bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of zoledronic acid derivatives with extended methylene linkers on osteoclastogenesis involve downregulation of JNK and Akt pathways
Authors: Peng Ying , Liu Qingzhu , Xu Dong , Li Ke , Li Hang , Qiu Ling , Lin Jianguo 
Published: January 2021

AbstractBisphosphonates (BPs), especially zoledronic acid (ZOL), are clinically used to treat osteolytic bone lesions. However, serious side‐effects may be also induced during the therapeutic process. To improve the BPs drugs, here, we investigated the effects of a series of ZOL derivatives with increasing number of methylene linker between the imidazole ring and the P–C–P backbone named IPrDP, IBDP, IPeDP, and IHDP on cell viability and receptor activator of nuclear factor‐κB ligand (RANKL)‐induced osteoclast differentiation, function and apoptosis induction in mouse bone marrow‐derived macrophages (BMMs). Our results suggested that IPeDP and IHDP, which contains 4 and 5 methylene linkers, respectively, exerted lower toxicity on BMMs compared with ZOL, IPrDP, and IBDP, which contains 1, 2, and 3 methylene linkers respectively. At concentrations below cytotoxicity threshold, IPeDP and IHDP possessed strong abilities of antiosteoclast formation, antibone absorption, and inducing osteoclast apoptosis, which were similar to ZOL and more powerful than IPrDP and IBDP. The mechanism behind these effects of IPeDP and IHDP might involve the interference of small GTPases prenylation through suppression of mevalonate pathway. The downregulation of JNK and Akt phosphorylation and subsequent inhibition of the expression of c‐Fos and NFATc1 might also be involved. Our results supported the potential usage of IPeDP and IHDP to treat bone‐related disorders involving increased osteoclastogenesis. Our attempt to extend the methylene linker between the imidazole ring and the P–C–P backbone of ZOL also reveals some regularities between the structure and properties of the BPs drugs.
Tunable Anticancer Activity of Furoylthiourea‐Based RuII–Arene Complexes and Their Mechanism of Action
Authors: Swaminathan Srividya , Haribabu Jebiti , Kalagatur Naveen Kumar , Nikhil Maroli , Balakrishnan Nithya , Bhuvanesh Nattamai S. P. , Kadirvelu Krishna , Kolandaivel Ponmalai , Karvembu Ramasamy 
Published: January 2021

AbstractFourteen new RuII–arene (p‐cymene/benzene) complexes (C1–C14) have been synthesized by varying the N‐terminal substituent in the furoylthiourea ligand and satisfactorily characterized by using analytical and spectroscopic techniques. Electrostatic potential maps predicted that the electronic effect of the substituents was mostly localized, with some influence seen on the labile chloride ligands. The structure–activity relationships of the Ru–p‐cymene and Ru–benzene complexes showed opposite trends. All the complexes were found to be highly toxic towards IMR‐32 cancer cells, with C5 (Ru–p‐cymene complex containing C6H2(CH3)3 as N‐terminal substituent) and C13 (Ru–benzene complex containing C6H4(CF3) as N‐terminal substituent) showing the highest activity among each set of complexes, and hence they were chosen for further study. These complexes showed different behavior in aqueous solutions, and were also found to catalytically oxidize glutathione. They also promoted cell death by apoptosis and cell cycle arrest. Furthermore, the complexes showed good binding ability with the receptors Pim‐1 kinase and vascular endothelial growth factor receptor 2, commonly overexpressed in cancer cells.
Multi‐functional, Low Symmetry Pd2L4 Nanocage Libraries**
Authors: Lewis James E. M. 
Published: January 2021

AbstractAlthough many impressive metallo‐supramolecular architectures have been reported, they tend towards high symmetry structures and avoid extraneous functionality to ensure high fidelity in the self‐assembly process. This minimalist approach, however, limits the range of accessible structures and thus their potential applications. Herein is described the synthesis of a family of ditopic ligands wherein the ligand scaffolds are both low symmetry and incorporate exohedral functional moieties. Key to this design is the use of CuI‐catalysed azide‐alkyne cycloaddition (CuAAC) chemistry, as the triazole is capable of acting as both a coordinating heterocycle and a tether between the ligand framework and functional unit simultaneously. A common precursor was used to generate ligands with various functionalities, allowing control of electronic properties whilst maintaining the core structure of the resultant cis‐Pd2L4 nanocage assemblies. The isostructural nature of the scaffold frameworks enabled formation of combinatorial libraries from the self‐assembly of ligand mixtures, generating a statistical mixture of multi‐functional, low symmetry architectures.
Antihypertensives and their relation to mortality by SARS‐CoV‐2 infection
Authors: Singh Sandeep , Widrich Christine , Nap Martijn , Schokker Emile , Zwinderman Aeilko H. , Pinto‐Sietsma Sara‐Joan 
Published: January 2021

AbstractThe role of antihypertensives, especially Renin–Angiotensin–Aldosterone System inhibitors, is still debatable in COVID‐19‐related severity and outcome. Therefore, we search for a more global analysis of antihypertensive medication in relation to SAS‐CoV‐2 severity using prescription data worldwide. The association between the percentage use of different types of antihypertensive medications and mortality rates due to a SARS‐CoV‐2 infection during the first 3 weeks of the pandemic was analyzed using random effects linear regression models for 30 countries worldwide. Higher percentages of prescribed angiotensin receptor blockers (ARBs) (β, 95% confidence interval [CI]; −0.02 [−0.04 to −0.0012]; p = .042) and calcium channel blockers (CCBs) (β, 95% CI; −0.023 [−0.05 to −0.0028]; p = .0304) were associated with a lower first 3‐week SARS‐CoV‐2‐related death rate, whereas a higher percentage of prescribed angiotensin‐converting enzyme inhibitors (ACEis) (β, 95% CI; 0.03 [0.0061–0.05]; p = .0103) was associated with a higher first 3‐week death rate, even when adjusted for age and metformin use. There was no association between the amount of prescribed beta‐blockers (BBs) and diuretics (Diu) and the first 3‐week death rate. When analyzing the combination of drugs that is used by at least 50% of antihypertensive users, within the different countries, countries with the lowest first 3‐week death rates had at least an angiotensin receptor blocker as one of the most often prescribed antihypertensive medications (ARBs/CCBs: [β, 95% CI; −0.02 [−0.03 to −0.004]; p = .009], ARBs/BBs: [β, 95% CI; −0.03 [−0.05 to −0.006]; p = .01]). Finally, countries prescribing high‐potency ARBs had lower first 3‐week ARBs. In conclusion, ARBs and CCB seem to have a protective effect against death from SARS‐CoV‐2 infection.
In silico analyses on the comparative sensing of SARS‐CoV‐2 mRNA by the intracellular TLRs of humans
Authors: Choudhury Abhigyan , Das Nabarun Chandra , Patra Ritwik , Mukherjee Suprabhat 
Published: January 2021

AbstractThe coronavirus disease‐2019 (COVID‐19) pandemic caused by severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) has already resulted in a huge setback to mankind in terms of millions of deaths, while the unavailability of an appropriate therapeutic strategy has made the scenario much more severe. Toll‐like receptors (TLRs) are crucial mediators and regulators of host immunity and the role of human cell surface TLRs in SARS‐CoV‐2 induced inflammatory pathogenesis has been demonstrated recently. However, the functional significance of the human intracellular TLRs including TLR3, 7, 8, and 9 is yet unclear. Hitherto, the involvement of these intracellular TLRs in inducing pro‐inflammatory responses in COVID‐19 has been reported but the identity of the interacting viral RNA molecule(s) and the corresponding TLRs have not been explored. This study hopes to rationalize the comparative binding of the major SARS‐CoV‐2 mRNAs to the intracellular TLRs, considering the solvent‐based force‐fields operational in the cytosolic aqueous microenvironment that predominantly drives these interactions. Our in silico study on the binding of all mRNAs with the intracellular TLRs depicts that the mRNA of NSP10, S2, and E proteins of SARS‐CoV‐2 are possible virus‐associated molecular patterns that bind to TLR3, TLR9, and TLR7, respectively, and trigger downstream cascade reactions. Intriguingly, binding of the viral mRNAs resulted in variable degrees of conformational changes in the ligand‐binding domain of the TLRs ratifying the activation of the downstream inflammatory signaling cascade. Taken together, the current study is the maiden report to describe the role of TLR3, 7, and 9 in COVID‐19 immunobiology and these could serve as useful targets for the conception of a therapeutic strategy against the pandemic.
Glial cell line‐derived neurotrophic factor increases matrix metallopeptidase 9 and 14 expression in microglia and promotes microglia‐mediated glioma progression
Authors: Huang Yimin , Zhang Baole , Haneke Hannah , Haage Verena , Lubas Malgorzata , Yuan Yang , Xia Pengfei , Motta Edyta , Nanvuma Cynthia , Dzaye Omar , Hu Feng , Kettenmann Helmut 
Published: January 2021

AbstractGlial cell line‐derived neurotrophic factor (GDNF) is released by glioma cells and promotes tumor growth. We have previously found that GDNF released from the tumor cells is a chemoattractant for microglial cells, the immune cells of the central nervous system. Here we show that GDNF increases matrix metalloproteinase (MMP) 9 and MMP14 expression in cultured microglial cells from mixed sexes of neonatal mice. The GDNF‐induced microglial MMP9 and MMP14 upregulation is mediated by GDNF family receptor alpha 1 receptors and dependent on p38 mitogen‐activated protein kinase signaling. In organotypic brain slices, GDNF promotes the growth of glioma and this effect depends on the presence of microglia. We also previously found that MMP9 and MMP14 upregulation can be mediated by Toll‐like receptor (TLR) 2 signaling and here we demonstrate that GDNF increases the expression of TLR1 and TLR2. In conclusion, GDNF promotes the pro‐tumorigenic phenotype of microglia.
H19 gene polymorphisms and Wilms tumor risk in Chinese children: a four‐center case‐control study
Authors: Li Wenya , Hua Rui‐Xi , Wang Mi , Zhang Da , Zhu Jinhong , Zhang Songyang , Yang Yang , Cheng Jiwen , Zhou Haixia , Zhang Jiao , He Jing 
Published: January 2021

AbstractBackgroundWilms tumor is the most common pediatric renal cancer. However, genetic bases behind Wilms tumor remain largely unknown. H19 is a critical maternally imprinted gene. Previous studies indicated that single nucleotide polymorphisms (SNPs) in the H19 can modify the risk of several human malignancies. Epigenetic errors at the H19 locus lead to biallelic silencing in Wilms tumors. Genetic variations in the H19 may be related to Wilms tumor susceptibility.MethodsWe conducted a four‐center study to investigate whether H19 SNP was a predisposing factor to Wilms tumor. Three polymorphisms in the H19 (rs2839698 G > A, rs3024270 C > G, rs217727 G > A) were genotyped in 355 cases and 1070 cancer‐free controls, using Taqman method. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the strength of the associations.ResultsWe found that all of these three polymorphisms were significantly associated with Wilms tumor risk alterations. The rs2839698 G > A polymorphism (AG vs. GG: adjusted OR = 0.74, 95% CI = 0.57–0.96, p = 0.024; AA vs. GG: adjusted OR = 1.52, 95% CI = 1.05–2.22, p = 0.027), the rs3024270 C > G polymorphism (CG vs. CC: adjusted OR = 0.61, 95% CI = 0.46–0.81, p = 0.0007; and the rs217727 polymorphism (AG vs. GG: adjusted OR = 0.76, 95% CI = 0.58–0.99, p = 0.035). The Carriers of 1, 2, and 1–2 risk genotypes were inclined to develop Wilms tumor compared with those without risk genotype (adjusted OR = 1.36, 95% CI = 1.02–1.80, p = 0.037; adjusted OR = 1.84, 95% CI = 1.27–2.67, p = 0.001; adjusted OR = 1.50, 95% CI = 1.17–1.92, p = 0.002, respectively). The stratified analysis further revealed that rs2839698 AA, rs217727 AA, and 1–2 risk genotypes could strongly increase Wilms tumor risk among children above 18 months of age, males, and with clinical stage I+II disease.ConclusionOur findings indicate that genetic variations in the H19 may confer Wilms tumor risk.
Lung ultrasound in the diagnosis and monitoring of 30 children with coronavirus disease 2019
Authors: Musolino Anna Maria , Supino Maria Chiara , Buonsenso Danilo , Papa Raffaele Edo , Chiurchiù Sara , Magistrelli Andrea , Barbieri Maria Antonietta , Raponi Massimiliano , D'Argenio Patrizia , Villani Alberto , Tomà Paolo ,   The LUS COVID Group
Published: January 2021

AbstractBackgroundThe coronavirus disease 2019 (COVID‐19) has caused a new global pandemic and is responsible for millions of infections and thousands of deaths in the world. The lung ultrasound (LUS) is a noninvasive and easily repeatable tool and can be carried out by the pediatrician at the bedside of children with a consequent reduction in the risk of transmission of the virus.ObjectiveWe hypothesized that ultrasound findings in these patients would (1) be associated with their disease severity and (2) change over time in alignment with clinical outcome.MethodsThe study was made in the emergency department (ED) in a tertiary level pediatric hospital. All patients with swab‐confirmed COVID‐19 infection were subjected to a LUS within 6 h from admission and after 96 h.ResultsAmong a total of 30 children, 18 (60%) were males, 4 reported exertional dyspnea, and only 1 chest pain. The mean oxygen saturation was 98.8 ± 1.0% in ambient air in the ED and no patient needed oxygen therapy during hospitalization. Children with moderate disease presented more B line (p = .03).After 96 h, we had observed ultrasound abnormality only in 20% of the children. We found a statistically significant reduction in pleural irregularities (30% vs. 16.7; p = .001) and in B lines (50% vs. 20%; p = .008).ConclusionsThe LUS is a useful, feasible, and safe tool for the clinician to complement the clinical evaluation and to monitor the evolution of lung disease in children with COVID‐19.
Uniform Lipschitz Functions on the Triangular Lattice Have Logarithmic Variations
Authors: Glazman Alexander , Manolescu Ioan 
Published: January 2021

AbstractUniform integer-valued Lipschitz functions on a domain of size N of the triangular lattice are shown to have variations of order $$\sqrt{\log N}$$

log
N

. The level lines of such functions form a loop O(2) model on the edges of the hexagonal lattice with edge-weight one. An infinite-volume Gibbs measure for the loop O(2) model is constructed as a thermodynamic limit and is shown to be unique. It contains only finite loops and has properties indicative of scale-invariance: macroscopic loops appearing at every scale. The existence of the infinite-volume measure carries over to height functions pinned at the origin; the uniqueness of the Gibbs measure does not. The proof is based on a representation of the loop O(2) model via a pair of spin configurations that are shown to satisfy the FKG inequality. We prove RSW-type estimates for a certain connectivity notion in the aforementioned spin model.
Complex Evolution of the Mismatch Repair System in Eukaryotes is Illuminated by Novel Archaeal Genomes
Authors: Hofstatter Paulo G. , Lahr Daniel J. G. 
Published: January 2021

AbstractRepairing DNA damage is one of the most important functions of the ‘housekeeping’ proteins, as DNA molecules are constantly subject to different kinds of damage. An important mechanism of DNA repair is the mismatch repair system (MMR). In eukaryotes, it is more complex than it is in bacteria or Archaea due to an inflated number of paralogues produced as a result of an extensive process of gene duplication and further specialization upon the evolution of the first eukaryotes, including an important part of the meiotic machinery. Recently, the discovery and sequencing of Asgard Archaea allowed us to revisit the MMR system evolution with the addition of new data from a group that is closely related to the eukaryotic ancestor. This new analysis provided evidence for a complex evolutionary history of eukaryotic MMR: an archaeal origin for the nuclear MMR system in eukaryotes, with subsequent acquisitions of other MMR systems from organelles.
Crick Wobble and Superwobble in Standard Genetic Code Evolution
Authors: Yarus Michael 
Published: January 2021

AbstractWobble coding is inevitable during evolution of the Standard Genetic Code (SGC). It ultimately splits half of NN U/C/A/G coding boxes with different assignments. Further, it contributes to pervasive SGC order by reinforcing close spacing for identical SGC assignments. But wobble cannot appear too soon, or it will inhibit encoding and more decisively, obstruct evolution of full coding tables. However, these prior results assumed Crick wobble, NN U/C and NN A/G, read by a single adaptor RNA. Superwobble translates NN U/C/A/G codons, using one adaptor RNA with an unmodified 5′ anticodon U (appropriate to earliest coding) in modern mitochondria, plastids, and mycoplasma. Assuming the SGC was selected when evolving codes most resembled it, characteristics of the critical selection events can be calculated. For example, continuous superwobble infrequently evolves SGC-like coding tables. So, continuous superwobble is a very improbable origin hypothesis. In contrast, late-arising superwobble shares late Crick wobble’s frequent resemblance to SGC order. Thus late superwobble is possible, but yields SGC-like assignments less frequently than late Crick wobble. Ancient coding ambiguity, most simply, arose from Crick wobble alone. This is consistent with SGC assignments to NAN codons.
Carbon stable isotope ratio as a revealer of incomplete decarbonation for particulate organic carbon measurement in river plumes
Authors: Blasco Thierry , Migon Christophe , Morin Guillaume , Dufour Aurélie , Vigier Nathalie , Marty Sabine , Doxaran David 
Published: January 2021

AbstractThe characterization of particles in suspension in river plumes contributes to the assessment of net particulate organic carbon (POC) fluxes and to a better understanding of the anthropogenic and climatic impact on blue carbon. Prior to POC analysis in natural waters, inorganic carbon (in the form of carbonates) must be removed. This step is generally carried out by acid leaching. However, the presence of mineral matrices (in turbid waters) may hinder total decarbonation, which may result in biased measurements. This work checks the quality of decarbonation through the analysis of carbon stable isotope ratio (δ13C), considering suspended particles discharged by three rivers into coastal waters under flooding conditions. Carbonates were removed by adding variable volumes of 2N hydrochloric acid (HCl) to filters. Carbon concentrations and stable isotopic ratios were analyzed. Values of δ13Corg (stable isotope ratio of organic carbon) allow the identification of incompletely decarbonated samples. If a small amount of detrital carbonates resists the usual decarbonation treatment, δ13Corg can be significantly shifted towards less negative values, suggesting the need of more efficient decarbonation methods in order to improve the accuracy of organic carbon measurements. Even in the case of a high Corg/Ctotal ratio, the impact of remaining carbonates on the δ13Corg value is strong because δ13Cinorg is significantly different. The sensitivity of δ13Corg measurement might therefore be used to validate POC measurements in estuarine and coastal waters.
A regenerated fiber from rennet-treated casein micelles
Authors: Thill Sebastian , Schmidt Thomas , Wöll Dominik , Gebhardt Ronald 
Published: January 2021

AbstractCasein as the major protein of milk is a promising protein source for biopolymer fibers. Current casein-based fibers are fabricated by dissolving caseins in alkaline media and wet spinning in a coagulation bath containing harsh chemicals. In milk, casein is present in so-called casein micelles (CMs). Based on the rennet-induced aggregation, we developed a process that can be applied for the spinning of micellar casein fibers in a sustainable way without the use of harsh chemicals. Fabricated fibers show a surface with a characteristic microstructure, which can also be detected embedded in a network structure inside the fiber. The fibers are stable under acidic and neutral conditions and decompose in alkaline media down to aggregates with sizes comparable to the characteristic microstructure. The so far reached tensile properties of the micellar fiber are between low and mid double-digit percentage range compared to casein azlons.
Diagnostic accuracy of postmortem computed tomography for bleeding source determination in cases with hemoperitoneum
Authors: Chatzaraki Vasiliki , Thali Michael J. , Ampanozi Garyfalia 
Published: January 2021

AbstractAimThe aim of this retrospective study was to determine the accuracy of postmortem computed tomography and different radiological signs for the determination of the bleeding source in cases with hemoperitoneum confirmed at autopsy.MethodsPostmortem computed tomography data of consecutive cases with hemoperitoneum confirmed at autopsy were reviewed by two raters, blinded to the autopsy findings. The determination of possible bleeding sources was based on the presence of the sentinel clot sign, blood or sedimented blood surrounding an organ, intraparenchymal abnormal gas distribution, and parenchymal disruption. The bleeding source and the cause of hemoperitoneum (traumatic, surgical, natural, or resuscitation) as reported in the autopsy report were noted. The survival intervals of the deceased were calculated when information about the time of an incident related to death was available in the autopsy reports.ResultsEighty-five cases were included in the study. Postmortem computed tomography showed 79% sensitivity and 92.1% specificity for the detection of the bleeding source. The sentinel clot sign was associated with surgical or natural causes of hemoperitoneum and longer survival intervals. Sedimented blood around the bleeding source was associated with resuscitation. Abnormal gas distribution within organs and combination of multiple radiological signs provided higher sensitivity.ConclusionPostmortem computed tomography provides moderate sensitivity and high specificity for determining the bleeding source in cases with hemoperitoneum. Different PMCT signs are associated with different causes of hemoperitoneum and survival intervals.