bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of histone H2B as a potential receptor for Mycoplasma genitalium protein of adhesion
Authors: Liao Yating , Deng Xiangying , Peng Kailan , Dai Pei , Luo Dan , Liu Peng , Chen Liesong , Li Xia , Ye Youyuan , Zeng Yanhua 
Published: November 2021

ABSTRACT
Mycoplasma genitalium, the smallest prokaryotic microorganism capable of independent replication, is increasingly recognized as a sexually transmitted pathogen. M. genitalium protein of adhesion (MgPa) plays a pivotal role in the process of M. genitalium adhesion to host cells. We previously identified cyclophilin A as a cellular receptor of MgPa using the virus overlay protein binding assay (VOPBA) together with liquid chromatography-mass spectrometry (LC-MS). In the current study, we have evaluated H2B as an alternative cellular receptor for MgPa since H2B was assigned the second higher score as a potential binding partner of MgPa in the VOPBA and LC-MS screen. It was found that recombinant MgPa specifically bind to H2B both in the SV-HUC-1 cell membrane and in form of a recombinant protein. H2B was detected throughout the SV-HUC-1 cells, including the cytoplasmic membrane, cytosol and nucleus. Importantly, H2B partially inhibited the adhesion of M. genitalium to SV-HUC-1 cells. Finally, H2B was both co-precipitated with recombinant MgPa and co-localized with M. genitalium and recombinant MgPa in SV-HUC-1 cells. The above observations suggest that H2B may act as a potential cellular receptor of MgPa for mediating M. genitalium adhesion to host cells.
Theoretical prediction of elastic modulus at different states and squirt-flow-related attenuation: extension of Cracks-Pores Effective Medium model
Authors: Zhao Liming , Yin Hanjun , Chen Tongjun , Tang Genyang , Sun Chao , Zhang Mingjin , Zhu Ningjun , Li Fanjia 
Published: November 2021

SUMMARYSquirt flow plays an essential role in elastic modulus dispersion and attenuation for fluid-saturated cracked porous rocks. The Mavko–Jizba model and relevant modified models can describe the squirt flow well based on the related elastic moduli, such as dry/drained bulk modulus. However, when these elastic moduli are challenging to attain, it is impossible to model the squirt-flow-related elastic moduli and attenuations with the models. On the other hand, the effective medium theory (EMT) model can estimate these elastic moduli, but cannot predict the undrained/relaxed and partially relaxed saturated elastic moduli and the squirt-flow-related attenuations. This paper extended an EMT model—Cracks–Pores Effective Medium (CPEM) model—to cover the undrained/relaxed and partially relaxed states following the elastic–viscoelastic correspondence principle. The proposed model [i.e. frequency-dependent CPEM (CPEMF) model] can thus estimate the elastic moduli over the different states (dry/drained, undrained/relaxed, partially relaxed and unrelaxed) and associated attenuations. It agrees well with the prediction of the modified Mavko–Jizba–Gurevich model (MJGZ-HF) at unrelaxed state and is precisely consistent with the prediction of Gassmann at undrained/relaxed state. Also, it analytically shows good consistency with the modified Mavko–Jizba–Gurevich model (MJGZ-MF) at partially relaxed state. The numerical simulations of CPEM/CPEMF models and MJGZ-HF/MJGZ-MF models show good agreement at the different states. Furthermore, we interpreted the experimental data on a basaltic sample and a sandstone sample with the CPEM/CPEMF models. The CPEMF model's predictions of elastic modulus at different states and associated modulus dispersion/attenuation are in good agreement with the corresponding measured ones, suggesting that the proposed CPEMF model can efficiently predict the elastic moduli at different states (dry/drained, undrained/relaxed, partially relaxed and unrelaxed) and quantify the squirt-flow-related elastic modulus dispersion and attenuation among different states well.
Judicialización de medicamentos huérfanos en Brasil: la justiciabilidad de un objeto políticamente “no palatable”Judicialization of orphan drugs in Brazil: the justiciability of a politically unpalatable issue
Authors: Cardoso João Vitor 
Published: November 2021

Abstract
Occasionally, elected officials invite the judiciary to resolve those particularly challenging problems for which there are no solutions or that they would rather not address. The access to orphan drugs in Brazil is a problem of such type. With the aim of illustrating how the judicial enforcement of social rights can favor vulnerable groups, this article deploys original data through a case study on the most prominently judicialized orphan drug in Brazil, reliant on quantitative as well as qualitative primary sources. Thus, it advances a twofold argument. First, when the exercise of a social right is associated with a politically unpalatable controversy, meaning one that does not foster enough political interest in a solution, despite embodying a pressing policy problem, elected officials are less likely to address it. Second, the expansion of judicial power would be defensible against the backdrop of an issue of such type. The empirical analysis yields new insights into normative debates concerning social rights judicial enforcement. When politically disadvantaged groups learn to use the constitutional framework to advance their interests by presenting rights claims, in the long term it can generate information about the scope of a legislative inertia, give a voice to silenced actors, and reallocate resources to care for urgent needs of minoritarian groups.
Identification of multiple transfer units and novel subtypes of tmexCD-toprJ gene clusters in clinical carbapenem-resistant Enterobacter cloacae and Klebsiella oxytoca
Authors: Sun Shijun , Wang Qi , Jin Longyang , Guo Yifan , Yin Yuyao , Wang Ruobing , Bi Lei , Zhang Renfei , Han Yungang , Wang Hui 
Published: November 2021

Abstract

Objectives
Tigecycline is a last-resort antibiotic used to treat lethal infections caused by carbapenem-resistant Enterobacterales; however, plasmid-borne tigecycline resistance tmexCD-toprJ gene clusters can confer tigecycline resistance. The aim of the study was to identify novel subtypes and the spread of tmexCD-toprJ.

Methods
Five non-duplicate isolates of different species, carrying tmexCD-toprJ gene clusters or novel subtypes, were isolated from patients across China between November 2018 and June 2019. WGS was performed using Illumina and Nanopore platforms. A phylogenetic tree was constructed using a dataset of 77 sequences carrying the tmexCD-toprJ gene clusters, 72 of which were downloaded from NCBI with a blastn identity cut-off of 95%.

Results
We detected six different transfer units and two novel subtypes (tmexC1D1.2-toprJ1 and tmexC2D2.2-toprJ2) of the tmexCD-toprJ gene clusters. Among the six transfer units, three were mediated by IS26, while the rest were presumably mediated by Tn5393, hypothetical integrases (xerD-hp clusters-umuC-integrases-tnfxB2-tmexC2D2-toprJ2-umuC) and hypothetical units (hp-hp-hp-tnfxB2-tmexC2D2.2-toprJ2-ΔTn5393-Tn6292). Moreover, two tmexCD-toprJ-like gene clusters co-located on the same plasmid with blaNDM in five isolates. Phylogenetic analysis revealed that tmexCD-toprJ gene clusters may have originated in Pseudomonas spp., being mainly distributed in Pseudomonas spp. and Klebsiella spp. (64/77). Most tmexCD-toprJ gene clusters in Enterobacterales were located on plasmids, indicating that the gene clusters have a high inter-species transfer risk after transfer to Enterobacterales.

Conclusions
In summary, to the best of our knowledge, this is the first report of tmexCD-toprJ gene clusters being isolated from Enterobacter cloacae and Klebsiella oxytoca, revealing that these multiple transfer units should be further studied because of their clinical significance.
Mitigation of Biotin Interference in Manual and Automated Immunoassays by Preconjugating Biotinylated Antibodies to the Streptavidin Surface as an Alternative to Biotin Depletion
Authors: Nelson Heather A , La’ulu Sonia L , Lu Jun , Doyle Kelly 
Published: November 2021

Abstract

Background
Streptavidin-to-biotin binding is one of the strongest noncovalent interactions in nature and incorporated into many immunoassays. Biotin-streptavidin coupling assays are susceptible to interference from free biotin in patient specimens, which may falsely decrease or increase results. To prevent biotin interference, we evaluated a method to preconjugate biotinylated antibodies to the assay’s streptavidin solid surface before adding patient specimen and compared this technique to a biotin depletion protocol.

Methods
Biotin interference in 3 manual ELISAs and 2 automated immunoassays was established. Mitigation of biotin interference by preincubation was evaluated in each assay by adding biotinylated antibody to the streptavidin-coated surface before adding biotin- or PBS-spiked serum. Lastly, the preincubation method was compared to a biotin-depletion protocol to compare the effectiveness of mitigating biotin interference.

Results
In the presence of 400 µg/L biotin, analyte detection was reduced to 10% to 15% of total in the ELISA assays and to 15.2% in the automated sandwich (thyroglobulin) immunoassay. In the automated competitive (free thyroxine) immunoassay, biotin caused an increased detection of 551.6%. Preconjugation of the biotinylated capture antibody to the streptavidin surface in the ELISA assays resulted in 84% to 99% activity recovery, compared to 84% to 97% by a biotin depletion protocol. Similarly, automated sandwich and competitive immunoassays obtained 97.1% and 116.5% recovery by preconjugation, compared to 95.6% and 100.3% by the depletion method, respectively.

Conclusion
This study demonstrates how assay redesign to include preconjugation of biotinylated capture antibody to streptavidin is an effective alternative to biotin-depletion methods to mitigate biotin interference.
Topology optimization of irregular flow domain by parametric level set method in unstructured mesh
Authors: Li Jiajing , Gao Liang , Ye Mengli , Li Hao , Li Lizhou 
Published: November 2021

ABSTRACT
In this study, we present a novel method for the topology optimization of the irregular flow domain using a parametric level set method (PLSM). Some improvement was applied on the CS-RBFs (radial basis functions with compact support)-based PLSM to make it suitable for nonuniform mesh, expanding the range field of engineering application of the PLSM. The optimization problem is solved by a gradient-based algorithm with Stokes equations as state constraints, and the objective is set to minimize the power dissipation subject to the volume constraint of flow channels. A PLSM is introduced to avoid the direct solving of the Hamilton–Jacobi partial differential equation, which can have the potential to break through the restriction of relying on structured meshes because no finite difference scheme is required. Then, a self-adaption support radius approach is presented to allow the parametric level set to be evolved on the nonuniformed mesh, which can expand the application of the PLSM to more complicated engineering problems with irregular geometric shapes. A volume integration scheme is applied during the design sensitivity analysis to calculate the shape derivatives, allowing the nucleation of new holes. Numerical examples in two and three dimensions are provided to demonstrate the effectiveness of the proposed method.
Accountability for Human Rights: Applying Business and Human Rights Instruments to Non-Governmental Organizations
Authors: Carolei Domenico , Bernaz Nadia 
Published: November 2021

Abstract
Often seen as selfless champions of human rights, non-governmental organizations are vulnerable to attacks from unscrupulous states, which makes NGO regulation and accountability for human rights a sensitive issue. Yet, like all organizations, NGOs can have negative human rights impacts. States and international organizations have developed business and human rights (BHR) instruments that apply to corporations but there is no equivalent for NGOs. This article assesses the extent to which BHR standards may be relevant to enhance NGO accountability for human rights. It argues that these instruments, although not designed with NGOs in mind, are relevant to their operations and provide an attractive and moderate avenue to enhance NGO accountability. Ultimately, it shows that applying BHR instruments to NGOs could strengthen these instruments.
Applications of deep learning in electron microscopy
Authors: Treder Kevin P , Huang Chen , Kim Judy S , Kirkland Angus I 
Published: November 2021

AbstractWe review the growing use of machine learning in electron microscopy (EM) driven in part by the availability of fast detectors operating at kiloHertz frame rates leading to large data sets that cannot be processed using manually implemented algorithms. We summarize the various network architectures and error metrics that have been applied to a range of EM-related problems including denoising and inpainting. We then provide a review of the application of these in both physical and life sciences, highlighting how conventional networks and training data have been specifically modified for EM.
Gas infall and radial transport in cosmological simulations of milky way-mass discs
Authors: Trapp Cameron W , Kereš Dušan , Chan Tsang Keung , Escala Ivanna , Hummels Cameron , Hopkins Philip F , Faucher-Giguère Claude-André , Murray Norman , Quataert Eliot , Wetzel Andrew 
Published: November 2021

ABSTRACT
Observations indicate that a continuous supply of gas is needed to maintain observed star formation rates in large, discy galaxies. To fuel star formation, gas must reach the inner regions of such galaxies. Despite its crucial importance for galaxy evolution, how and where gas joins galaxies is poorly constrained observationally and rarely explored in fully cosmological simulations. To investigate gas accretion in the vicinity of galaxies at low redshift, we analyse the FIRE-2 cosmological zoom-in simulations for 4 Milky Way mass galaxies (Mhalo ∼ 1012M⊙), focusing on simulations with cosmic ray physics. We find that at z ∼ 0, gas approaches the disc with angular momentum similar to the gaseous disc edge and low radial velocities, piling-up near the edge and settling into full rotational support. Accreting gas moves predominately parallel to the disc and joins largely in the outskirts. Immediately prior to joining the disc, trajectories briefly become more vertical on average. Within the disc, gas motion is complex, being dominated by spiral arm induced oscillations and feedback. However, time and azimuthal averages show slow net radial infall with transport speeds of 1–3 km s−1 and net mass fluxes through the disc of ∼M⊙ yr−1, comparable to the galaxies’ star formation rates and decreasing towards galactic centre as gas is sunk into star formation. These rates are slightly higher in simulations without cosmic rays (1–7 km s−1, ∼4–5 M⊙ yr−1). We find overall consistency of our results with observational constraints and discuss prospects of future observations of gas flows in and around galaxies.
Milky Way total mass derived by rotation curve and globular cluster kinematics from Gaia EDR3
Authors: Wang Jianling , Hammer Francois , Yang Yanbin 
Published: November 2021

ABSTRACT
Using action-based distribution function for the dynamical model of the Milky Way (MW) we have estimated its total mass and its density profile. Constraints are coming from the globular cluster proper motions from Gaia EDR3, from the rotation curve based on Gaia DR2 data, and from the vertical force data. We use Bayesian Markov chain Monte Carlo method to explore the parameters, for which the globular cluster distribution function and the Galactic potential are fully constrained. Numerical simulations are used to study the uncertainties on the potential constraint if considering a possible massive Large Magellanic Cloud (LMC). We found that a massive LMC (1.5 × 1011 M⊙) will affect the MW mass measurement at large radius, which includes both the MW and the LMC. We also use the FIRE2 Latte cosmological hydrodynamic simulations to make mock data set from an MW-like galaxy that includes many unrelaxed substructures. We test the effect of these unrelaxed substructures on the final results, and found that the measured rotation curve fluctuated around input value within 5 per cent. By keeping a large freedom in choosing a priori mass profile for both baryonic and dark matter leads a total mass of the MW that ranges from $5.36_{-0.68}^{+0.81}\times 10^{11}$ M⊙ to $7.84_{-1.97}^{+3.08} \times 10^{11}$ M⊙. This includes the contribution of a putative massive LMC and significantly narrows the MW total mass range published earlier. Such total mass leads to dark matter density at solar position of $0.34_{-0.02}^{+0.02}$ GeV cm−3.
Besca, a single-cell transcriptomics analysis toolkit to accelerate translational research
Authors: Mädler Sophia Clara , Julien-Laferriere Alice , Wyss Luis , Phan Miroslav , Sonrel Anthony , Kang Albert S W , Ulrich Eric , Schmucki Roland , Zhang Jitao David , Ebeling Martin , Badi Laura , Kam-Thong Tony , Schwalie Petra C , Hatje Klas 
Published: November 2021

Abstract
Single-cell RNA sequencing (scRNA-seq) revolutionized our understanding of disease biology. The promise it presents to also transform translational research requires highly standardized and robust software workflows. Here, we present the toolkit Besca, which streamlines scRNA-seq analyses and their use to deconvolute bulk RNA-seq data according to current best practices. Beyond a standard workflow covering quality control, filtering, and clustering, two complementary Besca modules, utilizing hierarchical cell signatures and supervised machine learning, automate cell annotation and provide harmonized nomenclatures. Subsequently, the gene expression profiles can be employed to estimate cell type proportions in bulk transcriptomics data. Using multiple, diverse scRNA-seq datasets, some stemming from highly heterogeneous tumor tissue, we show how Besca aids acceleration, interoperability, reusability and interpretability of scRNA-seq data analyses, meeting crucial demands in translational research and beyond.
Risk of hydroxychloroquine retinopathy in the community
Authors: Dabit Jesse Y , Hocaoglu Mehmet , Moder Kevin G , Barkmeier Andrew J , Smith Wendy M , O’Byrne Thomas J , Crowson Cynthia S , Duarte-García Alí 
Published: November 2021

Abstract

Objectives
We aimed to estimate the risk of HCQ retinopathy and its risk factors among incident users in the community.

Methods
Using the Rochester Epidemiology Project, a record-linkage system, a cohort of incident users of HCQ was identified from 27 counties in the American upper Midwest. HCQ retinopathy was defined based on characteristic paracentral automated 10-2 visual field (10-2 AVF) defects and parafoveal retinal photoreceptor layer changes on spectral domain optical coherence tomography. Cumulative incidence rates were estimated adjusting for competing risk of death. Risk factors for HCQ retinopathy were examined using Cox models.

Results
The study included 634 incident HCQ users (mean age at initial HCQ use was 53.7 years, 79% females, 91% white). Most common indications for HCQ were RA (57%) and SLE (19%). The average follow-up length was 7.6 years. Eleven patients developed HCQ retinopathy (91% females, 91% white). The majority used HCQ for RA (91%). The cumulative incidence rate at year 5 was 0%, which increased to 3.9% (95% CI 2.0, 7.4) by 10 years. Taking an HCQ dose ≥5 mg/kg was associated with a hazard ratio (HR) of 3.59 (95% CI 1.09, 11.84) compared with lower doses. There was a 48% increase [HR 1.48 (95% CI 1.03, 2.14)] in the risk of HCQ retinopathy for each 100 g of HCQ cumulative dose.

Conclusion
The risk of HCQ retinopathy at 10 years of use is lower compared with previous prevalence-based estimations. A dose ≥5 mg/kg was associated with higher HCQ retinopathy risk.
Diffuse Optical Tomography Using fNIRS Signals Measured from the Skull Surface of the Macaque Monkey
Authors: Hayashi Ryusuke , Yamashita Okito , Yamada Toru , Kawaguchi Hiroshi , Higo Noriyuki 
Published: November 2021

Abstract
Diffuse optical tomography (DOT), as a functional near-infrared spectroscopy (fNIRS) technique, can estimate three-dimensional (3D) images of the functional hemodynamic response in brain volume from measured optical signals. In this study, we applied DOT algorithms to the fNIRS data recorded from the surface of macaque monkeys’ skulls when the animals performed food retrieval tasks using either the left- or right-hand under head-free conditions. The hemodynamic response images, reconstructed by DOT with a high sampling rate and fine voxel size, demonstrated significant activations at the upper limb regions of the primary motor area in the central sulcus and premotor, and parietal areas contralateral to the hands used in the tasks. The results were also reliable in terms of consistency across different recording dates. Time-series analyses of each brain area revealed preceding activity of premotor area to primary motor area consistent with previous physiological studies. Therefore, the fNIRS–DOT protocol demonstrated in this study provides reliable 3D functional brain images over a period of days under head-free conditions for region-of-interest–based time-series analysis.
Transepithelial Diluted Alcohol and Iontophoresis-Assisted Corneal Crosslinking for Progressive Keratoconus in Adults: 4-Year Clinical Results
Authors: Bilgihan Kamil , Uysal Betul Seher , Özmen Mehmet Cüneyt , Eskalen Oguzcan , Gurelik Gokhan 
Published: November 2021

Purpose:
The aim of this study was to compare the 4-year clinical outcomes of transepithelial diluted alcohol and iontophoresis-assisted corneal crosslinking (DAI-CXL) and standard corneal crosslinking (S-CXL) in adults with progressive keratoconus.

Methods:
This retrospective study included 36 eyes of 36 keratoconic patients who underwent DAI-CXL (n = 18) or S-CXL (n = 18). Best spectacle-corrected visual acuity (BSCVA) and corneal topography parameters were analyzed at baseline and at 1, 2, 3, and 4 years of follow-up. Corneal demarcation line depth (DLD) at 1 month was measured, and the relation of DLD with corneal thickness (DL%) was assessed.

Results:
BSCVA improved significantly only in S-CXL (P = 0.01). A significant decrease in maximum keratometry and mean keratometry occurred at 4 years in both groups (all P < 0.05), and these changes were similar in both groups (all P > 0.05). There was a significant reduction in the thinnest corneal thickness in S-CXL (P = 0.01); however, the mean thinnest corneal thickness in DAI-CXL remained stable (P = 0.094). Higher-order aberrations and coma aberration decreased significantly in both groups at 4 years (all P < 0.05), with a higher decrease in S-CXL (all P < 0.05). Spherical aberration showed a significant reduction only in S-CXL (P = 0.005). In contrast to the similar mean DLD in both groups, DL% in DAI-CXL was significantly greater than that in S-CXL (P = 0.032). There were no correlations between the improvement in BSCVA, maximum keratometry, mean keratometry, higher-order aberrations, and the mean DLD and DL% (all P > 0.05).

Conclusions:
DAI-CXL was as effective as S-CXL in arresting the progression of keratoconus and showed similar clinical results to S-CXL at the 4-year follow-up.