bluuebunny/crossref_metadata_2025 huggingface dataset:
KLASIFIKASI TINGKAT KEMATANGAN BUAH NAGA KRISTAL BERDASARKAN WARNA KULIT MENGGUNAKAN ALGORITMA K-NEAREST NEIGHBORS
Authors: Hernando Erick , Chandra Saputra Ade , Parhusip Jadiaman
Published: December 2024

Penelitian ini bertujuan untuk mengembangkan sebuah metode yang efektif dalam menentukan tingkat kematangan buah naga pada kelas layak panen, matang, mentah secara otomatis dengan memanfaatkan algoritma K-Nearest Neighbors (K-NN) melalui proses Knowledge Discovery in Databases (KDD). Proses KDD, yang melibatkan serangkaian langkah mulai dari pemilihan data, praproses data, transformasi data, hingga penerapan algoritma untuk menghasilkan pengetahuan yang bermanfaat, digunakan dalam penelitian ini untuk mengolah dan menganalisis data citra buah naga.
Pada penelitian ini klasifikasi diolah melalui tahapan KDD, termasuk proses praproses untuk membersihkan dan mempersiapkan data, Penggunaan Min-Max Normalization untuk menstandarisasi data sehingga semua fitur berada pada skala yang sama, sangat penting untuk kinerja model K-NN, transformasi untuk mengekstraksi data kelas, dan penerapan algoritma K-NN untuk klasifikasi kematangan buah. Pemilihan algoritma K-NN dalam tahapan KDD didasarkan pada kesederhanaan serta kemampuannya dalam mengklasifikasikan data dengan tingkat akurasi yang tinggi.
Hasil penelitian menunjukkan bahwa metode KDD yang diterapkan dengan algoritma K-NN mampu mengklasifikasikan kematangan buah naga dengan Akurasi terbaik diperoleh pada nilai K = 3 dengan persentase akurasi sebesar 91% tanpa memerlukan pemotongan fisik pada buah. Dengan demikian, penelitian ini tidak hanya memberikan kontribusi dalam bidang pertanian presisi tetapi juga menunjukkan bagaimana metode KDD dapat diterapkan secara efektif untuk menyelesaikan masalah nyata di lapangan.
Assessment of srap markers effectiveness for analysis of forage legume crops
Authors: Dushkin Vladimir
Published: December 2024

Molecular and genetic analysis of forage legumes (red clover, different species of lupine, and bird's-foot trefoil) was conducted using 31 combinations of SRAP markers. The informative primers were selected for each plant species to assess the genetic diversity. Parameters of interspecies and inter-varietal DNA polymorphism were estimated: effective number of alleles, Nei’s genetic diversity index and Shannon’s index. Based on the genotyping data the dendrograms of genetic similarity were constructed using UPGMA method and PCoA-analysis. As a rule the samples were combined accordingly their origin. The values of PIC (polymorphism information content) indicator were high for every studied species with variations from 0.76 in red clover to 0.81 in lupine. The results obtained confirmed the SRAP-marking method effectiveness for the genetic structure analysis of legume grasses different species, as well as for inter-varietal genetic variability evaluation. The data can be used for legume crops breeding programs enhancing.
Study on inheritance pattern and nutritional analysis of ATGRF2 transgenic 'Burgaltai' (Medicago varia Marthz)
Authors: Uuganzaya M. , Altantsetse L , Bayarsaikhan Sh , Enkhchimeg V
Published: December 2024

Alfalfa (Medicago varia Marthz) 'Burgaltai' cultivar is one of the most important forages of its palatable and nutritional values. But still, national scientists had reported that there is lack of characteristic have been appeared in Mongolian cultivated Medicago sp., and it is the percentage of leaf in the yield is low (up to 45%) and it had decreased dramatically in development cycle. Over-expression of AtGRF2 resulted in larger leaves and cotyledons comparing to wild type. In this study, transgenic 'Burgaltai' with AtGRF2 gene had increased leaf area by 0.52 cm2 and leaves in percentage per bush up to 48.6%. The transgenic lines showed 3:1 segregation ratio in T1 progenies (χ2 = 0.04–0.42, p ≤ 0.52–0.84). Hygromycin antibiotic concentration is 50 mg/l for selective media. According to the feed evaluation, some chemical composition increased in transgenic 'Burgaltai' except total fat.
Brief description of new breeding samples alfalfa in the Moscow region
Authors: Lomov Mikhail
Published: December 2024

It is important for Russian agriculture to ensure high sustainability and productivity of natural land and agricultural landscapes, provided that the advanced adaptation of agroecosystems and agricultural landscapes is ready for expected climate and environmental changes. So that the natural vegetation of the agricultural landscape, thanks to controlled, managed and transformed human activities, can be replaced by planting and cultural crops. An adaptive evolutionary-ecological approach to this problem is increasingly being used in scientific breeding science. For all climatic and soil zones of the Russian Federation and various places of plant growth (drylands, floodplain meadows, etc.), it is necessary to create new varieties that would differ in maturity, growth rate of the crop, and also, when used in the early phases of vegetation, could actively accumulate the necessary nutrients for the following alienations. Blue hybrid alfalfa is a legume perennial crop that can be used to produce various types of feed: hay, green pasture feed, grass cutting, herbal protein-vitamin flour, feed pellets and briquettes, haylage, silage and protein concentrate for all types of farm animals and poultry. Scientific studies with this crop were carried out in the Moscow region (Non-Chernozem zone of Russia) on heavy sod-podzolic soils (FNC "VIK named after V.R. Williams") in 2021–2022 in the field crop rotation of perennial alfalfa in three breeding nurseries. The purpose of the research was to obtain new source material and evaluate it. In addition, the identification and involvement in the further breeding process of new biotypes and individual numbers with good indicators of adaptability to the soil and climatic conditions of the Central Non-Chernozem zone of the Moscow region, early spring and friendly regrowth, productive and long-term use, with high productivity and good resistance to alfalfa root rot and other crop diseases. The article presents the research results obtained in the third breeding nursery, at pH = 4.3.
Ambition and Competition among Hindu Bengali Elites in Eighteenth- and Nineteenth-Century Calcutta
Authors: Bhattacharyya Monolina
Published: December 2024

In eighteenth- and nineteenth-century urban colonial Calcutta, Hindu Bengali gentry celebrated numerous festivals at home, including Rathajatra, Doljatra, Jagaddhatri Puja, and Kali Puja, and even marked the birthdays and weddings of their pets with grandeur. Durga Puja, held in autumn, stood out as the most elaborate and significant. It provided affluent Bengali families with a chance to display opulence by hosting lavish gatherings and inviting prominent Europeans to their newly built mansions. Competition among them was fierce to showcase their wealth and status. For many of these families, Durga Puja was not just a personal celebration but also a means of cultivating relationships with British and other European residents who held positions of authority or influence, by which they sought to elevate their social standing and prosperity.
Science of Measuring God’s Time
Authors: Carneiro Larissa
Published: December 2024

By investigating two scientific enterprises, this article compares Catholic and Protestant quests in seventeenth-century Europe to measure time: the meridian line in the Roman Basilica of Santa Maria degli Angeli e dei Martiri and the Bishop Ussher chronology. I seek to show that both Catholic and Protestant projects brought science to the service of the priorities of religious life. Rival religious sensibilities led to different outcomes. In the Catholic initiative, the motion of the stars needed to match perfectly the liturgical calendar in order to determine the correct date of one of its major festivities—Easter; in the Protestant, history should conform to and confirm the Holy Scriptures. The Catholic scheme was designed to facilitate the consistency of the liturgical cycle and its festivities, the backbone of Catholic worship and devotional practice. By contrast, the Protestant biblical chronologist James Ussher used a temporal system that exhibited a linear rather than a cyclical structure, an approach that was committed to affirming the inerrancy of the biblical text. Both enterprises reflect the rich scientific environment of the seventeenth century, which saw the emergence of a range of different cultural practices and projects aimed at understanding, rationalizing, and controlling the natural world.
Drum and Bass and Sausage Rolls
Authors: Inglis Chris
Published: December 2024

This article explores the 2022 edition of Boomtown Fair, the UK's leading festival for alternative, underground music. This particular event was notable due to the surprising prevalence of participants dressed in clothing bearing the logo of Greggs, the high street bakery. This was the result of a partnership between Greggs and the fashion retailer Primark, who the weekend before Boomtown had released a "festival collection," featuring multiple items of clothing promoting the bakery. During the festival itself, hundreds of participants could be found proudly wearing items from this collection, to a degree that was difficult to ignore. An apparent affiliation between these three enterprises —Boomtown, Greggs, and Primark—had undeniably resonated with audiences, a situation worthy of study due to what may subsequently be revealed about contemporary attitudes to fashion, music, and festival culture. I argue that the primary explanation for this occurrence is the presence of a post-ironic mindset shared by many of the attendees of Boomtown Fair. First being used to describe the writings of 1990s authors such as David Foster Wallace, the notion of post-irony is characterized by its unconventional blend of both genuine sincerity and ironic detatchment. The concept has since been used to explain and rationalize numerous aspects of modern culture. Through an analysis of the post-ironic mindset, I present a case for why the Greggs-Primark range appealed so extensively to the Boomtown audience of 2022. I provide a comprehensive investigation that also reveals insights into contemporary trends surrounding the interaction between brands and consumers, considering the extent to which festivals and events like Boomtown have helped to facilitate this interaction.
Musical Stroll in Manchester with Éric Cantona, “The King”
Authors: Boli Claude , Fournier Laurent-Sébastien
Published: December 2024

In this autobiographical essay, a former football player reminisces about the musical strolls he took with footballer Éric Cantona in Manchester, England, in the 1990s, as well as the rituals that marked Cantona’s football games. This piece reflects on the musical atmosphere of the city that accompanies the practice of professional football. It reminds us how sport relies on the inventiveness of the fans, who, for example, sometimes change the words of pop tunes to celebrate their heroes. It also sheds light on the relationships between music, place, and time.
Review of Ritualising Cultural Heritage and Re-enchanting Rituals in Europe by Alessandro Testa
Authors: Stefano Michelle
Published: December 2024

Review of Ritualising Cultural Heritage and Re-enchanting Rituals in Europe by Alessandro Testa (Carolina Academic Press, 2023).
Amateur Working-Class Soccer
Authors: Mendes Machado da Silva Diana
Published: December 2024

The term “Futebol de Várzea” (Floodplain Soccer) has become synonymous with amateur working-class soccer in the city of São Paulo, Brazil. The multiple reasons for this connection relate to how soccer was appropriated by the city’s popular segments in various community “associations” of the várzeas (floodplains). The associative form grew historically from a combination of experiences of elite colleges, unions, and factory workers in England, and popular associativism was the basis for the organization of sport in such places as the suburbs of São Paulo. While tournaments and championships organized competitions in the context of European expansionism, community sports festivities and festivals introduced and incorporated soccer into the city’s suburban and várzea daily life. Thus, through immigrant associations for mutual aid, religious, and Black brotherhoods, among other institutions, Várzea Soccer figured as a kind of archive of non-hegemonic practices of playful, festive, and sports interaction with the (sub)urban space. These practices, which left deep marks, are still present in how sport is experienced in the country.
Introduction
Authors: Fournier Laurent-Sébastien
Published: December 2024

This introduction to the special section on sport and festivity considers these terms in multiple dimensions and stretches their definitions to the maximum, exploring how this intersection between sport and festivity can be productive not only for festive studies, but for the social sciences and the humanities in general. Through the different essays presented in this section, which demonstrate how competitive situations can be transformed into moments of festive and playful sharing around the world, the diverse relationships between festivity and sport bear witness to historical and social developments in modes of sociability from various cultural contexts.
Journal of Festive Studies Issue 8 Call for Papers
Authors: Elliott Journal of Festive Studies Editorial Team
Published: December 2024

In addition to our guest-edited section described below, we always welcome submissions on a rolling basis, with no deadline for consideration. Please do think of us if your research or professional background touches on festive practices!
Mixed Signals
Authors: Papushina Anastasia
Published: December 2024

The October Revolution of 1917 introduced a new array of revolutionary festivals, prompting a series of debates concerning the appropriate manner of their celebration and the significance they should hold within the unique context of Soviet Russia. Festival organizers endeavored to reimagine several foundational aspects of commemorating special dates. This article examines the paradoxes and inconsistencies between the intended meanings of early Soviet festivals and their actual manifestations. The author highlights the conflicting messages that characterized this aspect of early Soviet culture, revealing the underlying tensions in the attempt to establish a cohesive revolutionary identity through these celebrations.
Instituições financeiras brasileiras
Authors: Paula Wellington Vicente de , Ribeiro Suzana Salgado , Portugal Nilton dos Santos
Published: December 2024

Este artigo tem o propósito de analisar os impactos da estrutura brasileira na manutenção do racismo estrutural no Brasil, a partir da contextualização da formação de um dos componentes dessa superestrutura, as instituições financeiras. Após o reconhecimento público do Banco do Brasil, em 2023, da sua função convergente na articulação do capital financeiro advindo da economia escravagista brasileira até o fim da abolição no século XIX, investigam-se as formas pelas quais essa instituição contribuiu para a transição econômica do país. A pesquisa se baseia em documentos históricos submetidos ao Ministério Público Federal que demonstram o envolvimento de acionistas e fundadores do Banco do Brasil com o tráfico de pessoas escravizadas. O estudo revela que a exploração da mão de obra escravizada foi fundamental para a consolidação do capital inicial da instituição, e que, até os dias atuais, a população negra permanece excluída do acesso pleno às oportunidades financeiras. Conclui-se que o Banco do Brasil é um exemplo da perpetuação das desigualdades estruturais herdadas do período escravocrata, e discute-se a necessidade de reparações e de políticas públicas voltadas à emancipação econômica da população negra
PENGEMBANGAN APLIKASI KEAMANAN MOBILE UNTUK MENGAWASI JARINGAN RUMAH DARI JARAK JAUH
Authors: Winda Syukur Winda Syukur , Fajrin Alfannisa Annurullah
Published: December 2024

In the current era of globalization, the use of mobile devices has become an important part of daily life by providing easy internet access to various online service applications. Security is an important aspect to deal with increasing general crime in Indonesia, for this reason innovation is needed to develop a remote home security application to prevent theft. The solutionis to create a home monitoring tool that adopts CCTV cameras. Which uses ESP32-CAM as a microcontroller which can be monitored via the application, there is also a PIR Sensor to detect living objects. The output produced is a buzzer as an alarm sound warning and there is also a notification in the application.
PENGARUH UKURAN PERUSAHAAN, UKURAN KANTOR AKUNTAN PUBLIK (KAP) DAN OPINI AUDITOR TERHADAP AUDIT DELAY
Authors: Sihite Maria Veronica , Ramdani Edon
Published: December 2024

This research aims to examine the influence of company size, KAP size, and auditor's opinion on audit delay in industrial companies listed on the Indonesia Stock Exchange with a research period of 2017-2022. This research uses a quantitative approach and uses associative methods. The type of data used in this research is secondary data. The data analysis method used in this research is Panel Data Regression Analysis using the Eviews version 10 application and Microsoft Excel. The data collection technique in this research is a purposive sampling technique with 55 populations becoming 23 company samples processed in this research. The research results show that simultaneously company size, KAP size, and auditor opinion have an effect on audit delay. Partially, company size and KAP size have no effect on audit delay, while the auditor's opinion has an effect on audit delay.
pengaruh Kepemilikan Manajerial, Struktur Modal dan Investment Opportunity Set (IOS) Terhadap Kualitas Laba
Authors: Umammi Safira , Azzahra Khoirunnisa
Published: December 2024

This research aims to provide empirical evidence on the influence of the independence of Managerial Ownership, Capital Structure, Investment Opportunity Set on Profit Quality in consumer non-cylicals sector companies lister on the Indonesia Stock Exchange for the 2018-2022 period. The number of research samples is 15 consumer non-cylicals sector companies. Which is determined based on the purposive sampling method. The Methods used are multiple linear regression model analysis, common effect model selection test, classical assumption test, multiple linear test and hypothesis testing with the helm of statistical data processing e-views versin 12. Research results this shows thas Managerial Ownership, Capital Structure, Investment Opportunity Set simultaneously have a significant effect on Earnings Quality and the t test states that Capital Structure has a significant effect on Earnings Quality, on the Managerial Owneship variable, Investment Oppourtunity Set does no have significatnt effect on Earnings Qualtiy.
DETERMINAN PENCEGAHAN FRAUD PADA BANK BUMN DI KOTA BATAM
Authors: Prima Argo Putra , Janrosl Viola Syukrina E. , Mulawarman Mulawarman , Yusuf Muhammad
Published: December 2024

This study aims to analyze the influence of internal audit and internal control on fraud prevention at state-owned banks in Batam City. It's critical to comprehend the elements that can stop fraud. Employees of state-owned banks in Batam were given questionnaires as part of the quantitative approach utilized in this study to collect data. The results of the study indicate that internal audit has a significant influence on fraud prevention. This indicates that the effectiveness of the internal audit function in identifying weaknesses and ensuring compliance with operational procedures plays an important role in minimizing the potential for fraud. However, the results of the study also show that internal control does not have a significant influence on fraud prevention partially. However, when tested simultaneously, internal audit and internal control together have a significant influence on fraud prevention. This finding emphasizes the importance of synergy between internal audit and internal control in creating an effective system to prevent fraud in the banking sector. Therefore, banks need to increase the role of internal audit and ensure good coordination with the internal control system to achieve optimal results in fraud prevention efforts.
Impact of climatic variabilities and extreme incidences on the physical environment, public health, and people’s livelihoods in Ethiopia
Authors: Teku Degfie , Eshetu Sintayehu
Published: December 2024

Ethiopia’s vulnerability to climate change is exacerbated by high poverty rates, rapid population growth, increasing prevalence of vector-borne diseases, and heavy reliance on rain-fed agriculture. This narrative review aims to compile existing data on the impacts of climate extremes on the physical environment, public health, and livelihoods in Ethiopia, thereby highlighting the significance of this region for such a study. Data were sourced from peer-reviewed journal articles from databases like PubMed, Scopus, and Web of Science, as well as reports and other unpublished documents. Results show that Ethiopia is facing increasing frequency, severity, duration, and timing of climate-related extreme events. Key challenges include environmental degradation, reduced crop yields, recurring floods, droughts, famines, increased heat waves, and spread of infectious diseases. Average daily rainfall is projected to decrease from 2.04 mm (1961–1990) to 1.97 mm (2070–2099), indicating a worsening climate trend. Moreover, the average annual temperature has risen by 1.3°C since 1960, at a rate of 0.28°C per decade. Flood records indicate a sharp rise, with 274 flood incidents recorded in 2020, causing extensive damage, including an annual soil loss of 1 billion tons in the Ethiopian highlands, reducing land productivity by 2.2% annually. Droughts from 1964 to 2023 affected 96.5 million people, reduced GDP by 4%, decreased agricultural output by 12%, and increased inflation rates by 15%. The regions of Afar, Somali, Gambella, and Benshangul Gumuz exhibit extreme vulnerability to health impacts due to rising temperatures. Addressing climate extremes is critical to mitigate their adverse effects on Ethiopia’s environment, public health, and livelihoods.
Equity-centered knowledge brokering: taking stock of challenges, strategies, and possibilities
Authors: Malin Joel R. , Shewchuk Samantha
Published: December 2024

The pursuit of equity is a cornerstone of progress across diverse fields. Emerging literature across several fields has begun to focus on how knowledge brokers can take an equity-centered approach. This narrative synthesis draws upon that literature to explore what it means to be an equity-centered knowledge broker and to consider the challenges and possibilities inherent in that role. It identifies critical equity issues/dimensions vis-à-vis five main brokering strategies. From this review, the strategy facilitating relationships emerges as a first-order strategy for equity-centered brokers, with impacts stretching into all other areas. Therefore, equity-centered brokers should attend heavily to developing authentic, trusting relationships, value diversity, and elevate multiple forms of knowledge. This article also highlights some challenges and ongoing tensions relevant to equity-centered brokering. Relational, equity-centered knowledge brokering is time- and resource-intensive. Likewise, ongoing debates center on the merit of assuming a neutral brokering posture. Overall, it is hoped this article will benefit knowledge brokers, those with whom they partner, and those scholars who seek to understand and support them.
Fexuprazan safeguards the esophagus from hydrochloric acid-induced damage by suppressing NLRP1/Caspase-1/GSDMD pyroptotic pathway
Authors: Kim Seo Yeon , Yoon Jung-Ho , Jung Da Hyun , Kim Ga Hee , Kim Chul Hoon , Lee Sang Kil
Published: December 2024

Introduction

Proton pump inhibitors (PPIs) and potassium-competitive acid blockers (P-CABs) are widely used to manage gastric acid-related disorders by inhibiting hydrochloric acid (HCl) secretion from parietal cells in the stomach. Although PPIs are known to have anti-inflammatory properties beyond their role in inhibiting gastric acid secretion, research on P-CABs is lacking. In this study, we aimed to investigate whether all available P-CABs exhibit anti-inflammatory effects in gastroesophageal reflux-induced esophagitis and to elucidate the underlying mechanisms.

Methods

Het-1A cells, normal esophageal epithelial cells, were treated with HCl (pH 4) for 30 min. Esomeprazole, a representative PPI, and three currently marketed P-CABs (vonoprazan, tegoprazan, and fexuprazan) were used for pretreatment. Total RNA sequencing was performed using Het-1A cells pretreated with 1% DMSO or fexuprazan, followed by exposure to HCl. Pyroptosis was measured using lactate dehydrogenase (LDH) release and Annexin V-FITC/PI staining. Western blotting, qRT-PCR, and ELISA were used to determine the expression of the related genes.

Results

Pretreatment with esomeprazole, vonoprazan, tegoprazan, and fexuprazan significantly inhibited the HCl-induced pro-inflammatory cytokines, including IL-6, IL-8, IL-1β, and TNF-α. Fexuprazan and vonoprazan significantly attenuated the HCl-induced pyroptosis rate, as assessed by elevated LDH release and Annexin V-FITC/PI staining, whereas esomeprazole and tegoprazan did not. RNA sequencing revealed that NOD-like receptor (NLR) family pyrin domain-containing 1 (NLRP1) was significantly reduced in Het-1A cells pretreated with fexuprazan compared to those treated with DMSO. Fexuprazan and vonoprazan markedly reduced the HCl-induced transcriptional and translational expression of genes involved in the pyroptosis pathway, including NLRP1, Caspase-1, gasdermin D, and IL-1β. Notably, fexuprazan reduced the HCl-induced increase in pyroptosis and IL-1β using siRNA, even in the presence of NLRP1 knockdown. Fexuprazan, tested on inflammatory THP-1 macrophage cells, significantly reduced NLRP1 expression and inhibited lipopolysaccharide-induced pyroptosis.

Conclusion

Our findings reveal that all p-CABs exhibit anti-inflammatory properties, while fexuprazan inhibits inflammation and pyroptosis of esophageal cells caused by the gastric acid. Therefore, it is presumed to have additional benefits in gastroesophageal reflux disease in addition to suppressing gastric acid secretion.
The translational potential of inflammation-induced skin blister human models in exploring the pathogenesis of periodontitis and its systemic health implications
Authors: Irwandi Rizky Aditya , Marruganti Crystal , Collins George , Carvalho Jhonatan de Souza , Gilroy Derek , D’Aiuto Francesco
Published: December 2024

Periodontitis is a highly prevalent chronic disease. Despite decades of extensive research on the topic, a complete understanding of its immunopathogenesis, especially when linked to other inflammatory comorbidities, is lacking. Ex vivo human and in vivo animal experiments have shown the host inflammatory response’s crucial role in both the disease’s onset and its systemic implications. These approaches, however, remain questionable when translating these findings into real-world scenarios linked to periodontitis. A clear need for new in vivo human models is discussed, especially within the context of understanding the host response to key pathogens linked to periodontitis, such as Porphyromonas gingivalis (P. gingivalis). Therefore, a skin blister model was employed to describe the stages of the host immune response in humans after challenges by microbial and/or sterile insults. A novel human challenge model using UV-killed P. gingivalis holds promise in producing new evidence and bridging the gap of the host response to periodontitis and its links with other common chronic diseases.
Anti-Mesothelin CAR-NK cells as a novel targeted therapy against cervical cancer
Authors: Kutle Ivana , Polten Robert , Stalp Jan Lennart , Hachenberg Jens , Todzey Felix , Hass Ralf , Zimmermann Katharina , von der Ohe Juliane , von Kaisenberg Constantin , Neubert Lavinia , Kamp Jan C. , Schaudien Dirk , Seyda Ann-Kathrin , Hillemanns Peter , Klapdor Rüdiger , Morgan Michael Alexander , Schambach Axel
Published: December 2024

Resistance to the currently available treatment paradigms is one of the main factors that contributes to poor outcomes in patients with advanced cervical cancer. Novel targeted therapy approaches might enhance the patient’s treatment outcome and are urgently needed for this malignancy. While chimeric-antigen receptor (CAR)-based adoptive immunotherapy displays a promising treatment strategy for liquid cancers, their use against cervical cancer is largely unexplored. This study used alpharetroviral SIN vectors to equip natural killer (NK) cells with a third-generation CAR (including CD28 and 4-1BB co-stimulatory domains) targeting Mesothelin, which was identified to be highly expressed on primary human cervical cancer tissues and cervical cancer cell lines in this and other studies. Anti-Mesothelin CAR-NK cells demonstrated high cytotoxicity against cervical cancer cells in 2D and 3D culture models, which corresponded to increased degranulation of CAR-NK-92 cells upon exposure to Mesothelin+ target cells. Mesothelin- cervical cancer cells were generated by CRISPR-Cas9-mediated knockout and used to show target antigen specificity of anti-Mesothelin CAR-NK-92 cells and primary NK cells derived from different healthy donors in co-culture experiments. Combination of anti-Mesothelin CAR-NK-92 cells with chemotherapy revealed increased elimination of cancer cells as compared to monotherapy settings. Our findings indicate the promise of anti-Mesothelin CAR-NK cells as a potential treatment option against cervical cancer, as well as other Mesothelin+ malignancies.
US regulatory compliance for medical combination products: an overview
Authors: Singh Manav V. , Apshingekar Prafulla , Gandhi Sanyam , Singh Om V.
Published: December 2024

This article provides a high-level overview of US regulatory review and approval processes for the growing field of medical combination products (CPs; those merging drugs with devices and/or biological products). US law defines drugs, medical devices, and CPs in specific ways, and the components of a CP are still subject to their respective regulations while combined. The Food and Drug Administration's Office of Combination Products (OCP) oversees the review and classification of CPs, which is based on their primary mode of action. When a manufacturer submits a Request for Designation for a new CP, the OCP conducts a technical and clinical evaluation to identify risks and verify modes of action and therapeutic benefits. Evaluating the safety and efficacy of CPs and their constituent parts can be challenging due to the many potential interactions. However, as innovation continues in the health care landscape and the variety of CPs on the market increases, manufacturers must stay proactive in complying with regulatory standards and keeping their products safe.
Genetically predicted immune cells mediate the association between gut microbiota and autoimmune liver diseases
Authors: Zhang Jikang , Hu Yiqi , Xu Jin , Shao Hua , Zhu Qingping , Si Hao
Published: December 2024

Background

Increasing evidence suggests an association between gut microbiota and Autoimmune Liver Diseases (AILDs). However, causal inference remains controversial due to confounding bias in observational studies. Additionally, there is currently no clear evidence indicating that immune cells act as intermediate phenotypes in the pathogenesis of AILDs. This study utilizes the Mendelian Randomization (MR) method to investigate the causal relationships among gut microbiota, immune cells, and AILDs.

Methods

Initially, we conducted a two-sample MR analysis to predict the causal relationships among 412 gut microbiota, 731 immune phenotypes, and AILDs. Subsequently, a series of sensitivity analyses were performed to validate the initial MR results and reverse MR analysis was conducted to exclude reverse causality. Finally, a two-step MR analysis was utilized to quantify the proportion of the impact of gut microbiota on AILDs mediated by immune cells.

Results

Following rigorous MR analysis, our findings indicate that increased involvement of the gut microbiome in the superpathway of L-tryptophan biosynthesis is positively associated with an elevated risk of Autoimmune Hepatitis (AIH). The effect is partially mediated by the CD14+ CD16+ monocyte Absolute Count, which accounts for 17.47% of the total effect. Moreover, the species Ruminococcus obeum appears to mediate the development of Primary Sclerosing Cholangitis (PSC) through CD62L-CD86+ myeloid Dendritic Cell %Dendritic Cell, contributing to 32.47% of the total observed effect.

Conclusion

Our study highlights the potential mediating mechanisms of immune cells in the causal relationship between the gut microbiome and AILDs. These insights provide a foundation for developing preventive strategies for AILDs in clinical practice.
Assessment of bacterial communities of Coptotermes gestroi termite workers attacking Ironwood trees (Casuarina equisetifolia) in Guam for the presence of Ironwood tree decline-associated pathogens
Authors: Setia Garima , Chen Junyan , Schlub Robert , Husseneder Claudia
Published: December 2024

The Ironwood tree (Casuarina equisetifolia) holds a significant ecological role in Guam where a decline in Ironwood trees was first documented in 2002. Studies have linked the Ironwood tree decline (IWTD) to bacteria from the Ralstonia solanacearum complex and wetwood bacteria, specifically Klebsiella oxytoca and Klebsiella variicola. Presence of termites was first found to be associated with IWTD in 2010; however, the role of termites in IWTD is still not clear. The Asian subterranean termite, Coptotermes gestroi (Wasmann) (Blattodea: Rhinotermitidae) frequently attacks Ironwood trees. As workers of this soil-dwelling species of the lower termites harbor a diverse microbial community in their bodies, we examined whether C. gestroi workers carry IWTD-associated bacteria and could, therefore, act as vectors. We described the bacterial community in C. gestroi workers using 16S rRNA gene sequencing and tested the impact of factors related to the location and health of the Ironwood tree the termites were collected from on termite bacterial diversity. Feeding assays were performed to assess if workers show preference in consumption depending on the amount of Ralstonia and wetwood bacteria in the food source. Health of Ironwood trees and level of site management impacted the bacterial composition of C. gestroi termite workers attacking the trees. Although C. gestroi workers equally consumed food sources with high and low Ralstonia and wetwood bacteria load in lab experiments, Ralstonia and other IWTD-related bacteria were not detected in considerable amounts in termite workers collected from trees. Thus, C. gestroi workers are not a vector for bacteria associated with IWTD in Guam.
The study on cuproptosis in Alzheimer’s disease based on the cuproptosis key gene FDX1
Authors: Chen Guilin , Xi Erwei , Gu Xiaozhen , Wang Huili , Tang Qiqiang
Published: December 2024

Background

Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by memory and cognitive impairments. Previous studies have shown neuronal death in the brains of AD patients, but the role of cuproptosis and its associated genes in AD neurons remains unclear.

Methods

Intersection analysis was conducted using the AD transcriptome dataset GSE63060, neuron dataset GSE147528, and reported cuproptosis-related genes to identify the cuproptosis key gene FDX1 highly expressed in AD. Subsequently, cell experiments were performed by treating SH-SY5Y cells with Aβ25-35 to establish AD cell model. The real-time reverse transcriptase-polymerase chain reaction (RT-qPCR) and western blotting (WB) assays were employed to detect the expression levels of FDX1, DLAT, and DLST. Cell proliferation was analyzed by counting Kit-8 (CCK8), mitochondrial ROS levels were analyzed using flow cytometry. shRNA was used to downregulate FDX1 expression, followed by repetition of the aforementioned experiments. Clinical experiments utilized qPCR to detect FDX1 mRNA levels in peripheral venous blood of patients, and analyzed FDX1 expression differences in different APOE genotypes of AD patients. Finally, a protein–protein interaction (PPI) network of FDX1 was constructed based on the GeneMANIA database, immune infiltration analysis was conducted using R language, and transcription factors prediction for FDX1 was performed based on the ENCODE database.

Results

The cuproptosis key gene FDX1 showed significantly higher expression in peripheral blood and neuron models of AD compared to non-AD individuals, with significantly higher expression in APOE ε4/ε4 genotype than other APOE genotype of AD patients. Knockdown of FDX1 expression reduced the lipidation levels of DLAT and DLST in neurons, alleviated ROS accumulation in mitochondria, improved cell viability, and mitigated cuproptosis. Immune infiltration analysis results indicated a high enrichment of peripheral blood γδ-T lymphocytes in AD, and FDX1 was significantly associated with the infiltration of four immune cells and may be regulated by three transcription factors.

Conclusion

The cuproptosis key gene FDX1 is highly expressed in AD and may promote cuproptosis in AD neurons by regulating the lipidation levels of DLAT and DLST, thereby participating in the onset and development of AD. This provides a potential target for the diagnosis and treatment of AD.
Research progress and treatment status of malignant ascites
Authors: He Jing , Zhang Hui-ping
Published: December 2024

Malignant ascites (MA), a common and serious complication of various cancers in the abdominal cavity, originates from the extensive infiltration, metastasis, and growth of cancer cells in or on the abdominal cavity, leading to abnormal accumulation of fluid in the abdominal cavity and the formation of MA. MA seriously reduces the quality of life of cancer patients, shortens their survival period, and generally has a poor prognosis. Modern medicine has developed various strategies for the treatment of MA, including targeted supportive treatment, diuretic treatment, abdominal paracentesis, surgical intervention, and intraperitoneal administration therapy. Among them, chemotherapy, as one of the important treatment methods, includes both systemic chemotherapy and intraperitoneal chemotherapy, especially pressurized intraperitoneal aerosol chemotherapy (PIPAC), hyperthermic intraperitoneal chemotherapy (HIPEC), and foam-based intraperitoneal chemotherapy (FBIC), providing a new choice for the treatment of MA. In addition, innovative treatment methods such as gas-based intra-abdominal hyperthermia (GIH) combined with dehydration therapy have also shown promising application prospects. This article delves into multiple aspects of MA, including its concept, mechanism of occurrence, clinical manifestations, differential diagnostic methods, and current treatment status and research progress. This comprehensive review aims to provide valuable references for effectively controlling MA, improving cancer patients’ quality of life, and prolonging the survival cycle of cancer patients in clinical practice. Malignant ascites (MA) is a common complication of cancer, which originates from the extensive infiltration, metastasis, and growth of cancer cells in the abdominal cavity or peritoneum, leading to abnormal accumulation of peritoneal fluid. It is a common clinical manifestation in the late stage of cancer. Its symptoms are stubborn and recurrent, which can lead to abdominal pain, bloating, poor appetite, fatigue, breathing difficulties, and even multiple organ failure. The median survival time for cancer patients with MA is generally 5 to 6 months. The prognosis is poor, and it is imperative to seek more active and effective treatment plans. This article reviews the research and treatment status of MA, aiming to provide certain value for controlling MA and improving the quality of life of patients.
Unraveling IFI44L’s biofunction in human disease
Authors: Du Juan , Luo Hui , Ye Shuang , Zhang Hui , Zheng Zhen , Liu Kaitai
Published: December 2024

Interferon-induced protein 44-like (IFI44L) is regarded as an immune-related gene and is a member of interferon-stimulated genes (ISGs). They participate in network transduction, and its own epigenetic modifications, apoptosis, cell-matrix formation, and many other pathways in tumors, autoimmune diseases, and viral infections. The current review provides a comprehensive overview of the onset and biological mechanisms of IFI44L and its potential clinical applications in malignant tumors and non-neoplastic diseases.
Early life acute infections and risk for cow's milk protein allergy or atopic dermatitis at 6 months of age in high risk for allergy infants
Authors: Pancheva Rouzha , Illiodromiti Zoi , Moschonis George , Kontopodi Eva , Karapati Eleni , Nicolaou Nicolaos , Karaglani Eva , Sekkidou Mikaela , Popova Simoneta , Usheva Nataliya , Marinova Miglena , Xepapadaki Paraskevi , Sardeli Olympia , Kapetanaki Anastasia , Iacovidou Nicoletta , Boutsikou Theodora , Papathoma Evangelia , Manios Yannis
Published: December 2024

Background

Early life infections (ELIs), encompassing both viral and bacterial types, occur within the first six months of life. Influenced by genetic host factors and environmental conditions, the relationship between ELIs and subsequent allergic manifestations, particularly cow's milk protein allergy (CMPA) and atopic dermatitis (AD), is complex and not fully understood.

Objective

The aim of the current study was to examine the potential interplay between nutrition, infections, and allergic manifestations in the first six months of life in infants with a family history of allergies, who were either exclusively breastfed (EBF) or fed a combination of breast milk and standard (SF) or partially hydrolyzed infant formula (pHF).

Methods

The Allergy Reduction Trial (ART) is a multicenter, randomized controlled trial involving 551 participants. From birth, these participants were divided into three groups: Exclusive Breastfeeding (EBF), Partially Hydrolyzed Formula (pHF), and Standard Formula (SF). ELIs, defined as viral and bacterial infections occurring during the first 6 months, and outcomes (AD, CMPA) were recorded through questionnaires (i.e., SCORAD and CоMiSS) and clinical assessments.

Results

The relative risk (RR) for CMPA in infants with ELIs was 0.20 (95% CI: 0.07–0.58), highlighting a protective effect of ELIs against CMPA development. Notably, the incidence of CMPA was significantly lower in infants who experienced ELIs compared to those without (3% vs. 13.4%, p = 0.001), with no cases of CMPA observed at 6 months in exclusively breastfed (EBF) infants with ELIs. For AD, a trend was observed where the incidence was lower in infants with ELIs who were fed with pHF at 6.5%, compared to those fed with SF at 18.2% (p = 0.092), suggesting a potential protective effect of ELIs in the pHF group against AD development.

Conclusion

The study highlights a potential protective role of ELIs in reducing the risk of CMPA, particularly in EBF infants. Furthermore, it suggests a trend towards lower AD incidence in infants fed with pHF, highlighting the complex interplay between early microbial exposures, feeding practices, and immune development. Further research is warranted to unravel this challenging relationship and appropriately inform early life allergy prevention strategies
Population pharmacokinetic and pharmacodynamic model guided weight-tiered dose of AST-001 in pediatric patients with autism spectrum disorder
Authors: Lee Soyoung , Hwang Su-Kyeong , Cho Jung-Sook , Ryu Hyung Chul , Chung Jae-Yong
Published: December 2024

AST-001, a novel syrup formulation of L-serine, was developed for the treatment of autism spectrum disorders (ASD) in pediatric patients. This study aimed to establish a pharmacokinetic (PK)-pharmacodynamic (PD) model to elucidate the effect of AST-001 on adaptive behavior in children with ASD. Due to the absence of PK samples in pediatric patients, a previously published population PK model was used to link the PD model by applying an allometric scale to body weight. The time courses of Korean-Vineland Adaptive Behavior Scale-II Adaptive Behavior Composite (K-VABS-II-ABC) scores were best described by an effect compartment model with linear drug effects (Deff, 0.0022 L/μg) and linear progression, where an equilibration half-life to the effect compartment was approximately 15 weeks. Our findings indicated a positive correlation between the baseline K-VABS-II-ABC score (E0, 48.51) and the rate of natural progression (Kprog, 0.015 day−1), suggesting enhanced natural behavioral improvements in patients with better baseline adaptive behavior. Moreover, age was identified as a significant covariate for E0 and was incorporated into the model using a power function. Based on our model, the recommended dosing regimens for phase III trials are 2, 4, 6, 10, and 14 g, administered twice daily for weight ranges of 10–13, 14–20, 21–34, 35–49, and >50 kg, respectively. These doses are expected to significantly improve ASD symptoms. This study not only proposes an optimized dosing strategy for AST-001 but also provides valuable insights into the PK-PD relationship in pediatric ASD treatment.
The effects of student bullying on non-suicidal self-injurious behavior in rural adolescents: the chain-mediated effects of alexithymia and ruminate thinking
Authors: Wen Jing , Xu Qinghong , Jiang Yongzhi , Li Min
Published: December 2024

Bullying among students is a significant risk factor for non-suicidal self-injury (NSSI), which can adversely impact the physical and mental health development of individuals. To explore the mechanisms by which student bullying affects adolescent non-suicidal self-injury, 701 adolescents were selected as participants. The assessment tools included the Bullying Questionnaire, Toronto Alexithymia Scale, Ruminative Responses Scale, and Adolescents Non-suicidal Self-injury Assessment Questionnaire, which were used to measure the experiences of bullying, levels of alexithymia, rumination tendencies, and the severity of non-suicidal self-injury, respectively. This study aimed to examine whether there is a chain mediation effect of alexithymia and rumination in the relationship between student bullying and non-suicidal self-injury. The results indicated that: (1) Student bullying has a significant positive impact on adolescent non-suicidal self-injury (63.62%) and indirectly influences it through alexithymia and rumination (12.69%); (2) There are gender differences in the chain mediation effect between student bullying and non-suicidal self-injury, with the chain mediation effect of rumination and alexithymia being significantly greater in females (0.12) compared to males (0.06). This study not only provides a cognitive-emotional perspective and a gender difference perspective on the effects of bullying on adolescent non-suicidal self-injury but also focuses on rural adolescents, who often face more physical and mental health issues. Therefore, the conclusions enrich the understanding of the complex mechanisms between student bullying and non-suicidal self-injury, offering new theoretical guidance for preventing bullying and intervening with victims of bullying.