bluuebunny/crossref_metadata_2025_split huggingface dataset:
Statistics for the analysis of molecular dynamics simulations: providing P values for agonist-dependent GPCR activation
Authors: Bruzzese Agustín , Dalton James A. R. , Giraldo Jesús 
Published: November 2020

AbstractMolecular dynamics (MD) is the common computational technique for assessing efficacy of GPCR-bound ligands. Agonist efficacy measures the capability of the ligand-bound receptor of reaching the active state in comparison with the free receptor. In this respect, agonists, neutral antagonists and inverse agonists can be considered. A collection of MD simulations of both the ligand-bound and the free receptor are needed to provide reliable conclusions. Variability in the trajectories needs quantification and proper statistical tools for meaningful and non-subjective conclusions. Multiple-factor (time, ligand, lipid) ANOVA with repeated measurements on the time factor is proposed as a suitable statistical method for the analysis of agonist-dependent GPCR activation MD simulations. Inclusion of time factor in the ANOVA model is consistent with the time-dependent nature of MD. Ligand and lipid factors measure agonist and lipid influence on receptor activation. Previously reported MD simulations of adenosine A2a receptor (A2aR) are reanalyzed with this statistical method. TM6–TM3 and TM7–TM3 distances are selected as dependent variables in the ANOVA model. The ligand factor includes the presence or absence of adenosine whereas the lipid factor considers DOPC or DOPG lipids. Statistical analysis of MD simulations shows the efficacy of adenosine and the effect of the membrane lipid composition. Subsequent application of the statistical methodology to NECA A2aR agonist, with resulting P values in consistency with its pharmacological profile, suggests that the method is useful for ligand comparison and potentially for dynamic structure-based virtual screening.
Trophic sympathetic influence weakens pro-contractile role of Cl− channels in rat arteries during postnatal maturation
Authors: Kostyunina Daria S. , Zhang Lin , Shvetsova Anastasia A. , Selivanova Ekaterina K. , Tarasova Olga S. , Matchkov Vladimir V. , Gaynullina Dina K. 
Published: November 2020

AbstractMembrane transporters and their functional contribution in vasculature change during early postnatal development. Here we tested the hypothesis that the contribution of Cl− channels to arterial contraction declines during early postnatal development and this decline is associated with the trophic sympathetic influence. Endothelium‐denuded saphenous arteries from 1- to 2-week-old and 2- to 3-month-old male rats were used. Arterial contraction was assessed in the isometric myograph, in some experiments combined with measurements of membrane potential. mRNA and protein levels were determined by qPCR and Western blot. Sympathectomy was performed by treatment with guanethidine from the first postnatal day until 8–9-week age. Cl− substitution in the solution as well as Cl−-channel blockers (MONNA, DIDS) had larger suppressive effect on the methoxamine-induced arterial contraction and methoxamine-induced depolarization of smooth muscle cells in 1- to 2-week-old compared to 2- to 3-month-old rats. Vasculature of younger group demonstrated elevated expression levels of TMEM16A and bestrophin 3. Chronic sympathectomy increased Cl− contribution to arterial contraction in 2-month-old rats that was associated with an increased TMEM16A expression level. Our study demonstrates that contribution of Cl− channels to agonist-induced arterial contraction and depolarization decreases during postnatal development. This postnatal decline is associated with sympathetic nerves development.
Reliability of shear-wave elastography in assessing thoracolumbar fascia elasticity in healthy male
Authors: Chen Baizhen , Zhao Hongzhou , Liao Linrong , Zhang Zhijie , Liu Chunlong 
Published: November 2020

AbstractThe objectives of this study were to examine the intra and inter-operator reliability of shear wave elastography (SWE) device in quantifying the shear modulus of thoracolumbar fascia (TLF) and the device’s abilities to examine the shear modulus of the TLF during upper body forward. Twenty healthy male subjects participated in this study (mean age: 18.4 ± 0.7 years). Two independent operators performed the shear modulus of TLF during upper body forward using SWE, and interclass correlation coefficient (ICC) and minimum detectable change (MDC) were calculated. The shear modulus of the TLF was quantified by operator A using SWE at upper body forward 60°. The intra-operator (ICC = 0.860–0.938) and inter-operator (ICC = 0.904–0.944) reliabilities for measuring the shear modulus of the TLF with the upper body forward 0° were rated as both excellent, and the MDC was 4.71 kPa. The TLF shear modulus of upper body forward 60°was increased 45.5% (L3) and 55.0% (L4) than that of upper body forward 0°. The results indicate that the SWE is a dependable tool to quantify the shear modulus of TLF and monitor its dynamic changes. Therefore, this device can be used for biomechanical study and intervention experiments of TLF.
A ‘mixed’ dielectric response in langasite Ba3NbFe3Si2O14
Authors: Rathore Satyapal S. , Nathawat Rashi , Vitta Satish 
Published: November 2020

The combined structural and dielectric response of langasite, Ba3NbFe3Si2O14 shows unique temperature and frequency dependence, attributed to presence of distributed potential wells.
Marfan syndrome: whole-exome sequencing revealsde novomutations, second gene and genotype–phenotype correlations in the Chinese population
Authors: Wu Yuduo , Sun Hairui , Wang Jianbin , Wang Xin , Gong Ming , Han Lu , He Yihua , Zhang Hongjia 
Published: November 2020

AbstractMarfan syndrome (MFS) is a dominant monogenic disease caused by mutations in fibrillin 1 (FBN1). Cardiovascular complications are the leading causes of mortality among MFS. In the present study, a whole-exome sequencing of MFS in the Chinese population was conducted to investigate the correlation between FBNI gene mutation and MFS. Forty-four low-frequency harmful loci were identified for the FBN1 gene in HGMD database. In addition, 38 loci were identified in the same database that have not been related to MFS before. A strict filtering and screening protocol revealed two patients of the studied group have double mutations in the FBN1 gene. The two patients harboring the double mutations expressed a prominent, highly pathological phenotype in the affected family. In addition to the FBN1 gene, we also found that 27 patients had mutations in the PKD1 gene, however these patients did not have kidney disease, and 16 of the 27 patients expressed aortic related complications. Genotype-phenotype analysis showed that patients with aortic complications are older in the family, aged between 20 and 40 years.
Prognostic factors and predictors of outcome in patients with COVID-19 and related pneumonia: a retrospective cohort study
Authors: Boari Gianluca E.M. , Chiarini Giulia , Bonetti Silvia , Malerba Paolo , Bianco Gianluca , Faustini Cristina , Braglia-Orlandini Federico , Turini Daniele , Guarinoni Vittoria , Saottini Michele , Viola Sara , Ferrari-Toninelli Giulia , Pasini Giancarlo , Mascadri Cristina , Bonzi Bianca , Desenzani Paolo , Tusi Claudia , Zanotti Eros , Nardin Matteo , Rizzoni Damiano 
Published: November 2020

Abstract
The aim of the present study was to simultaneously assess several potential predictors of outcome (co-morbidity, previous and in-hospital treatment, radiologic Brixia score) in patients with COVID-19.
This retrospective cohort study included 258 consecutive patients with confirmed COVID-19 admitted to a medical ward at Montichiari Hospital, Brescia, Italy from February 28th to April 30rd, 2020. Patients had SARS-CoV-2 related pneumonia with respiratory failure, and were treated with hydroxychloroquine and lopinavir plus ritonavir. In some patients, additional treatment with tocilizumab, dexamethasone and enoxaparin was adopted. Outcomes (death or recovery) were assessed at the end of the discharge period or at the end of the follow-up (August 2020).
During hospitalization, 59 patients died, while 6 died after discharge. The following variables were demonstrated to be associated with a worse prognosis: Radiologic Brixia score higher than 8, presence at baseline of hypertension, diabetes, chronic obstructive pulmonary disease, heart disease, cancer, previous treatment with ACE-inhibitors or anti-platelet drugs. Anticoagulant treatment during hospital admission with enoxaparin at a dose higher than 4000 U once daily was associated with a better prognosis.
In conclusion, our study demonstrates that some co-morbidities and cardiovascular risk factors may affect prognosis. The radiologic Brixia score may be a useful tool to stratify the risk of death at baseline. Anticoagulant treatment with enoxaparin might be associated to a clinical benefit in terms of survival in patients with COVID-19.
Extreme ultra-soft X-ray variability in an eROSITA observation of the narrow-line Seyfert 1 galaxy 1H 0707−495
Authors: Boller Th. , Liu T. , Weber P. , Arcodia R. , Dauser T. , Wilms J. , Nandra K. , Buchner J. , Merloni A. , Freyberg M. J. , Krumpe M. , Waddell S. G. H. 
Published: November 2020

The ultra-soft narrow-line Seyfert 1 galaxy 1H 0707−495 is a well-known and highly variable active galactic nucleus (AGN), with a complex, steep X-ray spectrum, and has been studied extensively with XMM-Newton. 1H 0707−495 was observed with the extended ROentgen Survey with an Imaging Telescope Array (eROSITA) aboard the Spectrum-Roentgen-Gamma (SRG) mission on October 11, 2019, for about 60 000 s as one of the first calibration and pointed verification phase (CalPV) observations. The eROSITA light curves show significant variability in the form of a flux decrease by a factor of 58 with a 1 σ error confidence interval between 31 and 235. This variability is primarily in the soft band, and is much less extreme in the hard band. No strong ultraviolet variability has been detected in simultaneous XMM-Newton Optical Monitor observations. The UV emission is LUV ≈ 1044 erg s−1, close to the Eddington limit. 1H 0707−495 entered the lowest hard flux state seen in 20 yr of XMM-Newton observations. In the eROSITA All-Sky Survey (eRASS) observations taken in April 2020, the X-ray light curve is still more variable in the ultra-soft band, but with increased soft and hard band count rates more similar to previously observed flux states. A model including relativistic reflection and a variable partial covering absorber is able to fit the spectra and provides a possible explanation for the extreme light-curve behaviour. The absorber is probably ionised and therefore more transparent to soft X-rays. This leaks soft X-rays in varying amounts, leading to large-amplitude soft-X-ray variability.
Remarks on generating realistic synthetic meteoroid orbits
Authors: Jopek T. J. 
Published: November 2020

Context. To identify the real associations of small bodies, we can use synthetic sets of orbits generated by various methods. These are not perfect methods, therefore the assessment of their quality is an essential task.
Aims. In this study, we compared five methods for generating synthetic meteoroid orbits. Three of them (ME0, KD10, and KDns) had already been proposed in the literature, while two additional ones (ME1 and ME4) are new methods.
Methods. As far as possible, the synthetic orbits were compared with the orbits of the observed meteoroids. For quantitative comparison, we applied a few tests: the χ2-distance and the nearest neighbor NNN tests used in previous works, and one-dimensional χ2 and Kolmogorov-Smirnov (K-S) tests, as well as a two-dimensional K-S test implemented in this study. To estimate a general property of the orbital sample, we proposed the use of the entropy HN of the data set based on the nearest neighbor distances. Finally, we did a cluster analysis of the synthetic orbits. We calculated and compared the values of the orbital similarity thresholds.
Results. We showed that generating “realistic” meteoroid orbits and testing their quality is a complex issue. An assessment of the quality of the generated orbits depends on the type of test applied, and it refers to the sample of the observed orbits used. Different tests give different assessments. However, in practice, the investigated methods produced similar results if they were applied correspondingly.
Fetal Tachycardia in the Delivery Room: Fetal Distress, Supraventricular Tachycardia, or Both?
Authors: Bhatia Satvinder Singh , Burgess Wendy H. , Skinner Jonathan R. 
Published: November 2020

Abstract
Background Supraventricular tachycardia (SVT) is seldom considered a cause for fetal tachycardia; commoner etiologies including maternal fever and fetal distress are usually envisaged. Fetal arrhythmia can be missed as a diagnosis, potentially leading to suboptimal management.
Cases Three cases are described where detection of fetal tachycardia >200 beats per minute (bpm) at 36, 40, and 38 weeks gestation resulted in emergency cesarean section for presumed fetal distress. Retrospective review of the cardiotocograph in two cases revealed baseline heart rates 120 to 160 bpm, with loss of trace associated with auscultated rates over 200 bpm. The diagnosis of SVT was not initially considered and made later when the infants required cardioversion at the age of 3 weeks, 2 days, and 8 days, respectively. The 36-week infant required noninvasive ventilation for prematurity.
Conclusion SVT should be actively considered in the differential diagnosis of fetal tachycardia. Unrecognized fetal SVT may result in avoidable caesarean for suspected fetal distress, with potential prematurity-related problems. The cardiotocograph can be helpful if showing contact loss associated with rapid heart rate auscultation. The antenatal detection of fetal SVT is important as it can allow anticipation and prevention of neonatal SVT, which is potentially life-threatening if not detected and treated promptly.
Unbiased in vivo preclinical evaluation of anticancer drugs identifies effective therapy for the treatment of pancreatic adenocarcinoma
Authors: Grbovic-Huezo Olivera , Pitter Kenneth L. , Lecomte Nicolas , Saglimbeni Joseph , Askan Gokce , Holm Matilda , Melchor Jerry P. , Chandwani Rohit , Joshi Suhasini , Haglund Caj , Iacobuzio-Donahue Christine A. , Chiosis Gabriela , Tammela Tuomas , Leach Steven D. 
Published: November 2020

Significance
The clinical management of pancreatic cancer has not seen significant improvement in decades, in part because prediction of tumor drug sensitivity using in vitro assays has proven notoriously inaccurate in this disease. We performed a large-scale, unbiased in vivo screen of 57 different single agent and combination targeted therapies in an in vivo orthotopic mouse model. In this ambitious effort, we identified previously unsuspected synergy between HSP90 inhibition and MEK inhibition as effective combination therapy in this disease. The results underscore the utility of unbiased, in vivo drug screens in the identification of effective cancer therapies for evaluation in subsequent clinical trials.
A source for awareness-dependent figure–ground segregation in human prefrontal cortex
Authors: Huang Ling , Wang Lijuan , Shen Wangming , Li Mengsha , Wang Shiyu , Wang Xiaotong , Ungerleider Leslie G. , Zhang Xilin 
Published: November 2020

Significance
Figure–ground segregation, segmenting images by the visual system into figures and background, is the first processing step on the way to visual perception and relies on three complementary processes: boundary detection, region filling, and background suppression. By combining psychophysics, functional magnetic resonance imaging, and effective connectivity analysis, we showed that awareness was important for both region filling and background suppression, but less so for boundary detection. More importantly, we revealed that the awareness-dependent region-filling and background-suppression processes in V1 were derived by feedback from FEF and DLPFC, respectively. Our study indicates an awareness-dependent figure–ground segregation and identifies the human prefrontal cortex as a source of this fundamental process.
Aberrant expression of USF2 in refractory rheumatoid arthritis and its regulation of proinflammatory cytokines in Th17 cells
Authors: Hu Dan , Tjon Emily C. , Andersson Karin M. , Molica Gabriela M. , Pham Minh C. , Healy Brian , Murugaiyan Gopal , Pochet Nathalie , Kuchroo Vijay K. , Bokarewa Maria I. , Weiner Howard L. 
Published: November 2020

SignificanceIdentifying signaling pathways contributing to resistance to anti-TNF therapy in rheumatoid arthritis is crucial for the development of new therapeutic strategies for refractory rheumatoid arthritis. Th17 cells, a subset of proinflammatory CD4+T cells, are implicated in the pathogenesis of the disease. We analyzed the gene expression profiles of Th17-enriched CD4+T cells in anti-TNF–treated patients with rheumatoid arthritis and found that the elevated expression levels of transcription factor USF2 in anti-TNF refractory patients were associated with increased proinflammatory signaling of Th17 cells. USF2-knockdown experiments in Th17 cells revealed that USF2 promotes the pathogenicity of Th17 cells. These findings have implications for the development of new therapeutic strategies for refractory rheumatoid arthritis.
The confidence gap predicts the gender pay gap among STEM graduates
Authors: Sterling Adina D. , Thompson Marissa E. , Wang Shiya , Kusimo Abisola , Gilmartin Shannon , Sheppard Sheri 
Published: November 2020

Significance
Is there a gender pay gap among graduates in some science, technology, engineering, and math (STEM) fields? Women and men have near-identical human capital at college exit, but cultural beliefs about men as more fit for STEM professions than women may lead to self-beliefs that affect pay. We hypothesized that women and men would be paid differently upon college exit, and that gender gaps in self-beliefs about one's abilities, or self-efficacy, would correspond to this difference. Using data from a three-wave longitudinal study of graduates of engineering programs from 2015–2017, we find a confidence gap that aligns with a gender pay gap. Overall, these findings point to the role that cultural beliefs play in creating gender disparities among STEM degree-holders.
Mutation bias within oncogene families is related to proliferation-specific codon usage
Authors: Benisty Hannah , Weber Marc , Hernandez-Alias Xavier , Schaefer Martin H. , Serrano Luis 
Published: November 2020

SignificanceIn light of the genetic code, combinations of three nucleotides which are known as synonymous codons, can give rise to the same amino acid. Despite the homology at the protein level, these different codons are recognized distinctly by the translational machinery. The unequal use of synonymous codons influences protein expression. Surprisingly, we find that the coding sequences of KRAS and other frequently mutated cancer genes are adapted to be efficiently translated in proliferating cells in comparison to their family counterparts. Our work contributes to the unsolved question of why in tumors some members of cancer gene families show a higher mutation rate than their family counterparts. Thus, our results elucidate the relationship between tRNA expression, codon usage, and oncogenicity.
Fast recovery of disrupted tip links induced by mechanical displacement of hair bundles
Authors: Alonso R. G. , Tobin M. , Martin P. , Hudspeth A. J. 
Published: November 2020

Significance
Each of the sensory receptors responsible for hearing or balance—a hair cell—has a mechanosensitive hair bundle. Mechanical stimuli pull upon molecular filaments—the tip links—that open ionic channels in the hair bundle. Loud sounds can damage hearing by breaking the tip links; recovery by replacement of the constituent proteins then requires several hours. We disrupted the tip links in vitro by removing the calcium ions that stabilize them, and then monitored the electrical response or stiffness of hair bundles to determine whether the links could recover. We found that tip links recovered within seconds if their ends were brought back into contact. This form of repair might occur in normal ears to restore sensitivity after damage.
Constitutive relationship and governing physical properties for magnetophoresis
Authors: Ayansiji Ayankola O. , Dighe Anish V. , Linninger Andreas A. , Singh Meenesh R. 
Published: November 2020

Significance
The motion of magnetic particles under magnetic field, referred to as magnetophoresis, is fundamental to nature. While several empirical observations have been gathered, the multitude and complexity of magnetic-field-induced interactions on magnetic particles have prevented the full understanding of this phenomenon. The magnetophoresis is central to several advanced technologies such as magnetic drug targeting, bioseparation, and imaging, yet the efficient targeting of magnetic particles is hampered for the lack of a theoretical framework. We present a fundamental approach utilizing a detailed force balance on magnetic particles to develop a constitutive relationship for magnetophoresis that includes contributions from magnetic diffusion, magnetic convection, and residual magnetization. The application of this theory will enable the predictive design of magnetic targeting applications.
Isotropic compact stars in 4D Einstein–Gauss–Bonnet gravity
Authors: Hansraj Sudan , Banerjee Ayan , Moodly Lushen , Jasim M K 
Published: November 2020

Abstract
Recently it has been proposed that the Gauss–Bonnet coupling parameter of Lovelock gravity may suitably be rescaled in order to admit physically viable models of celestial phenomena such that higher curvature effects are active in standard four dimensions as opposed to the usual higher dimensions. We investigate the consequences of this modification in the context of stellar modelling. The evolution of perfect fluid distributions is governed by the pressure isotropy condition and through stipulation of one of the metric potentials complete models emerge from solutions of the master differential equation. New classes of exact solution with this approach have been reported. One particular model is analysed in detail and shown to comport with elementary physical requirements demanded of realistic compact stars suggesting that the modified theory is not inconsistent with observations.
Order–disorder, ferroelasticity and mobility of domain walls in multiferroic Cu–Cl boracite
Authors: Fernandez-Posada C M , Cochard C , Gregg J M , Whatmore R W , Carpenter M A 
Published: November 2020

Abstract
Domain walls in Cu–Cl boracite develop as a consequence of an improper ferroelastic, improper ferroelectric transition, and have attracted close interest because some are conductive and all can be mechanically written and repositioned by application of an electric field. The phase transition and its associated dynamical properties have been analysed here from the perspective of strain and elasticity. Determination of spontaneous strains from published lattice parameter data has allowed the equilibrium long-range order parameter for F

4

̄

3c → Pca21 to be modelled simply as being close to the order–disorder limit. High acoustic loss in the cubic phase, revealed by resonant ultrasound spectroscopy, is consistent with the presence of dynamical microdomains of the orthorhombic structure with relaxation times in the vicinity of ∼10−5–10−6 s. Low acoustic loss in the stability field of the orthorhombic structure signifies, on the other hand, that ferroelastic twin walls which develop as a consequence of the order–disorder process are immobile on this time scale. A Debye loss peak accompanied by ∼1% elastic stiffening at ∼40 K is indicative of some freezing of defects which couple with strain or of some more intrinsic freezing process. The activation energy of ⩾∼0.01–0.02 eV implies a mechanism which could involve strain relaxation clouds around local ferroelectric dipoles or freezing of polarons that determine the conductivity of twin walls.