bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analysis of miR-497/195 cluster identifies new therapeutic targets in cervical cancer
Authors: Karunakara Shreyas Hulusemane , Eswaran Sangavi , Mallya Sandeep , Suresh Padmanaban S. , Chakrabarty Sanjiban , Kabekkodu Shama Prasada 
Published: August 2024

Abstract
Objective
miR-497/195, located at 17p13.1, is a highly conserved miRNA cluster whose abnormal expression is a key regulator of carcinogenesis. We performed a comprehensive analysis of the miR-497/195 cluster to determine its prognostic utility and role in cervical cancer (CC) using publicly available datasets.

Results
In silico analysis and validation revealed that this cluster is downregulated in CC. A total of 60 target genes of miR-497/195 cluster were identified as differentially expressed between normal and CC samples. ShinyGO, STRING, CytoHubba, Timer 2.0, HPA, and HCMBD were used for functional enrichment, PPIN network construction, hub gene identification, immune infiltration correlation, histopathological expression, and determination of the metastatic potential of miR-497/195 cluster and their target genes. PPIN analysis identified CCNE1, CCNE2, ANLN, RACGAP1, KIF23, CHEK1, CDC25A, E2F7, CDK1, and CEP55 as the top 10 hub genes (HGs). Furthermore, the upregulation of RECK, ATD5, and BCL2, downregulation of OSBPL3, RCAN3, and HIST1H3H effected overall survival of CC patients. We identified 6 targets (TFAP2A, CLSPN, RASEF, HIST1H3H, AKT3, and ITPR1) of miR-497/195 cluster to influence metastasis. In addition, 8 druggable genes and 38 potential drugs were also identified. Our study identified miR-497/195 cluster target genes and pathways that could be used for prognostic and therapeutic applications in CC.
A case of an Angelman-syndrome caused by an intragenic duplication of UBE3A uncovered by adaptive nanopore sequencing
Authors: Holthöfer Laura , Diederich Stefan , Haug Verena , Lehmann Lioba , Hewel Charlotte , Paul Norbert W. , Schweiger Susann , Gerber Susanne , Linke Matthias 
Published: August 2024

AbstractAdaptive nanopore sequencing as a diagnostic method for imprinting disorders and episignature analysis revealed an intragenic duplication of Exon 6 and 7 in UBE3A (NM_000462.5) in a patient with relatively mild Angelman-like syndrome. In an all-in-one nanopore sequencing analysis DNA hypomethylation of the SNURF:TSS-DMR, known contributing deletions on the maternal allele and point mutations in UBE3A could be ruled out as disease drivers. In contrast, breakpoints and orientation of the tandem duplication could clearly be defined. Segregation analysis in the family showed that the duplication derived de novo in the maternal grandfather. Our study shows the benefits of an all-in-one nanopore sequencing approach for the diagnostics of Angelman syndrome and other imprinting disorders.
METTL3 restricts RIPK1-dependent cell death via the ATF3-cFLIP axis in the intestinal epithelium
Authors: Huang Meimei , Wang Xiaodan , Zhang Mengxian , Liu Yuan , Chen Ye-Guang 
Published: August 2024

AbstractIntestinal epithelial cells (IECs) are pivotal for maintaining intestinal homeostasis through self-renewal, proliferation, differentiation, and regulated cell death. While apoptosis and necroptosis are recognized as distinct pathways, their intricate interplay remains elusive. In this study, we report that Mettl3-mediated m6A modification maintains intestinal homeostasis by impeding epithelial cell death. Mettl3 knockout induces both apoptosis and necroptosis in IECs. Targeting different modes of cell death with specific inhibitors unveils that RIPK1 kinase activity is critical for the cell death triggered by Mettl3 knockout. Mechanistically, this occurs via the m6A-mediated transcriptional regulation of Atf3, a transcription factor that directly binds to Cflar, the gene encoding the anti-cell death protein cFLIP. cFLIP inhibits RIPK1 activity, thereby suppressing downstream apoptotic and necroptotic signaling. Together, these findings delineate the essential role of the METTL3-ATF3-cFLIP axis in homeostatic regulation of the intestinal epithelium by blocking RIPK1 activity.
Monocyte-macrophages modulate intestinal homeostasis in inflammatory bowel disease
Authors: Lu Huiying , Suo Zhimin , Lin Jian , Cong Yingzi , Liu Zhanju 
Published: August 2024

Abstract
Background
Monocytes and macrophages play an indispensable role in maintaining intestinal homeostasis and modulating mucosal immune responses in inflammatory bowel disease (IBD). Although numerous studies have described macrophage properties in IBD, the underlying mechanisms whereby the monocyte-macrophage lineage modulates intestinal homeostasis during gut inflammation remain elusive.

Main body
In this review, we decipher the cellular and molecular mechanisms governing the generation of intestinal mucosal macrophages and fill the knowledge gap in understanding the origin, maturation, classification, and functions of mucosal macrophages in intestinal niches, particularly the phagocytosis and bactericidal effects involved in the elimination of cell debris and pathogens. We delineate macrophage-mediated immunoregulation in the context of producing pro-inflammatory and anti-inflammatory cytokines, chemokines, toxic mediators, and macrophage extracellular traps (METs), and participating in the modulation of epithelial cell proliferation, angiogenesis, and fibrosis in the intestine and its accessory tissues. Moreover, we emphasize that the maturation of intestinal macrophages is arrested at immature stage during IBD, and the deficiency of MCPIP1 involves in the process via ATF3-AP1S2 signature. In addition, we confirmed the origin potential of IL-1B+ macrophages and defined C1QB+ macrophages as mature macrophages. The interaction crosstalk between the intestine and the mesentery has been described in this review, and the expression of mesentery-derived SAA2 is upregulated during IBD, which contributes to immunoregulation of macrophage. Moreover, we also highlight IBD-related susceptibility genes (e.g., RUNX3, IL21R, GTF2I, and LILRB3) associated with the maturation and functions of macrophage, which provide promising therapeutic opportunities for treating human IBD.

Conclusion
In summary, this review provides a comprehensive, comprehensive, in-depth and novel description of the characteristics and functions of macrophages in IBD, and highlights the important role of macrophages in the molecular and cellular process during IBD.
Adoption of smart watches as wearable technology in TESOL education among university students
Authors: Wardat Saja , Akour Mohammed 
Published: August 2024

AbstractThis research explores the key motivating factors that influence student engagement with wearable technology (WT) in teaching English to speakers of other languages (TESOL) education. The study employs a novel, integrated framework that merges elements from the established technology acceptance model (TAM), Flow Theory, and additional factors pivotal to WT's efficacy, namely content richness and personal innovativeness. TAM and Flow Theory are utilized to identify the variables that drive WT adoption. Data for the research was gathered through an online survey comprising 23 questions, distributed among students in the KSA, with a total of 468 participants. Analysis of the data was conducted using Smart PLS Software to evaluate the research model, constructs, and hypotheses. The findings reveal varying contributions of the model's main constructs to WT acceptance. Specifically, content richness and innovativeness significantly enhance the perceived usefulness of WT. Additionally, perceived ease of use is a strong predictor of perceived usefulness and behavioral intention. The results underscore a growing demand for WT in TESOL Education, highlighting its role in streamlining information exchange among students. The study underscores the significance of certain external factors in technology acceptance, offering a fresh perspective by incorporating a framework that links TAM's perceived usefulness and ease of use with user satisfaction, content richness, and innovativeness. Moreover, the inclusion of Flow Theory adds a unique dimension by assessing engagement and control over WT. The research contributes to understanding the underlying motivations for employing WT in TESOL Education, primarily aimed at enhancing the effectiveness of both instructors and students. A limitation of this study is its focused application of TAM and Flow Theory within a specific educational context, which may not fully capture the complex societal, psychological, and gender-specific factors influencing WT adoption across diverse settings.
Unpacking the role of AI ethics online education for science and engineering students
Authors: Usher Maya , Barak Miri 
Published: August 2024

Abstract
Background
As artificial intelligence (AI) technology rapidly advances, it becomes imperative to equip students with tools to navigate through the many intricate ethical considerations surrounding its development and use. Despite growing recognition of this necessity, the integration of AI ethics into higher education curricula remains limited. This paucity highlights an urgent need for comprehensive ethics education initiatives in AI, particularly for science and engineering students who are at the forefront of these innovations. Hence, this research investigates the role of an online explicit-reflective learning module in fostering science and engineering graduate students' ethical knowledge, awareness, and problem-solving skills. The study’s participants included 90 graduate students specializing in diverse science and engineering research tracks. Employing the embedded mixed-methods approach, data were collected from pre- and post-intervention questionnaires with closed-ended and open-ended questions.

Results
The study's results indicate that the online explicit-reflective learning module significantly enhanced students' knowledge of AI ethics. Initially, students exhibited a medium–high level of perceived ethical awareness, which saw a modest but statistically significant enhancement following the participation. Notably, a more distinct increase was observed in students' actual awareness of ethical issues in AI, before and after the intervention. Content analysis of students’ responses to the open-ended questions revealed an increase in their ability to identify and articulate concerns relating to privacy breaches, the utilization of flawed datasets, and issues of biased social representation. Moreover, while students initially displayed limited problem-solving abilities in AI ethics, a considerable enhancement in these competencies was evident post-intervention.

Conclusions
The study results highlight the important role of explicit-reflective learning in preparing future professionals in science and engineering with the skills necessary for ethical decision-making. The study highlights the need for placing more emphasis not only on students’ ability to identify AI-related ethical issues but also on their capacity to resolve and perhaps mitigate the impact of such ethical dilemmas.
A retrospective study examining the association between polypharmacy and complications after laparoscopic surgery for colorectal cancer
Authors: Watanabe Takashi , Kashiwagura Shota , Ouchi Ryusuke , Usui Kensuke , Shibata Chikashi , Okada Kouji 
Published: August 2024

Abstract
Background
Polypharmacy is an escalating public health concern across various healthcare settings worldwide. We aimed to comprehensively investigate postoperative complications after laparoscopic surgery for colorectal cancer and explore their association with polypharmacy. As laparoscopic surgery is widespread, clarifying the association between polypharmacy and postoperative complications is clinically important.

Methods
We retrospectively surveyed the medical charts of adult inpatients who underwent laparoscopic surgery for colorectal cancer at Tohoku Medical and Pharmaceutical University Hospital between April 2019 and March 2023. Postoperative complications were determined using the Clavien–Dindo classification. We explored the factors related to postoperative complications and calculated the cut-off values for the number of medication ingredients.

Results
Among the 236 patients, 32 (13.6%) developed postoperative complications. On multivariable logistic regression analysis, the number of regularly used medication ingredients (odds ratio = 1.160, 95% confidence interval 1.050–1.270, p = 0.002) was identified as a factor related to postoperative complications. The identified cut-off value for complications was 10 ingredients. Patients using 10 or more ingredients had approximately 3.5 times higher occurrence of postoperative complications than those using fewer than 10 ingredients (33.3% vs. 9.3%, p < 0.001, Fisher’s exact test).

Conclusions
Our study comprehensively investigated postoperative complications and examined their association with polypharmacy. We found that the number of regularly used medication ingredients may be linked to complications following laparoscopic surgery for colorectal cancer. These findings have important implications for perioperative management and patient care, providing valuable insights that may influence clinical practices and enhance patient outcomes.
A novel robust method for estimating the covariance matrix of financial returns with applications to risk management
Authors: Leccadito Arturo , Staino Alessandro , Toscano Pietro 
Published: August 2024

AbstractThis study introduces the dynamic Gerber model (DGC) and evaluates its performance in the prediction of Value at Risk (VaR) and Expected Shortfall (ES) compared to alternative parametric, non-parametric and semi-parametric methods for estimating the covariance matrix of returns. Based on ES backtests, the DGC method produces, overall, accurate ES forecasts. Furthermore, we use the Model Confidence Set procedure to identify the superior set of models (SSM). For all the portfolios and VaR/ES confidence levels we consider, the DGC is found to belong to the SSM.
Cyclotron production of manganese-52: a promising avenue for multimodal PET/MRI imaging
Authors: Porto Francesca , Cisternino Sara , Cazzola Emiliano , Speltri Giorgia , Mou Liliana , Boschi Alessandra , Marvelli Lorenza , Di Domenico Giovanni , Pagnoni Antonella , De Dominicis Lucia , Calliari Irene , Gennari Claudio , Uccelli Licia , Pupillo Gaia , Gorgoni Giancarlo , Esposito Juan , Martini Petra 
Published: August 2024

Abstract
Background
The integration of positron emission tomography (PET) and magnetic resonance imaging (MRI) holds promise for advancing diagnostic imaging capabilities. The METRICS project aims to develop cyclotron-driven production of 52Mn for PET/MRI imaging.

Results
Using the 52Cr(p,n)52Mn reaction, we designed chromium metal targets via Spark Plasma Sintering and developed a separation procedure for isolating 52Mn. Labeling tests were conducted with traditional chelators (i.e. S-2-(4-Isothiocyanatobenzyl)-1,4,7,10-tetraazacyclododecane tetraacetic acid) and the 1.4-dioxa-8-azaspiro[4.5]decane-8- carbodithioate ligand to produce radioactive complexes suitable for PET/MRI applications. Our methodology yielded high-quality 52Mn suitable for PET radiopharmaceuticals and PET/MRI imaging. Preliminary studies on phantom imaging using microPET and clinical MRI demonstrated the efficacy of our approach.

Conclusions
The developed technology offers a promising avenue for producing 52Mn and enhancing PET/MRI imaging capabilities. Further in vivo investigations are warranted to evaluate the potential advantages of this hybrid imaging technique.
Grewia flava twig extracts: phytochemical, antioxidant, and antimicrobial evaluations
Authors: Coin Gofaone , Lekutlane Disang , Masisi Kabo , Muzila Mbaki , Mazimba Ofentse 
Published: August 2024

Abstract
Background
Grewia flava infusions are consumed to assist with kidney problems and stomach ailments. However, there are no scientific data on the phytochemical profile or biological properties to validate its folklore use. Thus, the study aimed to assess the phytochemical profile, antioxidant, and antimicrobial activities of Grewia flava twig extracts.

Methodology
The antioxidant activities of the extracts were assayed using 1,1-diphenyl-2-picrylhydrazyl radical scavenging, reducing power, metal chelation, and total phenolic and flavonoid content assays. The agar well diffusion and microdilution methods were used for crude extracts and fractions (from 80% methanol extract) for antimicrobial screening against P. aeruginosa, S. aureus, E. coli, B. subtilis, A. niger, and R. oryzae.

Results
The 80% methanol twig extract (250.00 ± 2 GAE/g) exhibited a high concentration of phenolic content, followed by the distilled water extract (192.00 ± 2 mg GAE/g) and the hexane extract (43.10 ± 0.2 mg GAE/g). Fraction 14 of the methanol twig extract exhibited MIC values of 0.21–0.31 mg/mL against all test microorganisms. The root and twig extracts exhibited significant antioxidant and antimicrobial activities, which were attributed to the extracts of bioactive phytochemical compounds such as alkaloids, flavonoids, saponins, steroids, glycosides, anthraquinones, and tannins that were detected in the extracts. Also, the root and twig non-polar extracts were subjected to gas chromatography–mass spectrometry analysis, which identified several bioactive compounds like betulin, β-amyrin, palmitic acid, lupenone, and phytol, highlighting the potential of the plant species as a botanical drug.

Conclusions
The study supports the traditional use of plant roots and twigs for treating various ailments, indicating their medicinal value. The twigs can be used in place of the roots to guarantee Grewia flava harvesting that is sustainable. However, a comparison of the quantities of the active compound in the twigs and roots using LC–MS is crucial.
Classification of DDoS attack traffic on SDN network environment using deep learning
Authors: Clinton Urikhimbam Boby , Hoque Nazrul , Robindro Singh Khumukcham 
Published: August 2024

AbstractDistributed Denial of Service (DDoS) attack is a major threat to the Internet of Things (IoT), Software Defined Networks (SDN), and Cloud Computing Networks. Due to the tremendous applications of IoT networks, the number of DDoS attacks is increasing significantly, and most sophisticated DDoS attacks are generated through IoT botnets. An IoT botnet-based DDoS attack can disrupt the network quickly with a surge of malicious traffic. Especially in an SDN network, it is important to detect the DDoS attack before it occurs to the SDN controller. DDoS attacks on the centralized controller of the SDN can disrupt the whole network. So, identifying DDoS attacks at the earliest is a critical security measure for network experts and practitioners. In this paper, we analyze the DDoS attack on an SDN environment and develop a method to identify the DDoS attack using Deep Learning (DL). The proposed method converts the captured raw network traffic to image data and classifies the malicious data from normal data. The method is evaluated on our test-bed simulated dataset and two other benchmark datasets. The experimental comparison shows that the proposed method performs better on all three datasets, giving more than 99% classification accuracy.
Patterns in the spatial configuration of Sultani Mosques in the Qajar period: a comparative study using space syntax and layout-based analysis
Authors: Fadakari Mohammad Moein , Andaroodi Elham 
Published: August 2024

AbstractThe pattern of built heritage provides insights into spatial organisation principles, revealing recurring traits among buildings of a similar type. Such constructions illuminate how building components are aligned and interconnected to embody a unified design ethos. However, well-preserved instances of a sequential series of similar buildings that were built in the same period based on historical evidence are rarely located. Thus, the Sultani Mosques, a prominent collection of mosques built in Iran between 1806 and 1840 under King Fath-Ali Shah of the Qajar dynasty's auspices, are particularly noteworthy, attracting scholarly attention from figures such as Ritter, Hillenbrand, and Scarce for their distinctive spatial organisation of architectural elements such as iwans, domes, naves, and courtyards. To comprehensively study the shared spatial organisation concept within these mosques through a comparative study, this research aimed to verify the spatial layout using analytical techniques such as space syntax and layout-based justified graphs. By juxtaposing these graphs and depth values, this research elucidated the spatial integration and privacy delineation within these religious structures. Moreover, an examination of layout-based graphs and immersive three-dimensional assessments reinforced and confirmed the prevailing layout configuration. The research findings reveal a cohesive architectural concept in Sultani mosques, as multifaceted accessibility was emphasised, and spatial layouts were structured to facilitate movement and interactions. Qajar architects likely established a consistent design approach across these mosques, integrating essential elements while accommodating educational spaces. When schools were included, courtyard dynamics were reshaped, which impacted spatial connections and access routes. Variations in building division configurations, vault spans, and spatial relations tailored to local contexts highlight the unique design and spatial value of each mosque. Preserving these spatial relationships in restoration efforts is crucial for maintaining the intrinsic spatial language and historical design significance of these mosques.
11β-Hydroxysteroid dehydrogenase type 2 may mediate the stress-specific effects of cortisol on brain cell proliferation in adult zebrafish (Danio rerio)
Authors: Flatt E. Emma , Alderman Sarah L. 
Published: August 2024

ABSTRACT
Stress-induced increases in cortisol can stimulate or inhibit brain cell proliferation, but the mechanisms behind these opposing effects are unknown. We tested the hypothesis that 11β-hydroxysteroid dehydrogenase type 2 (Hsd11b2), a glucocorticoid-inactivating enzyme expressed in neurogenic regions of the adult zebrafish brain, mitigates cortisol-induced changes to brain cell proliferation, using one of three stress regimes: a single 1 min air exposure (acute stress), two air exposures spaced 24 h apart (repeat acute stress) or social subordination (chronic stress). Plasma cortisol was significantly elevated 15 min after air exposure and recovered within 24 h after acute and repeat acute stress, whereas subordinate fish exhibited significant and sustained elevations relative to dominant fish for 24 h. Following acute stress, brain hsd11b2 transcript abundance was elevated up to 6 h after a single air exposure but was unchanged by repeat acute stress or social subordination. A sustained increase in brain Hsd11b2 protein levels occurred after acute stress, but not after repeat or chronic stress. Following acute and repeat acute stress, brain pcna transcript abundance (a marker of cell proliferation) exhibited a prolonged elevation, but was unaffected by social subordination. Interestingly, the number of telencephalic BrdU+ cells increased in fish after a single air exposure but was unchanged by repeat acute stress. Following acute and repeat acute stress, fish expressed lower brain glucocorticoid and mineralocorticoid receptor (gr and mr) transcript abundance while subordinate fish exhibited no changes. Taken together, these results demonstrate stressor-specific regulation of Hsd11b2 in the zebrafish brain that could modulate rates of cortisol catabolism contributing to observed differences in brain cell proliferation.