bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential metal sensing and metal‐dependent degradation of the broad spectrum root metal transporter IRT1
Authors: Spielmann Julien , Cointry Virginia , Devime Fabienne , Ravanel Stéphane , Neveu Julie , Vert Grégory 
Published: October 2022

SUMMARYIron is an essential micronutrient for plant growth and development. Under low iron conditions, Arabidopsis plants take up soil iron using the root iron transporter IRT1. In addition to iron, IRT1 also transports others divalent metals, including cadmium, which consequently accumulates into plant tissues and enters the food chain. IRT1 expression was shown to be regulated at the transcriptional and post‐translational levels by its essential metal substrates to maximize iron uptake while limiting the accumulation of zinc, manganese, or cobalt. Here, we characterized the regulation of IRT1 by cadmium. A short‐term exposure to cadmium decreased the cell surface levels of IRT1 through endocytosis and degradation, but with a lower efficiency than observed for other IRT1 metal substrates. We demonstrated that IRT1 endocytosis in response to cadmium is mediated through the direct binding of cadmium to histidine residues within the regulatory loop of IRT1. However, we revealed that the affinity of the metal sensing motif is much lower for cadmium compared to other metal substrates of IRT1. Finally, we proved that cadmium‐induced IRT1 degradation takes place through ubiquitin‐mediated endocytosis driven by the UBC35/36 E2 ubiquitin‐conjugating enzymes and the IDF1 E3 ubiquitin ligase. Altogether, this work sheds light on the mechanisms of cadmium‐mediated downregulation of IRT1 and provides an additional molecular basis for cadmium accumulation and toxicity in plants.
Absence of pathogenic viruses in COVID‐19 convalescent plasma
Authors: Kandathil Abraham J. , Benner Sarah E. , Bloch Evan M. , Shrestha Ruchee , Ajayi Olivia , Zhu Xianming , Caturegli Patrizio P. , Shoham Shmuel , Sullivan David , Gebo Kelly , Quinn Thomas C. , Casadevall Arturo , Hanley Daniel , Pekosz Andrew , Redd Andrew D. , Balagopal Ashwin , Tobian Aaron A. R. 
Published: October 2022

AbstractBackgroundIt is important to maintain the safety of blood products by avoiding the transfusion of units with known and novel viral pathogens. It is unknown whether COVID‐19 convalescent plasma (CCP) may contain pathogenic viruses (either newly acquired or reactivated) that are not routinely screened for by blood centers.MethodsThe DNA virome was characterized in potential CCP donors (n = 30) using viral genome specific PCR primers to identify DNA plasma virome members of the Herpesviridae [Epstein Barr Virus (EBV), cytomegalovirus (CMV), human herpesvirus 6A/B, human herpesvirus 7] and Anelloviridae [Torque teno viruses (TTV), Torque teno mini viruses (TTMV), and Torque teno midi viruses (TTMDV)] families. In addition, the RNA plasma virome was characterized using unbiased metagenomic sequencing. Sequencing was done on a HiSeq2500 using high output mode with a read length of 2X100 bp. The sequencing reads were taxonomically classified using Kraken2. CMV and EBV seroprevalence were evaluated using a chemiluminescent immunoassay.ResultsTTV and TTMDV were detected in 12 (40%) and 4 (13%) of the 30 study participants, respectively; TTMDV was always associated with infection with TTV. We did not observe TTMV DNAemia. Despite CMV and EBV seroprevalences of 33.3% and 93.3%, respectively, we did not detect Herpesviridae DNA among the study participants. Metagenomic sequencing did not reveal any human RNA viruses in CCP, including no evidence of circulating SARS‐CoV‐2.DiscussionThere was no evidence of pathogenic viruses, whether newly acquired or reactivated, in CCP despite the presence of non‐pathogenic Anelloviridae. These results confirm the growing safety data supporting CCP.
Digestible and metabolizable energy values of faba beans and field peas fed to growing pigs
Authors: Adekoya Abidemi Abosede , Adeola Olayiwola 
Published: October 2022

The digestible energy (DE) and metabolizable energy (ME) in faba beans (FB) and field peas (FP) fed to growing pigs were estimated by the difference procedure in two experiments using the total collection method. Twenty-four barrows with mean initial body weight (BW) of 20.0 kg (SD = 1.13) and 20.4 kg (SD = 0.56) in the first (Exp. 1) and second experiments (Exp. 2), respectively, were assigned to three dietary treatments in a randomized complete block design with BW as a blocking factor. A reference diet was prepared using corn, soybean meal, and soybean oil as the energy-contributing ingredients. Organic FB and DS Admiral FP (FPD) in Exp. 1 and Hampton FP (FPH) and 4010 FP (FP4) in Exp. 2 were included at 30% in the reference diet. In Exp. 1, the determined DE and ME were 3772 and 3606 kcal·kg−1 dry matter (DM) in FB and 3683 and 3589 kcal·kg−1 DM in FPD, respectively. In Exp. 2, the respective DE and ME were 4164 and 4014 kcal·kg−1 DM in FPH and 3574 and 3467 kcal·kg−1 DM in FP4. In conclusion, the determined ME values for FB and FP were 77% to 90% of gross energy.
Comparison of the Therapeutic Effect of the Mini-Open Incision and Conventional Open Neurolysis of the Median Nerve for Carpal Tunnel Syndrome
Authors: Hu Feng , Lu Liang , Zeng Jianxue , Li Duoyu , Liu Bin 
Published: October 2022

Objective. The aim of this study was to compare the therapeutic effects of the mini-open incision and conventional open surgery for carpal tunnel syndrome (CTS). Methods. The clinical data of 52 patients with CTS treated at the First Affiliated Hospital of the University of Science and Technology of China from October 2020 to February 2022 were retrospectively analyzed. The patients were divided into the conventional open surgery group (28 cases) and the mini-open incision group (24 cases) according to different surgical incisions applied. The incision length, operation time, time until postoperative return to work, and complications were observed in the two groups. The Visual Analog Scale (VAS) for pain at one day, one month, and three months after surgery and the Boston Carpal Tunnel Questionnaire scores before, at one month, and at three months after surgery were compared between the two groups. Results. The incision length, operation time, and time until return to work in the mini-open incision group were all shorter than those in the conventional open surgery group (2.58 ± 0.35 vs. 7.32 ± 0.61 cm, 18.67 ± 2.62 vs. 29.46 ± 3.42 min, and 5.33 ± 1.40 vs. 13.86 ± 2.70 d, respectively), and differences were statistically significant (

P

< 0.05 in all). The VAS scores in the mini-open incision group were lower than those in the conventional open surgery group at one day and one month after surgery, while the difference in the VAS scores at three months after surgery was not statistically significant between the two groups. There was no statistically significant difference in neurological recovery between the two groups at postoperative follow-ups (

P

> 0.05). The incidences of postoperative scar hyperplasia and scar pain were higher in the conventional open surgery group than those in the mini-open incision group, and differences were statistically significant (

P

< 0.05 in both). Conclusion. Mini-open incision surgery for CTS was a safe and reliable procedure with a precise therapeutic effect, minimal surgical trauma, and high postoperative comfort for patients and could achieve enhanced recovery. Trial Registration. This trial is registered with ChiCTR2200064631.
Histone Lactylation Boosts Reparative Gene Activation Post–Myocardial Infarction
Authors: Wang Naixin , Wang Weiwei , Wang Xiaoqi , Mang Ge , Chen Jianfeng , Yan Xiangyu , Tong Zhonghua , Yang Qiannan , Wang Mengdi , Chen Liangqi , Sun Ping , Yang Yupeng , Cui Jingxuan , Yang Mian , Zhang Yafei , Wang Dongni , Wu Jian , Zhang Maomao , Yu Bo 
Published: October 2022

Background:
Inflammation resolution and cardiac repair initiation after myocardial infarction (MI) require timely activation of reparative signals. Histone lactylation confers macrophage homeostatic gene expression signatures via transcriptional regulation. However, the role of histone lactylation in the repair response post-MI remains unclear. We aimed to investigate whether histone lactylation induces reparative gene expression in monocytes early and remotely post-MI.

Methods:

Single-cell transcriptome data indicated that reparative genes were activated early and remotely in bone marrow and circulating monocytes before cardiac recruitment. Western blotting and immunofluorescence staining revealed increases in histone lactylation levels, including the previously identified histone H3K18 lactylation in monocyte-macrophages early post-MI. Through joint CUT&Tag and RNA-sequencing analyses, we identified
Lrg1, Vegf-a
, and
IL-10
as histone H3K18 lactylation target genes. The increased modification and expression levels of these target genes post-MI were verified by chromatin immunoprecipitation-qPCR and reverse transcription-qPCR.

Results:
We demonstrated that histone lactylation regulates the anti-inflammatory and pro-angiogenic dual activities of monocyte-macrophages by facilitating reparative gene transcription and confirmed that histone lactylation favors a reparative environment and improves cardiac function post-MI. Furthermore, we explored the potential positive role of monocyte histone lactylation in reperfused MI. Mechanistically, we provided new evidence that monocytes undergo metabolic reprogramming in the early stage of MI and demonstrated that dysregulated glycolysis and MCT1 (monocarboxylate transporter 1)-mediated lactate transport promote histone lactylation. Finally, we revealed the catalytic effect of IL (interleukin)-1β-dependent GCN5 (general control non-depressible 5) recruitment on histone H3K18 lactylation and elucidated its potential role as an upstream regulatory element in the regulation of monocyte histone lactylation and downstream reparative gene expression post-MI.

Conclusions:
Histone lactylation promotes early remote activation of the reparative transcriptional response in monocytes, which is essential for the establishment of immune homeostasis and timely activation of the cardiac repair process post-MI.
Defective Desmosomal Adhesion Causes Arrhythmogenic Cardiomyopathy by Involving an Integrin-αVβ6/TGF-β Signaling Cascade
Authors: Schinner Camilla , Xu Lifen , Franz Henriette , Zimmermann Aude , Wanuske Marie-Therès , Rathod Maitreyi , Hanns Pauline , Geier Florian , Pelczar Pawel , Liang Yan , Lorenz Vera , Stüdle Chiara , Maly Piotr I. , Kauferstein Silke , Beckmann Britt M. , Sheikh Farah , Kuster Gabriela M. , Spindler Volker 
Published: October 2022

Background:
Arrhythmogenic cardiomyopathy (ACM) is characterized by progressive loss of cardiomyocytes with fibrofatty tissue replacement, systolic dysfunction, and life-threatening arrhythmias. A substantial proportion of ACM is caused by mutations in genes of the desmosomal cell–cell adhesion complex, but the underlying mechanisms are not well understood. In the current study, we investigated the relevance of defective desmosomal adhesion for ACM development and progression.

Methods:
We mutated the binding site of DSG2 (desmoglein-2), a crucial desmosomal adhesion molecule in cardiomyocytes. This DSG2-W2A mutation abrogates the tryptophan swap, a central interaction mechanism of DSG2 on the basis of structural data. Impaired adhesive function of DSG2-W2A was confirmed by cell–cell dissociation assays and force spectroscopy measurements by atomic force microscopy. The DSG2-W2A knock-in mouse model was analyzed by echocardiography, ECG, and histologic and biomolecular techniques including RNA sequencing and transmission electron and superresolution microscopy. The results were compared with ACM patient samples, and their relevance was confirmed in vivo and in cardiac slice cultures by inhibitor studies applying the small molecule EMD527040 or an inhibitory integrin-αVβ6 antibody.

Results:
The DSG2-W2A mutation impaired binding on molecular level and compromised intercellular adhesive function. Mice bearing this mutation develop a severe cardiac phenotype recalling the characteristics of ACM, including cardiac fibrosis, impaired systolic function, and arrhythmia. A comparison of the transcriptome of mutant mice with ACM patient data suggested deregulated integrin-αVβ6 and subsequent transforming growth factor–β signaling as driver of cardiac fibrosis. Blocking integrin-αVβ6 led to reduced expression of profibrotic markers and reduced fibrosis formation in mutant animals in vivo.

Conclusions:
We show that disruption of desmosomal adhesion is sufficient to induce a phenotype that fulfils the clinical criteria to establish the diagnosis of ACM, confirming the dysfunctional adhesion hypothesis. Deregulation of integrin-αVβ6 and transforming growth factor–β signaling was identified as a central step toward fibrosis. A pilot in vivo drug test revealed this pathway as a promising target to ameliorate fibrosis. This highlights the value of this model to discern mechanisms of cardiac fibrosis and to identify and test novel treatment options for ACM.
Covert Brain Infarction as a Risk Factor for Stroke Recurrence in Patients With Atrial Fibrillation
Authors: Kim Do Yeon , Han Seok-Gil , Jeong Han-Gil , Lee Keon-Joo , Kim Beom Joon , Han Moon-Ku , Choi Kang-Ho , Kim Joon-Tae , Shin Dong-Ick , Cha Jae-Kwan , Kim Dae-Hyun , Kim Dong-Eog , Ryu Wi-Sun , Park Jong-Moo , Kang Kyusik , Kim Jae Guk , Lee Soo Joo , Oh Mi-Sun , Yu Kyung-Ho , Lee Byung-Chul , Park Hong-Kyun , Hong Keun-Sik , Cho Yong-Jin , Choi Jay Chol , Sohn Sung Il , Hong Jeong-Ho , Park Tai Hwan , Lee Kyung Bok , Kwon Jee-Hyun , Kim Wook-Joo , Lee Jun , Lee Ji Sung , Lee Juneyoung , Gorelick Philip B. , Bae Hee-Joon 
Published: October 2022

Background:
We aimed to evaluate covert brain infarction (CBI), frequently encountered during the diagnostic work-up of acute ischemic stroke, as a risk factor for stroke recurrence in patients with atrial fibrillation (AF).

Methods:
For this prospective cohort study, from patients with acute ischemic stroke hospitalized at 14 centers between 2017 and 2019, we enrolled AF patients without history of stroke or transient ischemic attack and divided them into the CBI (+) and CBI (−) groups. The 2 groups were compared regarding the 1-year cumulative incidence of recurrent ischemic stroke and all-cause mortality using the Fine and Gray subdistribution hazard model with nonstroke death as a competing risk and the Cox frailty model, respectively. Each CBI lesion was also categorized into either embolic-appearing (EA) or non-EA pattern CBI. Adjusted hazard ratios and 95% CIs of any CBI, EA pattern CBI only, non-EA pattern CBI only, and both CBIs were estimated.

Results:

Among 1383 first-ever stroke patients with AF, 578 patients (41.8%) had CBI. Of these 578 with CBI, EA pattern CBI only, non-EA pattern CBI only, and both CBIs were 61.8% (n=357), 21.8% (n=126), and 16.4% (n=95), respectively. The estimated 1-year cumulative incidence of recurrent ischemic stroke was 5.2% and 1.9% in the CBI (+) and CBI (−) groups, respectively (
P
=0.001 by Gray test). CBI increased the risk of recurrent ischemic stroke (adjusted hazard ratio [95% CI], 2.91 [1.44–5.88]) but did not the risk of all-cause mortality (1.32 [0.97–1.80]). The EA pattern CBI only and both CBIs elevated the risk of recurrent ischemic stroke (2.76 [1.32–5.77] and 5.39 [2.25–12.91], respectively), while the non-EA pattern only did not (1.44 [0.40–5.16]).

Conclusions:
Our study suggests that AF patients with CBI might have increased risk of recurrent stroke. CBI could be considered when estimating the stroke risk in patients with AF.
Self-Isolation and Testing Behaviour During the COVID-19 Pandemic: An Agent-Based Model
Authors: Gostoli Umberto , Silverman Eric 
Published: October 2022

Abstract
Since the beginning of the COVID-19 pandemic, various models of virus spread have been proposed. While most of these models focused on the replication of the interaction processes through which the virus is passed on from infected agents to susceptible ones, less effort has been devoted to the process through which agents modify their behaviour as they adapt to the risks posed by the pandemic. Understanding the way agents respond to COVID-19 spread is important, as this behavioural response affects the dynamics of virus spread by modifying interaction patterns. In this article, we present an agent-based model that includes a behavioural module determining agent testing and isolation propensity in order to understand the role of various behavioural parameters in the spread of COVID-19.
Relational Topology-based Heterogeneous Network Embedding for Predicting Drug-Target Interactions
Authors: Zhang Linlin , Ouyang Chunping , Hu Fuyu , Liu Yongbin , Gao Zheng 
Published: October 2022

ABSTRACT
Predicting interactions between drugs and target proteins has become an essential task in the drug discovery process. Although the method of validation via wet-lab experiments has become available, experimental methods for drug-target interaction (DTI) identification remain either time consuming or heavily dependent on domain expertise. Therefore, various computational models have been proposed to predict possible interactions between drugs and target proteins. However, most prediction methods do not consider the topological structures characteristics of the relationship. In this paper, we propose a relational topology-based heterogeneous network embedding method to predict drug-target interactions, abbreviated as RTHNE_ DTI. We first construct a heterogeneous information network based on the interaction between different types of nodes, to enhance the ability of association discovery by fully considering the topology of the network. Then drug and target protein nodes can be represented by the other types of nodes. According to the different topological structure of the relationship between the nodes, we divide the relationship in the heterogeneous network into two categories and model them separately. Extensive experiments on the real-world drug datasets, RTHNE_DTI produces high efficiency and outperforms other state-of-the-art methods. RTHNE_DTI can be further used to predict the interaction between unknown interaction drug-target pairs.
Evaluation of antibacterial activity of five biocides and the synergistic effect of biocide/EDTA combinations on biofilm-producing and non-producing Stenotrophomonas maltophilia strains isolated from clinical specimens in Iran
Authors: Anari Raana Kazemzadeh , Nikkhahi Farhad , Javadi Amir , Bakht Mehdi , Rostamani Mohammad , Kelishomi Fatemeh Zeynali , Alizadeh Safar Ali 
Published: October 2022

Abstract
Background
The overuse of biocides in healthcare-facilities poses risk for emergence and spread of antibiotic resistance among nosocomial pathogens. Hospital-acquired infections due to S. maltophilia have been increased in the recent years and with its various resistance mechanisms contribute to patient morbidity and mortality in hospitals. The current study aimed to evaluate the susceptibility of biofilm-producing and non-producing S. maltophilia clinical isolates to five commonly used hospital biocides, alone and in combination with EDTA to examine the synergistic effect of combining EDTA on the bactericidal activity of them by microbroth dilution method. As well as the frequency of efflux genes encoding resistance to biocides among isolates. This study also intended to assess the effect of exposure of S. maltophilia isolates to sub-inhibitory concentrations of sodium hypochlorite upon the antimicrobial susceptibility patterns.

Results
Based on minimum inhibitory and bactericidal concentrations of biocides sodium hypochlorite 5% (w/v) and ethyl alcohol 70% (v/v) were the strongest and weakest biocides against S. maltophilia isolates, respectively. The combination of EDTA with biocides significantly increased the effectiveness of the studied biocides. Exposure to sub-inhibitory concentration of sodium hypochlorite showed a significant change in the susceptibility of isolates towards ceftazidime (p = 0.019), ticarcillin/clavulanate (p = 0.009), and chloramphenicol (p = 0.028). As well as among the isolates examined, 94 (95%) were able to produce biofilm. The frequency of sugE1 resistance genes was found in 90.7% of our clinical S. maltophilia isolates. None of the isolates carried qacE and qacEΔ1 gene.

Conclusions
The current study recommended that using the mixture of biocides with EDTA can be effective in reducing nosocomial infections. Also, this study demonstrated that exposure to sub-inhibitory concentrations of sodium hypochlorite leads to reduced antibiotic susceptibility and development of multidrug-resistant S. maltophilia strains.
Comparisons of care practices for very preterm infants and their short-term outcomes in two tertiary centers in northwest and south China: A retrospective cohort study
Authors: Peng Haibo , Shi Yanling , Wang Fei , Jin Zhenchao , Li Cungui , Kang Jing , Zhang Guofei , Zhang Lian , Yao Yanli , Yu Zhangbin 
Published: October 2022

Abstract
Background
Care practices for very preterm infants and the mortality and morbidity of the infants vary widely among countries and regions with different levels of economic development, including the different areas in China. We aimed to compare the obstetric and delivery room practices of two representative tertiary newborn centers in the northwestern and southern regions of China and the mortality and morbidity of their very preterm infants.

Methods
A retrospective cohort study was conducted. Very preterm infants born between 220/7 and 316/7 weeks of gestation, and admitted to Qinghai Red Cross Hospital (QHH) and Shenzhen Baoan Women’s and Children’s Hospital (SZH) from January 1, 2018 to December 31, 2020, were included. The infants’ characteristics and short-term outcomes, and the hospitals’ care practices were compared between the two cohorts.

Results
Three hundred and two infants in QHH and 505 infants in SZH were enrolled, and the QHH cohort was more mature than the SZH cohort was (gestational age 30.14 (29.14–31.14) vs. 29.86 (27.86–31.00 weeks, respectively), p < 0.001). Fewer antenatal steroids and more tracheal intubations were used in QHH than in SZH [(73.8% vs. 90.9%, p < 0.001) and (68.2% vs. 35.0%, p < 0.001, respectively)]. The odds of mortality [aOR = 10.31, 95%CI: (6.04, 17.61)], mortality or major morbidity [aOR = 5.95, 95%CI: (4.05, 8.74)], mortality despite active treatment [aOR = 3.14, 95%CI: (1.31, 7.53)], mortality or major morbidity despite active treatment [aOR = 3.35, 95%CI: (2.17, 5.17)], moderate or severe bronchopulmonary dysplasia [aOR = 3.66, 95%CI: (2.20, 6.06)], and severe retinopathy of prematurity [aOR = 3.24, 95%CI: (1.19, 8.83)] were higher in the QHH cohort. No significant difference in the rate of severe neurological injury or necrotizing enterocolitis ≥ Stage 2 was found between the cohorts.

Conclusion
Obstetric and delivery room care practices used in the management of very preterm infants differed considerably between the QHH and SZH cohorts. Very preterm infants born in QHH have higher odds of mortality or severe morbidity compared with those born in SZH.