bluuebunny/crossref_metadata_2025 huggingface dataset:
Carbamazepine Increases the Risk of Sudden Cardiac Arrest by a Reduction of the Cardiac Sodium Current
Authors: Jia Lixia , Eroglu Talip E. , Wilders Ronald , Verkerk Arie O. , Tan Hanno L.
Published: June 2022

Aim: To assess the risk of sudden cardiac arrest (SCA) associated with the use of carbamazepine (CBZ) and establish the possible underlying cellular electrophysiological mechanisms.

Methods: The SCA risk association with CBZ was studied in general population cohorts using a case–control design (n = 5,473 SCA cases, 21,866 non-SCA controls). Effects of 1–100 µM CBZ on action potentials (APs) and individual membrane currents were determined in isolated rabbit and human cardiomyocytes using the patch clamp technique.

Results: CBZ use was associated with increased risk of SCA compared with no use (adjusted odds ratio 1.90 [95% confidence interval: 1.12–3.24]). CBZ reduced the AP upstroke velocity of rabbit and human cardiomyocytes, without prominent changes in other AP parameters. The reduction occurred at ≥30 µM and was frequency-dependent with a more pronounced reduction at high stimulus frequencies. The cardiac sodium current (INa) was reduced at ≥30 μM; this was accompanied by a hyperpolarizing shift in the voltage-dependency of inactivation. The recovery from inactivation was slower, which is consistent with the more pronounced AP upstroke velocity reduction at high stimulus frequencies. The main cardiac K+ and Ca2+ currents were unaffected, except reduction of L-type Ca2+ current by 100 µM CBZ.

Conclusion: CBZ use is associated with an increased risk of SCA in the general population. At concentrations of 30 µM and above, CBZ reduces AP upstroke velocity and INa in cardiomyocytes. Since the concentration of 30 µM is well within the therapeutic range (20–40 µM), we conclude that CBZ increases the risk of SCA by a reduction of the cardiac INa.
Integrated Analysis of Glutathione Metabolic Pathway in Pancreatic Cancer
Authors: Wu Xingui , Yu Ruyuan , Yang Meisongzhu , Hu Yameng , Tang Miaoling , Zhang Shuxia , Abudourousuli Ainiwaerjiang , Li Xincheng , Li Ziwen , Liao Xinyi , Xu Yingru , Li Man , Chen Suwen , Qian Wanying , Feng Rongni , Li Jun , Li Fenjie
Published: June 2022

Metabolic enzyme-genes (MEs) play critical roles in various types of cancers. However, MEs have not been systematically and thoroughly studied in pancreatic cancer (PC). Global analysis of MEs in PC will help us to understand PC progressing and provide new insights into PC therapy. In this study, we systematically analyzed RNA sequencing data from The Cancer Genome Atlas (TCGA) (n = 180 + 4) and GSE15471 (n = 36 + 36) and discovered that metabolic pathways are disordered in PC. Co-expression network modules of MEs were constructed using weighted gene co-expression network analysis (WGCNA), which identified two key modules. Both modules revealed that the glutathione signaling pathway is disordered in PC and correlated with PC stages. Notably, glutathione peroxidase 2 (GPX2), an important gene involved in glutathione signaling pathway, is a hub gene of the key modules. Analysis of immune microenvironment components reveals that PC stage is associated with M2 macrophages, the marker gene of which is significantly correlated with GPX2. The results indicated that GPX2 is associated with PC progression, providing new insights for future targeted therapy.
In Depth Exploration of the Alternative Proteome of Drosophila melanogaster
Authors: Fabre Bertrand , Choteau Sebastien A. , Duboé Carine , Pichereaux Carole , Montigny Audrey , Korona Dagmara , Deery Michael J. , Camus Mylène , Brun Christine , Burlet-Schiltz Odile , Russell Steven , Combier Jean-Philippe , Lilley Kathryn S. , Plaza Serge
Published: June 2022

Recent studies have shown that hundreds of small proteins were occulted when protein-coding genes were annotated. These proteins, called alternative proteins, have failed to be annotated notably due to the short length of their open reading frame (less than 100 codons) or the enforced rule establishing that messenger RNAs (mRNAs) are monocistronic. Several alternative proteins were shown to be biologically active molecules and seem to be involved in a wide range of biological functions. However, genome-wide exploration of the alternative proteome is still limited to a few species. In the present article, we describe a deep peptidomics workflow which enabled the identification of 401 alternative proteins in Drosophila melanogaster. Subcellular localization, protein domains, and short linear motifs were predicted for 235 of the alternative proteins identified and point toward specific functions of these small proteins. Several alternative proteins had approximated abundances higher than their canonical counterparts, suggesting that these alternative proteins are actually the main products of their corresponding genes. Finally, we observed 14 alternative proteins with developmentally regulated expression patterns and 10 induced upon the heat-shock treatment of embryos, demonstrating stage or stress-specific production of alternative proteins.
Epigenetic Clocks for Mice Based on Age-Associated Regions That are Conserved Between Mouse Strains and Human
Authors: Perez-Correa Juan-Felipe , Tharmapalan Vithurithra , Geiger Hartmut , Wagner Wolfgang
Published: June 2022

Aging of mice can be tracked by DNA methylation changes at specific sites in the genome. In this study, we used the recently released Infinium Mouse Methylation BeadChip to compare such epigenetic modifications in C57BL/6 (B6) and DBA/2J (DBA) mice. We observed marked differences in age-associated DNA methylation in these commonly used inbred mouse strains, indicating that epigenetic clocks for one strain cannot be simply applied to other strains without further verification. In B6 mice age-associated hypomethylation prevailed with focused hypermethylation at CpG islands, whereas in DBA mice CpG islands revealed rather hypomethylation upon aging. Interestingly, the CpGs with highest age-correlation were still overlapping in B6 and DBA mice and included the genes Hsf4, Prima1, Aspa, and Wnt3a. Notably, Hsf4 and Prima1 were also top candidates in previous studies based on whole genome deep sequencing approaches. Furthermore, Hsf4, Aspa, and Wnt3a revealed highly significant age-associated DNA methylation in the homologous regions in human. Subsequently, we used pyrosequencing of the four relevant regions to establish a targeted epigenetic clock that provided very high correlation with chronological age in independent cohorts of B6 (R2 = 0.98) and DBA (R2 = 0.91). Taken together, the methylome differs extensively between B6 and DBA mice, while prominent age-associated changes are conserved among these strains and even in humans. Our new targeted epigenetic clock with 4 CpGs provides a versatile tool for other researchers analyzing aging in mice.
Novel Stilbene-Nitroxyl Hybrid Compounds Display Discrete Modulation of Amyloid Beta Toxicity and Structure
Authors: Hilt Silvia , Liu Ruiwu , Maezawa Izumi , Rojalin Tatu , Aung Hnin H. , Budamagunta Madhu , Slez Ryan , Gong Qizhi , Carney Randy P. , Voss John C.
Published: June 2022

Several neurodegenerative diseases are driven by misfolded proteins that assemble into soluble aggregates. These “toxic oligomers” have been associated with a plethora of cellular dysfunction and dysregulation, however the structural features underlying their toxicity are poorly understood. A major impediment to answering this question relates to the heterogeneous nature of the oligomers, both in terms of structural disorder and oligomer size. This not only complicates elucidating the molecular etiology of these disorders, but also the druggability of these targets as well. We have synthesized a class of bifunctional stilbenes to modulate both the conformational toxicity within amyloid beta oligomers (AβO) and the oxidative stress elicited by AβO. Using a neuronal culture model, we demonstrate this bifunctional approach has the potential to counter the molecular pathogenesis of Alzheimer’s disease in a powerful, synergistic manner. Examination of AβO structure by various biophysical tools shows that each stilbene candidate uniquely alters AβO conformation and toxicity, providing insight towards the future development of structural correctors for AβO. Correlations of AβO structural modulation and bioactivity displayed by each provides insights for future testing in vivo. The multi-target activity of these hybrid molecules represents a highly advantageous feature for disease modification in Alzheimer’s, which displays a complex, multifactorial etiology. Importantly, these novel small molecules intervene with intraneuronal AβO, a necessary feature to counter the cycle of dysregulation, oxidative stress and inflammation triggered during the earliest stages of disease progression.
Genomic Characterization of Two Escherichia fergusonii Isolates Harboring mcr-1 Gene From Farm Environment
Authors: Liu Ruishan , Xu Hao , Guo Xiaobing , Liu Shuxiu , Qiao Jie , Ge Haoyu , Zheng Beiwen , Gou Jianjun
Published: June 2022

The prevalence and transmission of mobile colistin resistance (mcr) genes have led to a severe threat to humans and animals. Escherichia fergusonii is an emerging pathogen which is closely related to a variety of diseases. However, the report of mcr genes harboring E. fergusonii is still rare. One study in Brazil reported the E. fergusonii isolates with IncHI2-type plasmids harboring mcr-1. A Chinese study reported two strains carrying mcr-1 gene with the same plasmid type IncI2. Here, we identified two strains of E. fergusonii carrying mcr-1 gene from farm environments with IncX4-type and IncI2-type plasmids, respectively. To our best knowledge, this is the first report about mcr-1 gene located on IncX4-type plasmid in E. fergusonii. We investigate the resistance mechanism of colistin-resistant Escherichia fergusonii strains 6S41-1 and 5ZF15-2-1 and elucidate the genetic context of plasmids carrying mcr-1 genes. In addition, we also investigated chromosomal mutations mediated colistin resistance in these two strains. Species identification was performed using MALDI-TOF MS and 16S rRNA gene sequencing. The detection of mcr-1 gene was determined by PCR and Sanger sequencing. S1-pulsed-field gel electrophoresis (PFGE), Southern blotting, antimicrobial susceptibility testing, conjugation experiments, complete genome sequencing, and core genome analysis were conducted to investigate the characteristics of isolates harboring mcr-1. The mcr-1 genes on two strains were both plasmids encoded and the typical IS26-parA-mcr-1-pap2 cassette was identified in p6S41-1 while a nikA-nikB-mcr-1 locus sites on the conjugative plasmid p5ZF15-2-1. In addition, Core genome analysis reveals that E. fergusonii 6S41-1 and 5ZF15-2-1 have close genetic relationships. The mcr-1 gene is located on conjugative IncI2-type plasmid p5ZF15-2-1, which provides support for its further transmission. In addition, there’s the possibility of mcr-1 spreading to humans through farm environments and thereby threatening public health. Therefore, continuous monitoring and investigations of mcr-1 among Enterobacteriaceae in farm environments are necessary to control the spread.
Anaplasma phagocytophilum Ankyrin A Protein (AnkA) Enters the Nucleus Using an Importin-β-, RanGTP-Dependent Mechanism
Authors: Kim Yuri , Wang Jianyang , Clemens Emily G. , Grab Dennis J. , Dumler J. Stephen
Published: June 2022

Anaplasma phagocytophilum, a tick-borne obligately intracellular bacterium of neutrophils, causes human granulocytic anaplasmosis. Ankyrin A (AnkA), an effector protein with multiple ankyrin repeats (AR) is injected via type IV-secretion into the host neutrophil to gain access to the nucleus where it modifies the epigenome to promote microbial fitness and propagation. AR proteins transported into the host cell nucleus must use at least one of two known eukaryotic pathways, the classical importin β-dependent pathway, and/or the RanGDP- and AR (ankyrin-repeat)-dependent importin β-independent (RaDAR) pathway. Truncation of the first four AnkA N-terminal ARs (AR1-4), but not other regions, prevents AnkA nuclear accumulation. To investigate the mechanism of nuclear import, we created point mutations of AnkA N-terminal ARs, predicted to interfere with RaDAR protein import, and used importazole, a specific inhibitor of the importin α/β, RanGTP-dependent pathway. Nuclear colocalization analysis shows that nuclear localization of AnkA is unaffected by single AR1-4 mutations but is significantly reduced by single mutations in consecutive ARs suggesting RaDAR protein nuclear import. However, AnkA nuclear localization was also decreased with importazole, and with GTPγS. Furthermore, A. phagocytophilum growth in HL-60 cells was completely suppressed with importazole, indicating that A. phagocytophilum propagation requires a β-importin-dependent pathway. A typical classical NLS overlapping AR4 was subsequently identified suggesting the primacy of the importin-α/β system in AnkA nuclear localization. Whether the mutational studies of putative key residues support RaDAR NLS function or simply reflect structural changes that diminish engagement of an AR-NLS-importin pathway needs to be resolved through careful structure-function studies.
Proteomic Analysis of Extracellular Vesicles From Fasciola hepatica Hatching Eggs and Juveniles in Culture
Authors: Trelis María , Sánchez-López Christian M. , Sánchez-Palencia Liz F. , Ramírez-Toledo Victor , Marcilla Antonio , Bernal Dolores
Published: June 2022

The identification of extracellular vesicles (EVs) in Fasciola hepatica has provided a new way to understand parasite-host communication. Most of the studies on EVs have focused on the adult stage of F. hepatica, but recently, the presence of EVs from different developmental stages has been reported. To better understand the potential role of EVs in the biology of the parasite and in the infection process, the protein cargo of EVs from embryonated eggs and newly-excysted juvenile (NEJs) flukes cultured up to 28 days, has been analyzed. EVs were isolated by size exclusion chromatography and evaluated by nanoparticle tracking analysis and transmission electron microscopy. LC-MS/MS proteomic analysis of EVs revealed the presence of 23 different proteins from embryonated egg-derived EVs and 29 different proteins from NEJ-derived EVs. Most of the identified proteins had been previously described in EVs from F. hepatica adults, including cytoskeletal proteins, glycolytic enzymes, stress-related proteins and tetraspanins. Nevertheless, EVs from hatching eggs and NEJs exhibited qualitative differences in composition, when compared to EVs form adults, including the absence of cathepsin cysteine peptidases. The differential content of the EVs released by the different developmental stages of the parasite reflect the intense activity of NEJs at this early stage, with several proteins involved in membrane traffic and cell physiology. This new set of identified proteins could help to understand key metabolic, biochemical and molecular mechanisms mediated by EVs that take place upon egg hatching and after parasite excystment.
Prognostic Impact of Blood Pressure Change Patterns on Patients With Aortic Dissection After Admission
Authors: Wu Zhaoyu , Li Yixuan , Qiu Peng , Liu Haichun , Liu Kai , Li Weimin , Wang Ruihua , Chen Tao , Lu Xinwu
Published: June 2022

Objectives

Hypertension is a predominant risk factor for aortic dissection (AD), and blood pressure (BP) control plays a vital role in the management of AD. However, the correlation between BP change and the prognosis for AD remains unclear. This study aims to demonstrate the impact of BP change patterns on AD prognosis.

Methods

This retrospective study included AD patients at two institutions (Shanghai Ninth People's Hospital Affiliated with Shanghai Jiao Tong University School of Medicine and the Vascular Department of the First Affiliated Hospital of Anhui Medical University) between 2004 and 2018. The systolic BP (SBP) change patterns of these patients were analyzed by functional data analysis (FDA). The relationship between BP change patterns and the risk of adverse events (AEs) was assessed using survival analysis.

Results

A total of 458 patients with AD were eligible for analysis. The logistic regression analysis indicated that compared with that in patients with low SBP variation (SBPV), the incidence of AEs in patients with high SBPV was significantly higher (35.84 vs. 20.35%, OR 2.19, P < 0.001). The patients were divided into four categories (accelerating rise, accelerating drop, decelerating rise, and decelerating drop) based on their SBP patterns after FDA fitting. The results of Kaplan–Meier analysis showed that at the 15- and 20-min time points, the incidence of AEs in the decelerating-drop group was significantly lower than that in the accelerating-rise group (OR 0.19, P = 0.031 and OR 0.23, P = 0.050). However, at the 25- and 30-min time points, the difference between these four groups was not significant (OR 0.26, P = 0.08 and OR 0.29, P = 0.10).

Conclusions

This study classified AD patients into four groups according to the SBP change patterns the first 30 min following admission, of which those with accelerating rises in SBP are at the highest risk of AEs, while those with decelerating drops have the best prognosis in the first 24 h after admission. Clinical practitioners may benefit from analyzing patterns of in-hospital SBP.
Pre-infarction Angina: Time Interval to Onset of Myocardial Infarction and Comorbidity Predictors
Authors: Sotomi Yohei , Ueda Yasunori , Hikoso Shungo , Okada Katsuki , Dohi Tomoharu , Kida Hirota , Oeun Bolrathanak , Sunaga Akihiro , Sato Taiki , Kitamura Tetsuhisa , Mizuno Hiroya , Nakatani Daisaku , Sakata Yasuhiko , Sato Hiroshi , Hori Masatsugu , Komuro Issei , Sakata Yasushi
Published: June 2022

Aims

As part of efforts to identify candidates for patient education aimed at decreasing mortality from acute myocardial infarction, we investigated the prevalence of pre-infarction angina and its predictors among comorbidities in patients who were hospitalized with acute myocardial infarction (MI).

Methods

We conducted a prospective multicenter observational registry of MI patients from 1998 to 2014 (N = 12,093). The present study investigated the prevalence of pre-infarction angina and its predictors among comorbidities with a logistic regression model. Pre-infarction angina was defined as chest pain/oppression observed within 1 month before the onset of MI but which lasted <30 min.

Results

After excluding 976 (8.1%) patients with missing data on pre-infarction angina, 11,117 patients [66.4 ± 12.0 years, 9,096 (75.2%) male] were analyzed. Of these, 5,428 patients (48.8%) experienced pre-infarction angina before the onset of MI, while 5,689 (51.2%) experienced sudden onset of acute MI. Most patients experienced the first episode of angina >6 h before the onset of MI, while 15% did so ≤6 h before. Patients with hypertension, diabetes, dyslipidemia, or a family history of MI had a higher probability of pre-infarction angina than those without. Elderly patients and those with a history of cerebrovascular disease were less likely to experience pre-infarction angina.

Conclusions

Almost half of MI patients in our registry experienced pre-infarction angina before MI onset. Patients with hypertension, diabetes, dyslipidemia, or a family history of MI had a higher probability of experiencing pre-infarction angina than those without.
Extracorporeal Membrane Oxygenation—First Strategy for Acute Life-Threatening Pulmonary Embolism
Authors: Liu Zhenjie , Chen Jinyi , Xu Xin , Lan Fen , He Minzhi , Shao Changming , Xu Yongshan , Han Pan , Chen Yibing , Zhu Yongbin , Huang Man
Published: June 2022

Background

Both venoarterial extracorporeal membrane oxygenation (VA-ECMO) and percutaneous mechanical thrombectomy (PMT) are increasingly used to treat acute life-threatening pulmonary embolism (PE). However, there are little data regarding their effectiveness. This study aimed to present the short-term outcomes after managing nine patients with acute life-threatening massive or submassive PE by VA-ECMO with or without complemented PMT and propose a preliminary treatment algorithm.

Methods

This study was a single-center retrospective review of a prospectively maintained registry. It included nine consecutive patients with massive or submassive pulmonary embolism who underwent VA-ECMO for initial hemodynamic stabilization, with or without PMT, from August 2018 to November 2021.

Results

Mean patient age was 54.7 years. Four of nine patients (44.4%) required cardiopulmonary resuscitation before or during VA-ECMO cannulation. All cannulations (100%) were successfully performed percutaneously. Overall survival was 88.9% (8 of 9 patients). One patient died from a hemorrhagic stroke. Of the survivors, the median ECMO duration was 8 days in patients treated with ECMO alone and 4 days in those treated with EMCO and PMT. Five of nine patients (55.6%) required concomitant PMT to address persistent right heart dysfunction, with the remaining survivors (44.4%) receiving VA-ECMO and anticoagulation alone. For survivors receiving VA-ECMO plus PMT, median hospital lengths of stay were 7 and 13 days, respectively.

Conclusions

An ECMO-first strategy complemented with PMT can be performed effectively and safely for acute life-threatening massive or submassive PE. VA-ECMO is feasible for initial stabilization, serving as a bridge to therapy primarily in inoperable patients with massive PE. Further evaluation in a larger cohort of patients is warranted to assess whether VA-ECMO plus PMT may offer an alternative or complementary therapy to thrombolysis or surgical thrombectomy.

Type of Research

Single-center retrospective review of a prospectively maintained registry.
D-Dimer Is a Diagnostic Biomarker of Abdominal Aortic Aneurysm in Patients With Peripheral Artery Disease
Authors: Cai Huoying , Pan Baihong , Xu Jie , Liu Shuai , Wang Lei , Wu Kemin , Yang Pu , Huang Jianhua , Wang Wei
Published: June 2022

Background

Etiology and risk factors of peripheral artery disease (PAD) include age, smoking, and hypertension, etc. , which are shared by an abdominal aortic aneurysm (AAA). Concomitance with AAA in patients with PAD is not rare but is easily overlooked in the clinical situation, though management strategies are altered totally. This study aims to investigate diagnostic biomarkers for the prediction of AAA in patients with PAD.

Methods

A total of 684 patients diagnosed with AAA and/or PAD were enrolled and analyzed retrospectively. Each patient with PAD and AAA was gender and age-matched. Demographic data, medical history, and serum laboratory test profiles were obtained. Statistical analysis was performed to determine diagnostic biomarkers of AAA in patients with PAD.

Results

Firstly, 320 patients with PAD-only and 320 patients with AAA-only were compared. Levels of bilirubin and D-Dimer were decreased, while the incidence of diabetes mellitus, levels of fibrinogen, and platelet count were increased significantly in patients with PAD-only compared with those in patients with AAA-only (P < 0.001). Next, 364 patients with PAD (44 patients with AAA) and 364 patients with AAA (44 patients with PAD) were compared. Multivariate logistic regression analysis confirmed the differential distribution of bilirubin, D-dimer, fibrinogen, and platelet count between patients with AAA and patients with PAD (P < 0.05). Receiver operator curves (ROC) showed that the area under the curve (AUC) of total bilirubin, direct bilirubin, D-dimer, fibrinogen, and platelet count was 0.6113, 0.5849, 0.7034, 0.6473, and 0.6785, respectively. Finally, to further validate the predictive efficacy of mentioned markers, a multivariable logistics regression analysis was performed between the PAD only group and the PAD with AAA group. The results suggested increased levels of D-dimer in the PAD with AAA group compared to the PAD only group (OR: 2.630, 95% CI:1.639–4.221; P < 0.001). In particular, the Youden index suggested that the cut-off value of D-dimer for predicting AAA in patients with PAD was 0.675 mg/L with a sensitivity of 76.9% and a specificity of 84.9% (AUC = 0.8673; 95% CI, 0.8106–0.9240, P < 0.001). In all 364 patients with PAD, 41.46% patients were diagnosed AAA when D-dimer is >0.675 mg/L, while only 3.55% patients were diagnosed AAA when D-dimer ≤ 0.675 mg/L.

Conclusions

PAD and AAA exert different clinical and serum profiles; D-dimer (>0.675 mg/L) is a reliable biomarker for the prediction of AAA in patients with PAD.
Economic Evaluation of Transcatheter Aortic Valve Replacement Compared to Surgical Aortic Valve Replacement in Chinese Intermediate-Risk Patients
Authors: Zhang Weicong , Lou Yake , Liu Yujiang , Wang Hongwei , Zhang Chun , Qian Linxue
Published: June 2022

Background

Aortic stenosis (AS) is a severe disease that causes heart failure and sudden death. Transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) are both recommended for patients with intermediate surgical risk, but the cost-effectiveness of TAVR compared to SAVR in China has not been investigated.

Methods

A combined decision tree and Markov model were conducted to compare the cost-effectiveness of TAVR versus SAVR with a 5-year simulation. The primary outcome was the incremental cost-effectiveness ratio (ICER), a ratio of incremental costs to incremental quality-adjusted life-year (QALY). One-way sensitive analysis and probabilistic sensitivity analysis (PSA) were conducted to test the robustness of the model.

Results

After a simulation of 5 years, the costs of TAVR and SAVR were 54,573 and 35,002 USD, respectively, and the corresponding effectiveness was 2.826 versus 2.712 QALY, respectively. The ICER for the TAVR versus SAVR comparison was 170,056 USD/QALY, which was three times higher than the per capita gross domestic product (GDP) in China. One-way sensitive analysis showed that the cost of the TAVR device impacted the ICER. The TAVR could be cost-effective only in the case where its cost is lowered to 29,766 USD.

Conclusion

TAVR is currently not cost-effective in China, but it could be cost-effective with a reduction of costs to 29,766 USD, which is approximately 65% of the current price.
Case Report: Multimodal Imaging Guides the Management of an Eosinophilic Leukemia Patient With Eosinophilic Myocarditis and Intracardiac Thrombus
Authors: Si Jinping , Zhang Xinxin , Chen Na , Sun Fangfang , Du Ping , Li Zhiyong , Tian Di , Sun Xiuli , Sun Guozhen , Cong Tao , Du Xuemei , Liu Ying
Published: June 2022

Background

Eosinophilic leukemia (EL) is a rare, serious and potentially life-threatening condition characterized by the overproduction of eosinophils leading to tissue eosinophilic infiltration and damage. Although multiple organ systems may be involved, progressive eosinophilic myocarditis (EM) is the most common cause of morbidity and mortality. Early diagnosis and follow-up surveillance combined with multimodal imaging are crucial for appropriate treatment of EM.

Case Summary

It’s a rare case of EL with EM and intracardiac thrombus in a 59-year-old patient who presented with asthenia for 3 weeks. Full blood count analysis indicated significant eosinophilia. Bone marrow aspirate revealed dysplastic eosinophilia and a FIP1L1-PDGFRA fusion gene (4q12) was detected, confirming EL. Echocardiography revealed EM with intracardiac thrombus. This was later confirmed by cardiac magnetic resonance imaging. The patient was commenced on imatinib and prednisolone and good clinical response was obtained. Through 18F-FAPI PET/CT imaging, we obtained in vivo visualization of fibroblast activation changes in the early stage of cardiac structure remodeling. With anti-fibrotic therapy after heart failure, the patient achieved a good clinical response.

Conclusion

This case demonstrates in vivo visualization of fibroblast activation after EM. Multimodality imaging can provide early diagnosis and may guide tailored antifibrotic therapy in early stage of EM.
Transient Receptor Potential Channels, Natriuretic Peptides, and Angiotensin Receptor-Neprilysin Inhibitors in Patients With Heart Failure
Authors: Ding Kun , Gui Yang , Hou Xu , Ye Lifang , Wang Lihong
Published: June 2022

Heart failure (HF) remains the leading cause of death, morbidity, and medical expenses worldwide. Treatments for HF with reduced ejection fraction have progressed in recent years; however, acute decompensated heart failure remains difficult to treat. The transient receptor potential (TRP) channel family plays roles in various cardiovascular diseases, responding to neurohormonal and mechanical load stimulation. Thus, TRP channels are promising targets for drug discovery, and many studies have evaluated the roles of TRP channels expressed on pain neurons. The natriuretic peptide (NP) family of proteins regulates blood volume, natriuresis, and vasodilation and can antagonize the renin-angiotensin-aldosterone system and participate in the pathogenesis of major cardiovascular diseases, such as HF, coronary atherosclerotic heart disease, and left ventricular hypertrophy. NPs are degraded by neprilysin, and the blood level of NPs has predictive value in the diagnosis and prognostic stratification of HF. In this review, we discuss the relationships between typical TRP family channels (e.g., transient receptor potential cation channel subfamily V member 1 andTRPV1, transient receptor potential cation channel subfamily C member 6) and the NP system (e.g., atrial NP, B-type NP, and C-type NP) and their respective roles in HF. We also discuss novel drugs introduced for the treatment of HF.
Experimental Study on Directional Shear of Q2 Remolded Loess Considering the Direction of Principal Stress
Authors: Wang Sui , Zhao Peng , Gao Zhihua , Zhong Zuliang , Chen Bin , Wu Bo , Sun Qingjun , Song Chunxia
Published: June 2022

To investigate the strength and deformation characteristics of Q2 remodeled loess, soil samples from the Lishi area in Shanxi Province were adopted to examine the effects arising from the principal stress axis direction angle α and the medium principal stress ratio b on the shear and non-coaxial properties of remodeled loess based on the hollow cylindrical torsional shear system. As indicated by this study, when b was constant, the generalized shear stress ratio decreased with the increase in α at 0°–45°, while achieving the minimum value when α = 45°; α increased again with the increase in the principal stress axis direction angle at 45°–90°. When α was 0–45°, the generalized shear stress ratio tended to decrease with the increase in the intermediate principal stress ratio b. When α was 60°–90°, the shear strength ratios at different intermediate principal stress ratios were obtained as: strength at b = 0.5 > strength at b = 1 > strength at b = 0. Moreover, after the degree of strength volatility of this remodeled loess was defined to determine its breaking strain standard, it was found through a comparative analysis that when the generalized shear strain of this remodeled loess was 6.5%, the strength of this remodeled loess was over 90%. Thus, this study suggested the use of its generalized shear strain of 6.5% as its breaking strain standard. In addition, when α was at 0–45°, the direction angle of strain increment increased with the increase in the direction angle of the principal stress axis and reached the peak at 45°. When α was at 60°–90°, the direction angle of strain increment decreased with the increase in the direction angle of the principal stress axis, i.e., the non-coaxial characteristics of the remolded loess first increased, then decreased, and further tended to be coaxial.
Investigation of Snow Deposition on the Railway Cuttings During the Snowdrift
Authors: Ma Wenyong , Li Sai , Sun Yuanchun , Li Jianglong , Li Feiqiang
Published: June 2022

This study confirmed a mixture multiphase model based on the Euler–Euler method to predict snow deposition in road cuttings. A scaled model experiment was conducted in the Mayitas region of Xinjiang to verify the numerical simulation accuracy, which revealed a good agreement. Regarding the formation mechanism of drifting snow disasters in road cuttings, the wind speed in the simulation results was analyzed in detail. The results indicated that the low-wind speed area is positively correlated with the vortex size and that snow deposition occurs between the vortex separation point and vortex reattachment point. The appearance and disappearance of the secondary vortex can divide the snow cover process into three stages, and the second phase after secondary vortex emergence represents the period of a rapid increase in the snow thickness. Snow cornices are the leading emergence cause of secondary vortex. The related critical snow storage capacity should also be considered to measure the snow storage capacity of road cutting types.
Glacier Mass Balance Based on Two Digital Elevation Models and Ground Observation Records for the Baishui River Glacier No. 1 in Yulong Snow Mountain, Southeastern Qinghai–Tibet Plateau
Authors: Chen Lihua , Che Yanjun , Cao Yun , Wang Shijin , Ma Xinggang
Published: June 2022

Glacier mass balance is a key idea in understanding the relationship between glaciers and climate. In this study, Landsat images, Shuttle Radar Topography Mission, and Advance Land Operation Satellite digital elevation models, and ground observation records for 2000–2010 and 2019–2020 were used to analyze a mass balance of the Baishui River Glacier No. 1 (BRG1) in Yulong Snow Mountain, southeastern Qinghai–Tibet Plateau. Both glaciological and geodetic methods were used to understand the spatial pattern of the mass balance. A mass balance contour line map of the glacier was created for the first time. From 2000 to 2010, the mean annual mass balance of the BRG1 was calculated to be -0.99 m w.e., -1.01 m w.e., and −1.18 m w.e. using the contour line, profile curve, and geodetic methods, respectively. In addition, the analysis revealed that strong melting of the glacier occurred from July 27 to 15 September 2019, with an averaged glacier mass balance of -1.75 m w.e. and a mean daily melting rate of 35 mm w.e. The annual mass balance was assessed to be −1.31 m w.e. during 2019/20 using the contour line method. In addition, the spatial patterns on the mass balance contour maps for 2000–2010 and the summer of 2019, and the climate change in this region were analyzed. The results indicate that the increased air temperature was the main cause of the accelerated glacial melting.
Structural Characteristics and Deformation Evolution of an Intra-Continental Fold-Thrust Belt in Eastern Sichuan: Insights Into Analogue Sandbox Models
Authors: Wang Yang-Shuang , Xu Mo , Yang Yan-Na , Xia Qiang , Jiang Bing , Yang Chang , Zhang Heng
Published: June 2022

The Eastern Sichuan area is a typical fold-and-impulse zone. It is bounded by the Qiyue Mountain fault, with septal folds on the east and on the west. Based on previous geological mapping and surface geological structure research as well as the fault-related folding theory, in this study, tectonophysical simulation experiments were conducted to investigate the tectonic geometry and kinematics of the Eastern Sichuan fold-impulse zone. The experiments were conducted by selecting different experimental materials and changing the physical properties of the cover, the friction between the cover and the basement, the number of slip layers, the burial depth, and other factors. Finally, the similarity of the results to the morphological characteristics of the real geological structure was assessed. The results show that the deformation style is influenced to some extent by the brittle shear strength and the ductile shear strength of the basement, and the different interlayer cohesions between the competent and incompetent layers, the high rheology, and the burial depth of the slickensides played crucial roles in the formation of the final evolution of the Eastern Sichuan fold fault zone. The step-like system, composed of a lower crustal crystalline basement detachment surface, regional boundary fractures, and the overlying Cambrian and Triassic synclines, is a necessary condition for the formation of the Eastern Sichuan fold and fault zone and controls the overall evolution of the zone. Under the action of multiple phases of tectonic activity with different main stress orientations, the geological phenomenon of multiple superimposed phases of folding in different directions observed at present in the Eastern Sichuan area was formed. The well-developed karst features are not conducive to the construction of a project tunnel in the area where tightly closed back-slope, fissures, and normal faults have developed in the Eastern Sichuan fold and fault zone.
Quantitative Precipitation Estimation Model Integrating Meteorological and Geographical Factors at Multiple Spatial Scales
Authors: Tian Wei , Shen Kailing , Yi Lei , Zhang Lixia , Feng Yang , Chen Shiwei
Published: June 2022

Heavy precipitation tends to cause mountain torrents, urban waterlogging and other disasters. It poses a serious threat to people’s life and property safety. Therefore, real-time quantitative precipitation estimation is especially important to keep track of precipitation changes and reduce negative impacts. However, high-resolution and high-accuracy quantitative precipitation estimation is a challenging task due to the complex spatial and temporal variability of microphysics in precipitation processes. Previous studies have focused only on small-scale radar reflectivity factors above rain gauges and did not pay enough attention to the contribution of covariates to model performance. Meteorological and geographical factors play an important role in rain process, so these factors are taken into account during our research. In this study, a quantitative precipitation estimation model that can employ multi-scale radar reflectivity factors and fuse meteorological and geographical factors is proposed to further improve precipitation accuracy. In addition, we propose the muti-scale self-attention (MS-SA) module that can further utilize information at multiple spatial scales to improve the accurate precipitation estimation. The proposed model reduced the root mean square error of precipitation estimation by 83.8% compared to the conventional Z-R relationship that correlates the rainfall and radar reflectivity factors,  i.e., Z=aRb, and by 43.7, 24.6, and 22.7% compared to the back propagation neural network (BPNN), convolutional neural network (CNN), and convolutional neural network with the addition of meteorological factors and geographical factors as covariates in the proposed model, respectively. Therefore, we can conclude that multi-scale radar reflectivity factors fused with meteorological and geographical factors can produce more accurate precipitation estimation.
Translation and Validation of the Online Homework Distraction Scale for Peruvian University Students
Authors: Carranza Esteban Renzo Felipe , Mamani-Benito Oscar , Sarria-Arenaza Fiorella , Meza-Villafranca Anahí , Paula Alfaro Ana , Lingan Susana K.
Published: June 2022

The objective of this study was to translate and validate the Online Homework Distraction Scale (OHDS) for Peruvian university students. Accordingly, an instrumental cross-sectional study was conducted with 811 university students, including students of both sexes aged between 16 and 39 (M = 20.96 years; SD = 4.42) residing in the city of Lima. The content-based validity evidence was analyzed using Aiken’s V coefficient based on the internal structure through a confirmatory factor analysis and considered in relation to other variables a through correlation analysis. The reliability was calculated using the Omega coefficient. Expert opinions were favorable for all items (V > 0.70). The one-dimensional structure of the scale was confirmed, and it presented acceptable reliability (α > 0.70). Thus, the OHDS for university students is a measure with a valid and reliable scale.
Primary and Secondary School Teachers’ Perception of the Assessment of Historical Knowledge and Skills Based on Classroom Activities and Exercises
Authors: Trigueros-Cano Francisco Javier , Molina-Saorín Jesús , López-García Alejandro , Álvarez-Martínez-Iglesias José María
Published: June 2022

The aim of this paper is to identify the most suitable activities and exercises for the development of historical knowledge and skills and their subsequent evaluation. On this basis, a quantitative study has been carried out among primary and secondary school teachers in several Spanish regions in which their perception of what types of exercises and activities (of those proposed in their History or Social Science classes) are most suitable for assessing the historical knowledge and skills that students are expected to acquire has been extracted. The results show that exercises involving the interpretation of texts and images which require students to think about and apply the historical knowledge acquired are very useful, as are questions which seek historical explanation and causal reasoning; however, objective tests (multiple-choice tests, linking dates with events, etc.) or short questions about historical events or characters are not considered to be very suitable for the adequate development of historical knowledge and, therefore, of historical competences. Broadly speaking, it is recommended that this line of research be continued so that other authors can replicate these findings, deepening their knowledge of these instruments, whose didactic commitment could serve as an argument in the face of the excessive time pressure faced by today’s teachers.
Comorbidities in Recent-Onset Adult Type 1 Diabetes: A Comparison of German Cohorts
Authors: Zaharia Oana P. , Lanzinger Stefanie , Rosenbauer Joachim , Karges Wolfram , Müssig Karsten , Meyhöfer Sebastian M. , Burkart Volker , Hummel Michael , Raddatz Dirk , Roden Michael , Szendroedi Julia , Holl Reinhard W.
Published: June 2022

Aims

Restrictive exclusion criteria from different study populations may limit the generalizability of the observations. By comparing two differently designed German cohorts, we assessed the prevalence of cardiovascular risk factors and diabetes-related complications in recent-onset adult type 1 diabetes.

Methods

This study evaluated 1511 persons with type 1 diabetes of the prospective diabetes follow-up registry (DPV) and 268 volunteers of the prospective observational German Diabetes Study (GDS) with a known diabetes duration <1 year. Participants had similar age (36 years), sex distribution (41% female) and BMI (26 kg/m2) in both cohorts.

Results

The average HbA1c was 6.4 ± 0.8% in the GDS and 7.0 ± 1.1% in the DPV. Prevalence of hypertension (24%) was similar, while more DPV participants had dyslipidemia and lipid-lowering medication than GDS participants (77% vs. 41% and 7% vs. 2%, respectively; p<0.05). Prevalence of retinopathy and nephropathy was higher in DPV compared to GDS participants (10% vs. 3% and 18% vs. 7%, respectively; p<0.001).

Conclusions

Diabetic nephropathy and retinopathy are the most frequent complications in type 1 diabetes, affecting up to every 10th patient within the first year after diagnosis, underlining the need for more stringent risk factor management already at the time of diagnosis of type 1 diabetes.
Thyroid Autoimmunity in Female Infertility and Assisted Reproductive Technology Outcome
Authors: Bucci Ines , Giuliani Cesidio , Di Dalmazi Giulia , Formoso Gloria , Napolitano Giorgio
Published: June 2022

The regulation of the female reproductive system is one of the most relevant actions of thyroid hormones. Adequate thyroid hormones production is essential for normal menstrual function and fertility as well as for the successful maintenance of pregnancy. The relationship between reproductive failure and thyroid disorders is particularly relevant and attracts attention worldwide. Thyroid autoimmunity (TAI), defined by the presence of circulating antithyroid antibodies targeting thyroid peroxidase (TPOAb) and thyroglobulin (TgAb), is prevalent among women of reproductive age and is the most frequent cause of thyroid dysfunction. Several studies addressed the association between TAI, thyroid function, and fertility as well as pregnancy outcome after spontaneous or assisted conception. Infertility, miscarriages, and fetal-maternal complications are described in overt autoimmune hypothyroidism. More debatable is the role of mild thyroid dysfunction, mainly subclinical hypothyroidism (SCH), and TAI in the absence of thyroid dysfunction in infertility and reproductive outcome. Assisted reproductive technology (ART) has become an integral element of care for infertility. Women with TAI undergoing ART are of particular interest since they carry a higher risk of developing hypothyroidism after the ovarian stimulation but whether TAI, in absence of thyroid dysfunction, adversely affects ART outcome is still controversial. Likewise, the role of levothyroxine (LT4) in improving fertility and the success of ART in euthyroid women with TAI is unclear. This review discusses the role of TAI, in the absence of thyroid dysfunction, in infertility and in ART outcome.
Association of Paraspinal Muscle CSA and PDFF Measurements With Lumbar Intervertebral Disk Degeneration in Patients With Chronic Low Back Pain
Authors: Huang Yilong , Wang Ling , Zeng Xiaomin , Chen Jiaxin , Zhang Zhenguang , Jiang Yuanming , Nie Lisha , Cheng Xiaoguang , He Bo
Published: June 2022

There is an interaction between the lumbar spine and paraspinal muscles, which may play a role in the development of intervertebral disc (IVD) degeneration and may affect CLBP. The study aims to assess the relationship between IVD degeneration and paraspinal muscle fat infiltration in CLBP patients by quantitative MR imaging, and to evaluate the influence of sex and age on CLBP muscle fat infiltration. Sixty CLBP patients (46.3 years ±17.0) and thirty-two healthy subjects (44.9 years ±17.6) were recruited for this study. 3.0 T MRI was used to perform the sagittal and axial T1, T2 of the lumbar spine, and axial paraspinal muscle IDEAL imaging at the L4/5 and L5/S1 levels. Proton density fat fraction (PDFF) of the multifidus and erector spinae at two IVD levels were measured. The Pfirrmann grades of IVD degeneration, Oswestry Disability Index (ODI), and Visual Analog Scale (VAS) were also evaluated. Compare the cross-sectional area (CSA) and PDFF of the paraspinal muscles between CLBP patients and healthy subjects, and analyze the relationship between the muscle PDFF and Pfirrmann grades, gender, and age of CLBP patients. Compared with healthy subjects, the CSA of the multifidus muscle in CLBP patients decreased (1320.2±188.1mm2vs. 1228.7±191.0 mm2, p<0.05) at the L4/5 level, the average PDFF increased, (7.7±2.6% vs. 14.79±5.3%, 8.8±4.2% vs. 16.03±5.3%, all p<0.05) at both L4/5 and L5/S1 levels. The PDFF of paraspinal muscles were correlated with adjacent IVD degeneration, ODI and VSA in CLBP patients (all p<0.05). After using age and body mass index (BMI) as control variables, significance was retained (all p<0.05). Multiple regression analysis revealed sex and age also were significantly associated with multifidus PDFF (all p < 0.05). This study confirmed that the CSA decreased and the PDFF increased of the paraspinal muscles in CLBP patients. It reveals a significant correlation between the PDFF of CLBP paraspinal muscles and the grade of IVD degeneration. Sex and age are also important factors influencing CLBP paraspinal muscle infiltration.