bluuebunny/crossref_metadata_2025_split huggingface dataset:
A piggyBac-based platform for genome editing and clonal rhesus macaque iPSC line derivation
Authors: Rodriguez-Polo Ignacio , Mißbach Sophie , Petkov Stoyan , Mattern Felix , Maierhofer Anna , Grządzielewska Iga , Tereshchenko Yuliia , Urrutia-Cabrera Daniel , Haaf Thomas , Dressel Ralf , Bartels Iris , Behr Rüdiger 
Published: July 2021

AbstractNon-human primates (NHPs) are, due to their close phylogenetic relationship to humans, excellent animal models to study clinically relevant mutations. However, the toolbox for the genetic modification of NHPs is less developed than those for other species like mice. Therefore, it is necessary to further develop and refine genome editing approaches in NHPs. NHP pluripotent stem cells (PSCs) share key molecular signatures with the early embryo, which is an important target for genomic modification. Therefore, PSCs are a valuable test system for the validation of embryonic genome editing approaches. In the present study, we made use of the versatility of thepiggyBactransposon system for different purposes in the context of NHP stem cell technology and genome editing. These include (1) Robust reprogramming of rhesus macaque fibroblasts to induced pluripotent stem cells (iPSCs); (2) Culture of the iPSCs under feeder-free conditions even after removal of the transgene resulting in transgene-free iPSCs; (3) Development of a CRISPR/Cas-based work-flow to edit the genome of rhesus macaque PSCs with high efficiency; (4) Establishment of a novel protocol for the derivation of gene-edited monoclonal NHP-iPSC lines. These findings facilitate efficient testing of genome editing approaches in NHP-PSC before their in vivo application.
Equatorial pliosaurid from Venezuela marks the youngest South American occurrence of the clade
Authors: Bastiaans Dylan , Madzia Daniel , Carrillo-Briceño Jorge D. , Sachs Sven 
Published: July 2021

AbstractPliosaurids were the dominant macropredators in aquatic environments at least since the Middle Jurassic until their extinction in the early Late Cretaceous. Until very recently, the Cretaceous record of Pliosauridae has been poor and difficult to interpret from the taxonomic and phylogenetic perspective. Despite that the knowledge of Cretaceous pliosaurids improved in recent years, numerous aspects of their evolutionary history still remain only poorly known. Here, we report the first pliosaurid material from Venezuela. The taxon is most likely earliest Cenomanian in age, thus representing the youngest occurrence of Pliosauridae from South America. The Venezuelan taxon is based on a well-preserved tooth crown whose morphology and outer enamel structural elements appear to resemble especially those observable in the giant pliosaurid Sachicasaurus vitae from the Lower Cretaceous of Colombia. The new discovery extends the pliosaurid record on the continent by more than 10 million years and likely marks the southernmost Upper Cretaceous occurrence of Pliosauridae, worldwide. We also briefly discuss the affinities of the enigmatic Venezuelan elasmosaurid Alzadasaurus tropicus and highlight similarities to elasmosaurids from the Western Interior Seaway.
Morpho‐metabotyping the oxidative stress response
Authors: Rusz Mate , Del Favero Giorgia , El Abiead Yasin , Gerner Christopher , Keppler Bernhard K. , Jakupec Michael A. , Koellensperger Gunda 
Published: July 2021

AbstractOxidative stress and reactive oxygen species (ROS) are central to many physiological and pathophysiological processes. However, due to multiple technical challenges, it is hard to capture a comprehensive readout of the cell, involving both biochemical and functional status. We addressed this problem by developing a fully parallelized workflow for metabolomics (providing absolute quantities for > 100 metabolites including TCA cycle, pentose phosphate pathway, purine metabolism, glutathione metabolism, cysteine and methionine metabolism, glycolysis and gluconeogenesis) and live cell imaging microscopy. The correlative imaging strategy was applied to study morphological and metabolic adaptation of cancer cells upon short-term hydrogen peroxide (H2O2) exposure in vitro. The combination provided rich metabolic information at the endpoint of exposure together with imaging of mitochondrial effects. As a response, superoxide concentrations were elevated with a strong mitochondrial localization, and multi-parametric image analysis revealed a shift towards fragmentation. In line with this, metabolism reflected both the impaired mitochondrial function and shifts to support the first-line cellular defense and compensate for energy loss. The presented workflow combining high-end technologies demonstrates the applicability for the study of short-term oxidative stress, but it can be suitable for the in-depth study of various short-term oxidative and other cellular stress-related phenomena.
Predictors of chronic opioid therapy in Medicaid beneficiaries with HIV who initiated antiretroviral therapy
Authors: Oh GYeon , Brouwer Emily S. , Abner Erin L. , Fardo David W. , Freeman Patricia R. , Delcher Chris , Moga Daniela C. 
Published: July 2021

AbstractThe factors associated with chronic opioid therapy (COT) in patients with HIV is understudied. Using Medicaid data (2002–2009), this retrospective cohort study examines COT in beneficiaries with HIV who initiated standard combination anti-retroviral therapy (cART). We used generalized estimating equations on logistic regression models with backward selection to identify significant predictors of COT initiation. COT was initiated among 1014 out of 9615 beneficiaries with HIV (male: 10.4%; female: 10.7%). Those with older age, any malignancy, Hepatitis C infection, back pain, arthritis, neuropathy pain, substance use disorder, polypharmacy, (use of) benzodiazepines, gabapentinoids, antidepressants, and prior opioid therapies were positively associated with COT. In sex-stratified analyses, multiple predictors were shared between male and female beneficiaries; however, chronic obstructive pulmonary disease, liver disease, any malignancy, and antipsychotic therapy were unique to female beneficiaries. Comorbidities and polypharmacy were important predictors of COT in Medicaid beneficiaries with HIV who initiated cART.
Association of incremental pulse wave velocity with cardiometabolic risk factors
Authors: Nabeel P. M. , Chandran Dinu S. , Kaur Prabhdeep , Thanikachalam Sadagopan , Sivaprakasam Mohanasankar , Joseph Jayaraj 
Published: July 2021

AbstractWe investigate the association of incremental pulse wave velocity (ΔC; the change in pulse wave velocity over a cardiac cycle) with cardiometabolic risk factors and report the first and (currently) the largest population-level data. In a cross-sectional study performed in a cohort of 1373 general population participants, ΔC was measured using clinically validated ARTSENS devices. There were 455 participants in the metabolic syndrome (MetS) group whose average ΔC was ~ 28.4% higher than that of the non-metabolic syndrome (Non-MetS) group. Females with MetS showed ~ 10.9% elevated average ΔC compared to males of the Non-MetS group. As the number of risk factors increased from 0 to 5, the average ΔC escalated by ~ 55% (1.50 ± 0.52 m/s to 2.33 ± 0.91 m/s). A gradual increase in average ΔC was observed across each decade from the younger (ΔC = 1.53 ± 0.54 m/s) to geriatric (ΔC = 2.34 ± 0.59 m/s) populations. There was also a significant difference in ΔC among the blood pressure categories. Most importantly, ΔC ≥ 1.81 m/s predicted a constellation of ≥ 3 risks with AUC = 0.615, OR = 2.309, and RR = 1.703. All statistical trends remained significant, even after adjusting for covariates. The study provides initial evidence for the potential use of ΔC as a tool for the early detection and screening of vascular dysfunction, which opens up avenues for active clinical and epidemiological studies. Further investigations are encouraged to confirm and establish the causative mechanism for the reported associations.
Somatic cell hemoglobin modulates nitrogen oxide metabolism in the human airway epithelium
Authors: Marozkina Nadzeya , Smith Laura , Zhao Yi , Zein Joe , Chmiel James F. , Kim Jeeho , Kiselar Janna , Davis Michael D. , Cunningham Rebekah S. , Randell Scott H. , Gaston Benjamin 
Published: July 2021

AbstractEndothelial hemoglobin (Hb)α regulates endothelial nitric oxide synthase (eNOS) biochemistry. We hypothesized that Hb could also be expressed and biochemically active in the ciliated human airway epithelium. Primary human airway epithelial cells, cultured at air–liquid interface (ALI), were obtained by clinical airway brushings or from explanted lungs. Human airway Hb mRNA data were from publically available databases; or from RT-PCR. Hb proteins were identified by immunoprecipitation, immunoblot, immunohistochemistry, immunofluorescence and liquid chromatography- mass spectrometry. Viral vectors were used to alter Hbβ expression. Heme and nitrogen oxides were measured colorimetrically. Hb mRNA was expressed in human ciliated epithelial cells. Heme proteins (Hbα, β, and δ) were detected in ALI cultures by several methods. Higher levels of airway epithelial Hbβ gene expression were associated with lower FEV1 in asthma. Both Hbβ knockdown and overexpression affected cell morphology. Hbβ and eNOS were apically colocalized. Binding heme with CO decreased extracellular accumulation of nitrogen oxides. Human airway epithelial cells express Hb. Higher levels of Hbβ gene expression were associated with airflow obstruction. Hbβ and eNOS were colocalized in ciliated cells, and heme affected oxidation of the NOS product. Epithelial Hb expression may be relevant to human airways diseases.
AnnoMiner is a new web-tool to integrate epigenetics, transcription factor occupancy and transcriptomics data to predict transcriptional regulators
Authors: Meiler Arno , Marchiano Fabio , Haering Margaux , Weitkunat Manuela , Schnorrer Frank , Habermann Bianca H. 
Published: July 2021

AbstractGene expression regulation requires precise transcriptional programs, led by transcription factors in combination with epigenetic events. Recent advances in epigenomic and transcriptomic techniques provided insight into different gene regulation mechanisms. However, to date it remains challenging to understand how combinations of transcription factors together with epigenetic events control cell-type specific gene expression. We have developed the AnnoMiner web-server, an innovative and flexible tool to annotate and integrate epigenetic, and transcription factor occupancy data. First, AnnoMiner annotates user-provided peaks with gene features. Second, AnnoMiner can integrate genome binding data from two different transcriptional regulators together with gene features. Third, AnnoMiner offers to explore the transcriptional deregulation of genes nearby, or within a specified genomic region surrounding a user-provided peak. AnnoMiner’s fourth function performs transcription factor or histone modification enrichment analysis for user-provided gene lists by utilizing hundreds of public, high-quality datasets from ENCODE for the model organisms human, mouse,DrosophilaandC. elegans. Thus, AnnoMiner can predict transcriptional regulators for a studied process without the strict need for chromatin data from the same process. We compared AnnoMiner to existing tools and experimentally validated several transcriptional regulators predicted by AnnoMiner to indeed contribute to muscle morphogenesis inDrosophila. AnnoMiner is freely available athttp://chimborazo.ibdm.univ-mrs.fr/AnnoMiner/.
Molecular dynamics study on structural and atomic evolution between Au and Ni nanoparticles through coalescence
Authors: Li Bangquan , Li Jing , Su Xiaoqiang , Cui Yimin 
Published: July 2021

AbstractMotivated by the structure evolution experiments of Janus NiAu nanoparticles (NPs), we present a detailed study on the thermodynamic evolution of Ni and Au NPs with different ratios of Au and Ni through the molecular dynamics (MD) simulations. It is found that, for fixed Ni particle size (5.8 nm in diameter), the energy variation with the increasing temperature is related to the Au sizes (1.5–9.6 nm in diameter), due to the diverse atomic segregation modes. For a small Au particle, due to lattice induction, the structure will change from order to disorder and then to order. The interface defects of the merging NPs could be automatically eliminated by coalescence processes. The change in energy as the temperature increases is similar to that of monometallic NPs. For larger Au particles, the irregular variation of energy occurs and the atomic energy experience one or two reductions at least with the increase of the temperature. The segregation of Au atoms to the surface of Ni particle is dominant during the continuous heating process. The coalescence processes of Au atoms strongly determine the final morphology of the particles. Dumbbell-like, Janus and eccentric core–shell spherical structures could be obtained during the heating process. Our results will provide an effective approach to the design of novel materials with specific properties through thermal control.
Honing in on bioluminescent milky seas from space
Authors: Miller Steven D. , Haddock Steven H. D. , Straka William C. , Seaman Curtis J. , Combs Cynthia L. , Wang Menghua , Shi Wei , Nam SungHyun 
Published: July 2021

AbstractMilky seas are a rare form of marine bioluminescence where the nocturnal ocean surface produces a widespread, uniform and steady whitish glow. Mariners have compared their appearance to a daylit snowfield that extends to all horizons. Encountered most often in remote waters of the northwest Indian Ocean and the Maritime Continent, milky seas have eluded rigorous scientific inquiry, and thus little is known about their composition, formation mechanism, and role within the marine ecosystem. The Day/Night Band (DNB), a new-generation spaceborne low-light imager, holds potential to detect milky seas, but the capability has yet to be demonstrated. Here, we show initial examples of DNB-detected milky seas based on a multi-year (2012–2021) search. The massive bodies of glowing ocean, sometimes exceeding 100,000 km2 in size, persist for days to weeks, drift within doldrums amidst the prevailing sea surface currents, and align with narrow ranges of sea surface temperature and biomass in a way that suggests water mass isolation. These findings show how spaceborne assets can now help guide research vessels toward active milky seas to learn more about them.
Prognostic value of CD34 expression status in patients with myxofibrosarcomas and undifferentiated pleomorphic sarcomas
Authors: Sugiura Yoshiya , Machinami Rikuo , Matsumoto Seiichi , Kanda Hiroaki , Ae Keisuke , Takazawa Yutaka , Takeuchi Kengo 
Published: July 2021

AbstractIt is controversial whether patients with myxofibrosarcomas (MFSs) have better prognoses than those with undifferentiated pleomorphic sarcomas (UPSs). No useful prognostic factors have been established to date. We therefore aimed to evaluate the prognostic value of CD34 expression status in 192 patients with MFSs and UPSs. Using the log-rank test, we showed that patients with MFSs had a significantly better overall survival than did those with UPSs when defining the former as having a > 10% myxoid component (p = 0.03), but not when defining it as having a > 50% myxoid component (p = 0.1). Under the definition of MFSs as > 10% myxoid component, the log-rank test revealed that the diagnosis of the UPS and the CD34 loss (p < 0.001) were significant adverse predictors of overall survival. As per the Cox model, the CD34 loss remained an independent prognostic factor (hazard ratio = 3.327; 95% confidence interval 1.334–8.295), while the diagnosis of the UPS was a nonsignificant confounding factor (hazard ratio = 1.084; 95% confidence interval 0.679–1.727). In conclusion, CD34 expression status is a useful prognostic factor in patients with MFS and UPS, and it should be incorporated into grading systems that are used to predict outcomes.
KBoost: a new method to infer gene regulatory networks from gene expression data
Authors: Iglesias-Martinez Luis F. , De Kegel Barbara , Kolch Walter 
Published: July 2021

AbstractReconstructing gene regulatory networks is crucial to understand biological processes and holds potential for developing personalized treatment. Yet, it is still an open problem as state-of-the-art algorithms are often not able to process large amounts of data within reasonable time. Furthermore, many of the existing methods predict numerous false positives and have limited capabilities to integrate other sources of information, such as previously known interactions. Here we introduce KBoost, an algorithm that uses kernel PCA regression, boosting and Bayesian model averaging for fast and accurate reconstruction of gene regulatory networks. We have benchmarked KBoost against other high performing algorithms using three different datasets. The results show that our method compares favorably to other methods across datasets. We have also applied KBoost to a large cohort of close to 2000 breast cancer patients and 24,000 genes in less than 2 h on standard hardware. Our results show that molecularly defined breast cancer subtypes also feature differences in their GRNs. An implementation of KBoost in the form of an R package is available at: https://github.com/Luisiglm/KBoost and as a Bioconductor software package.
Association between short-term heart rate variability and blood coagulation in patients with breast cancer
Authors: Wang Lingling , Wang Jingfeng , Li Peng , Wang Xiangzhi , Wu Shuang , Shi Bo 
Published: July 2021

AbstractThe purpose of this study was to investigate the relationship between heart rate variability (HRV), a non-invasive tool for evaluating autonomic function, and routine coagulation indices (RCIs) in patients with breast cancer (BC). Forty-six BC patients were enrolled in this study. Blood biochemistry tests were performed to extract RCIs, including prothrombin time (PT), activated partial thromboplastin time (APTT), and thrombin time (TT). Five-minute electrocardiograms were collected for analysis of HRV parameters (SDNN, RMSSD, LF, HF, LF n.u., HF n.u., LF/HF). Multiple linear regression models examined the relationship of HRV parameters with RCIs. RMSSD, LF n.u., HF n.u., LF/HF were significantly associated with PT. Specifically, the value of PT increased by 0.192 ± 0.091 or 0.231 ± 0.088 s, respectively for each 1 standard deviation (SD) increase in RMSSD or HF n.u.; it increased by 0.230 ± 0.088 or 0.215 ± 0.088 s, respectively for each 1 − SD decrease in LF n.u. or ln (LF/HF) (all P < 0.05). RMSSD was significantly associated with APTT, i.e., the value of APTT increased by 1.032 ± 0.470 s for each 1 − SD increase in RMSSD (P < 0.05). HRV parameters were associated with RCIs in patients with BC. These observations suggest that the autonomic nervous system and coagulation indices in BC patients are linked, potentially explaining the reason that they are both associated with the prognosis.
Comprehensive virtual screening of 4.8 k flavonoids reveals novel insights into allosteric inhibition of SARS-CoV-2 MPRO
Authors: Jiménez-Avalos Gabriel , Vargas-Ruiz A. Paula , Delgado-Pease Nicolás E. , Olivos-Ramirez Gustavo E. , Sheen Patricia , Fernández-Díaz Manolo , Quiliano Miguel , Zimic Mirko ,   COVID-19 Working Group in Perú, Agurto-Arteaga Andres , Antiparra Ricardo , Ardiles-Reyes Manuel , Calderon Katherine , Cauna-Orocollo Yudith , de Grecia Cauti-Mendoza Maria , Chipana-Flores Naer , Choque-Guevara Ricardo , Chunga-Girón Xiomara , Criollo-Orozco Manuel , De La Cruz Lewis , Delgado-Ccancce Elmer , Elugo-Guevara Christian , Fernández-Sanchez Manolo , Guevara-Sarmiento Luis , Gutiérrez Kristel , Heredia-Almeyda Oscar , Huaccachi-Gonzalez Edison , Huerta-Roque Pedro , Icochea Eliana , Isasi-Rivas Gisela , Juscamaita-Bartra Romina A. , Licla-Inca Abraham , Montalvan Angela , Montesinos-Millan Ricardo , Núñez-Fernández Dennis , Ochoa-Ortiz Adiana , Páucar-Montoro Erika , Pauyac Kathy , Perez-Martinez Jose L. , Perez-M Norma , Poma-Acevedo Astrid , Quiñones-Garcia Stefany , Ramirez-Ortiz Ingrid , Ramos-Sono Daniel , Rios-Angulo Angela A. , Rios-Matos Dora , Rojas-Neyra Aldo , Romero Yomara K. , Salguedo-Bohorquez Mario I. , Sernaque-Aguilar Yacory , Soto Luis F. , Tataje-Lavanda Luis , Ticona Julio , Vallejos-Sánchez Katherine , Villanueva-Pérez Doris , Ygnacio-Aguirre Freddy 
Published: July 2021

AbstractSARS-CoV-2 main protease is a common target for inhibition assays due to its high conservation among coronaviruses. Since flavonoids show antiviral activity, several in silico works have proposed them as potential SARS-CoV-2 main protease inhibitors. Nonetheless, there is reason to doubt certain results given the lack of consideration for flavonoid promiscuity or main protease plasticity, usage of short library sizes, absence of control molecules and/or the limitation of the methodology to a single target site. Here, we report a virtual screening study where dorsilurin E, euchrenone a11, sanggenol O and CHEMBL2171598 are proposed to inhibit main protease through different pathways. Remarkably, novel structural mechanisms were observed after sanggenol O and CHEMBL2171598 bound to experimentally proven allosteric sites. The former drastically affected the active site, while the latter triggered a hinge movement which has been previously reported for an inactive SARS-CoV main protease mutant. The use of a curated database of 4.8 k flavonoids, combining two well-known docking software (AutoDock Vina and AutoDock4.2), molecular dynamics and MMPBSA, guaranteed an adequate analysis and robust interpretation. These criteria can be considered for future screening campaigns against SARS-CoV-2 main protease.
Multiplex gene analysis reveals T-cell and antibody-mediated rejection-specific upregulation of complement in renal transplants
Authors: Vonbrunn Eva , Ries Tajana , Söllner Stefan , Müller-Deile Janina , Büttner-Herold Maike , Amann Kerstin , Daniel Christoph 
Published: July 2021

AbstractIn renal transplantation, complement is involved in ischemia reperfusion injury, graft rejection and dysfunction. However, it is still unclear how induction of complement and its activation are initiated. Using allograft biopsies of a well-characterized cohort of 28 renal transplant patients with no rejection (Ctrl), delayed graft function (DGF), acute T-cell-mediated (TCMR) or antibody-mediated rejection (ABMR) we analyzed differences in complement reaction. For that mRNA was isolated from FFPE sections, quantified with a multiplex gene expression panel and correlated with transplant conditions and follow-up of patients. Additionally, inflammatory cells were quantified by multiplex immunohistochemistry. In allograft biopsies with TCMR and ABMR gene expression of C1QB was 2-4 fold elevated compared to Ctrl. In TCMR biopsies, mRNA counts of several complement-related genes including C1S, C3, CFB and complement regulators CFH, CR1 and SERPING1 were significantly increased compared to Ctrl. Interestingly, expression levels of about 75% of the analyzed complement related genes correlated with cold ischemia time (CIT) and markers of inflammation. In conclusion, this study suggest an important role of complement in transplant pathology which seems to be at least in part triggered by CIT. Multiplex mRNA analysis might be a useful method to refine diagnosis and explore new pathways involved in rejection.