bluuebunny/crossref_metadata_2025 huggingface dataset:
In Vitro Determination of Antimicrobial and Hypoglycemic Activities of Mikania cordata (Asteraceae) Leaf Extracts
Authors: Jayatilake Pavithra L. , Munasinghe Helani
Published: November 2020

Infectious diseases and diabetes mellitus are counted responsible for a substantial amount of mortality among the human population. The current study was performed to detect the antimicrobial activities and hypoglycemic potential of Mikania cordata (Asteraceae) leaves extracted into aqueous media and several organic solvents (ethyl acetate and methanol). The ethyl acetate extract of Mikania cordata (MEA) leaves was observed to possess significantly (

p
≤
0.05

) greater antimicrobial capabilities (susceptible against Bacillus cereus ATCC 11778 and Staphylococcus aureus ATCC 25923) when compared with that of the methanol (MME) and aqueous extracts (MDW) which were assessed based on Kirby-Bauer disk diffusion assay. The minimum inhibitory concentration of MEA (against B. cereus, S. aureus, and Escherichia coli ATCC 25922) and MME (against B. cereus, S. aureus, E. coli, and Candida albicans ATCC 10231) lies in a similar range of 1.13 > MIC>0.56 mg/ml. In the present study, a single compound (from MEA) of Rf value 0.64 was isolated by thin-layer chromatography (TLC) that was responsible for the zone of inhibition against B. cereus (20.3 ± 0.3 mm). The results of this study also depicted the antihyperglycemic properties of M. cordata leaves which followed the same trend as the commercial drug Metformin in a glucose concentration-independent manner when tested in a glucose uptake assay by yeast cells. Therefore, it is evident that Mikania cordata is a reservoir of useful bioactive compounds which with further research will be paving the path for drug commercialization. This is the first record of TLC-based isolation of antimicrobial compounds of M. cordata and analysis of the hypoglycemic properties of M. cordata leaves.
Determination of Methomyl Residues in Bohe by Ultrahigh-Performance Liquid Chromatography-Tandem Mass Spectrometry (UPLC-MS)
Authors: Zheng Yao , Naa Adoley Addotey Tracy , Fateh Benkhelifa , Wu Wei , Hu Gengdong , Qiu Liping , Chen Jiazhang
Published: November 2020

The aim of this work is to investigate the presence of methomyl pesticide residue and the rate of disappearance in mint cultivated in the aquaponics system based on the application of UPLC-MS to establish a safety time interval before crop harvesting. Results showed that an effective and sensitive method based on UPLC-MS has been used for the determination of methomyl pesticide residues in mint. The initial residue level was much higher in roots (79.52 μg/kg), and it can be decreased to 16.73 (after 15 days) μg/kg and 3.31 (20 days) μg/kg, while the least was detected on the mix leaves and stems (44.54 μg/kg), and it can be decreased to 15.35 (after 20 days). In our case, we suggest that a safety interval in the range of 15–20 days should be allowed after the detection of methomyl in water, and the concentration of methomyl was lower than the acceptable daily intake (ADI) of the China Food and Drug Administration (CFDA) (20 μg/kg).
High-Frequency Synchronization Improves Firing Rate Contrast and Information Transmission Efficiency in E/I Neuronal Networks
Authors: Han Fang , Wang Zhijie , Fan Hong , Zhang Yaopeng
Published: November 2020

High-frequency synchronization has been found in many real neural systems and is confirmed by excitatory/inhibitory (E/I) network models. However, the functional role played by it remains elusive. In this paper, it is found that high-frequency synchronization in E/I neuronal networks could improve the firing rate contrast of the whole network, no matter if the network is fully connected or randomly connected, with noise or without noise. It is also found that the global firing rate contrast enhancement can prevent the number of spikes of the neurons measured within the limited time window from being confused by noise, thereby enhancing the information encoding efficiency (quantified by entropy theory here) of the neuronal system. The mechanism of firing rate contrast enhancement is also investigated. Our work implies a possible functional role in information transmission of high-frequency synchronization in neuronal systems.
Characterization of Contact‐Type Defects in Mortar Using a Nonlinear Ultrasonic Method
Authors: Nie Zhichao , Wang Kui , Zhao Mingjie , Sun Xiao
Published: November 2020

Second harmonic generation (SHG) is one of the common techniques in the nonlinear ultrasonic test. The contact‐type defects play an important role in material damage, which are hard to be detected. The traditional nonlinear parameter β used to evaluate the micro damage in material is derived from the classical stress‐strain relation, which is more suitable for the anharmonicity of crystal rather than the contact‐type defects. Recently, the theoretical model based on the bilinear stiffness law was derived, and the validity and applicability need to be further studied. For this purpose, by the numerical method, the contact interface in mortar is characterized based on the damage indicator γ. The relation between the excitation voltage and γ is obtained. Moreover, the effects of the crack length and orientation on the damage indicator γ are also obtained. The experimental method is also used to characterize the contact interface in mortar. Combining with the existing work, the results obtained in this article are discussed, and further conclusions can be drawn. The conclusions in this article provide potential of quantitative detection of the contact interface and quality evaluation of bonding layers in materials.
A New Methodology for the Multilayer Tight Oil Reservoir Water Injection Efficiency Evaluation and Real-Time Optimization
Authors: Cao Lin , Xiu Jianlong , Cheng Hongjie , Wang Hui , Xie Shujian , Zhao Hui , Sheng Guanglong
Published: November 2020

It is important to determine the reasonable injection and production rates in the development of multilayer tight oil reservoir with water flooding treatment. Based on the INSIM (interconnection-based numeric simulation model), a connected network model, a new method is designed to evaluate the water injection efficiency of different layers in water flooding reservoirs and to optimize the injection-production system to produce more oil. Based on the types of sedimentary facies and corresponding injection-production data, the interwell connections are divided into four major categories (middle channel, channel edge, middle channel bar, and channel bar edge) and twelve subclasses. This classification standard of interwell connections could help to significantly improve the accuracy of judging the dominant flow path without constructing a complicated geological model. The interaction of interwells such as injection-production correlation and water injection efficiency could be revealed by simulating the production performance and computing the layer dividing coefficient and well dividing coefficient. A numerical example is used to validate this method by comparing results from FrontSim and this method, and the computational efficiency of this method is several dozen times faster than that of the traditional numerical simulation. This method is applied to quickly optimize the production schedule of a tight oil reservoir with the water flooding treatment, that is, the water injection rate of multilayer reservoirs could be optimized subtly by the injection efficiency of different layers, and the target of producing more oil with lower water cut could be achieved.
Establishment of the Causal Agent(s) of Spike Shedding and Stem Wilting of Pepper (Piper nigrum L.) in Morogoro District, Tanzania
Authors: Shango Abdul J. , Majubwa Ramadhani O. , Maerere Amon P.
Published: November 2020

Pepper (Piper nigrum L.) serves as a source of income to smallholder spice farmers in Morogoro district of Tanzania. Recently, spike shedding and stem wilting of pepper plants were reported to cause about 30% yield loss of the crop. This study was undertaken to identify the causal agent(s) of the problems. Three pepper gardens in each of the four hamlets (Nyange, Doga, Tandai, and Lukenge) in Tandai village (Kinole ward) were surveyed, and plant tissue and soil samples were collected for laboratory analysis. An experiment was laid out in a randomized complete block design with three replications. Pepper cultivars, Babu kubwa, Babu ndogo, Babu kati, and Ismailia grown in the study area, were used as treatments for evaluation of the prevalence of spike shedding and stem wilting. Treatments mean separation was conducted based on Duncan’s multiple range test atp=0.05. Regression (R2) and simple correlation (r) analyses between stem wilting (incidence and severity) and termite pest infestation were performed. The identified pathogen in most of the soil and plant tissue samples was Fusarium oxysporum. The nutrients, N, P, Mg, and Cu, concentration in soil and leaf samples was below the optimal ranges. Termite attacks were significantly high in some farmer’s gardens where up to 50.5% of the pepper plants was damaged. Hence, a significant positive correlation was observed between termite pest infestation in gardens and both incidence (r = 0.881, R2 = 0.74,p<0.001) and severity of stem wilting (r = 0.918, R2 = 0.84,p<0.001) of pepper plants. Most of the termite attacks and damages (70%) were observed on pepper plants supported on silver oak, unlike those trained on Jatropha. A higher percentage of undeveloped berries (36%) and intermediate-size berries (34%) was recorded on cultivars “Babu kati” and “Babu kubwa,” respectively. Multiple factors have been associated to be the causes of spike shedding and stem wilting of pepper, which could be used to develop appropriate control solutions useful to farmers. Confirmation of F. oxysporum pathogenicity is recommended. A comprehensive study is suggested on the repellent or lethal activities of Jatropha against F. oxysporum and termites. Furthermore, studies through field experiments are needed to generate site-specific soil nutrient improvement recommendations and design an integrated approach to control F. oxysporum and termites and to determine existing alternative host plants for these pests.
Amelioration of Rheumatoid Arthritis by Anacardium occidentale via Inhibition of Collagenase and Lysosomal Enzymes
Authors: Naz Rabiya , Ahmed Zaheer , Shahzad Muhammad , Shabbir Arham , Kamal Faiza
Published: November 2020

Anacardium occidentale (cashew) has been used in the traditional system of medicine for curing many inflammatory disorders. The present study investigates the antiarthritic effects of cashew leaves extract using the rat model of FCA‐induced rheumatoid arthritis. Arthritic rats were treated with 100 and 200 mg/kg b.w. ethanolic extract of cashew leaves. Animals were sacrificed at day 23, and before sacrificing the animals, gross pathological changes were observed. Histopathology of ankle joint was evaluated with hematoxylin and eosin staining, whereas the serum levels of C‐reactive protein (CRP) were evaluated by the agglutination method. Inflammatory cells and other hematological parameters were assessed by employing an automated hemocytometer and chemistry analyzer. Rheumatoid factor (Rf) and lysosomal enzymes levels were determined in blood. Results indicated that A. occidentale significantly decreased the CPR levels, macroscopic arthritic score, and rheumatoid factor as compared to the diseased group. Histopathological evaluation showed significant attenuation in bone erosion, joint inflammation, and pannus formation by plant extract. Treatment with A. occidentale significantly suppressed the levels of acid phosphatase, β‐galactosidase, β‐glucuronidase, N‐acetylglucosaminidase, and collagenase. Moreover, A. occidentale significantly raised the HB levels and RBCs counts which were found depleted in the diseased group. The raised counts of total leukocytes, platelets, neutrophils, lymphocytes, and monocytes were also significantly decreased by treatment with plant extract. Comparative analysis showed that higher dose of A. occidentale demonstrated superior amelioration of rheumatoid arthritis as compared to low dose. In conclusion, A. occidentale possesses significant antiarthritic potential, which may be attributed to the suppression of lysosomal enzymes and collagenase levels.
Robust Interacting Multiple Model Unscented Particle Filter for Navigation
Authors: Xue Li , Han Yulan , Na Chunning
Published: November 2020

In order to solve the problems of particle degradation and difficulty in selecting importance density function in particle filter algorithm, a robust interacting multiple model unscented particle filter algorithm is presented, which is based on the advantages of interacting multiple model and particle filter algorithms. This algorithm can use the unscented transformation to get the particles that contain the latest measurement information of each model and calculate the robust equivalent weight function. This robust factor is designed to adjust the estimation and variance, and the important distribution function adaptively obtained is closer to the true distribution. Then, the particles weights can be flexibly adjusted in real time by using Euclidean distance to improve the computational efficiency during the resampling process. In addition, this filter process can comprehensively describe the uncertainty of the statistics characteristic of observation noise between different models. The diversity of available particles is increased, and the filter precision is improved. The proposed algorithm is applied to the SINS/GPS integrated navigation system, and the simulation analysis results demonstrate that the algorithm can effectively improve the filter performance and the calculation precision in positioning of integrated navigation system; thus, it provides a new method for nonlinear model filter.
Managing Nonagenarians with Acute Myocardial Infarction: Invasive versus Conservative Treatment
Authors: Lee Jooho , Seo Kyoung-Woo , Park Jin-Sun , Yang Hyoung-Mo , Lim Hong-Seok , Choi Byoung-Joo , Choi So-Yeon , Yoon Myeong-Ho , Hwang Gyo-Seung , Tahk Seung-Jae , Shin Joon-Han
Published: November 2020

Background. Limited data are available to support an invasive treatment strategy in nonagenarians with acute myocardial infarction (AMI). We aimed to investigate whether percutaneous coronary intervention (PCI) is beneficial in this frail population. Methods. We retrospectively analyzed 41 nonagenarians with AMI (both ST-segment-elevation and non-ST-segment-elevation MI) between 2006 and 2015 in a single center. We assessed 30-day and one-year mortality rates according to the treatment strategy. Results. Among study subjects, 24 (59%) were treated with PCI (PCI group) and 17 (41%) were treated with conservative management (medical treatment group) per the clinician’s discretion. The median follow-up duration was 30 months (0–74 months). Thirty-day mortality was lower in the PCI group than in the medical treatment group (17% vs. 65%;

P
<
0.001

). One-year mortality was also lower in the PCI group than in the medical treatment group (21% vs. 76%;

P
<
0.001

). The PCI group presented a 73% decreased risk of death (adjusted hazard ratio: 0.269; 95% confidence interval: 0.126–0.571;

P
<
0.001

). In the Killip class 1 through 3 subgroups (n = 36), 30-day and one-year mortality were still higher among those in the medical treatment group (13% vs. 54% at 30 days;

P
<
0.001

and 17% vs. 69% at one year;

P
<
0.001

). Landmark analysis after 30 days revealed no significant difference in the cumulative mortality rate between the two groups, indicating that the mortality difference was mainly determined within the first 30 days after AMI. Conclusion. Mortality after AMI was decreased in correlation with the invasive strategy relative to the conservative strategy, even in nonagenarians. Regardless of age, PCI should be considered in AMI patients. However, large-scale randomized controlled trials are needed to support our conclusion.
A Comparison Investigation on Cylinder Test in Different Ambient Media by Experiment and Numerical Simulation
Authors: Zhang Fan , Shen Fei , Li Biaobiao , Yuan Baohui , Li Bing
Published: November 2020

When the detonation reaction occurs after the charge in the warhead is ignited, the propagation of the detonation wave and the expansion of the detonation product will interact with the wrapped metallic shell and cause the shell material to accelerate, extremely deform, and eventually rupture, which is a typical strong fluid-structure interaction problem. In this paper, a comparison investigation on a cylinder test in different ambient media was implemented by experiment and numerical simulation, respectively. In the experimental test, the attention was paid to discussing the differences of the accelerating process of the cylinder metal wall, the expansion modes, and the fragment shape of the cylinder due to the medium with different shock wave impedance which surrounds the cylinder shell. For the numerical simulation, a coupling scheme of a meshless method and finite element method called the coupled finite element material point method was used to reproduce the cylinder expansion problem driven by explosive sliding detonation where the interaction between the cylinder wall and the explosive/detonation product is enforced by using a point-to-surface contact scheme to accurately achieve contact and separation between material particles and finite elements. Lastly, the macroscopic and microscopic states of the cylinder failure were compared and discussed for further discussion.
Ecological Evaluation of Industrial Parks Using a Comprehensive DEA and Inverted-DEA Model
Authors: Zhang Bingjiang , Guo Jinling , Wen Zheng , Li Zhaoyao , Wang Ning
Published: November 2020

Data envelopment analysis (DEA) and inverted data envelopment analysis (inverted-DEA) are used so that the desirable and undesirable outputs of decision-making units (DMUs) exist simultaneously. We developed a new approach based on the concept of utilizing both DEA and inverted-DEA to enhance the discrimination power of DMUs with undesirable outputs. DMUs are ranked by the Z-score method and classified based on the efficiency scores of DEA and inverted-DEA. Then, the characteristics of the DMUs are analyzed based on the classification result. This paper performs an efficiency evaluation of 21 industrial parks in China in 2017 using this new approach. The overall evaluation results indicate that the proposed new approach increases the discrimination ability in this empirical study.
Turnover Modulates the Need for a Cost of Resistance in Adaptive Therapy
Authors: Strobl Maximilian A.R. , West Jeffrey , Viossat Yannick , Damaghi Mehdi , Robertson-Tessi Mark , Brown Joel S. , Gatenby Robert A. , Maini Philip K. , Anderson Alexander R.A.
Published: November 2020

Adaptive therapy seeks to exploit intratumoral competition to avoid, or at least delay, the emergence of therapy resistance in cancer. Motivated by promising results in prostate cancer, there is growing interest in extending this approach to other neoplasms. As such, it is urgent to understand the characteristics of a cancer that determine whether or not it will respond well to adaptive therapy. A plausible candidate for such a selection criterion is the fitness cost of resistance. In this article, we study a general, but simple, mathematical model to investigate whether the presence of a cost is necessary for adaptive therapy to extend the time to progression beyond that of a standard-of-care continuous therapy. Tumor cells were divided into sensitive and resistant populations and we model their competition using a system of two ordinary differential equations based on the Lotka–Volterra model. For tumors close to their environmental carrying capacity, a cost was not required. However, for tumors growing far from carrying capacity, a cost may be required to see meaningful gains. Notably, it is important to consider cell turnover in the tumor, and we discuss its role in modulating the impact of a resistance cost. To conclude, we present evidence for the predicted cost–turnover interplay in data from 67 patients with prostate cancer undergoing intermittent androgen deprivation therapy. Our work helps to clarify under which circumstances adaptive therapy may be beneficial and suggests that turnover may play an unexpectedly important role in the decision-making process.

Significance:

Tumor cell turnover modulates the speed of selection against drug resistance by amplifying the effects of competition and resistance costs; as such, turnover is an important factor in resistance management via adaptive therapy.

See related commentary by Strobl et al., p. 811
Frizzled-7 Identifies Platinum-Tolerant Ovarian Cancer Cells Susceptible to Ferroptosis
Authors: Wang Yinu , Zhao Guangyuan , Condello Salvatore , Huang Hao , Cardenas Horacio , Tanner Edward J. , Wei JianJun , Ji Yanrong , Li Junjie , Tan Yuying , Davuluri Ramana V. , Peter Marcus E. , Cheng Ji-Xin , Matei Daniela
Published: November 2020

Defining traits of platinum-tolerant cancer cells could expose new treatment vulnerabilities. Here, new markers associated with platinum-tolerant cells and tumors were identified using in vitro and in vivo ovarian cancer models treated repetitively with carboplatin and validated in human specimens. Platinum-tolerant cells and tumors were enriched in ALDH+ cells, formed more spheroids, and expressed increased levels of stemness-related transcription factors compared with parental cells. Additionally, platinum-tolerant cells and tumors exhibited expression of the Wnt receptor Frizzled-7 (FZD7). Knockdown of FZD7 improved sensitivity to platinum, decreased spheroid formation, and delayed tumor initiation. The molecular signature distinguishing FZD7+ from FZD7− cells included epithelial-to-mesenchymal (EMT), stemness, and oxidative phosphorylation-enriched gene sets. Overexpression of FZD7 activated the oncogenic factor Tp63, driving upregulation of glutathione metabolism pathways, including glutathione peroxidase 4 (GPX4), which protected cells from chemotherapy-induced oxidative stress. FZD7+ platinum-tolerant ovarian cancer cells were more sensitive and underwent ferroptosis after treatment with GPX4 inhibitors. FZD7, Tp63, and glutathione metabolism gene sets were strongly correlated in the ovarian cancer Tumor Cancer Genome Atlas (TCGA) database and in residual human ovarian cancer specimens after chemotherapy. These results support the existence of a platinum-tolerant cell population with partial cancer stem cell features, characterized by FZD7 expression and dependent on the FZD7–β-catenin–Tp63–GPX4 pathway for survival. The findings reveal a novel therapeutic vulnerability of platinum-tolerant cancer cells and provide new insight into a potential “persister cancer cell” phenotype.

Significance:

Frizzled-7 marks platinum-tolerant cancer cells harboring stemness features and altered glutathione metabolism that depend on GPX4 for survival and are highly susceptible to ferroptosis.
AXL Inhibition Induces DNA Damage and Replication Stress in Non–Small Cell Lung Cancer Cells and Promotes Sensitivity to ATR Inhibitors
Authors: Ramkumar Kavya , Stewart C. Allison , Cargill Kasey R. , Della Corte Carminia M. , Wang Qi , Shen Li , Diao Lixia , Cardnell Robert J. , Peng David H. , Rodriguez B. Leticia , Fan You-Hong , Heymach John V. , Wang Jing , Gay Carl M. , Gibbons Don L. , Byers Lauren A.
Published: November 2020

AXL, a TAM (TYRO3, AXL, and MERTK) family receptor tyrosine kinase, is increasingly being recognized as a key determinant of resistance to targeted therapies, as well as chemotherapy and radiation in non–small cell lung cancer (NSCLC) and other cancers. We further show here that high levels of AXL and epithelial-to-mesenchymal transition were frequently expressed in subsets of both treatment-naïve and treatment-relapsed NSCLC. Previously, we and others have demonstrated a role for AXL in mediating DNA damage response (DDR), as well as resistance to inhibition of WEE1, a replication stress response kinase. Here, we show that BGB324 (bemcentinib), a selective small-molecule AXL inhibitor, caused DNA damage and induced replication stress, indicated by ATR/CHK1 phosphorylation, more significantly in TP53-deficient NSCLC cell lines. Similar effects were also observed in large-cell neuroendocrine carcinoma (LCNEC) cell lines. High AXL protein levels were also associated with resistance to ATR inhibition. Combined inhibition of AXL and ATR significantly decreased cell proliferation of NSCLC and LCNEC cell lines. Mechanistically, combined inhibition of AXL and ATR significantly increased RPA32 hyperphosphorylation and DNA double-strand breaks and induced markers of mitotic catastrophe. Notably, NSCLC cell lines with low levels of SLFN11, a known predictive biomarker for platinum and PARP inhibitor sensitivity, were more sensitive to AXL/ATR cotargeting. These findings demonstrate a novel and unexpected role for AXL in replication stress tolerance, with potential therapeutic implications.

Implications:

These findings demonstrate that the combination of AXL and ATR inhibitors could be a promising therapeutic combination for NSCLC, LCNEC, and other cancers.
5-Azacytidine Transiently Restores Dysregulated Erythroid Differentiation Gene Expression in TET2-Deficient Erythroleukemia Cells
Authors: Reilly Brian M. , Luger Timothy , Park Soo , Lio Chan-Wang Jerry , González-Avalos Edahí , Wheeler Emily C. , Lee Minjung , Williamson Laura , Tanaka Tiffany , Diep Dinh , Zhang Kun , Huang Yun , Rao Anjana , Bejar Rafael
Published: November 2020

DNA methyltransferase inhibitors (DNMTI) like 5-Azacytidine (5-Aza) are the only disease-modifying drugs approved for the treatment of higher-risk myelodysplastic syndromes (MDS), however less than 50% of patients respond, and there are no predictors of response with clinical utility. Somatic mutations in the DNA methylation regulating gene tet-methylcytosine dioxygenase 2 (TET2) are associated with response to DNMTIs, however the mechanisms responsible for this association remain unknown. Using bisulfite padlock probes, mRNA sequencing, and hydroxymethylcytosine pull-down sequencing at several time points throughout 5-Aza treatment, we show that TET2 loss particularly influences DNA methylation (5mC) and hydroxymethylation (5hmC) patterns at erythroid gene enhancers and is associated with downregulation of erythroid gene expression in the human erythroleukemia cell line TF-1. 5-Aza disproportionately induces expression of these down-regulated genes in TET2KO cells and this effect is related to dynamic 5mC changes at erythroid gene enhancers after 5-Aza exposure. We identified differences in remethylation kinetics after 5-Aza exposure for several types of genomic regulatory elements, with distal enhancers exhibiting longer-lasting 5mC changes than other regions. This work highlights the role of 5mC and 5hmC dynamics at distal enhancers in regulating the expression of differentiation-associated gene signatures, and sheds light on how 5-Aza may be more effective in patients harboring TET2 mutations.

Implications:

TET2 loss in erythroleukemia cells induces hypermethylation and impaired expression of erythroid differentiation genes which can be specifically counteracted by 5-Azacytidine, providing a potential mechanism for the increased efficacy of 5-Aza in TET2-mutant patients with MDS.

Visual Overview:

http://mcr.aacrjournals.org/content/molcanres/19/3/451/F1.large.jpg.
Spine Metastasis of Thymic Carcinoma in a Pediatric Patient: A Case Report and Comprehensive Literature Review
Authors: Oktay Kadir , Guzel Ebru , Baykara Okay , Akbaba Mevlana , Sari Ibrahim , Guzel Aslan
Published: November 2020

Introduction: Thymic carcinoma metastases of the spinal column are very rare, especially in pediatric patients. To our knowledge, this is the first such pediatric case in the literature. Case Presentation: We report the case of a 14-year-old male patient with T12 and L1 metastases of thymic carcinoma. He had history of thymectomy and intrathoracic tumor resection 7 months previously. The patient’s neurological condition deteriorated; therefore, tumor resection and decompression of the spinal canal were performed. He underwent instrumentation and fusion procedures to prevent spinal instability. Conclusion: The main purpose of the treatment is gross total resection of the thymic carcinoma. However, adjuvant methods such as radiotherapy and chemotherapy should be added to the treatment protocol in patients who have higher stage diseases or those in whom total tumor resection cannot be achieved.
Intereye Comparison of Focal Lamina Cribrosa Defect in Normal-Tension Glaucoma Patients with Asymmetric Visual Field Loss
Authors: Sun Yunxiao , Guo Yiqin , Xie Yuan , Cao Kai , Liu Xiangxiang , Yang Yiquan , Shi Yan , Fan Sujie , Wang Huaizhou , Wang Ningli
Published: November 2020

Introduction: To evaluate the association of focal lamina cribrosa (LC) defect with asymmetric visual field (VF) loss in normal-tension glaucoma (NTG) through intereye comparisons. Methods: Paired eyes were divided into better and worse eyes according to the mean deviation (MD), and ocular parameters were compared between them. Furthermore, patients in the asymmetric group were classified as subgroup A (one eye with LC defect and the fellow one without), subgroup B (both eyes without LC defect), and subgroup C (both eyes with LC defect). Generalized estimation equation approach was used to evaluate the association between ocular parameters and asymmetric VF. Results: A total of 140 eyes of 70 NTG patients were included in the asymmetric group. LC defects were more common in better eyes than that in worse eyes (27/70 [38.57%] vs. 10/70 [14.29%], p = 0.001), and all eyes with LC defect had myopia. Multivariate analysis revealed that the presence of LC defect was significantly associated with better eyes in the asymmetric group (odds ratio, 0.27; p = 0.001). For subgroup A, eyes with LC defects exhibited lower peak IOP (p = 0.011) and lower mean IOP (p = 0.018) than the fellow eyes without. In addition, longer AL (p = 0.025) and larger tilt ratio (p = 0.032) were found in eyes with LC defects. For subgroup B without LC defects, larger tilt ratio was shown to be a risk factor for VF loss (odds ratio, 6.13; p = 0.001). There was no significant difference of binocular parameters except for MD (p < 0.001) in subgroup C. Conclusions: LC defects in myopia were suggested to be associated with better eyes in NTG with asymmetric VF loss. However, in patients without LC defect, larger tilt ratio was a risk factor for VF defect. There might be different pathological mechanisms in asymmetric VF loss for different NTG subtypes.
Call to Action: Structural Racism as a Fundamental Driver of Health Disparities: A Presidential Advisory From the American Heart Association
Authors: Churchwell Keith , Elkind Mitchell S.V. , Benjamin Regina M. , Carson April P. , Chang Edward K. , Lawrence Willie , Mills Andrew , Odom Tanya M. , Rodriguez Carlos J. , Rodriguez Fatima , Sanchez Eduardo , Sharrief Anjail Z. , Sims Mario , Williams Olajide ,   On behalf of the American Heart Association
Published: November 2020

Structural racism has been and remains a fundamental cause of persistent health disparities in the United States. The coronavirus disease 2019 (COVID-19) pandemic and the police killings of George Floyd, Breonna Taylor, and multiple others have been reminders that structural racism persists and restricts the opportunities for long, healthy lives of Black Americans and other historically disenfranchised groups. The American Heart Association has previously published statements addressing cardiovascular and cerebrovascular risk and disparities among racial and ethnic groups in the United States, but these statements have not adequately recognized structural racism as a fundamental cause of poor health and disparities in cardiovascular disease. This presidential advisory reviews the historical context, current state, and potential solutions to address structural racism in our country. Several principles emerge from our review: racism persists; racism is experienced; and the task of dismantling racism must belong to all of society. It cannot be accomplished by affected individuals alone. The path forward requires our commitment to transforming the conditions of historically marginalized communities, improving the quality of housing and neighborhood environments of these populations, advocating for policies that eliminate inequities in access to economic opportunities, quality education, and health care, and enhancing allyship among racial and ethnic groups. Future research on racism must be accelerated and should investigate the joint effects of multiple domains of racism (structural, interpersonal, cultural, anti-Black). The American Heart Association must look internally to correct its own shortcomings and advance antiracist policies and practices regarding science, public and professional education, and advocacy. With this advisory, the American Heart Association declares its unequivocal support of antiracist principles.
Balloon Angioplasty for Native Aortic Coarctation in 3- to 12-Month-Old Infants
Authors: Sandoval Juan Pablo , Kang Sok-Leng , Lee Kyong-Jin , Benson Lee , Asoh Kentaro , Chaturvedi Rajiv R.
Published: November 2020

Background:

Balloon angioplasty for native coarctation of the aorta (CoA) is successful in children and adults but in neonates results in frequent restenosis. The efficacy of balloon angioplasty for native CoA during infancy beyond the neonatal period was examined in infants aged 3 to 12 months of age.

Methods:

A retrospective review of 68 infants who underwent balloon angioplasty for native CoA. 95% CI are in parentheses.

Results:

Procedural age was (mean±SD) 6±3.4 months and weight was 7±1.8 kg. Balloon angioplasty produced a large decrease in both the noninvasive arm-to-leg blood pressure gradient (41.2±18.7 to 5.6±9.6 mm Hg) and the invasive peak systolic pressure gradient (34±12 to 11±9 mm Hg). Balloon angioplasty increased the CoA diameter from 2.7±1 mm to 4.6±1.2 mm. One patient was lost to follow-up. A catheter reintervention was required in 11.8% and surgery in 10.3%. The hazard of reintervention was highest early. Median freedom from reintervention was 89% (95% CI, 80%–96%) at 1 year, 83% (95% CI, 73%–92%) at 5 years, and 81% (95% CI, 69%–90%) at 10 years. Femoral artery thrombosis was documented in 6 (9%) infants without any long-term consequence. One patient developed a small aortic aneurysm late and has not required treatment. A robust estimate of the frequency of aortic aneurysms remains to be determined as the majority of subjects have not had cross-sectional imaging.

Conclusions:

Balloon angioplasty of native CoA is effective and safe in infants aged 3 to 12 months with outcomes comparable to those in older children and adults. Catheter reinterventions can avoid the need for surgery in most patients.
Circuit Determinants of Ventricular Tachycardia Cycle Length
Authors: Nishimura Takuro , Upadhyay Gaurav A. , Aziz Zaid A. , Beaser Andrew D. , Shatz Dalise Y. , Nayak Hemal M. , Tung Roderick
Published: November 2020

Background:

Fast ventricular tachycardias (VTs) have historically been attributed to shorter path lengths with smaller reentrant circuit dimensions in animal models. The relationship between the dimensions of the reentrant VT circuit and tachycardia cycle length (TCL) has not been examined in humans. This study aimed to analyze the determinants of the rate of human VT with comparison of circuit dimensions and conduction velocity (CV) across a wide range of both stable and unstable VTs delineated by high-resolution mapping.

Methods:

Fifty-four VTs with complete circuit delineation (>90% TCL) by high-resolution multielectrode mapping were analyzed in 49 patients (men, 88%; age, 65 years [58–71 years]; nonischemic, 47%). Fast VT was defined as TCL <333 milliseconds (rate >180 bpm). Unstable VT was defined by hemodynamic deterioration with an intrinsic mean arterial pressure <60 mm Hg during a sustained episode.

Results:

The median TCL of VT was 365 milliseconds (306–443 milliseconds), and 24 fast VTs were characterized. A wide range of CVs was observed within the entrance (0.03–0.55 m/s), common pathway (0.03–0.77 m/s), exit (0.03–0.53 m/s), and outer loop (0.17–1.13 m/s). There were no significant differences in the median dimensions of the isthmus and path length between fast and slow VTs and between unstable and stable VTs. The outer loop CV was the only circuit component that correlated with TCL in both ischemic cardiomyopathy (
r
=−0.5,
P
=0.006) and nonischemic cardiomyopathy (
r
=−0.45,
P
=0.028). The duration of the longest diastolic electrogram was inversely correlated with the dimensions of common pathway (length:
r
=−0.46,
P
=0.001, width:
r
=−0.3,
P
=0.047) and predictive of rapid VT termination by a single radiofrequency application (
r
=−0.41,
P
=0.023).

Conclusions:

Because of a wide spectrum of CV observed within the reentrant path during human VT, the dimensions of the circuit were not predictive of VT cycle length. For the first time, we demonstrate that the CV of the outer loop, rather than isthmus, is the principal determinant of the rate of VT. The size of the circuit was similar between fast and slow VTs and between unstable and stable VTs. Long, continuous electrograms were indicative of spatially confined isthmus dimensions, confirmed by rapid termination of VT during radiofrequency delivery.
Early Determinants of Childhood Blood Pressure at the Age of 6 Years: The GECKO Drenthe and ABCD Study Birth Cohorts
Authors: Xie Tian , Falahi Fahimeh , Schmidt‐Ott Tabea , Vrijkotte Tanja G. M. , Corpeleijn Eva , Snieder Harold
Published: November 2020

Background

There is still uncertainty about the nature and relative impact of early determinants on childhood blood pressure. This study explored determinants of blood pressure at the age of 6 years in 2 Dutch birth cohorts.

Methods and Results

Results of hierarchical multiple linear regression analyses in GECKO (Groningen Expert Center for Kids With Obesity) Drenthe study (n=1613) were replicated in ABCD (Amsterdam Born Children and Their Development) study (n=2052). All analyses were adjusted for child's age, sex, height, and body mass index (BMI), and maternal education and subsequently performed in the combined sample. No associations were found between maternal smoking during pregnancy and childhood blood pressure. In the total sample, maternal prepregnancy BMI was positively associated with systolic blood pressure (SBP) (β [95% CI], 0.09 [0.02–0.16] mm Hg) and diastolic blood pressure (β [95% CI], 0.11 [0.04–0.17] mm Hg). Children of women with hypertension had higher SBP (β [95% CI], 0.98 [0.17–1.79] mm Hg). Birth weight standardized for gestational age was inversely associated with SBP (β [95% CI], −6.93 [−9.25 to −4.61] mm Hg) and diastolic blood pressure (β [95% CI], −3.65 [−5.70 to −1.61] mm Hg). Longer gestational age was associated with lower SBP (β [95% CI] per week, −0.25 [−0.42 to −0.08] mm Hg). Breastfeeding for 1 to 3 months was associated with lower SBP (β [95% CI], −0.96 [−1.82 to −0.09] mm Hg) compared with no or <1 month of breastfeeding. Early BMI gain from the age of 2 to 6 years was positively associated with SBP (β [95% CI], 0.41 [0.08–0.74] mm Hg) and diastolic blood pressure (β [95% CI], 0.37 [0.07–0.66] mm Hg), but no effect modification by birth weight was found.

Conclusions

Higher maternal prepregnancy BMI, maternal hypertension, a relatively lower birth weight for gestational age, shorter gestational age, limited duration of breastfeeding, and more rapid early BMI gain contribute to higher childhood blood pressure at the age of 6 years.
Mechanistic Phase II Clinical Trial of Metformin in Pulmonary Arterial Hypertension
Authors: Brittain Evan L. , Niswender Kevin , Agrawal Vineet , Chen Xinping , Fan Run , Pugh Meredith E. , Rice Todd W. , Robbins Ivan M. , Song Haocan , Thompson Christopher , Ye Fei , Yu Chang , Zhu He , West James , Newman John H. , Hemnes Anna R.
Published: November 2020

Background

Metabolic dysfunction is highly prevalent in pulmonary arterial hypertension (PAH) and likely contributes to both pulmonary vascular disease and right ventricular (RV) failure in part because of increased oxidant stress. Currently, there is no cure for PAH and human studies of metabolic interventions, generally well tolerated in other diseases, are limited in PAH. Metformin is a commonly used oral antidiabetic that decreases gluconeogenesis, increases fatty acid oxidation, and reduces oxidant stress and thus may be relevant to PAH.

Methods and Results

We performed a single‐center, open‐label 8‐week phase II trial of up to 2 g/day of metformin in patients with idiopathic or heritable PAH with the co‐primary end points of safety, including development of lactic acidosis and study withdrawal, and plasma oxidant stress markers. Exploratory end points included RV function via echocardiography, plasma metabolomic analysis performed before and after metformin therapy, and RV triglyceride content by magnetic resonance spectroscopy in a subset of 9 patients. We enrolled 20 patients; 19/20 reached the target dose and all completed the study protocol. There was no clinically significant lactic acidosis or change in oxidant stress markers. Metformin did not change 6‐minute walk distance but did significantly improve RV fractional area change (23±8% to 26±6%,
P
=0.02), though other echocardiographic parameters were unchanged. RV triglyceride content decreased in 8/9 patients (3.2±1.8% to 1.6±1.4%,
P
=0.015). In an exploratory metabolomic analysis, plasma metabolomic correlates of ≥50% reduction in RV lipid included dihydroxybutyrate, acetylputrescine, hydroxystearate, and glucuronate (
P
<0.05 for all). In the entire cohort, lipid metabolites were among the most changed by metformin.

Conclusions

Metformin therapy was safe and well tolerated in patients with PAH in this single‐arm, open‐label phase II study. Exploratory analyses suggest that metformin may be associated with improved RV fractional area change and, in a subset of patients, reduced RV triglyceride content that correlated with altered lipid and glucose metabolism markers.

Registration

URL:
http://www.clinicaltrials.gov
; Unique identifier: NCT01884051.
Recognizing Cardiovascular Risk After Preeclampsia: The P4 Study
Authors: Brown Mark A. , Roberts Lynne , Hoffman Anna , Henry Amanda , Mangos George , O’Sullivan Anthony , Pettit Franziska , Youssef George , Xu Lily , Davis Gregory K.
Published: November 2020

Background

There is increased risk of hypertension, early cardiovascular disease, and premature mortality in women who have had preeclampsia. This study was undertaken to determine the upper limit of normal blood pressure (BP) 6 months postpartum and the frequency of women with prior preeclampsia who had BP above these limits, as part of the P4 (Post‐Partum Physiology, Psychology and Pediatric) follow‐up study.

Methods and Results

BP was measured by sphygmomanometer, 24‐hour ambulatory BP monitoring, and non‐invasive central BP at 6 months postpartum in 302 women who had normotensive pregnancy and 90 who had preeclampsia. The upper limit of normal BP (mean+2 SD) for women with normotensive pregnancy was 122/79 mm Hg for routine BP, 115/81 mm Hg for central BP, and 121/78 mm Hg for 24‐hour ambulatory BP monitoring. Traditional normal values detected only 3% of women who had preeclampsia as having high BP 6 months postpartum whereas these new values detected between 13% and 19%. Women with preeclampsia had greater body mass index (27.8 versus 25.0,
P
<0.001) and left ventricular wall thickness but similar augmentation index. They also had lower high‐density lipoprotein (59±15 versus 65±16 mg/dL,
P
=0.002), higher triglycerides (77±51 versus 61±35 mg/dL,
P
=0.005), and higher homeostatic model assessment score (2.1±1.8 versus 1.3±1.9,
P
<0.001).

Conclusions

Clinicians wishing to detect high BP in these women should be aware of the lower than usual upper limit of normal for this young cohort and where possible should use 24‐hour ambulatory BP monitoring to detect these changes. This may define a subgroup of women who had preeclampsia for whom targeted BP lowering therapy would be successful.

Registration

URL:
https://anzctr.org.au/Trial/Registration/TrialReview.aspx?id=365295&isReview=true
; Unique identifier: ACTRN12613001260718.
Why Socrates’ Legs Didn’t Run Off to Megara
Authors: Wasmuth Ellisif
Published: November 2020

I argue that the arguments presented in Socrates’ dialogue with the personified Laws of the Crito are arguments Socrates endorses and relies upon when deciding to remain in prison. They do not, however, entail blind obedience to every court verdict, nor do they provide necessary and sufficient conditions for resolving every dilemma of civil disobedience. Indeed, lacking definitional knowledge of justice, we should not expect Socrates to be able to offer such conditions. Instead, the Laws present an argument that is sufficient for resolving Socrates’ specific dilemma, showing us how Socrates can deliberate and act despite his lack of knowledge.
Duces caecorum: On Two Recent Translations of Wyclif
Authors: Thakkar Mark
Published: November 2020

Two recent publications have greatly increased the amount of Wyclif available in translation: the Trialogus, translated by Stephen Lahey, and a thematic anthology translated by Stephen Penn. This review article documents the failings that make these translations worse than useless. A post mortem leads the author to claim that the publication of these volumes, the first of which has already been warmly received, is a sign of a gathering crisis in medieval studies, and one that we should take steps to avert.
Crustacean zooplankton communities, mixotrophic cililates, and optical properties in North Patagonian lakes, investigated by remote sensing
Authors: De los Ríos-Escalante Patricio , Woelfl Stefan , Acevedo Patricio , Castro Manuel
Published: November 2020

North Patagonian lakes are characterized by their oligotrophic or oligo-mesotrophic status. These conditions bring with them, respectively, the presence of abundant mixotrophic ciliates and a low species number of crustacean zooplankton under oligotrophic status, and low numbers of mixotrophic ciliates and a high species number of zooplankton under oligo-mesotrophic status. The aims of the present study are, (1) to use remote sensing techniques for determining abundances of mixotrophic ciliates and crustacean zooplankton, and (2) to characterize these mixotrophic and zooplankton communities by using null models. The sensing was accomplished from a satellite, i.e., by measuring the reflectance of the sunlight on a waterbody, which result will vary according to the contents of the water column. The results of Principal Component Analysis (PCA) revealed that sites with low reflectance of all bands have a high abundance of Stentor accompanied by low zooplankton absolute abundance, whereas a markedly opposite situation was observed under high reflectance, where Stentor has low abundance in conjunction with high zooplankton absolute abundances. The null models revealed that the communities in the studied sites do not have structured species associations, and that there is an overlap of niches. These results obtained agree with similar observations for Argentinean Patagonian lakes.