bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular docking and dynamics studies to identify novel active compounds targeting potential breast cancer receptor proteins from an indigenous herb Euphorbia thymifolia Linn
Authors: Kumblekar Vasavi , Kumarchandra Reshma , Ranganath Pai K Sreedhara , K ShamaPrasada , Manandhar Suman , Shastry Rajeshwari , Rai Sharada
Published: April 2024

Background Breast cancer has become the most prevalent disease and its incidence has almost doubled in the Indian population. This increased burden demands new targeted therapies with novel compounds either synthetically produced or derived from indigenous plants, which could be a promising approach for the development of drugs. Euphorbia thymifolia L is a widely growing tropical herb that has been reported to have various ethnopharmacological properties, including anticancer properties. Therefore, the aim of the present study was to screen the phytoconstituents and identify the active compounds present in the methanolic extract of E. thymifolia (ME.ET) as ligands to inhibit potential protein targets implicated in breast cancer using an In-silico approach. Methods ME.ET was subjected to GC-MS analysis to screen the phytoconstituents, and the identified compounds were docked with protein targets such as extracellular signal-regulated kinases (ERK1), a serine/threonine kinase-1(AKT1), human epidermal growth factor 2 (HER2), estrogen receptor (ER), maternal embryonic leucine zipper kinase (MELK), polo-like kinase-1(PLK1), and protein tyrosine kinase (PTK6). Compounds with good docking scores were further subjected to dynamic studies to understand the protein ligand binding stability, ligand pathway calculation, and molecular mechanics energies combined with Poisson-Boltzmann (MM/PBSA) calculations using the Schrodinger suite. Results GC-MS analysis revealed the presence of 245 phytoconstituents, 219 of which were unique. When subjected to docking, these phytocompounds, namely 3,6,9,12-tetraoxatetradecane-1,14-diyl dibenzoate (TTDB) and succinic acid, 2-(dimethylamino) ethyl 4-isopropylphenyl ester (SADPE), showed good docking scores. Molecular dynamics studies showed a high affinity and low binding energy for TTDB with HER2, ERK1, and SADPE with ER. Conclusions Hence, in this study, we identified two lead compounds in E.thymifolia linn. Further invitro and invivo anticancer studies can be performed to confirm these results and to understand the molecular mechanism by which they exhibit anticancer activity against breast cancer.
Development and validation of an interprofessional collaborative educational module on the self-management of foot for individuals with type II diabetes mellitus
Authors: Prabhath Sushma , Ramanathan Harihara Prakash , Kamath M Ganesh , Karkada Gagana , Handady Ganesh , Mohammed Ciraj Ali , Maiya Arun G.
Published: April 2024

Background Insufficient awareness of foot self-care among diabetic individuals results in diabetic foot ulcers. The management of diabetes and diabetic foot ulcers demands a well-coordinated approach that involves multiple healthcare providers (HCPs). The present study aims to develop and validate an interprofessional collaborative (IPC) educational program involving HCPs to efficiently oversee and instruct the public on appropriate strategies for self-managing diabetic foot health. Methods The research group worked on creating an educational module titled ‘An Interprofessional Collaborative Educational Module on Self-Management of Foot for Individuals with Type II Diabetes Mellitus.’ The objective of this module was to promote the adoption of proper practices in self-managing foot health for individuals with type 2 diabetes mellitus. A panel of 13 experts participated in a two-stage validation process using the Delphi method to assess the module and its educational resources. Subsequently, the module was tested on a group of 30 participants, i.e., individuals with diabetes, with its efficacy evaluated through conversation analysis and in-depth interviews. Results The three-month-long module included three sessions • 1: Diabetes and its health implications • 2: Diabetic foot and self-management • 3: Interprofessional education in diabetic foot care The mode of content delivery was via Whatsapp, and the educational resources, in the form of pamphlets, flowcharts, handouts, case-based cartoons, and videos on diabetes, including diabetic foot, its risks, and self-management, were shared regularly. All participating experts consensually validated the module and educational resources. Analysis of in-depth interviews revealed that the module immensely benefitted the participants and helped them improve their knowledge and practices of foot care in diabetes. Conclusions The study concludes that IPC educational modules can enhance adherence to proper diabetic foot care practices, potentially reducing the occurrence of foot ulcers and amputations, and ultimately improving the quality of life for individuals with diabetes.
The central concepts of civic competence for social studies
Authors: Haav Kaarel
Published: April 2024

Autori eesmärk on näidata demokraatiahariduse põhimõistete tundmise ja kasutamise olulisust kodanikupädevuse arendamisel ühiskonnaõpetuse tundides. Keskseks mõisteks on kodanik, kes on osa riigist ja kultuurist ning riigi ja kultuuri subjekt. Kodanike ja riigi suhet avab mõistepaar sotsiaalsed subjektid ja struktuurid. Demokraatlikus riigis on nende subjektide põhitüüpideks kodanikud, poliitikud, ametnikud ja administraatorid. Neil sotsiaalsetel subjektidel on ebavõrdsed võimalused kasutada ja käsutada teisi inimesi. Seda ebavõrdsust võimaldab vähendada osalusdemokraatia ehk kaasamine juhtimisse. Autor arvustab ühiskonnaõpetuse mõistete puudulikku seost üldise kodanikupädevusega Eesti üldhariduse õppekavas, näiteks ei kasutata osalusdemokraatia kontseptsiooni ega puudutata võimuprobleemi ühiskonnas. Artikkel kirjeldab, kuidas Eesti tööandjate esindajad eitavad ebaõigluse esinemist ettevõtetes. Seega on ühiskonnaõpetuse ja kodanikupädevuse seostamine võimalik, kui viia mõisted teaduslikele alustele.
Summary
Selected nursing diagnoses and interventions in patients with COVID-19 hospitalized during pandemic
Authors: Araminowicz-Kierklo Elżbieta , Sierpińska Lidia
Published: April 2024

Introduction. In March 2020, the WHO announced global pandemic due to the outbreak of coronavirus disease (COVID-19) caused by the SARS-CoV-2 virus. COVID-19 is considered as a highly infectious disease, with a considerable mortality rate, especially among older people with concomitant diseases (heart failure, pulmonary diseases, arterial hypertension, diabetes). The pathogen affects mainly the respiratory system, and may also lead to acute respiratory distress syndrome, sepsis. In a severe state of health of a patient nurses make many nursing diagnoses, based on which they plan and implement nursing interventions to limit the risk of complications/death.
Objective. The aim of the study was presentation of selected nursing diagnoses and interventions in patients hospitalized due to COVID-19 during the period of pandemic.
Materials and Method. Nursing diagnoses and nursing interventions associated with these diagnoses were analyzed among patients hospitalized due to COVID-19 during pandemic, based on practical experiences in Poland.  
Results. The COVID-19 pandemic was a new challenge for nurses in inpatient health care to provide patients with attentive care in a severe health condition. The efforts of nurses had to be focused on solving many care problems in the bio-psycho-social sphere in order to limit the risk of complications/death. The implementation of nursing interventions had to proceed smoothly, with consideration of the provision of secure environment of patient care and personal protection.
Conclusions. The symptoms of COVID-19 are frequently multisystemic and are related with the risk of complications/death.  The presented nursing diagnoses and interventions in patients ill with COVID-19 disease are an example of the provision of high quality care of patients infected with SARS-CoV-2 virus. Nursing care of a patient with COVID-19 should be characterized by the subjective approach to the patient in accordance with the holistic concept of solving health problems in the bio-psycho-social sphere.
Propaganda und Manipulation in der Sprache Anhand der offiziellen Stellungnahmen des Russischen Aussenministeriums
Authors: Owsiński Piotr A.
Published: April 2024

THE PROPAGANDA AND LINGUISTIC MANIPULATION IN THE LANGUAGE OF POLITICS ON THE BASIS OF THE OFFICIAL STATEMENTS OF THE RUSSIAN FOREIGN OFFICE ABOUT THE RUSSIAN INVASION OF UKRAINE (2022)
Persuasion, disinformation, manipulation, censorship, which are elements of propaganda, can be regarded as central terms of the language of politics, especially during conflict situations and wars. The question of interest is in what ways the specific language techniques are used by the Russian Foreign Affairs Department for the purposes of propaganda in the context of the 2022 Russian invasion of Ukraine. The paper analyzes the official statements of Maria Zakharova, the Director of the Information and Press Department of the Ministry of Foreign Affairs of the Russian Federation that are available on the web page of the Embassy of Russia in Berlin. The following examinations are confronted with the well-documented nature of the persuasive language in Nazi propaganda before and during World War II. The aim of such analysis is to examine in what ways and to what extent the specific propaganda techniques they are used to justify the war that Russia has started by invading Ukraine.
Model polityki zagranicznej Polski w XXI wieku w myśli politycznej głównych orientacji ideologiczno-programowych
Authors: Maj Ewa , Sanecka-Tyczyńska Joanna , Trembicka Krystyna , Wicha Tomasz
Published: April 2024

THE MODEL OF POLAND’S FOREIGN POLICY IN THE 21ST CENTURY IN THE POLITICAL THOUGHT OF MAIN IDEOLOGICAL AND PROGRAMMATIC ORIENTATIONS
The aim of the article was to show various ways of creating a model of Polish foreign policy in contemporary political thought situated in the context of the Polish raison d’état in the 21st century. The subjects of the research were the main ideological and political orientations: conservative, liberal, agrarian, social democratic, and nationalist with its derivatives, which had their external emanations in the form of political parties: Law and Justice, Civic Platform, Polish People’s Party, Democratic Left Alliance and New Left, as well as the League of Polish Families and the National Movement including related groups belonging to the ideological family. The structure of the article includes references to the model of foreign policy, taking into account: 1) the characteristics of specific currents of political thought, 2) the prospects of competition for power within the state; 3) shaping the course of Poland’s policy in external relations.
La crítica del Sur global: reflexiones sobre los estudios constitucionales comparados
Authors: García-Herreros Nicolás Figueroa
Published: April 2024

Este capítulo analiza los desafíos que la crítica del Sur global plantea a la agenda universalista de los estudios constitucionales comparados.1 En la primera parte, se ofrece una reconstrucción de esta crítica, con la intención de rescatar su denuncia de la desigualdad epistémica que caracteriza los estudios constitucionales comparados. Esta reconstrucción concluye con la necesidad de interiorizar los aportes de la crítica del Sur global, principalmente su llamado a la pluralización de las experiencias constitucionales estudiadas y al reconocimiento de la igual capacidad de todas las culturas y tradiciones jurídicas para participar en la discusión global sobre el constitucionalismo moderno. Sin embargo, se advierte la necesidad de trascender esta crítica para escapar a las dificultades que genera el concepto de Sur global. Se identifican tres dificultades: a) la rigidez metodológica a la que conduce el determinismo geográfico prevalente en el uso de este concepto, b) la tendencia de este discurso crítico hacia el separatismo epistémico y el particularismo que interpone serios obstáculos a la construcción de un lenguaje común sobre el constitucionalismo moderno y c) los riesgos de reificación conceptual generados por el proyecto político de resistencia que motiva esta crítica. En la segunda parte, se ofrece un análisis de las propuestas epistemológicas y metodológicas planteadas por Bruce Ackerman en su libro Revolutionary constitutions: Charismatic leadership and the rule of law. El trabajo de Ackerman busca ilustrar tan solo una forma, que no pretende ser la única, en que los estudios constitucionales comparados pueden, por un lado, interiorizar los aportes de esta crítica y, por otro, trascenderla, en el sentido de prescindir del concepto de Sur global como categoría guía del análisis comparado. Por último, se ofrecen unas breves conclusiones.
Frontiers: Can Large Language Models Capture Human Preferences?
Authors: Goli Ali , Singh Amandeep
Published: April 2024

This paper examines the potential of large language models to mimic human survey respondents and to derive their preferences.
Studierfähigkeit als soziales Konstrukt
Authors: Fellner Magdalena
Published: April 2024

Wer gilt heute als »studierfähig«? Und wer bestimmt darüber? Auf welche Art und Weise formen strukturell-institutionelle Bedingungen und gesellschaftliche Vorstellungen die Möglichkeiten, ein Studium an einer Universität aufzugreifen – und es auch abzuschließen? Und wie hat sich das im Laufe der Zeit verändert? Magdalena Fellner untersucht in ihrer historisch-vergleichenden Studie, welchen Machenschaften die Bedeutungen und Zuschreibungen des Begriffs der Studierfähigkeit von den Anfängen der Hochschulgeschichte bis heute unterliegen. Erfüllen die potenziellen Studierenden nicht die Anforderungen der herrschenden Machtelite einer Zeit, führt dies zum Ausschluss sozialer Gruppen und damit zur Aufrechterhaltung einer hierarchischen Klassengesellschaft. Deutlich wird, dass der klassische Begriff der Studierfähigkeit Probleme birgt, die soziale Ungleichheiten verstärken, anstatt ihnen entgegenzuwirken. Auf Grundlage der theoretischen und empirischen Analysen wird die Dynamik zwischen normativen Erwartungen und kollektiven sowie individuellen Lebenswelten veranschaulicht. Die Studie schlägt schließlich eine Rekonzeptualisierung des Begriffs der Studierfähigkeit aus einer relationalen Perspektive vor. https://creativecommons.org/licenses/by/4.0/legalcode
Importance of Flora in the Economy of Local Inhabitants of Karnah in Jammu and Kashmir India
Authors: Ahad Laraib , Mir Rayees Afzal , Hassan Musheerul
Published: April 2024

Present study, conducted in Karnah, Jammu and Kashmir, from February 2022 to August 2023, rigorously collected data through interviews, discussions, and observations. The Study investigated the economic significance of local flora, documenting 28 plant species across 20 families. Pinaceae (14%) stood out. Trees (n=18), herbs (n=10), and one shrub (n=1) were noted. Wild species (16) surpassed cultivated (12). Plant parts had varied economic uses; a significant difference (χ2=90.587, df=7, p<0.001) was observed. Notably, Juglans regia, Prunus cornuta, Celtis tetrandra, Ficus carica, Morus alba, and Cynodia oblang were highlighted for economic applications. "Whole plant" (51%), leaves (20%), fruits (17%), bulb and seeds (6% each) were the most used components. Six uses (Medicine, food, timber, fuel, aesthetic, and industrial) contributed to the local economy. This pioneering study sheds light on the economic role of plant taxa in the Karnah region of Jammu and Kashmir.
Evaluation of Antifungal Activity of Bacterial Endophytes Against Fusarium Oxysporum Causing Wilt Disease
Authors: Srivastava Pratima , Tiwari Shree Prakash , Srivastava Alok Kumar , Sharma Rajesh
Published: April 2024

Fusarium oxysporum is main causative agent behind the most destructive soil-borne plant disease, fusarium wilt, which damages economically significant food crops like bananas, sweet potatoes, tomatoes, legumes and melons. Traditionally, the disease is controlled by physical and chemical methods that affect the environment adversely. One of the ecofriendly approach of plant disease prevention is biological control. Plant growth promoting rhizobacteria and endophytes are now consider as promising agent for disease control. In the present study bulb of Allium sativum plant were used for isolation of endophytes and the endophytes were screened for their bio-control potential. Thirteen bacterial endophytes (ESS01, ESS02, ESS03, ESS06, ESS023, ESS024, ESS025, ESS072, ESS073, ESS074, ESS075, ESS076 and ESS077) exhibited antifungal activity against Fusarium oxysporum f. sp. ciceris. All the isolates inhibited more than 59% mycelial growth on dual-culture assay. However isolate ESS01 and ESS02 exhibited higher antifungal activity (74.81% & 71.48%) against the pathogen Fusarium oxysporum f. sp. ciceris. Only five endophytic isolates (ESS01, ESS02, ESS023, ESS076 & ESS077) out of thirteen endophytes were selected for the pot experiment because of having plant growth promoting attributes and inhibiting more than 70% mycelia growth of Fusarium oxysporum. Biocontrol technique of production of plant against harmful pathogen is now a promising approach for ecofriendly and sustainable agriculture. In this context endophytic isolates were analysed for their antifungal properties especially on Fusarium oxysporum. The endophytic isolates Bacillus aerius ESS02, Bacillus velezensis ESS076, and Bacillus siamensis ESS077 significantly enhanced the plant biomass in chick pea plant even in presence of pathogen and eliminating the harmful effect of Fusarium oxysporum on chick pea plant. Overall, present investigation indicate that Allium sativum harbors various endophytic bacteria that possess excellent antifungal activity and can be used as bio-control agent to control wilt disease of various plants.
Experimental and Biological Approaches for Genotype X Environment Interactions Estimation for Wheat Genotypes Evaluated Under Multi Locational Trials
Authors: Verma* Ajay , Tyagi Bhudev Singh , Singh Gyanendra
Published: April 2024

Genotypes VL907, HS562, HPW484 were ranked as topped three in comparison to the other during the evaluation of nine wheat genotypes at major locations of the north hills zone of the country under rain fed conditions. The least values of AMMI stability measure (ASV) had expressed the desirability of HPW484, HS562, VL2041 genotypes whereas the genotypes HS562, HPW484, VL2041 had been identified by least values of Modified Ammi Stability Value (MASV). The minimum value of simultaneous selection index measure based on the MASV (ssiMASV) had selected HS562, HPW484, VL2041 wheat genotypes while values of ssiWAASB measure found the suitability of HPW484, HS562, HS691 wheat genotypes. The composite non parametric measure NPi (2) had favoured the VL892, HS562 genotypes and values of NPi (3) measure had settled for VL892, HS562 genotypes while VL892, HPW349 wheat genotypes had been pointed by the last composite measure NPi (4). The Ward’s method of Hierarchical Clustering had placed the VL907 genotype in a separate group as compared to others. The shorter rays of measures IPC2, IPC5, IPC3, SD had reflected the less contribution of the joint effects of genotypes and measures in the biplot analysis. Non parametric composite measure NPi (1) had expressed tight direct relation with Si1,Si3,Si4,Si5,Si6,Si7 values. The values of IPC6 & IPC4 had maintained the direct association with BLUP based analytic measures HMGV, RPGV, HMPRVG*Meanb, GAI, Meanb, RPGV*Meanb values. Moreover the values of CV measure had clustered with Si2, Si3, Si4,Si5, Si7 measures of this study.
The Causes and Trends in the Arrivals of Apple and Tomato to some Selected Sub-Market Yards of Himachal Pradesh
Authors: Kumar Dharmender , Mukherjee Doel
Published: April 2024

Apple and tomato are important cash crops of Himachal Pradesh. Although, production of apple and tomato is very high but less arrival is coming in sub market yards (SMY). This paper attempts to identify the arrivals of apple and tomato in some markets namely Bandrol, Bhuntar, Kangra, Kullu and Solan of Himachal Pradesh in India. This study is based on secondary data sourced from government data records of agricultural arrival, production and heavy rainfall in selected places for ten years under study (2011-12 to 2020-21). The main motive of this study was to assess the trends in annual, main seasonal arrivals of apple and tomato with the help of tabular data, correlation and forecasting technique. The impact of climate change has been become a major reason in the state which affects the production of apple and tomato that states lesser the production lesser the arrival in the markets. After evaluating the data, it has been revealed that arrival in all the selected markets had showed scattered annual and main seasonal fluctuations during the period of ten years. Also, by using correlation method it was seen that only Bhuntar market was negatively impacted by heavy rainfall in the arrival of tomato and similar arrivals will come in next ten years.
Saúde Sexual E Reprodutiva Nas Adolescências No Contexto Brasileiro: O Que Sabemos Sobre Isso?
Authors: Dos Santos Catiele , Roso Adriane
Published: April 2024

Os direitos sexuais e reprodutivos têm sido alvo de disputas e contestações no contemporâneo. Trata-se de uma revisão integrativa, com o intuito de analisar como tem sido abordada a Saúde Sexual e Reprodutiva de adolescentes no Brasil em artigos científicos. A construção das informações consistiu em uma busca de publicações, entre 2010 e 2021, nasbases de dados: Portal de Revistas CAPES, Biblioteca Virtual em Saúde e Biblioteca Eletrônica Científica Online. Os espaços de discussão acerca dos Direitos Sexuais e Reprodutivos de adolescentes se restringem à perspectiva da gravidez e prevenção de doenças. Constatou-se que as sexualidades adolescentes permanecem estigmatizadas e asdesigualdades de gênero ganham destaque. Há necessidade de incorporação da noção de direitos sexuais e reprodutivos nas ações desenvolvidas na Atenção Básica e nas escolas, bem como de educação continuada para os professores e profissionais da saúde e de fomento à participação familiar nas ações educativas realizadas com adolescentes.
The global rise of extremisms: towards a gendered analytical framework
Authors: Stenger Helen , True Jacqui
Published: April 2024

In recent years, feminist scholarship has contributed gender perspectives to examine extremist narratives, motivations and recruitment, as well as gender-responsive strategies to counter extremism. A systematic framework for analysing how gender operates at multiple levels to promote or counter extremisms, however, does not exist. To address this need, we offer a typology with three dimensions drawn from feminist theory: gendered identity, referring to the concept of a person’s gender; gendered ideology, referring to the role gender plays in the mobilising myths of states and non-state organisations; and gendered power dynamics, referring to the hierarchical order of femininities and masculinities structuring the environments in which extremism takes root. The article applies the gender typology to far-right, Buddhist and Islamist extremisms, illustrating the analytical power of gender to explain and interpret diverse extremisms while highlighting patterns and relationships across them in broader global politics. We argue that it is vital to study the intersecting dynamics of gender in order to both understand and challenge extremisms that are increasingly prevalent globally.
Regis's Sweeping and Costly Anti-Spinozism
Authors: Newlands Samuel
Published: April 2024

abstract: Pierre-Sylvain Regis, once a well-known defender of Cartesianism, offers an unusually rich and innovative refutation of Spinoza. While many of his early modern contemporaries raised narrower objections to particular claims in Spinoza's Ethics , Regis develops a broader anti-Spinozistic position, one that threatens the very core of Spinoza's metaphysical ambitions and offers a philosophically robust alternative. However, as with any far-reaching philosophical commitment, Regis's gambit comes with substantive costs of its own, including creating instabilities within the core of his own philosophical system. Far from diminishing the significance of Regis's anti-Spinozism, this critical appraisal helps us better appreciate both the conceptual pull of Spinozism within early modern metaphysics and one sweeping, albeit costly way of escaping its orbit.
Made for Hong Kong: Transborder Staffing, Flexible Strategizing, and the Making of Communist Propaganda Outlets in Hong Kong (1945–1956)
Authors: Chen Mian
Published: April 2024

Abstract: This article examines the processes through which the Chinese Communist Party (CCP) developed its propaganda outlets in Hong Kong during the mid-twentieth century. I argue that the CCP’s operations in 1940s Hong Kong laid the foundation for its propaganda machinery in the 1950s through transborder staffing and a repertoire of flexible strategies. During the 1940s, the party trained a group of propagandists who were well acquainted with Hong Kong and frequently crossed the Hong Kong–Guangdong border to preserve the party’s power base. These propagandists developed a series of strategies, including infiltration, camouflage, and diversification. In the 1950s, the party employed these seasoned operatives in Hong Kong and Guangdong to coordinate propaganda campaigns and utilized the preestablished strategies to navigate the new Cold War geopolitics. This study also highlights the Guangdong–Hong Kong nexus, the CCP’s flexibility, and the continuities surrounding the foundation of the People’s Republic of China.
Corneal topography using a smartphone-based corneal topographer considering a biconical model for the corneal surface
Authors: Campos-García Manuel , Huerta-Carranza Oliver , Moreno-Oliva Víctor Iván , Aguirre-Aguirre Daniel , Pantoja-Arredondo Luis Ángel
Published: April 2024

In this paper, we propose a generalization in both null-screen design and corneal surface topography retrieval algorithms to assess the nonsymmetric surface of the human cornea using a compact smartphone-based corneal topographer. The proposed new null-screen design considers the corneal surface to be a biconic surface, and the evaluation algorithms assume a general biconic shape with decentering, defocus, tilt, and rotation around the z-axis. We discussed how to integrate the measurement system to obtain geometric parameters of the corneal surface such as radius of curvature, conic constants, as well as elevation map, and sagittal and meridional curvature maps. To demonstrate that our proposed smartphone-based corneal topographer provides reliable measurements of corneal topography, we conducted measurements on a well-known biconic surface and two human corneas.
COVID-19 cluster surveillance using exposure data collected from routine contact tracing: The genomic validation of a novel informatics-based approach to outbreak detection in England
Authors: Packer Simon , Patrzylas Piotr , Smith Iona , Chen Cong , Wensley Adrian , Nsonwu Olisaeloka , Dack Kyle , Turner Charlie , Anderson Charlotte , Kwiatkowska Rachel , Oliver Isabel , Edeghere Obaghe , Fraser Graham , Hughes Gareth
Published: April 2024

Contact tracing was used globally to prevent onwards transmission of COVID-19. Tracing contacts alone is unlikely to be sufficient in controlling community transmission, due to the pre-symptomatic, overdispersed and airborne nature of COVID-19 transmission. We describe and demonstrate the validity of a national enhanced contact tracing programme for COVID-19 cluster surveillance in England. Data on cases occurring between October 2020 and September 2021 were extracted from the national contact tracing system. Exposure clusters were identified algorithmically by matching ≥2 cases attending the same event, identified by matching postcode and event category within a 7-day rolling window. Genetic validity was defined as exposure clusters with ≥2 cases from different households with identical viral sequences. Exposure clusters were fuzzy matched to the national incident management system (HPZone) by postcode and setting description. Multivariable logistic regression modelling was used to determine cluster characteristics associated with genetic validity. Over a quarter of a million (269,470) exposure clusters were identified. Of the eligible clusters, 25% (3,306/13,008) were genetically valid. 81% (2684/3306) of these were not recorded on HPZone and were identified on average of one day earlier than incidents recorded on HPZone. Multivariable analysis demonstrated that exposure clusters occurring in workplaces (aOR = 5·10, 95% CI 4·23–6·17) and education (aOR = 3·72, 95% CI 3·08–4·49) settings were those most strongly associated with genetic validity. Cluster surveillance using enhanced contact tracing in England was a timely, comprehensive and systematic approach to the detection of transmission events occurring in community settings. Cluster surveillance can provide intelligence to stakeholders to support the assessment and management of clusters of COVID-19 at a local, regional, and national level. Future systems should include predictive modelling and network analysis to support risk assessment of exposure clusters to improve the effectiveness of enhanced contract tracing for outbreak detection.
The actin binding sites of talin have both distinct and complementary roles in cell-ECM adhesion
Authors: Camp Darius , Venkatesh Bhavya , Solianova Veronika , Varela Lorena , Goult Benjamin T. , Tanentzapf Guy
Published: April 2024

Cell adhesion requires linkage of transmembrane receptors to the cytoskeleton through intermediary linker proteins. Integrin-based adhesion to the extracellular matrix (ECM) involves large adhesion complexes that contain multiple cytoskeletal adapters that connect to the actin cytoskeleton. Many of these adapters, including the essential cytoskeletal linker Talin, have been shown to contain multiple actin-binding sites (ABSs) within a single protein. To investigate the possible role of having such a variety of ways of linking integrins to the cytoskeleton, we generated mutations in multiple actin binding sites inDrosophilatalin. Using this approach, we have been able to show that different actin-binding sites in talin have both unique and complementary roles in integrin-mediated adhesion. Specifically, mutations in either the C-terminal ABS3 or the centrally located ABS2 result in lethality showing that they have unique and non-redundant function in some contexts. On the other hand, flies simultaneously expressing both the ABS2 and ABS3 mutants exhibit a milder phenotype than either mutant by itself, suggesting overlap in function in other contexts. Detailed phenotypic analysis of ABS mutants elucidated the unique roles of the talin ABSs during embryonic development as well as provided support for the hypothesis that talin acts as a dimer inin vivocontexts. Overall, our work highlights how the ability of adhesion complexes to link to the cytoskeleton in multiple ways provides redundancy, and consequently robustness, but also allows a capacity for functional specialization.
Dendrite intercalation between epidermal cells tunes nociceptor sensitivity to mechanical stimuli in Drosophila larvae
Authors: Luedke Kory P. , Yoshino Jiro , Yin Chang , Jiang Nan , Huang Jessica M. , Huynh Kevin , Parrish Jay Z.
Published: April 2024

An animal’s skin provides a first point of contact with the sensory environment, including noxious cues that elicit protective behavioral responses. Nociceptive somatosensory neurons densely innervate and intimately interact with epidermal cells to receive these cues, however the mechanisms by which epidermal interactions shape processing of noxious inputs is still poorly understood. Here, we identify a role for dendrite intercalation between epidermal cells in tuning sensitivity of Drosophila larvae to noxious mechanical stimuli. In wild-type larvae, dendrites of nociceptive class IV da neurons intercalate between epidermal cells at apodemes, which function as body wall muscle attachment sites, but not at other sites in the epidermis. From a genetic screen we identified miR-14 as a regulator of dendrite positioning in the epidermis: miR-14 is expressed broadly in the epidermis but not in apodemes, and miR-14 inactivation leads to excessive apical dendrite intercalation between epidermal cells. We found that miR-14 regulates expression and distribution of the epidermal Innexins ogre and Inx2 and that these epidermal gap junction proteins restrict epidermal dendrite intercalation. Finally, we found that altering the extent of epidermal dendrite intercalation had corresponding effects on nociception: increasing epidermal intercalation sensitized larvae to noxious mechanical inputs and increased mechanically evoked calcium responses in nociceptive neurons, whereas reducing epidermal dendrite intercalation had the opposite effects. Altogether, these studies identify epidermal dendrite intercalation as a mechanism for mechanical coupling of nociceptive neurons to the epidermis, with nociceptive sensitivity tuned by the extent of intercalation.
Empowering healthcare professionals in West Africa—A feasibility study and qualitative assessment of a dietary screening tool to identify adults at high risk of hypertension
Authors: Batubo Nimisoere P. , Nwanze Nnenna M. , Alikor Chizindu A. , Auma Carolyn I. , Moore J. Bernadette , Zulyniak Michael A.
Published: April 2024

Dietary risks significantly contribute to hypertension in West Africa. Food frequency questionnaires (FFQs) can provide valuable dietary assessment but require rigorous validation and careful design to facilitate usability. This study assessed the feasibility and interest of a dietary screening tool for identifying adults at high risk of hypertension in Nigeria. Fifty-eight (58) consenting adult patients with hypertension and their caregivers and 35 healthcare professionals from a single-centre Nigerian hospital were recruited to complete a 27-item FFQ at two-time points and three 24-hour recalls for comparison in a mixed method study employing both quantitative questionnaires and qualitative techniques to elicit free form text. Data analyses were conducted using R software version 4.3.1 and NVivo version 14. The trial was registered with ClinicalTrials.gov: NCT05973760. The mean age of patients was 42.6 ± 11.9 years, with an average SBP of 140.3 ± 29.8 mmHg and a BMI of 29.5 ± 7.1 Kg/m2. The adherence rate was 87.9%, and the mean completion time was 7:37 minutes. 96.6% of patients found the FFQ easy to complete, comprehensive, and valuable. A minority reported difficulty (3.4%), discomfort (10.3%), and proposed additional foods (6.9%). Healthcare professionals considered the dietary screening tool very important (82.9%) and expressed a willingness to adopt the tool, with some suggestions for clarification. Patients and healthcare professionals found the screening tool favourable for dietary counselling in hypertension care. The tailored dietary screening tool (FFQ) demonstrated promising feasibility for integration into clinical care as assessed by patients and healthcare professionals. Successful implementation may benefit from proactive time management and addressing training needs. This user-centred approach provided key insights to refine FFQ and set the foundation for ongoing validity testing and evaluation in clinical practice.
Blockchain technology for supply chain traceability: A game-theoretic analysis between e-platforms
Authors: Chen Qian , Yang Xuejian , Yang Dan , Liu Sen , Liao Chuchu
Published: April 2024

In view of the rapid development and application of blockchain technology, this paper considers a secondary supply chain system consisting of a single upstream supplier and a downstream e-tailer that implements blockchain technology and a traditional e-tailer that does not implement blockchain technology. We establish the demand function of two channels based on consumers’ sensitivity to the blockchain and use the Stackelberg game model to compare and analyse the e-tailers’ profits from the two channels. For the basic properties, interestingly, we find that there exists a critical threshold on the cost sensitivity to effort that helps each e-tailer decide whether to implement effort. If the cost sensitivity to effort is high, the two-sided e-tailers will reduce their effort as much as possible to obtain greater profits. Conversely, if the cost sensitivity to effort is low, they will increase their effort to obtain more benefits. We also discuss the role of blockchain technology in competition between e-tailers and analyse the impact of the product brand effect brought by the traceability characteristic of blockchain on the competition between e-tailers. To check the robustness of the core results and to investigate different forms of supply chain configurations, this paper further develops the analysis of the supplier entering agency agreements with two-sided e-tailers. Under this scenario, the supplier sells their products directly to consumers through two-sided e-platforms and shares revenue with e-tailers as platform agency fees. These core ideas remain valid in the extended model.
Predicting the immunity landscape and prognosis with an NCLs signature in liver hepatocellular carcinoma
Authors: Ji Zhangxin , Zhang Chenxu , Yuan Jingjing , He Qing , Zhang Xinyu , Yang Dongmei , Xu Na , Chu Jun
Published: April 2024

Background

Activated neutrophils release depolymerized chromatin and protein particles into the extracellular space, forming reticular Neutrophil Extracellular Traps (NETs). This process is accompanied by programmed inflammatory cell death of neutrophils, known as NETosis. Previous reports have demonstrated that NETosis plays a significant role in immune resistance and microenvironmental regulation in cancer. This study sought to characterize the function and molecular mechanism of NETosis-correlated long non-coding RNAs (NCLs) in the prognostic treatment of liver hepatocellular carcinoma (LIHC).

Methods

We obtained the transcriptomic and clinical data from The Cancer Genome Atlas (TCGA) and evaluated the expression of NCLs in LIHC. A prognostic signature of NCLs was constructed using Cox and Last Absolute Shrinkage and Selection Operator (Lasso) regression, while the accuracy of model was validated by the ROC curves and nomogram, etc. In addition, we analyzed the associations between NCLs and oncogenic mutation, immune infiltration and evasion. Finally, LIHC patients were classified into four subgroups based on consensus cluster analysis, and drug sensitivity was predicted.

Results

After screening, we established a risk model combining 5 hub-NCLs and demonstrated its reliability. Independence checks suggest that the model may serve as an independent predictor of LIHC prognosis. Enrichment analysis revealed a concentration of immune-related pathways in the high-risk group. Immune infiltration indicates that immunotherapy could be more effective in the low-risk group. Upon consistent cluster analysis, cluster subgroup 4 presented a better prognosis. Sensitivity tests showed the distinctions in therapeutic effectiveness among various drugs in different subgroups.

Conclusion

Overall, we have developed a prognostic signature that can discriminate different LIHC subgroups through the 5 selected NCLs, with the objective of providing LIHC patients a more precise, personalized treatment regimen.
Increased hepatoprotective effects of the novel farnesoid X receptor agonist INT-787 versus obeticholic acid in a mouse model of nonalcoholic steatohepatitis
Authors: Adorini Luciano , Rigbolt Kristoffer , Feigh Michael , Roth Jonathan , Erickson Mary
Published: April 2024

The nuclear farnesoid X receptor (FXR), a master regulator of bile acid and metabolic homeostasis, is a key target for treatment of nonalcoholic steatohepatitis (NASH). This study compared efficacy of FXR agonists obeticholic acid (OCA) and INT-787 by liver histopathology, plasma biomarkers of liver damage, and hepatic gene expression profiles in the Amylin liver NASH (AMLN) diet–induced and biopsy-confirmed Lepob/ob mouse model of NASH. Lepob/ob mice were fed the AMLN diet for 12 weeks before liver biopsy and subsequent treatment with vehicle, OCA, or INT-787 for 8 weeks. Hepatic steatosis, inflammation, and fibrosis (liver lipids, galectin-3, and collagen 1a1 [Col1a1], respectively), as well as plasma alanine transaminase (ALT) and aspartate transaminase (AST) levels, were assessed. Hepatic gene expression was assessed in Lepob/ob mice that were fed the AMLN diet for 14 weeks then treated with vehicle, OCA, or INT-787 for 2 weeks. INT-787, which is equipotent to OCA but more hydrophilic, significantly reduced liver lipids, galectin-3, and Col1a1 compared with vehicle, and to a greater extent than OCA. INT-787 significantly reduced plasma ALT and AST levels, whereas OCA did not. INT-787 modulated a substantially greater number of genes associated with FXR signaling, lipid metabolism, and stellate cell activation relative to OCA in hepatic tissue. These findings demonstrate greater efficacy of INT-787 treatment compared with OCA in improving liver histopathology, decreasing liver enzyme levels, and enhancing gene regulation, suggesting superior clinical potential of INT-787 for the treatment of NASH and other chronic liver diseases.
Water intake and obesity: By amount, timing, and perceived temperature of drinking water
Authors: Khil Jaewon , Chen Qiao-Yi , Lee Dong Hoon , Hong Kyung-Won , Keum NaNa
Published: April 2024

Water intake has been suggested to be associated with weight control, but evidence for optimal water intake in terms of amount, timing, and temperature is sparse. Additionally, genetic predisposition to obesity, which affects satiety and energy expenditure, might interact with water intake in regulating individual adiposity risk. We conducted a cross-sectional study recruiting 172 Korean adults. Information on water intake and lifestyle factors was collected through self-reported questionnaires, and height, weight, and waist circumference (WC) were measured by researchers. The oral buccal swab was performed for genotyping of FTO rs9939609, MC4R rs17782313, BDNF rs6265 and genetic risk of obesity was calculated. Linear regression was performed to estimate mean difference in body mass index (BMI) and WC by water intake and its 95% confidence interval (95% CI). As a sensitivity analysis, logistic regression was performed to estimate odds ratio (OR) of obesity/overweight (BMI of ≥23kg/m2; WC of ≥90cm for men and of ≥80cm for women) and its 95% CI. Drinking >1L/day was significantly associated with higher BMI (mean difference: 0.90, 95% CI 0.09, 1.72) and WC (mean difference: 3.01, 95% CI 0.62, 5.41) compared with drinking ≤1L/day. Independent of total water intake, drinking before bedtime was significantly associated with lower BMI (mean difference: -0.98, 95% CI -1.91, -0.05). The results remained consistent when continuous BMI and WC were analyzed as categorical outcomes. By perceived temperature, drinking >1L/day of cold water was associated with higher BMI and WC compared with drinking ≤1L/day of water at room-temperature. By genetic predisposition to obesity, a positive association between water intake and WC was confined to participants with low genetic risk of obesity (P interaction = 0.04). In conclusion, amount, timing, and perceived temperature of water intake may be associated with adiposity risk and the associations might vary according to genetic predisposition to obesity.
Use of bio-information and communication technology shortens time to peak at a lower height of the epidemic curve: An alternative to flattening for countries with early COVID-19 outbreaks
Authors: Hong Song Hee , Jiang Xinying , Kwon HyeYoung
Published: April 2024

Introduction

The traditional approach to epidemic control has been to slow down the rate of infection while building up healthcare capacity, resulting in a flattened epidemic curve. Advancements in bio-information-communication technology (BICT) have enabled the preemptive isolation of infected cases through efficient testing and contact tracing. This study aimed to conceptualize the BICT-enabled epidemic control (BICTEC) and to document its relationships with epidemic curve shaping and epidemic mitigation performance.

Methods

Daily COVID-19 incidences were collected from outbreak to Aug. 12, 2020, for nine countries reporting the first outbreak on or before Feb. 1, 2020. Key epidemic curve determinants–peak height (PH), time to peak (TTP), and area under the curve (AUC)–were estimated for each country, and their relationships were analyzed to test if epidemic curves peak quickly at a shorter height. CFR (Case Fatality Rate) and CI (Cumulative Incidence) were compared across the countries to identify relationships between epidemic curve shapes and epidemic mitigation performance.

Results

China and South Korea had the quickest TTPs (40.70 and 45.37 days since outbreak, respectively) and the shortest PHs (2.95 and 4.65 cases per day, respectively). Sweden, known for its laissez-faire approach, had the longest TTP (120.36) and the highest PH (279.74). Quicker TTPs were correlated with shorter PHs (ρ = 0·896, p = 0·0026) and lower AUCs (0.790, p = 0.0028), indicating that epidemic curves do not follow a flattened trajectory. During the study period, countries with quicker TTPs tended to have lower CIs (ρ = .855, P = .006) and CFRs (ρ = 0.684, P = .061). For example, South Korea, with the second-quickest TTP, reported the second lowest CI and the lowest CFR.

Conclusions

Countries that experienced early COVID-19 outbreaks demonstrated the epidemic curves that quickly peak at a shorter height, indicating a departure from the traditional flattened trajectory. South Korea’s BICTEC was found to be at least as effective as most lockdowns in reducing CI and CFR.
Corporate ESG and total factor productivity: Will the fulfillment of social responsibility sacrifice productivity?
Authors: Chen Jian
Published: April 2024

With the increasing prominence of climate and energy issues, enterprises, as the micro-subjects of economic activities, need to pay attention to environmental responsibility to promote sustainable and high-quality economic development. However, one of the crucial controversies is whether enterprises will sacrifice efficiency to fulfill their environmental responsibilities. To try our best to answer the controversy, this paper explores the impact of ESG on total factor productivity and its mechanism. The research conclusion shows that Chinese enterprises fulfilling ESG responsibilities can improve staff efficiency, reduce financing costs, ease financing constraints, and increase innovation investment, thus effectively improving total factor productivity. Compared to non-state-owned enterprises, this effect is more significant in state-owned enterprises. In addition, the promotion of ESG construction on the total factor productivity of enterprises also presents specific acceleration characteristics. This shows that in the socialist market economy environment, there is an obvious "social responsibility dividend" in the implementation of the ESG concept by Chinese enterprises, which is helpful to enhance their long-term value and realize a win-win of social value and commercial value. The conclusions of this study help deal correctly with the relationship between business value and social value of enterprises and provide inspiration for promoting healthy and sustainable economic development.