bluuebunny/crossref_metadata_2025_split huggingface dataset:
Numerical studies of the influence of seeding locations on D-SOL plasmas in EAST
Authors: WANG Min , XIAO Qingmei , WANG Xiaogang , LIU Daoyuan 
Published: October 2021

Abstract
Impurity seeding has been found effective for divertor detachment operations and the seeding location plays a key role in this process. In this work, we use the fluid code SOLPS-ITER to study the influence of seeding locations on divertor and scrape-off layer (D-SOL) plasmas in Experimental Advanced Superconducting Tokamak (EAST) with neon seeding. Simulation results indicate that the neon is a highly effective impurity in mitigating the heat flux and electron temperature peaks on the target of the divertor and achieving the partial detachment on both inner and outer targets. Further, by comparing results of the seeding at the private-flux region (PFR) plate (called ‘TP’ location) and the outer target (called ‘XP’ location), we find that the impurity density and power radiation for TP case are higher in core and upstream regions and lower in the divertor region than that for seeding at the XP, and the difference becomes more and more obvious as the seeding rate increases. It clearly demonstrates that the seeding at the XP location is more appropriate than at the TP location, especially in high seeding rate conditions.
A computational methodology to diagnose sequence-variant dynamic perturbations by comparing atomic protein structures
Authors: Pacini Lorenza , Lesieur Claire 
Published: October 2021

Abstract

Motivation
The objective is to diagnose dynamics perturbations caused by amino-acid mutations as prerequisite to assess protein functional health or drug failure, simply using network models of protein X-ray structures.

Results
We find that the differences in the allocation of the atomic interactions of each amino acid to 1D, 2D, 3D, 4D structural levels between variants structurally robust, recover experimental dynamic perturbations. The allocation measure validated on two B-pentamers variants of AB5 toxins having 17 mutations, also distinguishes dynamic perturbations of pathogenic and non-pathogenic Transthyretin single-mutants. Finally, the main proteases of the coronaviruses SARS-CoV and SARS-CoV-2 exhibit changes in the allocation measure, raising the possibility of drug failure despite the main proteases structural similarity.

Availability and implementation
The Python code used for the production of the results is available at github.com/lorpac/protein_partitioning_atomic_contacts. The authors will run the analysis on any PDB structures of protein variants upon request.

Supplementary information
Supplementary data are available at Bioinformatics online.
Regression-based causal inference with factorial experiments: estimands, model specifications and design-based properties
Authors: Zhao Anqi , Ding Peng 
Published: October 2021

Summary
Factorial designs are widely used because of their ability to accommodate multiple factors simultaneously. Factor-based regression with main effects and some interactions is the dominant strategy for downstream analysis, delivering point estimators and standard errors simultaneously via one least-squares fit. Justification of these convenient estimators from the design-based perspective requires quantifying their sampling properties under the assignment mechanism while conditioning on the potential outcomes. To this end, we derive the sampling properties of the regression estimators under a wide range of specifications, and establish the appropriateness of the corresponding robust standard errors for Wald-type inference. The results help to clarify the causal interpretation of the coefficients in these factor-based regressions, and motivate the definition of general factorial effects to unify the definitions of factorial effects in various fields. We also quantify the bias-variance trade-off between the saturated and unsaturated regressions from the design-based perspective.
Distributional data analysis via quantile functions and its application to modeling digital biomarkers of gait in Alzheimer’s Disease
Authors: Ghosal Rahul , Varma Vijay R , Volfson Dmitri , Hillel Inbar , Urbanek Jacek , Hausdorff Jeffrey M , Watts Amber , Zipunnikov Vadim 
Published: October 2021

SummaryWith the advent of continuous health monitoring with wearable devices, users now generate their unique streams of continuous data such as minute-level step counts or heartbeats. Summarizing these streams via scalar summaries often ignores the distributional nature of wearable data and almost unavoidably leads to the loss of critical information. We propose to capture the distributional nature of wearable data via user-specific quantile functions (QF) and use these QFs as predictors in scalar-on-quantile-function-regression (SOQFR). As an alternative approach, we also propose to represent QFs via user-specific L-moments, robust rank-based analogs of traditional moments, and use L-moments as predictors in SOQFR (SOQFR-L). These two approaches provide two mutually consistent interpretations: in terms of quantile levels by SOQFR and in terms of L-moments by SOQFR-L. We also demonstrate how to deal with multi-modal distributional data via Joint and Individual Variation Explained using L-moments. The proposed methods are illustrated in a study of association of digital gait biomarkers with cognitive function in Alzheimers disease. Our analysis shows that the proposed methods demonstrate higher predictive performance and attain much stronger associations with clinical cognitive scales compared to simple distributional summaries.
Biallelic FRA10AC1 variants cause a neurodevelopmental disorder with growth retardation
Authors: von Elsner Leonie , Chai Guoliang , Schneeberger Pauline E , Harms Frederike L , Casar Christian , Qi Minyue , Alawi Malik , Abdel-Salam Ghada M H , Zaki Maha S , Arndt Florian , Yang Xiaoxu , Stanley Valentina , Hempel Maja , Gleeson Joseph G , Kutsche Kerstin 
Published: October 2021

Abstract
The major spliceosome mediates pre-mRNA splicing by recognizing the highly conserved sequences at the 5′ and 3′ splice sites and the branch point. More than 150 proteins participate in the splicing process and are organized in the spliceosomal A, B, and C complexes. FRA10AC1 is a peripheral protein of the spliceosomal C complex and its ortholog in the green alga facilitates recognition or interaction with splice sites. We identified biallelic pathogenic variants in FRA10AC1 in five individuals from three consanguineous families. The two unrelated Patients 1 and 2 with loss-of-function variants showed developmental delay, intellectual disability, and no speech, while three siblings with the c.494_496delAAG (p.Glu165del) variant had borderline to mild intellectual disability. All patients had microcephaly, hypoplasia or agenesis of the corpus callosum, growth retardation, and craniofacial dysmorphism. FRA10AC1 transcripts and proteins were drastically reduced or absent in fibroblasts of Patients 1 and 2. In a heterologous expression system, the p.Glu165del variant impacts intrinsic stability of FRA10AC1 but does not affect its nuclear localization. By co-immunoprecipitation, we found ectopically expressed HA-FRA10AC1 in complex with endogenous DGCR14, another component of the spliceosomal C complex, while the splice factors CHERP, NKAP, RED, and SF3B2 could not be co-immunoprecipitated. Using an in vitro splicing reporter assay, we did not obtain evidence for FRA10AC1 deficiency to suppress missplicing events caused by mutations in the highly conserved dinucleotides of 5′ and 3′ splice sites in an in vitro splicing assay in patient-derived fibroblasts. Our data highlight the importance of specific peripheral spliceosomal C complex proteins for neurodevelopment. It remains possible that FRA10AC1 may have other and/or additional cellular functions, such as coupling of transcription and splicing reactions.
DNMT3A epigenetically regulates key microRNAs involved in epithelial-to-mesenchymal transition in prostate cancer
Authors: Mancini Monica , Grasso Margherita , Muccillo Livio , Babbio Federica , Precazzini Francesca , Castiglioni Ilaria , Zanetti Valentina , Rizzo Francesca , Pistore Christian , De Marino Maria Giovanna , Zocchi Michele , Del Vescovo Valerio , Licursi Valerio , Giurato Giorgio , Weisz Alessandro , Chiarugi Paola , Sabatino Lina , Denti Michela Alessandra , Bonapace Ian Marc 
Published: October 2021

Abstract
Epithelial-to-mesenchymal transition (EMT) is involved in prostate cancer (PCa) metastatic progression, and its plasticity suggests epigenetic implications. Deregulation of DNA methyltransferases (DNMTs) and several microRNAs (miRNAs) plays a relevant role in EMT, but their interplay has not been clarified yet. In this study, we provide evidence that DNMT3A interaction with several miRNAs has a central role in an ex vivo EMT PCa model obtained via exposure of PC3 cells to conditioned media from cancer-associated fibroblasts. The analysis of the alterations of the miRNA profile shows that miR-200 family (miR-200a/200b/429, miR-200c/141), miR-205 and miR-203, known to modulate key EMT factors, are down-regulated and hyper-methylated at their promoters. DNMT3A (mainly isoform a) is recruited onto these miRNA promoters, coupled with the increase of H3K27me3/H3K9me3 and/or the decrease of H3K4me3/H3K36me3. Most interestingly, our results reveal the differential expression of two DNMT3A isoforms (a and b) during ex vivo EMT and a regulatory feedback loop between miR-429 and DNMT3A that can promote and sustain the transition towards a more mesenchymal phenotype. We demonstrate the ability of miR-429 to target DNMT3A 3′UTR and modulate the expression of EMT factors, in particular ZEB1. Survey of the PRAD-TCGA dataset shows that patients expressing an EMT-like signature are indeed characterized by down-regulation of the same miRNAs with a diffused hyper-methylation at miR-200c/141 and miR-200a/200b/429 promoters. Finally, we show that miR-1260a also targets DNMT3A, although it does not seem to be involved in EMT in PCa.
Recent progress in Cr-based catalysts for oxidative dehydrogenation of light alkanes by employing CO2 as a soft oxidant
Authors: Liu Pengyu , Zhang Lina , Li Minkang , Sun Nannan , Wei Wei 
Published: October 2021

Abstract
CO2 can be used as a soft oxidant for oxidative dehydrogenation of light alkanes (CO2-ODH), which is beneficial to realize the reuse of CO2 and meet the demand for olefins. The core of this reaction is the catalyst. Cr-based catalysts have attracted much attention for their excellent catalytic performance in CO2-ODH reactions due to their various oxidation states and local electronic structures. In this paper, the synthesis and modification methods of Cr-based catalysts for CO2-ODH are reviewed. The structure–activity relationship and reaction mechanism are also summarized. Moreover, the reasons for the deactivation of Cr-based catalysts are analysed and the main challenges faced by Cr-based catalysts in the CO2-ODH process, as well as the future development trend and prospect, are discussed.
Interpersonal conflict increases interpersonal neural synchronization in romantic couples
Authors: Long Yuhang , Chen Chuansheng , Wu Karen , Zhou Siyuan , Zhou Faxin , Zheng Lifen , Zhao Hui , Zhai Yu , Lu Chunming 
Published: October 2021

Abstract
Previous studies on dual-brain social interaction have shown different patterns of interpersonal neural synchronization (INS) between conflictual and supportive interactions, but the role of emotion in the dual-brain mechanisms of such interactions is not well understood. Furthermore, little is known about how the dual-brain mechanisms are affected by relationship type (e.g., romantic relationship vs. friendship) and interaction mode (e.g., verbal vs. nonverbal). To elaborate on these issues, this study used functional near-infrared spectroscopy to collect hemodynamic signals from romantic couples and cross-sex friends while they were discussing conflictual, neutral, or supportive topics. For the couples but not the friends, INS between the sensorimotor cortex of both participants was greater when discussing the conflictual topic than when discussing the supportive topic. INS was positively correlated with the arousal level but not the valence level of communication contents. INS was also positively correlated with interpersonal physiological synchronization based on galvanic skin response, a physiological measure of arousal. Furthermore, the differences in INS between the conflictual and supportive topics were closely associated with verbal rather than nonverbal behaviors. Together, these findings suggest that it is the arousal level induced by verbal interactions during interpersonal conflicts that increases romantic couples’ INS.
Orienting to different dimensions of word meaning alters the representation of word meaning in early processing regions
Authors: Meersmans Karen , Storms Gerrit , De Deyne Simon , Bruffaerts Rose , Dupont Patrick , Vandenberghe Rik 
Published: October 2021

Abstract
Conscious processing of word meaning can be guided by attention. In this event-related functional magnetic resonance imaging study in 22 healthy young volunteers, we examined in which regions orienting attention to two fundamental and generic dimensions of word meaning, concreteness versus valence, alters the semantic representations coded in activity patterns. The stimuli consisted of 120 nouns in written or spoken modality which varied factorially along the concreteness and valence axis. Participants performed a forced-choice judgement of either concreteness or valence. Rostral and subgenual anterior cingulate were strongly activated during valence judgement, and precuneus and the dorsal attention network during concreteness judgement. Task and stimulus type interacted in right posterior fusiform gyrus, left lingual gyrus, precuneus, and insula. In the right posterior fusiform gyrus and the left lingual gyrus, the correlation between the pairwise similarity in activity patterns evoked by words and the pairwise distance in valence and concreteness was modulated by the direction of attention, word valence or concreteness. The data indicate that orienting attention to basic dimensions of word meaning exerts effects on the representation of word meaning in more peripheral nodes, such as the ventral occipital cortex, rather than the core perisylvian language regions.
Myocarditis following COVID-19 vaccination: magnetic resonance imaging study
Authors: Shiyovich Arthur , Witberg Guy , Aviv Yaron , Eisen Alon , Orvin Katia , Wiessman Maya , Grinberg Tzlil , Porter Avital , Kornowski Ran , Hamdan Ashraf 
Published: October 2021

Abstract

Aims
To describe the cardiac magnetic resonance (CMR) imaging findings of patients who developed myocarditis following messenger RNA (mRNA) coronavirus disease 2019 (COVID-19) vaccination.

Methods and results
The present study retrospectively evaluated patients with clinically adjudicated myocarditis within 42 days of the first Pfizer-BNT162b2 mRNA COVID-19 vaccination, between 20 December 2020 and 24 May 2021 who underwent CMR. A total of 15 out 54 patients (28%) with myocarditis underwent a CMR and were included, 100% males, median age of 32 years (interquartile range = 22.5–40). Most patients presented with chest pain (87%) and had an abnormal electrocardiogram (79%). The severity of the disease was mild in 67% and intermediate in 33%. All patients survived and one patient was readmitted during the study period. CMR was performed at a median of 65 days (range 3–130 days) following diagnosis. Median ejection fraction was 58% (range 51–74%) global- and regional wall motion abnormalities were present in one and three patients, respectively. Native T1 was available in 13/15 patients (2/3 in 3 T and 11/12 in the 1.5 T), with increased values among 6/13. Late gadolinium enhancement (LGE) was found among 13/15 patients with a median of 2% (range 0–15%) with inferolateral wall being the most common location (8/13). The patterns of the LGE were: mid-wall in six patients; epicardial in five patients; and mid-wall and epicardial in two patients.

Conclusions
Among patients who were diagnosed with post-vaccination clinical myocarditis, CMR imaging findings are mild and consistent with ‘classical myocarditis’. The short-term clinical course and outcomes were favourable.
Integrating evolutionary aspects into dual-use discussion: the cases of influenza virus and enterohemorrhagic Escherichia coli
Authors: Gati Noble Selasi , Altinok Ozan Altan , Kumar Sriram , Ferrando Verónica A , Kurtz Joachim , Quante Michael , Ludwig Stephan , Mellmann Alexander 
Published: October 2021

Abstract
Research in infection biology aims to understand the complex nature of host–pathogen interactions. While this knowledge facilitates strategies for preventing and treating diseases, it can also be intentionally misused to cause harm. Such dual-use risk is potentially high for highly pathogenic microbes such as Risk Group-3 (RG3) bacteria and RG4 viruses, which could be used in bioterrorism attacks. However, other pathogens such as influenza virus (IV) and enterohemorrhagic Escherichia coli (EHEC), usually classified as RG2 pathogens, also demonstrate high dual-use risk. As the currently approved therapeutics against these pathogens are not satisfactorily effective, previous outbreaks of these pathogens caused enormous public fear, media attention and economic burden. In this interdisciplinary review, we summarize the current perspectives of dual-use research on IV and EHEC, and further highlight the dual-use risk associated with evolutionary experiments with these infectious pathogens. We support the need to carry out experiments pertaining to pathogen evolution, including to gain predictive insights on their evolutionary trajectories, which cannot be otherwise achieved with stand-alone theoretical models and epidemiological data. However, we also advocate for increased awareness and assessment strategies to better quantify the risks-versus-benefits associated with such evolutionary experiments. In addition to building public trust in dual-use research, we propose that these approaches can be extended to other pathogens currently classified as low risk, but bearing high dual-use potential, given the particular pressing nature of their rapid evolutionary potential.
Serum anion gap predicts in-hospital and 1-year mortality in cardiac care unit patients
Authors: Nilmoje M R 
Published: October 2021

Abstract

Background
Anion gap (AG) has been used as a prognostic indicator in critical care setting as well ascardiovascular fields such as coronary artery and aortic disease. However, there were few studies about the association of AG in cardiac care unit (CCU) for in-hospital mortality and none of them for the 1-year mortality.

Objective
To assess a predictive ability of AG for in-hospital and 1-year mortality in CCU patients in a tertiary hospital in Thailand.

Methods
This is a retrospective cohort study in the single tertiary care hospital in the Southern Thailand. The data were extracted from the Hospital information System (HIS) database of the hospital. Patients admitted from emergency department (ED) to CCU from July 2015 to December 2019 were included. Anion gap was calculated from serum electrolytes obtained at emergency room or within 1 hour of CCU admission by using the follow formula: [(Na (mmol/L)) − (Cl (mmol/L) + HCO3 (mmol/L))]. The associations between anion gap and in-hospital and 1-year mortality were analyzed in the logistic and Cox regression model respectively.

Results
A total of 1271 patients were included in this study. There were higher prevalence of diabetesmellitus and chronic kidney disease (CKD) in patients with wide AG than in normal AG. Hemoglobin level,blood urea nitrogen and serum creatinine were higher whereas mean Braden score was lower in the wide AG group than normal AG group.
The 1-year survival rate of patients with AG ≥14 was significantly lower than patients with AG &lt;14 (Figure 1). The survival rate of patients with AG ≤12 was not significantly different from that between 12 and 14, since survival curves of the two groups were overlapping. Figure 2 illustrated strong linear relationships between baseline AG and in-hospital (A) and 1-yr mortality risk (B). The c-statistics of AG for in-hospital (A) and 1-yr mortality (B) were 0.822 (95% CI 0.763–0.878) and 0.787 (95% CI 0.75–0.824) respectively.
In multivariable analysis, AG gap was an independent predictor for both in-hospital (odd ratio 1.13, 95% CI 1.07–1.19, p&lt;0.ehab724.15231) and 1-year mortality (HR 1.09, 95% CI 1.07–1.12, p&lt;0.0001) after adjusted for age, sex, diabetes, CKD, chronic lung disease, history of cancer, prior stroke, Braden score and cardiogenic shock.

Conclusions
Anion gap, costless fifth electrolyte - calculated from 3 out of 4 routine basic electrolytes (Na KCl HCO3), was a strong independent predictor of in-hospital and 1-year mortality in CCU patients. Moreover, in the future, it may lead to web-based risk calculator development for CCU patients.

Funding Acknowledgement
Type of funding sources: Public hospital(s). Main funding source(s): Prince of Songkla University Hospital KM curve of all cause mortalityLinear and ROC curve
Infective endocarditis after transcatheter aortic valve implantation
Authors: Arellano Serrano C , Oteo Dominguez J F , Garcia Touchard A , Fernandez Diaz J A , Del Trigo Espinosa M , Calderon Parra J , Ramos Martinez A , Cobo Marcos M , Dominguez Rodriguez F , Monivas Palomero V , Mingo Santos S , Goicolea Ruigomez J , Segovia Cubero J 
Published: October 2021

Abstract

Introduction
Infective endocarditis (IE) is a potentially serious complication in patients with prosthetic heart valves. The objective of this study is to analyze and describe the incidence, baseline characteristics, risks factors and in-hospital evolution in IE after Transcatheter Aortic Valve Implantation (IE-TAVI).

Methods
All the TAVI implanted in our center since the beginning of the program have been included consecutively. Patients with a confirmed diagnosis of IE according to the “ESC Guidelines for the management of infective endocarditis” are identified and analyzed.

Results
331 TAVI have been implanted in our center from June 2009 to February 2021. IE-TAVI incidence in our series is 2.7% (n=9 cases). In baseline analysis, we observed that insulin dependent diabetes mellitus, Barthel Score and Pulmonary systolic pressure &gt;50mmHg are significantly associated with the appearance of IE-TAVI (TABLE 1).
The most frequently microorganism is Enterococcus faecalis (44.4%; n=4) followed by Staphylococcus aureus (22.2%; n=2), Coagulase-negative staphylococci (22.2%; n=2) and Streptococcus viridans (11.1%; n=1).
77.8% of IE-TAVI (n=7) are Nosocomial IE or non-nosocomial healthcare-associated IE. 2 of them have been related to implantation (1 Enterococcus faecalis and 1 Coagulase-negative staphylococci) and 5 have been related to other interventions (2 after gastroscopy, 1 after percutaneous vascular intervention, 1 hemodialysis catheter infection and 2 unknown focus).
44.4% of IE-TAVI (n=4) were confirmed after performing Positron Emission Tomography (PET) scan. 3 cases (33.3%) were diagnosed with the initial Transthoracic Echocardiogram (TTE) and 2 cases (22.2%) were diagnosed after performing a Transesophageal Echocardiogram (TEE) (TABLE 2)
4 patients had an indication for surgery according to the ESC Guidelines (3 for persistent bacteremia and 1 for severe aortic regurgitation), but all were ruled out due to high surgical risk. Hospital mortality was 44.4% (n=4). The main predictor of hospital mortality was having an indication for surgery (p=0.028), which was present in 3 of the 4 deaths. The other death was due to digestive bleeding during hospitalization.

Conclusions
IE-TAVI is a serious disease with high in-hospital mortality. Insulin dependent diabetes mellitus, Barthel Score and Pulmonary systolic pressure &gt;50mmHg are risk factors for IE-TAVI. PET-scan is the imaging test of choice when there were no echocardiographic findings. The main predictor of mortality is having an indication for surgery according to the ESC Guidelines.

Funding Acknowledgement
Type of funding sources: None.