bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptomic signature, bioactivity and safety of a non-hepatoxic analgesic generating AM404 in the mid-brain PAG region
Authors: Bazan Hernan , Bhattacharjee Surjyadipta , Reid Madigan , Jun Bokkyoo , Polk Connor , Strain Madeleine , Pierre Linsey St , Desai Neehar , Daly Patrick , Cucinello-Ragland Jessica , Edwards Scott , Alvarez-Builla Julio , Cai James , Bazan Nicolas 
Published: May 2023

Abstract

The safe and effective management of pain is a critical healthcare and societal need. The potential for misuse and addiction associated with opioids, nephrotoxicity, and gastrointestinal damage from chronic non-steroidal anti-inflammatory drug (NSAID) use, as well as acute liver injury from paracetamol (ApAP) overdose, are unresolved challenges. To address them, we developed a non-opioid and non-hepatotoxic small molecule, SRP-001. Compared to ApAP, SRP-001 is not hepatotoxic as it does not produce N-acetyl-p-benzoquinone-imine (NAPQI) and maintains hepatic tight junction integrity at high doses. SRP-001 has comparable analgesia in pain models, including the complete Freund’s adjuvant (CFA) inflammatory von Frey. Both induce analgesia via N-arachidonoylphenolamine (AM404) formation in the midbrain periaqueductal grey (PAG) nociception area, with SRP-001 generating higher amounts of AM404 than ApAP. Single-cell transcriptomics of PAG uncovered that SRP-001 and ApAP also share modulation of pain-related gene expression and cell signaling pathways, including the endocannabinoid, mechanical nociception, and fatty acid amide hydrolase (FAAH) pathways. Both regulate the expression of key genes encoding FAAH, 2-AG, CNR1, CNR2, TRPV4, and voltage-gated Ca2+ channel. Interim Phase 1 trial results demonstrate SRP-001’s safety, tolerability, and favorable pharmacokinetics (NCT05484414). Given its non-hepatotoxicity and clinically validated analgesic mechanisms, SRP-001 offers a promising alternative to ApAP, NSAIDs, and opioids for safer pain treatment.
Development of a novel outlier index for real-time detection of water level outliers for open-channel water transfer projects
Authors: Zhou Luyan , Qiao Yu , Zhang Zhao , Han Zhongkai , Lei Xiaohui , Qin Yufeng , Wang Hao 
Published: May 2023

AbstractReal-time detection of water level outliers is critical for real-time regulation of gates or pump stations in open-channel water transfer projects. However, this remains a challenging task because of the lack of definition of water level outliers and the imbalance of flow monitoring data. In this study, we define the water level outliers and then propose a highly accurate outlier index for real-time detection of water level outliers based on the water level-flow relationship, and the thresholds for water level outliers are determined based on the order of magnitude of flow and water level differences. A case study is performed with the South-to-North Water Diversion Project of China. A random noise is added to 15 randomly selected non-adjacent monitoring datasets to verify the accuracy of the index, and the noise is increased from 4 to 9 cm at a step of 1 cm. The results show that a total of 159 outliers are detected out of 180 outliers with an accuracy rate of 88.3%.
Natural Anticancer Agents: Their Therapeutic Potential, Challenges
and Promising Outcomes
Authors: Tauro Savita , Dhokchawle Bharat , Mohite Popat , Nahar Deepali , Nadar Sahaya , Coutinho Evans 
Published: May 2023

Abstract:
Cancer, the second leading cause of death worldwide, is a major health
problem. Chemotherapy, radiation therapy and surgery are current treatments for cancer.
Most anticancer drugs have severe toxic effects and are required to be administered in cycles
to reduce toxicity and prevent resistance. Plant-based drugs have shown a potential
for treatment of cancer, and various plant secondary metabolites have shown promising
antitumor activity against several cancer cell lines, such as leukemia, colon cancer, prostate
cancer, breast cancer and lung cancer. Vincristine, etoposide, topotecan and paclitaxel,
which are of natural origin, are successfully used in clinical practice, and this has generated
interest in natural compounds as anticancer agents. Some phytoconstituents like
curcumin, piperine, allicin, quercetin and resveratrol have been extensively researched
and reviewed. In the current study, we have reviewed several plants like Athyrium hohenackerianum,
Aristolochia baetica, Boswellia serrata, Panax ginseng, Berberis vulgaris,
Tanacetum parthenium, Glycine max, Combretum fragrans, Persea americana,
Raphanus sativus, Camellia sinensis, and Nigella sativa for their source, key phytoconstituents,
and anticancer activity along with their toxicity profile. Few phytoconstituents
like boswellic acid, sulforaphane and ginsenoside showed excellent anticancer activity
compared to standard drugs and are potential clinical candidates.
Recent Updates on Oncogenic Signaling of Aurora Kinases in
Chemosensitive, Chemoresistant Cancers: Novel Medicinal Chemistry
Approaches for Targeting Aurora Kinases
Authors: Kumari Pooja , Beeraka Narasimha Murthy , Tengli Anandkumar , Bannimath Gurupadayya , Baath Ramandeep Kaur , Patil Mayuri 
Published: May 2023

Abstract:
The Aurora Kinase family (AKI) is composed of serine-threonine protein kinases
involved in the modulation of the cell cycle and mitosis. These kinases are required
for regulating the adherence of hereditary-related data. Members of this family can be categorized
into aurora kinase A (Ark-A), aurora kinase B (Ark-B), and aurora kinase C
(Ark-C), consisting of highly conserved threonine protein kinases. These kinases can modulate
cell processes such as spindle assembly, checkpoint pathway, and cytokinesis during
cell division. The main aim of this review is to explore recent updates on the oncogenic
signaling of aurora kinases in chemosensitive/chemoresistant cancers and to explore
the various medicinal chemistry approaches to target these kinases. We searched
Pubmed, Scopus, NLM, Pubchem, and Relemed to obtain information pertinent to the updated
signaling role of aurora kinases and medicinal chemistry approaches and discussed
the recently updated roles of each aurora kinases and their downstream signaling cascades
in the progression of several chemosensitive/chemoresistant cancers; subsequently,
we discussed the natural products (scoulerine, Corynoline, Hesperidin Jadomycin-B, fisetin),
and synthetic, medicinal chemistry molecules as aurora kinase inhibitors (AKIs). Several
natural products' efficacy was explained as AKIs in chemosensitization and chemoresistant
cancers. For instance, novel triazole molecules have been used against gastric cancer,
whereas cyanopyridines are used against colorectal cancer and trifluoroacetate derivatives
could be used for esophageal cancer. Furthermore, quinolone hydrazine derivatives
can be used to target breast cancer and cervical cancer. In contrast, the indole derivatives
can be preferred to target oral cancer whereas thiosemicarbazone-indole could be
used against prostate cancer, as reported in an earlier investigation against cancerous
cells. Moreover, these chemical derivatives can be examined as AKIs through preclinical
studies. In addition, the synthesis of novel AKIs through these medicinal chemistry substrates
in the laboratory using in silico and synthetic routes could be beneficial to develop
prospective novel AKIs to target chemoresistant cancers. This study is beneficial to oncologists,
chemists, and medicinal chemists to explore novel chemical moiety synthesis
to target specifically the peptide sequences of aurora kinases in several chemoresistant
cancer cell types.
The Natural Sweetener Stevia: An Updated Review on its Phytochemistry,
Health Benefits, and Anti-diabetic Study
Authors: Patel Shraddha , Navale Archana 
Published: May 2023

Abstract:
Stevia rebaudiana Bertoni is one of the significant high qualities of non-caloric sugar
substitute sweetener plants against diabetes disease. Diabetes mellitus is one of the most common
metabolic diseases caused by insulin secretion defects, insulin resistance in peripheral tissues, or
both. Stevia rebaudiana is a perennial shrub of the Compositae family that is grown in several
places around the world. It contains a plethora of different bioactive constituents which are responsible
for several activities and sweetness. This sweetness is due to the presence of steviol glycosides
which is 100-300 times sweeter than sucrose. Furthermore, stevia reduces oxidative stress,
lowering the risk of diabetes. Its leaves have been used to control and treat diabetes and a variety
of other metabolic diseases. This review summarizes the history, bioactive constituents of S. rebaudiana
extract, pharmacology, anti-diabetic activity, and its application, especially in food supplements.
A Comprehensive Review of Modern Methods for Load Prediction in the
Smart Grid
Authors: Attiwal Pushpa , Indora Sanjeev 
Published: May 2023

:
Load forecasting plays a crucial role in mitigating risks for utilities by predicting future
usage of commodity markets transmission or supplied by the utility. To achieve this, various techniques
such as price elastic demand, climate and consumer response, load analysis, and sustainable
energy generation predictive modelling are used. As both supply and demand fluctuate, and weather
and power prices can rise significantly during peak periods, accurate load forecasting becomes
critical for utilities. By providing brief demand forecasts, load forecasting can assist in estimating
load flows and making decisions that prevent overloading. Therefore, load forecasting is crucial in
helping electric utilities make informed decisions related to power, load switching, voltage regulation,
switching, and infrastructure development. Forecasting is a methodology used by electricity
companies to forecast the amount of electricity or power production needed to maintain constant
supply as well as load demand balance. It is required for the electrical industry to function properly.
The smart grid is a new system that enables electricity providers and customers to communicate
in real-time. The precise energy consumption sequence of the consumers is required to enhance the
demand schedule. This is where predicting the future comes into play. Forecasting future power
system load (electricity consumption) is a critical task in providing intelligence to the power grid.
Accurate forecasting allows utility companies to allocate resources and assume system control in
order to balance the same demand and availability for electricity. In this article, a study on load
forecasting algorithms based on deep learning, machine learning, hybrid methods, bio-inspired
techniques, and other techniques is carried out. Many other algorithms based on load forecasting
are discussed in this study. Different methods of load forecasting were compared using three performance
indices: RMSE (Root Mean Square Error), MAE (Mean Absolute Error), MAPE (Mean
Absolute Percentage Error), and Accuracy. Machine learning-based techniques showed a reduction
of 9.17% in MAPE, 0.0429% in RMSE, and 5.23% in MSE, and achieved 90% accuracy. Deep
learning-based techniques resulted in a 9.61% decrease in MAPE and achieved 91% accuracy. Bioinspired
techniques provided a reduction of 9.66% in MAPE, 0.026% in RMSE, and 5.24% in
MSE, and achieved 95% accuracy. These findings concluded that optimization techniques are more
encouraging in predicting load demand and, as a result, can represent a reliable decision-making
tool.
Microspheres: A Novel Approach for Sustained Colon Targeted Drug
Delivery
Authors: Jaunjalkar Vaibhavi , Chopade Shakuntala 
Published: May 2023

Abstract:
Colon targeted medication delivery is a field of study for disorders including colon can-cer and inflammatory bowel disease (IBD), with the goal of delivering localised therapy with mini-mal systemic damage. In recent decades, the global prevalence of colonic problems has increased, demanding more local treatment of colonic disorders, which will lead to the development of more effective and safe pharmaceutical regimens. When developing a formulation for colonic administra-tion, it's critical to consider both the physiological characteristics of the colon and the environment surrounding the disease site (s). The GI tract experiences dynamic changes in motility, fluid vol-ume, enzyme activity, and pH from the stomach to the intestine. The current review focuses on Bio-degradable polymers or protein‑based microspheres having free‑flowing properties and particle size 5200 nm have a variety of advantages over conventional colon targeted drug delivery systems. Dur-ing drug transit through the GIT, polysaccharides maintain their integrity and inhibit drug release. When it comes into contact with colonic fluid, however, it is attacked by anaerobic microbes, and the imprisoned medication is released. In this review, several methods of microsphere formulation and characterization were investigated along with its in vitro and in vivo study methodology.
Review on Diabetes Mellitus: An Insight into the Current Scenarios, the Challenges of Therapy, and Application of Traditional Drugs
Authors: Mishra Ashwini Kumar , Pandey Mukesh , Pannu Arzoo , Dewangan Hitesh Kumar , Sahoo P.K. 
Published: May 2023

Abstract:Diabetes mellitus, an epidemic of the 21st century, is listed as one of the top ten causes of death around the world by the World Health Organization and is a complicated disease to deal with. Medically, a metabolic disorder characterized by elevated blood glucose levels and altered metabolism of biological macromolecules, mainly carbohydrates. Diabetes mellitus has a worldwide prevalence, and populations of all high, middle, as well as low-income countries, are affected by it. More than 400 million persons are currently living with diabetes. Many risk factors, such as lack of exercise, irregular diet, drinking, and smoking habits, as well as genetic factors, also contribute to the increased incidence of diabetes mellitus in the modern era. The conventional therapies for diabetes are based on insulin, insulin analogues, peptides, and oral hypoglycemics. The primary objective is to lower the elevated blood glucose levels and manage the distress to enhance the quality of life of the patient. The management of diabetes is very crucial to avoid complications having serious consequences such as the extra economic burden due to these complications. Conventional drug therapy has its own adverse effects, and its timely availability and cost are still an issue in many low and middle-income countries. Diabetes mellitus has been reported in various ancient kinds of literature along with various natural remedies (plants/herbals) useful in it. These plant-based remedies offer the benefits of lesser or no adverse effects, easy availability due to natural abundance, and low cost. Therefore, extensive research work is carried out in the past few decades to identify and understand the underlying principles of plant-based/herbal medicines to develop new potential lead molecules and a relatively safer, easily available and more economical alternative treatment therapy for diabetes mellitus.
Permittivity-customizable Low-cost Laminated PET Sheet Multilayer Substrate
to Design Flexible and Conformal Planar Inverted F Antenna
Authors: Maithani Sachin , Bansal Shivam , Saini Garima , Dhaliwal Balwinder Singh 
Published: May 2023

Abstract:
In this article, a Planar Inverted F Antenna (PIFA) has been designed using low-cost
commercially available transparent laminated sheets. Energy Dispersive X-ray (EDX) analysis is
used to acquire the element composition of the transparent laminated sheet.

Methods:
The flexibility is attained using a market-available low-cost Polyethylene Terephthalate
(PET) sheet as a substrate. The dielectric properties of this non-conventional laminated sheet need
to be identified for antenna design and the microstrip ring resonator test method is used to determine
the dielectric properties of the multilayer PET sheets.

Results:
The linear match has been observed on multilayer laminated PET sheets for dielectric
properties and radiation characteristics. Adhesive copper foil of a thickness of 0.08 mm has been
used as for conducting layer on the PET lamination sheet. As per the literature survey, it is evident
that this is the first attempt to use the reported methodology for PIFA design application. The gain
of proposed antenna is 5.2dB.

Conclusion:
The designed flexible antenna has been developed for wearable and IoT applications
in 2.45 GHz ISM band. A good match has been observed between the simulated and measured
characteristics.
Selection of Digital Watermarking Techniques for Medical Image Security by
Using the Fuzzy Analytical Hierarchy Process
Authors: Ahmad Masood , Nadeem Mohd , Islam Mohd , Ali Saquib , Agrawal Alka , Ahmad Khan Raees 
Published: May 2023

Background:
The watermarking technique is a security algorithm for medical images and the patient's information. Watermarking is used for maintaining the robustness, integrity, confidentiality, authentication, and complexity of medical images.

Objective:
The selection of medical image watermarking technique is multi-criteria decision-making and an automatic way of algorithm selection for security and privacy. However, it is difficult to select a better watermarking technique through traditional selection techniques.

Methods:
To deal with this problem, a multicriteria-based fuzzy analytic hierarchy process (FAHP) was proposed. This method is applied for algorithm selection for the security of medical images in healthcare. In this method, we first determined the list of criteria and alternatives, which directly affect the decision of the medical image security algorithm. Then, the proposed method was applied to the criteria and alternatives.

Results:
We provided the rank according to the obtained weights of the algorithm. Furthermore, the overall results and ranking of the algorithms were also presented in this article.

Conclusion:
Integrity was found to have the highest weight (0.509) compared to the other criteria. The weight of the other criteria, namely authentication, was 0.165, robustness was 0.151, confidentiality was 0.135, and complexity was 0.038. Thus, in terms of ranking, integrity was reported to be of the highest priority among the five criteria attributes.
The economic feasibility analysis of innovative megaprojects for the benefit of construction enterprises: the case of the Republic of Tatarstan
Authors: Grabovyy Petr Grigorievich , Azhimov Timur Zagidovich , Volkov Roman Vyacheslavovich 
Published: May 2023

The strategic development of the Republic of Tatarstan determines its development prospects for the coming 10–20 years. Its land zoning has shown that Kazan, Kama and Almetyevsk are the three fastest developing agglomerations in the republic. Nonetheless, many areas cannot benefit from the flow of goods and resources. A research on logistics allows to assume that the development of a road transportation network, including the construction of bridges, tunnels and the use of the river transport (as the cheapest means of transport) is a must. Along with the development of transport arteries, the republic needs advanced development points, the construction industry growth triggers, modernization and reconstruction of construction industry enterprises.
In the article, the co-authors analyze the natural resources, available in Tatarstan and the prospects for the establishment of enterprises for the production of construction materials in Tatarstan.
The co-authors consider alternative cement delivery routes, key products needed for the development of housing and industrial construction to ensure the economic prosperity of Tatarstan. The co-authors have also analyzed the economic efficiency of investment projects to be implemented in Tatarstan Republic, including the launch of a cement production facility that will take advantage of the mineral resources in the Ulyanovsk region minerals and the imported clinker to be delivered from Iran by water. The co-authors have also considered the potential construction of the toll highway “Shali (M-7) – Bavly (M-5)”.
The Verhulst equation in managing the life cycle of a real estate facility
Authors: Volkov Roman  Vyacheslavovich 
Published: May 2023

Managing the lifecycle of a real estate facility is an important part of the reproduction process. A brief analysis of corporate lifecycle models is provided. As a scientific research hypothesis, it is assumed that the initial stage lifecycle is based on consumption of external resources, while at the final stage internal resources are consumed. The concepts of “resource consumption lifecycle model” and “resource consumption rate” are introduced. It is the rate of resource consumption that determines the end of the real estate facility lifecycle. The Verhulst differential equation for the population growth model is used as a mathematical basis. The lifecycle model has three phases: growth, stability, and degradation. This model can be applied to change the lifecycle of a construction facility. Synchronous and asynchronous types of management are described. It is proven that monitoring and forecasting are components of synchronous management of a real estate lifecycle.
Methodological approaches to the formation of flexible structures for managing construction groups
Authors: Zhelikhovskiy Denis Olegovich , Beliakov Sergei Igorevich 
Published: May 2023

In the article the main aspects of the formation of flexible management structures of corporate associations of construction enterprises — construction groups are considered. The subjects of the investment and construction complex must quickly respond to changes in the external environment, should have possibility to adjust to possible changes in the economy and other spheres. Such an opportunity can be realized on the basis of the formation of flexible management structures of organizations. A flexible management structure is an organizational structure that allows an enterprise to respond quickly and effectively to the changes in the external or internal environment. In general, flexible management structures are a set of system elements that can adapt to changing environmental conditions in order to ensure an acceptable level of efficiency and production optimization and management processes under conditions of changing environment. In this case, the formation of organizational structures is implemented at the following levels: intra-company level, organizational and functional level, organizational and contractual level. Formation of flexible organizational structures for the management of a construction group should be realized within the limits of the certain strategy, while fulfilling the conditions for maximizing the level of strategic development while ensuring a sufficient level of general stability of the construction group.
Epistemology of Ngelmu in Wedhatama Fibers
Authors: Alfiana Nur 
Published: May 2023

The purpose of this study is to uncover the epistemology of ngelmu in Wedhatama Fiber. Science and ngelmu in Javanese tradition are different. If science is rational and intellectual, it is more ruhaniah, high value, and becomes the basis of human behavior. This research method is qualitative. Data obtained through literature studies. Journals and books that discuss ngelmu in Serat Wedhatama become databases and analyses. The result of this study is that in Serat Wedhatama, ngelmu is also not limited to theory and intellectuals alone, but a practice that is aware of the noble values of teachings (piwulang). Between science and deeds must be balanced. People who try to find ngelmu (makrifat) by going through suluk or Sufism are called Sufis or mystics.