bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of goods and services tax (GST) on Indian economy
Authors: Bansal Ramita , Shrivastava Preeti , Kumar Amar
Published: March 2024

India has implemented the Goods and Services Tax, an indirect tax, to help and promote the nation’s economic expansion. The Goods and Services Tax Bill has been enacted in the majority of developed nations. In India, GST was established in 1999. A committee was set up to design the model of GST. But GST was re-launched on 1 July 2017 by the Indian government. There was a lot of uproar in favor of its introduction. All of the different taxes levied by the federal and state governments were replaced with the GST. The phrase “One Nation, One Tax” refers to the fact that all taxes must be paid in one location nationwide. The report thoroughly examines the effects of GST in India. The study offers sentiment analysis and bibliometric visualization of GST. It was discovered that the government implemented the GST in order to tax everyone in the nation and stop the flow of illicit money. However, it was noted that many Indian residents’ feelings were conflicted. Therefore, it is advised to review the structure and maintain a focus on ongoing development.
Micropolar theory of solid subjected to initial stress
Authors: Lianngenga R. , Laldinmawia T. B. C.
Published: March 2024

The basic of the initial stress in an elastic continuum is revisited, then this investigation studies micropolar elastic solid subjected to initial stress using the classical method. The strain energy density function was developed to derive the constitutive relations and field equations when the influence of initial stress is taken into account. The case of linear-homogeneous isotropic and anisotropic condition of field and constitutive relations of the solid is obtained.
Analyzing polycyclic aromatic hydrocarbons using topological indices and QSPR analysis to reveal molecular complexity
Authors: Ahmed Wakeel , Zaman Shahid , Khalid Farhana
Published: March 2024

Polycyclic aromatic hydrocarbons (PAHs) have distinctive chemical structures and are well known for their wide range of uses and environmental relevance. This work explores the impact of these structural characteristics on eccentricity-based topological indices offering information about the arrangement of atoms within the molecules. This study uses quantitative structure-property relationship (QSPR) analysis to construct prediction models for understanding and forecasting specific PAHs including Dibenzo[e,l]Pyrene, Heptacence, Heptaphene, Naphthacene, Naphthalene, Naphto[1,2a]pyrene, Naphtho[2,3a]pyrene, perylene, Perylene, Picene, Phenanthrene, Pyrene, Tetraphene, Tribenzo[b,n,pqr]perylene, Tribenzo[a,fg,op]tetracene and Triphenylene. Furthermore, regression analysis applies to clarify the quantitative correlations between the factors under study and improves the interpretability of the data produced. The combined use of these diverse approaches advances a thorough comprehension of the mutual influence of chemical structure, topological indices and predictive modeling about PAHs.
Editorial — From Habitat to Climate: The Evolution of Building Materials in Response to Environmental Imperatives
Authors: Kumar Sanjeev
Published: March 2024

In the grand narrative of human civilization, the evolution of materials stands as a testament to our journey from rudimentary shelters to towering edifices that define our contemporary landscapes. This transformation of materials, which initially served basic sheltering needs, has been driven by the pressing demands of a rapidly changing planet. This discourse embarks on an exploration of this evolutionary trajectory, tracing the symbiotic relationship between humanity and the materials it has shaped, from the simplicity of ancient caves to the complexity of modern skyscrapers. Woven through this narrative is a thread that transcends time, highlighting the critical intersection of architectural innovation, ever-evolving materials and environmental stewardship. From the dawn of civilization, the manipulation of materials has not only influenced the form and function of our habitats but also reflected our evolving relationship with the environment. As we stand at the precipice of environmental challenges, these materials have undergone a metamorphosis, adapting to the multifaceted demands of a planet in flux. This editorial underscores the imperative of this transformation, advocating for a fusion of innovative design, responsible materials work and sustainable practices in the face of a dynamic climate. As we navigate the ages from rudimentary shelters to the urgent demands of a changing climate, the narrative of material evolution is a profound reflection of our collective journey.
Equilibria and bifurcations in contact dynamics
Authors: Montaldi James
Published: March 2024

We provide a systematic study of equilibria of contact vector fields and the bifurcations that occur generically in 1-parameter families, and express the conclusions in terms of the Hamiltonian functions that generate the vector fields. Equilibria occur at points where the zero-level set of the Hamiltonian function is either singular or is tangent to the contact structure. The eigenvalues at an equilibrium have an interesting structure: there is always one particular real eigenvalue of any equilibrium, related to the contact structure, that we call the principal coefficient, while the other eigenvalues arise in quadruplets, similar to the symplectic case except they are translated by a real number equal to half the principal coefficient. There are two types of codimension 1 equilibria, named Type I, arising where the zero-set of the Hamiltonian is singular, and Type II where it is not, but there is a degeneracy related again to the principal coefficient and the contact of the zero-level set of the Hamiltonian with the contact structure. Both give rise generically to saddle-node bifurcations. Some special features include: (i) for Type II singularities, Hopf bifurcations cannot occur in dimension 3, but they may in dimension 5 or more; (ii) for Type I singularities, a fold-Hopf bifurcation can occur with codimension 1 in any dimension, and (iii) again for Type I, and in dimension at least 5, a fold-multi-Hopf bifurcation (where several pairs of eigenvalues pass through the imaginary axis simultaneously together with one through the origin) may also occur with codimension 1.
The Atlantic Jigsaw Puzzle and the geoheritage of Angola
Authors: Jacobs Louis L. , Schröder Stefan , de Sousa Nair , Dixon Richard , Fiordalisi Edoardo , Marechal Arthur , Mateus Octávio , Nsungani Pedro Claude , Polcyn Michael J. , Pereira Gustavo do Couto Ramos , Rochelle-Bates Nathan , Schulp Anne S. , Scotese Christopher R. , Sharp Ian , Silvano Carlos Gaudari , Swart Roger , Vineyard Diana P.
Published: March 2024

The jigsaw-puzzle fit of South America and Africa is an icon of plate tectonics and continental drift. Fieldwork in Angola since 2002 allows the correlation of onshore outcrops and offshore geophysical and well-core data in the context of rift, sag, salt, and post-salt drift phases of the opening of the central South Atlantic. These outcrops, ranging in age from >130 Ma to <71 Ma, record Early Cretaceous outpouring of the Etendeka–Paraná Large Igneous Province (Bero Volcanic Complex) and rifting, followed by continental carbonate and siliciclastic deposition (Tumbalunda Formation) during the sagging of the nascent central South Atlantic basin. By the Aptian, evaporation of sea water resulted in thick salt deposits (Bambata Formation), terminated by seafloor spreading. The Equatorial Atlantic Gateway began opening by the early Late Cretaceous (100 Ma) and allowed flow of currents between the North and South Atlantic, creating environmental conditions that heralded the introduction of marine reptiles. These dramatic outcrops are a unique element of geoheritage because they arguably comprise the most complete terrestrially exposed geological record of the puzzle-like icon of continental drift.
Lessons Learned from Developing a Sustainability Awareness Framework for Software Engineering Using Design Science
Authors: Betz Stefanie , Penzenstadler Birgit , Duboc Leticia , Chitchyan Ruzanna , Kocak Sedef Akinli , Brooks Ian , Oyedeji Shola , Porras Jari , Seyff Norbert , Venters Colin C.
Published: March 2024

To foster a sustainable society within a sustainable environment, we must dramatically reshape our work and consumption activities, most of which are facilitated through software. Yet, most software engineers hardly consider the effects on the sustainability of the IT products and services they deliver. This issue is exacerbated by a lack of methods and tools for this purpose. Despite the practical need for methods and tools that explicitly support consideration of the effects that IT products and services have on the sustainability of their intended environments, such methods and tools remain largely unavailable. Thus, urgent research is needed to understand how to design such tools for the IT community properly. In this article, we describe our experience using design science to create the Sustainability Awareness Framework (SusAF), which supports software engineers in anticipating and mitigating the potential sustainability effects during system development. More specifically, we identify and present the challenges faced during this process. The challenges that we have faced and addressed in the development of the SusAF are likely to be relevant to others who aim to create methods and tools to integrate sustainability analysis into their IT products and services development. Thus, the lessons learned in SusAF development are shared for the benefit of researchers and other professionals who design tools for that end.
Construction of Nickel Tungsten Oxide Anchored Carbon Nanofibers Modified with Glassy Carbon Electrode for Enhanced Electrochemical Detection of Metronidazole in Urine and Environmental Water Sample
Authors: Mariappan Kiruthika , Sakthinathan Subramanian , Chen Tse-Wei , Chen Shen-Ming , Alagarsamy Saran Vignesh , Chiu Te-Wei , Al-Mohaimeed Amal M. , Al-onazi Wedad A. , Elshikh Mohamed S.
Published: March 2024

Metronidazole (MTD) is an antibiotic that is commonly used to treat pathogens and protozoal infections, which have a highly harmful impact on human health and domestic animals. Hence, the detection of MTD is highly necessary to avoid environmental pollution. The hydrothermal technique has been utilized to prepare Nickel Tungsten oxide (NiWO4) nanosheets which were anchored with the carbon nanofiber (CNF) to produce CNF/NiWO4 nanocomposite, the nanocomposite coated on the glassy carbon electrode (GCE) and applied to the electrochemical detection of MTD. Besides, field emission scanning electron microscope (FESEM), transmission electron microscope (TEM), energy dispersive X-ray analysis (EIS), Fourier-transform infrared spectroscopy (FTIR), X-ray diffraction analysis (XRD), and X-ray photoelectron spectroscopy. Moreover, electrochemical impedance spectroscopy (EIS), cyclic voltammetry studies (CV), and differential pulse voltammetry (DPV) were also handled for the identification of the electrochemical behavior of the GCE/CNF/NiWO4 electrode responses. Finally, the CNF/NiWO4 electrode shows a low detection limit of 0.4 μM, a wide linear response range of 0.01–650 μM, and a higher sensitivity of 0.274 μA μM−1 cm−2, with better repeatability, reproducibility, and excellent stability. Finally, the prepared GCE/CNF/NiWO4 electrodes were employed to detect MTD in tap water and urine samples with acceptable recoveries.
Porous Zinc Oxide and Functionalized Multiwalled Carbon Nanotubes Composite as Electrode Material for Enhanced Electrochemical Sensing of an Anticancer Drug, Dasatinib
Authors: Korgaonkar Karuna , Agadi Naveenkumar P. , Seetharamappa J.
Published: March 2024

An anticancer drug, dasatinib (DAS), is used to treat prostate cancer, chronic myelogenous leukaemia, and acute lymphoblastic leukaemia. In the present work, we describe the preparation of zinc oxide (ZnO) nanoparticles (NPs) using Averrhoa bilimbi leaf extract. These ZnO NPs were combined with functionalized multi-walled carbon nanotubes (f-MWCNT) to prepare a ZnO@f-MWCNT nanocomposite for electrochemical sensing of DAS. The prepared electrode materials, ZnO NPs, f-MWCNT, and ZnO@f-MWCNT, were characterised by powder X-ray diffraction (XRD), scanning electron microscopy (SEM), the Fourier-transform infrared (FT-IR) spectroscopy, atomic force microscopy (AFM), zeta potential, and the dynamic light scattering (DLS) techniques. DAS exhibited a significant enhancement (18-fold) in the oxidation peak current at ZnO@f-MWCNT, 10-fold at f-MWCNT, and 6-fold at ZnO NPs as compared to that at bare GCE. Under optimised conditions, a linear relationship was noticed among the peak current and concentration of DAS in the range of 0.03–82.65 μM and 0.01–122.45 μM for the differential pulse voltammetric (DPV), and square wave voltammetric (SWV) methods, respectively. Further, the applicability of the proposed sensor was demonstrated by analysing pharmaceutical and biological samples containing DAS. Higher percentage recovery values, and lower relative standard deviation (RSD) values highlighted the accuracy and precision proposed electrochemical methods.
Review—Aptamers and Biomimetic Receptors in Biosensing: Innovations and Applications
Authors: Tripathi Anjali , Pandey Vinay Kumar , Mishra Hridyanshi , Rustagi Sarvesh , Dar Aamir Hussain , Malik Sumira
Published: March 2024

The fields of biosensing have been transformed by the discovery of extraordinary molecular recognition components, such as aptamers and biomimetic receptors. Systematic Evolution of Ligands by Exponential Enrichment (SELEX) is a method used to select aptamers, or short sequences of single-stranded DNA (ssDNA) or RNA (ssRNA), based on their unique binding affinity to target molecules. Molecularly imprinted polymers (MIPs) are a type of biomimetic receptor that mimics the selectivity of natural receptors inside a synthetic matrix. They make it possible to identify pathogens, and illness biomarkers with accuracy. Aptamers and biomimetic receptors play crucial roles in various fields including diagnostics, therapeutics, and biosensing. Their high specificity, versatility, and adaptability enable targeted detection, drug delivery, and biomolecule manipulation, thereby contributing to advancements in personalized medicine, biotechnology, and disease diagnosis. Aptamers and biomimetic receptors have been combined with cutting-edge technologies, like nanotechnology and lab-on-a-chip systems, to create biosensors that are quick, portable, and extremely sensitive. These recognition features are anticipated to become more important as technology develops, helping to address global issues, advance biosensing capabilities, and raise people’s standard of living everywhere. Recent advancements and innovation on Aptamers and Biomimetic Receptors in Biosensing have been discussed in this review article.
Enantioanalysis of Cysteine Using an Enantioselective Stochastic Platform: A Key Factor on Early Diagnosis of Breast Cancer
Authors: Cioates Negut Catalina , Stefan-van Staden Raluca-Ioana
Published: March 2024

Proteomics and metabolomics have identified novel biomarkers, such as enantiomers of amino acids, that can be used for the early detection of cancer. This paper proposed a 3D enantioselective stochastic platform that contains a mixture of powder (diamond powder and TiO2) modified with calix [6] arene and has been used for the enantioanalysis of L- and D-Cysteine in biological samples. The results demonstrated an extended linear concentration range (up to 10−18mol l−1) and sensitivities of 1.00 × 107 s mol l−1 magnitude order. The recoveries of the enantiomers in biological samples were higher than 98.00%.
Advanced maternal age alters cardiac functional and structural adaptations to pregnancy in rats
Authors: Wooldridge Amy L. , Kirschenman Raven , Spaans Floor , Pasha Mazhar , Davidge Sandra T. , Cooke Christy-Lynn M.
Published: March 2024

We demonstrated that even before the age of reproductive senescence, rats show signs of age-related alterations in cardiac structure that suggests increased cardiac work. Our data also demonstrate, using an in vivo echocardiographic approach, that advanced maternal age in a rat model is associated with altered cardiac function and structure relative to younger pregnant controls.
Transient low shear-stress preconditioning influences long-term endothelial traction and alignment under high shear flow
Authors: Chandurkar Mohanish K. , Mittal Nikhil , Royer-Weeden Shaina P. , Lehmann Steven D. , Michels Etienne B. , Haarman Samuel E. , Severance Scott A. , Rho Yeonwoo , Han Sangyoon J.
Published: March 2024

In our study, we uncover that preconditioning with low shear stress yields enduring impacts on endothelial cell traction and orientation, persisting even after transitioning to high-shear conditions. Using Granger causality analysis, we demonstrate a functional link between the direction of cell traction and subsequent cellular alignment across varying shear environments.
Delivering Patient Education in Healthcare Organizations: An Integrative Review of the Nursing Administrative Actions
Authors: Linnavuori Elina , Inkeroinen Saija , Kostylev Anna , Seel Mariella , Virmajoki Milka , Virtanen Heli , Leino-Kilpi Helena
Published: March 2024

Aim. To analyze the literature on nursing administrative actions related to patient education to inform healthcare organizations for the development of patient education and identify the knowledge gaps for future research. Background. Patient education is a patient’s right, yet numerous organizational factors can hinder the effective delivery of patient education. Nursing administrative actions can mediate these factors, but little is known about nursing administration in patient education. Evaluation. A systematic integrative review was conducted in October 2022 on five databases (CINAHL (Ebsco), PubMed, Web of Science, ABI/Inform, and Business Source Complete). No time limitations were set. Empirical research articles reporting nursing administrative actions related to educational actions as a main topic were screened and evaluated. The data analysis was based on a constant comparison method. Key Issues. There were 3,110 studies identified, of which five quantitative and four qualitative studies were included. Three main themes were generated from the data describing nursing administrative actions related to patient education: (1) strengthen the commitment to patient education, (2) ensure the necessary resources for patient education, and (3) enhance patient education policies. Conclusion. This review provides insights into nursing administration in patient education, focusing on commitment, resources, and policies. It not only highlights the critical role of nurse administrators but also calls for further research to assess the impact of these actions. Implications for Nursing Management. The findings of this review will be useful for nurse administrators by providing knowledge about nursing administrative actions in patient education and underlining the need for them to pay more attention to it. The implications for nursing management also include supporting further research in the field.
Thiamine Deficiency Neuropathy in a Patient with Malnutrition due to Melancholic Depression
Authors: Melki Rihene , Ben Soussia Rim , Mrabet Houcem Elomma , Bouali Walid , Zarrouk Lazhar
Published: March 2024

Introduction. Melancholic depression is a daily clinical reality in psychiatry. It is a therapeutic emergency that can jeopardize life if not promptly and adequately treated. Apart from its high suicidal risk, complications related to the under-nourishment state are to be feared. Case Presentation. A 36-year-old woman was admitted with depressive symptoms, significant weight loss, and total functional impotence. Laboratory investigations revealed severe thiamine (vitamin B1) deficiency. An electromyography confirmed a sensory axonal neuropathy involving all four extremities suggesting a deficiency origin. Discussion. Vitamin and mineral deficiencies have been described in patients with malnutrition resulting from psychiatric illness (anorexia nervosa, eating disorders, severe depression, etc.). Thiamine is an essential cofactor in several biochemical pathways. Its deficiency can lead to neuropsychiatric morbidity. Conclusion. In our case, the rapid weight loss facilitated a cascade of complications related to nutritional deficiencies. Based on our clinical observations and the literature, thiamine deficiency should be considered in the presence of malnutrition and vulnerability, both on an organic and psychiatric level.
Effects of Black Quinoa Polysaccharides on Obesity and Intestinal Flora Dysbiosis in T2DM Mice
Authors: Zang Yanqing , Wu Kaiming , Liu Jiaci , Cao Yang , Wang Changyuan
Published: March 2024

To explore the mechanism of the hypoglycemic effect of BQP in type 2 diabetic mice induced by the combination of high-fat diet (HFD) and streptozotocin (STZ). Treatment with BQP significantly ameliorated blood glucose and lipid levels and improved oxidative stress levels and liver injury levels. The results of the intestinal flora study showed that the concentration of short-chain fatty acids (SCFAs) in cecum contents of BQP group mice was significantly higher than those of the diabetic mice. BQP treatment improved microbial disorders in feces, altered the diversity of intestinal flora, reduced the Bacteroidota to Firmicutes (B/F) ratio in diabetic mice, and increased the abundance of Dubosiella, Akkermansia, Faecalibaculum, and Allobaculum. Spearman correlation analysis showed that changes in intestinal microorganisms were closely related to biochemical parameters. The function’s prediction of gut microbiota indicated that the microbial compositions involving chemoheterotrophy, aerobic chemoheterotrophy, Gram-negative, potential pathogenicity, and sulfur cycle were changed. Conclusion. Intake of BQP can effectively regulate the blood glucose level of diabetic mice through improving glucose and lipid metabolism, and its mechanism may be related to the improvement of obesity and intestinal microecological balance.
Supplementary Table 7 from Gigaxonin Suppresses Epithelial-to-Mesenchymal Transition of Human Cancer Through Downregulation of Snail
Authors: Veena Mysore S. , Gahng Jungmo J. , Alani Mustafa , Ko Albert Y. , Basak Saroj K. , Liu Isabelle Y. , Hwang Kimberly J. , Chatoff Jenna R. , Venkatesan Natarajan , Morselli Marco , Yan Weihong , Ali Ibraheem , Kaczor-Urbanowicz Karolina Elżbieta , Gowda Bhavani Shankara , Frost Patrick , Pellegrini Matteo , Moatamed Neda A. , Wilczynski Sharon P. , Bomont Pascale , Wang Marilene B. , Shin Daniel Sanghoon , Srivatsan Eri S.
Published: March 2024

Neurodegenerative diseases and cancer
FIGURE 4 from Gigaxonin Suppresses Epithelial-to-Mesenchymal Transition of Human Cancer Through Downregulation of Snail
Authors: Veena Mysore S. , Gahng Jungmo J. , Alani Mustafa , Ko Albert Y. , Basak Saroj K. , Liu Isabelle Y. , Hwang Kimberly J. , Chatoff Jenna R. , Venkatesan Natarajan , Morselli Marco , Yan Weihong , Ali Ibraheem , Kaczor-Urbanowicz Karolina Elżbieta , Gowda Bhavani Shankara , Frost Patrick , Pellegrini Matteo , Moatamed Neda A. , Wilczynski Sharon P. , Bomont Pascale , Wang Marilene B. , Shin Daniel Sanghoon , Srivatsan Eri S.
Published: March 2024

Re-expression of gigaxonin leads to reversal of NFκB pathway. A, Re-expression of gigaxonin in GAN edited cells showed an intermediate epithelial morphology with a brighter light transmission than GAN edited cells or control lentiviral clones. B, Circos plots of the exome sequence analysis showing similar peaks for SNP in chromosomes 9 and 11 and intrachromosomal deletions (indels) for chromosomes 7, 15, and 16 in the parental ME180, GAN edited, and the lentiviral transfected clones. C, Re-expression of gigaxonin leads to increased expression of epithelial marker e-cadherin. Loss of n-cadherin and Snail expression are seen in gigaxonin re-expressing cells confirming inverse relationship between the gigaxonin and EMT markers. D, GO program of the RNA-seq data shows reversal to myogenesis signaling, and TNFα signaling via NFκB pathways in GAN re-expressing ME180/C4.15.1/LV GAN 50 cells. Lentiviral aliquots 25, 50, and 250 represent transfection of 5 × 103, 1 × 104, and 5 × 104 viral particles.
Remarkable Improvement of Diabetic Nephropathy in Transplanted Allograft after Kidney Transplantation
Authors: Tanaka Ryo , Imamura Ryoichi , Matsumura Soichi , Fukae Shota , Taniguchi Ayumu , Nakazawa Shigeaki , Yamanaka Kazuaki , Namba-Hamano Tomoko , Kakuta Yoichi , Takao Tetsuya , Fushimi Hiroaki , Nonomura Norio
Published: March 2024

Although glomerular damage caused by diabetic nephropathy was thought to be irreversible, in recent years, there have been reports on improvement in glomerular damage with strict glycemic control. However, few reports are available on the pathologic course after renal transplantation of donor-derived grafts with findings of diabetic nephropathy. A 53-year-old woman underwent an ABO blood-type compatible living-donor renal transplant. The recipient had no history of diabetes, and fasting blood glucose and hemoglobin A1c levels were both normal. The donor was a 57-year-old male who had received treatment for type 2 diabetes mellitus for 10 years. Transplant renal biopsy performed 1 h after revascularization showed mesangial matrix expansion and arterial hyalinosis due to diabetic nephropathy. The blood glucose level was within the normal range after transplantation. Mesangial matrix expansion and arterial hyalinosis disappeared in allograft biopsy samples 7 years after transplantation. We observed significant improvement in the pathological findings of donor-derived diabetic nephropathy after renal transplantation in the subsequent follow-ups.
Ocular Necessities: A Neuroethological Perspective on Vertebrate Visual Development
Authors: Hunt Jasper Elan , Pratt Kara Geo , Molnár Zoltán
Published: March 2024

Background: By examining species-specific innate behaviours, neuroethologists have characterized unique neural strategies and specializations from throughout the animal kingdom. Simultaneously, the field of evolutionary developmental biology (informally, “evo-devo”) seeks to make inferences about animals’ evolutionary histories through careful comparison of developmental processes between species, because evolution is the evolution of development. Yet despite the shared focus on cross-species comparisons, there is surprisingly little crosstalk between these two fields. Insights can be gleaned at the intersection of neuroethology and evo-devo. Every animal develops within an environment, wherein ecological pressures advantage some behaviours and disadvantage others. These pressures are reflected in the neurodevelopmental strategies employed by different animals across taxa. Summary: Vision is a system of particular interest for studying the adaptation of animals to their environments. The visual system enables a wide variety of animals across the vertebrate lineage to interact with their environments, presenting a fantastic opportunity to examine how ecological pressures have shaped animals’ behaviours and developmental strategies. Applying a neuroethological lens to the study of visual development, we advance a novel theory that accounts for the evolution of spontaneous retinal waves, an important phenomenon in the development of the visual system, across the vertebrate lineage. Key Messages: We synthesize literature on spontaneous retinal waves from across the vertebrate lineage. We find that ethological considerations explain some cross-species differences in the dynamics of retinal waves. In zebrafish, retinal waves may be more important for the development of the retina itself, rather than the retinofugal projections. We additionally suggest empirical tests to determine whether Xenopus laevis experiences retinal waves.
Diagnostic Accuracy of Point-of-Care Testing of C-Reactive Protein, Interleukin-6, and Procalcitonin in Neonates with Clinically Suspected Sepsis: A Prospective Observational Study
Authors: Goyal Medha , Mascarenhas Dwayne , RR Prashanth , Haribalakrishna Anitha
Published: March 2024

Objective: Sepsis often prompts clinicians to start empirical antibiotics in suspected neonates while awaiting diagnosis. The next-generation testing with point-of-care (POC) techniques offers a lead-time advantage that could bridge the gap by providing a timely diagnosis. Materials and Methods: We conducted a prospective diagnostic study in 82 neonates enrolled between May and October 2022 in a level III neonatal intensive care unit. All neonates with a new episode of clinically suspected sepsis were included. Diagnostic accuracy of POC testing of C-reactive protein (CRP), interleukin-6 (IL-6), and procalcitonin (PCT) with standard laboratory methods was performed. Results: The mean gestation age and birth weight of the neonates were 33.17 ± 4.25 weeks and 1,695.4 ± 700.74 grams, respectively. Most neonates were preterm (75%) with nearly equal proportions of early (51.22%) and late-onset (48.78%) sepsis. The POC CRP correlated well with standard CRP (r = 0.8001, 95% CI: 0.706–0.867, p < 0.0001). Among the three biomarkers, CRP had the maximum diagnostic accuracy (area under the curve [AUC] – 0.73) followed by PCT (AUC – 0.65) and IL-6 (0.55). There was no significant difference in the diagnostic accuracy of CRP (p = 0.46), PCT (p = 0.29), and IL-6 (p = 0.60) in early- and late-onset sepsis. The mean time for POC estimation of IL-6, PCT, and CRP was 12 ± 3 min which was significantly less compared to 366 ± 61 min for standard techniques (p < 0.001). Conclusion: POC CRP correlates well with standard techniques of estimation, and CRP alone and in combination with PCT has good diagnostic accuracy in neonatal sepsis.
Advances in Prehospital Management of Intracerebral Hemorrhage
Authors: Gioia Laura Catherine , Mendes George Nunes , Poppe Alexandre Yves , Stapf Christian
Published: March 2024

Background: Spontaneous acute intracerebral hemorrhage (ICH) is associated with greater stroke-related disability and mortality than acute ischemic stroke. Hematoma expansion (HME), an important treatment target in acute ICH, is time-dependent, with a greater probability of hematoma growth occurring <3 h from ICH onset. Summary: Promising treatment options to reduce HME include early intensive blood pressure reduction and the administration of hemostatic or anticoagulant reversal agents, yet large phase III clinical trials have so far failed to show overwhelming benefit for these interventions in acute ICH. Post hoc analyses provide evidence, however, that the therapeutic benefit of such treatments is enhanced by rapid and ultra-early intervention, likely driven in large part by attenuation of early HME. Clinical trials assessing ultra-rapid treatments (<2 h from ICH onset), including study procedures in the ambulance setting, are currently underway and demonstrate that the prehospital phase is a critical window for ICH management and an indispensable area of ICH research. Mobile stroke units, specialized ambulances equipped with imaging capabilities, can provide confirmatory diagnosis and expedite treatments. Nevertheless, multiple barriers (financial, organizational, geographical among others) hinder worldwide implementation. Emerging portable technologies as well as point-of-care measures of blood biomarkers show promise as feasible adjunct tools to discriminate ICH from acute ischemic stroke in the field and have the potential for widespread accessibility. Key Messages: Ultra-early interventions in acute ICH are likely necessary to mitigate the risk of HME, and as such, the prehospital setting is ideal to initiate time-sensitive ICH therapies. Reliable prehospital acute ICH detection is essential to provide disease-specific treatments. Overall, it is imperative that “Time is Brain” become the mantra not only for ischemic stroke but for ICH as well, and that the promise of ultra-early therapies for ICH be translated into concrete benefits for patients with this devastating condition.
Investigation of Novel Urinary Biomarkers in Hepatocellular Carcinoma Risk in a Predominantly African American Population: A Case-Control Study
Authors: Shingina Alexandra , Han Xijing , Fan Lei , Murff Harvey , Coffey Robert , Milne Ginger L. , Dai Qi , Shrubsole Martha
Published: March 2024

Introduction: African Americans are at increased risk of hepatocellular carcinoma (HCC) compared to other racial and ethnic groups. We investigated the associations of four urinary biomarkers of prostaglandin E2 (PGE-M), prostacyclin (PGI-M), and thromboxane (11dTxB2) synthesis and the ratio of PGI-M to 11dTXB2 with HCC risk in a cohort of predominantly African American populations. Methods: We conducted a nested case-control study (50 cases; 43 with HCC, 151 controls) in the Southern Community Cohort Study (SCCS), a large prospective cohort study including over 80,000 study participants, of whom two-thirds are African Americans. Urine samples were collected at enrollment and subsequently analyzed to assess biomarker levels. Multivariable regression models adjusted for age, race, sex, BMI, smoking status, NSAID use, education level, income, and alcohol consumption were used to assess the relationship between the biomarker and HCC risk. Results: Only 11dTxB2 (OR = 11.50; 95% CI [2.34–56.47] for highest tertile vs. lowest tertile, p = 0.004) and the PGI-M/11dTXB2 ratio of the second quartile (0.25–0.49) (OR = 5.16; 95% CI [1.44–18.47]; p = 0.01) were significantly associated with increased risk of liver cancer. Conclusion: 11dTXB2 and PGI-M/11dTXB2 ratio may be urinary markers of HCC risk, particularly among African Americans, and future prospective studies are needed to evaluate this finding further and to develop accessible methods.
The Comprehensive Complication Index in Ulcerative Colitis: A Comparison with the Clavien‒Dindo Classification
Authors: Horio Yuki , Uchino Motoi , Igeta Masataka , Nagano Kentaro , Kusunoki Kurando , Kuwahara Ryuichi , Sato Toshiyuki , Shinzaki Shinichiro , Ikeuchi Hiroki
Published: March 2024

Introduction: The comprehensive complication index (CCI), which weights all postoperative complications according to severity and integrates them into a single formula, has been reported as a new evaluation system. We aimed to compare the CCI with the Clavien‒Dindo Classification (CDC) to patients with ulcerative colitis (UC).
Methods: Patients who underwent initial surgery for UC from April 2012 to March 2020 were included. The patients were classified into a length of stay (LOS) >30 days group or an LOS ≤30 days group. We performed a multivariate analysis of risk factors for LOS >30 days in the model with the factors identified in the univariate analysis plus the CCI (the CCI model) and plus CDC (the CDC model). An ROC curve was used to test the difference in the area under the curve (AUC) between the CCI model and the CDC model.
Results: The median LOS was 21 days (IQR: 16-29 days), and the rate of LOS >30 days was 119/588 (20.2%). In the CCI model, age at the time of surgery (OR=1.24, 95% CI 1.07-1.45, p=0.01), ASA score ≥3 (OR=1.94, 95% CI 1.00-3.76, p=0.04), and CCI (OR=1.07, 95% CI 1.05-1.09; p<0.01) were identified as independent risk factors for LOS >30 days. The AUC value of the CCI model (0.86) was significantly better in relation to LOS > 30 days than that of the CDC model (0.82) (p =0.02).
Conclusion: The CCI was a better measure of LOS than was the CDC and was found to be a useful indicator in UC.
CNP Ameliorates Macrophage Inflammatory Response and Atherosclerosis
Authors: Bao Qiankun , Zhang Bangying , Zhou Lu , Yang Qian , Mu Xiaofeng , Liu Xing , Zhang Shiying , Yuan Meng , Zhang Yue , Che Jingjin , Wei Wen , Liu Tong , Li Guangping , He Jinlong
Published: March 2024

BACKGROUND:

CNP (C-type natriuretic peptide), an endogenous short peptide in the natriuretic peptide family, has emerged as an important regulator to govern vascular homeostasis. However, its role in the development of atherosclerosis remains unclear. This study aimed to investigate the impact of CNP on the progression of atherosclerotic plaques and elucidate its underlying mechanisms.

METHODS:

Plasma CNP levels were measured in patients with acute coronary syndrome. The potential atheroprotective role of CNP was evaluated in apolipoprotein E-deficient (ApoE
−/−
) mice through CNP supplementation via osmotic pumps, genetic overexpression, or LCZ696 administration. Various functional experiments involving CNP treatment were performed on primary macrophages derived from wild-type and CD36 (cluster of differentiation 36) knockout mice. Proteomics and multiple biochemical analyses were conducted to unravel the underlying mechanism.

RESULTS:

We observed a negative correlation between plasma CNP concentration and the burden of coronary atherosclerosis in patients. In early atherosclerotic plaques, CNP predominantly accumulated in macrophages but significantly decreased in advanced plaques. Supplementing CNP via osmotic pumps or genetic overexpression ameliorated atherosclerotic plaque formation and enhanced plaque stability in ApoE
−/−
mice. CNP promoted an anti-inflammatory macrophage phenotype and efferocytosis and reduced foam cell formation and necroptosis. Mechanistically, we found that CNP could accelerate HIF-1α (hypoxia-inducible factor 1-alpha) degradation in macrophages by enhancing the interaction between PHD (prolyl hydroxylase domain–containing protein) 2 and HIF-1α. Furthermore, we observed that CD36 bound to CNP and mediated its endocytosis in macrophages. Moreover, we demonstrated that the administration of LCZ696, an orally bioavailable drug recently approved for treating chronic heart failure with reduced ejection fraction, could amplify the bioactivity of CNP and ameliorate atherosclerotic plaque formation.

CONCLUSIONS:

Our study reveals that CNP enhanced plaque stability and alleviated macrophage inflammatory responses by promoting HIF-1α degradation, suggesting a novel atheroprotective role of CNP. Enhancing CNP bioactivity may offer a novel pharmacological strategy for treating related diseases.
Stroke Causes DNA Methylation at
Ncx1
Heart Promoter in the Brain Via DNMT1/MeCP2/REST Epigenetic Complex
Authors: Guida Natascia , Serani Angelo , Sanguigno Luca , Mascolo Luigi , Cuomo Ornella , Fioriniello Salvatore , Marano Domenico , Ragione Floriana Della , Anzilotti Serenella , Brancaccio Paola , Molinaro Pasquale , Pignataro Giuseppe , Annunziato Lucio , Formisano Luigi
Published: March 2024

Background

REST (Repressor‐Element 1 [RE1]‐silencing transcription factor) inhibits Na
+
/Ca
2+
exchanger‐1 (
Ncx1
) transcription in neurons through the binding of RE1 site on brain promoter
(Br)
after stroke. We identified a new putative RE1 site in
Ncx1
heart promoter
(Ht)
sequence (
Ht
‐RE1) that participates in neuronal
Ncx1
transcription. Because REST recruits DNA‐methyltransferase‐1 (DNMT1) and MeCP2 (methyl‐CpG binding protein 2) on different neuronal genes, we investigated the role of this complex in
Ncx1
transcriptional regulation after stroke.

Methods and Results

Luciferase experiments performed in SH‐SY5Y cells demonstrated that
Br
activity was selectively decreased by REST, whereas
Ht
activity was reduced by DNMT1, MeCP2, and REST. Notably, site‐direct mutagenesis of
Ht‐
RE1 prevented REST‐dependent downregulation of
Ncx1
. Furthermore, in temporoparietal cortex of 8‐week‐old male wild‐type mice (C57BL/6) subjected to transient middle cerebral artery occlusion, DNMT1, MeCP2, and REST binding to
Ht
promoter was increased, with a consequent DNA promoter hypermethylation. Intracerebroventricular injection of siREST prevented DNMT1/MeCP2 binding to
Ht
and
Ncx1
downregulation, thus causing a reduction in stroke‐induced damage. Consistently, in cortical neurons subjected to oxygen and glucose deprivation plus reoxygenation
Ncx1
knockdown counteracted neuronal protection induced by the demethylating agent 5‐azacytidine. For comparisons between 2 experimental groups, Student's
t
 test was used, whereas for more than 2 experimental groups, 1‐way ANOVA was used, followed by Tukey or Newman Keuls. Statistical significance was set at
P
<0.05.

Conclusions

If the results of this study are confirmed in humans, it could be asserted that DNMT1/MeCP2/REST complex disruption could be a new pharmacological strategy to reduce DNA methylation of
Ht
in the brain, ameliorating stroke damage.
Ankle–Brachial Index and Risk of Sudden Cardiac Death in the Community: The ARIC Study
Authors: Suzuki Takeki , Zhu Xiaoqian , Adabag Selcuk , Matsushita Kunihiro , Butler Kenneth R. , Griswold Michael E. , Alonso Alvaro , Rosamond Wayne , Sotoodehnia Nona , Mosley Thomas H.
Published: March 2024

Background

Sudden cardiac death (SCD) is a significant global public health problem accounting for 15% to 20% of all deaths. A great majority of SCD is associated with coronary heart disease, which may first be detected at autopsy. The ankle–brachial index (ABI) is a simple, noninvasive measure of subclinical atherosclerosis. The purpose of this study was to examine the relationship between ABI and SCD in a middle‐aged biracial general population.

Methods and Results

Participants of the ARIC (Atherosclerosis Risk in Communities) study with an ABI measurement between 1987 and 1989 were included. ABI was categorized as low (≤0.90), borderline (0.90–1.00), normal (1.00–1.40), and noncompressible (>1.40). SCD was defined as a sudden pulseless condition presumed to be caused by a ventricular tachyarrhythmia in a previously stable individual and was adjudicated by a committee of cardiac electrophysiologists, cardiologists, and internists. Cox proportional hazards models were used to evaluate the associations between baseline ABI and incident SCD. Of the 15 081 participants followed for a median of 23.5 years, 556 (3.7%) developed SCD (1.96 cases per 1000 person‐years). Low and borderline ABIs were associated with an increased risk of SCD (demographically adjusted hazard ratios [HRs], 2.27 [95% CI, 1.64–3.14] and 1.52 [95% CI, 1.17–1.96], respectively) compared with normal ABI. The association between low ABI and SCD remained significant after adjustment for traditional cardiovascular risk factors (HR, 1.63 [95% CI, 1.15–2.32]).

Conclusions

Low ABI is independently associated with an increased risk of SCD in a middle‐aged biracial general population. ABI could be incorporated into future SCD risk prediction models.
Relationship of Mild to Moderate Impairment of Left Ventricular Ejection Fraction With Fatal Ventricular Arrhythmic Events in Cardiac Sarcoidosis
Authors: Akama Yuka , Fujimoto Yudai , Matsue Yuya , Maeda Daichi , Yoshioka Kenji , Dotare Taishi , Sunayama Tsutomu , Nabeta Takeru , Naruse Yoshihisa , Kitai Takeshi , Taniguchi Tatsunori , Sato Shuntaro , Tanaka Hidekazu , Okumura Takahiro , Baba Yuichi , Minamino Tohru
Published: March 2024

Background

Current guidelines recommend placing an implantable cardiac defibrillator for patients with cardiac sarcoidosis and a severely impaired left ventricular ejection fraction (LVEF) of ≤35%. In this study, we determined the association between mild or moderate LVEF impairment and fatal ventricular arrhythmic event (FVAE).

Methods and Results

We retrospectively analyzed 401 patients with cardiac sarcoidosis without sustained ventricular arrhythmia at diagnosis. The primary end point was an FVAE, defined as the combined endpoint of documented ventricular tachycardia or ventricular fibrillation and sudden cardiac death. Two cutoff points for LVEF were used: a sex‐specific lower threshold of normal range of LVEF (52% for men and 54% for women) and an LVEF of 35%, which is used in the current guidelines. During a median follow‐up of 3.2 years, 58 FVAEs were observed, and the 5‐ and 10‐year estimated incidences of FVAEs were 16.8% and 23.0%, respectively. All patients were classified into 3 groups according to LVEF: impaired LVEF group, mild to moderate impairment of LVEF group, and maintained LVEF group. Multivariable competing risk analysis showed that both the impaired LVEF group (hazard ratio [HR], 3.24 [95% CI, 1.49–7.04]) and the mild to moderate impairment of LVEF group (HR, 2.16 [95% CI, 1.04–4.46]) were associated with a higher incidence of FVAEs than the maintained LVEF group after adjustment for covariates.

Conclusions

Patients with cardiac sarcoidosis are at a high risk of FVAEs, regardless of documented ventricular arrhythmia at the time of diagnosis. In patients with cardiac sarcoidosis, mild to moderate impairment of LVEF is associated with FVAEs.
Latino–White Disparities in Identification and Control of Elevated Blood Pressure Among Adults With Hypertension
Authors: Boston David , Hwang Jun , Lucas Jennifer A. , Marino Miguel , Larson Zoe , Sun Evelyn , Giebultowicz Sophia , Crookes Danielle M. , Rodriguez Carlos J. , Heintzman John
Published: March 2024

Background

Studies analyzing blood pressure (BP) management using the hypertension control cascade have consistently shown disparities in hypertension awareness, treatment, and BP control between Latino patients and non‐Latino White patients. We analyze this cascade using electronic health record data from a multistate network of community health centers.

Methods and Results

Data from 790 clinics in 23 US states from 2012 to 2020, including 1 270 174 patients, were analyzed to compare BP documentation in the electronic health record, clinician acknowledgment (diagnosis or treatment) of incident hypertension (BP ≥140/90), medication prescription, and BP control between non‐Latino White patients, English‐preferring Latino patients, and Spanish‐preferring Latino patients, adjusted for patient‐level covariates, and clustered on patients' primary clinics. Among the 429 182 patients with elevated BP (≥140/90) during ambulatory visits from 2012 to 2020, we found that clinician acknowledgment of hypertension was more likely in Spanish‐preferring and English‐preferring Latino patients versus non‐Latino White patients (adjusted odds ratio [aOR], 1.17 [95% CI, 1.11–1.24]; aOR, 1.07 [95% CI, 1.02–1.12], respectively). In addition, Spanish‐preferring Latino patients were more likely to receive a medication versus non‐Latino White patients (aOR, 1.21 [95% CI, 1.16–1.28]). Among those receiving medication, Latino patients were as likely as non‐Latino White patients to have their BP controlled (<140/90).

Conclusions

In a large retrospective study of community health center patients with incident hypertension, the expected disparities in hypertension management between Spanish‐preferring Latino, English‐preferring Latino, and non‐Latino White patients were not identified. These findings add to the hypertension control cascade by examining robust electronic health record data from community health centers and may provide clues to reducing disparities in hypertension management.