO switch in the guest molecules triggers a large conductance bistability through the host SWCNT. Moreover, the SCO transition shifts to higher temperatures and displays hysteresis cycles, and thus memory effect, not present in crystalline samples. Our results demonstrate how encapsulation in SWCNTs provides the backbone for the readout and positioning of SCO molecules into nanodevices, and can also help to tune their magnetic properties at the nanoscale.
Asc-1 regulates white versus beige adipocyte fate in a subcutaneous stromal cell population
Authors: Suwandhi Lisa , Altun Irem , Karlina Ruth , Miok Viktorian , Wiedemann Tobias , Fischer David , Walzthoeni Thomas , Lindner Christina , Böttcher Anika , Heinzmann Silke S. , Israel Andreas , Khalil Ahmed Elagamy Mohamed Mahmoud , Braun Alexander , Pramme-Steinwachs Ines , Burtscher Ingo , Schmitt-Kopplin Philippe , Heinig Matthias , Elsner Martin , Lickert Heiko , Theis Fabian J. , Ussar Siegfried 
Published: March 2021

AbstractAdipose tissue expansion, as seen in obesity, is often metabolically detrimental causing insulin resistance and the metabolic syndrome. However, white adipose tissue expansion at early ages is essential to establish a functional metabolism. To understand the differences between adolescent and adult adipose tissue expansion, we studied the cellular composition of the stromal vascular fraction of subcutaneous adipose tissue of two and eight weeks old mice using single cell RNA sequencing. We identified a subset of adolescent preadipocytes expressing the mature white adipocyte marker Asc-1 that showed a low ability to differentiate into beige adipocytes compared to Asc-1 negative cells in vitro. Loss of Asc-1 in subcutaneous preadipocytes resulted in spontaneous differentiation of beige adipocytes in vitro and in vivo. Mechanistically, this was mediated by a function of the amino acid transporter ASC-1 specifically in proliferating preadipocytes involving the intracellular accumulation of the ASC-1 cargo D-serine.
Calcium calmodulin kinase II activity is required for cartilage homeostasis in osteoarthritis
Authors: Nalesso Giovanna , Thorup Anne-Sophie , Eldridge Suzanne Elizabeth , De Palma Anna , Kaur Amanpreet , Peddireddi Kiran , Blighe Kevin , Rana Sharmila , Stott Bryony , Vincent Tonia Louise , Thomas Bethan Lynne , Bertrand Jessica , Sherwood Joanna , Fioravanti Antonella , Pitzalis Costantino , Dell’Accio Francesco 
Published: March 2021

AbstractWNT ligands can activate several signalling cascades of pivotal importance during development and regenerative processes. Their de-regulation has been associated with the onset of different diseases. Here we investigated the role of the WNT/Calcium Calmodulin Kinase II (CaMKII) pathway in osteoarthritis. We identified Heme Oxygenase I (HMOX1) and Sox-9 as specific markers of the WNT/CaMKII signalling in articular chondrocytes through a microarray analysis. We showed that the expression of the activated form of CaMKII, phospho-CaMKII, was increased in human and murine osteoarthritis and the expression of HMOX1 was accordingly reduced, demonstrating the activation of the pathway during disease progression. To elucidate its function, we administered the CaMKII inhibitor KN93 to mice in which osteoarthritis was induced by resection of the anterior horn of the medial meniscus and of the medial collateral ligament in the knee joint. Pharmacological blockade of CaMKII exacerbated cartilage damage and bone remodelling. Finally, we showed that CaMKII inhibition in articular chondrocytes upregulated the expression of matrix remodelling enzymes alone and in combination with Interleukin 1. These results suggest an important homeostatic role of the WNT/CaMKII signalling in osteoarthritis which could be exploited in the future for therapeutic purposes.
Value of CT features for predicting EGFR mutations and ALK positivity in patients with lung adenocarcinoma
Authors: Han Xiaoyu , Fan Jun , Li Yumin , Cao Yukun , Gu Jin , Jia Xi , Wang Yuhui , Shi Heshui 
Published: March 2021

AbstractThe aim of this study was to identify the relationships of epidermal growth factor receptor (EGFR) mutations and anaplastic large-cell lymphoma kinase (ALK) status with CT characteristics in adenocarcinoma using the largest patient cohort to date. In this study, preoperative chest CT findings prior to treatment were retrospectively evaluated in 827 surgically resected lung adenocarcinomas. All patients were tested for EGFR mutations and ALK status. EGFR mutations were found in 489 (59.1%) patients, and ALK positivity was found in 57 (7.0%). By logistic regression, the most significant independent prognostic factors of EGFR effective mutations were female sex, nonsmoker status, GGO air bronchograms and pleural retraction. For EGFR mutation prediction, receiver operating characteristic (ROC) curves yielded areas under the curve (AUCs) of 0.682 and 0.758 for clinical only or combined CT features, respectively, with a significant difference (p < 0.001). Furthermore, the exon 21 mutation rate in GGO was significantly higher than the exon 19 mutation rate(p = 0.029). The most significant independent prognostic factors of ALK positivity were age, solid-predominant-subtype tumours, mucinous lung adenocarcinoma, solid tumours and no air bronchograms on CT. ROC curve analysis showed that for predicting ALK positivity, the use of clinical variables combined with CT features (AUC = 0.739) was superior to the use of clinical variables alone (AUC = 0.657), with a significant difference (p = 0.0082). The use of CT features for patients may allow analyses of tumours and more accurately predict patient populations who will benefit from therapies targeting treatment.
Effect of co-inoculation with arbuscular mycorrhizal fungi and phosphate solubilizing fungi on nutrient uptake and photosynthesis of beach palm under salt stress environment
Authors: Zai Xue-Ming , Fan Jun-Jun , Hao Zhen-Ping , Liu Xing-Man , Zhang Wang-Xiang 
Published: March 2021

AbstractBeach plum (Prunus maritima) is an ornamental plant, famous for its strong salt and drought stress tolerance. However, the poor growth rate of transplanted seedlings has seriously restricted its application in salinized soil. This study investigated the effects of inoculation with arbuscular mycorrhizal fungus (AMF), Funneliformis mosseae, and phosphate-solubilizing fungus (PSF), Apophysomyces spartima, on the growth, nutrient (N, P, and K) uptake, and photosynthesis of beach plum under saline (170 mM NaCl) and non-saline (0 mM NaCl) conditions. We aimed to find measures to increase the growth rate of beach plum in saline-alkali land and to understand the reasons for this increase. The results showed that salinization adversely affected colonization by AMF but positively increased PSF populations (increased by 33.9–93.3% over non-NaCl treatment). The dual application of AMF and PSF mitigated the effects of salt stress on all growth parameters and nutrient uptake, significantly for roots (dry weight and P and N contents increased by 91.0%, 68.9%, and 40%, respectively, over non-NaCl treatment). Salinization caused significant reductions in net photosynthetic rate (Pn), stomatal conductance (Gs), transpiration rate (E), and intercellular CO2 concentration (Ci) value, while inoculation with AMF and PSF inoculations significantly abated such reductions. The maximum efficiency of photosystem II (PSII) (Fv/Fm), the photochemical quenching coefficient (qP), and the nonphotochemical quenching (NPQ) values were affected little by inoculation with AMF, PSF, or both under non-NaCl treatments. However, plants inoculated with AMF and/or PSF had higher Fv/Fm, qP, and ФPSII values (increased by 72.5–188.1%) than the control under NaCl treatment, but not a higher NPQ value. We concluded that inoculation with AMF or PSF increased nutrient uptake and improved the gas-exchange and Chl fluorescence parameters of beach plum under salt stress environment. These effects could be strengthened by the combination of AMF and PSF, especially for nutrient uptake, root growth, and Pn, thereby alleviating the deleterious effects of NaCl stress on beach plum growth.
Premating barriers in young sympatric snail species
Authors: Maltseva Arina L. , Varfolomeeva Marina A. , Lobov Arseniy A. , Tikanova Polina O. , Repkin Egor A. , Babkina Irina Y. , Panova Marina , Mikhailova Natalia A. , Granovitch Andrei I. 
Published: March 2021

AbstractSympatric coexistence of recently diverged species raises the question of barriers restricting the gene flow between them. Reproductive isolation may be implemented at several levels, and the weakening of some, e.g. premating, barriers may require the strengthening of the others, e.g. postcopulatory ones. We analysed mating patterns and shell size of mates in recently diverged closely related species of the subgenus Littorina Neritrema (Littorinidae, Caenogastropoda) in order to assess the role of premating reproductive barriers between them. We compared mating frequencies observed in the wild with those expected based on relative densities using partial canonical correspondence analysis. We introduced the fidelity index (FI) to estimate the relative accuracy of mating with conspecific females and precopulatory isolation index (IPC) to characterize the strength of premating barriers. The species under study, with the exception of L. arcana, clearly demonstrated preferential mating with conspecifics. According to FI and IPC, L. fabalis and L. compressa appeared reliably isolated from their closest relatives within Neritrema. Individuals of these two species tend to be smaller than those of the others, highlighting the importance of shell size changes in gastropod species divergence. L. arcana males were often found in pairs with L. saxatilis females, and no interspecific size differences were revealed in this sibling species pair. We discuss the lack of discriminative mate choice in the sympatric populations of L. arcana and L. saxatilis, and possible additional mechanisms restricting gene flow between them.
Rapid coupling between solid earth and ice volume during the Quaternary
Authors: Kuwahara Yusuke , Yasukawa Kazutaka , Fujinaga Koichiro , Nozaki Tatsuo , Ohta Junichiro , Sato Honami , Kimura Jun-Ichi , Nakamura Kentaro , Yokoyama Yusuke , Kato Yasuhiro 
Published: March 2021

AbstractThe solid earth plays a major role in controlling Earth’s surface climate. Volcanic degassing of carbon dioxide (CO2) and silicate chemical weathering are known to regulate the evolution of climate on a geologic timescale (> 106 yr), but the relationship between the solid earth and the shorter (< 105 yr) fluctuations of Quaternary glacial–interglacial cycles is still under debate. Here we show that the seawater osmium isotope composition (187Os/188Os), a proxy for the solid earth’s response to climate change, has varied during the past 300,000 years in association with glacial–interglacial cycles. Our marine Os isotope mass-balance simulation reveals that the observed 187Os/188Os fluctuation cannot be explained solely by global chemical weathering rate changes corresponding to glacial–interglacial climate changes, but the fluctuation can be reproduced by taking account of short-term inputs of (1) radiogenic Os derived from intense weathering of glacial till during deglacial periods and (2) unradiogenic Os derived from enhanced seafloor hydrothermalism triggered by sea-level falls associated with increases of ice sheet volume. Our results constitute the first evidence that ice sheet recession and expansion during the Quaternary systematically and repetitively caused short-term (< 105 yr) solid earth responses via chemical weathering of glacial till and seafloor magmatism. This finding implies that climatic changes on < 105 yr timescales can provoke rapid feedbacks from the solid earth, a causal relationship that is the reverse of the longer-term (> 106 yr) causality that has been conventionally considered.
New estimate of chemical weathering rate in Xijiang River Basin based on multi-model
Authors: Zhang Yong , Yu Shi , He Shiyi , Sun Pingan , Wu Fu , Liu Zhenyu , Zhu Haiyan , Li Xiao , Zeng Peng 
Published: March 2021

AbstractHydrochemistry and Sr isotope compositions were measured in water samples collected during high- and low-water periods from the main stream and tributaries of the Xijiang River Basin in southern China. The primary weathering end-members were analyzed and calculated using the multi-model combination and classic hydrogeochemical method. During the high-water period, structural factors were found to be the main factors controlling chemical weathering in the basin, whereas anthropogenic activity and other random factors had a negligible influence. During the low-water period, both structural and random factors controlled chemical weathering. Through path-model and semi-variance analyses, we determined and quantified the relationship between the main weathering sources, whose results were stable; this is consistent with the inversion model. The total dissolved substances were mainly derived from carbonate weathering, which was approximately 76% (0–96%) while silicate weathering accounted for only 14% (5–19%). The inversion model results showed that the optimum silicate weathering rate was 7.264–35.551 × 103 mol/km2/year, where carbonic acid was the main factor that induces weathering. The CO2 flux consumed by rock weathering in the basin during the study period was 150.69 × 109 mol/year, while the CO2 flux consumed by carbonic acid weathering of carbonate (CCW) and silicate rocks (CSW) was 144.47 and 29.45 × 109 mol/year, respectively. The CO2 flux produced by H2SO4 weathered carbonate (SCW) was 23.23 × 109 mol/year.
DBnorm as an R package for the comparison and selection of appropriate statistical methods for batch effect correction in metabolomic studies
Authors: Bararpour Nasim , Gilardi Federica , Carmeli Cristian , Sidibe Jonathan , Ivanisevic Julijana , Caputo Tiziana , Augsburger Marc , Grabherr Silke , Desvergne Béatrice , Guex Nicolas , Bochud Murielle , Thomas Aurelien 
Published: March 2021

AbstractAs a powerful phenotyping technology, metabolomics provides new opportunities in biomarker discovery through metabolome-wide association studies (MWAS) and the identification of metabolites having a regulatory effect in various biological processes. While mass spectrometry-based (MS) metabolomics assays are endowed with high throughput and sensitivity, MWAS are doomed to long-term data acquisition generating an overtime-analytical signal drift that can hinder the uncovering of real biologically relevant changes. We developed “dbnorm”, a package in the R environment, which allows for an easy comparison of the model performance of advanced statistical tools commonly used in metabolomics to remove batch effects from large metabolomics datasets. “dbnorm” integrates advanced statistical tools to inspect the dataset structure not only at the macroscopic (sample batches) scale, but also at the microscopic (metabolic features) level. To compare the model performance on data correction, “dbnorm” assigns a score that help users identify the best fitting model for each dataset. In this study, we applied “dbnorm” to two large-scale metabolomics datasets as a proof of concept. We demonstrate that “dbnorm” allows for the accurate selection of the most appropriate statistical tool to efficiently remove the overtime signal drift and to focus on the relevant biological components of complex datasets.
Molecular imaging of a fluorescent antibody against epidermal growth factor receptor detects high-grade glioma
Authors: Zhou Quan , Vega Leonel Johana C. M. , Santoso Michelle Rai , Wilson Christy , van den Berg Nynke S. , Chan Carmel T. , Aryal Muna , Vogel Hannes , Cayrol Romain , Mandella Michael J. , Schonig Frank , Lu Guolan , Gambhir Sanjiv S. , Moseley Michael E. , Rosenthal Eben L. , Grant Gerald A. 
Published: March 2021

AbstractThe prognosis for high-grade glioma (HGG) remains dismal and the extent of resection correlates with overall survival and progression free disease. Epidermal growth factor receptor (EGFR) is a biomarker heterogeneously expressed in HGG. We assessed the feasibility of detecting HGG using near-infrared fluorescent antibody targeting EGFR. Mice bearing orthotopic HGG xenografts with modest EGFR expression were imaged in vivo after systemic panitumumab-IRDye800 injection to assess its tumor-specific uptake macroscopically over 14 days, and microscopically ex vivo. EGFR immunohistochemical staining of 59 tumor specimens from 35 HGG patients was scored by pathologists and expression levels were compared to that of mouse xenografts. Intratumoral distribution of panitumumab-IRDye800 correlated with near-infrared fluorescence and EGFR expression. Fluorescence distinguished tumor cells with 90% specificity and 82.5% sensitivity. Target-to-background ratios peaked at 14 h post panitumumab-IRDye800 infusion, reaching 19.5 in vivo and 7.6 ex vivo, respectively. Equivalent or higher EGFR protein expression compared to the mouse xenografts was present in 77.1% HGG patients. Age, combined with IDH-wildtype cerebral tumor, was predictive of greater EGFR protein expression in human tumors. Tumor specific uptake of panitumumab-IRDye800 provided remarkable contrast and a flexible imaging window for fluorescence-guided identification of HGGs despite modest EGFR expression.
EMeth: An EM algorithm for cell type decomposition based on DNA methylation data
Authors: Zhang Hanyu , Cai Ruoyi , Dai James , Sun Wei 
Published: March 2021

AbstractWe introduce a new computational method named EMeth to estimate cell type proportions using DNA methylation data. EMeth is a reference-based method that requires cell type-specific DNA methylation data from relevant cell types. EMeth improves on the existing reference-based methods by detecting the CpGs whose DNA methylation are inconsistent with the deconvolution model and reducing their contributions to cell type decomposition. Another novel feature of EMeth is that it allows a cell type with known proportions but unknown reference and estimates its methylation. This is motivated by the case of studying methylation in tumor cells while bulk tumor samples include tumor cells as well as other cell types such as infiltrating immune cells, and tumor cell proportion can be estimated by copy number data. We demonstrate that EMeth delivers more accurate estimates of cell type proportions than several other methods using simulated data and in silico mixtures. Applications in cancer studies show that the proportions of T regulatory cells estimated by DNA methylation have expected associations with mutation load and survival time, while the estimates from gene expression miss such associations.
Pattern discovery and disentanglement on relational datasets
Authors: Wong Andrew K. C. , Zhou Pei-Yuan , Butt Zahid A. 
Published: March 2021

AbstractMachine Learning has made impressive advances in many applications akin to human cognition for discernment. However, success has been limited in the areas of relational datasets, particularly for data with low volume, imbalanced groups, and mislabeled cases, with outputs that typically lack transparency and interpretability. The difficulties arise from the subtle overlapping and entanglement of functional and statistical relations at the source level. Hence, we have developed Pattern Discovery and Disentanglement System (PDD), which is able to discover explicit patterns from the data with various sizes, imbalanced groups, and screen out anomalies. We present herein four case studies on biomedical datasets to substantiate the efficacy of PDD. It improves prediction accuracy and facilitates transparent interpretation of discovered knowledge in an explicit representation framework PDD Knowledge Base that links the sources, the patterns, and individual patients. Hence, PDD promises broad and ground-breaking applications in genomic and biomedical machine learning.