bluuebunny/crossref_metadata_2025_split huggingface dataset:
The hidden waves in the ECG uncovered revealing a sound automated interpretation method
Authors: Rueda Cristina , Larriba Yolanda , Lamela Adrian 
Published: February 2021

AbstractA novel approach for analysing cardiac rhythm data is presented in this paper. Heartbeats are decomposed into the five fundamental P, Q, R, S and T waves plus an error term to account for artifacts in the data which provides a meaningful, physical interpretation of the heart’s electric system. The morphology of each wave is concisely described using four parameters that allow all the different patterns in heartbeats to be characterized and thus differentiated This multi-purpose approach solves such questions as the extraction of interpretable features, the detection of the fiducial marks of the fundamental waves, or the generation of synthetic data and the denoising of signals. Yet the greatest benefit from this new discovery will be the automatic diagnosis of heart anomalies as well as other clinical uses with great advantages compared to the rigid, vulnerable and black box machine learning procedures, widely used in medical devices. The paper shows the enormous potential of the method in practice; specifically, the capability to discriminate subjects, characterize morphologies and detect the fiducial marks (reference points) are validated numerically using simulated and real data, thus proving that it outperforms its competitors.
Targeting galectin-3 with a high-affinity antibody for inhibition of high-grade serous ovarian cancer and other MUC16/CA-125-expressing malignancies
Authors: Stasenko Marina , Smith Evan , Yeku Oladapo , Park Kay J. , Laster Ian , Lee Kwangkook , Walderich Sven , Spriggs Elizabeth , Rueda Bo , Weigelt Britta , Zamarin Dmitriy , Rao Thapi Dharma , Spriggs David R. 
Published: February 2021

AbstractThe lectin, galectin-3 (Gal3), has been implicated in a variety of inflammatory and oncogenic processes, including tumor growth, invasion, and metastasis. The interactions of Gal3 and MUC16 represent a potential targetable pathway for the treatment of MUC16-expressing malignancies. We found that the silencing of Gal3 in MUC16-expressing breast and ovarian cancer cells in vitro inhibited tumor cell invasion and led to attenuated tumor growth in murine models. We therefore developed an inhibitory murine monoclonal anti–Gal3 carbohydrate-binding domain antibody, 14D11, which bound human and mouse Gal3 but did not bind human Galectins-1, -7, -8 or -9. Competition studies and a docking model suggest that the 14D11 antibody competes with lactose for the carbohydrate binding pocket of Gal3. In MUC16-expressing cancer cells, 14D11 treatment blocked AKT and ERK1/2 phosphorylation, and led to inhibition of cancer cell Matrigel invasion. Finally, in experimental animal tumor models, 14D11 treatment led to prolongation of overall survival in animals bearing flank tumors, and retarded lung specific metastatic growth by MUC16 expressing breast cancer cells. Our results provide evidence that antibody based Gal3 blockade may be a viable therapeutic strategy in patients with MUC16-expressing tumors, supporting further development of human blocking antibodies against Gal3 as potential cancer therapeutics.
High levels of 27-hydroxycholesterol results in synaptic plasticity alterations in the hippocampus
Authors: Loera-Valencia Raul , Vazquez-Juarez Erika , Muñoz Alberto , Gerenu Gorka , Gómez-Galán Marta , Lindskog Maria , DeFelipe Javier , Cedazo-Minguez Angel , Merino-Serrais Paula 
Published: February 2021

AbstractAlterations in brain cholesterol homeostasis in midlife are correlated with a higher risk of developing Alzheimer’s disease (AD). However, global cholesterol-lowering therapies have yielded mixed results when it comes to slowing down or preventing cognitive decline in AD. We used the transgenic mouse model Cyp27Tg, with systemically high levels of 27-hydroxycholesterol (27-OH) to examine long-term potentiation (LTP) in the hippocampal CA1 region, combined with dendritic spine reconstruction of CA1 pyramidal neurons to detect morphological and functional synaptic alterations induced by 27-OH high levels. Our results show that elevated 27-OH levels lead to enhanced LTP in the Schaffer collateral-CA1 synapses. This increase is correlated with abnormally large dendritic spines in the stratum radiatum. Using immunohistochemistry for synaptopodin (actin-binding protein involved in the recruitment of the spine apparatus), we found a significantly higher density of synaptopodin-positive puncta in CA1 in Cyp27Tg mice. We hypothesize that high 27-OH levels alter synaptic potentiation and could lead to dysfunction of fine-tuned processing of information in hippocampal circuits resulting in cognitive impairment. We suggest that these alterations could be detrimental for synaptic function and cognition later in life, representing a potential mechanism by which hypercholesterolemia could lead to alterations in memory function in neurodegenerative diseases.
Pupil dilation reflects the authenticity of received nonverbal vocalizations
Authors: Cosme Gonçalo , Rosa Pedro J. , Lima César F. , Tavares Vânia , Scott Sophie , Chen Sinead , Wilcockson Thomas D. W. , Crawford Trevor J. , Prata Diana 
Published: February 2021

AbstractThe ability to infer the authenticity of other’s emotional expressions is a social cognitive process taking place in all human interactions. Although the neurocognitive correlates of authenticity recognition have been probed, its potential recruitment of the peripheral autonomic nervous system is not known. In this work, we asked participants to rate the authenticity of authentic and acted laughs and cries, while simultaneously recording their pupil size, taken as proxy of cognitive effort and arousal. We report, for the first time, that acted laughs elicited higher pupil dilation than authentic ones and, reversely, authentic cries elicited higher pupil dilation than acted ones. We tentatively suggest the lack of authenticity in others’ laughs elicits increased pupil dilation through demanding higher cognitive effort; and that, reversely, authenticity in cries increases pupil dilation, through eliciting higher emotional arousal. We also show authentic vocalizations and laughs (i.e. main effects of authenticity and emotion) to be perceived as more authentic, arousing and contagious than acted vocalizations and cries, respectively. In conclusion, we show new evidence that the recognition of emotional authenticity can be manifested at the level of the autonomic nervous system in humans. Notwithstanding, given its novelty, further independent research is warranted to ascertain its psychological meaning.
Capturing yeast associated with grapes and spontaneous fermentations of the Negro Saurí minority variety from an experimental vineyard near León
Authors: González-Alonso Isora , Walker Michelle Elisabeth , Vallejo-Pascual María-Eva , Naharro-Carrasco Gérmán , Jiranek Vladimir 
Published: February 2021

Abstract‘Microbial terroir’ relates to the influence of autochthonous yeasts associated with a grape cultivar on the resultant wine. Geographic region, vineyard site and topography, climate and vintage influence the biodiversity of these microbial communities. Current research focus attempts to correlate their ‘microbial fingerprint’ to the sensorial and chemical characteristics of varietal wines from distinct geographical wine regions. This study focuses on the minor red grape variety, Negro Saurí, which has seen a resurgence in the León Appellation of Origin in Spain as a varietal wine. An experimental vineyard at Melgarajo S.A. (42° 15′ 48.68_N 5° 9′ 56.66_W) was sampled over four consecutive vintages, with autochthonous yeasts being isolated from grapes, must and pilot-scale un-inoculated fermentations, and identified by ITS sequencing. Forty-nine isolates belonging toMetschnikowia pulcherrima,Lachancea thermotolerans,Hanseniaspora uvarumandTorulaspora delbrueckiiwere isolated from grapes and must, and early stages of fermentation dependent on seasonal variation.Saccharomyces cerevisiaepredominated throughout fermentation, as a heterogeneous and dynamic population, with seven major biotypes identified amongst 110 isolates across four consecutive vintages. Twenty-fourS. cerevisiaeisolates representing five strains dominated in two or more vintages. Their persistence through fermentation warrants further validation of their oenological properties as starter cultures.
Highly conductive anion exchange membranes based on polymer networks containing imidazolium functionalised side chains
Authors: Abouzari-Lotf Ebrahim , Jacob Mohan V. , Ghassemi Hossein , Zakeri Masoumeh , Nasef Mohamed Mahmoud , Abdolahi Yadollah , Abbasi Ali , Ahmad Arshad 
Published: February 2021

AbstractTwo novel types of anion exchange membranes (AEMs) having imidazolium-type functionalised nanofibrous substrates were prepared using the facile and potentially scalable method. The membranes’ precursors were prepared by graft copolymerization of vinylbenzyl chloride (VBC) onto syndiotactic polypropylene (syn-PP) and polyamide-66 (PA-66) nanofibrous networks followed by crosslinking with 1,8-octanediamine, thermal treatment and subsequent functionalisation of imidazolium groups. The obtained membranes displayed an ion exchange capacity (IEC) close to 1.9 mmol g–1 and ionic (OH-) conductivity as high as 130 mS cm–1 at 80 °C. This was coupled with a reasonable alkaline stability representing more than 70% of their original conductivity under accelerated degradation test in 1 M KOH at 80 °C for 360 h. The effect of ionomer binder on the performance of the membrane electrode assembly (MEA) in AEM fuel cell was evaluated with the optimum membrane. The MEA showed a power density of as high as 440 mW cm−2 at a current density is 910 mA cm−2 with diamine crosslinked quaternized polysulfone (DAPSF) binder at 80 °C with 90% humidified H2 and O2 gases. Such performance was 2.3 folds higher than the corresponding MEA performance with quaternary ammonium polysulfone (QAPS) binder at the same operating conditions. Overall, the newly developed membrane was found to possess not only an excellent combination of physico-chemical properties and a reasonable stability but also to have a facile preparation procedure and cheap ingredients making it a promising candidate for application in AEM fuel cell.
Fish ecotyping based on machine learning and inferred network analysis of chemical and physical properties
Authors: Wei Feifei , Ito Kengo , Sakata Kenji , Asakura Taiga , Date Yasuhiro , Kikuchi Jun 
Published: February 2021

AbstractFunctional diversity rather than species richness is critical for the understanding of ecological patterns and processes. This study aimed to develop novel integrated analytical strategies for the functional characterization of fish diversity based on the quantification, prediction and integration of the chemical and physical features in fish muscles. Machine learning models with an improved random forest algorithm applied on 1867 muscle nuclear magnetic resonance spectra belonging to 249 fish species successfully predicted the mobility patterns of fishes into four categories (migratory, territorial, rockfish, and demersal) with accuracies of 90.3–95.4%. Markov blanket-based feature selection method with an ecological–chemical–physical integrated network based on the Bayesian network inference algorithm highlighted the importance of nitrogen metabolism, which is critical for environmental adaptability of fishes in nutrient-rich environments, in the functional characterization of fish biodiversity. Our study provides valuable information and analytical strategies for fish home-range assessment on the basis of the chemical and physical characterization of fish muscle, which can serve as an ecological indicator for fish ecotyping and human impact monitoring.
Mechanism of karyopherin-β2 binding and nuclear import of ALS variants FUS(P525L) and FUS(R495X)
Authors: Gonzalez Abner , Mannen Taro , Çağatay Tolga , Fujiwara Ayano , Matsumura Hiroyoshi , Niesman Ashley B. , Brautigam Chad A. , Chook Yuh Min , Yoshizawa Takuya 
Published: February 2021

AbstractMutations in the RNA-binding protein FUS cause familial amyotropic lateral sclerosis (ALS). Several mutations that affect the proline-tyrosine nuclear localization signal (PY-NLS) of FUS cause severe juvenile ALS. FUS also undergoes liquid–liquid phase separation (LLPS) to accumulate in stress granules when cells are stressed. In unstressed cells, wild type FUS resides predominantly in the nucleus as it is imported by the importin Karyopherin-β2 (Kapβ2), which binds with high affinity to the C-terminal PY-NLS of FUS. Here, we analyze the interactions between two ALS-related variants FUS(P525L) and FUS(R495X) with importins, especially Kapβ2, since they are still partially localized to the nucleus despite their defective/missing PY-NLSs. The crystal structure of the Kapβ2·FUS(P525L)PY-NLS complex shows the mutant peptide making fewer contacts at the mutation site, explaining decreased affinity for Kapβ2. Biochemical analysis revealed that the truncated FUS(R495X) protein, although missing the PY-NLS, can still bind Kapβ2 and suppresses LLPS. FUS(R495X) uses its C-terminal tandem arginine-glycine-glycine regions, RGG2 and RGG3, to bind the PY-NLS binding site of Kapβ2 for nuclear localization in cells when arginine methylation is inhibited. These findings suggest the importance of the C-terminal RGG regions in nuclear import and LLPS regulation of ALS variants of FUS that carry defective PY-NLSs.
Cholesterol as a modulator of cannabinoid receptor CB2 signaling
Authors: Yeliseev Alexei , Iyer Malliga R. , Joseph Thomas T. , Coffey Nathan J. , Cinar Resat , Zoubak Lioudmila , Kunos George , Gawrisch Klaus 
Published: February 2021

AbstractSignaling through integral membrane G protein-coupled receptors (GPCRs) is influenced by lipid composition of cell membranes. By using novel high affinity ligands of human cannabinoid receptor CB2, we demonstrate that cholesterol increases basal activation levels of the receptor and alters the pharmacological categorization of these ligands. Our results revealed that (2-(6-chloro-2-((2,2,3,3-tetramethylcyclopropane-1-carbonyl)imino)benzo[d]thiazol-3(2H)-yl)ethyl acetate ligand (MRI-2646) acts as a partial agonist of CB2 in membranes devoid of cholesterol and as a neutral antagonist or a partial inverse agonist in cholesterol-containing membranes. The differential effects of a specific ligand on activation of CB2 in different types of membranes may have implications for screening of drug candidates in a search of modulators of GPCR activity. MD simulation suggests that cholesterol exerts an allosteric effect on the intracellular regions of the receptor that interact with the G-protein complex thereby altering the recruitment of G protein.
Trends in osteoporosis and mean bone density among type 2 diabetes patients in the US from 2005 to 2014
Authors: Xu Yingke , Wu Qing 
Published: February 2021

AbstractThis study aimed to examine how bone health changed among T2DM patients in the past decade. Continuous National Health and Nutrition Examination Survey (NHANES) data from 2005–2006 to 2013–2014 were analyzed to examine the trends of bone mineral density (BMD) and the prevalence trends of osteoporosis osteopenia among T2DM patients and non-diabetic people aged 40 years and older. The age- and BMI-adjusted mean BMD of the femur neck for the four NHANES cycles decreased linearly in both T2DM patients and non-diabetic people (both Plinear trend ≤ 0.009). Among women with T2DM, the mean BMD in 2013–2014 was significantly lower than that in 2005–2006, even after adjusting for multiple covariates. During 2005–2014, the prevalence of osteoporosis among T2DM patients and non-diabetic people increased but with no significant linear trend (both Plinear trend > 0.05), while the prevalence of osteopenia in the two populations increased linearly (both Plinear trend < 0.04). Age- and BMI-adjusted mean BMD decreased in 2013–2014 in patients with T2DM and non-diabetic people, while the prevalence of osteoporosis and osteopenia increased in both groups.
Evaluation of the usefulness of saliva for mosaic loss of chromosome Y analysis
Authors: Hachiya Tsuyoshi , Kobayashi Takuro , Tsutae Wataru , Gan Pamela Hui Peng , Baran Iri Sato , Horie Shigeo 
Published: February 2021

AbstractMosaic loss of chromosome Y (mLOY) in leukocytes has attracted much attention as an emerging biomarker of aging and aging-related diseases. We evaluated the usefulness of saliva for mLOY analysis and showed that saliva-derived mLOY is significantly associated with aging and increased physical activity, but not with smoking. While these data support the robust association between saliva-derived mLOY and aging, caution is required when comparing data from saliva-derived and blood-derived mLOY.
Soluble urokinase-type plasminogen activator receptor (suPAR) is a risk indicator for eGFR loss in kidney transplant recipients
Authors: Jehn Ulrich , Schütte-Nütgen Katharina , Henke Ute , Pavenstädt Hermann , Suwelack Barbara , Reuter Stefan 
Published: February 2021

AbstractThe prognostic significance of suPAR in various kidney diseases has recently been demonstrated. Its role in transplantation-specific outcomes is still largely unknown. Therefore, we prospectively investigated the prognostic relevance of suPAR in patients before and one year after kidney transplantation (KTx). We included 100 patients who had received a kidney transplantation between 2013 and 2015. The plasma concentration of suPAR was measured by ELISA assay. In recipients of living donations (LD), pre-transplant suPAR levels were significantly lower than those of recipients of deceased donations (DD). After KTx, suPAR levels significantly declined in LD and DD recipients, without a detectable difference between both groups any more. Higher suPAR levels in recipients one year after KTx were associated with a more severe eGFR loss in the following three years in multivariable cox-regression (n = 82, p = 0.021). suPAR-levels above 6212 pg/ml one year after KTx are associated with eGFR loss > 30%, which occurred almost twice as fast as in patients with suPAR ≤ 6212 pg/ml (p < 0.001). Hence, suPAR level at one year mark might be a risk indicator of increased eGFR loss.
The acute transcriptional responses to dietary methionine restriction are triggered by inhibition of ternary complex formation and linked to Erk1/2, mTOR, and ATF4
Authors: Stone Kirsten P. , Ghosh Sujoy , Kovalik Jean Paul , Orgeron Manda , Wanders Desiree , Sims Landon C. , Gettys Thomas W. 
Published: February 2021

AbstractThe initial sensing of dietary methionine restriction (MR) occurs in the liver where it activates an integrated stress response (ISR) that quickly reduces methionine utilization. The ISR program is regulated in part by ATF4, but ATF4’s prototypical upstream regulator, eIF2α, is not acutely activated by MR. Bioinformatic analysis of RNAseq and metabolomics data from liver samples harvested 3 h and 6 h after initiating MR shows that general translation is inhibited at the level of ternary complex formation by an acute 50% reduction of hepatic methionine that limits formation of initiator methionine tRNA. The resulting ISR is induced by selective expression of ATF4 target genes that mediate adaptation to reduced methionine intake and return hepatic methionine to control levels within 4 days of starting the diet. Complementary in vitro experiments in HepG2 cells after knockdown of ATF4, or inhibition of mTOR or Erk1/2 support the conclusion that the early induction of genes by MR is partially dependent on ATF4 and regulated by both mTOR and Erk1/2. Taken together, these data show that initiation of dietary MR induces an mTOR- and Erk1/2-dependent stress response that is linked to ATF4 by the sharp, initial drop in hepatic methionine and resulting repression of translation pre-initiation.
The relation between Lyαabsorbers and local galaxy filaments
Authors: Bouma S. J. D. , Richter P. , Wendt M. 
Published: February 2021

Context.The intergalactic medium (IGM) is believed to contain the majority of baryons in the universe and to trace the same dark matter structure as galaxies, forming filaments and sheets. Lyαabsorbers, which sample the neutral component of the IGM, have been extensively studied at low and high redshift, but the exact relation between Lyαabsorption, galaxies, and the large-scale structure is observationally not well constrained.Aims.In this study, we aim at characterising the relation between Lyαabsorbers and nearby over-dense cosmological structures (galaxy filaments) at recession velocities Δv ≤ 6700 km s−1by using archival observational data from various instruments.Methods.We analyse 587 intervening Lyαabsorbers in the spectra of 302 extragalactic background sources obtained with the Cosmic Origins Spectrograph (COS) installed on theHubbleSpace Telescope (HST). We combine the absorption line information with galaxy data of five local galaxy filaments from the V8k catalogue.Results.Along the 91 sightlines that pass close to a filament, we identify 215 (227) Lyαabsorption systems (components). Among these, 74 Lyαsystems are aligned in position and velocity with the galaxy filaments, indicating that these absorbers and the galaxies trace the same large-scale structure. The filament-aligned Lyαabsorbers have a ∼90% higher rate of incidence (d𝒩/dz = 189 for logN(H I) ≥ 13.2) and a slightly shallower column density distribution function slope (−β = −1.47) relative to the general Lyαpopulation atz = 0, reflecting the filaments’ matter over-density. The strongest Lyαabsorbers are preferentially found near galaxies or close to the axis of a filament, although there is substantial scatter in this relation. Our sample of absorbers clusters more strongly around filament axes than a randomly distributed sample would do (as confirmed by a Kolmogorov–Smirnov test), but the clustering signal is less pronounced than for the galaxies in the filaments.
Frame decompositions of bounded linear operators in Hilbert spaces with applications in tomography
Authors: Hubmer Simon , Ramlau Ronny 
Published: February 2021

Abstract
We consider the decomposition of bounded linear operators on Hilbert spaces in terms of functions forming frames. Similar to the singular-value decomposition, the resulting frame decompositions encode information on the structure and ill-posedness of the problem and can be used as the basis for the design and implementation of efficient numerical solution methods. In contrast to the singular-value decomposition, the presented frame decompositions can be derived explicitly for a wide class of operators, in particular for those satisfying a certain stability condition. In order to show the usefulness of this approach, we consider different examples from the field of tomography.