bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing Eddying (1/12°) Ocean Reanalysis GLORYS12 Using the 14‐yr Instrumental Record From 59.5°N Section in the Atlantic
Authors: Verezemskaya Polina , Barnier Bernard , Gulev Sergey K. , Gladyshev Sergey , Molines Jean‐Marc , Gladyshev Vsevolod , Lellouche Jean‐Michel , Gavrikov Alexander 
Published: June 2021

AbstractThe eddy‐resolving (1/12°) global ocean reanalysis GLORYS12 is assessed against 14 years (2002–2015) of independent hydrographic observations collected at 59.5°N in the North Atlantic. Two multi‐observations statistical analyses, ISAS‐15 and ARMOR‐3D, and an eddy‐permitting (1/4°) reanalysis, GLORYS025, also contribute to this comparison. The mean thermohaline structure along the 59.5°N section revealed by the observations is well‐reproduced by GLORYS12, except for the overflow waters. A good agreement with observations is found for linear trends over the whole period, exhibiting a dipole‐like pattern with a cooling/freshening in the main thermocline and a warming/salinization below. However, localized discrepancies with observations suggest the need for improvement in the reanalysis system (especially in the overflows representation and the consistency between the forcing and data assimilation system) and the deep observational array. The reanalysis reliably represents the ocean heat content in the upper 700‐m layer but shows significant differences with observations between 700 and 2,000 m. The meridional volume and heat transports across the 59.5°N section are compared for years when ADCP observations were available. The reanalysis does not reproduce the variability observed in the western boundary current but agrees well with observed transports in the other parts of the section. The reanalysis reproduces the major mesoscale eddy features that contribute to the meridional transport and provides the large‐scale context of their location. The analysis of time correlation at all measurement points demonstrated that GLORYS12 is the most accurate among the analyzed datasets used in this study to represent and explain the observed ocean characteristics and variability along that section.
Prioritization framework for improving the value of care for very low birth weight and very preterm infants
Authors: King Brian C. , Richardson Troy , Patel Ravi M. , Lee Henry C. , Bamat Nicolas A. , Hall Matthew , Slaughter Jonathan L. 
Published: June 2021

AbstractObjectiveCreate a prioritization framework for value-based improvement in neonatal care.Study designA retrospective cohort study of very low birth weight (<1500 g) and/or very preterm (<32 weeks) infants discharged between 2012 and 2019 using the Pediatric Health Information System Database. Resource use was compared across hospitals and adjusted for patient-level differences. A prioritization score was created combining cost, patient exposure, and inter-hospital variability to rank resource categories.ResultsResource categories with the greatest cost, patient exposure, and inter-hospital variability were parenteral nutrition, hematology (lab testing), and anticoagulation (for central venous access and therapy), respectively. Based on our prioritization score, parenteral nutrition was identified as the highest priority overall.ConclusionsWe report the development of a prioritization score for potential value-based improvement in neonatal care. Our findings suggest that parenteral nutrition, central venous access, and high-volume laboratory and imaging modalities should be priorities for future comparative effectiveness and quality improvement efforts.
Long non-coding RNA Lnc-408 promotes invasion and metastasis of breast cancer cell by regulating LIMK1
Authors: Qiao Yina , Jin Ting , Guan Shengdong , Cheng Shaojie , Wen Siyang , Zeng Huan , Zhao Maojia , Yang Liping , Wan Xueying , Qiu Yuxiang , Li Qiao , Liu Manran , Hou Yixuan 
Published: June 2021

AbstractInvasion and metastasis are the leading causes of death in patients with breast cancer (BC), and epithelial-mesenchymal transformation (EMT) plays an essential role in this process. Here, we found that Lnc-408, a novel long noncoding RNA (lncRNA), is significantly upregulated in BC cells undergoing EMT and in BC tumor with lymphatic metastases compared with those without lymphatic metastases. Lnc-408 can enhance BC invasion and metastasis by regulating the expression of LIMK1. Mechanistically, Lnc-408 serves as a sponge for miR-654-5p to relieve the suppression of miR-654-5p on its target LIMK1. Knockdown or knockout of Lnc-408 in invasive BC cells clearly decreased LIMK1 levels, and ectopic Lnc-408 in MCF-7 cells increased LIMK1 expression to promote cell invasion. Lnc-408-mediated enhancement of LIMK1 plays a key role in cytoskeletal stability and promotes invadopodium formation in BC cells via p-cofilin/F-actin. In addition, the increased LIMK1 also facilitates the expression of MMP2, ITGB1, and COL1A1 by phosphorylating CREB. In conclusion, our findings reveal that Lnc-408 promotes BC invasion and metastasis via the Lnc-408/miR-654-5p/LIMK1 axis, highlighting a novel promising target for the diagnosis and treatment of BC.
Genetic underpinnings of affective temperaments: a pilot GWAS investigation identifies a new genome-wide significant SNP for anxious temperament in ADGRB3 gene
Authors: Gonda Xenia , Eszlari Nora , Torok Dora , Gal Zsofia , Bokor Janos , Millinghoffer Andras , Baksa Daniel , Petschner Peter , Antal Peter , Breen Gerome , Juhasz Gabriella , Bagdy Gyorgy 
Published: June 2021

AbstractAlthough recently a large-sample GWASs identified significant loci in the background of depression, the heterogeneity of the depressive phenotype and the lack of accurate phenotyping hinders applicability of findings. We carried out a pilot GWAS with in-depth phenotyping of affective temperaments, considered as subclinical manifestations and high-risk states for affective disorders, in a general population sample of European origin. Affective temperaments were measured by TEMPS-A. SNP-level association was assessed by linear regression models, assuming an additive genetic effect, using PLINK1.9. Gender, age, the first ten principal components (PCs) and the other four temperaments were included in the regression models as covariates. SNP-level relevances (p-values) were aggregated to gene level using the PEGASUS method1. In SNP-based tests, a Bonferroni-corrected significance threshold of p ≤ 5.0 × 10−8 and a suggestive significance threshold of p ≤ 1.0 × 10−5, whereas in gene-based tests a Bonferroni-corrected significance of 2.0 × 10−6 and a suggestive significance of p ≤ 4.0 × 10−4 was established. To explore known functional effects of the most significant SNPs, FUMA v1.3.5 was used. We identified 1 significant and 21 suggestively significant SNPs in ADGRB3, expressed in the brain, for anxious temperament. Several other brain-relevant SNPs and genes emerged at suggestive significance for the other temperaments. Functional analyses reflecting effect on gene expression and participation in chromatin interactions also pointed to several genes expressed in the brain with potentially relevant phenotypes regulated by our top SNPs. Our findings need to be tested in larger GWA studies and candidate gene analyses in well-phenotyped samples in relation to affective disorders and related phenotypes.
Transcriptome-(phospho)proteome characterization of brain of a germline model of cytoplasmic-predominant Pten expression with autism-like phenotypes
Authors: Thacker Stetson , Eng Charis 
Published: June 2021

AbstractPTEN has a strong Mendelian association with autism spectrum disorder (ASD), representing a special case in autism’s complex genetic architecture. Animal modeling for constitutional Pten mutation creates an opportunity to study how disruption of Pten affects neurobiology and glean potential insight into ASD pathogenesis. Subsequently, we comprehensively characterized the neural (phospho)proteome of Ptenm3m4/m3m4 mice, which exhibits cytoplasmic-predominant Pten expression, by applying mass spectrometry technology to their brains at two-weeks- (P14) and six-weeks-of-age (P40). The differentially expressed/phosphorylated proteins were subjected to gene enrichment, pathway, and network analyses to assess the affected biology. We identified numerous differentially expressed/phosphorylated proteins, finding greater dysregulation at P40 consistent with prior transcriptomic data. The affected pathways were largely related to PTEN function or neurological processes, while scant direct overlap was found across datasets. Network analysis pointed to ASD risk genes like Pten and Psd-95 as major regulatory hubs, suggesting they likely contribute to initiation or maintenance of cellular and perhaps organismal phenotypes related to ASD.
The prevalence, genetic complexity and population-specific founder effects of human autosomal recessive disorders
Authors: Xiao Qingyang , Lauschke Volker M. 
Published: June 2021

AbstractAutosomal recessive (AR) disorders pose a significant burden for public health. However, despite their clinical importance, epidemiology and molecular genetics of many AR diseases remain poorly characterized. Here, we analyzed the genetic variability of 508 genes associated with AR disorders based on sequencing data from 141,456 individuals across seven ethnogeographic groups by integrating variants with documented pathogenicity from ClinVar, with stringent functionality predictions for variants with unknown pathogenicity. We first validated our model using 85 diseases for which population-specific prevalence data were available and found that our estimates strongly correlated with the respective clinically observed disease frequencies (r = 0.68; p < 0.0001). We found striking differences in population-specific disease prevalence with 101 AR diseases (27%) being limited to specific populations, while an additional 305 diseases (68%) differed more than tenfold across major ethnogeographic groups. Furthermore, by analyzing genetic AR disease complexity, we confirm founder effects for cystic fibrosis and Stargardt disease, and provide strong evidences for >25 additional population-specific founder mutations. The presented analyses reveal the molecular genetics of AR diseases with unprecedented resolution and provide insights into epidemiology, complexity, and population-specific founder effects. These data can serve as a powerful resource for clinical geneticists to inform population-adjusted genetic screening programs, particularly in otherwise understudied ethnogeographic groups.
Optimal teleportation via noisy quantum channels without additional qubit resources
Authors: Im Dong-Gil , Lee Chung-Hyun , Kim Yosep , Nha Hyunchul , Kim M. S. , Lee Seung-Woo , Kim Yoon-Ho 
Published: June 2021

AbstractQuantum teleportation exemplifies how the transmission of quantum information starkly differs from that of classical information and serves as a key protocol for quantum communication and quantum computing. While an ideal teleportation protocol requires noiseless quantum channels to share a pure maximally entangled state, the reality is that shared entanglement is often severely degraded due to various decoherence mechanisms. Although the quantum noise induced by the decoherence is indeed a major obstacle to realizing a near-term quantum network or processor with a limited number of qubits, the methodologies considered thus far to address this issue are resource-intensive. Here, we demonstrate a protocol that allows optimal quantum teleportation via noisy quantum channels without additional qubit resources. By analyzing teleportation in the framework of generalized quantum measurement, we optimize the teleportation protocol for noisy quantum channels. In particular, we experimentally demonstrate that our protocol enables to teleport an unknown qubit even via a single copy of an entangled state under strong decoherence that would otherwise preclude any quantum operation. Our work provides a useful methodology for practically coping with decoherence with a limited number of qubits and paves the way for realizing noisy intermediate-scale quantum computing and quantum communication.
Preclinical assessment on neuronal regeneration in the injury-related microenvironment of graphene-based scaffolds
Authors: Qian Yun , Wang Xu , Song Jialin , Chen Wei , Chen Shuai , Jin Yi , Ouyang Yuanming , Yuan Wei-En , Fan Cunyi 
Published: June 2021

AbstractAs the application of graphene nanomaterials gets increasingly attractive in the field of tissue engineering and regenerative medicine, the long-term evaluation is necessary and urgent as to their biocompatibility and regenerative capacity in different tissue injuries, such as nerve, bone, and heart. However, it still remains controversial about the potential biological effects of graphene on neuronal activity, especially after severe nerve injuries. In this study, we establish a lengthy peripheral nerve defect rat model and investigate the potential toxicity of layered graphene-loaded polycaprolactone scaffold after implantation during 18 months in vivo. In addition, we further identify possible biologically regenerative effects of this scaffold on myelination, axonal outgrowth, and locomotor function recovery. It is confirmed that graphene-based nanomaterials exert negligible toxicity and repair large nerve defects by dual regulation of Schwann cells and astroglia in the central and peripheral nervous systems. The findings enlighten the future of graphene nanomaterial as a key type of biomaterials for clinical translation in neuronal regeneration.
Change by challenge: A common genetic basis behind childhood cognitive development and cognitive training
Authors: Sauce Bruno , Wiedenhoeft John , Judd Nicholas , Klingberg Torkel 
Published: June 2021

AbstractThe interplay of genetic and environmental factors behind cognitive development has preoccupied multiple fields of science and sparked heated debates over the decades. Here we tested the hypothesis that developmental genes rely heavily on cognitive challenges—as opposed to natural maturation. Starting with a polygenic score (cogPGS) that previously explained variation in cognitive performance in adults, we estimated its effect in 344 children and adolescents (mean age of 12 years old, ranging from 6 to 25) who showed changes in working memory (WM) in two distinct samples: (1) a developmental sample showing significant WM gains after 2 years of typical, age-related development, and (2) a training sample showing significant, experimentally-induced WM gains after 25 days of an intense WM training. We found that the same genetic factor, cogPGS, significantly explained the amount of WM gain in both samples. And there was no interaction of cogPGS with sample, suggesting that those genetic factors are neutral to whether the WM gains came from development or training. These results represent evidence that cognitive challenges are a central piece in the gene-environment interplay during cognitive development. We believe our study sheds new light on previous findings of interindividual differences in education (rich-get-richer and compensation effects), brain plasticity in children, and the heritability increase of intelligence across the lifespan.
Alterations in lipid profile upon uterine fibroids and its recurrence
Authors: Tonoyan Narine M. , Chagovets Vitaliy V. , Starodubtseva Natalia L. , Tokareva Alisa O. , Chingin Konstantin , Kozachenko Irena F. , Adamyan Leyla V. , Frankevich Vladimir E. 
Published: June 2021

AbstractUterine fibroids (UF) is the most common (about 70% cases) type of gynecological disease, with the recurrence rate varying from 11 to 40%. Because UF has no distinct symptomatology and is often asymptomatic, the specific and sensitive diagnosis of UF as well as the assessment for the probability of UF recurrence pose considerable challenge. The aim of this study was to characterize alterations in the lipid profile of tissues associated with the first-time diagnosed UF and recurrent uterine fibroids (RUF) and to explore the potential of mass spectrometry (MS) lipidomics analysis of blood plasma samples for the sensitive and specific determination of UF and RUF with low invasiveness of analysis. MS analysis of lipid levels in the myometrium tissues, fibroids tissues and blood plasma samples was carried out on 66 patients, including 35 patients with first-time diagnosed UF and 31 patients with RUF. The control group consisted of 15 patients who underwent surgical treatment for the intrauterine septum. Fibroids and myometrium tissue samples were analyzed using direct MS approach. Blood plasma samples were analyzed using high performance liquid chromatography hyphened with mass spectrometry (HPLC/MS). MS data were processed by discriminant analysis with projection into latent structures (OPLS-DA). Significant differences were found between the first-time UF, RUF and control group in the levels of lipids involved in the metabolism of glycerophospholipids, sphingolipids, lipids with an ether bond, triglycerides and fatty acids. Significant differences between the control group and the groups with UF and RUF were found in the blood plasma levels of cholesterol esters, triacylglycerols, (lyso) phosphatidylcholines and sphingomyelins. Significant differences between the UF and RUF groups were found in the blood plasma levels of cholesterol esters, phosphotidylcholines, sphingomyelins and triacylglycerols. Diagnostic models based on the selected differential lipids using logistic regression showed sensitivity and specificity of 88% and 86% for the diagnosis of first-time UF and 95% and 79% for RUF, accordingly. This study confirms the involvement of lipids in the pathogenesis of uterine fibroids. A diagnostically significant panel of differential lipid species has been identified for the diagnosis of UF and RUF by low-invasive blood plasma analysis. The developed diagnostic models demonstrated high potential for clinical use and further research in this direction.
Greater genetic risk for adult psychiatric diseases increases vulnerability to adverse outcome after preterm birth
Authors: Cullen Harriet , Selzam Saskia , Dimitrakopoulou Konstantina , Plomin Robert , Edwards A. David 
Published: June 2021

AbstractPreterm birth is an extreme environmental stress associated with an increased risk of later cognitive dysfunction and mental health problems. However, the extent to which preterm birth is modulated by genetic variation remains largely unclear. Here, we test for an interaction effect between psychiatric polygenic risk and gestational age at birth on cognition at age four. Our sample comprises 4934 unrelated individuals (2066 individuals born < 37 weeks, 918 born <  = 34 weeks). Genome-wide polygenic scores (GPS’s) were calculated for each individual for five different psychiatric pathologies: Schizophrenia, Bipolar Disorder, Major Depressive Disorder, Attention Deficit Hyperactivity Disorder and Autism Spectrum Disorder. Linear regression modelling was used to estimate the interaction effect between psychiatric GPS and gestational age at birth (GA) on cognitive outcome for the five psychiatric disorders. We found a significant interaction effect between Schizophrenia GPS and GA (β = 0.038 ± 0.013, p = 6.85 × 10–3) and Bipolar Disorder GPS and GA (β = 0.038 ± 0.014, p = 6.61 × 10–3) on cognitive outcome. Individuals with greater genetic risk for Schizophrenia or Bipolar Disorder are more vulnerable to the adverse effects of birth at early gestational age on brain development, as assessed by cognition at age four. Better understanding of gene-environment interactions will inform more effective risk-reducing interventions for this vulnerable population.
Genomic analysis and phylogenetic position of the complex IncC plasmid found in the Spanish monophasic clone of Salmonella enterica serovar Typhimurium
Authors: Vázquez Xenia , García Patricia , García Vanesa , de Toro María , Ladero Víctor , Heinisch Jürgen J. , Fernández Javier , Rodicio Rosaura , Rodicio M. Rosario 
Published: June 2021

AbstractpUO-STmRV1 is an IncC plasmid discovered in the Spanish clone of the emergent monophasic variant of Salmonella enterica serovar Typhimurium, which has probably contributed to its epidemiological success. The sequence of the entire plasmid determined herein revealed a largely degenerated backbone with accessory DNA incorporated at four different locations. The acquired DNA constitutes more than two-thirds of the pUO-STmRV1 genome and originates from plasmids of different incompatibility groups, including IncF (such as R100 and pSLT, the virulence plasmid specific of S. Typhimurium), IncN and IncI, from the integrative element GIsul2, or from yet unknown sources. In addition to pSLT virulence genes, the plasmid carries genes conferring resistance to widely-used antibiotics and heavy metals, together with a wealth of genetic elements involved in DNA mobility. The latter comprise class 1 integrons, transposons, pseudo-transposons, and insertion sequences, strikingly with 14 copies of IS26, which could have played a crucial role in the assembly of the complex plasmid. Typing of pUO-STmRV1 revealed backbone features characteristically associated with type 1 and type 2 IncC plasmids and could therefore be regarded as a hybrid plasmid. However, a rooted phylogenetic tree based on core genes indicates that it rather belongs to an ancient lineage which diverged at an early stage from the branch leading to most extant IncC plasmids detected so far. pUO-STmRV1 may have evolved at a time when uncontrolled use of antibiotics and biocides favored the accumulation of multiple resistance genes within an IncC backbone. The resulting plasmid thus allowed the Spanish clone to withstand a wide variety of adverse conditions, while simultaneously promoting its own propagation through vertical transmission.
57Fe and 151Eu Mössbauer studies of 3d-4f spin interplay in EuFe2−xNixAs2
Authors: Komędera K. , Gatlik J. , Błachowski A. , Żukrowski J. , Rybicki D. , Delekta A. , Babij M. , Bukowski Z. 
Published: June 2021

AbstractThe EuFe2−xNixAs2 (with 0 ≤ x ≤ 0.4) compounds exhibiting 3d and/or 4f magnetic order were investigated by means of 57Fe and 151Eu Mössbauer spectroscopy. Additionally, results for EuNi2As2 are reported for comparison. It was found that spin-density-wave order of the Fe itinerant moments is monotonically suppressed by Ni-substitution. However, the 3d magnetic order survives at the lowest temperature up to at least x = 0.12 and it is certainly completely suppressed for x = 0.20. The Eu localized moments order regardless of the Ni concentration, but undergo a spin reorientation with increasing x from alignment parallel to the a-axis in the parent compound, toward c-axis alignment for x > 0.07. Change of the 4f spins ordering from antiferromagnetic to ferromagnetic takes place simultaneously with a disappearance of the 3d spins order what is the evidence of a strong coupling between magnetism of Eu2+ ions and the conduction electrons of [Fe2−xNixAs2]2- layers. The Fe nuclei experience the transferred hyperfine magnetic field due to the Eu2+ ordering for Ni-substituted samples with x > 0.04, while the transferred field is undetectable in EuFe2As2 and for compound with a low Ni-substitution level. It seems that the 4f ferromagnetic component arising from a tilt of the Eu2+ moments to the crystallographic c-axis leads to the transferred magnetic field at the Fe atoms. Superconductivity is not observed down to 1.8 K, although a comparison with 57Fe and 151Eu Mössbauer data for EuFe2As2-based superconductors indicates a similar magnetic structure.