bluuebunny/crossref_metadata_2025_split huggingface dataset:
RAS-inhibiting biologics identify and probe druggable pockets including an SII-α3 allosteric site
Authors: Haza Katarzyna Z. , Martin Heather L. , Rao Ajinkya , Turner Amy L. , Saunders Sophie E. , Petersen Britta , Tiede Christian , Tipping Kevin , Tang Anna A. , Ajayi Modupe , Taylor Thomas , Harvey Maia , Fishwick Keri M. , Adams Thomas L. , Gaule Thembaninkosi G. , Trinh Chi H. , Johnson Matthew , Breeze Alexander L. , Edwards Thomas A. , McPherson Michael J. , Tomlinson Darren C. 
Published: June 2021

AbstractRAS mutations are the most common oncogenic drivers across human cancers, but there remains a paucity of clinically-validated pharmacological inhibitors of RAS, as druggable pockets have proven difficult to identify. Here, we identify two RAS-binding Affimer proteins, K3 and K6, that inhibit nucleotide exchange and downstream signaling pathways with distinct isoform and mutant profiles. Affimer K6 binds in the SI/SII pocket, whilst Affimer K3 is a non-covalent inhibitor of the SII region that reveals a conformer of wild-type RAS with a large, druggable SII/α3 pocket. Competitive NanoBRET between the RAS-binding Affimers and known RAS binding small-molecules demonstrates the potential to use Affimers as tools to identify pharmacophores. This work highlights the potential of using biologics with small interface surfaces to select unseen, druggable conformations in conjunction with pharmacophore identification for hard-to-drug proteins.
Multifunctional antiperovskites driven by strong magnetostructural coupling
Authors: Singh Harish K. , Samathrakis Ilias , Fortunato Nuno M. , Zemen Jan , Shen Chen , Gutfleisch Oliver , Zhang Hongbin 
Published: June 2021

AbstractBased on density functional theory calculations, we elucidated the origin of multifunctional properties for cubic antiperovskites with noncollinear magnetic ground states, which can be attributed to strong isotropic and anisotropic magnetostructural coupling. Of 54 stable magnetic antiperovskites M3XZ (M = Cr, Mn, Fe, Co, and Ni; X = selected elements from Li to Bi except for noble gases and 4f rare-earth metals; and Z = C and N), 14 are found to exhibit the Γ4g/Γ5g (i.e., characterized by irreducible representations) antiferromagnetic magnetic configurations driven by frustrated exchange coupling and strong magnetocrystalline anisotropy. Using the magnetic deformation as an effective proxy, the isotropic magnetostructural coupling is characterized, and it is observed that the paramagnetic state is critical to understand the experimentally observed negative thermal expansion and to predict the magnetocaloric performance. Moreover, the piezomagnetic and piezospintronic effects induced by biaxial strain are investigated. It is revealed that there is not a strong correlation between the induced magnetization and anomalous Hall conductivities by the imposed strain. Interestingly, the anomalous Hall/Nernst conductivities can be significantly tailored by the applied strain due to the fine-tuning of the Weyl points energies, leading to promising spintronic applications.
Spatio-temporal distribution patterns of Plutella xylostella (Lepidoptera: Plutellidae) in a fine-scale agricultural landscape based on geostatistical analysis
Authors: Li Jian-Yu , Chen Yan-Ting , Shi Meng-Zhu , Li Jian-Wei , Xu Rui-Bin , Pozsgai Gabor , You Min-Sheng 
Published: June 2021

AbstractA detailed knowledge on the spatial distribution of pests is crucial for predicting population outbreaks or developing control strategies and sustainable management plans. The diamondback moth, Plutella xylostella, is one of the most destructive pests of cruciferous crops worldwide. Despite the abundant research on the species’s ecology, little is known about the spatio-temporal pattern of P. xylostella in an agricultural landscape. Therefore, in this study, the spatial distribution of P. xylostella was characterized to assess the effect of landscape elements in a fine-scale agricultural landscape by geostatistical analysis. The P. xylostella adults captured by pheromone-baited traps showed a seasonal pattern of population fluctuation from October 2015 to September 2017, with a marked peak in spring, suggesting that mild temperatures, 15–25 °C, are favorable for P. xylostella. Geostatistics (GS) correlograms fitted with spherical and Gaussian models showed an aggregated distribution in 21 of the 47 cases interpolation contour maps. This result highlighted that spatial distribution of P. xylostella was not limited to the Brassica vegetable field, but presence was the highest there. Nevertheless, population aggregations also showed a seasonal variation associated with the growing stage of host plants. GS model analysis showed higher abundances in cruciferous fields than in any other patches of the landscape, indicating a strong host plant dependency. We demonstrate that Brassica vegetables distribution and growth stage, have dominant impacts on the spatial distribution of P. xylostella in a fine-scale landscape. This work clarified the spatio-temporal dynamic and distribution patterns of P. xylostella in an agricultural landscape, and the distribution model developed by geostatistical analysis can provide a scientific basis for precise targeting and localized control of P. xylostella.
High resolution nanoscale chemical analysis of bitumen surface microstructures
Authors: Koyun Ayse N. , Zakel Julia , Kayser Sven , Stadler Hartmut , Keutsch Frank N. , Grothe Hinrich 
Published: June 2021

AbstractSurface microstructures of bitumen are key sites in atmospheric photo-oxidation leading to changes in the mechanical properties and finally resulting in cracking and rutting of the material. Investigations at the nanoscale remain challenging. Conventional combination of optical microscopy and spectroscopy cannot resolve the submicrostructures due to the Abbe restriction. For the first time, we report here respective surface domains, namely catana, peri and para phases, correlated to distinct molecules using combinations of atomic force microscopy with infrared spectroscopy and with correlative time of flight—secondary ion mass spectrometry. Chemical heterogeneities on the surface lead to selective oxidation due to their varying susceptibility to photo-oxidation. It was found, that highly oxidized compounds, are preferentially situated in the para phase, which are mainly asphaltenes, emphasising their high oxidizability. This is an impressive example how chemical visualization allows elucidation of the submicrostructures and explains their response to reactive oxygen species from the atmosphere.
Assessment of risk factors responsible for rapid deterioration of lung function over a period of one year in patients with chronic obstructive pulmonary disease
Authors: Rehman Anees ur , Shah Shahid , Abbas Ghulam , Harun Sabariah Noor , Shakeel Sadia , Hussain Rabia , Hassali Mohamed Azmi Ahmad , Rasool Muhammad Fawad 
Published: June 2021

AbstractCompromised lung function is a common feature of COPD patients, but certain factors increase the rate of lung function decline in COPD patients. The objective of the current study was to investigate the effect of different clinically important factors responsible for rapid deterioration of lung function quantified as ≥ 60 ml decline in FEV1 over a period of one year. COPD patients recruited from the chest clinic of Penang hospital were followed-up for one year from August 2018 to August 2019. Rapid deterioration of lung function was defined as greater than 60 ml/year decline in force expiratory volume in one second. Among 367 included patients 73.84% were male, with mean age 65.26 (9.6) years and % predicted FEV1 51.07 (11.84). 30.27% patients showed mean decline of ≥ 60 ml in FEV1. The regression analysis showed that current smoking relative risk (RR) = 2.38 (1.78–3.07), p < 0.001); GOLD Stage III& IV RR = 1.43 (1.27–1.97), p < 0.001); mMRC score 3 to 4 RR = 2.03 (1.74–2.70), p < 0.01); SGRQ-C score ≥ 10 points difference RR = 2.01 (1.58–2.73), p < 0.01); SGRQ-C symptoms Score ≥ 10 points difference RR = 1.48 (1.23–2.29), p < 0.001); 6MWT < 350 m RR = 2.29 (1.87–3.34), p < 0.01); ≥ 3 exacerbation in study year RR = 2.28 (1.58–2.42, p < 0.001); 8 or more hospital admission days (RR = 3.62 (2.66–4.20), p < 0.001); Charlson comorbidity index ≥ 3 RR = 3.18 (2.23–3.76), p < 0.01) and emphysema RR = 1.31 (1.15–1.79), p < 0.01) were significant risk factors for the rapid deterioration of lung function (FEV1 decline ≥ 60 ml). Among different factors CCI score ≥ 3, abrupt decline in health status, exacerbation frequency ≥ 3, hospital admission days ≥ 8 and emphysema were reported as risk factors for rapid deterioration of lung function.
Increasing selection gain and accuracy of harvest prediction models in Jatropha through genome-wide selection
Authors: dos Santos Adriano , Rodrigues Erina Vitório , Laviola Bruno Galvêas , Teodoro Larissa Pereira Ribeiro , Teodoro Paulo Eduardo , Bhering Leonardo Lopes 
Published: June 2021

AbstractGenome-wide selection (GWS) has been becoming an essential tool in the genetic breeding of long-life species, as it increases the gain per time unit. This study had a hypothesis that GWS is a tool that can decrease the breeding cycle in Jatropha. Our objective was to compare GWS with phenotypic selection in terms of accuracy and efficiency over three harvests. Models were developed throughout the harvests to evaluate their applicability in predicting genetic values in later harvests. For this purpose, 386 individuals of the breeding population obtained from crossings between 42 parents were evaluated. The population was evaluated in random block design, with six replicates over three harvests. The genetic effects of markers were predicted in the population using 811 SNP's markers with call rate = 95% and minor allele frequency (MAF) > 4%. GWS enables gains of 108 to 346% over the phenotypic selection, with a 50% reduction in the selection cycle. This technique has potential for the Jatropha breeding since it allows the accurate obtaining of GEBV and higher efficiency compared to the phenotypic selection by reducing the time necessary to complete the selection cycle. In order to apply GWS in the first harvests, a large number of individuals in the breeding population are needed. In the case of few individuals in the population, it is recommended to perform a larger number of harvests.
Somatic inhibition by microscopic magnetic stimulation
Authors: Ye Hui , Barrett Lauryn 
Published: June 2021

AbstractElectric currents can produce quick, reversible control of neural activity. Externally applied electric currents have been used in inhibiting certain ganglion cells in clinical practices. Via electromagnetic induction, a miniature-sized magnetic coil could provide focal stimulation to the ganglion neurons. Here we report that high-frequency stimulation with the miniature coil could reversibly block ganglion cell activity in marine mollusk Aplysia californica, regardless the firing frequency of the neurons, or concentration of potassium ions around the ganglion neurons. Presence of the ganglion sheath has minimal impact on the inhibitory effects of the coil. The inhibitory effect was local to the soma, and was sufficient in blocking the neuron’s functional output. Biophysical modeling confirmed that the miniature coil induced a sufficient electric field in the vicinity of the targeted soma. Using a multi-compartment model of Aplysia ganglion neuron, we found that the high-frequency magnetic stimuli altered the ion channel dynamics that were essential for the sustained firing of action potentials in the soma. Results from this study produces several critical insights to further developing the miniature coil technology for neural control by targeting ganglion cells. The miniature coil provides an interesting neural modulation strategy in clinical applications and laboratory research.
Estimating the incidence of cocaine use and mortality with music lyrics about cocaine
Authors: Hswen Yulin , Zhang Amanda , Brownstein John S. 
Published: June 2021

AbstractIn the United States, cocaine use and mortality have surged in the past 5 years. Considering cocaine’s reputation as a fashionable social drug, the rise of cocaine mentions in popular music may provide a signal of epidemiological trends of cocaine use. We characterized the relationship between mentions of cocaine in song lyrics and incidence of cocaine use and mortality in the US. Incidence of cocaine use from 2002 to 2017 was obtained from the National Survey on Drug Use and Health and cocaine overdose mortality rate from 2000 to 2017 was obtained from the Centers for Disease Control. Distributed lag models were fit using ordinary least squares on the first difference to identify associations between changes in cocaine lyric mentions and changes in incidence of cocaine use and mortality. A total of 5955 song lyrics with cocaine mentions were obtained from Lyrics.com. Cocaine mentions in song lyrics were stable from 2000 to 2010 then increased by 190% from 2010 to 2017. The first-order distributed lag model estimated that a 0.01 increase in mentions of cocaine in song lyrics is associated with an 11% increase in incidence of cocaine use within the same year and a 14% increase in cocaine mortality with a 2-year lag. Lag-times were confirmed with cross-correlation analyses and the association remained after accounting for street pricing of cocaine. Mentions of cocaine in song lyrics are associated with the rise of incidence of cocaine use and cocaine overdose mortality. Popular music trends are a potentially valuable tool for understanding cocaine epidemiology trends.
Auranofin prevents liver fibrosis by system Xc-mediated inhibition of NLRP3 inflammasome
Authors: Kim Hyun Young , Choi Young Jae , Kim Sang Kyum , Kim Hyunsung , Jun Dae Won , Yoon Kyungrok , Kim Nayoun , Hwang Jungwook , Kim Young-Mi , Lim Sung Chul , Kang Keon Wook 
Published: June 2021

AbstractDemand for a cure of liver fibrosis is rising with its increasing morbidity and mortality. Therefore, it is an urgent issue to investigate its therapeutic candidates. Liver fibrosis progresses following ‘multi-hit’ processes involving hepatic stellate cells, macrophages, and hepatocytes. The NOD-like receptor protein 3 (NLRP3) inflammasome is emerging as a therapeutic target in liver fibrosis. Previous studies showed that the anti-rheumatic agent auranofin inhibits the NLRP3 inflammasome; thus, this study evaluates the antifibrotic effect of auranofin in vivo and explores the underlying molecular mechanism. The antifibrotic effect of auranofin is assessed in thioacetamide- and carbon tetrachloride-induced liver fibrosis models. Moreover, hepatic stellate cell (HSC), bone marrow-derived macrophage (BMDM), kupffer cell, and hepatocyte are used to examine the underlying mechanism of auranofin. Auranofin potently inhibits activation of the NLRP3 inflammasome in BMDM and kupffer cell. It also reduces the migration of HSC. The underlying molecular mechanism was inhibition of cystine-glutamate antiporter, systemXc. Auranofin inhibits systemXcactivity and instantly induced oxidative burst, which mediated inhibition of the NLRP3 inflammasome in macrophages and HSCs. Therefore, to the best of our knowledge, we propose the use of auranofin as an anti-liver fibrotic agent.
Analysis of sex-specific risk factors and clinical outcomes in COVID-19
Authors: Jun Tomi , Nirenberg Sharon , Weinberger Tziopora , Sharma Navya , Pujadas Elisabet , Cordon-Cardo Carlos , Kovatch Patricia , Huang Kuan-lin 
Published: June 2021

Abstract
Background
Sex has consistently been shown to affect COVID-19 mortality, but it remains unclear how each sex’s clinical outcome may be distinctively shaped by risk factors.

Methods
We studied a primary cohort of 4930 patients hospitalized with COVID-19 in a single healthcare system in New York City from the start of the pandemic till August 5, 2020, and a validation cohort of 1645 patients hospitalized with COVID-19 in the same healthcare system from August 5, 2020, to January 13, 2021.

Results
Here we show that male sex was independently associated with in-hospital mortality, intubation, and ICU care after adjusting for demographics and comorbidities. Using interaction analysis and sex-stratified models, we found that hypoxia interacted with sex to preferentially increase women’s mortality risk while obesity interacted with sex to preferentially increase women’s risk of intubation and intensive care in our primary cohort. In the validation cohort, we observed that male sex remained an independent risk factor for mortality, but sex-specific interactions were not replicated.

Conclusions
We conducted a comprehensive sex-stratified analysis of a large cohort of hospitalized COVID-19 patients, highlighting clinical factors that may contribute to sex differences in the outcome of COVID-19.
Delivery of novel coumarin–dihydropyrimidinone conjugates through mixed polymeric nanoparticles to potentiate therapeutic efficacy against triple-negative breast cancer
Authors: Ghosh Avijit , Upadhyay Priyanka , Sarker Sushmita , Das Shaswati , Bhattacharjee Mousumi , Bhattacharya Saurav , Ahir Manisha , Guria Subhajit , Gupta Payal , Chattopadhyay Sreya , Ghosh Swatilekha , Adhikari Susanta , Adhikary Arghya 
Published: June 2021

Coumarin–dihydropyrimidinone conjugates (CDHPs) and their poly(lactic-co-glycolic acid) (PLGA)-PEG4000 mixed copolymer nanoparticles as excellent chemotherapeutic nanomedicine to control TNBC.
P-type cobaltite oxide spinels enable efficient electrocatalytic oxygen evolution reaction
Authors: Doppelbauer David , Aljabour Abdalaziz , Coskun Halime , Sun He , Gusenbauer Markus , Lumetzberger Julia , Primetzhofer Daniel , Faina Bogdan , Duchoslav Jiri , Kehrer Matthias , Stifter David , Groiss Heiko , Ney Verena , Ney Andreas , Stadler Philipp 
Published: June 2021

Zinc cobaltite spinels show enhanced electrocatalytic activity for oxygen evolution. The spinels evolve O2 at Tafel slopes between 40.5 and 48 mV dec−1 and at overpotentials between 0.35 and 0.43 V at 10 mA cm−2. Their stability underlines their utility as 3d-metal anodes.
TOI-674b: An oasis in the desert of exo-Neptunes transiting a nearby M dwarf
Authors: Murgas F. , Astudillo-Defru N. , Bonfils X. , Crossfield I. , Almenara J. M. , Livingston J. , Stassun K. G. , Korth J. , Orell-Miquel J. , Morello G. , Eastman J. D. , Lissauer J. J. , Kane S. R. , Morales F. Y. , Werner M. W. , Gorjian V. , Benneke B. , Dragomir D. , Matthews E. C. , Howell S. B. , Ciardi D. , Gonzales E. , Matson R. , Beichman C. , Schlieder J. , Collins K. A. , Collins K. I. , Jensen E. L. N. , Evans P. , Pozuelos F. J. , Gillon M. , Jehin E. , Barkaoui K. , Artigau E. , Bouchy F. , Charbonneau D. , Delfosse X. , Díaz R. F. , Doyon R. , Figueira P. , Forveille T. , Lovis C. , Melo C. , Gaisné G. , Pepe F. , Santos N. C. , Ségransan D. , Udry S. , Goeke R. F. , Levine A. M. , Quintana E. V. , Guerrero N. M. , Mireles I. , Caldwell D. A. , Tenenbaum P. , Brasseur C. E. , Ricker G. , Vanderspek R. , Latham D. W. , Seager S. , Winn J. , Jenkins J. M. 
Published: June 2021

Context. The NASA mission TESS is currently doing an all-sky survey from space to detect transiting planets around bright stars. As part of the validation process, the most promising planet candidates need to be confirmed and characterized using follow-up observations.
Aims. In this article, our aim is to confirm the planetary nature of the transiting planet candidate TOI-674b using spectroscopic and photometric observations.
Methods. We use TESS, Spitzer, ground-based light curves, and HARPS spectrograph radial velocity measurements to establish the physical properties of the transiting exoplanet candidate TOI-674b. We perform a joint fit of the light curves and radial velocity time series to measure the mass, radius, and orbital parameters of the candidate.
Results. We confirm and characterize TOI-674b, a low-density super-Neptune transiting a nearby M dwarf. The host star (TIC 158588995, V = 14.2 mag, J = 10.3 mag) is characterized by its M2V spectral type with M⋆ = 0.420 ± 0.010 M⊙, R⋆ = 0.420 ± 0.013 R⊙, and Teff = 3514 ± 57 K; it is located at a distance d = 46.16 ± 0.03 pc. Combining the available transit light curves plus radial velocity measurements and jointly fitting a circular orbit model, we find an orbital period of 1.977143 ± 3 × 10−6 days, a planetary radius of 5.25 ± 0.17 R⊕, and a mass of 23.6 ± 3.3 M⊕ implying a mean density of ρp =0.91 ± 0.15 g cm−3. A non-circular orbit model fit delivers similar planetary mass and radius values within the uncertainties. Given the measured planetary radius and mass, TOI-674b is one of the largest and most massive super-Neptune class planets discovered around an M-type star to date. It is found in the Neptunian desert, and is a promising candidate for atmospheric characterization using the James Webb Space Telescope.
Fine-Tuning of Platelet Responses by Serine/Threonine Protein Kinases and Phosphatases—Just the Beginning
Authors: Shiravand Yavar , Walter Ulrich , Jurk Kerstin 
Published: June 2021

AbstractComprehensive proteomic analyses of human and murine platelets established an extraordinary intracellular repertoire of signaling components, which control crucial functions. The spectrum of platelet serine/threonine protein kinases (more than 100) includes the AGC family (protein kinase A, G, C [PKA, PKG, PKC]), the mitogen-activated protein kinases (MAPKs), and others. PKA and PKG have multiple significantly overlapping substrates in human platelets, which possibly affect functions with clear “signaling nodes” of regulation by multiple protein kinases/phosphatases. Signaling nodes are intracellular Ca2+ stores, the contractile system (myosin light chains), and other signaling components such as G-proteins, protein kinases, and protein phosphatases. An example for this fine-tuning is the tyrosine kinase Syk, a crucial component of platelet activation, which is controlled by several serine/threonine and tyrosine protein kinases as well as phosphatases. Other protein kinases including PKA/PKG modulate protein phosphatase 2A, which may be a master regulator of MAPK signaling in human platelets. Protein kinases and in particular MAPKs are targeted by an increasing number of clinically used inhibitors. However, the precise regulation and fine-tuning of these protein kinases and their effects on other signaling components in platelets are only superficially understood—just the beginning. However, promising future approaches are in sight.
Spontaneous Fracture of Plastic Stents: A Rare Complication of Long-Term Indwelling Transmural Endoprosthesis
Authors: Rana Surinder Singh , Sharma Ravi , Gupta Rajesh 
Published: June 2021

AbstractPermanent indwelling transmural stents is a safe and effective strategy for prevention of recurrence of pancreatic fluid collections following successful endoscopic transmural drainage of walled-off necrosis (WON) with coexistent disconnected pancreatic duct syndrome (DPDS). Long-term studies have shown this strategy to be safe and effective with rarely reported adverse effects. In this case series, we describe three patients of successfully treated WON and DPDS presenting later with a rare complication of permanent indwelling transmural plastic stents.
Clearance of Cystic Duct Remnant Stones Using a SpyGlass Retrieval Basket during Single-Operator Cholangioscopy at ERCP
Authors: Hawken James , Portal Jim 
Published: June 2021

AbstractExtraction of stones from a cystic duct remnant following cholecystectomy poses a significant therapeutic dilemma. Surgical intervention has historically been required due to difficulty accessing the cystic duct remnant during conventional endoscopic retrograde cholangiopancreatography. Single-operator cholangioscopy can access the cystic duct remnant, enabling electrohydraulic lithotripsy and stone extraction. Method of stone extraction has seldom been described in this developing field. Clearing duct remnant stones using guidewire placement and an extractor balloon have been reported. This is the first reported case of cystic duct remnant stone extraction using a SpyGlass retrieval basket.