bluuebunny/crossref_metadata_2025 huggingface dataset:
Sitagliptin eye drops prevent the impairment of retinal neurovascular unit in the new Trpv2+/− rat model
Authors: Ramos Hugo , Augustine Josy , Karan Burak M. , Hernández Cristina , Stitt Alan W. , Curtis Tim M. , Simó Rafael
Published: November 2024

Impaired function of the retinal neurovascular unit (NVU) is an early event in diabetic retinopathy (DR). It has been previously shown that topical delivery of the dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin can protect against diabetes-mediated dysfunction of the retinal NVU in the db/db mouse. The aim of the present study was to examine whether sitagliptin could prevent the DR-like lesions within the NVU of the new non-diabetic model of DR, the Trpv2 knockout rat (Trpv2+/−). For that purpose, at 3 months of age, Trpv2+/− rats were topically treated twice daily for two weeks with sitagliptin or PBS-vehicle eyedrops. Trpv2+/+ rats treated with vehicle served as the control group. Body weight and glycemia were monitored. Optical coherence tomography recordings, fundus images and retinal samples were obtained to evaluate sitagliptin effects. The results revealed that sitagliptin eye drops had no effect on body weight or glycemia. Vehicle-treated Trpv2+/− rats exhibited retinal thinning and larger diameters of major retinal blood vessels, upregulation of inflammatory factors and oxidative markers, glial activation and formation of acellular capillaries. However, topical administration of sitagliptin significantly prevented all these abnormalities. In conclusion, sitagliptin eye drops exert a protective effect against DR-like lesions in Trpv2+/− rats. Our results suggest that sitagliptin eye drops carry significant potential to treat not only early-stages of DR but also other diseases with impairment of the NVU unrelated to diabetes.
The role of autoantibodies in bridging obesity, aging, and immunosenescence
Authors: Valentino Taylor R. , Chen Nan , Makhijani Priya , Khan Saad , Winer Shawn , Revelo Xavier S. , Winer Daniel A.
Published: November 2024

Antibodies are essential to immune homeostasis due to their roles in neutralizing pathogenic agents. However, failures in central and peripheral checkpoints that eliminate autoreactive B cells can undermine self-tolerance and generate autoantibodies that mistakenly target self-antigens, leading to inflammation and autoimmune diseases. While autoantibodies are well-studied in autoimmune and in some communicable diseases, their roles in chronic conditions, such as obesity and aging, are less understood. Obesity and aging share similar aspects of immune dysfunction, such as diminished humoral responses and heightened chronic inflammation, which can disrupt immune tolerance and foster autoantigen production, thus giving rise to autoreactive B cells and autoantibodies. In return, these events may also contribute to the pathophysiology of obesity and aging, to the associated autoimmune disorders linked to these conditions, and to the development of immunosenescence, an age-related decline in immune function that heightens vulnerability to infections, chronic diseases, and loss of self-tolerance. Furthermore, the cumulative exposure to antigens and cellular debris during obesity and aging perpetuates pro-inflammatory pathways, linking immunosenescence with other aging hallmarks, such as proteostasis loss and mitochondrial dysfunction. This review examines the mechanisms driving autoantibody generation during obesity and aging and discusses key putative antigenic targets across these conditions. We also explore the therapeutic potential of emerging approaches, such as CAR-T/CAAR-T therapies, vaccines, and BiTEs, to tackle autoimmune-related conditions in aging and obesity.
Molecular characterization of circulating infectious bursal disease viruses in chickens from different Egyptian governorates during 2023
Authors: Abd El-Fatah Amr H. , Ayman Dalia , Samir Mahmoud , Eid Soad , Elgamal Mahmoud , El-sanousi A. A. , Ibrahim Mahmoud , AlKhazindar M. , Ali M. M. , Afify Amira
Published: November 2024

Infectious bursal disease virus (IBDV) induces severe immunosuppression in chickens, leading to significant economic losses in the global poultry industry. This study investigated 52 chicken flocks, including commercial broilers, layers, and baladi, from various Egyptian governorates in 2023. These flocks exhibited symptoms of depression, along with kidney and bursa lesions, indicative of IBDV infection. Pooled Bursal homogenates were tested using RT-PCR with VP2-specific primers, revealing that 20 flocks tested positive for IBDV. Six representative samples were selected from 20 positive flocks for isolation in embryonated chicken eggs. The embryonic lesions observed included haemorrhage, skull swelling, and liver necrosis with a pale-yellow appearance, in addition to congestion and thickening in the chorioallantoic membrane (CAM). Partial amplification of the VP2 gene from the harvested embryo suspensions of the six IBDV isolates was performed for sequencing. Phylogenetic analysis of the sequences revealed that five IBDV isolates (VV4, VV5, VV6, VV10, and VV16) belonged to the very virulent strain group A3 cluster, whereas one isolate (VV2) clustered with Chinese Variant strains in the A2d group. Sequence analysis of the hypervariable region (HVR) of VP2 compared to that of Egypt-USC-IBD-1-2019 and vvIBDV/Beh21/Egypt/18 highly virulent IBDV strains revealed several amino acid mutations. The VP2 HVR of all isolates maintained the serine-rich heptapeptide sequence SWSASGS, which is adjacent to the major hydrophilic peak B and serves as a virulence marker. Histopathological examination revealed that bursae from chickens infected with vvIBDV exhibited marked interlobular oedema and lymphoid depletion. In contrast, bursae from chickens infected with Variant IBDV showed massive lymphoid depletion, with hyperplasia of the bursal capsule. These findings highlight the circulation of both virulent and Variant IBDV strains in Egyptian chicken flocks, complicating disease control. Consequently, there is a need to update vaccination programs and vaccine strains for IBDV in Egypt.
Ferroptosis and the tumor microenvironment
Authors: Cui Kaisa , Wang Kang , Huang Zhaohui
Published: November 2024

Ferroptosis is a type of regulated cell death characterized by its non-apoptotic, iron-dependent and oxidative nature. Since its discovery in 2012, extensive research has demonstrated its pivotal roles in tumorigenesis, metastasis and cancer therapy. The tumor microenvironment (TME) is a complex ecosystem comprising cancer cells, non-cancer cells, extracellular matrix, metabolites and cytokines. Recent studies have underscored a new paradigm in which non-cancer cells in the TME, such as immune and stromal cells, also play significant roles in regulating tumor progression and therapeutic resistance typically through complicated crosstalk with cancer cells. Notably, this crosstalk in the TME were partially mediated through ferrotopsis-related mechanisms. This review provides a comprehensive and systematic summary of the current findings concerning the roles of ferroptosis in the TME and how ferroptosis-mediated TME reprogramming impacts cancer therapeutic resistance and progression. Additionally, this review outlines various ferroptosis-related therapeutic strategies aimed at targeting the TME.
Targeting PRMT5 through PROTAC for the treatment of triple-negative breast cancer
Authors: Guo Yaxun , Li Yuzhan , Zhou Zhongmei , Hou Lei , Liu Wenjing , Ren Wenlong , Mi Dazhao , Sun Jian , Dai Xueqin , Wu Yingying , Cheng Zhuo , Wu Tingyue , Luo Qianmei , Tian Cong , Li Fubing , Yu Zhigang , Chen Yihua , Chen Ceshi
Published: November 2024

Background

Triple-negative breast cancer (TNBC) is currently the most aggressive subtype of breast cancer, characterized by high heterogeneity and strong invasiveness, and currently lacks effective therapies. PRMT5, a type II protein arginine methyltransferase, is upregulated in numerous cancers, including TNBC, and plays a critical role, marked it as an attractive therapeutic target. PROTAC (Proteolysis Targeting Chimeras) is an innovative drug development technology that utilizes the ubiquitin-proteasome system (UPS) to degrade target proteins, which is characterized by higher activity, enhanced safety, lower resistance, and reduced toxicity, offering significant value for clinical translation.

Methods

This study utilizes the PROTAC technology to develop potential degraders targeting PRMT5 in vitro and in vivo.

Results

Through the design, synthesis and screening of a series of targeted compounds, we identified YZ-836P as an effective compound that exerted cytotoxic effects and reduced the protein levels of PRMT5 and its key downstream target protein KLF5 in TNBC after 48 h. Its efficacy was significantly superior to the PRMT5 PROTAC degraders that had been reported. YZ-836P induced G1 phase cell cycle arrest and significantly induced apoptosis in TNBC cells. Additionally, we demonstrated that YZ-836P promoted the ubiquitination and degradation of PRMT5 in a cereblon (CRBN)-dependent manner. Notably, YZ-836P exhibited pronounced efficacy in inhibiting the growth of TNBC patient-derived organoids and xenografts in nude mice.

Conclusions

These findings position YZ-836P as a promising candidate for advancing treatment modalities for TNBC.

Trial registration

Ethics Committee of Yunnan Cancer Hospital, KYCS2023-078. Registered 7 June 2023.
Advances in non-small cell lung cancer mechanomedicine: deciphering the signaling networks that govern tumor-TME interactions
Authors: Gargalionis Antonios N. , Papavassiliou Kostas A. , Basdra Efthimia K. , Papavassiliou Athanasios G.
Published: November 2024

Cells from the tumor microenvironment (TME) interact with tumor cells in non-small cell lung cancer (NSCLC) to form a reciprocal crosstalk which influences tumor growth, proliferation, metastasis and multidrug response. This crosstalk is modulated by TME mechanical inputs, which elicit the processes of mechanosensing and mechanotransduction. Recent advances in unveiling these signaling networks establish the interdisciplinary field of mechanomedicine to exploit emerging diagnostic, predictive and therapeutic tools for more effective NSCLC treatments.
Valorization of milling byproducts and ergot-sclerotia-contaminated rye via clostridial ABE fermentation
Authors: Edelmann Holger , Thieme Nils , Ehrenreich Armin , Zverlov Vladimir , Liebl Wolfgang
Published: November 2024

Background

Acetone–butanol–ethanol (ABE) fermentation by solventogenic clostridia can be harnessed to produce CO2 emission neutral bio-based 1-butanol, a valuable compound with a broad range of applications, e.g., in industrial production, as a solvent and as a fuel additive or replacement. However, the relatively low butanol titers and high feedstock costs prevent bio-butanol production on an industrial scale. Agricultural side-stream materials, like milling byproducts, are starch-rich, low-cost and produced all year round. They could be suitable substrates for bio-butanol production by ABE fermentation.

Results

The milling byproducts wheat red dog (WRD), rye second flour (RSF), wheat bran (WB), rye bran (RB) and ergot sclerotia-containing rye waste stream (ER) were found to contain between ~ 30 and ~ 85% glucan, most of which was starch based. WRD, RSF and ER had the highest glucan content, while the brans contained significant xylan concentrations. Four strains selected from the collection of solventogenic clostridia available in our group produced > 6 g/L butanol on the majority of these substrates, with Clostridium beijerinckii NCIMB 8052 showing the best ABE production performance when regarding all tested substrates. Toxic ergot sclerotia-containing waste material was found to be a suited substrate for ABE fermentation. Strain NCIMB 8052 exhibited butanol titers of up to 9 g/L on substrate mixtures of WRD plus ER and the highest butanol yield per used sugars. Finally, a semi-continuous ABE fermentation of C. beijerinckii NCIMB 8052 on WRD plus ER could be maintained for 96 h. The volumetric ABE productivity during the continuous phase of fermentation was ~ 0.41 g L−1 h−1 and a total of 37.7 g ABE was produced out of 168.2 g substrate.

Conclusions

Based on their carbohydrate composition, WRD, RSF and ER were the milling byproducts best suited as substrates for bio-butanol production by clostridial ABE fermentation. Importantly, also ergot sclerotia-containing waste materials can be used as substrates, which can help to reduce process costs. The semi-continuous fermentation showed that clostridial ABE fermentation on milling byproducts may represent a suitable avenue for commercial butanol production after further process and/or strain optimization.
Genus Bithynia: morphological classification to molecular identification
Authors: Huang Guoyang , Peng Xiaohong
Published: November 2024

Snails of the genus Bithynia, whose primary habitat is slow-flowing ponds and ditches, serve as the first intermediate hosts of liver fluke. Currently, approximately 200 million individuals worldwide are at risk of liver fluke infection, yet questions still persist regarding the taxonomic identification of Bithynia genus, a crucial player in the transmission of this disease. Accurate taxonomic classification of the Bithynia genus could significantly enhance current understanding of the disease’s transmission mechanisms. In this article we comprehensively review the extensive research conducted on Bithynia genus, spanning past inquiries up to the latest findings. The primary emphasis is placed on exploring the taxonomic identification of this genus within various technological settings. We then present a consolidated analysis of the morphological taxonomic identification methods, highlighting their strengths and limitations. We also introduce a novel perspective on the future direction of identification and classification efforts for the members of this genus, emphasizing the crucial role Bithynia plays in the epidemiological cycle of liver fluke transmission. We conclude by urging researchers to prioritize the significance of the members of this genus in the epidemiological cycle of liver fluke transmission and in control measures for disease dissemination, within the context of the vector organisms.

Graphical Abstract
Alzheimer’s disease-specific transcriptomic and epigenomic changes in the tryptophan catabolic pathway
Authors: Choe Kyonghwan , Ali Muhammad , Lardenoije Roy , Riemens Renzo J.M. , Pishva Ehsan , Bickel Horst , Weyerer Siegfried , Hoffmann Per , Pentzek Michael , Riedel-Heller Steffi , Wiese Birgitt , Scherer Martin , Wagner Michael , Mastroeni Diego , Coleman Paul D. , Ramirez Alfredo , Ramakers Inez H.G.B. , Verhey Frans R.J. , Rutten Bart P.F. , Kenis Gunter , van den Hove Daniel L.A.
Published: November 2024

Background

Neurodegenerative disorders, including Alzheimer’s disease (AD), have been linked to alterations in tryptophan (TRP) metabolism. However, no studies to date have systematically explored changes in the TRP pathway at both transcriptional and epigenetic levels. This study aimed to investigate transcriptomic, DNA methylomic (5mC) and hydroxymethylomic (5hmC) changes within genes involved in the TRP and nicotinamide adenine dinucleotide (NAD) pathways in AD, using three independent cohorts.

Methods

DNA derived from post-mortem middle temporal gyrus (MTG) tissue from AD patients (n = 45) and age-matched controls (n = 35) was analyzed, along with DNA derived from blood samples from two independent cohorts: the German Study on Ageing, Cognition, and Dementia in Primary Care Patients (AgeCoDe) cohort (n = 96) and the Dutch BioBank Alzheimer Center Limburg (BBACL) cohort (n = 262). Molecular profiling, including assessing mRNA expression and DNA (hydroxy)methylation levels, was conducted using HumanHT-12 v4 Expression BeadChip and HM 450 K BeadChip arrays, respectively. Functional interactions between genes and identification of common phenotype-specific positive and negative elementary circuits were conducted using computational modeling, i.e. gene regulatory network (GRN) and network perturbational analysis. DNA methylation of IDO2 (cg11251498) was analyzed using pyrosequencing.

Results

Twelve TRP- and twenty NAD-associated genes were found to be differentially expressed in the MTG of AD patients. Gene sets associated in the kynurenine pathway, the most common TRP pathway, and NAD pathway, showed enrichment at the mRNA expression level. Downstream analyses integrating data on gene expression, DNA (hydroxy)methylation, and AD pathology, as well as GRN and network perturbation analyses, identified IDO2, an immune regulatory gene, as a key candidate in AD. Notably, one CpG site in IDO2 (cg11251498) exhibited significant methylation differences between AD converters and non-converters in the AgeCoDe cohort.

Conclusion

These findings reveal substantial transcriptional and epigenetic alterations in TRP- and NAD-pathway-associated genes in AD, highlighting IDO2 as a key candidate gene for further investigation. These genes and their encoded proteins hold potential as novel biomarkers and therapeutic targets for AD.
Spectroelectrochemical insights into the intrinsic nature of lead halide perovskites
Authors: Min Seonhong , Jeon Minwook , Cho Junsang , Bang Jin Ho , Kamat Prashant V.
Published: November 2024

Lead halide perovskites have emerged as a new class of semiconductor materials with exceptional optoelectronic properties, sparking significant research interest in photovoltaics and light-emitting diodes. However, achieving long-term operational stability remains a critical hurdle. The soft, ionic nature of the halide perovskite lattice renders them vulnerable to various instabilities. These instabilities can be triggered by factors such as photoexcitation, electrical bias, and the surrounding electrolyte/solvent or atmosphere under operating conditions. Spectroelectrochemistry offers a powerful approach to bridge the gap between electrochemistry and photochemistry (or spectroscopy), by providing a comprehensive understanding of the band structure and excited-state dynamics of halide perovskites. This review summarizes recent advances that highlight the fundamental principles, the electronic band structure of halide perovskite materials, and the photoelectrochemical phenomena observed upon photo- and electro-chemical charge injections. Further, we discuss halide instability, encompassing halide oxidation, vacancy formation, ion migration, degradation, and sequential expulsion under electrical bias. Spectroelectrochemical studies that provide a deeper understanding of interfacial processes and halide mobility can pave the way for the design of more robust perovskites, accelerating future research and development efforts.

Graphical Abstract
Significance of climate change in the emergence of human fascioliasis in Upper Egypt
Authors: Zanaty Naglaa , Ibrahim Nagat , Ramadan Haidi Karam-Allah , Ahmad Alzahraa Abdelraouf , Saad-Hussein Amal
Published: November 2024

Background

Climate change in the upcoming years will raise the health burden of zoonotic parasites. As a liver fluke, Fasciola depends on certain climate conditions to complete its life cycle and is significantly influenced by climate changes. We aimed to investigate the relationship between the increasing prevalence of human fascioliasis and climate changes in Upper Egypt.

Methods

Records of Fasciola cases in Assiut Governorate in Upper Egypt were evaluated between September 2018 and March 2023. The annual and monthly climate parameters of the region’s temperature and humidity acquired from ERA5 and FLDAS were investigated between 2000 and 2023.

Results

A total of 303 patients were included. The mean age was 33.9 ± 17.4 years; 57.1% were females, and the majority were rural residents. Positive correlations were found between temperature and the recorded cases in 2018, 2020, 2021, and 2022 (r = 0.92, 0.41, 0.61, and 0.60, respectively). In 2018 and 2022, humidity and Fasciola frequency had a significant positive correlation (r = 0.97 and 0.49, respectively). An outbreak of fascioliasis was recorded in September 2018, coinciding with the peak temperature and high humidity levels, exceeding the average climatology range from 2000 to 2017. The recorded cases exhibited a seasonal pattern, with peaks in hot, humid summer and autumn.

Conclusion

The rise of human fascioliasis in Upper Egypt is influenced by local climate characteristics. A climate-based map of Fasciola distribution using forecast risk models is needed to predict future outbreaks and for better control.
A call for a coherent One Health strategy for the surveillance of climate-sensitive infectious diseases in the Canadian Arctic and subarctic regions
Authors: Daigle Laurence , Nury Charlotte , Delesalle Léa , Villeneuve Carol-Anne , Colinas Juliette , Leighton Patrick A. , Carabin Hélène , Zinszer Kate , Hillier Sean , Jenkins Emily , Aenishaenslin Cécile
Published: November 2024

Introduction

The increased burden of climate-sensitive infectious diseases (CSIDs) within the circumpolar region, one of the many impacts of climate change, is impacting human, animal and ecosystem health. An integrated One Health approach to surveillance of CSIDs has been promoted by the scientific community as a prerequisite to enhance preparedness and response. Up to now, little is known about how the One Health approach has been implemented in surveillance systems for CSIDs in the Arctic and surrounding regions.

Objectives

The objectives of this study were to map surveillance activities currently implemented in the Canadian Arctic and subarctic for the 16 CSID identified by the Arctic Council, to describe how One Health has been operationalized in these activities, and to explore the integration and leadership of Indigenous partners in current surveillance systems.

Method

We performed the mapping in three steps: a rapid review of the scientific literature, a review of the grey literature and an online questionnaire sent to key stakeholders involved in CSID surveillance in the Canadian Arctic and subarctic regions.

Results and conclusions

We identified 37 scientific peer-reviewed and 58 grey literature records. We mapped (1) surveillance of mandatory notifiable diseases at the federal, provincial or territorial levels not specific to the Arctic and subarctic regions, and (2) non-mandatory surveillance programs specific to the Arctic and subarctic regions. We described programs targeting either a single disease, human populations or wildlife. In most programs, there was no explicit mention of the integration of the One Health approach, and little information was available on collaboration efforts between sectors. Programs involved Indigenous communities at various levels, ranging from very low communication to community members, to high involvement and leadership in program management. Improvement in current CSID surveillance activities in Canada should include enhancing information accessibility, ensuring geographic representation, fostering sustainability in implementation of One Health strategies, and stronger involvement of Indigenous communities in the leadership of surveillance systems. An internationally harmonised approach across the Arctic and subarctic regions for all CSIDs has the potential to unify circumpolar surveillance efforts, save resources, and ultimately better inform public health authorities on the actions to prioritize in the context of climate change.
Ties that bind: understanding One Health networks and participation for zoonoses prevention and control in India
Authors: Asaaga Festus A. , Shakeer Irfan , Sriram Aditi , Chhotaria Kashish , Dutta Seshadri , Narayanaswamy Darshan , Amankwaa Godfred , Chanda Mohammed M. , Hoti Subhash L. , Young Juliette C. , Purse Bethan V.
Published: November 2024

Background

Cross-sectoral collaborations as exemplified by the One Health approach, are widely endorsed as pragmatic avenues for addressing zoonotic diseases, but operationalisation remain limited in low-and-middle income countries (LMICs). Complexities and competing interests and agendas of key stakeholders and the underlying politico-administrative context can all shape outcomes of collaborative arrangements. Evidence is building that organised collaborations are complex political initiatives where different objectives; individual and institutional agendas need to be reconciled to incentivise collaborations.

Methods

Drawing on a qualitative network analysis of published sources on ‘One Health’ stakeholders supplemented with 26 multi-scale (national-state-district level) key-informant interviews (including policymakers, disease managers and public health experts), this paper characterises the fragmented and complex characteristics of institutional networks involved in zoonoses prevention and control in India.

Results

Our results highlight how the local socio-political and institutional contexts interact to modulate how and when collaborations occur (or not), the associated contingencies and stakeholder innovations in circumventing existing barriers (e.g. competing interests, distrust between actors, departmental bureaucracy) to cross-sector collaborations and zoonoses management. Aside from principal actors negotiating common ground in some instance, they also capitalised on political/institutional pressure to subtly ‘manipulate’ their subordinates as a way of fostering collaboration, especially in instances when the institutional and political stakes are high.

Conclusion

Altogether our findings suggest that cross-sectoral collaborations are by-product of political and institutional tinkering as long as individual actors and institutional interests converge and these dynamics must be embraced to embed meaningful and sustainable collaborations in local socio-political and administrative contexts.
Decoding the role of NOS3 rs1799983 and PON1 rs662 variants in cardiovascular diseases
Authors: Aamir Kainat , Aslam Sara , Suleman Hafiz Muhammed , Khalid Ammara
Published: November 2024

Background

Cardiovascular diseases (CVDs) are complex diseases determined by various environmental risk factors and genetic susceptibility, and NOS3 and PON1 are considered one of the susceptible genes for CVD. Our study aims to evaluate the association of NOS3 rs1799983 and PON1 rs662 variants with CVD.

Methods

A case–control study was conducted among equal number (252) of cases and controls in the Pakistani population to investigate the significance of NOS3 (rs1799983) and PON1 (rs662) variants in causing CVD risk. Genotyping was performed using Tetra-ARMS PCR to evaluate the genotype–phenotype correlation. For meta-analysis, the case–control studies of NOS3 rs1799983 and PON1 (rs662) variants and CVD were included by searching various databases according to PRISMA guideline. Eligible data were extracted and pooled and were analyzed using Review Manager version 5.4 based on four different genetic models.

Results

Our case–control study showed that both NOS3 rs1799983 (OR = 2.39, p =  < 0.0001, AIC value = 710.50) and PON1 rs662 (OR = 7.30, p =  < 0.0001, AIC value = 680.10) variants significantly increase the risk of CVD under recessive genetic contrast model. The meta-analysis of NOS3 rs1799983 showed association with CVD under all four genetic model's understudy, however, no heterogeneity was found under recessive model only. Meta-analysis for PON1 rs662 showed association with homozygous genetic contrast model only, whereas heterogeneity was observed under all the genetic model's understudy.

Conclusions

We found NOS3 rs1799983 was associated with the increased risk of CVD under four genetic contrast models, while PON1 rs662 polymorphisms associated with homozygous genetic contrast model in different populations only. These results can be utilized to identify individuals at high risk of CVDs and for disease management.
Retinoic acid inhibition of cell proliferation via activation of CDKN1B signaling in the forebrain and spinal cord during mouse embryonic development
Authors: Said Ahmed , AbdElkhalek Amira S. , Sherief Mariam , Amir Lydia , Samy Maysem , Nabil Mariam S. , Safwat Gehan , Diab Ayman A. , Nasraldin Karima
Published: November 2024

Background

The active metabolite of vitamin A (retinol) is retinoic acid (RA). RA is essential for developing several organs as a signaling molecule that is tightly regulated during embryogenesis. We explored the teratogenic effects of RA on forebrain and spinal cord development modified by cyclin-dependent kinase inhibitor 1B (CDKN1B), as the mechanism underlying RA's teratogenic impacts requires further investigation. The study involved four groups of pregnant mice: the negative control group, the positive control group treated with dimethyl sulfoxide (DMSO) diluted in sunflower oil, the RA-treated group receiving a low dosage (5 mg/kg), and the RA-treated group receiving a high dosage (10 mg/kg). The treatment groups received daily intraperitoneal RA dissolved in DMSO and diluted with sunflower oil on gestational days 10.5, 11.5, and 12.5. On day 13.5 of pregnancy, the pregnant mice were euthanized by cervical dislocation, and immunohistochemical analyses of brain and spinal cord tissues were performed.

Results

Morphologically, we observed a decrease in the number of implantation sites and the presence of hematomas in several uterus areas in the high-dose RA (10 mg/kg) group. Additionally, RA was shown to cause adverse changes in uterine weight and length. RA treatment indicated elevated levels of CDKN1B expression in spinal cord development, the diencephalon, and the telencephalon.

Conclusion

Our findings demonstrated that by activating CDKN1B as an RA target gene for cell cycle arrest, an excess of RA during brain development in mouse embryos can induce cell undifferentiation during development.
Advanced testing and biocompatibility strategies for sustainable biomaterials
Authors: Sharma Shraddha Jain , Gupta Ratnalata , Gupta Mayank
Published: November 2024

To ensure the quality, dependability, and long life of sustainable biomaterials, we need comprehensive testing methods. These are for use in varied applications. This chapter provides an in-depth examination. It is of both destructive and non-destructive testing techniques. The techniques are for sustainable biomaterials. Recent advancements in testing technologies are also discussed. This includes machine learning and multi-modal imaging. Destructive testing techniques are used. Tensile testing, impact testing, chemical analysis, and accelerated aging evaluations are employed. These gather essential data. The data is regarding properties and performance of materials. In contrast to this, non-destructive testing methods are used. These include ultrasound, infrared spectroscopy, and imaging techniques. They allow for evaluation without causing damage to the biomaterials. Incorporating environmental impact assessments is discussed. It includes life cycle analysis. It underscores the significance of sustainability in evaluating testing procedures. The section focuses on techniques and approaches. These are required to ensure compatibility of materials in various fields. The aim of this chapter is to equip researchers. It is to equip engineers and practitioners with necessary knowledge and resources. The aim is to assess the efficiency and suitability of sustainable biomaterials. The materials are for various applications. This is done by delving into these evaluation techniques.

Graphical abstract
Insulinoma With Ambiguous Biochemistry, Positive 68Ga-DOTA-Exendin-4 PET-CT, and Effective Endoscopic Ablation
Authors: Loo Fernando Jia Jing , Lee Melvin Kok Seng , Huang Hian Liang , Vu Charles Kien Fong , Kon Yin Chian
Published: November 2024

A 75-year-old female presented with fasting hypoglycemic episodes. A supervised fast ended at 72 hours fulfilling Whipple triad, with suppressed insulin and C-peptide levels, but discordantly suppressed serum β-hydroxybutyrate levels. After 21 months of recurring symptoms, a repeat fast ended at 48 hours with Whipple triad, suppressed serum β-hydroxybutyrate level, and borderline nonsuppressed C-peptide level, suggesting endogenous hyperinsulinism. Serum insulin levels were discordantly suppressed. Computed tomography (CT) of the abdomen demonstrated an enhancing 1.36 × 0.93-cm nodule in the head of the pancreas. Endoscopic ultrasound (EUS)-guided fine-needle aspirate of the lesion derived cytology consistent with a neuroendocrine tumor, but fine-needle core biopsy returned normal pancreatic tissue. Because the results were equivocal, functional imaging with 68Gallium-DOTA-exendin-4 positron emission tomography CT was performed, which confirmed the diagnosis of a single head-of-pancreas insulinoma. The patient declined surgical resection. Oral diazoxide therapy resulted in significant peripheral edema. Hence, EUS-guided radiofrequency ablation of the lesion was performed, and the patient remains symptom free 10 months postprocedure. This case illustrates that (1) exendin-4–based positron emission tomography may help one confidently diagnose and localize insulinoma when prior biochemical or endoscopic biopsy results are ambiguous; and (2) EUS-guided radiofrequency ablation is an efficacious alternative option to surgical resection in the frail, elderly patient with insulinoma.
THE SACRED SPACE OF THE ETHNOREGIONAL ALTAI CULTURES
Authors: Gorshkova Vera S.
Published: November 2024

Goal. The article is devoted to the analysis of the phenomenon of the sacred (sacred, revered, especially significant) space of the «other world» of a Person - a representative of the ethnic group of the Greater Altai, where images and substantial meanings of individual and collective existence are of key importance in culture.
Tasks. The author will have to highlight the features of the sacred space of the ethnoregional culture of the region by highlighting and understanding the value-normative certainty of the elements of spiritual, material and artistic culture of the ethnic groups of Altai.
Method and methodology of the work. The basis of the presented research is formed by phenomenological, cultural philosophical and culturological research methods that allow to reveal the essence and specific content of the values and norms of the sacred space of Altai, forming the world order, the image of the universe and the world order.
Results. The author comes to the conclusion that the phenomenon of sacred space is based on the normative and value basis of the ethnoregional culture of Altai, reflected in its spiritual, material and artistic sides according to the principle of the trinity «Creator-Man-World».
The scope of the results. The results of the research can be applied in the field of cultural, philosophical, socio-philosophical and sociological design and forecasting.
POWER OF WOMAN: GLENN CLOSE’S HEROINES AS THE EMBODIMENT OF STRONG FEMALE CHARACTERS IN CINEMA (SOCIOLOGICAL ANALYSIS)
Authors: Podolskaya Anna A.
Published: November 2024

The article is devoted to the sociological analysis of films featuring Hollywood actress Glenn Close. The purpose of the research is to analyze in what image the heroines appear, how their characters relate to the time of action in films.
In this research, the author also had the task within the framework of Glenn's film career to show which ideas are broadcast in films with the participation of the actress, to illustrate which gender issues came to the fore in society at the time of the release of a particular film.
Among the problems considered by the author are: a woman’s career in “male” professions, the balance between work and family, the problem of a female leader, the reality that a woman at work is forced to “behave like a man in a “man’s world”, finally, the unwillingness of society and even relatives to accept a woman’s professional ambitions.
The empirical basis of the study consists of the following films: “Jagged Edge” (1985), “Dangerous Liaisons” (1988), “101 Dalmatians” (1996), the TV series “Damages” (2008-2012), “Albert Nobbs” (2011), “The Wife” (2017). Research method: semiotic analysis of film material.
The article concludes that most of the characters embodied by Glenn are women who had career aspirations and achieved success in their chosen profession. For their self-realization, they are usually forced to accept the “rules of the game of men”, to a greater extent to show “masculine qualities. It is shown that a woman’s ambition and her desire for career growth are not always perceived in society. Her high position invariably entails a number of gender issues, primarily in maintaining a balance between work and other areas of life. At the same time, in one of the films, the emphasis is placed on the fact that the unrealized potential leads to the accumulation of resentment and emotional emptiness.
At the same time, the actress has heroines in her arsenal who failed to realize their potential, and as a result – emotional emptiness, a real life tragedy. Glenn’s heroines convincingly talk about the problems faced by ambitious women in modern society.
Using Role-Playing Techniques with Generative AI Chatbots for Foreign Language Learning and Practice
Authors: Mineralov Georgiy
Published: November 2024

In recent years, the rise of neural networks and generative artificial intelligence has significantly impacted many professions. Language teachers and programmers, both in Russia and internationally, are exploring how this technology can be applied to foreign language learning. This study aims to showcase the potential of these tools, highlighting their capabilities and possible challenges from the perspectives of both teachers integrating them into their teaching methods and students using them for self-study. The AI models «GPT-3», «GPT-4», «Mistral», and «Character.ai» have been chosen for this research.
The problems of adaptation of children in foster families
Authors: Rassadina O. , Buslaeva Mariya
Published: November 2024

The article explores the process of adaptation of orphaned children in foster families, analyzing the stages and features of the process. In particular, the influence of the age, gender, and social experience of the orphaned child (prior to living in a foster family) on the process of their adaptation is examined. The article also analyzes the individual adaptation of the child's personality to certain family traditions as a foster family member. The article is aimed at finding more effective ways of adapting orphaned children to living in foster families using scientific and professional knowledge in the field of social work.
Features of designing health-saving activities of students in the digital environment
Authors: Komarova E. , Aristova I.
Published: November 2024

The paper is devoted to the problem of designing health-saving activities for students in a digital educational environment; the concepts of “design”, “soft” skills, and “health-saving training” are revealed. The article identifies the features of designing health-saving activities for students based on “soft” skills in the digital environment.
MENTORING IN ASSESSMENTS OF DENTAL RESIDENTS OF THE CENTRAL RESEARCH INSTITUTE OF DENTISTRY AND MAXILLOFACIAL SURGERY
Authors: Kalinina Yuliya
Published: November 2024

It is noted that the key figures in the mentoring process in medicine are those employees of specialized organizations or educational institutions who are highly qualified and are responsible for the professional adaptation of doctors and researchers; They train mentees both in groups and mostly individually. According to the results of a questionnaire survey of students at the Central Research Institute of Physiotherapy, it turned out that mentors provide professional counseling to residents, graduate students and students of additional vocational training, and residents speaking in the focus group agreed that the training of medical personnel here is carried out at a high level due to well-organized mentoring. Within its framework, it is ensured that feedback is established with students both directly within the educational structures of the Central Scientific Research Institute of Physics and Chronology, and indirectly through telecommunications with the regions.Mentors of the Central Scientific Research Institute of Physics and Chronology demonstrate increasing productivity of educational activities, improve the clinical practice of residents, including work in hospitals; in graduate school they identify new topics and even new directions for scientific research; In additional education, established training cycles are modified and new ones are introduced.
Pedagogical heritage of T.N. Malkovskaya as an object of research
Authors: Atomanova Nadezhda
Published: November 2024

The article presents the results of solving one of the research problems “Education of social activity of senior schoolchildren in the pedagogical heritage of T.N. Malkovskaya". The concept of “pedagogical heritage of a scientist” is clarified, the essence and structure of the concept is revealed. The characteristics of the components of the scientist’s pedagogical heritage are given.
The influence of extracurricular activities on the formation of the value attitude of primary school students to Russian culture
Authors: Bol'shakova A.
Published: November 2024

In the modern educational context, extracurricular activities are an important direction, influencing the formation of students' value attitude to national culture. In the journal "Teaching History at School" it can be seen that various forms of extracurricular activities for schoolchildren in the field of history and social studies have become widespread. These forms include excursions, clubs, working in a museum, holding school evenings, organizing school clubs and decorating classrooms. The purpose of this study is to identify the main factors of the influence of extracurricular activities on the formation of the value attitude of primary school students to Russian culture. To achieve the goal, the following tasks were set: to analyze theoretical approaches to the concept of "extracurricular work" and "value attitude"; to identify the main types of extracurricular work that contribute to the formation of students' value attitude to national culture; to determine effective methods and forms of extracurricular activities to achieve this goal.
The practical application of the research results will optimize extracurricular activities in educational institutions, as well as develop recommendations for teachers on organizing events that contribute to the formation of a positive value attitude of students to national culture. This can be useful for enhancing patriotic education, developing cultural identity and active participation of students in society.
The evolution of the children's and youth epistolary genre: from the period of perestroika to the digital age
Authors: Makeeva T.
Published: November 2024

The article is devoted to the problem of studying the transformation of the life worlds of children and youth using epistolary sources of the period of perestroika in the USSR. The relevance of the article is dictated by the insufficiency of scientific developments based on letters from children and youth as a subject of research. Attention is focused on the consideration of the epistolary genre as an attribute of the everyday life of a Soviet schoolboy. The author of the article analyzes children's texts stored in his own collection - letters from peers from socialist countries (GDR, Bulgaria, Poland, Romania). Socio-psychological portraits of children from different countries, their interests, values, described and experienced events are presented. As an example of children's diplomacy, the biographies and quotations of children's letters by Samantha Smith and Katya Lycheva, who played a significant role in shaping the worldview and value orientations of the perestroika generation, are given.
Fostering national identification and patriotism based on folk art
Authors: Mihaylova N.
Published: November 2024

The article examines the modern problems of the formation of national identity and patriotic education of the younger generation based on traditional applied art. Particular attention is paid to the interpretation in modern conditions of such concepts as "national identification," "folk art," "traditional art crafts." The preservation of the cultural heritage of Russia is considered in the article through the prism of transferring traditions, technologies, worldview and the spiritual component of folk art to the younger generation, through the professional education of creators of new highly artistic products of traditional applied art and the education of connoisseurs of this unique cultural experience.
A new approach in the methodology of teaching painting
Authors: Golyshev A.
Published: November 2024

This technique, developed and introduced by the author of the article at the Moscow State Academic Art Institute named after V.I. Surikov, is offered as an initial training for students of art schools and colleges, students of technical schools and institutes in order to familiarize them with both three-dimensional forms, and with color space, and color relations, as well as with an understanding of the basics of painting crafts, with the influence of color spaces on each other.
Enhancing Helpdesk Efficiency through Management Information System – A Resource Allocation Study in Technology Firms
Authors: Osman Bashir Mohamed , Muse Abdillahi Mohamoud Sheikh
Published: November 2024

Purpose: This paper aims to enhance helpdesk efficiency by integrating deep reinforcement learning for resource allocation and customer satisfaction improvement.
Methodology/Approach: The study implemented a deep Q-learning algorithm within a helpdesk management system. The dataset was divided into training and testing sets in an 80:20 ratio. The architectural and computational parameters of the model were optimised, focusing on resource utilisation and workload distribution.
Findings: The proposed method reduced the normal resolution time from 3.5 hours to 2.65 hours, representing a 24.3% improvement. Customer satisfaction improved, averaging a score of 3.85. The allocation of support staff workloads was enhanced, leading to a more balanced distribution across different locations.
Research Limitation/Implication: Various parameter patterns for the proposed method were tested, revealing the approach's computational expense.
Originality/Value of paper: The study proposes a novel use of deep Q-learning for helpdesk management, significantly improving classification accuracy and workload distribution over conventional methods.
The Relationship between Hexa Helix and Marketing Performance of Food Product SMEs for Souvenirs: The Mediating Effect of Product Innovation and Integrated Marketing
Authors: Melany Melany , Pasla Peter Remy Yosy , Widyaningrum Santi , Taneo Stefanus Yufra Menahen , Noya Sunday , Christian Aland
Published: November 2024

Purpose: Small and Medium Enterprises (SMEs) play an important role in the Indonesian economy, yet their marketing performance remains low due to various interrelated causal factors. This study aims to explore the Hexa Helix as an independent variable that affects the marketing performance of SMEs producing food products for souvenirs, with product innovation and integrated marketing as mediating factors.
Methodology/Approach: Data were collected from 448 respondents, who are owners and managers of SMEs in Malang Regency. Data were analysed using WarpPLS due to its flexibility in analysing mediating variables.
Findings: The results showed that the Hexa Helix significantly and positively affects the marketing performance of food SMEs for souvenirs.
Research Limitation/Implication: This study did not analyse the interactions between helices but looked at the six components as a whole. Future research can reveal the role of each actor and their interactions that determine the important role of the hexa helix. The implications for integrated marketing strategies for SMEs.
Originality/Value of paper: Previous studies placed the hexa helix or other helix as a moderating or mediating variable. This research places the hexa helix as an independent variable and proves that multi-stakeholders affect product innovation and integrated marketing in improving marketing performance.