bluuebunny/crossref_metadata_2025 huggingface dataset:
Research Contributions with Algorithmic Comparison on the Diagnosis of Diabetic Retinopathy
Authors: Nair Arun T , Muthuvel K.
Published: October 2020

The medical field has been revolutionized by the medical imaging system, which plays a key role in providing information on the early life-saving detection of dreadful diseases. Diabetic retinopathy is a chronic visual disease that is the primary reason for the vision loss in most of the patients, who left undiagnosed at the initial stage. As the count of the diabetic retinopathy affected people kept on increasing, there is a necessity to have an automated detection method. The accuracy of the diagnosis of the automatic detection model is related to image acquisition as well as image interpretation. In contrast to this, the analysis of medical images by using computerized models is still a limited task. Thus, different kinds of detection methods are being developed for early detection of diabetic retinopathy. Accordingly, this paper focuses on the various literature analyses on different detection algorithms and techniques for diagnosing diabetic retinopathy. Here, it reviews several research papers and exhibits the significance of each detection method. This review deals with the analysis on the segmentation as well as classification algorithms that are included in each of the researches. Besides, the adopted environment, database collection and the tool for each of the research are portrayed. It provides the details of the performance analysis of the various diabetic detection models and reveals the best value in the case of each performance measure. Finally, it widens the research issues that can be accomplished by future researchers in the detection of diabetic retinopathy.
Food Sustenance Estimation Using Food Image
Authors: Jiji G. Wiselin , Rajesh A.
Published: October 2020

The upcoming generation is at high risk of developing many health issues like heart diseases, metabolic diseases and other life-threatening problems with high mortality as a consequence of obesity due to intake of unhealthy food which is totally deviated from a normal balanced diet with appropriate calories, proteins, vitamins and carbohydrates. In this work, the nutrient intake is calculated using food image. Our system provides efficient segmentation algorithms for separating food items from the plate. The given 2D image of food is converted into 3D image by generating its depth map for volume generation and color, texture and shape features are extracted. These features are fed as input into multi-class support vector machine classifier for learning. The learning phase involves training of various mixed and non mixed food items. The testing phase includes query image segmentation and classification for identifying the type of food and then finding calories using the nutrition data table. We have also estimated the ingredient and decay of food items. Our result shows accurate calorie estimation for various kinds of food items.
Statistical Analysis of HRV Parameters for the Detection of Arrhythmia
Authors: Tripathi Kirthi , Sohal Harsh , Jain Shruti
Published: October 2020

The repolarization and depolarization in heart generate electrical signals in the form of an ECG wave. The condition of the heart can be indicated by using Heart Rate Variability (HRV) features. In this work, FIR filter is used at the pre-processing phase for denoising, and then statistical analysis is applied for time-domain HRV feature extraction and selection. This algorithm is evaluated on different records of MIT/BIH Normal Sinus Rhythm and Arrhythmia database. The [Formula: see text]-test implementation in both databases shows that there are significant variations in HRV features, where meanRR and HR have suggestive significant ([Formula: see text]) changes, while maxRR, minRR, maxminRR, and SDNN have strongly significant ([Formula: see text]) changes. To validate the statistical analysis of HRV, feature classification has been done using SVM and kNN classifiers. A significant improvement of 2% and 14.02% has been observed in the overall accuracy of SVM and kNN classifiers after feature selection, respectively. These HRV features can be used for the early prediction of various Cardio-Vascular Diseases (CVD).
Moroccan Data-Driven Spelling Normalization Using Character Neural Embedding
Authors: Tachicart Ridouane , Bouzoubaa Karim
Published: October 2020

With the increase of Web use in Morocco today, Internet has become an important source of information. Specifically, across social media, the Moroccan people use several languages in their communication leaving behind unstructured user-generated text (UGT) that presents several opportunities for Natural Language Processing. Among the languages found in this data, Moroccan Arabic (MA) stands with an important content and several features. In this paper, we investigate online written text generated by Moroccan users in social media with an emphasis on Moroccan Arabic. For this purpose, we follow several steps, using some tools such as a language identification system, in order to conduct a deep study of this data. The most interesting findings that have emerged are the use of code-switching, multi-script and low amount of words in the Moroccan UGT. Moreover, we used the investigated data in order to build a new Moroccan language resource. The latter consists in building a Moroccan words orthographic variants lexicon following an unsupervised approach and using character neural embedding. This lexicon can be useful for several NLP tasks such as spelling normalization.
Toward an Axiomatization of Strongly Possible Functional Dependencies
Authors: Alattar Munqath , Sali Attila
Published: October 2020

In general, there are two main approaches to handle the missing data values problem in SQL tables. One is to ignore or remove any record with some missing data values. The other approach is to fill or impute the missing data with new values [A. Farhangfar, L. A. Kurgan and W. Pedrycz, A novel framework for imputation of missing values in databases, IEEE Trans. Syst. Man Cybern. A, Syst. Hum. 37(5) (2007) 692–709]. In this paper, the second method is considered. Possible worlds, possible and certain keys, and weak and strong functional dependencies were introduced in Refs. 4 and 2 [H. Köhler, U. Leck, S. Link and X. Zhou, Possible and certain keys for SQL, VLDB J. 25(4) (2016) 571–596; M. Levene and G. Loizou, Axiomatisation of functional dependencies in incomplete relations, Theor. Comput. Sci. 206(1) (1998) 283–300]. We introduced the intermediate concept of strongly possible worlds in a preceding paper, which are obtained by filling missing data values with values already existing in the table. Using strongly possible worlds, strongly possible keys and strongly possible functional dependencies (spFDs) were introduced in Refs. 5 and 1 [M. Alattar and A. Sali, Keys in relational databases with nulls and bounded domains, in ADBIS 2019: Advances in Databases and Information Systems, Lecture Notes in Computer Science, Vol. 11695 (Springer, Cham, 2019), pp. 33–50; Functional dependencies in incomplete databases with limited domains, in FoiKS 2020: Foundations of Information and Knowledge Systems, Lecture Notes in Computer Science, Vol. 12012 (Springer, Cham, 2020), pp. 1–21]. In this paper, some axioms and rules for strongly possible functional dependencies are provided, These axioms and rules form the basis for a possible axiomatization of spFDs. For that, we analyze which weak/strong functional dependency and certain functional dependency axioms remain sound for strongly possible functional dependencies, and for the axioms that are not sound, we give appropriate modifications for soundness.
X-Ray Flow Visualization in Multiphase Flows
Authors: Aliseda Alberto , Heindel Theodore J.
Published: October 2020

The use of X-ray flow visualization has brought a powerful new tool to the study of multiphase flows. Penetrating radiation can probe the spatial concentration of the different phases without the refraction, diffraction, or multiple scattering that usually produce image artifacts or reduce the signal-to-noise ratio below reliable values in optical visualization of multiphase flows; hence, X-ray visualization enables research into the three-dimensional (3D) structure of multiphase flows characterized by complex interfaces. With the commoditization of X-ray laboratory sources and wider access to synchrotron beam time for fluid mechanics, this novel imaging technique has shed light onto many multiphase flows of industrial and environmental interest under realistic 3D configurations and at realistic operating conditions (high Reynolds numbers and high volume fractions) that had defied study for decades. We present a broad survey of the most commonly studied multiphase flows (e.g., sprays, fluidized beds, bubble columns) in order to highlight the progress X-ray imaging has made in understanding the internal structure and multiphase coupling of these flows, and we discuss the potential of advanced tomography and time-resolved and particle tracking radiography for further study of multiphase flows.
Is Emigration Harmful to Those Left Behind?
Authors: Docquier Frédéric , Veljanoska Stefanija
Published: October 2020

From the perspective of sending countries, international migrants are positively selected in terms of schooling, particularly in low-income countries. While emigration affects human capital accumulation, it also induces positive spin-offs in the form of remittances, incentives to acquire education, and diffusion of technology and democratic ideas. The net income implications for those left behind are uncertain. This article reviews the main transmission channels investigated in the existing literature and uses a standard development accounting framework to provide estimates of their relative strength and of their combined effect. Although skill biased, emigration increases the disposable income of those left behind in no fewer than three-quarters of the countries of the world. This result is robust to variations in the set of parameter values within a reasonable spectrum established in the empirical literature.
Accelerated Failure in Li[Ni0.5Mn0.3Co0.2]O2/Graphite Pouch Cells Due to Low LiPF6 Concentration and Extended Time at High Voltage
Authors: Aiken C. P. , Harlow J. E. , Tingley Rebecca , Hynes Toren , Logan E. R. , Glazier S. L. , Keefe A. S. , Dahn J. R.
Published: October 2020

Li[Ni0.5Mn0.3Co0.2]O2/graphite pouch cells were cycled using protocols that included 24 h spent at high voltage (≥ 4.3 V) under constant voltage or open circuit conditions to accelerate failure. Compared to traditional cycling, failure was reached up to 3.5 times faster. When this protocol was applied to cells containing low LiPF6 concentrations (≤ 0.4 M) failure was achieved up to 17.5 times faster than traditional cycling with normal LiPF6 concentrations. This represents a time improvement on the order of years and therefore can be used as a high-throughput screening method. Failure mechanisms for cells containing a range of LiPF6 concentrations undergoing these aggressive protocols were investigated using charge-discharge cycling, impedance spectroscopy (including symmetric cell analysis) and isothermal microcalorimetry. Long times at high voltage rapidly increase positive electrode impedance but do not seem to consume lithium inventory. The use of lower LiPF6 concentrations does not seem to introduce new failure mechanisms but makes cells less tolerant to positive electrode impedance growth. The utility of this method is demonstrated by screening cells with a variety of electrolyte additive combinations. Fewer than 3 months were required to distinguish cells containing 1% lithium difluorophospate as superior to cells with other additive combinations.
Effects of Voltage-Dependence of the Constant Phase Element and Ohmic Parameters in the Modeling and Simulation of Cyclic Voltammograms
Authors: Charoen-amornkitt Patcharawat , Suzuki Takahiro , Tsushima Shohji
Published: October 2020

Although the constant phase element (CPE) parameters have been found to vary with DC bias voltage in electrochemical impedance spectroscopy measurement, to date, the CPE parameters are assumed to be constant within the voltage window in cyclic voltammetry (CV) simulation. This leads to failure in predicting the voltammetric response of a double layer in some cases. In this study, the voltage-dependent CPE and ohmic parameters are used to simulate the capacitive current. The results show good agreement with the experimental measurements of commercial electrical double layer capacitors. The model is extended to predict the response of a system involving both Faradaic and capacitive currents by combining the conventional physicochemical transport model with circuit analysis to include effects of the resistances and CPE. To accurately predict the entire CV responses, a modified Randles circuit with an additional resistance connected in series with the CPE is proposed to be an equivalent circuit of the system. Furthermore, the closed-form analytical solution of the time-domain response of CPE under CV conditions is also derived and presented to gain better understanding of the CPE response. Using the derived equation, CV can serve as an alternative approach for determining the CPE parameters.
GLP1 receptor agonism protects against acute olanzapine-induced hyperglycemia
Authors: Medak Kyle D. , Shamshoum Hesham , Peppler Willem T. , Wright David C.
Published: October 2020

Antipsychotic drugs cause rapid perturbations in glucose and lipid metabolism. In the present study we have demonstrated that cotreatment with glucagon-like peptide 1 (GLP1) receptor agonists, such as liraglutide, protects against metabolic dysregulation caused by the antipsychotic drug olanzapine. These findings suggest that pharmacological targeting of the GLP1 receptor could be an effective adjunct approach to mitigate the harmful acute metabolic side effects of antipsychotic drugs.
Effect of angiotensin II on diabetic glomerular hyperpermeability: an in vivo permeability study in rats
Authors: Nalin Nima , Al Dhanhani Ali , AlBawardi Alia , Sharma Charu , Chandran Sanjana , Yasin Javed , Bakoush Omran
Published: October 2020

Angiotensin II drives the pathogenesis of diabetic kidney disease, and its systemic administration induces glomerular hyperpermeability in normal rats. However, the response of diabetic glomerular permeability to angiotensin II is largely unknown. In the present study, we investigated the impact of extended systemic administration of angiotensin II on the glomerular permeability of streptozotocin (STZ)-induced late diabetes in rats. We examined the changes in the glomerular permeability after subcutaneous infusion of angiotensin II at 200 ng·kg−1·min−1for 7 days in male Wistar diabetic rats with 3 mo of STZ-induced diabetes (i.e., blood glucose of ∼20 mmol/L). We also compared these changes with the effects on nondiabetic rats. The sieving coefficients (θ) for inert polydisperse Ficoll molecules, which had a radius of 10–90 Å (Ficoll70–90 Å), were measured in vivo. The θ for large Ficoll molecules was selectively enhanced after infusion of extended angiotensin II in both diabetic (θ for Ficoll70–90 Å = 0.00244 vs. 0.00079, P < 0.001) and nondiabetic animals (θ for Ficoll70–90 Å = 0.00029 vs. 0.00006, P < 0.001). These changes were compatible with the more than twofold increase in the macromolecular glomerular transport through the large-pore pathways after infusion of angiotensin II in both diabetic and nondiabetic animals. Angiotensin II infusion enhanced the large shunt-like glomerular transport pathway of STZ-induced late diabetes. Such defects can account for the large-molecular-weight IgM-uria that is observed in severe diabetic kidney disease.
Protein kinase A catalytic-α and catalytic-β proteins have nonredundant regulatory functions
Authors: Raghuram Viswanathan , Salhadar Karim , Limbutara Kavee , Park Euijung , Yang Chin-Rang , Knepper Mark A.
Published: October 2020

Vasopressin regulates osmotic water transport in the renal collecting duct by protein kinase A (PKA)-mediated control of the water channel aquaporin-2 (AQP2). Collecting duct principal cells express two seemingly redundant PKA catalytic subunits, PKA catalytic α (PKA-Cα) and PKA catalytic β (PKA-Cβ). To identify the roles of these two protein kinases, we carried out deep phosphoproteomic analysis in cultured mpkCCD cells in which either PKA-Cα or PKA-Cβ was deleted using CRISPR-Cas9-based genome editing. Controls were cells carried through the genome editing procedure but without deletion of PKA. TMT mass tagging was used for protein mass spectrometric quantification. Of the 4,635 phosphopeptides that were quantified, 67 phosphopeptides were significantly altered in abundance with PKA-Cα deletion, whereas 21 phosphopeptides were significantly altered in abundance with PKA-Cβ deletion. However, only four sites were changed in both. The target proteins identified in PKA-Cα-null cells were largely associated with cell membranes and membrane vesicles, whereas target proteins in PKA-Cβ-null cells were largely associated with the actin cytoskeleton and cell junctions. In contrast, in vitro incubation of mpkCCD proteins with recombinant PKA-Cα and PKA-Cβ resulted in virtually identical phosphorylation changes. In addition, analysis of total protein abundances in in vivo samples showed that PKA-Cα deletion resulted in a near disappearance of AQP2 protein, whereas PKA-Cβ deletion did not decrease AQP2 abundance. We conclude that PKA-Cα and PKA-Cβ serve substantially different regulatory functions in renal collecting duct cells and that differences in phosphorylation targets may be due to differences in protein interactions, e.g., mediated by A-kinase anchor proteins, C-kinase anchoring proteins, or PDZ binding.
Time-course analysis of the effect of embedded metal on skeletal muscle gene expression
Authors: Wen Yuan , Vechetti Ivan J. , Alimov Alexander P. , Hoffman Jessica F. , Vergara Vernieda B. , Kalinich John F. , McCarthy John J. , Peterson Charlotte A.
Published: October 2020

As a consequence of military operations, many veterans suffer from penetrating wounds and long-term retention of military-grade heavy metal fragments. Fragments vary in size and location, and complete surgical removal may not be feasible or beneficial in all cases. Increasing evidence suggests retention of heavy metal fragments may have serious biological implications, including increased risks for malignant transformation. Previous studies assessed the tumorigenic effects of metal alloys in rats, demonstrating combinations of metals are sufficient to induce tumor formation after prolonged retention in skeletal muscle tissue. In this study, we analyzed transcriptional changes in skeletal muscle tissue in response to eight different military-relevant pure metals over 12 mo. We found that most transcriptional changes occur at 1 and 3 mo after metal pellets are embedded in skeletal muscle and these effects resolve at 6 and 12 mo. We also report significant immunogenic effects of nickel and cobalt and suppressive effects of lead and depleted uranium on gene expression. Overall, skeletal muscle exhibits a remarkable capacity to adapt to and recover from internalized metal fragments; however, the cellular response to chronic exposure may be restricted to the metal-tissue interface. These data suggest that unless affected regions are specifically captured by biopsy, it would be difficult to reliably detect changes in muscle gene expression that would be indicative of long-term adverse health outcomes.
Penalized Quadratic Inference Function-Based Variable Selection for Generalized Partially Linear Varying Coefficient Models with Longitudinal Data
Authors: Zhang Jinghua , Xue Liugen
Published: October 2020

Semiparametric generalized varying coefficient partially linear models with longitudinal data arise in contemporary biology, medicine, and life science. In this paper, we consider a variable selection procedure based on the combination of the basis function approximations and quadratic inference functions with SCAD penalty. The proposed procedure simultaneously selects significant variables in the parametric components and the nonparametric components. With appropriate selection of the tuning parameters, we establish the consistency, sparsity, and asymptotic normality of the resulting estimators. The finite sample performance of the proposed methods is evaluated through extensive simulation studies and a real data analysis.
The Role of Inflammation in the Pathogenesis of Preeclampsia
Authors: Michalczyk Michał , Celewicz Aleksander , Celewicz Marta , Woźniakowska-Gondek Paula , Rzepka Rafał
Published: October 2020

Preeclampsia (PE) affects 5-8% of pregnant women, and it is the major cause of perinatal morbidity and mortality. It is defined as arterial hypertension in women after 20 weeks of gestation which cooccurs with proteinuria (300 mg/d) or as arterial hypertension which is accompanied by one of the following: renal failure, liver dysfunction, hematological or neurological abnormalities, intrauterine growth restriction, or uteroplacental insufficiency. Currently, pathophysiology of preeclampsia poses a considerable challenge for perinatology. Preeclampsia is characterized by excessive and progressive activation of the immune system along with an increase in proinflammatory cytokines and antiangiogenic factors in fetoplacental unit as well as in vascular endothelium in pregnant women. A single, major underlying mechanism of preeclampsia is yet to be identified. This paper discusses the current understanding of the mechanisms which underlie the development of the condition. Some significant factors responsible for PE development include oxidative stress, abnormal concentration and activity in mononuclear phagocytic system, altered levels of angiogenic and antiangiogenic factors, and impaired inflammatory response triggered by inflammasomes. Detailed understanding of pathophysiology of inflammatory process in PE can largely contribute to new, targeted anti-inflammatory therapies that may improve perinatal outcomes in PE patients.
Efficiency of High‐Flow Nasal Cannula on Pulmonary Rehabilitation in COPD Patients: A Meta‐Analysis
Authors: Fu Cuiping , Liu Xin , Zhu Qingqing , Wu Xu , Hao Shengyu , Xie Liang , Li Shanqun
Published: October 2020

Introduction. The clinical benefit of high‐flow nasal cannula (HFNC) on factors related to pulmonary rehabilitation in chronic obstructive pulmonary disease (COPD) patients remains unclear. This meta‐analysis aimed at synthesizing the available evidence on the efficacy of HFNC on exercise capacity, lung function, and other factors related to pulmonary rehabilitation in COPD patients. Methods. Electronic databases (MEDLINE, Embase, Cochrane Central Register of Controlled Trials, Web of Science) were searched for randomized trials comparing with conventional oxygen therapy (COT) or noninvasive ventilation (NIV). Primary outcomes were respiratory rate, FEV1, tidal volume, oxygen partial pressure, total score of St. George’s respiratory questionnaire, 6‐minute walk test, and exercise endurance time. Results. Ten trials met the criteria for inclusion. Combined data from six studies showed that HFNC showed a lower respiratory rate in COPD patients [mean difference ‐1.27 (95% CI: ‐1.65–(‐0.89)]. Combined data from three studies showed a lower forced expiratory volume in one second (FEV1) in the group of HFNC. No difference in tidal volume was showed between the HFNC and control groups in COPD patients. No significant oxygen improvement between the HFNC groups and control groups. The total score of St. George’s respiratory questionnaire was improved by the subgroup analysis of HFNC versus COT but no NIV. Two multicenter RCTs showed the six‐minute walk test, and statistical results showed that the length of the six‐minute walk capacity was increased after usage of HFNC compared to the control group [mean difference ‐8.65 (95% CI: ‐9.12–(‐8.19)]. No increase of exercise capacity after usage of HFNC (mean difference ‐12.65). Conclusion. In the first meta‐analysis of the area, the current evidence did not show so much positive effect on tidal volume or oxygen improvement in COPD patients. Length of the six‐minute walk capacity was increased after using HFNC, while other pulmonary rehabilitation parameters, namely, the score of St. George’s respiratory questionnaire and exercise capacity show no increase in the group of HFNC. The variance in the quality of the evidence included in this meta‐analysis highlights the need for this evidence to be followed up with further high‐quality and more randomized trials.
99‐Case Study of Sporadic Aortic Dissection by Whole Exome Sequencing Indicated Novel Disease‐Associated Genes and Variants in Chinese Population
Authors: Wang Zanxin , Zhuang Xianmian , Chen Bailang , Wen Junmin , Peng Fang , Liu Xiling , Wei Minxin
Published: October 2020

Background. In this study, the whole exome sequencing in human aortic dissection, a highly lethal cardiovascular disease, was investigated to explore the aortic dissection‐associated genes and variants in Chinese population. Methods. Whole exome sequencing was performed in 99 cases of aortic dissection. All single nucleotide polymorphisms (SNPs), insertions/deletions (InDels), and copy number variations (CNVs) were filtered to exclude the benign variants. Enrichment analysis and disease‐gene correlation analysis were performed. Results. 3425873 SNPs, 685245 InDels, and 1177 CNVs were identified, and aortic dissection‐associated SNPs, InDels, and CNVs were collected. After the disease correlation analysis, 20 candidate genes were identified. Part of these genes such as MYH11, FBN1, and ACTA2 were consistent with previous studies, while MLX, DAB2IP, EP300, ZFYVE9, PML, and PRKCD were newly identified as candidate aortic dissection‐associated genes. Conclusion. The pathogenic and likely pathogenic variants in most of AD‐associated genes (FBN1, MYH11, EFEMP2, TGFBR2, FBN2, COL3A1, and MYLK) were identified in our cohort study, and pathogenic CNVs involved in MYH11, COL family, and FBN were also identified which are not detectable by other NGS analysis. The correlation between MLX, DAB2IP, EP300, ZFYVE9, PML, PRKCD, and aortic dissection was identified, and EP300 may play a key role in AD.
A Blockchain-Based Public Auditing Scheme for Cloud Storage Environment without Trusted Auditors
Authors: Li Song , Liu Jian , Yang Guannan , Han Jinguang
Published: October 2020

In the cloud storage applications, the cloud service provider (CSP) may delete or damage the user’s data. In order to avoid the responsibility, CSP will not actively inform the users after the data damage, which brings the loss to the user. Therefore, increasing research focuses on the public auditing technology recently. However, most of the current auditing schemes rely on the trusted third public auditor (TPA). Although the TPA brings the advantages of fairness and efficiency, it cannot get rid of the possibility of malicious auditors, because there is no fully trusted third party in the real world. As an emerging technology, blockchain technology can effectively solve the trust problem among multiple individuals, which is suitable to solve the security bottleneck in the TPA-based public auditing scheme. This paper proposed a public auditing scheme with the blockchain technology to resist the malicious auditors. In addition, through the experimental analysis, we demonstrate that our scheme is feasible and efficient.
Effect of Mesenchymal Stem Cell-Derived Exosomes on Retinal Injury: A Review of Current Findings
Authors: Nuzzi Raffaele , Caselgrandi Paolo , Vercelli Alessandro
Published: October 2020

In recent years, various studies have followed in the literature on the therapeutic effects of mesenchymal stem cells (MSC) on damage in retinal cells. The evidence that MSCs exert their regenerative and damage reduction effect in a paracrine way, through the release of soluble factors and exosomes, is now consolidated. Exosomes are microvesicles formed by a double layer of phospholipid membrane and carry proteins and RNA, through which they play a therapeutic role on target cells. Scientific research has recently focused on the use of exosomes derived from MSC in various models of retinal damage in vitro and in vivo as they, compared to MSCs, have similar functions and at the same time have different advantages such as greater stability and handling, a lower chance of immunological rejection and no risk of malignant transformation. The purpose of this review is to summarize current knowledge on the therapeutic use of exosomes derived from MSCs in retinal damage and to stimulate new clinical perspectives regarding their use.
Exploiting Replication Stress as a Novel Therapeutic Intervention
Authors: Martin Jeffrey C. , Hoegel Tamara J. , Lynch Miranda L. , Woloszynska Anna , Melendy Thomas , Ohm Joyce E.
Published: October 2020

Ewing sarcoma is an aggressive pediatric tumor of the bone and soft tissue. The current standard of care is radiation and chemotherapy, and patients generally lack targeted therapies. One of the defining molecular features of this tumor type is the presence of significantly elevated levels of replication stress as compared with both normal cells and many other types of cancers, but the source of this stress is poorly understood. Tumors that harbor elevated levels of replication stress rely on the replication stress and DNA damage response pathways to retain viability. Understanding the source of the replication stress in Ewing sarcoma may reveal novel therapeutic targets. Ewing sarcomagenesis is complex, and in this review, we discuss the current state of our knowledge regarding elevated replication stress and the DNA damage response in Ewing sarcoma, one contributor to the disease process. We will also describe how these pathways are being successfully targeted therapeutically in other tumor types, and discuss possible novel, evidence-based therapeutic interventions in Ewing sarcoma. We hope that this consolidation will spark investigations that uncover new therapeutic targets and lead to the development of better treatment options for patients with Ewing sarcoma.

Implications:

This review uncovers new therapeutic targets in Ewing sarcoma and highlights replication stress as an exploitable vulnerability across multiple cancers.
Subungual Nail Erythrasma Presenting as Melanonychia: A Rare Finding
Authors: Maghfour Jalal , Kane Jennifer , Robinson-Bostom Leslie , Kawaoka John , Jellinek Nathaniel
Published: October 2020

Nail pathology may reflect a wide array of localized and systemic dermatological conditions. Certain nail findings such as melanonychia can create diagnostic challenges even to nail experts. We report a case of a 78-year-old man who presented with melanonychia of the great toe. Nail clipping showed focal melanin deposition, and dermoscopy demonstrated a region of localized erythema in the lunula concerning for possible melanocytic neoplasm. Subsequent nail biopsy showed numerous vertically oriented filamentous bacteria and coccobacilli within the nail plate consistent with a diagnosis of subungual nail erythrasma. Nail erythrasma is a rare entity. Additionally, this case highlights a new clinical presentation of nail erythrasma as melanonychia.
Becker’s Nevus Coexisting with Morphea: A Rare Case Report
Authors: Kumar Pradeep , Sanke Sarita , Chander Ram , Nangia Anita
Published: October 2020

Becker’s nevus (BN) is an acquired unilateral hyperpigmented hairy macule, whereas morphea is a chronic connective tissue disease of unknown etiology, characterized by skin thickening with increased quantities of collagen in the indurated lesion, usually involving the upper trunk and proximal extremity. The occurrence of both disease in the same anatomical site and individual was not reported previously. We report this rare case in a 17-year-old, Indian girl and was diagnosed after clinical histopathology and dermoscopic correlation. Morphea can be an interesting incidental occurrence within a large plaque of BN.
Prognostic Significance of Hyponatremia in Acute Stroke: A Systematic Review and Meta-Analysis
Authors: Shima Shogo , Niimi Yasunari , Moteki Yosuke , Takahashi Osamu , Sato Shinsuke , Inoue Tatsuya , Okada Yoshikazu
Published: October 2020

Objective: Hyponatremia is a common electrolyte disorder in patients with stroke, which leads to various fatal complications. We performed a systematic review and meta-analysis to investigate the outcomes of acute stroke patients with hyponatremia. Methods: We searched MEDLINE, EMBASE, and the Cochrane Library databases for relevant literature in English published up to March 2020. Two review authors independently screened and selected the studies by assessing the eligibility and validity based on the inclusion criteria. Mortality at 90 days was set as the primary end point, and in-hospital mortality and length of hospital stay were set as the secondary end points. We conducted the data synthesis and analyzed the outcomes by calculating the odds ratio (OR) and mean difference. Results: Of 835 studies, 15 studies met the inclusion criteria (n = 10,745). The prevalence rate of stroke patients with hyponatremia was 7.0–59.2%. They had significantly higher 90-day mortality (OR, 1.73; 95% confidence interval (CI), 1.24–2.42) and longer length of hospital stay (mean difference, 10.68 days; 95% CI, 7.14–14.22) than patients without hyponatremia. Patients with hyponatremia had a higher tendency of in-hospital mortality than those without hyponatremia (OR, 1.61; 95% CI, 0.97–2.69). Conclusions: The development of hyponatremia in the clinical course of stroke is associated with higher short-term mortality and a longer hospital stay. Although the causal relationship is unclear, hyponatremia could be a significant predictor of poor outcomes after stroke.
Increased Use of Blood Transfusions to Manage Urological Conditions during the COVID-19 Pandemic
Authors: Capogrosso Paolo , Candela Luigi , Rossi Piercarlo , Guarasci Cristian , Muttin Fabio , Roscigno Marco , Chianese Rosa , Santoleri Luca , Tassara Michela , Carcano Giulio , Naspro Richard , Da Pozzo Luigi , Montorsi Francesco , Salonia Andrea , Dehò Federico
Published: October 2020

Introduction: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) led to an extensive reorganization of the healthcare system in Italy, with significant deferment of the treatment of urology patients. We aimed to assess the impact of deferred treatment during the SARS-CoV-2 pandemic on the need for blood transfusions in 3 Italian urology departments. Methods: We reviewed hospital chart data on blood transfusions at the urology units of 3 academic centers in the north of Italy from March to April 2020. Data were compared with values from the same time frame in 2019 (March to April 2019). Results: We observed significant reductions of the number of patients admitted to the urology units from March to April 2020 (373 vs. 119) and the number of performed surgeries (242 vs. 938) compared to 2019. Though, the number of transfused blood units was comparable between the 2 years (182 vs. 252), we found a greater mean number of blood units transfused per admission in 2020 (0.49 vs. 0.22; p < 0.0001). As a whole, the transfusion rate for hematuria was higher in 2020 than in 2019 (36 vs. 7.9%; p < 0.0001). Discussion/Conclusion: The observed increased number of blood transfusions needed throughout the SARS-CoV-2 era could have had a negative impact on both patients and the healthcare system. It is possible to speculate that this is the consequence of a delayed diagnosis and deferred treatment of acute conditions.
Unveiling the trap-nesting bees and wasps’ fauna (Hymenoptera: Apocrita) and associated organisms of the Jardim Botânico do Rio de Janeiro, Brazil
Authors: Marinho Diego , Vivallo Felipe
Published: October 2020

Urban areas, as cities, are frequently overlooked as refuges for the native fauna. However, these places may support several species and house relevant biodiversity contributing to important ecosystemic functions. Wasps and bees (Hymenoptera: Apocrita) are important faunistic elements acting as predators/parasitoids and pollinators, respectively. Therefore, they must be surveyed and inventoried for conservation purposes, especially in cities located in the Atlantic Forest domain, a ravaged Brazilian biome. Accordingly, this study presents a species list of trap-nesting bees and wasps that occurs at the Jardim Botânico do Rio de Janeiro. The survey was conducted using the trap-nest method. Three types of trap-nests were offered totalizing 1,038 traps: rubber hose, bamboo cane and plastic straw. The plastic straw traps were the most effective followed by the bamboo cane ones at attracting nesting wasps and bees. Between April/2017 and February/2019, 12 foundress species built nests: Tetrapedia curvitarsis (Apidae) (33 nests), Hylaeus sp. (Colletidae) (6), Auplopus cf. rufipes (Pompilidae) (5), Trypoxylon sp. (Crabronidae) (4), Pachodynerus nasidens (Vespidae) (3), Auplopus cf. brasiliensis (Pompilidae), Megachile benigna and Megachile sp. (Megachilidae), Euglossa pleosticta, Euglossa sp., and Eufriesea sp. (Apidae) and Penepodium sp. (Sphecidae) all with one nest. Also, four natural enemies were recorded: Chaenotetrastichus neotropicalis (Eulophidae), Gasteruption brachychaetum (Gasterupteiidae), Caenochrysis crotonis (Chrysididae) and Amobia sp. (Diptera: Sarcophagidae). Most bee nests were restrained to the matrix forest and nearby areas, whereas wasps built their nests predominantly in open areas. Regarding seasonality, bees tended to nest in the summer and early autumn influenced by mean temperature, in contrast of wasps that nested in late autumn, winter and spring, influenced by pluviosity. Besides many rare species, which suggests environmental disturbance, the Jardim Botânico do Rio de Janeiro showed a fairly diverse fauna and shows how forest fragment in cities may harbour important representatives of the native fauna.
Mitochondrial Isolevuglandins Contribute to Vascular Oxidative Stress and Mitochondria-Targeted Scavenger of Isolevuglandins Reduces Mitochondrial Dysfunction and Hypertension
Authors: Dikalova Anna , Mayorov Vladimir , Xiao Liang , Panov Alexander , Amarnath Venkataraman , Zagol-Ikapitte Irene , Vergeade Aurelia , Ao Mingfang , Yermalitsky Valery , Nazarewicz Rafal R. , Boutaud Olivier , Lopez Marcos G. , Billings Frederic T. , Davies Sean , Roberts L. Jackson , Harrison David G. , Dikalov Sergey
Published: October 2020

Hypertension remains a major health problem in Western Societies, and blood pressure is poorly controlled in a third of patients despite use of multiple drugs. Mitochondrial dysfunction contributes to hypertension, and mitochondria-targeted agents can potentially improve treatment of hypertension. We have proposed that mitochondrial oxidative stress produces reactive dicarbonyl lipid peroxidation products, isolevuglandins, and that scavenging of mitochondrial isolevuglandins improves vascular function and reduces hypertension. To test this hypothesis, we have studied the accumulation of mitochondrial isolevuglandins-protein adducts in patients with essential hypertension and Ang II (angiotensin II) model of hypertension using mass spectrometry and Western blot analysis. The therapeutic potential of targeting mitochondrial isolevuglandins was tested by the novel mitochondria-targeted isolevuglandin scavenger, mito2HOBA. Mitochondrial isolevuglandins in arterioles from hypertensive patients were 250% greater than in arterioles from normotensive subjects, and ex vivo mito2HOBA treatment of arterioles from hypertensive subjects increased deacetylation of a key mitochondrial antioxidant, SOD2 (superoxide dismutase 2). In human aortic endothelial cells stimulated with Ang II plus TNF (tumor necrosis factor)-α, mito2HOBA reduced mitochondrial superoxide and cardiolipin oxidation, a specific marker of mitochondrial oxidative stress. In Ang II–infused mice, mito2HOBA diminished mitochondrial isolevuglandins-protein adducts, raised Sirt3 (sirtuin 3) mitochondrial deacetylase activity, reduced vascular superoxide, increased endothelial nitric oxide, improved endothelium-dependent relaxation, and attenuated hypertension. Mito2HOBA preserved mitochondrial respiration, protected ATP production, and reduced mitochondrial permeability pore opening in Ang II–infused mice. These data support the role of mitochondrial isolevuglandins in endothelial dysfunction and hypertension. We conclude that scavenging of mitochondrial isolevuglandins may have therapeutic potential in treatment of vascular dysfunction and hypertension.
Postnatal Enalapril to Improve Cardiovascular Function Following Preterm Preeclampsia (PICk-UP):
Authors: Ormesher Laura , Higson Suzanne , Luckie Matthew , Roberts Stephen A , Glossop Heather , Trafford Andrew , Cottrell Elizabeth , Johnstone Edward D. , Myers Jenny E.
Published: October 2020

Hypertensive disease in pregnancy is associated with future cardiovascular disease and, therefore, provides an opportunity to identify women who could benefit from targeted interventions aimed at reducing cardiovascular morbidity. This study focused on the highest-risk group, women with preterm preeclampsia, who have an 8-fold risk of death from future cardiovascular disease. We performed a single-center feasibility randomized controlled trial of 6 months’ treatment with enalapril to improve postnatal cardiovascular function. Echocardiography and hemodynamic measurements were performed at baseline (<3 days), 6 weeks, and 6 months postdelivery on 60 women. At randomization, 88% of women had diastolic dysfunction, and 68% had concentric remodeling/hypertrophy. No difference was seen in total vascular resistance (
P
=0.59) or systolic function (global longitudinal strain:
P
=0.14) between groups at 6 months. However, women treated with enalapril had echocardiographic measurements consistent with improved diastolic function (E/E′[the ratio of early mitral inflow velocity and early mitral annular diastolic velocity]:
P
=0.04) and left ventricular remodeling (relative wall thickness:
P
=0.01; left ventricular mass index:
P
=0.03) at 6 months, compared with placebo. Urinary enalapril was detectable in 85% and 63% of women in the enalapril arm at 6 weeks and 6 months, respectively. All women responded positively to taking enalapril in the future. Our study confirmed acceptability and feasibility of the study protocol with a recruitment to completion rate of 2.2 women per month. Importantly, postnatal enalapril treatment was associated with improved echocardiographic measurements; these early improvements have the potential to reduce long-term cardiovascular disease risk. A definitive, multicenter randomized controlled trial is now required to confirm these findings.

Registration—

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT03466333.
Sodium Intake Is Associated With Renal Resistive Index in an Adult Population-Based Study
Authors: Jaques David A. , Pruijm Menno , Ackermann Daniel , Vogt Bruno , Guessous Idris , Burnier Michel , Pechere-Bertschi Antoinette , Bochud Murielle , Ponte Belen
Published: October 2020

Renal resistive index (RRI) has been associated with adverse renal and cardiovascular outcomes. Although traditionally considered a marker of intrinsic renal damage, RRI could also reflect systemic vascular dysfunction. As sodium intake was linked to alterations in vascular properties, we wished to characterize the association of salt consumption with RRI in the general adult population. Participants were recruited in a population-based study in Switzerland. RRI was measured by ultrasound in 3 segmental arteries. Sodium intake (UNa; mmol/24 h) was estimated on 24-hour urine samples. Carotido-femoral pulse wave velocity was obtained by applanation tonometry. Mixed multivariate regression models were used with RRI or pulse wave velocity as independent variables and UNa as dependent variable, adjusting for possible confounders. We included 1002 patients in the analyses with 528 (52.7%) women and mean age of 47.2±17.4. Mean values of UNa and RRI were 141.8±61.1 mmol/24 h and 63.8±5.5%, respectively. In multivariate analysis, UNa was positively associated with RRI (
P
=0.002) but not with pulse wave velocity (
P
=0.344). Plasma renin activity and aldosterone did not modify the relationship between UNa and RRI (
P
=0.087 for interaction). UNa/urinary potassium ratio was positively associated with pulse wave velocity ≥12 m/s (
P
=0.033). Our results suggest that dietary salt consumption has a direct impact on renal hemodynamic in the adult general population. Alterations in vascular properties likely explain those findings, but inadequate renal vaso-motor response is also possible. Sodium intake could thus potentially be linked to underlying structural systemic damages affecting this population.
Perceived Threat of a Linguistic Community and Context Effect on Attitude toward Immigration in Hong Kong
Authors: Lee Francis L.F. , Liang Hai
Published: October 2020

Typically grounded in a discussion of contact vs. threat theory, much research has examined the impact of the presence of ethnic minorities in residential contexts on people’s attitude toward immigration. Yet, there has not been much evidence regarding whether the presence of a linguistically-defined minority can create similar impact under specific political conditions. This article examines Hong Kong, where the arrival of immigrants from mainland China has aroused controversies. The presence of Mandarin speakers, under the contemporary conditions, could be perceived as representing the cultural threat posed by China onto the city. Data from representative surveys were combined with district-level census data. The analysis shows that people living in a district with higher proportions of residents using Mandarin as the usual spoken language indeed favored more restrictive immigration policies. Contextual presence of Mandarin speakers also moderated the impact of tolerance and holding of negative stereotypes on attitude toward immigration.
Sultanates and the Making of Nationhood in Indonesia and Malaysia
Authors: Ikhwan Hakimul , Aidulsyah Fachri
Published: October 2020

This paper seeks to answer the question of how the sultanates of Malaysia maintained their authority in the current nation-state era as almost all of Indonesia’s hundreds of sultanates (except for the Sultanate of Yogyakarta in Java) lost formal power. It proposes three findings. First, Dutch and British colonialism had different legacies in Indonesia and Malaysia, respectively. Second, following their independence, Indonesia and Malaysia adopted different government systems, with the former becoming a unitary republic and the latter becoming a federal state; consequently, the sultanates of Indonesia had to submit themselves to the central government in Indonesia, whereas those in Malaysia were given broader space to exercise their authority within a federal state. Third, the sultanates of Malaysia have a two-layered identity, resulting from the convergence of ethnic Malay and Islamic identities that eventually strengthened the Sultanate’s authority and legitimacy in the eyes of the people and the federal state; conversely, convergence between ethnic and religious identity was limited in Indonesia’s sultanates, subsequently undermining the sultans’ ability to uphold authority and power.