bluuebunny/crossref_metadata_2025 huggingface dataset:
COMMUNICATION PROCESSES OF GASTRONOMIC ESTABLISHMENTS: SPECIFICS, DIGITAL TOOLS, AND THE ROLE OF COMMUNITY MANAGEMENT
Authors: Svitlychna V. , Aleksandrova S.
Published: October 2024

The article explores the issues of the relevance and necessity of improving the communication processes’ effectiveness in gastronomic establishments. It highlights the meaningful advantages of establishing well-organised communication processes to enhance gastronomic establishment operations, refine communication strategies, and strengthen their competitive positions in the market.
The study aims to systematise methodological approaches to the communication processes implemented by gastronomic establishments and to substantiate the content and benefits of using community management in building effective communication processes for these establishments.
The authors point out that the operations of gastronomic establishments have always been highly profitable. However, global crises, COVID-19 restrictions, and military actions have posed significant challenges for the gastronomy industry in Ukraine.
The study focuses on the fact that building effective communications in gastronomic establishments is an efficient measure to ensure their stable development, provide substantial competitive advantages, and improve their financial condition.
The work presents the authors’ interpretation of the ‘communication process of a gastronomic establishment’ concept. By this, the authors mean a targeted interaction with their consumers, including using various communication channels, providing timely and clear information, actively receiving and analysing feedback, and personalising services to meet the needs and expectations of consumers, increase their loyalty, and promote stable functional development.
The article emphasises the significant impact of digitalisation on the communication processes of gastronomic establishments. The authors propose a vision of digital options and the positive consequences of building communication processes in gastronomic establishments.
Additionally, the authors focus on the essence and relevance of community management in gastronomic establishments, presenting their definition of this concept and substantiating the advantages of its implementation by gastronomic establishments.
Keywords: gastronomic establishments, communication processes, community management, digitalisation, organisational support, web analytics.
ARTES VISUAIS E EDUCAÇÃO INFANTIL:
Authors: Varela Simone , Schütz Jenerton Arlan
Published: October 2024

O presente artigo explora a importância das artes visuais na educação infantil, destacando como essa prática contribui para o desenvolvimento integral das crianças. As artes visuais desempenham um papel fundamental no fortalecimento de habilidades cognitivas, motoras, emocionais e sociais, promovendo uma aprendizagem significativa e criativa. Ao longo do texto, discutem-se os benefícios que as atividades artísticas, como desenho, pintura e escultura, trazem para o desenvolvimento cognitivo das crianças, estimulando o pensamento crítico, a resolução de problemas e o pensamento simbólico, essenciais para outras áreas do conhecimento. Além disso, as artes visuais têm um impacto direto no desenvolvimento da coordenação motora fina e grossa, através de atividades que envolvem o uso de diferentes materiais e técnicas. A expressão emocional também é facilitada pela arte, oferecendo às crianças um meio seguro para externalizar sentimentos e fortalecer a autoestima. No âmbito social, a arte promove a interação e o trabalho em equipe, estimulando habilidades de colaboração e respeito mútuo. Outro aspecto importante abordado é o uso das artes visuais como ferramenta de aprendizagem interdisciplinar, integrando áreas como matemática, ciências, história e linguagem, e oferecendo uma forma mais prática e envolvente de entender conceitos complexos. Conclui-se que as artes visuais são essenciais para a formação integral das crianças, proporcionando um ambiente de aprendizado que une mente, corpo e emoções, desenvolvendo indivíduos criativos, resilientes e capazes de enfrentar desafios futuros com confiança.
Product Design and Its Role in Improving the Daily Lives of Poverty-Stricken Societies
Authors: Wan Edrin Wan Ardini , Zaim Nur Hatice
Published: October 2024

This article examines the role of product design in improving the lives of individuals from poverty-stricken societies. Despite the perception of well-designed products being a privilege, it is essential to recognize the universal need for functional and purposeful products. As issues related to climate change and economic recession disproportionately affect lower-income communities, creative problem-solving can become an effective way to support them in overcoming these issues. Issues ranging from water scarcity to underdeveloped agriculture systems have been addressed through the introduction of new products into underprivileged communities. The impact of these products is evaluated based on user feedback and their effectiveness in improving users' lives. The outcome will identify the significance of the role of product design in improving the livelihood of poverty-stricken societies. This will benefit governmental and non-governmental organisations seeking effective solutions to support individuals in need and product designers who are interested in designing for humanitarian purposes. By highlighting successful instances where product design has positively impacted the lives of impoverished individuals, these organisations may be more inclined to collaborate with designers and provide the necessary funding for such initiatives.
Digital Storytelling in Public Health: Lessons from COVID-19- Related Instagram Stories for Future Crises
Authors: Ameer Fathima Musfira , Harun Harryizman , Ibrahim Nurulhuda
Published: October 2024

The COVID-19 pandemic underscored the critical need for effectively disseminating public health information to prevent the spread of disease. Social media platforms, particularly Instagram stories, played a significant role in conveying health messages to younger audiences and professionals. This study explores how Instagram stories created awareness during the COVID-19 pandemic, identifying persuasive elements and their impact on public health communication. Using qualitative content analysis (QCA), this article analyses COVID-19-related Instagram stories from the World Health Organization (WHO), UNICEF, and medical influencers to categorise key storytelling techniques. In addition, thematic analysis was conducted based on interviews with seven active Instagram story viewers to assess the perceived persuasiveness of these stories in raising awareness. The QCA revealed five categories of Instagram stories, while thematic analysis uncovered eight primary themes and 45 sub-themes related to persuasion. The findings provide valuable insights into creating effective digital storytelling strategies for public health, offering lessons to inform health communication efforts in future crises.
ARTICLE RETRACTED
Authors: --
Published: October 2024

ARTICLE RETRACTED
De las Externalidades Ambientales Negativas a nuevos enfoques económicos en los océanos
Authors: Aguilar Aguilar Rosenda , García Espinosa Salvador
Published: October 2024

El principio fundamental de la economía del bienestar propuesta por A. Pigou consistió en que, con la participación del Estado, se podría elevar la eciencia de la economía y mejorar las condiciones de vida de la gente a través de impuestos y subvenciones públicas. Su propuesta establecía que el mayor bienestar económico se conseguiría con tres acciones: producir lo más posible, distribuir lo más igualitariamente posible, y recticar las producciones rentables que acarrearan perjuicios a terceros. El presente artículo pone énfasis en que el discurso pigouviano es esencialmente económico y propicia perjuicios ambientales que hoy en día demandan reconsideraciones respecto al concepto de externalidad. Se ejemplica a partir del caso de los océanos, en los que ha quedado de maniesto que el concepto actual de externalidades ha propiciado la evasión de responsabilidades sobre los daños que las actividades económicas causan sobre los ecosistemas marinos.
Análisis de factores determinantes en la permanencia de las pequeñas y medianas empresas en Ensenada, Baja California
Authors: Palacios Valenzuela César Augusto , Acosta Haro Elizabeth , Soto Medina Nereyda
Published: October 2024

En la actualidad, el sector empresarial de Ensenada se enfrenta a nuevos retos que, si bien en la última década han permitido la apertura de nuevos negocios, por otra han dicultado la permanencia de otros. Por lo que esta investigación pretende establecer cuáles son los factores determinantes de las pequeñas y medianas empresas (PYMES en adelante) de la región que han ayudado en su permanencia y crecimiento. Para lo que será necesaria la aplicación de un instrumento que ayude a evaluar las condiciones de trabajo y desarrollo de cada empresa que integre la muestra. Dada la importancia que tiene el desarrollo efectivo de PYMES, este estudio pretende impulsar el sector económico del país, a través de la creación de herramientas que ayuden en la planeación, crecimiento y permanencia a las empresas establecidas en Ensenada, Baja California.
Lit. tautà und ung. tót Ein slawisch-ungarischer Beitrag zu einem alten baltischen etymologischen Problem
Authors: Simon Zsolt
Published: October 2024

A litván tautà és a magyar tót szavak eredete: szláv és magyar adalékok egy régi balti etimológiai problémáhozBár a litván tautà ’nép, ország’ szó nyilvánvalóan összefügg az indoeurópai *teu̯téh2 ’nép’ szó családjával, a részletek bizonytalanok, mivel a litván szó egy szabálytalan, o-vokalizmusú alakra megy vissza. Ez a tanulmány egy mindeddig figyelmen kívül hagyott aspektussal járul hozzá ezen etimológiai probléma megoldásához: a magyar tót szóval, melynek legkorábbi jelentése ’Kárpát-medencei szláv’. Jelen dolgozat kimutatja, hogy a tót szónak se a népszerű germán, se az újonnan javasolt balti etimológiája nem helytálló, noha az alapgondolat, a fentebbi *teu̯téh2 szóval való összefüggése logikus. Helyette azt a történetileg, szociolingvisztikailag és tipológiailag kézenfekvő és (a részletes tárgyalás alapján) formailag lehetséges javaslatot teszi, hogy a tót eredetileg a Kárpát-medencei szlávság önelnevezése volt s ezt vette át a honfoglaló magyarság. Ha ez helytálló, akkor a tautà o-vokalizmusa valójában nem balti, hanem balto-szláv probléma, ugyanis a tót szó ugyanarra az o-vokalizmusú formára megy vissza. Mivel ez fonológiai vagy morfológiai alapon nem magyarázható, jelen írás J. E. Rasmussen kelta jövevényszó-javaslatát támogatja és részletesen elemzi, mely kölcsönzési forgatókönyvek (milyen nyelvek és nyelvfázisok) jöhetnek számításba.
Ein indogermanisches Wort für ‚Bart‘ und die lateinische palma-Regel
Authors: Samberger Gudrun
Published: October 2024

A PIE word for ‘beard’ and the Latin palma ruleThis article discusses one of the words for ‘beard’ reconstructible for the IE protolanguage based on Latin, Germanic, Baltic, and Slavic evidence. It is usually reconstructed as PIE *bhar(s)dh-o/eh2- with *-a- of unknown origin. In this article, a new etymology will be proposed: The word for ‘beard’ stems from an underlying compound consisting of an s-stem *bherH-e/os- ‘sth. sharp, point, tip’ and zero-grade *dheh1- ‘to set, place, lay’. This compound was later remodelled into an o-stem *bhorHs-dh-ó- displaying a o-grade in the root (a so-called τομός-formation) meaning ‘the one who sets points’ accounting for the Germanic forms. Additionally, a zero-grade eh2-collective *bhŕ̥Hs-dh-eh2 ‘mass of points’ was formed eventually leading to Latin barba. Finally, a contamination of the two stems *bhorHs-dh-eh2- develops into the Baltic and Slavic forms.
A novel liquid biopsy assay for detection of ERBB2 (HER2) amplification in circulating tumor cells (CTCs)
Authors: Di Caro Giuseppe , Lam Ernest , Bourdon David , Blankfard Martin , Dharajiya Nilesh , Slade Megan , Williams Emily , Zhang Dong , Wenstrup Rick , Schwartzberg Lee
Published: October 2024

Purpose: Circulating tumor cell (CTC)-based ERBB2 (HER2) assay is a laboratory test developed by Epic Sciences using single-cell genomics to detect ERBB2 (HER2) amplification in CTCs found in the peripheral blood of metastatic breast cancer (MBC) patients.
Patients and methods: Peripheral blood was collected in Streck tubes and centrifugation was used to remove plasma and red blood cells. The remaining nucleated cells were deposited on glass slides, immunofluorescent-stained with proprietary antibodies, scanned by a high-definition digital scanner, and analyzed by a proprietary algorithm. In addition, single-cell genomics was performed on selected CTC. Analytical validation was performed using white blood cells from healthy donors and breast cancer cell lines with known levels of ERBB2 amplification. Clinical concordance was assessed on MBC patients whose blood was tested by the CTC ERBB2 (HER2) assay and those results are compared to results of matched metastatic tissue biopsy (immunohistochemistry [IHC] 3+ or IHC2+/in situ hybridization [ISH+]).
Results: Epic’s ERBB2 (HER2) assay detected 2-fold ERBB2 amplification with 85% sensitivity and 94% specificity. In the clinical concordance study, among the 50% of the cases that had ERBB2 status results from CTCs found to be chromosomally-unstable, the CTC ERBB2 (HER2) assay showed sensitivity of 69% and specificity of 78% when compared to HER2 status by metastatic tissue biopsy.
Conclusions: The CTC ERBB2 (HER2) assay can consistently detect ERBB2 status in MBC cell lines and in the population of patients with MBC with detectable chromosomally unstable CTCs for whom tissue biopsy is not available or is infeasible.
Workplace Diversity: Hidden Treasure for Boosting Organizational Performance
Authors: Korovyakovskaya Inessa
Published: October 2024

Today, many organizations recognize the significant impact of workplace diversity on performance outcomes at all organizational levels. Managers and leaders have embraced differences in organizational workforce members through diversity management initiatives, training and programs that yield competitive advantages. The present study contributes to the extant research by developing a new conceptual model that demonstrates relationships between workplace diversity and organizational performance as mediated by diversity management and moderated by multi-level organizational variables. A strong relationship between workforce diversity and excellence in organizational outcomes has grown constantly during the last decade. Practical implications and recommendations are discussed.
ZHADAN’S EVOLUTION AS A POET: REASONS AND ESSENCE
Authors: Kharchuk Roxana
Published: October 2024

Professional Ukrainian critics have traditionally focused more on Zhadan’s prose, with his poetry receiving thorough analysis mainly from Ivan Dziuba, a critic from an older generation. Given Zhadan’s prolific output — 16 collections with over 700 texts — a systematic approach to his work is essential. Currently, Zhadan’s work is either identified with the stages of the formation of Ukrainian society (Babenko), or his poetry is considered as the history of Ukrainian society after 1991 and the process of growing up (Boichenko). The paper’s author identifies two distinct periods in Zhadan’s poetic career: pre-2014, before Russia’s invasion of Ukraine, and post-2014. The war and personal experiences marked significant shifts in his creative expression. In the first period, Zhadan’s work is known for intertwining literature and politics, showcasing an anarchistic worldview, focusing on social issues, and challenging traditional values. Following 2014, his work took a philosophical turn, delving into existential themes, language reform, nature, and interpersonal relationships. Post-2014 interviews reveal Zhadan’s shift from anarchism to embracing the issue of a national state. Aesthetic changes are slower than ideological ones. The poet mythologizes the Russian-Ukrainian war as much as possible; the war appears as an existential state in his work. He looks to Czeslaw Milosz’s poetry as a template for articulating the Russian-Ukrainian war experience. The paper also underscores the significant role of biblical motifs, evangelical imagery and narratives in Zhadan’s body of work across both periods. Whereas prior to 2014, Zhadan’s use of New Testament imagery often bordered on politicized parody, the onset of the Russian-Ukrainian war prompted a departure from such desacralization. He moved from postmodernist aesthetics to a ‘New Sincerity’ approach, reflecting a profound transformation in his poetic vision.
Arguing The Unarguable
Authors: Teeluckdharry Guru Dev
Published: October 2024

This article is about legal ethics. It analyses the debate on Lord Brougham in Queen Caroline’s Case in 1820. The eminent Professor Monroe Henry Freedman argued in the article ‘Henry Lord Brougham, Written by Himself’ that: "[A]n advocate, in the discharge of his duty, knows but one person in all the world, and that person is his client". As to whether Lord Brougham fulfilled his moral duty in line with Kant’s Ethics of Duty to defend his client's interests resolutely and without fear of judicial disfavour or public unpopularity to attain an ultimate ‘Good Will’ is indeed a dilemmatic question. According to many critics, he had resorted to derogatory tactics considered as being unethical from the standpoint of Virtue Ethics in order to attain that ultimate 'Good Will'. Which is which as far as this ethical oxymoron is concerned?
Petrography and classification of NWA 14801, 14802 and 14803, HED meteorites.
Authors: Garcia Jose
Published: October 2024

In this report I present the petrographic characteristics and official classification of meteorites NWA 14801, NWA 14802 and NWA 14803, all of the HED group of achondrites, whose samples arrived at the laboratory during 2021 for research in order to certify them. Since the samples of scientific interest are accumulating in the laboratory repository, the process of classifying them has begun, in order to give part of them to scientific research, and officially record them with their corresponding classifications. The three meteorites were presented for official classification to The Meteoritical Bulletin in 2022, during this phase of relevant samples classification.
Communication media in electronic negotiations: how the individual x medium fit influences negotiation behaviors and outcomes
Authors: Lipp Wolfram , Mohnen Alwine
Published: October 2024

Researchers and practitioners alike are interested in understanding the specifics of electronic negotiations as more and more negotiations are conducted electronically. Intuitively, we would expect differences across negotiation media, but research provides diverging results as to the impact of the medium. This research contributes to this discourse and aims to uncover differences across media and investigates the impact of individual factors on e-negotiation behavior and outcomes. While we know from previous research that individual factors influence job performance and preference for negotiation media, the impact on behaviors and outcomes in different computer-mediated negotiation media is yet to be explored. This paper proposes the individual x medium fit hypothesis, which asserts that individual factors play a distinct role in different electronic negotiation media. We tested this hypothesis using an online, mixed-motive negotiation simulation in which participants (n = 187) negotiated either in a chat or in a video conference system. The impacts of individual factors on the outcome and mediator variables were estimated with a structural equation model. We confirmed the hypothesis that individual factors have different impacts in a video and a chat negotiation: In the video negotiation, gender significantly predicted negotiation outcomes. Women used fewer words compared to men, which leads both to a lower individual profit and a better subjective value. In the chat negotiation, openness, conscientiousness, and extraversion predicted negotiation outcomes. In addition, individual factors affected attitudes toward the negotiation and behaviors. The results indicate that some individuals have an advantage in certain media. Overall, the impact of individual factors in e-negotiations seems to be limited even though such an impact is intuitively assumed by many negotiators.
COVID-19 and persistent symptoms: implications for polycystic ovary syndrome and its management
Authors: Zhang Shanshan , Wu Yanqun , Mprah Richard , Wang Mingming
Published: October 2024

The COVID-19 pandemic has left a profound mark on global health, leading to substantial morbidity and mortality worldwide. Beyond the immediate symptoms of infection, the emergence of “long COVID”, the long-term effects of SARS-CoV-2, has become a significant public health concern. Long COVID is a multifaceted condition affecting various organs and systems, including the cardiovascular, digestive, nervous, and endocrine systems. Individuals diagnosed with polycystic ovary syndrome (PCOS) may face an increased risk of severe COVID-19 symptoms and infection. It is crucial to comprehend how long COVID affects PCOS patients to devise effective treatment and care strategies. Here, we review the detrimental effects of COVID-19 and its long-term effects on reproductive health, endocrine function, inflammation, metabolism, cardiovascular health, body composition, lifestyle, and mental health in patients with PCOS. We offer recommendations for the post-covid-19 management of PCOS, emphasizing the necessity of a comprehensive, multidisciplinary approach to patient care. Furthermore, we discuss prospective research directions, highlighting the significance of continued investigations and clinical trials to evaluate treatment approaches for long COVID and its ramifications in individuals with PCOS.
Determinant genetic markers of semen quality in livestock
Authors: Khan Muhammad Zahoor , Chen Wenting , Naz Saima , Liu Xiaotong , Liang Huili , Chen Yinghui , Kou Xiyan , Liu Yihong , Ashraf Iqra , Han Ying , Peng Yongdong , Wang Changfa , Zahoor Muhammad
Published: October 2024

The reproductive efficiency of livestock is crucial for agricultural productivity and economic sustainability. One critical factor in successful fertilization and the viability of offspring is the quality of semen. Poor semen quality, especially in frozen-thawed semen used in artificial insemination (AI) have been shown to influence conception outcomes, resulting a negative impact on livestock production. Recent advancements in genetic research have identified specific markers linked to semen quality traits in various livestock species, such as cattle, sheep, goats, pigs, buffalo, and equines. These genetic markers are essential in screening males for breeding suitability, which in turn enhances selective breeding programs. Understanding these markers is crucial for improving reproductive performance and increasing productivity in livestock populations. This review offers a comprehensive overview of the genetic markers associated with semen quality in key livestock. It explores the underlying genetic mechanisms and their practical implications in animal breeding and management. The review underscores the importance of integrating genetic insights into breeding strategies to optimize reproductive efficiency and ensure the sustainable development of livestock industries.
Genome-wide mapping uncovers significant quantitative trait loci associated with yam mosaic virus infection, yield and dry matter content in White Guinea yam (Dioscorea rotundata Poir.)
Authors: Adjei Emmanuel Amponsah , Odong Thomas Lapaka , Esuma Williams , Bhattacharjee Ranjana , Agre Paterne Angelot , Adebola Patrick Olusanmi , Chamba Emmanuel Boache , Asfaw Asrat , Dramadri Isaac Onziga , Mbabazi Sharon Tusiime , Edema Richard , Ozimati Alfred Adebo , Ochwo-Ssemakula Mildred , Alicai Titus
Published: October 2024

Introduction

Yam is an important crop for food security in East and West Africa due to its high market value and customer demand. High tuber quality with yield and disease resistance are the main traits for acceptability of yam cultivars across the tropical zone. There has been limited progress in enhancing the production and quality traits of yams, despite the significant socio-economic significance of this crop.

Method

To expedite the development of high-quality yam cultivars in Uganda, traits association study was conducted to identify genomic regions associated with key traits such as disease resistance, high yields, and dry matter content. The association mapping was conducted with multi-random mixed linear model (mrMLM) to compute the associations using five genetic models.

Results

A total of 16 significant single nucleotide polymorphisms (SNPs) markers were identified to be associated with the traits studied. Gene identification analysis revealed the presence of key putative genes such as Vicilin-like seed storage protein At2g28490 (ARATH)and Growth-regulating factor 1 involved in a variety of functions ranging from storage and gene regulation for disease resistance.

Discussion

The results obtained from this work have significant implications for the in-depth analysis of the genetic structure underlying key traits in yam. Additionally, this study emphasizes the identification of SNP variants and genes that may be utilized for genomic-informed selection in order to enhance yield and disease resistance in yams.
An investigation of how to address climate change-induced land degradation in Balaka, Malawi, by reconciling indigenous and scientific knowledge
Authors: Chamasula Victoria , Rabumbulu Mulalo
Published: October 2024

Malawi, like the majority of African countries, is experiencing land degradation as a result of climate change and unsustainable farming methods. Land degradation is a worldwide problem, but Africa is the worst affected, with 75% of arable land already degraded. Malawi is primarily an agricultural country, with 11 million people practicing small-scale subsistence farming. Given the hilly terrain, forests, and tough pastures, only one-third of the county is considered cultivable. However, agriculture accounts for 30% of Malawi’s GDP, exporting 80% of its agricultural produce. Small-scale farmers are essential producers, farming 5.3 million hectares of land and accounting for over 70% of Malawi’s food consumption. Unfortunately, as climate change and economic demands increase, so does land degradation. Even though indigenous knowledge has been used for generations to adapt to changing environments, there is an unmistakable distinction between scientific and indigenous knowledge, with scientific being seen as far superior. Several studies have revealed that depending entirely on one knowledge system is insufficient for effectively addressing environmental concerns. Thus, there is a need for more comparisons that allow for a complementary application of the two knowledge systems rather than their contradiction. In this work, we identify indigenous indicators of land degradation and land management practices utilized by Malawian farmers, and we investigate how indigenous and scientific knowledge systems might be combined to adapt and address the issue of land degradation swiftly. To do this, 100 semi-structured interviews were conducted with farmers in five villages. Atlas-ti software was used to do thematic content analysis on the dataset. Our findings show farmers’ coping techniques are still based on IK and motivated by experiential learning from earlier climatic crises. Though most farmers know scientific land management practices, current adaption strategies rely on expensive resources and are inappropriate for indigenous farmers. The study investigates various ways scientific and indigenous knowledge could be integrated to enhance climate change adaptation against land degradation. These encompass developing indigenous indicator baselines, including new measures for measuring soil fertility, and more effective and energy-efficient irrigation technologies.
Clinical phenotype, NOD2 genotypes, and treatment observations in Yao syndrome: a retrospective case series
Authors: Williamson Katrina A. , Samec Matthew J. , Patel Jenny A. , Orandi Amir B. , Wang Benjamin , Crowson Cynthia S. , Loftus Edward V. , Alavi Afsaneh , Moyer Ann M. , Davis John M.
Published: October 2024

Objective

The aim of this study was to characterize the phenotype and genotype of patients with Yao syndrome (YAOS), with focus on comparing to prior cohorts, identifying novel features, and describing treatment observations.

Methods

A retrospective medical records review of patients with YAOS seen at Mayo Clinic was conducted to characterize clinical features, NOD2 genotypes, and therapeutic trials and responses.

Results

Twenty-two patients diagnosed with YAOS were included. Eighteen patients (81.8%) were female and twenty (90.9%) were White. Mean age at symptom onset was 24.0 ± 14.8 years. Common clinical manifestations included fever (81.8% of patients), rash (95.5%), chronic gastrointestinal symptoms (100%), arthralgia/arthritis (95.5%), and sicca symptoms (68.2%). NOD2 genotypes as single variants included IVS8 + 158 in 14 patients (63.6%), R702W in 8 patients (36.4%), 1007fs in 4 (18.2%), and one patient had only a previously unreported rare variant. Eight patients (36.4%) had compound (two or more) NOD2 variants. Potential comorbidities of YAOS observed in this cohort included gastrointestinal dysmotility, autonomic dysfunction, and mast cell activation-like symptoms. Glucocorticoid responsiveness was observed in 15 of 20 patients exposed (75%). Eleven patients (50.0%) received IL-1 inhibitor therapy, and one patient (4.5%) received IL-6 inhibitor therapy with adequate disease control.

Conclusion

Our findings substantiate the occurrence of fevers, arthralgia/arthritis, rash, chronic gastrointestinal symptoms, and sicca-like symptoms described previously in patients with YAOS. Novel clinical features and one NOD2 variant not previously described were identified. Glucocorticoids, biologic IL-1 inhibitors, and IL-6 receptor inhibitors appeared to be effective for treatment of patients with YAOS.
Integrating genomics and AI to uncover molecular targets for mRNA vaccine development in lupus nephritis
Authors: Mou Lisha , Lu Ying , Wu Zijing , Pu Zuhui , Wang Meiying
Published: October 2024

Lupus nephritis (LN), a complex complication of systemic lupus erythematosus, requires in-depth cellular and molecular analysis for advanced treatment strategies, including mRNA vaccine development. In this study, we analyzed single-cell RNA sequencing data from 24 LN patients and 10 healthy controls, supplemented by bulk RNA-seq data from additional LN patients and controls. By applying non-negative matrix factorization (NMF), we identified four distinct leukocyte meta-programs in LN, highlighting diverse immune functions and potential mRNA vaccine targets. Utilizing 12 machine learning algorithms, we developed 417 predictive models incorporating gene sets linked to key biological pathways, such as MTOR signaling, autophagy, Toll-like receptor, and adaptive immunity pathways. These models were instrumental in identifying potential targets for mRNA vaccine development. Our functional network analysis further revealed intricate gene interactions, providing novel insights into the molecular basis of LN. Additionally, we validated the mRNA expression levels of potential vaccine targets across multiple cohorts and correlated them with clinical parameters such as the glomerular filtration rate (GFR) and pathological stage. This study represents a significant advance in LN research by merging single-cell genomics with the precision of NMF and machine learning, broadening our understanding of LN at the cellular and molecular levels. More importantly, our findings shed light on the development of targeted mRNA vaccines, offering new possibilities for diagnostics and therapeutics for this complex autoimmune disease.
A comparison of haploidentical versus HLA-identical sibling outpatient hematopoietic cell transplantation using reduced intensity conditioning in patients with acute leukemia
Authors: Jaime-Pérez José Carlos , Valdespino-Valdes Jorge , Gómez-De León Andrés , Barragán-Longoria Renata Valeria , Dominguez-Villanueva Adriana , Cantú-Rodríguez Olga Graciela , Gutiérrez-Aguirre César Homero , Gómez-Almaguer David
Published: October 2024

Background

Hematopoietic cell transplantation (HCT) increases survival for acute leukemia. Outpatient allogeneic HCT reduces costs and increases transplant rates in developing countries. We report outcomes of outpatient HLA-identical and haploidentical HCT in acute leukemia.

Methods

This single-center retrospective cohort study analyzed 121 adult patients with acute myeloblastic (AML) and acute lymphoblastic leukemia (ALL) receiving an outpatient allogeneic HCT with peripheral blood allografts after reduced-intensity conditioning (RIC) from 2012-2022.

Results

There were 81 (67%) haploidentical and 40 (33%) HLA-identical transplants. Complete chimerism (CC) at day +100 was not different in HLA-identical compared to haploidentical HCT (32.5% and 38.2%, P=0.054). Post-HCT complications, including neutropenic fever (59.3% vs. 40%), acute graft-versus-host-disease (aGVHD) (46.9% vs. 25%), cytokine release syndrome (CRS) (18.5% vs. 2.5%), and hospitalization (71.6% vs 42.5%) were significantly more frequent in haploidentical HCT. Two-year overall survival (OS) was 60.6% vs. 46.9%, (P=0.464) for HLA-identical and haplo-HCT, respectively. There was no difference in the 2-year disease-free-survival (DFS) (33.3% vs. 35%, P=0.924) between transplant types. In multivariate analysis, positive measurable residual disease (MRD) at 30 days (HR 8.8, P=0.018) and 100 days (HR 28.5, P=0.022) was associated with lower OS, but not with non-relapse mortality (NRM) (P=0.252 and P=0.123, univariate). In univariate analysis, both 30-day and 100-day MRD were associated with lower DFS rates (P=0.026 and P=0.006), but only day 30 MRD was significant in multivariate analysis (P=0.050). In the case of relapse, only MRD at day 100 was associated with increased risk in the univariate and multivariate analyses (HR 4.48, P=0.003 and HR 4.67, P=0.008). Chronic graft-versus-host-disease (cGVHD) was protective for NRM (HR 0.38, P=0.015). There was no difference in cumulative incidence of relapse (CIR) between transplant types (P=0.126). Forty-four (36.4%) patients died, with no difference between HCT type (P=0.307). Septic shock was the most frequent cause of death with 17 cases, with no difference between transplant types

Conclusions

Outpatient peripheral blood allogenic HCT after RIC is a valid and effective alternative for adult patients suffering acute myeloblastic or lymphoblastic leukemia in low-income populations.
A structural, genetic and clinical comparison of CAR-T cells and CAR-NK cells: companions or competitors?
Authors: Andrea Alain E. , Chiron Andrada , Sarrabayrouse Guillaume , Bessoles Stéphanie , Hacein-Bey-Abina Salima
Published: October 2024

In recent years, following the groundbreaking achievements of chimeric antigen receptor (CAR) T cell therapy in hematological cancers, and advancements in cell engineering technologies, the exploration of other immune cells has garnered significant attention. CAR-Therapy extended beyond T cells to include CAR natural killer (NK) cells and CAR-macrophages, which are firmly established in the clinical trial landscape. Less conventional immune cells are also making their way into the scene, such as CAR mucosal-associated invariant T (MAIT) cells. This progress is advancing precision medicine and facilitating the development of ready-to-use biological treatments. However, in view of the unique features of natural killer cells, adoptive NK cell immunotherapy has emerged as a universal, allogenic, “off-the shelf” therapeutic strategy. CAR-NK cytotoxic cells present targeted tumor specificity but seem to be devoid of the side effects associated with CAR-T cells. CAR-NK cells appear to be potentially promising candidates for cancer immunotherapy. However, their application is hindered by significant challenges, particularly the limited persistence of CAR-NK cells in the body, which poses a hurdle to their sustained effectiveness in treating cancer. Based upon the foregoing, this review discusses the current status and applications of both CAR-T cells and CAR-NK cells in hematological cancers, and provides a comparative analysis of the structure, genetics, and clinical outcomes between these two types of genetically modified immune cells.
Sex- and time-dependent role of insulin regulated aminopeptidase in lipopolysaccharide-induced inflammation
Authors: Vear Anika , Chakraborty Amlan , Fahimi Farnaz , Ferens Dorota , Widdop Robert , Samuel Chrishan S. , Gaspari Tracey , van Endert Peter M. , Chai Siew Yeen
Published: October 2024

The enzyme, insulin regulated aminopeptidase (IRAP), is expressed in multiple immune cells such as macrophages, dendritic cells and T cells, where it plays a role in regulating the innate and adaptive immune response. There is a genetic association between IRAP and survival outcomes in patients with septic shock where a variant of its gene was found to be associated with increased 28-day mortality. This study investigated the role for IRAP in a lipopolysaccharide (LPS)-induced inflammatory response which is thought to model facets of the systemic inflammation observed in the early stages of human gram-negative sepsis. The frequencies and activation of splenic immune cell populations were investigated in the IRAP knockout (KO) mice compared to the wildtype controls over a period of 4-, 24-, or 48-hours following LPS stimulation. Dendritic cells isolated from the spleen of female IRAP KO mice, displayed significant increases in the activation markers CD40, CD86 and MHCII at 24 hours after LPS induction. A modest heightened pro-inflammatory response to LPS was observed with increased expression of activation marker CD40 in M1 macrophages from male IRAP knockout mice. Observations in vitro in bone marrow-derived macrophages (BMDM) revealed a heightened pro-inflammatory response to LPS with significant increases in the expression of CD40 in IRAP deficient cells compared with BMDM from WT mice. The heightened LPS-induced response was associated with increased pro-inflammatory cytokine secretion in these BMDM cells. A genotype difference was also detected in the BMDM from female mice displaying suppression of the LPS-induced increases in the activation markers CD40, CD86, CD80 and MHCII in IRAP deficient cells. Thus, this study suggests that IRAP plays specific time- and sex-dependent roles in the LPS-induced inflammatory response in dendritic cells and macrophages.
Impaired Mycobacterium tuberculosis-specific T-cell memory phenotypes and functional profiles among adults with type 2 diabetes mellitus in Uganda
Authors: Ssekamatte Phillip , Nabatanzi Rose , Sitenda Diana , Nakibuule Marjorie , Bagaya Bernard Ssentalo , Kibirige Davis , Kyazze Andrew Peter , Kateete David Patrick , Sande Obondo James , Crevel Reinout van , Cose Stephen , Biraro Irene Andia
Published: October 2024

Background

Efforts to eradicate tuberculosis (TB) are threatened by diabetes mellitus (DM), which confers a 3-fold increase in the risk of TB disease. The changes in the memory phenotypes and functional profiles of Mycobacterium tuberculosis (Mtb)-specific T cells in latent TB infection (LTBI)-DM participants remain poorly characterised. We, therefore, assessed the effect of DM on T-cell phenotype and function in LTBI and DM clinical groups.

Methods

We compared the memory phenotypes and function profiles of Mtb-specific CD4+ and CD8+ T cells among participants with LTBI-DM (n=21), LTBI-only (n=17) and DM-only (n=16). Peripheral blood mononuclear cells (PBMCs) were stimulated with early secretory antigenic 6 kDa (ESAT-6) and culture filtrate protein 10 (CFP-10) peptide pools or phytohemagglutinin (PHA). The memory phenotypes (CCR7/CD45RA), and functional profiles (HLA-DR, PD-1, CD107a, IFN-γ, IL-2, TNF, IL-13, IL-17A) of Mtb-specific CD4+ and CD8+ T cells were characterised by flow cytometry.

Results

Naïve CD4+ T cells were significantly decreased in the LTBI-DM compared to the LTBI-only participants [0.47 (0.34-0.69) vs 0.91 (0.59-1.05); (p<0.001)]. Similarly, CD8+ HLA-DR expression was significantly decreased in LTBI-DM compared to LTBI-only participants [0.26 (0.19-0.33) vs 0.52 (0.40-0.64); (p<0.0001)], whereas CD4+ and CD8+ PD-1 expression was significantly upregulated in the LTBI-DM compared to the LTBI-only participants [0.61 (0.53-0.77) vs 0.19 (0.10-0.28); (p<0.0001) and 0.41 (0.37-0.56) vs 0.29 (0.17-0.42); (p=0.007)] respectively. CD4+ and CD8+ IFN-γ production was significantly decreased in the LTBI-DM compared to the LTBI-only participants [0.28 (0.19-0.38) vs 0.39 (0.25-0.53); (p=0.030) and 0.36 (0.27-0.49) vs 0.55 (0.41-0.88); (p=0.016)] respectively. CD4+ TNF and CD8+ IL-17A production were significantly decreased in participants with LTBI-DM compared to those with LTBI-only [0.38 (0.33-0.50) vs 0.62 (0.46-0.87); (p=0.004) and 0.29 (0.16-0.42) vs 0.47 (0.29-0.52); (0.017)] respectively. LTBI-DM participants had significantly lower dual-functional (IFN-γ+IL-2+ and IL-2+TNF+) and mono-functional (IFN-γ+ and TNF+) CD4+ responses than LTBI-only participants. LTBI-DM participants had significantly decreased dual-functional (IFN-γ+IL-2+, IFN-γ+ TNF+ and IL-2+TNF+) and mono-functional (IFN-γ+, IL-2+ and TNF+) central and effector memory CD4+ responses compared to LTBI-only participants.

Conclusion

Type 2 DM impairs the memory phenotypes and functional profiles of Mtb-specific CD4+ and CD8+ T cells, potentially indicating underlying immunopathology towards increased active TB disease risk.
Unveiling ferroptosis: a new frontier in skin disease research
Authors: Wang Ke , Lin Yumeng , Zhou Dan , Li Peipei , Zhao Xiaoying , Han Zhongyu , Chen Haoran
Published: October 2024

Ferroptosis, a form of regulated cell death distinct from apoptosis, necrosis, and autophagy, is increasingly recognized for its role in skin disease pathology. Characterized by iron accumulation and lipid peroxidation, ferroptosis has been implicated in the progression of various skin conditions, including psoriasis, photosensitive dermatitis, and melanoma. This review provides an in-depth analysis of the molecular mechanisms underlying ferroptosis and compares its cellular effects with other forms of cell death in the context of skin health and disease. We systematically examine the role of ferroptosis in five specific skin diseases, including ichthyosis, psoriasis, polymorphous light eruption (PMLE), vitiligo, and melanoma, detailing its influence on disease pathogenesis and progression. Moreover, we explore the current clinical landscape of ferroptosis-targeted therapies, discussing their potential in managing and treating skin diseases. Our aim is to shed light on the therapeutic potential of modulating ferroptosis in skin disease research and practice.
Marine heatwaves and cold spells in the Northeast Atlantic: what should the UK be prepared for?
Authors: Jacobs Zoe Louisa , Jebri Fatma , Wakelin Sarah , Strong James , Popova Ekaterina , Srokosz Meric , Loveridge Alexandra
Published: October 2024

Up to now, the UK has avoided major marine heatwaves (MHWs) that cause severe damage to marine ecosystems and the blue economy. However, an unprecedented in its intensity, though short-lived, MHW occurred in UK waters in June 2023. This event sounded an alarm bell, highlighting gaps in our understanding of MHW characteristics and their potential future impacts in the UK. Here, we use a combination of remote sensing data and model output to characterise MHWs and Marine Cold Spells (MCSs) around the UK and the wider North Atlantic, and to assess the potential for concurrent biogeochemical extreme events. Results indicate that across the wider North Atlantic, the UK is not a hot spot for MHWs or MCSs but, regionally, the southern North Sea experiences the most activity. This is also the location of extreme chlorophyll-a concentrations, here termed blue waves (low chlorophyll-a) and green waves (high chlorophyll-a). However, there is not a very pronounced relationship between temperature and chlorophyll-a extremes, which may be impacted by the exact location, drivers and season of occurrence. In contrast, the southern North Sea and English Channel may experience a MHW and low near-bottom oxygen compound events year-round, which, due to the combination of thermal stress and reduced oxygen availability, may negatively impact benthic marine ecosystems. While MHWs in UK waters do not appear to be as long-lasting or intense as other well-documented events around the world, they are projected to increase. Thus, the UK has a unique opportunity to learn from other nations and so develop robust and comprehensive policies to increase preparedness and response capability for future extreme events.
Provenance and transport mechanism of marine sediments in the Zhongjiannan Basin
Authors: Wu Xuewan , Shi Chaoqi , Guo Feng , Li Zihan , Luo Junsheng , Li Peipeng , Wang Ziwen , Wang Guifeng , Wan Zhifeng
Published: October 2024

The research on the source of marine sediments has a vital impact on identifying material sources, transport mechanism, and the evolution of sedimentary environments. Previous studies have shown many outstanding achievements on the source analysis of the South China Sea, but there are still some controversies over the complex source and transport mechanisms of the Zhongjiannan Basin. In this study, we took a gravity core (583cm) from the Zhongjiannan Basin and analyzed the particle size, rare earth elements, and Sr-Nd isotopes of the core sediments to further reveal the source and transport mechanism. The surface sediments in the Zhongjiannan Basin were relatively stable, with an average particle size ranging from 5.66 to 17.74 μm. The normalized standard curve of chondrite exhibited the depletion of Eu, with LREE dominated in REE. As the depth increased, 87Sr/86Sr ratios showed a gradually increasing trend, while δNd change was relatively complex. On the whole, 87Sr/86Sr ratios (from 0.721537 to 0.725322) and δNd (from -11.561617 to -12.289374) were in a relatively narrow range. Based on the particle size characteristics, we found the geochemical characteristics of sediment largely resulted from different sediment sources. By comparing rare earth elements and Sr-Nd isotopes, we concluded the sediment of the Zhongjiannan Basin was from mainly terrigenous contribution. In addition, taking into account factors such as terrain, migration distance, and river drainage system, we conclude the sediment were mainly from the Mekong River, the Red River, Taiwan Island, and Hainan Island. The surface current along the northeast direction was the main transportation route for the sediments of the Mekong River. The Guangdong coastal current and the southwest surface current transported sediment from the Red River and Hainan Island to the Zhongjiannan Basin. The surface current and deep-water current in the southwest direction carried sediment from Taiwan Island to the study area, while the Kuroshio also had some impacts on the sediment transportation of Taiwan Island. This study has reinforced the research on provenance in the South China Sea Basin and has an important significance on evolution of sedimentary environments, evolution of ancient oceans.