bluuebunny/crossref_metadata_2025 huggingface dataset:
Copper Metabolism in Naegleria gruberi and Its Deadly Relative Naegleria fowleri
Authors: Ženíšková Kateřina , Grechnikova Maria , Sutak Robert
Published: April 2022

Although copper is an essential nutrient crucial for many biological processes, an excessive concentration can be toxic and lead to cell death. The metabolism of this two-faced metal must be strictly regulated at the cell level. In this study, we investigated copper homeostasis in two related unicellular organisms: nonpathogenic Naegleria gruberi and the “brain-eating amoeba” Naegleria fowleri. We identified and confirmed the function of their specific copper transporters securing the main pathway of copper acquisition. Adjusting to different environments with varying copper levels during the life cycle of these organisms requires various metabolic adaptations. Using comparative proteomic analyses, measuring oxygen consumption, and enzymatic determination of NADH dehydrogenase, we showed that both amoebas respond to copper deprivation by upregulating the components of the branched electron transport chain: the alternative oxidase and alternative NADH dehydrogenase. Interestingly, analysis of iron acquisition indicated that this system is copper-dependent in N. gruberi but not in its pathogenic relative. Importantly, we identified a potential key protein of copper metabolism of N. gruberi, the homolog of human DJ-1 protein, which is known to be linked to Parkinson’s disease. Altogether, our study reveals the mechanisms underlying copper metabolism in the model amoeba N. gruberi and the fatal pathogen N. fowleri and highlights the differences between the two amoebas.
A Non-Synonymous Point Mutation in a WD-40 Domain Repeat of EML5 Leads to Decreased Bovine Sperm Quality and Fertility
Authors: Nogueira Eriklis , Tirpák Filip , Hamilton Lauren E. , Zigo Michal , Kerns Karl , Sutovsky Miriam , Kim JaeWoo , Volkmann Dietrich , Jovine Luca , Taylor Jeremy F. , Schnabel Robert D. , Sutovsky Peter
Published: April 2022

This study is part of a concerted effort to identify and phenotype rare, deleterious mutations that adversely affect sperm quality, or convey high developmental and fertility potential to embryos and ensuing progeny. A rare, homozygous mutation in EML5 (EML5R1654W), which encodes a microtubule-associated protein with high expression in testis and brain was identified in an Angus bull used extensively in artificial insemination (AI) for its outstanding progeny production traits. The bull’s fertility was low in cross-breeding timed AI (TAI) (Pregnancy/TAI = 25.2%; n = 222) and, in general, AI breeding to Nellore cows (41%; n = 822). A search of the 1,000 Bull Genomes Run9 database revealed an additional 74 heterozygous animals and 8 homozygous animals harboring this exact mutation across several different breeds (0.7% frequency within the 6,191 sequenced animals). Phenotypically, spermatozoa from the homozygous Angus bull displayed prominent piriform and tapered heads, and outwardly protruding knobbed acrosomes. Additionally, an increased retention of EML5 was also observed in the sperm head of both homozygous and heterozygous Angus bulls compared to wild-type animals. This non-synonymous point mutation is located within a WD40 signaling domain repeat of EML5 and is predicted to be detrimental to overall protein function by genomic single nucleotide polymorphism (SNP) analysis and protein modeling. Future work will examine how this rare mutation affects field AI fertility and will characterize the role of EML5 in spermatogenesis.
Multinucleated Giant Cells: Current Insights in Phenotype, Biological Activities, and Mechanism of Formation
Authors: Ahmadzadeh Kourosh , Vanoppen Margot , Rose Carlos D. , Matthys Patrick , Wouters Carine Helena
Published: April 2022

Monocytes and macrophages are innate immune cells with diverse functions ranging from phagocytosis of microorganisms to forming a bridge with the adaptive immune system. A lesser-known attribute of macrophages is their ability to fuse with each other to form multinucleated giant cells. Based on their morphology and functional characteristics, there are in general three types of multinucleated giant cells including osteoclasts, foreign body giant cells and Langhans giant cells. Osteoclasts are bone resorbing cells and under physiological conditions they participate in bone remodeling. However, under pathological conditions such as rheumatoid arthritis and osteoporosis, osteoclasts are responsible for bone destruction and bone loss. Foreign body giant cells and Langhans giant cells appear only under pathological conditions. While foreign body giant cells are found in immune reactions against foreign material, including implants, Langhans giant cells are associated with granulomas in infectious and non-infectious diseases. The functionality and fusion mechanism of osteoclasts are being elucidated, however, our knowledge on the functions of foreign body giant cells and Langhans giant cells is limited. In this review, we describe and compare the phenotypic aspects, biological and functional activities of the three types of multinucleated giant cells. Furthermore, we provide an overview of the multinucleation process and highlight key molecules in the different phases of macrophage fusion.
Microfluidic Reproduction of Dynamic Bioreactor Environment Based on Computational Lifelines
Authors: Ho Phuong , Täuber Sarah , Stute Birgit , Grünberger Alexander , von Lieres Eric
Published: April 2022

The biotechnological production of fine chemicals, proteins and pharmaceuticals is usually hampered by loss of microbial performance during scale-up. This challenge is mainly caused by discrepancies between homogeneous environmental conditions at laboratory scale, where bioprocesses are optimized, and inhomogeneous conditions in large-scale bioreactors, where production takes place. Therefore, to improve strain selection and process development, it is of great interest to characterize these fluctuating conditions at large-scale and to study their effects on microbial cells. In this paper, we demonstrate the potential of computational fluid dynamics (CFD) simulation of large-scale bioreactors combined with dynamic microfluidic single-cell cultivation (dMSCC). Environmental conditions in a 200 L bioreactor were characterized with CFD simulations. Computational lifelines were determined by combining simulated turbulent multiphase flow, mass transport and particle tracing. Glucose availability for Corynebacterium glutamicum cells was determined. The reactor was simulated with average glucose concentrations of 6 g m−3, 10 g m−3 and 16 g m−3. The resulting computational lifelines, discretized into starvation and abundance regimes, were used as feed profiles for the dMSCC to investigate how varying glucose concentration affects cell physiology and growth rate. In this study, each colony in the dMSCC device represents a single cell as it travels through the reactor. Under oscillating conditions reproduced in the dMSCC device, a decrease in growth rate of about 40% was observed compared to continuous supply with the same average glucose availability. The presented approach provides insights into environmental conditions observed by microorganisms in large-scale bioreactors. It also paves the way for an improved understanding of how inhomogeneous environmental conditions influence cellular physiology, growth and production.
Hydrazones and Thiosemicarbazones Targeting Protein-Protein-Interactions of SARS-CoV-2 Papain-like Protease
Authors: Ewert Wiebke , Günther Sebastian , Miglioli Francesca , Falke Sven , Reinke Patrick Y. A. , Niebling Stephan , Günther Christian , Han Huijong , Srinivasan Vasundara , Brognaro Hévila , Lieske Julia , Lorenzen Kristina , Garcia-Alai Maria M. , Betzel Christian , Carcelli Mauro , Hinrichs Winfried , Rogolino Dominga , Meents Alke
Published: April 2022

The papain-like protease (PLpro) of SARS-CoV-2 is essential for viral propagation and, additionally, dysregulation of the host innate immune system. Using a library of 40 potential metal-chelating compounds we performed an X-ray crystallographic screening against PLpro. As outcome we identified six compounds binding to the target protein. Here we describe the interaction of one hydrazone (H1) and five thiosemicarbazone (T1-T5) compounds with the two distinct natural substrate binding sites of PLpro for ubiquitin and ISG15. H1 binds to a polar groove at the S1 binding site by forming several hydrogen bonds with PLpro. T1-T5 bind into a deep pocket close to the polyubiquitin and ISG15 binding site S2. Their interactions are mainly mediated by multiple hydrogen bonds and further hydrophobic interactions. In particular compound H1 interferes with natural substrate binding by sterical hindrance and induces conformational changes in protein residues involved in substrate binding, while compounds T1-T5 could have a more indirect effect. Fluorescence based enzyme activity assay and complementary thermal stability analysis reveal only weak inhibition properties in the high micromolar range thereby indicating the need for compound optimization. Nevertheless, the unique binding properties involving strong hydrogen bonding and the various options for structural optimization make the compounds ideal lead structures. In combination with the inexpensive and undemanding synthesis, the reported hydrazone and thiosemicarbazones represent an attractive scaffold for further structure-based development of novel PLpro inhibitors by interrupting protein-protein interactions at the S1 and S2 site.
Sol-Gel Combustion-Assisted Electrostatic Spray Deposition for Durable Solid Oxide Fuel Cell Cathodes
Authors: Lee Jongseo , Bang Sehee , Lee Wonyoung
Published: April 2022

The chemical instability of perovskite oxides containing Sr is a critical issue for the long-term operation of solid oxide fuel cells. In this study, we demonstrate a remarkable improvement in the chemical and electrochemical stability of a heterostructured La0.6Sr0.4CoO3-δ (LSC)-Ce0.9Gd0.1O1.95 (GDC) electrode. Electrostatic spray deposition was employed to fabricate heterostructured nanoparticles in a single step with a coaxial nozzle supplying the LSC powders in the core nozzle and the GDC precursors in the shell nozzle. Moreover, the reducing fuel added to the GDC precursor solution induced the sol-gel combustion reaction in the droplet to form a uniform nanocrystalline GDC coating with high surface coverage. The high surface coverage of GDC on the LSC more significantly improved long-term stability compared with than of the bare LSC cathode at a constant current density of 1 A/cm2 at 600°C for 100 h.
Application of Ginsenoside Rd in Periodontitis With Inhibitory Effects on Pathogenicity, Inflammation, and Bone Resorption
Authors: Zhou Shuhui , Ji Yaoting , Yao Hantao , Guo Haiying , Zhang Zichen , Wang Zijun , Du Minquan
Published: April 2022

Periodontitis is a worldwide oral disease induced by the interaction of subgingival bacteria and host response and is characterized by local inflammation, bone resorption, and tooth loss. Ginsenoside Rd (Rd) is a biologically active component derived from Panax ginseng and has been demonstrated to exert antibacterial and anti-inflammatory activities. This study aims to investigate the inhibitory efficiency of Rd towards Porphyromonas gingivalis (P. gingivalis), periodontal inflammatory response, and osteoclastogenesis in vitro and to further validate the results in a mouse periodontitis model, thus, evaluate the potential effects of Rd on the control and prevention of periodontitis. According to the results, Rd exerted excellent antibacterial activities against planktonic P. gingivalis, along with attenuating P. gingivalis virulence and inhibiting its biofilms. Meanwhile, the inflammatory cytokine production and osteoclastogenesis were remarkably inhibited by Rd both in vitro and in vivo. Furthermore, Rd efficiently ameliorated the subgingival P. gingivalis abundance and suppressed the alveolar bone resorption in vivo as well. In conclusion, Rd has the potential to be developed as a promising medication in the control and prevention of periodontitis.
Use of Bulk Segregant Analysis for Determining the Genetic Basis of Azole Resistance in the Opportunistic Pathogen Aspergillus fumigatus
Authors: Ashton George D. , Sang Fei , Blythe Martin , Zadik Daniel , Holmes Nadine , Malla Sunir , Camps Simone M. T. , Wright Victoria , Melchers Willem J. G. , Verweij Paul E. , Dyer Paul S.
Published: April 2022

A sexual cycle was described in 2009 for the opportunistic fungal pathogen Aspergillus fumigatus, opening up for the first time the possibility of using techniques reliant on sexual crossing for genetic analysis. The present study was undertaken to evaluate whether the technique ‘bulk segregant analysis’ (BSA), which involves detection of differences between pools of progeny varying in a particular trait, could be applied in conjunction with next-generation sequencing to investigate the underlying basis of monogenic traits in A. fumigatus. Resistance to the azole antifungal itraconazole was chosen as a model, with a dedicated bioinformatic pipeline developed to allow identification of SNPs that differed between the resistant progeny pool and resistant parent compared to the sensitive progeny pool and parent. A clinical isolate exhibiting monogenic resistance to itraconazole of unknown basis was crossed to a sensitive parent and F1 progeny used in BSA. In addition, the use of backcrossing and increasing the number in progeny pools was evaluated as ways to enhance the efficiency of BSA. Use of F1 pools of 40 progeny led to the identification of 123 candidate genes with SNPs distributed over several contigs when aligned to an A1163 reference genome. Successive rounds of backcrossing enhanced the ability to identify specific genes and a genomic region, with BSA of progeny (using 40 per pool) from a third backcross identifying 46 genes with SNPs, and BSA of progeny from a sixth backcross identifying 20 genes with SNPs in a single 292 kb region of the genome. The use of an increased number of 80 progeny per pool also increased the resolution of BSA, with 29 genes demonstrating SNPs between the different sensitive and resistant groupings detected using progeny from just the second backcross with the majority of variants located on the same 292 kb region. Further bioinformatic analysis of the 292 kb region identified the presence of a cyp51A gene variant resulting in a methionine to lysine (M220K) change in the CYP51A protein, which was concluded to be the causal basis of the observed resistance to itraconazole. The future use of BSA in genetic analysis of A. fumigatus is discussed.
Sociometric Status in Bullying Perpetrators: A Systematic Review
Authors: Cañas Elizabeth , Estevez Estefania , Estevez Jesus F.
Published: April 2022

Numerous studies have analyzed the relationship between sociometric status and bullying but it is difficult to reach a consensus regarding this issue.

Objective

The present study carried out a systematic review on the sociometric status of adolescent bullies.

Design

The bibliographic search was carried out in the mainly databases.

Results

The findings of 29 studies selected defend three positions. First, bullying is associated with the popular status in their peer group. Second, rejected or unpopular adolescents tend to perpetrate bullying as a response to the frustration generated by their status. Finally, other group the perpetrators of bullying is among these two poles.

Conclusions

The students' sociometric status is necessary for designing bullying intervention programs at school.
Pleasantness and Wellbeing in Poem Declamation in European and Brazilian Portuguese Depends Mostly on Pausing and Voice Quality
Authors: Barbosa Plinio A.
Published: April 2022

This work investigates the relationship between the sensations of pleasantness and wellbeing and the acoustics of poem declamation in two varieties of Portuguese: European and Brazilian. Ten speakers in each variety recited Alberto Caeiro's poem “Quando vier a primavera” to which dataset the declamation by two actors was added. Ten listeners in each variety participated in three perception tests for evaluating the degree of pleasantness and wellbeing of the entire reading in two different sessions by using a 5-degree Likert scale, and for choosing the more pleasant recitation from two recitations of a chunk of the poem. Both reciters and listeners were balanced in gender. A set of 22 prosodic parameters was used for predicting the listeners' evaluations in logistic regression models and linear discriminant analysis. Results showed that the parameters related to pausing and voice quality are the main explanatory variables with a minor role for the F0 median. The actors' recitations are preferred and gender differences are related to reciters, not listeners. Minor differences across the varieties were found.
Circulating Autoantibodies Recognizing Immunodominant Epitopes From Human Apolipoprotein B Associate With Cardiometabolic Risk Factors, but Not With Atherosclerotic Disease
Authors: Marchini Timoteo , Malchow Sara , Caceres Lourdes , El Rabih Abed Al Hadi , Hansen Sophie , Mwinyella Timothy , Spiga Lisa , Piepenburg Sven , Horstmann Hauke , Olawale Tijani , Li Xiaowei , Mitre Lucia Sol , Gissler Mark Colin , Bugger Heiko , Zirlik Andreas , Heidt Timo , Hilgendorf Ingo , Stachon Peter , von zur Muehlen Constantin , Bode Christoph , Wolf Dennis
Published: April 2022

Rationale

Atherosclerosis is a chronic inflammatory disease of large arteries that involves an autoimmune response with autoreactive T cells and auto-antibodies recognizing Apolipoprotein B (ApoB), the core protein of low-density lipoprotein (LDL). Here, we aimed to establish a clinical association between circulating human ApoB auto-antibodies with atherosclerosis and its clinical risk factors using a novel assay to detect auto-antibodies against a pool of highly immunogenic ApoB-peptides.

Methods and Results

To detect polyclonal IgM- and IgG-antibodies recognizing ApoB, we developed a chemiluminescent sandwich ELISA with 30 ApoB peptides selected by an in silico assay for a high binding affinity to MHC-II, which cover more than 80% of known MHC-II variants in a Caucasian population. This pre-selection of immunogenic self-peptides accounted for the high variability of human MHC-II, which is fundamental to allow T cell dependent generation of IgG antibodies. We quantified levels of ApoB-autoantibodies in a clinical cohort of 307 patients that underwent coronary angiography. Plasma anti-ApoB IgG and IgM concentrations showed no differences across healthy individuals (n = 67), patients with coronary artery disease (n = 179), and patients with an acute coronary syndrome (n = 61). However, plasma levels of anti-ApoB IgG, which are considered pro-inflammatory, were significantly increased in patients with obesity (p = 0.044) and arterial hypertension (p < 0.0001). In addition, patients diagnosed with the metabolic syndrome showed significantly elevated Anti-ApoB IgG (p = 0.002). Even when normalized for total plasma IgG, anti-ApoB IgG remained highly upregulated in hypertensive patients (p < 0.0001). We observed no association with triglycerides, total cholesterol, VLDL, or LDL plasma levels. However, total and normalized anti-ApoB IgG levels negatively correlated with HDL. In contrast, total and normalized anti-ApoB IgM, that have been suggested as anti-inflammatory, were significantly lower in diabetic patients (p = 0.012) and in patients with the metabolic syndrome (p = 0.005).

Conclusion

Using a novel ELISA method to detect auto-antibodies against ApoB in humans, we show that anti-ApoB IgG associate with cardiovascular risk factors but not with the clinical appearance of atherosclerosis, suggesting that humoral immune responses against ApoB are shaped by cardiovascular risk factors but not disease status itself. This novel tool will be helpful to develop immune-based risk stratification for clinical atherosclerosis in the future.
Enhancing Palliative Care for Patients With Advanced Heart Failure Through Simple Prognostication Tools: A Comparison of the Surprise Question, the Number of Previous Heart Failure Hospitalizations, and the Seattle Heart Failure Model for Predicting 1-Year Survival
Authors: Blum Moritz , Gelfman Laura P. , McKendrick Karen , Pinney Sean P. , Goldstein Nathan E.
Published: April 2022

Background

Score-based survival prediction in patients with advanced heart failure (HF) is complicated. Easy-to-use prognostication tools could inform clinical decision-making and palliative care delivery.

Objective

To compare the prognostic utility of the Seattle HF model (SHFM), the surprise question (SQ), and the number of HF hospitalizations (NoH) within the last 12 months for predicting 1-year survival in patients with advanced HF.

Methods

We retrospectively analyzed data from a cluster-randomized controlled trial of advanced HF patients, predominantly with reduced ejection fraction. Primary outcome was the prognostic discrimination of SHFM, SQ (“Would you be surprised if this patient were to die within 1 year?”) answered by HF cardiologists, and NoH, assessed by receiver operating characteristic (ROC) curve analysis. Optimal cut-offs were calculated using Youden’s index (SHFM: <86% predicted 1-year survival; NoH ≥ 2).

Results

Of 535 subjects, 82 (15.3%) had died after 1-year of follow-up. SHFM, SQ, and NoH yielded a similar area under the ROC curve [SHFM: 0.65 (0.60–0.71 95% CI); SQ: 0.58 (0.54–0.63 95% CI); NoH: 0.56 (0.50–0.62 95% CI)] and similar sensitivity [SHFM: 0.76 (0.65–0.84 95% CI); SQ: 0.84 (0.74–0.91 95% CI); NoH: 0.56 (0.45–0.67 95% CI)]. As compared to SHFM, SQ had lower specificity [SQ: 0.33 (0.28–0.37 95% CI) vs. SHFM: 0.55 (0.50–0.60 95% CI)] while NoH had similar specificity [0.56 (0.51–0.61 95% CI)]. SQ combined with NoH showed significantly higher specificity [0.68 (0.64–0.73 95% CI)].

Conclusion

SQ and NoH yielded comparable utility to SHFM for 1-year survival prediction among advanced HF patients, are easy-to-use and could inform bedside decision-making.
Assisted Reproductive Technology Outcomes in Women With Heart Disease
Authors: Quien Mary M. , Hausvater Anaïs , Maxwell Susan M. , Weinberg Catherine R.
Published: April 2022

Background

Women with infertility and heart disease (HD) are increasingly seeking assisted reproductive technology (ART). There is only one other study that examines the safety profile of ART in this population. This study aims to evaluate the cardiac, reproductive, and obstetric outcomes of ART in women with HD.

Methods

We conducted a retrospective case-control study of women with underlying congenital or acquired HD who underwent ART at a single University fertility center from 1/2010–3/2019. Women undergoing in-vitro fertilization (IVF), oocyte cryopreservation (OC) or embryo banking (EB) with HD were included. Cases were matched 3:1 with age-, cycle type- and cycle start date- matched controls without HD. Outcomes included cardiovascular (CV), reproductive, and obstetric complications during or following ART.

Results

Twenty women with HD were included. 15 (75%) had congenital HD, 1 (5%) had valvular disease, 1 (5%) had acquired cardiomyopathy, and 3 (15%) had arrhythmias. 90% were New York Heart Association class I. 55% of HD cases were modified WHO (mWHO) risk classification 1-2, 40% were mWHO 2-3 or 3, 5% were mWHO 4. Cases underwent 25 IVF, 5 OC, and 5 EB cycles and were compared with 79 controls who underwent 174 cycles. No CV complications or deaths occurred amongst cases following ART or pregnancy. There was no difference in risk of ART or obstetric outcomes amongst cases versus controls.

Conclusion

For women with HD in this small, low -risk cohort, ART posed few risks that were similar in frequency to healthy controls.
Effect of Early Pharmacologic Cardioversion vs. Non-early Cardioversion in the Patients With Recent-Onset Atrial Fibrillation Within 4-Week Follow-Up Period: A Systematic Review and Network Meta-Analysis
Authors: Tang Yan , Wang Yujie , Sun Xuejing , Shi Yunmin , Liu Suzhen , Jiang Weihong , Yuan Hong , Lu Yao , Cai Jingjing , Wu Junru
Published: April 2022

Background

Whether early pharmacologic cardioversion is necessary for recent-onset atrial fibrillation is still controversial. Current meta-analyses were limited to evaluating the effects within 24 h without sufficient considering longer follow-up outcomes. We aimed to compare the effect of early pharmacologic cardioversion and non-early cardioversion in patients with recent-onset atrial fibrillation within 4-weeks of follow-up.

Methods

We searched the Cochrane Library, EMBASE, MEDLINE, PubMed, Web of Science, ClinicalTrials.gov, and Clinicaltrialsregister. eu for randomized controlled trials (RCTs) published before November 2021 comparing early pharmacologic cardioversion and non-early cardioversion in recent-onset atrial fibrillation and synthesized data in accordance with PRISMA-Systematic Reviews and Network Meta-Analysis (NMA). Early pharmacological cardioversion referred to immediate cardioversion with antiarrhythmic drugs (i.e., amiodarone, propafenone, flecainide, tedisamil, vernakalant, vanoxerine, and sotalol) upon admission, while non-early cardioversion involved the administration of rate-control or placebo medication without immediate cardioversion.

Results

16 RCTs with 2,395 patients were included. Compared to non-early cardioversion, a systematic review showed that early pharmacologic cardioversion resulted in a higher probability of sinus rhythm maintenance within 24 h (odds ratios [OR] 2.50, 95% credible interval [CrI] 1.76 to 3.54) and 1-week (2.50, 1.76 to 3.54), however, there was no significant difference in sinus rhythm maintenance within 4-weeks (1.37, 0.90 to 2.09). In subgroup analysis, the Bayesian NMA revealed that vernakalant may be successful in sinus rhythm maintenance within both 24 h (3.55, 2.28 to 5.55) and 1-week (2.72, 1.72 to 4.31). The results were consistent with the frequentist NMA.

Conclusions

Non-early pharmacologic cardioversion may not be inferior to early cardioversion within a 4-week follow-up period in patients with recent-onset atrial fibrillation. The evidence remains insufficient to determine which antiarrhythmic agent is optimal in the longer run. Further high-quality relevant RCTs are necessary.

Clinical Trial Registration

PROSPERO CRD42020166862.
Involvement of Polyamines From Cardiac Mast Cells in Myocardial Remodeling Induced by Pressure Overload Through Mitochondrial Permeability Transition Pore Opening
Authors: Xiong Xiaolan , Li Junming , Zhang Shizhong , Jia Xiaoli , Xiao Chao
Published: April 2022

Objective

Polyamines mainly contain spermine (SPM), spermidine (SPD), and putrescine (PUT). Many research results suggest that polyamines participate in cell proliferation, differentiation, and the regulation of gene expression, and have a close relationship with the occurrence and development of many diseases. However, the role and possible mechanisms of action of polyamines from cardiac mast cells in myocardial remodeling induced by pressure overload remain to be elucidated.

Methods

Pressure overload was induced by abdominal aortic constriction (AAC). Toluidine blue staining was used to visualize mast cells in cardiac tissue. The polyamine content of cardiac tissue was analyzed using high-performance liquid chromatography. Opening of the mitochondrial permeability transition pore (MPTP) was determined by the Ca2+-induced swelling of isolated cardiac mitochondria, measured as a reduction in A520.

Results

Compared with sham rats, the cardiac mast cell density, the polyamine content (PUT, SPB, and SPM), and myocardial MPTP opening in rats with AAC were significantly increased (P < 0.05), and were accompanied by increased myocardial fibrosis and heart weight/body weight ratio. Intraperitoneal injection of polyamines mimicked these results, and these effects were reversed by cromolyn sodium, a mast cell stabilizer (P < 0.05). Myocardial MPTP opening increased in rats with AAC (P < 0.05), and the three polyamines also increased myocardial MPTP opening (P < 0.05).

Conclusion

Mast cell-derived polyamines are involved in pressure overload-induced myocardial remodeling by increasing opening of the MPTP.
Exploring the Causal Effects of Circulating ST2 and Galectin-3 on Heart Failure Risk: A Mendelian Randomization Study
Authors: Wang Xizhi , Wang Xingchen , Zhu Jun , Liu Yu , Zhuang Lenan , Zhang Zhe , Zhong Danfeng , Zhang Wenbin , Lai Dongwu
Published: April 2022

Background

Heart failure (HF), primarily caused by conditions such as coronary heart disease or cardiomyopathy, is a global health problem with poor prognosis and heavy burden on healthcare systems. As biomarkers of myocardial injury and fibrosis, suppression of tumorigenicity 2 (ST2) and galectin-3 were recommended for prognosis stratification in HF guidelines. However, the causality between these two mediators and HF remains obscure. This study aimed to explore the causal relationship of genetically determined ST2 and galectin-3 with the risk of HF.

Methods

We used the two-sample Mendelian randomization (MR) method, incorporating available genome-wide association summary statistics, to investigate the causal association of ST2 and galectin-3 with HF risk. We applied inverse-variance weighted analysis as the main method of analysis.

Results

In our final MR analysis, 4 single-nucleotide polymorphisms (SNPs) of ST2 and galectin-3, respectively, were identified as valid instrumental variables. Fixed-effect inverse variance weighted (IVW) analysis indicated that genetically predicted ST2 and galectin-3 were not causally associated with HF risk 3. [odds ratio (OR) = 0.9999, 95% confidence interval [CI] = 0.9994–1.0004, p = 0.73; OR = 1.0002, 95% CI = 0.9994–1.0010, p = 0.60, respectively]. These findings were robust in sensitivity analyses, including MR-Egger regression and leave-one-out analysis.

Conclusion

This MR study provided no evidence for the causal effects of ST2 and galectin-3 on HF risk.
Impact of COPD or Asthma on the Risk of Atrial Fibrillation: A Systematic Review and Meta-Analysis
Authors: Xue Zhengbiao , Guo Siyu , Liu Xiao , Ma Jianyong , Zhu Wengen , Zhou Yue , Liu Fuwei , Luo Jun
Published: April 2022

Background:

Respiratory diseases related to chronic pulmonary ventilation dysfunction are mainly composed of chronic obstructive pulmonary disease (COPD) and asthma. Our meta-analysis aimed to illustrate the association of COPD or asthma with risk of atrial fibrillation (AF).

Methods

We systematically searched the databases of the PubMed, Embase, and Cochrane library until December 2021 for studies focusing on the relationship between COPD or asthma and AF risk. Due to the potential heterogeneity across studies, the random-effects model was used to pool the studies.

Results

Our meta-analysis included 14 studies. Based on the random-effects model, the pooled analysis showed that COPD (risk ratio[RR] = 1.74, 95% confidence interval [CI]: 1.70–1.79) and asthma (RR = 1.08, 95% CI: 1.04–1.12) were significantly associated with an increased risk of AF. The results did not change after each study was excluded.

Conclusion

Our current data suggested that COPD or asthma with associated with an increased risk of AF.
In-Hospital Cardiac Arrest in United States Emergency Departments, 2010–2018
Authors: Sung Chih-Wei , Lu Tsung-Chien , Wang Chih-Hung , Chou Eric H. , Ko Chia-Hsin , Huang Chien-Hua , Chen Wen-Jone , Tsai Chu-Lin
Published: April 2022

Background

Little is known about the in-hospital cardiac arrest (IHCA) in the US emergency department (ED). This study aimed to describe the incidence and mortality of ED-based IHCA visits and to investigate the factors associated with higher incidence and poor outcomes of IHCA.

Materials and Methods

Data were obtained from the National Hospital Ambulatory Medical Care Survey (NHAMCS) between 2010 and 2018. Adult ED visits with IHCA were identified using the cardiopulmonary resuscitation code, excluding those with out-of-hospital cardiac arrest. We used descriptive statistics and multivariable logistic regression accounting for NHAMCS’s complex survey design. The primary outcome measures were ED-based IHCA incidence rates and ED-based IHCA mortality.

Results

Over the 9-year study period, there were approximately 1,114,000 ED visits with IHCA. The proportion of IHCA visits in the entire ED population (incidence rate, 1.2 per 1,000 ED visits) appeared stable. The mean age of patients who visited the ED with IHCA was 60 years, and 65% were men. Older age, male, arrival by ambulance, and being uninsured independently predicted a higher incidence of ED-based IHCA. Approximately 51% of IHCA died in the ED, and the trend remained stable. Arrival by ambulance, nighttime, or weekend arrival, and being in the non-Northeast were independently associated with a higher mortality rate after IHCA.

Conclusion

The high burden of ED visits with IHCA persisted through 2010–2018. Additionally, ED-based IHCA survival to hospital admission remained poor. Some patients were disproportionately affected, and certain contextual factors were associated with a poorer outcome.
Palaeoglaciation in the Low Latitude, Low Elevation Tropical Andes, Northern Peru
Authors: Lee Ethan , Ross Neil , Henderson Andrew C. G. , Russell Andrew J. , Jamieson Stewart S. R. , Fabel Derek
Published: April 2022

Characterising glaciological change within the tropical Andes is important because tropical glaciers are sensitive to climate change. Our understanding of glacier dynamics and how tropical glaciers respond to global climate perturbations is poorly constrained. Studies of past glaciation in the tropical Andes have focused on locations where glaciers are still present or recently vacated cirques at high elevations. Few studies focused on lower elevation localities because it was assumed glaciers did not exist or were not as extensive. We present the first geomorphological evidence for past glaciations of the Lagunas de Las Huaringas, northern Peru, at elevations of 3,900–2,600 m a.s.l. Mapping was conducted using remotely-sensed optical imagery and a newly created high-resolution (∼2.5 m) digital elevation model (DEM). The area has abundant evidence for glaciation, including moraines, glacial cirques, hummocky terrain, glacial lineations and ice-sculpted bedrock. Two potential models for glaciation are hypothesised: 1) plateau-fed ice cap, or 2) valley glaciation. Assuming glaciers reached their maximum extent during the Local Last Glacial Maximum (LLGM), between 23.5 ± 0.5 and 21.2 ± 0.8 ka, the maximum reconstructed glacial area was 75.6 km2. A mean equilibrium line altitude (ELA) of 3,422 ± 30 m was calculated, indicating an ELA change of −1,178 ± 10 m compared to modern snowline elevation. There is an east to west ELA elevation gradient, lower in the east and higher in the west, in-line with modern day transfer of moisture. Applying lapse rates between 5.5 and 7.5°C/km provides a LLGM temperature cooling of between 6.5–8.8°C compared to present. These values are comparable to upper estimates from other studies within the northern tropical Andes and from ice-core reconstructions. The mapping of glacial geomorphology within the Lagunas de las Huaringas, evidences, for the first time, extensive glaciation in a low elevation region of northern Peru, with implications for our understanding of past climate in the sub-tropics. Observations and reconstructions support a valley, rather than ice cap glaciation. Further work is required to constrain the timing of glaciations, with evidence of moraines younger than the LLGM up-valley of maximum glacier extents. Numerical modelling will also enable an understanding of the controls of glaciation within the region.
Geochemical Characteristics and Organic Matter Provenance of Shale in the Jurassic Da’anzhai Member, Northeastern Sichuan Basin
Authors: Li Qianwen , Liu Zhongbao , Chen Feiran , Liu Guangxiang , Zhang Dianwei , Li Peng , Wang Pengwei
Published: April 2022

Rock pyrolysis, organic petrology, vitrinite reflectance, gas chromatography-mass spectrometry (GC-MS) analysis, and biomarker compound analysis were performed to comprehensively analyze the organic geochemical characteristics of the Jurassic Da’anzhai Member (J1da) shale strata in Yuanba and Puguang areas in the northeastern Sichuan Basin. Then the organic matter provenance and sedimentary environment were further analyzed. Finally, the significance of oil and gas exploration in J1da shale strata was discussed. Results show that the second section of the Da’anzhai Member (J1da2) has relatively high organic matter abundance (1.24%TOC), type Ⅱ-dominated organic matter type, which is the most favorable section of wells Y1 and T1 in the study area. The organic matter maturity and the hydrocarbon phases are quite different, which is 1.01%Ro dominated by oil generation in Puguang area, while it is 1.67%Ro dominated by gas generation in Yuanba area. Content and chromatograms of biomarkers including n-alkanes, tricyclic terpanes, C24 tetracyclic terpanes, and C27-C28-C29 regular steranes show that the organic matters of J1da shale strata derive from both terrestrial higher plants and lower aquatic organisms, with slightly differentiated mixed ratio of each sublayer. Characteristics of Pr/Ph, γ-cerane and hopanes compounds indicate that the overall depositional environment of J1da is a freshwater lacustrine environment, with saline lake deposits in local areas and intervals in the study area. The rapid changes of sedimentary environment have resulted in obvious stratification of water body, frequent interbeds, and strong heterogeneity of J1da shale strata. Comprehensive analysis shows the shale/mud microfacies in the semi-deep lake subfacies and shale/mud interbedded with siltstone and shell bank microfacies in the shallow lake subfacies are the most favorable sedimentary facies for J1da hydrocarbon enrichment. Deeper burial depth and higher maturity make for oil and gas enrichment with higher gas/oil ratio (GOR); moreover, the thicker intervals with organic-rich shale are favorable targets for geochemical evaluation.
A Novel Tracer Technique to Quantify the Lithogenic Input Flux of Trace Elements to Qinghai Lake
Authors: Zhang Pu , Pei Xuezheng , Cao Chenyang , Chen Chi , Gong Ziqin , Li Xuerou , Pang Jingya , Liang Lihua , Li Xiangzhong , Ning Youfeng , Edwards R.Lawrence
Published: April 2022

Thorium (Th) isotopes were applied to quantify the contributions of lithogenic inputs to the Qinghai Lake (QHH). Concentrations of dissolved 232Th and 230Th were measured in 59 water samples collected from Qinghai Lake and its exogenous recharge rivers. There are significant differences in the concentration of 232Th of the sampled water in QHH that confirm the input of variable lithogenic material sources. The 230Th concentrations were used to calculate a scavenging residence time for Th, which was then applied to calculate the flux of dissolved 232Th by matching the measured concentrations of dissolved 232Th. Then the 232Th content of lithogenic material was used with the solubility of Th from the preliminary particle data from the Qinghai–Qaidam district. When using a Th solubility from particles of 1%, the fluxes of lithogenic material range from 0.03 to 25.25 g/m2/yr in the surface water, consistent with the flux results of settled particles from the previous study. When a large number of exogenous recharge rivers are mixed into the northwest basin of Qinghai Lake, the 232Th content and lithogenic flux of the lake water are mainly influenced by the type and content of the particles in the Buha and Shaliu rivers. Conversely, in south basin with limited recharging rivers, the 232Th content of the lake water away from the estuary is mainly influenced by atmospheric dust. Furthermore, based on the 230Th normalization method (combining with 232Th and τTh), the Buha and Shaliu rivers located in the northwest basin contribute about 90% of the detrital flux to the lake. The lithogenic flux in the southeast lake is dominated by dust flux with a value of ∼0.109 g/m2/yr, while the higher lithogenic flux at the bottom of the lake was likely generated by accumulated sinking particulate matter and resuspension of bottom sediments in September. This study confirms the utility of long-lived Th isotopes to quantify lithogenic inputs based on the Th content of the dissolved lake water and also supply deposition resolution information for QHH sediment records with some certainty.
Microstructural and Geomechanical Study on Microbial-Carbonized Sand Using Streptomyces Microflavus for Dust Control
Authors: Yu Xiaoniu , Meng Qingxiang , Yang Yang , Zhang Wengang , Cheng Liang
Published: April 2022

Microbial carbonization based on carbon-capturing bacteria induced calcium carbonate precipitation has become a new construction material for soil improvement. This paper presents a new technique for dust control in sand usingStreptomyces microflavusinduced calcium carbonate precipitation.This kind of carbon-capturing bacteria can capture and transform CO2into carbonate then precipitate calcium carbonate crystals through the microbial carbonization process, which then acts as cementitious materials to bind sand particles. In this way, loose sand particles can be bridged and increase their hardness, consequently forming a consolidated layer for dust control. The Shore hardness of the consolidated layer usingStreptomyces microflavuscould be improved to 25 HD with a calcium carbonate content of 5.5% after 7 times of carbonization treatment. The microstructure, Shore hardness, and obtained calcium carbonate content were also compared with sand samples treated byPaenibacillus mucilaginosus.These results reveal that the consolidated sand layer usingStreptomyces microflavusis sufficient to against wind erosion or rainfall erosion and has better geomechanical performance thanPaenibacillus mucilaginosus.
Factors From Middle Childhood That Predict Academic Attainment at 15–17 Years in the UK: A Systematic Review
Authors: Williams Margiad E. , Clarkson Susan , Hastings Richard P. , Watkins Richard C. , McTague Phil , Hughes J. Carl
Published: April 2022

Success in adult life is associated with end of school academic attainment, but educational inequality is a major issue in the UK. Contextual background factors and personal attributes associated with student academic attainment have been identified in cross-sectional research. However, there has not been a systematic synthesis of these factors from longitudinal studies particularly with a focus on factors from middle childhood. The aim of this systematic review was to identify factors from middle childhood (6–12 years) that are associated with academic attainment at 15–17 years. Ninety UK studies met the inclusion criteria. Factors identified related to the student, socioeconomic, academic attainment, and the school. The quality of studies was generally rated as poor, and evidence for most factors was sparse, suggesting caution in interpretation. The middle childhood factors with the strongest evidence of association with later attainment were: prior attainment at the student level, student mental health, and gender. Generally, the results supported UK Government guidance on narrowing the education inequality gap although there was a lack of high-quality studies. The findings could be potentially useful for policymakers and schools in making decisions on effective interventions, policy choices, and funding allocations, particularly in the context of a socioecological framework. However, further research is needed in this area.

Systematic Review Registration

https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=136747, identifer: 136747.
Reservoir Computing for Temporal Data Classification Using a Dynamic Solid Electrolyte ZnO Thin Film Transistor
Authors: Gaurav Ankit , Song Xiaoyao , Manhas Sanjeev , Gilra Aditya , Vasilaki Eleni , Roy Partha , De Souza Maria Merlyne
Published: April 2022

The processing of sequential and temporal data is essential to computer vision and speech recognition, two of the most common applications of artificial intelligence (AI). Reservoir computing (RC) is a branch of AI that offers a highly efficient framework for processing temporal inputs at a low training cost compared to conventional Recurrent Neural Networks (RNNs). However, despite extensive effort, two-terminal memristor-based reservoirs have, until now, been implemented to process sequential data by reading their conductance states only once, at the end of the entire sequence. This method reduces the dimensionality, related to the number of signals from the reservoir and thereby lowers the overall performance of reservoir systems. Higher dimensionality facilitates the separation of originally inseparable inputs by reading out from a larger set of spatiotemporal features of inputs. Moreover, memristor-based reservoirs either use multiple pulse rates, fast or slow read (immediately or with a delay introduced after the end of the sequence), or excitatory pulses to enhance the dimensionality of reservoir states. This adds to the complexity of the reservoir system and reduces power efficiency. In this paper, we demonstrate the first reservoir computing system based on a dynamic three terminal solid electrolyte ZnO/Ta2O5 Thin-film Transistor fabricated at less than 100°C. The inherent nonlinearity and dynamic memory of the device lead to a rich separation property of reservoir states that results in, to our knowledge, the highest accuracy of 94.44%, using electronic charge-based system, for the classification of hand-written digits. This improvement is attributed to an increase in the dimensionality of the reservoir by reading the reservoir states after each pulse rather than at the end of the sequence. The third terminal enables a read operation in the off state, that is when no pulse is applied at the gate terminal, via a small read pulse at the drain. This fundamentally allows multiple read operations without increasing energy consumption, which is not possible in the conventional two-terminal memristor counterpart. Further, we have also shown that devices do not saturate even after multiple write pulses which demonstrates the device’s ability to process longer sequences.
Thada Is Dispensable for Female Fertility in Mice
Authors: Han Shan , Zhang Yuqing , Zheng Yukun , Liu Congcong , Jiang Yonghui , Zhao Shigang , Zhao Han
Published: April 2022

Genome-wide association studies (GWAS) have identified THADA as one of the susceptibility genes for polycystic ovary syndrome (PCOS). Single nucleotide polymorphisms (SNPs) in the THADA gene showed significant over-transmission in PCOS and strong correlations with testosterone level. However, there was insufficient evidence to verify the effect of THADA in vivo on female reproductive system. In this study, we investigated the impacts of Thada ablation on ovarian function and reproductive outcomes with knockout (KO) mice. The results showed that the Thada deletion was insufficient to affect ovarian folliculogenesis, steroidogenesis, and female fertility. Additionally, we stressed the mice with high-fat-high-sugar diet (HFHS). In this case, the KO mice still merely had a negligible impact on ovarian function. These findings indicated that Thada deficiency was dispensable for female fertility in mice, which enriched our knowledge about in vivo functions of PCOS susceptibility genes.