bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transplant Center Attitudes Toward Early Liver Transplant for Alcohol-associated Liver Disease
Authors: Mitchell Jonathan , Herrick-Reynolds Kayleigh , Motter Jennifer D. , Teles Mayan , Kates Olivia , Sung Hannah , Chen Po-Hung , King Elizabeth , Cameron Andrew 
Published: August 2023

Background.
Many centers have removed 6-mo pretransplant alcohol abstinence requirements to provide early liver transplant (ELT) for individuals with severe alcohol-associated liver disease (ALD), but the practice remains controversial. Using data collected from a nationally distributed survey, this study examines the practices and attitudes of transplant centers in the United States regarding ELT.

Methods.
A 20-item survey designed to assess center practices and provider attitudes was distributed to 225 medical and surgical directors from 143 liver transplant centers via email.

Results.
Surveys were completed by 28.9% (n = 65) of directors and 39% (n = 56) of transplant centers. All responding centers reported evaluating patients for ELT. Circumstances for considering ELT included <6 mo of survival without a transplant (96.4%) and inability to participate in alcohol addiction therapy pretransplant (75%). Most (66%) directors indicated their center had established criteria for listing candidates with severe ALD for ELT. Regarding important factors for ELT candidate listing, 57.1% indicated patient survival, 37.5% indicated graft survival, and 55.4% indicated having a low risk of relapse. Only 12.7% of directors affirmed the statement, “Six months of pretransplant abstinence decreases the risk of relapse.”

Conclusions.
More centers are providing ELT for severe ALD. Inability to participate in alcohol addiction therapy and <6 mo of survival are commonly reported circumstances for considering ELT. Continued investigation of posttransplant outcomes in patients receiving ELT is essential to establishing a national consensus for distributing this valuable resource.
Clustering of fluoride and phosphate ions in bioactive glass from computer simulation
Authors: Christie Jamieson K. 
Published: August 2023

In order to understand the nature of ionic clustering in bioactive glass compositions, computer simulation was used to model four different compositions of bioactive glass with various amounts of flouride and phosphate. Fluoride ions were chemically bonded only to sodium and calcium, creating regions rich in fluoride and modifiers, and fluoride clustering was seen to be present in all compositions. The majority of phosphate groups are present as orthophosphate and phosphate clustering is also seen, and shown to be stronger in compositions with a lower phosphate content.
This article is part of the theme issue ‘Exploring the length scales, timescales and chemistry of challenging materials (Part 1)’.
Effect of water on the glass transition of a potassium-magnesium carbonate melt
Authors: Weidendorfer Daniel , Hess Kai-Uwe , Ruhekenya Ruben M. , Schawe Jürgen E. K. , Wilding Martin C. , Dingwell Donald B. 
Published: August 2023

Calorimetric measurements of the glass transition temperatures (Tg) of hydrous carbonate melts are reported on a near-eutectic composition of 55 mol% K2CO3– 45 mol% MgCO3with up to 42 mol% bulk H2O dissolved in the carbonate melt. Hydrous melts were quenched from 750°C to transparent and crystal-free glasses and were subsequently analysed for water content before and after measuringTgby high-sensitivity differential scanning calorimetry. The glass transition and limited fictive temperatures as a function of the water content were determined at 10 K/min cooling/heating rates resulting inTgranging from 245°C at nominally anhydrous conditions to 83°C in the presence of 42 mol% H2O in the glass. Through a generalized Gordon–Taylor analysis, the factorsk(7.27),k0(3.2) and the interaction parameterAx(0.49) were derived. The limited fictive temperature of a hypothetically, zero water containing 55 mol% K2CO3– 45 mol% MgCO3glass is 232 ± 5°C (505 K). The high value of the interaction parameterAindicates strong specific molecular interactions between water and the carbonates in the glassy state and a large decrease in the excess enthalpy of mixing during the conversion of the glassy into the liquid state at the glass transition.This article is part of the theme issue 'Exploring the length scales, timescales and chemistry of challenging materials (Part 1)'.
Elastic moduli and refractive index of γ-Ge
3
N
4
Authors: Li Chen-Hui , Djemia Philippe , Chigarev Nikolay , Sodki Siham , Roussigné Yves , Manthilake Geeth , Tessier Franck , Raetz Samuel , Gusev Vitalyi E. , Zerr Andreas 
Published: August 2023

Germanium nitride, having cubic spinel structure, γ-Ge
3
N
4
, is a wide band-gap semiconductor with a large exciton binding energy that exhibits high hardness, elastic moduli and elevated thermal stability up to approximately 700°C. Experimental data on its bulk and shear moduli (
B
0
and
G
0
, respectively) are strongly limited, inconsistent and, thus, require verification. Moreover, earlier first-principles density functional calculations provided significantly scattering
B
0
values but consistently predicted
G
0
much higher than the so far available experimental value. Here, we examined the elasticity of polycrystalline γ-Ge
3
N
4
, densified applying high pressures and temperatures, using the techniques of laser ultrasonics (LU) and Brillouin light scattering (BLS) and compared with our extended first-principles calculations. From the LU measurements, we obtained its longitudinal- and Rayleigh wave sound velocities and, taking into account the sample porosity, derived
B
0
= 322(44) GPa and
G
0
= 188(7) GPa for the dense polycrystalline γ-Ge
3
N
4
. While our calculations underestimated
B
0
by approximately 17%, most of the predicted
G
0
matched well with our experimental value. Combining the LU- and BLS data and taking into account the elastic anisotropy, we determined the refractive index of γ-Ge
3
N
4
in the visible range of light to be
n
= 2.4, similarly high as that of diamond or GaN, and matching our calculated value.

This article is part of the theme issue 'Exploring the length scales, timescales and chemistry of challenging materials (Part 1)'.
Flow: a web platform and open database to analyse, store, curate and share bioinformatics data at scale
Authors: Capitanchik Charlotte , Ireland Sam , Harston Alex , Cheshire Chris , Jones D. Marc , Lee Flora C.Y. , Ruiz de los Mozos Igor , Iosub Ira A. , Kuret Klara , Faraway Rupert , Wilkins Oscar G. , Arora Rahul , Hallegger Martina , Modic Miha , Chakrabarti Anob M. , Luscombe Nicholas M. , Ule Jernej 
Published: August 2023

AbstractEver-increasing volumes of sequencing data offer potential for large-scale meta-analyses to address significant biological questions. However, challenges such as insufficient data processing information, data quality concerns, and issues related to accessibility and curation often present obstacles. Additionally, most experimental biologists lack the time and expertise needed to independently analyse, manage and share their own data. To overcome these hurdles, we present Flow, a web-based platform that links bioinformatic analysis and database solutions with a user-friendly interface and web API. Flow currently accommodates a range of genomics methods and further DSL2-compliant Nextflow pipelines can be added via a simple JSON schema file. Deployable on local systems or cloud services, an instance is freely accessible to academic researchers athttps://flow.bio.
Inferring single-cell protein levels and cell cycle behavior in heterogeneous cell populations
Authors: Thijssen Bram , Segeren Hendrika A. , Liu Qingwu , Wessels Lodewyk F.A. , Westendorp Bart 
Published: August 2023

AbstractIndividual cells in a genetically identical population can show highly variable behavior. Single-cell measurements allow us to study this variability, but the available measurement techniques have limitations: live-cell microscopy is typically restricted to one or a few molecular markers, while techniques that simultaneously measure large numbers of molecular markers are destructive and cannot be used to follow cells over time. To help overcome these limitations, we present here scMeMo (single cell Mechanistic Modeler): a mechanistic modeling framework that can leverage diverse sets of measurements in order to infer unobserved variables in heterogeneous single cells. We used this framework to construct a model describing cell cycle progression in human cells, and show that it can predict the levels of several proteins in individual cells, based on live-cell microscopy measurements of only one marker and information learned from other experiments. The framework incorporates an uncertainty calibration step that makes the posterior distributions robust against partial model misspecification. Our modeling framework can be used to integrate information from separate experiments with diverse readouts, and to infer single cell variables that may be difficult to measure directly.
Gene editing ofSAMHD1in macrophage-like cells reveals complex relationships between SAMHD1 phospho-regulation, HIV-1 restriction and cellular dNTP levels
Authors: Schüssler Moritz , Schott Kerstin , Fuchs Nina Verena , Oo Adrian , Zahadi Morssal , Rauch Paula , Kim Baek , König Renate 
Published: August 2023

AbstractSterile α motif (SAM) and HD domain-containing protein 1 (SAMHD1) is a dNTP triphosphate triphosphohydrolase (dNTPase) and a potent restriction factor for immunodeficiency virus 1 (HIV-1), active in myeloid and resting CD4+T cells. The anti-viral activity of SAMHD1 is regulated by dephosphorylation of the residue T592. However, the impact of T592 phosphorylation on dNTPase activity is still under debate. Whether additional cellular functions of SAMHD1 impact anti-viral restriction is not completely understood.We report BLaER1 cells as a novel human macrophage HIV-1 infection model combined with CRISPR/Cas9 knock-in (KI) introducing specific mutations into theSAMHD1locus to study mutations in a physiological context. Transdifferentiated BLaER1 cells harbor active dephosphorylated SAMHD1 that blocks HIV-1 reporter virus infection. As expected, homozygous T592E mutation, but not T592A, relieved a block to HIV-1 reverse transcription. Co-delivery of VLP-Vpx to SAMHD1 T592E KI mutant cells did not further enhance HIV-1 infection indicating the absence of an additional SAMHD1-mediated antiviral activity independent of T592 de-phosphorylation. T592E KI cells retained dNTP levels similar to WT cells indicating uncoupling of anti-viral and dNTPase activity of SAMHD1. The integrity of the catalytic site in SAMHD1 was critical for anti-viral activity, yet poor correlation of HIV-1 restriction and global cellular dNTP levels was observed in cells harboring catalytic core mutations. Together, we emphasize the complexity of the relationship between HIV-1 restriction, SAMHD1 enzymatic function and T592 phospho-regulation and provide novel tools for investigation in an endogenous and physiological context.ImportanceWe introduce BLaER1 cells as an alternative myeloid cell model in combination with CRISPR/Cas9-mediated gene editing to study the influence of SAMHD1 T592 Mophosphorylation on anti-viral restriction and the control of cellular dNTP levels in an endogenous, physiological relevant context. Proper understanding of the mechanism of the anti-viral function of SAMHD1 will provide attractive strategies aiming at selectively manipulating SAMHD1 without affecting other cellular functions.Even more, our toolkit may inspire further genetic analysis and investigation of restriction factors inhibiting retroviruses, their cellular function and regulation, leading to a deeper understanding of intrinsic anti-viral immunity.
Fe-TAMLs as a new class of small molecule peroxidase probes for correlated light and electron microscopy
Authors: Adams Stephen R. , Mackey Mason R. , Ramachandra Ranjan , Deerinck Thomas J. , Castillon Guillaume A. , Phan Sebastien , Hu Junru , Boassa Daniela , Ngo John T. , Ellisman Mark H. 
Published: August 2023

ABSTRACTWe introduce Fe-TAML, a small molecule-based peroxidase as a versatile new member of the correlated fluorescence and electron microscopy toolkit. The utility of the probe is demonstrated by high resolution imaging of newly synthesized DNA (through biorthogonal labeling), genetically tagged proteins (using HaloTag), and untagged endogenous proteins (via immunostaining). EM visualization in these applications is facilitated by exploiting Fe-TAML’s catalytic activity for the deposition of localized osmiophilic precipitates based on polymerized 3,3’-diaminobenzidine. Optimized conditions for synthesizing and implementing Fe-TAML based probes are also described. Overall, Fe-TAML is a new chemical biology tool that can be used to visualize diverse biomolecular species along nanometer and micron scales within cells.
Structural mechanism of synergistic targeting of theCX3CR1nucleosome by PU.1 and C/EBP⍺
Authors: Lian Tengfei , Guan Ruifang , Zhou Bing-Rui , Bai Yawen 
Published: August 2023

AbstractPioneer transcription factors are vital for cell fate changes. PU.1 and C/EBP⍺ work together to regulate hematopoietic stem cell differentiation. However, how they recognizein vivonucleosomal DNA targets remain elusive. Here we report the structures of the nucleosome containing the mouse genomicCX3CR1enhancer DNA and its complexes with PU.1 alone and with both PU.1 and the C/EBP⍺ DNA binding domain. Our structures reveal that PU.1 binds the DNA motif at the exit linker, shifting 17 bp of DNA into the core region through interactions with H2A, unwrapping ∼20 bp of nucleosomal DNA. C/EBP⍺ binding, aided by PU.1’s repositioning, unwraps ∼25 bp entry DNA. The PU.1 Q218H mutation, linked to acute myeloid leukemia, disrupts PU.1-H2A interactions. PU.1 and C/EBP⍺ jointly displace linker histone H1 and open the H1-condensed nucleosome array. Our study unveils how two pioneer factors can work cooperatively to open closed chromatin by altering DNA positioning in the nucleosome.
Random walk and cell morphology dynamics inNaegleria gruberi
Authors: Uwamichi Masahito , Miura Yusuke , Kamiya Ayako , Imoto Daisuke , Sawai Satoshi 
Published: August 2023

AbstractAmoeboid cell movement and migration are wide-spread across various cell types and species. Microscopy-based analysis of the model systemsDictyosteliumand neutrophils over the years have uncovered generality in their overall cell movement pattern. Under no directional cues, the centroid movement can be quantitatively characterized by their persistence to move in a straight line and the frequency of re-orientation. Mathematically, the cells essentially behave as a persistent random walker with memory of two characteristic time-scale. Such quantitative characterization is important from a cellular-level ethology point of view as it has direct connotation to their exploratory and foraging strategies. Interestingly, outside the amoebozoa and metazoa, there are largely uncharacterized species in the excavate taxon Heterolobosea including amoeboflagellateNaegleria. While classical works have shown that these cells indeed show typical amoeboid locomotion on an attached surface, their quantitative features are so far unexplored. Here, we analyzed the cell movement ofNaegleria gruberiby employing long-time phase contrast imaging to automatically track individual cells. We show that the cells move as a persistent random walker with two time-scales that are close to those known inDictyosteliumand neutrophils. Similarities were also found in the shape dynamics which is characterized by the appearance, splitting and annihilation of the curvature waves along the cell edge. Our analysis based on the Fourier descriptor and a neural network classifier point to importance of morphology features unique toNaegleriaincluding complex protrusions and the transient bipolar dumbbell morphologies.
Thyroid hormones mediate the impact of early-life stress on ventral tegmental area gene expression and behavior
Authors: Bennett Shannon N. , Chang Austin B. , Rogers Forrest D. , Jones Parker , Peña Catherine Jensen 
Published: August 2023

ABSTRACTProper thyroid function is essential to the developing brain, including dopamine neuron differentiation, growth, and maintenance. Stress across the lifespan impacts thyroid hormone signaling and anxiety disorders and depression have been associated with thyroid dysfunction (both hypo- and hyper-active). However, less is known about how stress during postnatal development impacts thyroid function and related brain development. Our previous work in mice demonstrated that early-life stress (ELS) transiently impinged on expression of a transcription factor in dopamine neurons shown to be regulated by thyroid hormones. We hypothesized that thyroid hormone signaling may link experience of ELS with transcriptional dysregulation within the dopaminergic midbrain, and ultimately behavior. Here, we find that ELS transiently increases thyroid-stimulating hormone levels (inversely related to thyroid signaling) in both male and female mice at P21, an effect which recovers by adolescence. We next tested whether transient treatment of ELS mice with synthetic thyroid hormone (levothyroxine, LT4) could ameliorate the impact of ELS on sensitivity to future stress, and on expression of genes related to dopamine neuron development and maintenance, thyroid signaling, and plasticity within the ventral tegmental area. Among male mice, but not females, juvenile LT4 treatment prevented hypersensitivity to adult stress. We also found that rescuing developmental deficits in thyroid hormone signaling after ELS restored levels of some genes altered directly by ELS, and prevented alterations in expression of other genes sensitive to the second hit of adult stress. These findings suggest that thyroid signaling mediates the deleterious impact of ELS on VTA development, and that temporary treatment of hypothyroidism after ELS may be sufficient to prevent future stress hypersensitivity.
Hawkes process modelling for chemical reaction networks in a random environment
Authors: Sinzger-D’Angelo Mark , Koeppl Heinz 
Published: August 2023

AbstractCellular processes are open systems, situated in a heterogeneous context, rather than operating in isolation. Chemical reaction networks (CRNs) whose reaction rates are modelled as external stochastic processes account for the heterogeneous environment when describing the embedded process. A marginal description of the embedded process is of interest for (i) fast simulations that bypass the co-simulation of the environment, (ii) obtaining new process equations from which moment equations can be derived, (iii) the computation of information-theoretic quantities, and (iv) state estimation. It is known since Snyder’s and related works that marginalization over a stochastic intensity turns point processes into self-exciting ones. While the Snyder filter specifies the exact history-dependent propensities in the framework of CRNs in Markov environment, it was recently suggested to use approximate filters for the marginal description. By regarding the chemical reactions as events, we establish a link between CRNs in a linear random environment and Hawkes processes, a class of self-exciting counting processes widely used in event analysis. The Hawkes approximation can be obtained via moment closure scheme or as the optimal linear approximation under the quadratic criterion. We show the equivalence of both approaches. Furthermore, we use martingale techniques to provide results on the agreement of the Hawkes process and the exact marginal process in their second order statistics, i.e., covariance, auto/cross-correlation. We introduce an approximate marginal simulation algorithm and illustrate it in case studies.AMS subject classifications37M05, 60G35, 60G55, 60J28, 60K37, 62M15
Variable PD-1 glycosylation modulates the activity of immune checkpoint inhibitors
Authors: Chu Chih-Wei , Čaval Tomislav , Alisson-Silva Frederico , Tankasala Akshaya , Guerrier Christina , Czerwieniec Gregg , Läubli Heinz , Schwarz Flavio 
Published: August 2023

AbstractMonoclonal antibodies targeting the immune checkpoint PD-1 have provided significant clinical benefit across a number of solid tumors, with differences in efficacy and toxicity profiles possibly related to their intrinsic molecular properties. Here, we report that camrelizumab and cemiplimab engage PD-1 through interactions with its fucosylated glycan. Using a combination of protein and cell glycoengineering, we demonstrate that the two antibodies bind preferentially to PD-1 with a core fucose at the asparagine N58 residue. We then provide evidence that the concentration of fucosylated PD-1 in the blood of non-small cell lung cancer patients varies across different stages of disease. This study illustrates how glycoprofiling of surface receptors and related circulating forms can inform the development of differentiated antibodies that discriminate glycosylation variants and achieve enhanced selectivity and paves the way towards the implementation of personalized therapeutic approaches.
Unravelling Genomic Origins of Lumpy Skin Disease Virus in Recent Outbreaks
Authors: Yadav Priya , Kumar Ankeet , Nath Sujith S , Shashidhar Geetha , Joshi Madhvi , Puvar Apurva , Sharma Sonal , Raval Janvi , Pandit Rameshchandra , Chavada Priyank , Nagaraj Sudheep , Revanaiah Yogesharadhya , Patil Deepak , Raval S K , Raval Jigar , Kanani Amit , Thakar Falguni , Kumar Naveen , Reddy Gundallhalli Bayyappa Manjunatha , Joshi Chaitanya , Gulati Baldev Raj , Tatu Utpal 
Published: August 2023

ABSTRACTLumpy skin disease virus (LSDV) belongs to the genusCapripoxvirus and familyPoxviridae. LSDV was endemic in most of Africa, Middle east and Turkey, but since 2015, several outbreaks have been reported in Asian countries. In this study we used Whole Genome Sequence (WGS) approach to investigate the origin of the outbreak and understand the genomic landscape of the virus. Our study showed that the LSDV strain of 2022 outbreak exhibited many genetic variations, compared to the Reference Neethling strain sequence and the previous field strains from India. A total of 1819 variations were found in 22 genome sequences, which includes 399 extragenic mutations, 153 insertion frameshift mutations, 234 deletion frameshift mutations, 271 Single nucleotide polymorphisms (SNPs) and 762 silent SNPs. 38 genes have more than 2 variations per gene and these genes belong to viral-core protein, viral binding proteins, replication and RNA polymerase proteins. We highlight the importance of several SNPs in various genes which may play an essential role in pathogenesis of LSDV. Phylogenetic analysis performed on all whole genome sequences of LSDV showed two types of variants in India. One group of the variant with fewer mutations was found to lie closer to the LSDV 2019 strain from Ranchi while the other group clustered with previous Russian outbreaks from 2015. Our study highlights the importance of genomic characterization of viral outbreaks to not only monitor the frequency of mutations but also address its role in pathogenesis of LSDV as the outbreak continues.