bluuebunny/crossref_metadata_2025 huggingface dataset:
Potential Gene Association Studies of Chemotherapy-Induced Cardiotoxicity: A Systematic Review and Meta-Analysis
Authors: Yang Xinyu , Li Guoping , Guan Manke , Bapat Aneesh , Dai Qianqian , Zhong Changming , Yang Tao , Luo Changyong , An Na , Liu Wenjing , Yang Fan , Pan Haie , Wang Pengqian , Gao Yonghong , Gong Ye , Das Saumya , Shang Hongcai , Xing Yanwei
Published: June 2021

Chemotherapy is widely used in the treatment of cancer patients, but the cardiotoxicity induced by chemotherapy is still a major concern to most clinicians. Currently, genetic methods have been used to detect patients with high risk of chemotherapy-induced cardiotoxicity (CIC), and our study evaluated the correlation between genomic variants and CIC. The systematic literature search was performed in the PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), China Biology Medicine disc (CBMdisc), the Embase database, China National Knowledge Internet (CNKI) and Wanfang database from inception until June 2020. Forty-one studies were identified that examined the relationship between genetic variations and CIC. And these studies examined 88 different genes and 154 single nucleotide polymorphisms (SNPs). Our study indicated 6 variants obviously associated with the increased risk for CIC, including CYBA rs4673 (pooled odds ratio, 1.93; 95% CI, 1.13–3.30), RAC2 rs13058338 (2.05; 1.11–3.78), CYP3A5 rs776746 (2.15; 1.00–4.62) ABCC1 rs45511401 (1.46; 1.05–2.01), ABCC2 rs8187710 (2.19; 1.38–3.48), and HER2-Ile655Val rs1136201 (2.48; 1.53–4.02). Although further studies are required to validate the diagnostic and prognostic roles of these 6 variants in predicting CIC, our study emphasizes the promising benefits of pharmacogenomic screening before chemotherapy to minimize the CIC.
Long-Term Visit-to-Visit Mean Arterial Pressure Variability and the Risk of Heart Failure and All-Cause Mortality
Authors: Liu Menghui , Chen Xiaohong , Zhang Shaozhao , Lin Yifen , Xiong Zhenyu , Zhong Xiangbin , Guo Yue , Sun Xiuting , Zhou Huimin , Xu Xingfeng , Wang Lichun , Liao Xinxue , Zhuang Xiaodong
Published: June 2021

Background: Systolic or diastolic blood pressure (BP) variability is associated with an increased risk of cardiovascular events. We assessed whether BP variability measured by mean arterial pressure (MAP) was associated with increased risk of heart failure (HF) and death in individuals with or without hypertension.

Methods: We evaluated 9,305 Atherosclerosis Risk in Communities (ARIC) study participants with or without hypertension and calculated BP variability based on MAP values from visit 1 to 4 [expressed as standard deviation (SD), average real variability (ARV), coefficient of variation (CV), and variability independent of the mean (VIM)]. Multivariate-adjusted Cox regression model and restricted cubic spline curve were used to evaluate the associations of MAP variability with all-cause mortality and HF.

Results: During a median follow-up of 16.8 years, 1,511 had an HF event and 2,903 died. Individuals in the highest quartile of VIM were both associated with a 21% higher risk of all-cause mortality [hazard ratio (HR), 1.21; 95% CI, 1.09–1.35] and HF (HR, 1.21; 95% CI, 1.04–1.39) compared with the lowest quartile of VIM. Cubic spline curves reveal that the risk of deaths and HF increased with MAP variability when it reached a higher level. Results were similar in individuals with normotension (all-cause mortality: HR, 1.30; 95% CI, 1.09–1.55; HF, HR, 1.49; 95% CI, 1.12–1.98).

Conclusions: In individuals with or without hypertension, greater visit-to-visit MAP variability was associated with a higher risk of all-cause mortality and HF, indicating that the BP variability assessed by MAP might be a potential risk factor for HF and death.
Clinical and Technical Challenges of Prosthesis–Patient Mismatch After Transcatheter Aortic Valve Implantation
Authors: Leone Pier Pasquale , Fazzari Fabio , Cannata Francesco , Sanz-Sanchez Jorge , Mangieri Antonio , Monti Lorenzo , Cozzi Ottavia , Stefanini Giulio Giuseppe , Bragato Renato , Colombo Antonio , Reimers Bernhard , Regazzoli Damiano
Published: June 2021

Prosthesis–patient mismatch (PPM) is present when the effective area of a prosthetic valve inserted into a patient is inferior to that of a normal human valve; the hemodynamic consequence of a valve too small compared with the size of the patient's body is the generation of higher than expected transprosthetic gradients. Despite evidence of increased risk of short- and long-term mortality and of structural valve degeneration in patients with PPM after surgical aortic valve replacement, its clinical impact in patients subject to transcatheter aortic valve implantation (TAVI) is yet unclear. We aim to review and update on the definition and incidence of PPM after TAVI, and its prognostic implications in the overall population and in higher-risk subgroups, such as small aortic annuli or valve-in-valve procedures. Last, we will focus on the armamentarium available in order to reduce risk of PPM when planning a TAVI procedure.
The Synergy of ADAM17-Induced Myocardial Inflammation and Metabolic Lipids Dysregulation During Acute Stress: New Pathophysiologic Insights Into Takotsubo Cardiomyopathy
Authors: Adu-Amankwaah Joseph , Adzika Gabriel Komla , Adekunle Adebayo Oluwafemi , Ndzie Noah Marie Louise , Mprah Richard , Bushi Aisha , Akhter Nazma , Xu Yaxin , Huang Fei , Chatambarara Benard , Sun Hong
Published: June 2021

Due to its reversible nature, Takotsubo cardiomyopathy (TTC) is considered an intriguing and fascinating cardiovascular disease characterized by a transient wall motion abnormality of the left ventricle, affecting more than one coronary artery territory, often in a circumferential apical distribution. Takotsubo cardiomyopathy was discovered by a Japanese cardiovascular expert and classified as acquired primary cardiomyopathy by the American Heart Association (AHA) in 1990 and 2006, respectively. Regardless of the extensive research efforts, its pathophysiology is still unclear; therefore, there are no well-established guidelines specifically for treating and managing TTC patients. Increasing evidence suggests that sympatho-adrenergic stimulation is strongly associated with the pathogenesis of this disease. Under acute stressful conditions, the hyperstimulation of beta-adrenergic receptors (β-ARs) resulting from excessive release of catecholamines induces intracellular kinases capable of phosphorylating and activating “A Disintegrin and Metalloprotease 17” (ADAM17), a type-I transmembrane protease that plays a central role in acute myocardial inflammation and metabolic lipids dysregulation which are the main hallmarks of TTC. However, our understanding of this is limited; hence this concise review provides a comprehensive insight into the key role of ADAM17 in acute myocardial inflammation and metabolic lipids dysregulation during acute stress. Also, how the synergy of ADAM17-induced acute inflammation and lipids dysregulation causes TTC is explained. Finally, potential therapeutic targets for TTC are also discussed.
Case Report: Assessing the Position of Pacemaker Leads via Transthoracic Echocardiography: Additional Value of the Subcostal En Face View
Authors: Deichl Andrea Simone , Lacour Philipp , Belyavskiy Evgeny , Pieske Burkert , Pieske-Kraigher Elisabeth , Blaschke Florian , Schneider Matthias
Published: June 2021

There is an association between presence of cardiac implantable electronic devices (CIED) and development of tricuspid regurgitation (TR). Mechanisms proposed to explain CIED-induced TR can be classified as implantation-related, lead-related, and pacing-related. Lead-related TR results from the direct interaction of the lead with the tricuspid valve (TV). The localization of the lead at the TV level directly influences the probability of subsequent development of significant TR. A transthoracic subcostal en face view of the TV can be acquired in most patients through a 90° rotation from the subcostal 4-chamber view with clear anatomic delineation of the TV and the commissures including lead position. This case-series presents three examples where the transthoracic en face view could add incremental information on the position of the pacemaker leads and on the mechanism of TR.

Conclusion: When performing transthoracic echocardiography in patients with trans-tricuspid CIED lead(s), an en face view of the TV with exact reporting of the position of the lead(s) should be included.
Accelerated Atomistic Modeling of Solid-State Battery Materials With Machine Learning
Authors: Guo Haoyue , Wang Qian , Stuke Annika , Urban Alexander , Artrith Nongnuch
Published: June 2021

Materials for solid-state batteries often exhibit complex chemical compositions, defects, and disorder, making both experimental characterization and direct modeling with first principles methods challenging. Machine learning (ML) has proven versatile for accelerating or circumventing first-principles calculations, thereby facilitating the modeling of materials properties that are otherwise hard to access. ML potentials trained on accurate first principles data enable computationally efficient linear-scaling atomistic simulations with an accuracy close to the reference method. ML-based property-prediction and inverse design techniques are powerful for the computational search for new materials. Here, we give an overview of recent methodological advancements of ML techniques for atomic-scale modeling and materials design. We review applications to materials for solid-state batteries, including electrodes, solid electrolytes, coatings, and the complex interfaces involved.
Bidirectional Crosstalk Between Hypoxia Inducible Factors and Glucocorticoid Signalling in Health and Disease
Authors: Vanderhaeghen Tineke , Beyaert Rudi , Libert Claude
Published: June 2021

Glucocorticoid-induced (GC) and hypoxia-induced transcriptional responses play an important role in tissue homeostasis and in the regulation of cellular responses to stress and inflammation. Evidence exists that there is an important crosstalk between both GC and hypoxia effects. Hypoxia is a pathophysiological condition to which cells respond quickly in order to prevent metabolic shutdown and death. The hypoxia inducible factors (HIFs) are the master regulators of oxygen homeostasis and are responsible for the ability of cells to cope with low oxygen levels. Maladaptive responses of HIFs contribute to a variety of pathological conditions including acute mountain sickness (AMS), inflammation and neonatal hypoxia-induced brain injury. Synthetic GCs which are analogous to the naturally occurring steroid hormones (cortisol in humans, corticosterone in rodents), have been used for decades as anti-inflammatory drugs for treating pathological conditions which are linked to hypoxia (i.e. asthma, ischemic injury). In this review, we investigate the crosstalk between the glucocorticoid receptor (GR), and HIFs. We discuss possible mechanisms by which GR and HIF influence one another, in vitro and in vivo, and the therapeutic effects of GCs on HIF-mediated diseases.
Transnational Municipal Networks as a Mechanism for Marine Governance Toward Climate Change Adaptation and Mitigation: Between Potential and Practice
Authors: Dumała Hanna , Łuszczuk Michał , Piwowarczyk Joanna , Zieliński Tymon
Published: June 2021

Many municipalities undertake actions individually and/or collectively, in cooperation with central administrations, regional authorities, the private sector, and other municipalities (both nationally and internationally). This paper aims to examine how they use transnational municipal networks (TMNs) as a tool for cooperation that supports marine governance in the context of climate change adaptation and mitigation. The analysis is carried out at two dimensions: spatial range (global or regional) and spatial identity (coastal or inland). Three case studies of TMNs are examined in detail: the C40 Cities Climate Leadership Group (C40); Connecting Delta Cities (CDC) and the Union of Baltic Cities (UBC). As research has shown, due to their organizational and normative limitations and a lack of maturity in ocean literacy, TMNs are not able to fully engage in all the activities related to climate change adaptation and mitigation as suggested by the UNEP. The TMNs implement both mitigation and adaptation measures, although ‘soft’ mitigation actions seem to be the most common. While the scale and innovativeness of a networks’ operation are determined by their specificity resulting from their spatial identity, the effectiveness of jointly developed strategies and actions depend heavily on the allocation of human resources and the level of commitment of the involved cities toward becoming leaders.
Temperature Significantly Regulates Gene Expressions of Vertebrae Chondrocytes and Osteoblasts in Juvenile Golden Pompano (Trachinotus ovatus)
Authors: Han Mingyang , Fu Zhengyi , Yang Rui , Qin Jian G. , Ma Zhenhua
Published: June 2021

To elucidate the possible molecular reaction of vertebral fusion in juvenile golden pompano at high temperature, we examined the changes in growth, vertebral fusion incidence, histological differences and transcription levels of genes related to bone development in juvenile golden pompano at 27 and 33°C for 30 days, respectively. The growth rate of juvenile fish was faster when the water temperature was 33°C, but the incidence of vertebral fusion was higher. Prolonged high water temperature reduced the osteogenic layer in the growth zone of the vertebral endplate and the elastic externa. The endplate growth areas of the fused vertebrae were transformed into cartilage tissue, which was then remodeled into bone. The intervertebral notochord tissue was transformed into bone and the intervertebral space disappeared. In normal phenotypes of vertebrae, short-term high temperature could promote the expression of genes related to cartilage differentiation and maturation, as well as genes related to osteoblastic differentiation. With the increase of culture time, the expression of genes related to cartilage and osteogenesis development was inhibited. In fused vertebrae, cartilage proliferation was enhanced, osteogenic differentiation was inhibited, and matrix mineralization may be enhanced. Genes associated with the development of chondrocytes and osteoblasts in the vertebrae of juvenileTrachinotus ovatuswere significantly regulated by temperature and time. The results may contribute to further understanding of the occurrence of vertebral fusion at high temperature.
Genotype, Nursery Design, and Depth Influence the Growth of Acropora cervicornis Fragments
Authors: Maneval Paul , Jacoby Charles A. , Harris Holden E. , Frazer Thomas K.
Published: June 2021

Growing fragments of corals in nurseries and outplanting them to supplement declining natural populations have gained significant traction worldwide. In the Caribbean, for example, this approach provides colonies of Acropora cervicornis with minimal impacts to existing wild colonies. Given the impetus to scale up production to augment limited natural recovery, managers and researchers should consider how the design and location of the nurseries affect the growth of different genotypes of corals and the effort required for maintenance. To elucidate such influences, we grew fragments of different genotypes (five varieties) on differing structures (trees and frames) at two depths (6–8 and 16–18 m). The sum of the lengths of all branches or total linear extensions (TLEs) and accumulation of biofouling were measured over 198 days from May to December 2016 to assess the growth of fragments and the effort required to maintain nurseries. TLEs for all fragments increased linearly throughout the incubation period. Mean daily incremental growth rates varied among the genotypes, with one genotype growing significantly faster than all others, two genotypes growing at intermediate rates, and two genotypes growing more slowly. Mean daily incremental growth rates were higher for all genotypes suspended from vertical frames at both sites, and mean daily incremental growth rates were higher for all fragments held on both types of nurseries in deeper water. If linear growth continued, a fragment of the fastest growing genotype held on a frame in deeper water was estimated to increase the sum of the length of all its branches by an average of 88 cm y–1, which was over two times higher than the estimated mean annual growth rate for a fragment of the slowest growing genotype held on a tree in shallow water. Nurseries in deeper water had significantly less biofouling and appeared to be buffered against daily fluctuations in temperature. Overall, the results demonstrated that increased production and reduced maintenance can result from considering the genotype of fragments to be cultured and the design and location of nurseries.
Hadal Mud Dragons: First Insight Into the Diversity of Kinorhyncha From the Atacama Trench
Authors: Grzelak Katarzyna , Zeppilli Daniela , Shimabukuro Mauricio , Sørensen Martin V.
Published: June 2021

Deep-sea trenches are one of the last frontiers for deep-sea exploration and represent a large reservoir of undiscovered biodiversity. This applies in particular to organisms belonging to smaller-size classes, such as meiofauna. Among different meiofauna taxa, kinorhynchs represent a large gap in our knowledge about global marine biodiversity in general, but primarily in extreme deep-sea environments. Out of the more than 300 known mud dragon species, only a single species has ever been described from hadal depths (> 6000 m), i.e., Echinoderes ultraabyssalis from the Kuril-Kamchatka Trench. The results presented in this paper are based on material collected during a research expedition in 2018 investigating the Atacama Trench environment. We provide a first overview and comparison of the diversity and abundance of mud dragons in the Atacama Trench, the adjacent abyssal plain and continental slope off Chile. The study revealed six species of Echinoderes. Of these, Echinoderes mamaqucha sp. nov. is described as a new species and morphological data of three undescribed species are given. Because of the low number of available specimens, we provide only a brief description of these three species and comparison with their morphologically closest congeners, but formal descriptions are not given. Moreover, Echinoderes juliae and Echinoderes pterus were also recovered. Echinoderes juliae was described from the abyssal plain off Oregon and along the continental rise off California, at 2702 to 3679 m depth. Echinoderes pterus is known from the high Arctic, the North Atlantic, and the Mediterranean Sea, and has also been reported to show a wide bathymetric distribution, from 675 to 4403 m. Interestingly, E. mamaqucha sp. nov. dominated at the trench stations and it reached its highest abundance at the deepest station, at 8085 m water depth. The only other single individual that was found in the Atacama Trench was Echinoderes sp.1. The remaining four species were all found at the abyssal and slope stations. The obtained results seem to confirm previous hypotheses about geographic isolation of deep-sea trenches and relatively low connectivity with other habitats, reflected by limited diversity of sediment dwelling fauna, particularly in the deepest parts of trenches.
Growth, Immunity, and Transcriptome Response to Dietary Wnt/β-Catenin Pathway Activator TWS119 in Penaeus vannamei
Authors: Hou Cuihong , Song Shougang , Zhu Lulu , Shi Lili , Tan Beiping , Zhang Shuang
Published: June 2021

Wnt/β-catenin signalling plays an essential role in the immunity of Penaeus vannamei. In this study, the effects of dietary Wnt/β-catenin pathway activator TWS119 on the growth, immunity, and transcriptome response in P. vannamei were investigated. Penaeus vannamei were fed diets with added TWS119 at doses of 0 (T0), 0.25 (T0.25), 1 (T1), 4 (T4), 16 (T16), or 64 mg·kg−1 (T64), respectively. LvGSK3β activity was effectively inhibited in P. vannamei given TWS119. The growth of P. vannamei in the T16 group was significantly improved when compared with the control group. After Vibrio parahaemolyticus infection, the survival rates (SRs) of P. vannamei in all experimental groups except the T64 group were significantly higher than in the T0 group. Compared with the control group, the immune enzymes’ activities in the serum of P. vannamei increased in all the experimental groups, while the malondialdehyde (MDA) contents decreased. Transcriptome analysis identified 5,073 differentially expressed genes (DEGs) for P. vannamei in the T0 and T16 groups. Most of the DEGs are involved in the ribosome pathway, endocytosis, glycerophospholipid metabolism, Wnt signalling, and FoxO =signalling pathways. The majority of the DEGs were from the ribosome pathway, which is also the most significantly enriched pathway. The study confirmed that the growth and immunity status of P. vannamei could improve by increasing dietary TWS119, which probably regulates the activity of the Wnt/β-catenin pathway and may be closely related to ribosome function and energy metabolism.
Magneto-Sensitive Rubber in a Vehicle Application Context – Exploring the Potential
Authors: Wang Bochao , Hu Tao , Shen Longjiang , Li Jun , Xu Zhenbang , Kari Leif , Gong Xinglong
Published: June 2021

The application of magneto-sensitive (MS) rubber in a vehicle vibration control area is likely to be expected. This conclusion is based on the following two reasons: the maturity of fabrication of MS rubber which meets the application requirement and the feasibility of the constitutive model of MS rubber that accurately reflects its mechanical performance. Compared with the traditional rubber, small ferromagnetic particles are embedded in the elastomer of MS rubber, leading to a change of mechanical properties when an external magnetic field is applied. Therefore, devices with MS rubber, can be viewed as a semi-active actuator. In this study, MS rubber with a relative high increase in the magneto-induced modulus is fabricated and characterized. Furthermore, a one-dimensional constitutive model to depict the magnetic field-, frequency-, and strain amplitude-dependent dynamic modulus of MS rubber is applied. Finally, simulations of a MS rubber semi-active suspension under a bump and a random ground excitation with different control strategies on a quarter vehicle model are conducted to illustrate the feasibility of the MS rubber in the vehicle vibration control application context.
Sodium-Glucose Co-transporter-2 Inhibitors and Nephroprotection in Diabetic Patients: More Than a Challenge
Authors: Provenzano Michele , Pelle Maria Chiara , Zaffina Isabella , Tassone Bruno , Pujia Roberta , Ricchio Marco , Serra Raffaele , Sciacqua Angela , Michael Ashour , Andreucci Michele , Arturi Franco
Published: June 2021

Diabetic nephropathy is the most common cause of end-stage renal disease worldwide. Control of blood glucose and blood pressure (BP) reduces the risk of developing this complication, but once diabetic nephropathy is established, it is then only possible to slow its progression. Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are a novel class of oral hypoglycemic agents that increase urinary glucose excretion by suppressing glucose reabsorption at the renal proximal tubule. SGLT2is lower glycated hemoglobin (HbA1c) without increasing the risk of hypoglycemia, induce weight loss and improve various metabolic parameters including BP, lipid profile, albuminuria and uric acid. Several clinical trials have shown that SGLT2is (empagliflozin, dapagliflozin canagliflozin, and ertugliflozin) improve cardiovascular and renal outcomes and mortality in patients with type 2 diabetes. Effects of SGLT2is on the kidney can be explained by multiple pathways. SGLT2is may improve renal oxygenation and intra-renal inflammation thereby slowing the progression of kidney function decline. Additionally, SGLT2is are associated with a reduction in glomerular hyperfiltration, an effect which is mediated by the increase in natriuresis, the re-activation of tubule-glomerular feedback and independent of glycemic control. In this review, we will focus on renal results of major cardiovascular and renal outcome trials and we will describe direct and indirect mechanisms through which SGLT2is confer renal protection.
Comparison of Mean and Centroid of Surgically Induced Astigmatism After Standard Cataract Surgery
Authors: Kamiya Kazutaka , Iijima Kei , Ando Wakako , Shoji Nobuyuki
Published: June 2021

Purpose: To compare the arithmetic mean of surgically induced astigmatism (M-SIA) and the centroid of surgically induced astigmatism (C-SIA) after standard cataract surgery.

Methods: We retrospectively examined 200 eyes of 100 consecutive patients undergoing bilateral cataract surgery through a 2.8 mm temporal clear corneal incision. We quantitatively measured the magnitude and axis of corneal astigmatism preoperatively and 3 months postoperatively using an automated keratometer (TONOREFF-II, Nidek). We assessed the M-SIA, the C-SIA, and the double angle plots for the display of the individual SIA distributions.

Results: For bilateral data analysis, the magnitude of corneal astigmatism significantly increased from 0.66 ± 0.39 D preoperatively to 0.74 ± 0.46 D postoperatively (paired t-test, p = 0.012). The M-SIA was 0.50 ± 0.36 D. On the other hand, the C-SIA was 0.18 ± 0.60 D at an axis of 97°. For unilateral analysis, we obtained similar outcomes between the right and left eye groups.

Conclusions: According to our experience, standard cataract surgery induces the M-SIA by approximately 0.5 D. The magnitude of the C-SIA largely decreased to approximately 40% of the M-SIA, and the direction of the C-SIA showed a tendency toward with-the-rule astigmatism. It should be noted that the M-SIA was considerably different from the C-SIA, especially when selecting the appropriate toric IOL model and power.
Macrophage Activation Syndrome in Pediatric Systemic Lupus Erythematosus: A Systematic Review of the Diagnostic Aspects
Authors: Abdirakhmanova Altynay , Sazonov Vitaliy , Mukusheva Zaure , Assylbekova Maykesh , Abdukhakimova Diyora , Poddighe Dimitri
Published: June 2021

Macrophage Activation Syndrome (MAS) is a very severe complication of different rheumatic diseases, including pediatric Systemic Lupus Erythematosus (pSLE). MAS is not considered as a frequent complication of pSLE; however, its occurrence could be under-estimated and the diagnosis can be challenging. In order to address this issue, we performed a systematic review of the available medical literature, aiming to retrieve all those papers providing diagnostic (clinical/laboratory) data on patients with pSLE-related MAS, in individual or aggregated form. The selected case reports and series provided a pool of 46 patients, accounting for 48 episodes of MAS in total. We re-analyzed these patients in light of the diagnostic criteria for MAS validated in systemic Juvenile Idiopathic Arthritis (sJIA) patients and the preliminary diagnostic criteria for MAS in pSLE, respectively. Five clinical studies were also selected and used to support this analysis. This systematic review confirms that MAS diagnosis in pSLE patients is characterized by several diagnostic challenges, which could lead to delayed diagnosis and/or under-estimation of this complication. Specific criteria should be considered to diagnose MAS in different rheumatic diseases; as regards pSLE, the aforementioned preliminary criteria for MAS in pSLE seem to perform better than the sJIA-related MAS criteria, because of a lower ferritin cut-off.
Myocardial Flow Reserve Measurement During CZT-SPECT Perfusion Imaging for Coronary Artery Disease Screening: Correlation With Clinical Findings and Invasive Coronary Angiography—The CFR-OR Study
Authors: Bailly Matthieu , Thibault Frédérique , Courtehoux Maxime , Metrard Gilles , Angoulvant Denis , Ribeiro Maria Joao
Published: June 2021

Purpose: The aim of this study was to assess the results of cadmium zinc telluride (CZT)- single-photon emission computed tomography (SPECT) myocardial flow reserve (MFR) in coronary artery disease (CAD) screening regarding clinical risk and its correlation to invasive coronary angiography (ICA).

Methods: A total of 137 patients (61 male and 76 female) referred for CAD screening myocardial perfusion imaging (MPI) between November 2018 and April 2020 were included in the CFR-OR prospective trial. The 10-year risk of cardiovascular death according to the European Society of Cardiology (SCORE) was calculated. SPECT 1-day 99mTc-tetrofosmin protocol was acquired on CZT cardiac-dedicated pinhole cameras. Low-dose thoracic CT was used for coronary calcium score (CCS) evaluation. ICA, when performed within 3 months, was also analyzed.

Results: Mean SCORE and mean global MFR were, respectively, 4 ± 3.1% and 2.50 ± 0.74; 34 patients had impaired CFR (using a threshold of 2). There was a significant inverse correlation between MFR and SCORE (p = 0.006), gender (p = 0.019), and number of cardiovascular risk factors (p = 0.01). MFR was significantly reduced in patients with CCS above 1 (p = 0.01). No significant correlation was found between MFR and individual cardiovascular risk factors (dyslipidemia, hypertension, diabetes, or family history of CAD). A total of 23 patients underwent ICA. Global MFR SPECT sensitivity and specificity were 83.3 and 100 %, respectively, with an area under the curve of 0.94.

Conclusion: Adding MFR to SPECT MPI for CAD screening on CZT camera may contribute to high-risk patient identification and enhance diagnostic performances. MFR could help physician decision to perform ICA.
Investigation of Plasmids Among Clinical Staphylococcus aureus and Staphylococcus haemolyticus Isolates From Egypt
Authors: Mores Carine R. , Montelongo Cesar , Putonti Catherine , Wolfe Alan J. , Abouelfetouh Alaa
Published: June 2021

Staphylococci can cause a wide array of infections that can be life threatening. These infections become more deadly when the isolates are antibiotic resistant and thus harder to treat. Many resistance determinants are plasmid-mediated; however, staphylococcal plasmids have not yet been fully characterized. In particular, plasmids and their contributions to antibiotic resistance have not been investigated within the Arab states, where antibiotic use is not universally regulated. Here, we characterized the putative plasmid content among 56 Staphylococcus aureus and 10 Staphylococcus haemolyticus clinical isolates from Alexandria, Egypt. Putative plasmid sequences were detected in over half of our collection. In total, we identified 72 putative plasmid sequences in 27 S. aureus and 1 S. haemolyticus isolates. While these isolates typically carried one or two plasmids, we identified one isolate—S. aureus AA53—with 11 putative plasmids. The plasmid sequences most frequently encoded a Rep_1, RepL, or PriCT_1 type replication protein. As expected, antibiotic resistance genes were widespread among the identified plasmid sequences. Related plasmids were identified amongst our clinical isolates; homologous plasmids present in multiple isolates clustered into 11 groups based upon sequence similarity. Plasmids from the same cluster often shared antibiotic resistance genes, including blaZ, which is associated with β-lactam resistance. Our analyses suggest that plasmids are a key factor in the pathology and epidemiology of S. aureus in Egypt. A better characterization of plasmids and the role they contribute to the success of Staphylococci as pathogens will guide the design of effective control strategies to limit their spread.
Sex-Related Overactivation of NLRP3 Inflammasome Increases Lethality of the Male COVID-19 Patients
Authors: Zhang Hongliang , Tang Yujie , Tao Jinhui
Published: June 2021

The COVID-19 pandemic, caused by SARS-CoV-2 infection, remains a dramatic threat to human life and economic well-being worldwide. Significant heterogeneity in the severity of disease was observed for patients infected with SARS-CoV-2 ranging from asymptomatic to severe cases. Moreover, male patients had a higher probability of suffering from high mortality and severe symptoms linked to cytokine storm and excessive inflammation. The NLRP3 inflammasome is presumably critical to this process. Sex differences may directly affect the activation of NLRP3 inflammasome, impacting the severity of observed COVID-19 symptoms. To elucidate the potential mechanisms underlying sex based differences in NLRP3 activation during SARS-CoV-2 infection, this review summarizes the reported mechanisms and identifies potential therapeutic targets.
A Staphylococcus aureus clpX Mutant Used as a Unique Screening Tool to Identify Cell Wall Synthesis Inhibitors that Reverse β-Lactam Resistance in MRSA
Authors: Bæk Kristoffer T. , Jensen Camilla , Farha Maya A. , Nielsen Tobias K. , Paknejadi Ervin , Mebus Viktor H. , Vestergaard Martin , Brown Eric D. , Frees Dorte
Published: June 2021

Staphylococcus aureus is a leading cause of bacterial infections world-wide. Staphylococcal infections are preferentially treated with β-lactam antibiotics, however, methicillin-resistant S. aureus (MRSA) strains have acquired resistance to this superior class of antibiotics. We have developed a growth-based, high-throughput screening approach that directly identifies cell wall synthesis inhibitors capable of reversing β-lactam resistance in MRSA. The screen is based on the finding that S. aureus mutants lacking the ClpX chaperone grow very poorly at 30°C unless specific steps in teichoic acid synthesis or penicillin binding protein (PBP) activity are inhibited. This property allowed us to exploit the S. aureus clpX mutant as a unique screening tool to rapidly identify biologically active compounds that target cell wall synthesis. We tested a library of ∼50,000 small chemical compounds and searched for compounds that inhibited growth of the wild type while stimulating growth of the clpX mutant. Fifty-eight compounds met these screening criteria, and preliminary tests of 10 compounds identified seven compounds that reverse β-lactam resistance of MRSA as expected for inhibitors of teichoic acid synthesis. The hit compounds are therefore promising candidates for further development as novel combination agents to restore β-lactam efficacy against MRSA.
A Microstructural Analysis of 2D Halide Perovskites: Stability and Functionality
Authors: Bhattacharya Susmita , Chandra Goutam Kumar , Predeep P.
Published: June 2021

Recent observations have demonstrated that the photoelectric conversion properties of perovskite materials are intimately related to the presence of superlattice structures and other unusual nanoscale features in them. The low-dimensional or mixed-dimensional halide perovskite families are found to be more efficient materials for device application than three-dimensional halide perovskites. The emergence of perovskite solar cells has revolutionized the solar cell industry because of their flexible architecture and rapidly increased efficiency. Tuning the dielectric constant and charge separation are the main objectives in designing a photovoltaic device that can be explored using the two-dimensional perovskite family. Thus, revisiting the fundamental properties of perovskite crystals could reveal further possibilities for recognizing these improvements toward device functionality. In this context, this review discusses the material properties of two-dimensional halide perovskites and related optoelectronic devices, aiming particularly for solar cell applications.
The IntelliCage System: A Review of Its Utility as a Novel Behavioral Platform for a Rodent Model of Substance Use Disorder
Authors: Iman Ismail Nurul , Yusof Nurul Aiman Mohd , Talib Ummi Nasrah , Ahmad Nur Aimi Zawami , Norazit Anwar , Kumar Jaya , Mehat Muhammad Zulfadli , Jayabalan Nanthini , Muthuraju Sangu , Stefaniuk Marzena , Kaczmarek Leszek , Muzaimi Mustapha
Published: June 2021

The use of animal models for substance use disorder (SUD) has made an important contribution in the investigation of the behavioral and molecular mechanisms underlying substance abuse and addiction. Here, we review a novel and comprehensive behavioral platform to characterize addiction-like traits in rodents using a fully automated learning system, the IntelliCage. This system simultaneously captures the basic behavioral navigation, reward preference, and aversion, as well as the multi-dimensional complex behaviors and cognitive functions of group-housed rodents. It can reliably capture and track locomotor and cognitive pattern alterations associated with the development of substance addiction. Thus, the IntelliCage learning system offers a potentially efficient, flexible, and sensitive tool for the high-throughput screening of the rodent SUD model.
Neurodegenerative Disease Risk in Carriers of Autosomal Recessive Disease
Authors: Vieira Sophia R. L. , Morris Huw R.
Published: June 2021

Genetics has driven significant discoveries in the field of neurodegenerative diseases (NDDs). An emerging theme in neurodegeneration warrants an urgent and comprehensive update: that carrier status of early-onset autosomal recessive (AR) disease, typically considered benign, is associated with an increased risk of a spectrum of late-onset NDDs. Glucosylceramidase beta (GBA1) gene mutations, responsible for the AR lysosomal storage disorder Gaucher disease, are a prominent example of this principle, having been identified as an important genetic risk factor for Parkinson disease. Genetic analyses have revealed further examples, notably GRN, TREM2, EIF2AK3, and several other LSD and mitochondria function genes. In this Review, we discuss the evidence supporting the strikingly distinct allele-dependent clinical phenotypes observed in carriers of such gene mutations and its impact on the wider field of neurodegeneration.
Oxaliplatin Depolarizes the IB4– Dorsal Root Ganglion Neurons to Drive the Development of Neuropathic Pain Through TRPM8 in Mice
Authors: Wu Bin , Su Xiaolin , Zhang Wentong , Zhang Yi-Hong , Feng Xinghua , Ji Yong-Hua , Tan Zhi-Yong
Published: June 2021

Use of chemotherapy drug oxaliplatin is associated with painful peripheral neuropathy that is exacerbated by cold. Remodeling of ion channels including TRP channels in dorsal root ganglion (DRG) neurons contribute to the sensory hypersensitivity following oxaliplatin treatment in animal models. However, it has not been studied if TRP channels and membrane depolarization of DRG neurons serve as the initial ionic/membrane drives (such as within an hour) that contribute to the development of oxaliplatin-induced neuropathic pain. In the current study, we studied in mice (1) in vitro acute effects of oxaliplatin on the membrane excitability of IB4+ and IB4– subpopulations of DRG neurons using a perforated patch clamping, (2) the preventative effects of a membrane-hyperpolarizing drug retigabine on oxaliplatin-induced sensory hypersensitivity, and (3) the preventative effects of TRP channel antagonists on the oxaliplatin-induced membrane hyperexcitability and sensory hypersensitivity. We found (1) IB4+ and IB4– subpopulations of small DRG neurons displayed previously undiscovered, substantially different membrane excitability, (2) oxaliplatin selectively depolarized IB4– DRG neurons, (3) pretreatment of retigabine largely prevented oxaliplatin-induced sensory hypersensitivity, (4) antagonists of TRPA1 and TRPM8 channels prevented oxaliplatin-induced membrane depolarization, and (5) the antagonist of TRPM8 largely prevented oxaliplatin-induced sensory hypersensitivity. These results suggest that oxaliplatin depolarizes IB4– neurons through TRPM8 channels to drive the development of neuropathic pain and targeting the initial drives of TRPM8 and/or membrane depolarization may prevent oxaliplatin-induce neuropathic pain.
Dynamically Optimizing Network Structure Based on Synaptic Pruning in the Brain
Authors: Zhao Feifei , Zeng Yi
Published: June 2021

Most neural networks need to predefine the network architecture empirically, which may cause over-fitting or under-fitting. Besides, a large number of parameters in a fully connected network leads to the prohibitively expensive computational cost and storage overhead, which makes the model hard to be deployed on mobile devices. Dynamically optimizing the network architecture by pruning unused synapses is a promising technique for solving this problem. Most existing pruning methods focus on reducing the redundancy of deep convolutional neural networks by pruning unimportant filters or weights, at the cost of accuracy drop. In this paper, we propose an effective brain-inspired synaptic pruning method to dynamically modulate the network architecture and simultaneously improve network performance. The proposed model is biologically inspired as it dynamically eliminates redundant connections based on the synaptic pruning rules used during the brain's development. Connections are pruned if they are not activated or less activated multiple times consecutively. Extensive experiments demonstrate the effectiveness of our method on classification tasks of different complexity with the MNIST, Fashion MNIST, and CIFAR-10 datasets. Experimental results reveal that even for a compact network, the proposed method can also remove up to 59–90% of the connections, with relative improvement in learning speed and accuracy.
Hydrogen Sulfide Inhibits Enzymatic Browning of Fresh-Cut Chinese Water Chestnuts
Authors: Dou Yuan , Chang Chunmei , Wang Jing , Cai Zhipeng , Zhang Wei , Du Huaying , Gan Zengyu , Wan Chunpeng , Chen Jinyin , Zhu Liqin
Published: June 2021

This work investigates the role of hydrogen sulfide (H2S) in the browning and regulating the antioxidant defensive system in fresh-cut Chinese water chestnuts. The samples were fumigated with 0, 10, and 15 μl L−1 of H2S and stored at 10°C for 8 days. The results indicated that the H2S treatment significantly inhibited the browning of fresh-cut Chinese water chestnuts, reduced superoxide anion (O2·-) production rate and H2O2 content accumulation, promoted the increase of total phenol content, and enhanced activities of catalase (CAT), superoxide dismutase (SOD), ascorbate peroxidase (APX), and glutathione reductase (GR) (P < 0.05). On the other hand, phenylalanine ammonia lyase (PAL), polyphenol oxidase (PPO), and peroxidase (POD) activities remained at a low level in the H2S treatment (P < 0.05). This result suggested that H2S treatment might be a promising approach to inhibit browning and prolong the shelf life by enhancing oxidation resistance and inhibiting browning enzyme activity of fresh-cut Chinese water chestnuts during storage. Among them, the 15 μl L−1 H2S treatment had the best effect on fresh-cut Chinese water chestnuts.
Omega-3 Fatty Acids and Vitamin D Decrease Plasma T-Tau, GFAP, and UCH-L1 in Experimental Traumatic Brain Injury
Authors: Scrimgeour Angus G. , Condlin Michelle L. , Loban Andrei , DeMar James C.
Published: June 2021

Traumatic brain injury (TBI) results in neuronal, axonal and glial damage. Interventions targeting neuroinflammation to enhance recovery from TBI are needed. Exercise is known to improve cognitive function in TBI patients. Omega-3 fatty acids and vitamin D reportedly reduce inflammation, and in combination, might improve TBI outcomes. This study examined how an anti-inflammatory diet affected plasma TBI biomarkers, voluntary exercise and behaviors following exposure to mild TBI (mTBI). Adult, male rats were individually housed in cages fitted with running wheels and daily running distance was recorded throughout the study. A modified weight drop method induced mTBI, and during 30 days post-injury, rats were fed diets supplemented with omega-3 fatty acids and vitamin D3 (AIDM diet), or non-supplemented AIN-76A diets (CON diet). Behavioral tests were periodically conducted to assess functional deficits. Plasma levels of Total tau (T-tau), glial fibrillary acidic protein (GFAP), ubiquitin c-terminal hydrolase L1 (UCH-L1) and neurofilament light chain (NF-L) were measured at 48 h, 14 days, and 30 days post-injury. Fatty acid composition of food, plasma, and brain tissues was determined. In rats exposed to mTBI, NF-L levels were significantly elevated at 48 h post-injury (P < 0.005), and decreased to levels seen in uninjured rats by 14 days post-injury. T-tau, GFAP, and UCH-L1 plasma levels did not change at 48 h or 14 days post-injury. However, at 30 days post-injury, T-tau, GFAP and UCH-L1 all significantly increased in rats exposed to mTBI and fed CON diets (P < 0.005), but not in rats fed AIDM diets. Behavioral tests conducted post-injury showed that exercise counteracted cognitive deficits associated with mTBI. The AIDM diets significantly increased docosahexaenoic acid levels in plasma and brain tissue (P < 0.05), and in serum levels of vitamin D (P < 0.05). The temporal response of the four injury biomarkers examined is consistent with studies by others demonstrating acute and chronic neural tissue damage following exposure to TBI. The anti-inflammatory diet significantly altered the temporal profiles of plasma T-tau, GFAP, and UCH-L1 following mTBI. Voluntary exercise protected against mTBI-induced cognitive deficits, but had no impact on plasma levels of neurotrauma biomarkers. Thus, the prophylactic effect of exercise, when combined with an anti-inflammatory diet, may facilitate recovery in patients with mTBI.
Association of Vitamin D, Zinc and Selenium Related Genetic Variants With COVID-19 Disease Severity
Authors: Kotur Nikola , Skakic Anita , Klaassen Kristel , Gasic Vladimir , Zukic Branka , Skodric-Trifunovic Vesna , Stjepanovic Mihailo , Zivkovic Zorica , Ostojic Olivera , Stevanovic Goran , Lavadinovic Lidija , Pavlovic Sonja , Stankovic Biljana
Published: June 2021

Background: COVID-19 pandemic has proved to be an unrelenting health threat for more than a year now. The emerging amount of data indicates that vitamin D, zinc and selenium could be important for clinical presentation of COVID-19. Here, we investigated association of genetic variants related to the altered level and bioavailability of vitamin D, zinc and selenium with clinical severity of COVID-19.

Methods: We analyzed variants in genes significant for the status of vitamin D (DHCR7/NADSYN1 rs12785878, GC rs2282679, CYP2R1 rs10741657, and VDR rs2228570), zinc (PPCDC rs2120019) and selenium (DMGDH rs17823744) in 120 Serbian adult and pediatric COVID-19 patients using allelic discrimination. Furthermore, we carried out comparative population genetic analysis among European and other worldwide populations to investigate variation in allelic frequencies of selected variants.

Results: Study showed that DHCR7/NADSYN rs12785878 and CYP2R1 rs10741657 variants were associated with severe COVID-19 in adults (p = 0.03, p = 0.017, respectively); carriers of DHCR7/NADSYN TG+GG and CYP2R1 GG genotypes had 0.21 and 5.9 the odds for developing severe disease, OR 0.21 (0.05–0.9) and OR 5.9 (1.4–25.2), respectively. There were no associations between selected genetic variants and disease severity in pediatric patients. Comparative population genetic analysis revealed that Serbian population had the lowest frequency of CYP2R1 rs10741657 G allele compared to other non-Finish Europeans (0.58 compared to 0.69 and 0.66 in Spanish and Italian population, respectively), suggesting that other populations should also investigate the relationship of CYP2R1 variant and the COVID-19 disease course.

Conclusion: The results of the study indicated that vitamin D related genetic variants were implicated in severe COVID-19 in adults. This could direct prevention strategies based on population specific nutrigenetic profiles.