bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vivo adenine base editing of PCSK9 in macaques reduces LDL cholesterol levels
Authors: Rothgangl Tanja , Dennis Melissa K. , Lin Paulo J. C. , Oka Rurika , Witzigmann Dominik , Villiger Lukas , Qi Weihong , Hruzova Martina , Kissling Lucas , Lenggenhager Daniela , Borrelli Costanza , Egli Sabina , Frey Nina , Bakker Noëlle , Walker John A. , Kadina Anastasia P. , Victorov Denis V. , Pacesa Martin , Kreutzer Susanne , Kontarakis Zacharias , Moor Andreas , Jinek Martin , Weissman Drew , Stoffel Markus , van Boxtel Ruben , Holden Kevin , Pardi Norbert , Thöny Beat , Häberle Johannes , Tam Ying K. , Semple Sean C. , Schwank Gerald 
Published: May 2021

AbstractMost known pathogenic point mutations in humans are C•G to T•A substitutions, which can be directly repaired by adenine base editors (ABEs). In this study, we investigated the efficacy and safety of ABEs in the livers of mice and cynomolgus macaques for the reduction of blood low-density lipoprotein (LDL) levels. Lipid nanoparticle–based delivery of mRNA encoding an ABE and a single-guide RNA targetingPCSK9, a negative regulator of LDL, induced up to 67% editing (on average, 61%) in mice and up to 34% editing (on average, 26%) in macaques. Plasma PCSK9 and LDL levels were stably reduced by 95% and 58% in mice and by 32% and 14% in macaques, respectively. ABE mRNA was cleared rapidly, and no off-target mutations in genomic DNA were found. Re-dosing in macaques did not increase editing, possibly owing to the detected humoral immune response to ABE upon treatment. These findings support further investigation of ABEs to treat patients with monogenic liver diseases.
COVID-19 non-pharmaceutical intervention portfolio effectiveness and risk communication predominance
Authors: Chan Louis Yat Hin , Yuan Baoyin , Convertino Matteo 
Published: May 2021

AbstractNon-pharmaceutical interventions (NPIs) including resource allocation, risk communication, social distancing and travel restriction, are mainstream actions to control the spreading of Coronavirus disease 2019 (COVID-19) worldwide. Different countries implemented their own combinations of NPIs to prevent local epidemics and healthcare system overloaded. Portfolios, as temporal sets of NPIs have various systemic impacts on preventing cases in populations. Here, we developed a probabilistic modeling framework to evaluate the effectiveness of NPI portfolios at the macroscale. We employed a deconvolution method to back-calculate incidence of infections and estimate the effective reproduction number by using the package EpiEstim. We then evaluated the effectiveness of NPIs using ratios of the reproduction numbers and considered them individually and as a portfolio systemically. Based on estimates from Japan, we estimated time delays of symptomatic-to-confirmation and infection-to-confirmation as 7.4 and 11.4 days, respectively. These were used to correct surveillance data of other countries. Considering 50 countries, risk communication and returning to normal life were the most and least effective yielding the aggregated effectiveness of 0.11 and − 0.05 that correspond to a 22.4% and 12.2% reduction and increase in case growth. The latter is quantified by the change in reproduction number before and after intervention implementation. Countries with the optimal NPI portfolio are along an empirical Pareto frontier where mean and variance of effectiveness are maximized and minimized independently of incidence levels. Results indicate that implemented interventions, regardless of NPI portfolios, had distinct incidence reductions and a clear timing effect on infection dynamics measured by sequences of reproduction numbers. Overall, the successful suppression of the epidemic cannot work without the non-linear effect of NPI portfolios whose effectiveness optimality may relate to country-specific socio-environmental factors.
Involvement of the dopaminergic system in the reward-related behavior of pregabalin
Authors: Althobaiti Yusuf S. , Almutairi Farooq M. , Alshehri Fahad S. , Altowairqi Ebtehal , Marghalani Aliyah M. , Alghorabi Amal A. , Alsanie Walaa F. , Gaber Ahmed , Alsaab Hashem O. , Almalki Atiah H. , Hakami Alqassem Y. , Alkhalifa Turki , Almalki Ahmad D. , Hardy Ana M. G. , Shah Zahoor A. 
Published: May 2021

AbstractThere has been an increase in cases of drug addiction and prescription drug abuse worldwide. Recently, pregabalin abuse has been a focus for many healthcare agencies, as highlighted by epidemiological studies. We previously evaluated the possibility of pregabalin abuse using the conditioned place preference (CPP) paradigm. We observed that a 60 mg/kg dose could induce CPP in mice and that pregabalin-rewarding properties were mediated through glutamate neurotransmission. Notably, the dopaminergic reward circuitry is also known to play a crucial role in medication-seeking behavior. Therefore, this study aimed to explore the possible involvement of dopaminergic receptor-1 in pregabalin-induced CPP. Mice were randomly allocated to receive saline or the dopamine-1 receptor antagonist SKF-83566 (0.03 mg/kg, intraperitoneal). After 30 min, the mice received either saline or pregabalin (60 mg/kg) during the conditioning phase. Among the control groups that received saline or SKF-83566, the time spent in the two conditioning chambers was not significantly altered. However, among the pregabalin-treated group, there was a marked increase in the time spent in the drug-paired chamber compared to the time spent in the vehicle-paired chamber. Notably, blocking dopamine-1 receptors with SKF-83566 completely prevented pregabalin-induced place preference, thus demonstrating the engagement of the dopaminergic system in pregabalin-induced reward-related behavior.
Hidden order across online extremist movements can be disrupted by nudging collective chemistry
Authors: Velásquez N. , Manrique P. , Sear R. , Leahy R. , Restrepo N. Johnson , Illari L. , Lupu Y. , Johnson N. F. 
Published: May 2021

AbstractDisrupting the emergence and evolution of potentially violent online extremist movements is a crucial challenge. Extremism research has analyzed such movements in detail, focusing on individual- and movement-level characteristics. But are there system-level commonalities in the ways these movements emerge and grow? Here we compare the growth of the Boogaloos, a new and increasingly prominent U.S. extremist movement, to the growth of online support for ISIS, a militant, terrorist organization based in the Middle East that follows a radical version of Islam. We show that the early dynamics of these two online movements follow the same mathematical order despite their stark ideological, geographical, and cultural differences. The evolution of both movements, across scales, follows a single shockwave equation that accounts for heterogeneity in online interactions. These scientific properties suggest specific policies to address online extremism and radicalization. We show how actions by social media platforms could disrupt the onset and ‘flatten the curve’ of such online extremism by nudging its collective chemistry. Our results provide a system-level understanding of the emergence of extremist movements that yields fresh insight into their evolution and possible interventions to limit their growth.
Recognising the dynamic form of fire
Authors: Nagle Fintan , Johnston Alan 
Published: May 2021

AbstractEncoding and recognising complex natural sequences provides a challenge for human vision. We found that observers could recognise a previously presented segment of a video of a hearth fire when embedded in a longer sequence. Recognition performance declined when the test video was spatially inverted, but not when it was hue reversed or temporally reversed. Sampled motion degraded forwards/reversed playback discrimination, indicating observers were sensitive to the asymmetric pattern of motion of flames. For brief targets, performance increased with target length. More generally, performance depended on the relative lengths of the target and embedding sequence. Increased errors with embedded sequence length were driven by positive responses to non-target sequences (false alarms) rather than omissions. Taken together these observations favour interpreting performance in terms of an incremental decision-making model based on a sequential statistical analysis in which evidence accrues for one of two alternatives. We also suggest that prediction could provide a means of providing and evaluating evidence in a sequential analysis model.
Flux-pinning behaviors and mechanism according to dopant level in (Fe, Ti) particle-doped $$\text {MgB}_2$$ superconductor
Authors: Lee H. B. , Kim G. C. , Shon Young Jin , Kim Dongjin , Kim Y. C. 
Published: May 2021

AbstractWe have studied flux-pinning effects of $$\text {MgB}_2$$

MgB
2

superconductor by doping (Fe, Ti) particles of which radius is 163 nm on average. 5 wt.% (Fe, Ti) doped $$\text {MgB}_2$$

MgB
2

among the specimens showed the best field dependence of magnetization and 25 wt.% one did the worst at 5 K. The difference of field dependence of magnetization of the two specimens increased as temperature increased. Here we show experimental results of (Fe, Ti) particle-doped $$\text {MgB}_2$$

MgB
2

specimens according to dopant level and the causes of the behaviors. Flux-pinning effect of volume defects-doped superconductor was modeled in ideal state and relative equations were derived. During the study, we had to divide M-H curve of volume defect-dominating superconductor as three discreet regions for analyzing flux-pinning effects, which are diamagnetic increase region after $$\text {H}_{c1}$$

H

c
1

, $$\Delta \text {H}=\Delta \text {B}$$

Δ
H
=
Δ
B

region, and diamagnetic decrease region. As a result, flux-pinning effects of volume defects decreased as dopant level increased over the optimal dopant level, which was caused by decrease of flux-pinning limit of a volume defect. And similar behaviors are obtained as dopant level decreased below the optimal dopant level, which was caused by the decreased number of volume defects. Comparing the model with experimental results, deviations increased as dopant level increased over the optimal dopant level, whereas the two was well matched on less dopant level. The behavior is considered to be caused by the segregation of the volume defects. On the other hand, the cause that diamagnetic properties of over-doped $$\text {MgB}_2$$

MgB
2

specimens dramatically decreased as temperature increased was the double decreases of flux-pinning limit of a volume defect and the segregation effect, which are caused by over-doping and temperature increase.
En route to single-step, two-phase purification of carbon nanotubes facilitated by high-throughput spectroscopy
Authors: Podlesny Blazej , Olszewska Barbara , Yaari Zvi , Jena Prakrit V. , Ghahramani Gregory , Feiner Ron , Heller Daniel A. , Janas Dawid 
Published: May 2021

AbstractChirality purification of single-walled carbon nanotubes (SWCNTs) is desirable for applications in many fields, but general utility is currently hampered by low throughput. We discovered a method to obtain single-chirality SWCNT enrichment by the aqueous two-phase extraction (ATPE) method in a single step. To achieve appropriate resolution, a biphasic system of non-ionic tri-block copolymer surfactant is varied with an ionic surfactant. A nearly-monochiral fraction of SWCNTs can then be harvested from the top phase. We also found, via high-throughput, near-infrared excitation-emission photoluminescence spectroscopy, that the parameter space of ATPE can be mapped to probe the mechanics of the separation process. Finally, we found that optimized conditions can be used for sorting of SWCNTs wrapped with ssDNA as well. Elimination of the need for surfactant exchange and simplicity of the separation process make the approach promising for high-yield generation of purified single-chirality SWCNT preparations.
Towards water-soluble [60]fullerenes for the delivery of siRNA in a prostate cancer model
Authors: Korzuch Julia , Rak Monika , Balin Katarzyna , Zubko Maciej , Głowacka Olga , Dulski Mateusz , Musioł Robert , Madeja Zbigniew , Serda Maciej 
Published: May 2021

AbstractThis paper presents two water-soluble fullerene nanomaterials (HexakisaminoC60 and monoglucosamineC60, which is called here JK39) that were developed and synthesized as non-viral siRNA transfection nanosystems. The developed two-step Bingel–Hirsch reaction enables the chemical modification of the fullerene scaffold with the desired bioactive fragments such as d-glucosamine while keeping the crucial positive charged ethylenediamine based malonate. The ESI–MS and 13C-NMR analyses of JK39 confirmed its high Th symmetry, while X-ray photoelectron spectroscopy revealed the presence of nitrogen and oxygen-containing C–O or C–N bonds. The efficiency of both fullerenes as siRNA vehicles was tested in vitro using the prostate cancer cell line DU145 expressing the GFP protein. The HexakisaminoC60 fullerene was an efficient siRNA transfection agent, and decreased the GFP fluorescence signal significantly in the DU145 cells. Surprisingly, the glycofullerene JK39 was inactive in the transfection experiments, probably due to its high zeta potential and the formation of an extremely stable complex with siRNA.
A physicochemical assessment of the thermal stability of dextrin–colistin conjugates
Authors: Chiron Emilie , Varache Mathieu , Stokniene Joana , Thomas David W. , Ferguson Elaine L. 
Published: May 2021

AbstractAttachment of polysaccharide carriers is increasingly being used to achieve precision delivery and improved effectiveness of protein and peptide drugs. Although it is clear that their clinical effectiveness relies on the purity and integrity of the conjugate in storage, as well as following administration, instability of polysaccharide-based conjugates can reduce the protective efficacy of the polymer, which may adversely affect the bioactive’s potency. As a model, these studies used dextrin–colistin conjugates, with varying degrees of polymer modification (1, 2.5 and 7.5 mol% succinoylation) to assess the effect of storage temperature (− 20, 4, 21 and 37 °C) and duration (up to 12 months) on saccharide and colistin release and antimicrobial activity. Estimation of the proportion of saccharide release (by comparison of area under the curve from size exclusion chromatograms) was more pronounced at higher temperatures (up to 3 and 35% at − 20 °C and 37 °C, respectively after 12 months), however, repeated freeze–thaw did not produce any measurable release of saccharides, while addition of amylase (20, 100, 500 IU/L) caused rapid release of saccharides (> 70% total within 24 h). At all temperatures, conjugates containing the lowest degree of succinoylation released the highest proportion of free colistin, which increased with storage temperature, however no trend in saccharide release was observed. Despite the clear physical effects of prolonged storage, antimicrobial activity of all samples was only altered after storage at 37 °C for 12 months (> threefold decreased activity). These results demonstrate significant release of saccharides from dextrin–colistin conjugates during prolonged storage in buffered solution, especially at elevated temperature, which, in most cases, did not affect antimicrobial activity. These findings provide vital information about the structure–activity relationship of dextrin–colistin conjugates, prior to full-scale commercial development, which can subsequently be applied to other polysaccharide-protein and -peptide conjugates.
Profiling of tumour-associated microbiota in human hepatocellular carcinoma
Authors: Komiyama Seiga , Yamada Takahiro , Takemura Nobuyuki , Kokudo Norihiro , Hase Koji , Kawamura Yuki I. 
Published: May 2021

AbstractLiver cancer is the fourth leading cause of cancer-related death. Hepatocellular carcinoma (HCC) is a primary liver cancer that results from chronic hepatitis caused by multiple predisposing factors such as viral infection, alcohol consumption, and non-alcoholic fatty liver disease. Accumulating studies have indicated that dysfunction of the gut epithelial barrier and hepatic translocation of gut microbes may be implicated in the pathogenesis of HCC. However, the translocated bacteria in HCC patients remains unclear. Here, we characterised tumour-associated microbiota in patients with liver cancer and focused on HCC. We observed that the number of amplicon sequence variants in tumour-associated microbiota was significantly higher compared with that in non-tumour regions of the liver. The tumour-associated microbiota consisted of Bacteroidetes, Firmicutes, and Proteobacteria as the dominant phyla. We identified an unclassified genus that belonged to the Bacteroides, Romboutsia, uncultured bacterium of Lachnospiraceae as a signature taxon for primary liver cancer. Additionally, we identified Ruminococcus gnavus as a signature taxon for HCC patients infected with hepatitis B and/or hepatitis C viruses. This study suggests that tumour microbiota may contribute to the pathology of HCC.
Data-science based analysis of perceptual spaces of odors in olfactory loss
Authors: Lötsch Jörn , Ultsch Alfred , Hähner Antje , Willgeroth Vivien , Bensafi Moustafa , Zaliani Andrea , Hummel Thomas 
Published: May 2021

AbstractDiminished sense of smell impairs the quality of life but olfactorily disabled people are hardly considered in measures of disability inclusion. We aimed to stratify perceptual characteristics and odors according to the extent to which they are perceived differently with reduced sense of smell, as a possible basis for creating olfactory experiences that are enjoyed in a similar way by subjects with normal or impaired olfactory function. In 146 subjects with normal or reduced olfactory function, perceptual characteristics (edibility, intensity, irritation, temperature, familiarity, hedonics, painfulness) were tested for four sets of 10 different odors each. Data were analyzed with (i) a projection based on principal component analysis and (ii) the training of a machine-learning algorithm in a 1000-fold cross-validated setting to distinguish between olfactory diagnosis based on odor property ratings. Both analytical approaches identified perceived intensity and familiarity with the odor as discriminating characteristics between olfactory diagnoses, while evoked pain sensation and perceived temperature were not discriminating, followed by edibility. Two disjoint sets of odors were identified, i.e., d = 4 “discriminating odors” with respect to olfactory diagnosis, including cis-3-hexenol, methyl salicylate, 1-butanol and cineole, and d = 7 “non-discriminating odors”, including benzyl acetate, heptanal, 4-ethyl-octanoic acid, methional, isobutyric acid, 4-decanolide and p-cresol. Different weightings of the perceptual properties of odors with normal or reduced sense of smell indicate possibilities to create sensory experiences such as food, meals or scents that by emphasizing trigeminal perceptions can be enjoyed by both normosmic and hyposmic individuals.
A nanoparticle-mist deposition method: fabrication of high-performance ITO flexible thin films under atmospheric conditions
Authors: Suzuki Ryoko , Nishi Yasutaka , Matsubara Masaki , Muramatsu Atsushi , Kanie Kiyoshi 
Published: May 2021

AbstractIndium tin oxide (ITO) thin films with low resistivity and high transparency in the visible light region have been prepared on flexible plastic films by a deposition method using water mist containing ITO nanoparticles (NPs) under atmospheric conditions. The ITO NP-mist was generated by ultrasonic irradiation of a water dispersion. Our developed protrusion-rich ITO NPs were applied as the ITO NPs. The ITO NPs show high dispersion stability in water without the use of any dispersant. Comparison investigations revealed that utilization of the ITO NPs played a critical role in fabricating high-performance ITO thin films on flexible films, and the resistivity reached 9.0 × 10−3 Ω cm. The system could be expected to provide promising advances in the development of a mild and sustainable fabrication procedure for ITO thin films under mild atmospheric conditions without the use of expensive vacuum production systems or harmful and environmentally undesirable chemicals.
Ultralight graphene oxide/polyvinyl alcohol aerogel for broadband and tuneable acoustic properties
Authors: Rapisarda Mario , Malfense Fierro Gian-Piero , Meo Michele 
Published: May 2021

AbstractAn ultralight graphene oxide (GO)/polyvinyl alcohol (PVA) aerogel (GPA) is proposed as a new class of acoustic materials with tuneable and broadband sound absorption and sound transmission losses. The interaction between GO sheets and PVA molecules is exploited in our environmentally friendly manufacturing process to fabricate aerogels with hierarchical and tuneable porosity embedded in a honeycomb scaffold. The aerogels possess an enhanced ability to dissipate sound energy, with an extremely low density of 2.10 kg m−3, one of the lowest values ever reported for acoustic materials. We have first experimentally evaluated and optimised the effects of composition and thickness on the acoustic properties, namely sound absorption and sound transmission losses. Subsequently, we have employed a semi-analytical approach to evaluate the effect of different processing times on acoustic properties and assessed the relationships between the acoustic and non-acoustic properties of the materials. Over the 400–2500 Hz range, the reported average sound absorption coefficients are as high as 0.79, while the average sound transmission losses can reach 15.8 dB. We envisage that our subwavelength thin and light aerogel-based materials will possess other functional properties such as fire resistance and EMI shielding, and will prove to be novel acoustic materials for advanced engineering applications.
Arylmethylene hydrazine derivatives containing 1,3-dimethylbarbituric moiety as novel urease inhibitors
Authors: Pedrood Keyvan , Azizian Homa , Montazer Mohammad Nazari , Mohammadi‐Khanaposhtani Maryam , Asgari Mohammad Sadegh , Asadi Mehdi , Bahadorikhalili Saeed , Rastegar Hossein , Larijani Bagher , Amanlou Massoud , Mahdavi Mohammad 
Published: May 2021

AbstractA new series of arylmethylene hydrazine derivatives bearing 1,3-dimethylbarbituric moiety 7a–o were designed, synthesized, and evaluated for their in vitro urease inhibitory activity. All the title compounds displayed high anti-urease activity, with IC50 values in the range of 0.61 ± 0.06–4.56 ± 0.18 µM as compared to the two standard inhibitors hydroxyurea (IC50 = 100 ± 0.15 μM) and thiourea (IC50 = 23 ± 1.7 μM). Among the synthesized compounds, compound 7h with 2-nitro benzylidene group was found to be the most potent compound. Kinetic study of this compound revealed that it is a mix-mode inhibitor against urease. Evaluation of the interaction modes of the synthesized compounds in urease active site by molecular modeling revealed that that compounds with higher urease inhibitor activity (7h, 7m, 7c, 7l, 7i, and 7o, with IC50 of 0.61, 0.86, 1.2, 1.34, 1.33, 1.94 μM, respectively) could interact with higher number of residues, specially Arg609, Cys592 (as part of urease active site flap) and showed higher computed free energy, while compounds with lower urease activity (7f, 7n, 7g, and 7a with IC50 of 3.56, 4.56, 3.62 and 4.43 μM, respectively) and could not provide the proper interaction with Arg609, and Cys592 as the key interacting residues along with lower free binding energy. MD investigation revealed compound 7h interacted with Arg609 and Cys592 which are of the key residues at the root part of mobile flap covering the active site. Interacting with the mentioned residue for a significant amount of time, affects the flexibility of the mobile flap covering the active site and causes inhibition of the ureolytic activity. Furthermore, in silico physico-chemical study of compounds 7a–o predicted that all these compounds are drug-likeness with considerable orally availability.