bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synthesis of Some New Phthalazine−piperazine−pyrazole Conjugates; In vitro Anti‐Cancer, ADMET And Molecular Docking Studies
Authors: Badithapuram Vinitha , Kumar Nukala Satheesh , Dasari Gouthami , Swamy Thirukovela Narasimha , Bandari Srinivas 
Published: March 2023

AbstractA new series of phthalazine−piperazine−pyrazole conjugates were synthesised and evaluated for their in vitro anticancer activity against three human cancer cell lines including MCF‐7 (breast), A549 (lung) and DU‐145 (prostate). The result data showed that compound 2‐((3‐(3,5‐dimethoxyphenyl)‐1H‐pyrazol‐5‐yl)methyl)‐4‐(piperazin‐1‐yl methyl)phthalazin‐1(2H)‐one (5 i) showed comparable activity against all the cell lines with the standard drug Etoposide. As well, compounds 2‐((3‐(3‐methoxyphenyl)‐1H‐pyrazol‐5‐yl) methyl)‐4‐(piperazin‐1‐ylmethyl) phthalazin‐1(2H)‐one (5 j) and 2‐((3‐(3,5‐dimethylphenyl)‐1H‐pyrazol‐5‐yl) methyl)‐4‐(piperazin‐1‐ylmethyl) phthalazin‐1(2H)‐one (5 l) exhibited promising activity against three cancer cell lines as compared to Etoposide. Three potent compounds (5 i, 5 j, and 5 l) were examined against the normal breast cell line in a cell viability assay (MCF‐10A), but none of them showed any apparent cytotoxicity with IC50 values above 78 μM. In addition, compounds 5 i, 5 j, and 5 l were screened for the VEGFR‐2 tyrosine kinase inhibitory activity using sorafenib as the standard drug and found that compound 5 i exhibited more potency in inhibiting the VEGFR‐2 tyrosine kinase as compared to sorafenib. Finally, molecular docking studies of compounds 5 i, 5 j and 5 l were also revealed that these compounds showed more binding interactions with VEGFR‐2 than VEGFR‐1. In accumulation to this, in silico pharmacokinetic profile was carried out for the potent compounds 5 i, 5 j and 5 l by SWISS/ADME and pkCSM. Whereas, 5 i, 5 j and 5 l compounds followed Lipinski, Veber, Egan, and Muegge rules without any deviation.
t‐BuOH Solvent for CuSeO3CatalyzedCsp2‐SeCross‐coupling of Diaryldiselenide with Arylhalides and Boronic acids
Authors: Kumar Pradhan Amit , Kumar Behera Pradyota , Choudhury Prabhupada , Behera Papita , Swain Amlan , Bag Priyanka , Pany Debiprasad , Rout Laxmidhar 
Published: March 2023

AbstractFormation of carbon‐selenium bond byCsp2‐Secross‐coupling using diaryldiselenides and arylhalides are very few in literature. Herein we report CuSeO3.2H2O as an efficient catalyst for directCsp2‐Secross‐coupling of diaryldiselenides with aryl iodides, bromides and aryl boronic acids. The reaction is performed at low temperature (70 °C) intert‐butanol solvent in absence of ligand. Arylboronic acids are more reactive than aryliodides and bromides.
Oncolytic Virus‐Driven Biotherapies from Bench to Bedside
Authors: Duan Shijie , Wang Shuhang , Qiao Lei , Yu Xinbo , Wang Nan , Chen Liting , Zhang Xinyuan , Zhao Xu , Liu Hongyu , Wang Tianye , Wu Ying , Li Ning , Liu Funan 
Published: March 2023

AbstractWith advances in cancer biology and an ever‐deepening understanding of molecular virology, oncolytic virus (OV)‐driven therapies have developed rapidly and become a promising alternative to traditional cancer therapies. In recent years, satisfactory results for oncolytic virus therapy (OVT) are achieved at both the cellular and organismal levels, and efforts are being increasingly directed toward clinical trials. Unfortunately, OVT remains ineffective in these trials, especially when performed using only a single OV reagent. In contrast, integrated approaches, such as using immunotherapy, chemotherapy, or radiotherapy, alongside OVT have demonstrated considerable efficacy. The challenges of OVT in clinical efficacy include the restricted scope of intratumoral injections and poor targeting of intravenous administration. Further optimization of OVT delivery is needed before OVs become a viable therapy for tumor treatment. In this review, the development process and antitumor mechanisms of OVs are introduced. The advances in OVT delivery routes to provide perspectives and directions for the improvement of OVT delivery are highlighted. This review also discusses the advantages and limitations of OVT monotherapy and combination therapy through the lens of recent clinical trials and aims to chart a course toward safer and more effective OVT strategies.
MXene‐Based Aptameric Fluorosensor for Sensitive and Rapid Detection of COVID‐19
Authors: Luo Yao , Jiang Xin , Zhang Rong , Shen Chen , Li Mei , Zhao Zhenzhen , Lv Mengyuan , Sun Shengjun , Sun Xuping , Ying Binwu 
Published: March 2023

AbstractThe severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2)‐caused COVID‐19 pandemic has rapidly escalated into the largest global health emergency, which pushes to develop detection kits for the detection of COVID‐19 with high sensitivity, specificity, and fast analysis. Here, aptamer‐functionalized MXene nanosheet is demonstrated as a novel bionanosensor that detects COVID‐19. Upon binding to the spike receptor binding domain of SARS‐CoV‐2, the aptamer probe is released from MXene surface restoring the quenched fluorescence. The performances of the fluorosensor are evaluated using antigen protein, cultured virus, and swab specimens from COVID‐19 patients. It is evidenced that this sensor can detect SARS‐CoV‐2 spike protein at final concentration of 38.9 fg mL−1 and SARS‐CoV‐2 pseudovirus (limit of detection: 7.2 copies) within 30 min. Its application for clinical samples analysis is also demonstrated successfully. This work offers an effective sensing platform for sensitive and rapid detection of COVID‐19 with high specificity.
Photocatalytic Activity of the Oxidation Stabilized Ti3C2Tx MXene in Decomposing Methylene Blue, Bromocresol Green and Commercial Textile Dye
Authors: Bury Dominika , Jakubczak Michał , Purbayanto Muhammad Abiyyu Kenichi , Wojciechowska Anita , Moszczyńska Dorota , Jastrzębska Agnieszka Maria 
Published: March 2023

AbstractTwo‐dimensional MXenes are excellent photocatalysts. However, their low oxidation stability makes controlling photocatalytic processes challenging. For the first time, this work elucidates the influence of the oxidation stabilization of model 2D Ti3C2Tx MXene on its optical and photocatalytic properties. The delaminated MXene is synthesized via two well‐established approaches: hydrofluoric acid/tetramethylammonium hydroxide (TMAOH‐MXene) and minimum intensive layer delamination with hydrochloric acid/lithium fluoride (MILD‐MXene) and then stabilized by L‐ascorbic acid. Both MXenes at a minimal concentration of 32 mg L−1 show almost 100% effectiveness in the 180‐min photocatalytic decomposition of 25 mg L−1 model methylene blue and bromocresol green dyes. Industrial viability is achieved by decomposing a commercial textile dye having 100 times higher concentration than that of model dyes. In such conditions, MILD‐MXene is the most efficient due to less wide optical band gap than TMAOH‐MXene. The MILD‐MXene required only few seconds of UV light, simulated white light, or 500 nm (cyan) light irradiation to fully decompose the dye. The photocatalytic mechanism of action is associated with the interplay between surface dye adsorption and the reactive oxygen species generated by MXene under light irradiation. Importantly, both MXenes are successfully reused and retained approximately 70% of their activity.
Digital Language Learning: A Sociocultural Theory Perspective
Authors: Lantolf James P. , Xi Jiao 
Published: March 2023

AbstractThe article reviews Digital Language Learning (DLL) research that has used principles and concepts of Sociocultural Theory (SCT) to support the research. We explain several key principles of the theory and shows how they have been misused or used in a superficial way in the DLL research. These include the assumption that SCT is a social rather than a psychological theory as well as misinterpretation of the central concepts of imitation and the Zone of Proximal Development. The article argues that the assumption that Virtual Reality pedagogy—which claims it is a means to avoid a parasitic relationship between L1 and L2—is problematic and not supported by an SCT perspective because the theory assigns a central role to L1 in all aspects of psychological development. It also argues that DLL pedagogy that seeks to avoid explicit instruction in favor of implicit learning through comprehensible input may well hinder full development of a new language. Finally, the article suggests ways in which DLL and SCT‐based language pedagogy can be integrated into a coherent instructional program.
Swietenine inhibited oxidative stress through AKT/Nrf2/HO‐1 signal pathways and the liver‐protective effect in T2DM mice: In vivo and in vitro study
Authors: Duan Jingyu , Zhao Yangqi , Pei Feilong , Deng Wenhao , He Liangliang , Rao Chengdian , Zhai Yutong , Zhang Chunping 
Published: March 2023

AbstractSwietenia macrophylla King, belongs to the Meliaceae family, is a valuable medicinal plant and its fruits have been processed commercially to a variety of health foods. The seeds have long been known for their ethnomedicinal significance against these diseases. Swietenine (Swi) was isolated from S. macrophylla and could ameliorate inflammation and oxidative stress. In this study, HepG2 cells induced by H2O2 were used to construct oxidative stress model in vitro. The aim of this study was to investigate the protective effect of Swi on H2O2 induced oxidative injury in HepG2 cells and its molecular mechanism, and to explore the effect of Swi on liver injury in db/db mice and its possible mechanism. The results showed that Swi significantly inhibited HepG2 cells viability and reduced oxidative damage in a dose‐dependent manner as evidenced by a range of biochemical analysis and immunoblotting study. Moreover, it induced the protein and mRNA expression of HO‐1 together with its upstream mediator Nrf2 and activated the phosphorylation of AKT in HepG2 cells. LY294002, a PI3K/AKT inhibitor, significantly suppressed the Nrf2 nuclear translocation and HO‐1 expression in H2O2 induced HepG2 cells treated with Swi. In addition, RNA interference with Nrf2 significantly reduced the expression level of Nrf2 and HO‐1 in the nucleus. Swi has a significant protective effect on cell damage in H2O2 induced HepG2 cells by increasing the antioxidant capacity which is achieved through the AKT/Nrf2/HO‐1 pathway. Additionally, in vivo, Swi could protect the liver of type 2 diabetic mice by improving lipid deposition in liver tissue and inhibiting oxidative stress. These findings indicated that Swi can be a promising dietary agent to improve type 2 diabetes.
Ecosystem Processes and Dynamics in Mesic Savannas
Authors: Huntley Brian John 
Published: March 2023

AbstractAn introduction is presented to systems ecology, through models of the pathways, pools and fluxes of materials in terrestrial ecosystems, and the role of feedback mechanisms, and of the first and second laws of thermodynamics. Food chains, food webs and trophic levels provide structure to ecosystem processes. The importance of the C4 photosynthetic pathway of the tropical grasses that dominate mesic and arid savanna biomes is emphasised. Details of the production, consumption and decomposition processes revealed in studies of mesic savanna in southern, central and western Africa illustrate the dynamics of carbon through terrestrial ecosystems. At landscape scale, the dynamics of the savanna/forest interface, that characterise much of northern Angola, is discussed in terms of tree-grass interactions and the existence of alternative stable states determined by fire.
The Mesic Savanna Biome
Authors: Huntley Brian John 
Published: March 2023

AbstractThe Savanna Biomes (Mesic/Dystrophic and Arid/Eutrophic) of Angola cover over 90% of the country. This Chapter presents the case for the recognition, across Africa, of these two distinctive savanna biomes, both defined by the co-dominance of fire-tolerant trees and C4 grasses, falling within seasonal climates of warm, wet summers and mild, dry winters. The Mesic Savanna Biome occurs predominantly on the dystrophic (nutrient-poor) soils of the old peneplains of the Central African Plateau, mostly between 900 and 1400 m above sea level, and where rainfall ranges from 650 to 1400 mm per year. Fire is the main consumer of the grasslands, and is the key determinant of tree/grass dynamics. The biome covers 68% of Angola, and includes six ecoregions, to which may be added two ecoregions with a mosaic of tallgrass mesic savanna and forest patches occupying a further 16%, where Guineo-congolian forests and Zambezian mesic savannas interdigitate in northern Angola. Trees of the genera Brachystegia and Julbernardia characterise what is regionally know as miombo woodland. The physical, physiognomic, floristic and faunistic characteristics and unique natural phenomena of the biome are described in detail. The importance of the catena as a landscape feature determining vegetation pattern, and the role of termitaria in providing nutrient-rich islands in a sea of nutrient-poor soils, plus the abundance of ‘underground forests’ created by woody geoxyles, represent some of the special features of the biome.
The Namib Desert Biome
Authors: Huntley Brian John 
Published: March 2023

AbstractThe Namib Desert is recognised as one of the oldest deserts in the world. In this Chapter, its age and evolution through the past 55 million years are described, and the source and mechanisms of transportation and deposition of the dunes that cover large areas of the Namib coast are summarised. The role of the South Atlantic Anticyclone, the Benguela Current, and wind and fog as key factors in the evolution and maintenance of the desert ecosystems are described. The Namib Desert ecoregion occurs along the Angolan coast as a narrow belt from the Cunene River to the Carunjamba River. The diverse landscapes and their sparse vegetation mantle are photographically illustrated. Both flora and fauna have many disjunct distributions linking them with the Horn of Africa suggesting the existence of an arid corridor across eastern Africa during the Pleistocene. The flora and fauna of the Namib Desert, and in particular, the biology of the enigmatic gymnosperm, Welwitschia mirabilis, are discussed.
Biomes: Concepts, Characteristics and Terminology
Authors: Huntley Brian John 
Published: March 2023

AbstractA cornerstone of ecology is the mapping and classification of biogeographical and ecological diversity, defining patterns in species distribution and abundance. This Chapter presents the concepts of biomes, biogeographical realms and centres of endemism, and the relationship of Angolan and southern African biogeographic units to the rest of the continent. Key ecological terms are defined and characterised using Angolan examples, within the context of the biomes and transitional mosaics found across Africa. The 16 ecoregions of Angola are mapped and their surface area, altitudinal range, and mean annual rainfall quantified. The ecological characterisation of rain forest, mesic savanna and arid savanna biomes are explained in quantitative and graphic detail.
Landscapes: Geology, Geomorphology and Hydrology
Authors: Huntley Brian John 
Published: March 2023

AbstractThe long history of Angola’s physical environment goes back to its Gondwanan origins, 550 million years ago. To give context to the present landscapes of Angola, a brief geological history of the Earth provides a backdrop to the dramatic evolutionary innovations that occurred in terrestrial ecosystems during the Miocene Epoch (23-5.3 million years ago), which shaped Africa’s savanna biomes as we know them today. The geomorphological patterns of Angola developed in response to periods of uplift (the Mayombe and Bié swells, the Angolan Escarpment), subsidence (the Congo and Kalahari Basins), erosion and deposition (the Planalto, Congo and Zambezian Peneplains). Angola has 12 main landscape groups, with which its ecoregions are closely aligned. The country is drained by six major transnational hydrological basins, providing the ‘water towers’ of southern and central Africa. The ecosystem services which these water resources provide to the region are described in terms of their role in pollution regulation, hydro-electric power generation and biodiversity maintenance.
Soil, Water and Nutrients
Authors: Huntley Brian John 
Published: March 2023

AbstractThis Chapter provides an introduction to basic elements of soil science, from an understanding of the soil profile, its develop and its importance to plant growth. The processes of weathering and the development of laterites, calcretes, salinised and other major soil types and their distribution in Angola are described. Soil water relations and soil chemistry and thus the availability of water and nutrients are fundamental determinants of plant growth, species composition and productivity. The differences between dystrophic (low base status) and eutrophic (high base status) soils and the distribution of the mesic/dystrophic savanna biome and the arid/eutrophic savanna biome, which dominate Angolan landscapes (totaling over 90% of the vegetation mantle of the country) are emphasised. The Key Soil Groups of Angola are mapped and their characteristics summarised. Sandy arenosols cover 53% of Angola, mainly comprising the Kalahari sands of the eastern half of Angola. Ferralsols cover 23% of Angola, occupying the spine of crystalline rocks along the western highlands. Both are of low nutrient status but carry dense miombo woodlands where they have not been transformed by human activities. Richer soils occur along the escarpment and hot coastal lowlands. The processes of land degradation, due to inappropriate soil management threaten the livelihoods of communities living on these fragile soils, are described.
Interprofessional Learning Outcomes-Based Curriculum to Support Behaviour Change in Persons Self-Managing Chronic Disease
Authors: Kerkstra Afke , Baixinho Cristina Lavareda , Félix Isa Brito , Strawbridge Judith , Guerreiro Mara Pereira 
Published: March 2023

AbstractThis chapter sets the stage for the remaining book, by introducing the Train4Health project and by explaining how the learning outcomes presented in subsequent chapters have been derived and linked with content of the book. Firstly, the Train4Health interprofessional competency framework to support behaviour change in persons self-managing chronic disease is briefly presented. This European competency framework was the starting point for developing the learning outcomes-based curriculum, which is succinctly addressed in the subsequent section. Finally, practical considerations about the Train4Health curriculum are discussed, including opportunities and challenges for interprofessional education.
Municipal Cybersecurity—A Neglected Research Area? A Survey of Current Research
Authors: Vestad Arnstein , Yang Bian 
Published: March 2023

AbstractMunicipalities are tasked with ensuring the cybersecurity of critical public services and functions in diverse areas such as safe water supply, healthcare, child protective services, and education with vastly different security requirements—all usually served from a common infrastructure with limited technical and organizational cybersecurity capabilities. This literature review identifies recent research on municipal and local government cybersecurity to identify current research areas, state of the art, and research methods used in research so far. We found research in the areas of smart cities, elections, human factors, operational technology, and crisis management. We also give suggestions for further research to develop better models for cybersecurity in cross-disciplinary organizations.
Heavy neutral leptons at the Electron-Ion Collider
Authors: Batell Brian , Ghosh Tathagata , Han Tao , Xie Keping 
Published: March 2023

Abstract
The future Electron-Ion Collider (EIC) at Brookhaven National Laboratory, along with its primary capacity to elucidate the nuclear structure, will offer new opportunities to probe physics beyond the Standard Model coupled to the electroweak sector. Among the best motivated examples of such new physics are new heavy neutral leptons (HNLs), which are likely to play a key role in neutrino mass generation and lepton number violation. We study the capability of the EIC to search for HNLs, which can be produced in electron- proton collisions through charged current interactions as a consequence of their mixing with light neutrinos. We find that, with the EIC design energy and integrated luminosity, one is able to probe HNLs in the mass range of 1 – 100 GeV with mixing angles down to the order of 10−4 − 10−3 through the prompt decay signatures, and in the mass range of 1 10 GeV with |Ue|2 ~ 10−6 – 10−4 via the displaced decay signatures. We also consider the invisible mode where an HNL is undetected or decaying to dark sector particles. One could potentially probe heavy HNLs for mixing angles in the window 10−3 – 10−2, provided SM background systematics can be brought under control. These searches are complementary to other probes of HNLs, such as neutrino-less double-β decay, meson decay, fixed-target, and high-energy collider experiments.
No insulin degludec dose adjustment required after aerobic exercise for people with type 1 diabetes: the ADREM study
Authors: Drenthen Linda C. A. , Ajie Mandala , Abbink Evertine J. , Rodwell Laura , Thijssen Dick H. J. , Tack Cees J. , de Galan Bastiaan E. 
Published: March 2023

Abstract
Aims/hypothesis
It is generally recommended to reduce basal insulin doses after exercise to reduce the risk of post-exercise nocturnal hypoglycaemia. Based on its long t½, it is unknown whether such adjustments are required or beneficial for insulin degludec.

Methods
The ADREM study (Adjustment of insulin Degludec to Reduce post-Exercise (nocturnal) hypoglycaeMia in people with diabetes) was a randomised controlled, crossover study in which we compared 40% dose reduction (D40), or postponement and 20% dose reduction (D20-P), with no dose adjustment (CON) in adults with type 1 diabetes at elevated risk of hypoglycaemia, who performed a 45 min aerobic exercise test in the afternoon. All participants wore blinded continuous glucose monitors for 6 days, measuring the incidence of (nocturnal) hypoglycaemia and subsequent glucose profiles.

Results
We recruited 18 participants (six women, age 38 ± 13 years, HbA1c 56 ± 8 mmol/mol [7.3 ± 0.8%], mean ± SD). Time below range (i.e. glucose <3.9 mmol/l) the night after the exercise test was generally low and occurrence did not differ between the treatment regimens. During the subsequent whole day, time below range was lower for D40 compared with CON (median [IQR], 0 [0–23] vs 18 [0–55] min, p=0.043), without differences in the number of hypoglycaemic events. Time above range (i.e. glucose >10 mmol/l) was greater for D20-P vs CON (mean ± SEM, 584 ± 81 vs 364 ± 66 min, p=0.001) and D40 (385 ± 72 min, p=0.003).

Conclusions/interpretation
Post-exercise adjustment of degludec does not mitigate the risk of subsequent nocturnal hypoglycaemia in people with type 1 diabetes. Although reducing degludec reduced next-day time below range, this did not translate into fewer hypoglycaemic events, while postponing degludec should be avoided because of increased time above range. Altogether, these data do not support degludec dose adjustment after a single exercise bout.

Trial registration
EudraCT number 2019-004222-22

Funding
The study was funded by an unrestricted grant from Novo Nordisk, Denmark.

Graphical abstract