bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring Patients’ Perspectives on Late Complications after Colorectal and Anal Cancer Treatment: A Qualitative Study
Authors: Oggesen Birthe Thing , Hamberg Marie Louise Sjødin , Thomsen Thordis , Rosenberg Jacob
Published: August 2023

Background: Patients often experience late complications following treatment for colorectal and anal cancer. Although several measurement tools exist to classify the severity of these symptoms, little is known about how patients personally experience and adapt to these complications. This study aimed to investigate patients’ experiences and coping strategies in relation to these symptoms. Methods: We conducted an explorative qualitative interview study to gather data. Results: Our findings revealed two main categories: How patients react after treatment for colorectal and anal cancer, and Experienced symptoms. Additionally, we identified four sub-categories: the period after discharge, coping strategies, stool symptoms, and other symptoms. Patients commonly feel abandoned once their surgical and oncological treatments are completed. It is typical for patients to turn to the internet for guidance on managing late complications, despite being aware that evidence-based options are limited. Stool-related issues significantly impact patients’ personal and professional lives, requiring constant preparedness for accidents, the use of diapers, and the need for extra clothing at all times. Furthermore, patients experience additional troublesome symptoms such as urinary incontinence, fatigue, pain, and sexual dysfunction, which further affect their daily lives. Conclusions: Patients experience multiple problems after colorectal cancer surgery, and this warrants more focused attention.
An Overview of Pancreatic Neuroendocrine Tumors and an Update on Endoscopic Techniques for Their Management
Authors: Elkelany Osama O. , Karaisz Fred G. , Davies Benjamin , Krishna Somashekar G.
Published: August 2023

The growing importance of advanced endoscopy in the diagnosis and treatment of pancreatic neuroendocrine neoplasms (PanNETs) necessitates a comprehensive understanding of various biochemical markers, genetic testing methods, radiological techniques, and treatment approaches that encompass multiple disciplines within and beyond gastrointestinal oncology. This review aims to highlight key aspects of these topics, with a specific focus on emerging EUS-guided procedures for the management of PanNETs.
Abstracts of the 2023 Canadian Association of Medical Oncologists Annual Scientific Meeting
Authors: Campbell Alexi , Gill Sharlene , Hao Desiree , Powell Erin , Snow Stephanie , Veitch Zachary , Welch Stephen
Published: August 2023

On behalf of the Canadian Association of Medical Oncologists, we are pleased to present the abstracts of the 2023 Annual Scientific Meeting. The CAMO Annual Scientific Meeting (ASM) took place on 27 April 2023 in an in-person event in Toronto, ON. Thirty-two (32) abstracts were selected for presentation as oral presentations, in-person poster presentations, and virtual poster presentations. Awards for the top four (4) abstracts were presented during the ASM; they have been marked as “Award Recipient”. We congratulate all presenters on their research work and contribution.
Density-Based Entropy Centrality for Community Detection in Complex Networks
Authors: Žalik Krista Rizman , Žalik Mitja
Published: August 2023

One of the most important problems in complex networks is the location of nodes that are essential or play a main role in the network. Nodes with main local roles are the centers of real communities. Communities are sets of nodes of complex networks and are densely connected internally. Choosing the right nodes as seeds of the communities is crucial in determining real communities. We propose a new centrality measure named density-based entropy centrality for the local identification of the most important nodes. It measures the entropy of the sum of the sizes of the maximal cliques to which each node and its neighbor nodes belong. The proposed centrality is a local measure for explaining the local influence of each node, which provides an efficient way to locally identify the most important nodes and for community detection because communities are local structures. It can be computed independently for individual vertices, for large networks, and for not well-specified networks. The use of the proposed density-based entropy centrality for community seed selection and community detection outperforms other centrality measures.
A Multi-Path MAC Scheduling Scheme for Multi-Channel Wireless Sensor Networks
Authors: Zhang Fan , Yang Gangqiang
Published: August 2023

Designing reasonable MAC scheduling strategies is an important means to ensure transmission quality in wireless sensor networks (WSNs). When there exist multiple available routes from the source to the destination, it is necessary to combine a data traffic allocation mechanism and design a multi-path MAC scheduling scheme in order to ensure QoS. This paper develops a multi-path resource allocation method for multi-channel wireless sensor networks, which uses random-access technology to complete MAC scheduling and selects the transmission path for each packet according to the probability. Through theoretical analysis and simulation experiments, it can be found that the proposed strategy can provide a reliable throughput capacity region. Meanwhile, due to the use of random-access technology, the computational complexity of the proposed algorithm can be independent of the number of links and channels.
Distributed Consensus Algorithms in Sensor Networks with Higher-Order Topology
Authors: Chen Qianyi , Shi Wenyuan , Sui Dongyan , Leng Siyang
Published: August 2023

Information aggregation in distributed sensor networks has received significant attention from researchers in various disciplines. Distributed consensus algorithms are broadly developed to accelerate the convergence to consensus under different communication and/or energy limitations. Non-Bayesian social learning strategies are representative algorithms for distributed agents to learn progressively an underlying state of nature by information communications and evolutions. This work designs a new non-Bayesian social learning strategy named the hypergraph social learning by introducing the higher-order topology as the underlying communication network structure, with its convergence as well as the convergence rate theoretically analyzed. Extensive numerical examples are provided to demonstrate the effectiveness of the framework and reveal its superior performance when applying to sensor networks in tasks such as cooperative positioning. The designed framework can assist sensor network designers to develop more efficient communication topology, which can better resist environmental obstructions, and also has theoretical and applied values in broad areas such as distributed parameter estimation, dispersed information aggregation and social networks.
Advanced Research on Internal Combustion Engines and Engine Fuels
Authors: Yue Zongyu , Liu Haifeng
Published: August 2023

Internal combustion (IC) engines serve as power devices that are widely applied in the fields of transport, engineering machinery, stationary power generation, etc., and are evolving towards the goal of higher efficiency and lower environmental impacts. In this Editorial, the role of IC engines for future transport and energy systems is discussed, and research directions for advancing IC engine and fuel technologies are recommended. Finally, we introduce the 14 technical papers collected for this Special Issue, which cover a wide range of research topics, including diesel spray characteristics, combustion technologies for low- and zero-carbon fuels, advanced combustion mode, fuel additive effects, engine operation under extreme conditions and advanced materials and manufacturing processes.
Effect of Microporous Layer Ink Homogenisation on the Through-Plane Gas Permeability of PEFC Porous Media
Authors: Neehall Narvin D. , Ismail Mohammed S. , Hughes Kevin J. , Pourkashanian Mohamed
Published: August 2023

The through-plane gas permeability and morphology of PEFC gas diffusion media (GDM) is investigated for different microporous layer (MPL) ink homogenisation techniques (bath sonication and magnetic stirring) for low- (Vulcan XC-72R) and high (Ketjenblack EC-300J)-surface-area carbon powders. The MPL composition is held constant at 80 wt.% carbon powder and 20 wt.% PTFE for a carbon loading of 1.0 mg cm−2. The MPL ink homogenisation time is held constant at two hours for both techniques and increased by one hour for bath sonication to compare with previous investigations. The results show that the through-plane gas permeability of the GDM is approximately doubled using magnetic stirring when compared with bath sonication for MPLs composed of Vulcan XC-72R, with a negligible change in surface morphology between the structures produced from either homogenisation technique. The variation in through-plane gas permeability is almost negligible for MPLs composed of Ketjenblack EC-300J compared with Vulcan XC-72R; however, MPL surface morphology changes considerably with bath sonication, producing smoother, less cracked surfaces compared to the large cracks produced via magnetic stirring for a large-surface-area carbon powder. An MPL ink sonication time of three hours results in a percentage reduction in through-plane gas permeability from the GDL substrate permeability by ~72% for Ketjenblack EC-300J compared to ~47% for two hours.
Ribosomal Biogenesis and Heterogeneity in Development, Disease, and Aging
Authors: Islam Rowshan Ara , Rallis Charalampos
Published: August 2023

Although reported in the literature, ribosome heterogeneity is a phenomenon whose extent and implications in cell and organismal biology is not fully appreciated. This has been the case due to the lack of the appropriate techniques and approaches. Heterogeneity can arise from alternative use and differential content of protein and RNA constituents, as well as from post-transcriptional and post-translational modifications. In the few examples we have, it is apparent that ribosomal heterogeneity offers an additional level and potential for gene expression regulation and might be a way towards tuning metabolism, stress, and growth programs to external and internal stimuli and needs. Here, we introduce ribosome biogenesis and discuss ribosomal heterogeneity in various reported occasions. We conclude that a systematic approach in multiple organisms will be needed to delineate this biological phenomenon and its contributions to growth, aging, and disease. Finally, we discuss ribosome mutations and their roles in disease.
On Bounds of k-Fractional Integral Operators with Mittag-Leffler Kernels for Several Types of Exponentially Convexities
Authors: Farid Ghulam , Khan Hala Safdar , Tawfiq Ferdous M. O. , Ro Jong-Suk , Zainab Saira
Published: August 2023

This paper aims to study the bounds of k-integral operators with the Mittag-Leffler kernel in a unified form. To achieve these bounds, the definition of exponentially (α,h−m)−p-convexity is utilized frequently. In addition, a fractional Hadamard type inequality which shows the upper and lower bounds of k-integral operators simultaneously is presented. The results are directly linked with the results of many published articles.
Fractal Parameters as Independent Biomarkers in the Early Diagnosis of Pediatric Onset Inflammatory Bowel Disease
Authors: Makević Vedrana , Milovanovich Ivan D. , Popovac Nevena , Janković Radmila , Trajković Jelena , Vuković Andrija , Milosević Bojana , Jevtić Jovan , de Luka Silvio R. , Ilić Andjelija Ž.
Published: August 2023

Inflammatory bowel disease (IBD), which encompasses two different phenotypes—Crohn’s disease (CD) and ulcerative colitis (UC)—consists of chronic, relapsing disorders of the gastrointestinal tract. In 20–30% of cases, the disease begins in the pediatric age. There have been just a few studies that used fractals for IBD investigation, but none of them analyzed intestinal cell chromatin. The main aim of this study was to assess whether it is possible to differentiate between the two phenotypes in pediatric patients, or either of the phenotypes versus control, using the fractal dimension and lacunarity of intestinal cell chromatin. We analyzed nuclei from at least seven different intestinal segments from each group. In the majority of colon segments, both the fractal dimension (FD) and the lacunarity significantly differed between the UC group and CD group, and the UC group and control group. In addition, the ileocecal valve and rectum were the only segments in which CD could be differentiated from the controls based on the FD. The potential of the fractal analysis of intestinal cell nuclei to serve as an observer-independent histological tool for ulcerative colitis diagnosis was identified for the first time in this study. Our results pave the way for the development of computer-aided diagnosis systems that will assist the physicians in their clinical practice.
Green Synthesized Silver Nanoparticles Loaded in Polysaccharide Hydrogel Applied to Chronic Wound Healing in Mice Models
Authors: Aldakheel Fahad M. , Mohsen Dalia , El Sayed Marwa M. , Fagir Mohammed H. , El Dein Dalia K.
Published: August 2023

The prevalence of chronic wounds is increasing owing to the expanding population and the growing number of individuals suffering from diabetes. Such a chronic wound continues to be a significant healthcare burden for diabetic patients because it frequently carries a high chance of limb loss due to amputation and reduces survival as a result. Development of innovative wound dressing materials with the potential to stop bacterial infections and accelerate the process of tissue regeneration is needed to increase the effectiveness of diabetic wound healing. In the current study, a co-polymerization process based on a free radical reaction was used to create a hydrogel of polysaccharides blend graft acrylamide (PsB-g-Am). Starch, chitosan, and alginate make up the polysaccharides blend (PsB). The produced hydrogel’s structure was characterized using FTIR spectroscopy. The antibacterial activities of silver nanoparticles synthesized through the green method using garlic bulb (Allium sativum) is reported. The silver nanoparticles’ physical characteristics were examined using scanning electron microscopy, transmission electron microscopy analysis, and UV-visible spectroscopy and they were found to range in size from 50 to 100 nm. The agar well diffusion technique is used to investigate the antibacterial characteristics. Inclusion of silver nanoparticles in the hydrogels demonstrated concentration-dependent antibacterial behavior against Gram-negative Klebsiella pneumoniae and Gram-positive Staphylococcus aureus during antimicrobial testing of the hydrogels. When hydrogels were applied to diabetic mice, the system was examined for its healing abilities, and positive therapeutic results were obtained in as little as 14 days. Thus, it can be inferred that graft copolymer of chitosan-AgNPs hydrogels can promote healing in chronic wounds over time and can be utilized as an alternative to conventional therapies for chronic wounds (such as those brought on by diabetes) in mouse models.
Bigels as Delivery Systems: Potential Uses and Applicability in Food
Authors: Francavilla Alyssa , Corradini Maria G. , Joye Iris J.
Published: August 2023

Bigels have been mainly applied in the pharmaceutical sector for the controlled release of drugs or therapeutics. However, these systems, with their intricate structures, hold great promise for wider application in food products. Besides their classical role as carrier and target delivery vehicles for molecules of interest, bigels may also be valuable tools for building complex food structures. In the context of reducing or even eliminating undesirable (but often highly functional) food components, current strategies often critically affect food structure and palatability. The production of solid fat systems that are trans-fat-free and have high levels of unsaturated fatty acids is one of the challenges the food industry currently faces. According to recent studies, bigels can be successfully used as ingredients for total or partial solid fat replacement in complex food matrices. This review aims to critically assess current research on bigels in food and pharmaceutical applications, discuss the role of bigel composition and production parameters on the characteristics of bigels and further expand the use of bigels as solid fat replacers and functional food ingredients. The hydrogel:oleogel ratio, selected gelators, inclusion of surfactants and encapsulation of molecules of interest, and process parameters (e.g., temperature, shear rate) during bigel production play a crucial role in the bigel’s rheological and textural properties, microstructure, release characteristics, biocompatibility, and stability. Besides exploring the role of these parameters in bigel production, future research directions for bigels in a food context are explored.
Seafloor and Ocean Crust Structure of the Kerguelen Plateau from Marine Geophysical and Satellite Altimetry Datasets
Authors: Lemenkova Polina
Published: August 2023

The volcanic Kerguelen Islands are formed on one of the world’s largest submarine plateaus. Located in the remote segment of the southern Indian Ocean close to Antarctica, the Kerguelen Plateau is notable for a complex tectonic origin and geologic formation related to the Cretaceous history of the continents. This is reflected in the varying age of the oceanic crust adjacent to the plateau and the highly heterogeneous bathymetry of the Kerguelen Plateau, with seafloor structure differing for the southern and northern segments. Remote sensing data derived from marine gravity and satellite radar altimetry surveys serve as an important source of information for mapping complex seafloor features. This study incorporates geospatial information from NOAA, EMAG2, WDMAM, ETOPO1, and EGM96 datasets to refine the extent and distribution of the extracted seafloor features. The cartographic joint analysis of topography, magnetic anomalies, tectonic and gravity grids is based on the integrated mapping performed using the Generic Mapping Tools (GMT) programming suite. Mapping of the submerged features (Broken Ridge, Crozet Islands, seafloor fabric, orientation, and frequency of magnetic anomalies) enables analysis of their correspondence with free-air gravity and magnetic anomalies, geodynamic setting, and seabed structure in the southwest Indian Ocean. The results show that integrating the datasets using advanced cartographic scripting language improves identification and visualization of the seabed objects. The results include 11 new maps of the region covering the Kerguelen Plateau and southwest Indian Ocean. This study contributes to increasing the knowledge of the seafloor structure in the French Southern and Antarctic Lands.
One Step at a Time: Improving Gait Speed Measurement in a Geriatric Medicine Clinic
Authors: James Kirstyn , Growdon Matthew E. , Orkaby Ariela R. , Schwartz Andrea Wershof
Published: August 2023

(1) Background: Mobility assessment is a key component of the assessment of an older adult as a part of the Age-Friendly Health System (AFHS) “geriatric 4Ms” framework. Several validated tools for assessing mobility and estimating fall risk in older adults are available. However, they are often under-utilized in daily practice even in specialty geriatric medicine care settings. We aimed to increase formal mobility assessment with brief gait speed measurement in a geriatric medicine outpatient clinic using phased change interventions. (2) Methods: This quality improvement (QI) initiative was conducted in a single outpatient geriatric medicine clinic. All clinic attendees who could complete a gait speed measurement were eligible for inclusion. The outcome measure was the completion of a 4 m gait speed. Several change interventions were implemented on a phased basis using the Model for Improvement methodology during the period from December 2018 to March 2020. Statistical process control charts were used to record gait speed measurements and detect non-random shifts. (3) Results: During this QI initiative, 80 patients were seen, accounting for 142 clinic visits. In response to change interventions, gait speed measurement at clinic visits increased from a median of 25% of visits to 67% by March 2020. (4) Conclusions: Adopting an AFHS care model is an urgent and challenging task to improve the quality of care for older adults. This initiative details how to effectively incorporate a brief, validated assessment of mobility using gait speed measurement into every geriatric medicine outpatient visit and progresses implementation of the AFHS “geriatric 4Ms”. Mobility assessment can aid in identifying older adults at increased fall risk.
Genome-Wide Identification of Laccase Gene Family from Punica granatum and Functional Analysis towards Potential Involvement in Lignin Biosynthesis
Authors: Shi Jiangli , Yao Jianan , Tong Ruiran , Wang Sen , Li Ming , Song Chunhui , Wan Ran , Jiao Jian , Zheng Xianbo
Published: August 2023

Laccase (LAC) is the key enzyme responsible for lignin biosynthesis. Here, 57 PgLACs from pomegranate were identified and distributed on eight chromosomes and one unplaced scaffold. They were divided into six groups containing three typical Cu-oxidase domains. Totally, 51 cis-acting elements in the promoter region of PgLACs are involved in response to ABA, GA, light, stress, etc., indicating diverse functions of PgLACs. The expression profiles of 13 PgLACs during the seed development stage showed that most PgLACs expressed at a higher level earlier than at the later seed development stage in two pomegranate cultivars except PgLAC4. Also, PgLAC1/6/7/16 expressed at a significantly higher level in soft-seed ‘Tunisia’; on the contrary, PgLAC37 and PgLAC50 with a significantly higher expression in hard-seed ‘Taishanhong’. Combined with their distinguishing cis-acting elements, it was concluded that PgLAC1/6/7 may respond to GA via TATC-box and GARE-motif, and PgLAC16 repressed the promotor activity of embryo mid-maturation genes via RY-element so as to contribute to softer seed formation, whereas PgLAC37/50 may participate in seed formation and accelerate seed maturity via ABRE and G-box elements. Collectively, the dramatic gene expressions of PgLAC1/6/7/16/37/50 will provide valuable information to explore the formation of soft- and hard-seed in pomegranate.
Peat Substitution in Horticulture: Interviews with German Growing Media Producers on the Transformation of the Resource Base
Authors: Hirschler Olivier , Thrän Daniela
Published: August 2023

Peat is the major constituent of horticultural growing media. Due to its high climate footprint, its extraction and use are controversial and the need to limit its use is widely recognised. The Peat Use Reduction Strategy of the German government aims to phase out its use and replace it with renewable materials. Despite large potential, stakeholders consider the availability of peat substitutes in sufficient quantity and quality as a critical issue. The goal of this research is to systematically investigate the challenges and opportunities for substituting peat in the resource base of the growing media industry. Based on deep-dive interviews with German growing media producers, the factors determining the supply and use of the main growing media constituents—peat, green compost, wood fibres, composted bark and coir products—were analysed. The results show the critical role of the processing infrastructure on transportation distances and the quality and quantity of the market supply. Additionally, competition with other sectors affects the availability of materials for the growing media industry. Moreover, peat is still economically advantageous compared with its substitutes. Even if this advantage declines due to consumer awareness and the end of domestic extraction, the end of peat use would probably imply new policy measures.
The Impact of COVID-19 on Active Living and Life Satisfaction of Rowers
Authors: Pöschl Maximilian , Jungwirth David , Haluza Daniela
Published: August 2023

The broad variety of measures that governments worldwide took against the COVID-19 pandemic led to restrictions in our everyday life, including the practice of sports such as rowing. This study aimed to examine changes in the daily life of rowers and their rowing engagement. We distributed an online questionnaire in German among rowers in 2021. In total, 234 (48.7% females, mean age 45.01 years, SD 16.94) participants met the inclusion criteria. We found that the amount of time spent rowing was significantly lower during the COVID-19 crisis. Additionally, we detected a notable shift in the rowing landscape, with a marked increase in home-based training and a complete cessation of rowing activities. Moreover, the life satisfaction of both female and male rowers witnessed a significant decline during the pandemic when compared to before. The present findings showed that the pandemic led to far-reaching changes in sports activities among rowers. Most rowers had to deal with negative effects not only on their rowing engagement, but also on life satisfaction. In view of future pandemics, it becomes crucial to prioritize and ensure the continuity of active sports engagement, including that of rowers, in a safe and secure manner.
Beyond Bullying, Aggression, Discrimination, and Social Safety: Development of an Integrated Negative Work Behavior Questionnaire (INWBQ)
Authors: Verschuren Cokkie , Tims Maria , De Lange Annet H.
Published: August 2023

Negative work behavior (NWB) threatens employee well-being. There are numerous constructs that reflect NWBs, such as bullying, aggression, and discrimination, and they are often examined in isolation from each other, limiting scientific integration of these studies. We aim to contribute to this research field by developing a diagnostic tool with content validity on the full spectrum of NWBs. First, we provide a full description of how we tapped and organized content from 44 existing NWB measurement instruments and 48 studies. Second, we discussed our results with three experts in this research field to check for missing studies and to discuss our integration results. This two-stage process yielded a questionnaire measuring physical, material, psychological, sociocultural, and digital NWB. Furthermore, the questions include a range of potential actors of NWB, namely, internal (employees, managers) and external actors (clients, customers, public, and family members) at work and their roles (i.e., target, perpetrator, perpetrator’s assistant, target’s defender, outsider, and witness of NWBs). Finally, the questionnaire measures what type of harm is experienced (i.e., bodily, material, mental, and social harm).
Methylation Profile of Small Breast Cancer Tumors Evaluated by Modified MS–HRM
Authors: Krasnyi Aleksey M. , Sadekova Alsu A. , Kometova Vlada V. , Rodionov Valeriy V. , Yarotskaya Ekaterina L. , Sukhikh Gennadiy T.
Published: August 2023

The DNA methylation profile of breast cancer differs from that in healthy tissues and can be used as a diagnostic and prognostic biomarker. Aim of this study: To compare the levels of gene methylation in small malignant breast cancer tumors (<2 cm), in healthy tissue, and in fibroadenoma, and to evaluate the effectiveness of the modified Methylation Sensitive–High Resolution Melting (MS–HRM) method for this analysis. Analysis was performed using the modified MS–HRM method. For validation, the methylation levels of five genes were confirmed by pyrosequencing. The main study group included 96 breast cancer samples and the control group included 24 fibroadenoma samples and 24 healthy tissue samples obtained from patients with fibroadenoma. Breast cancer samples were divided into two subgroups (test set and validation set). The methylation of the following 15 genes was studied: MAST1, PRDM14, ZNF177, DNM2, SSH1, AP2M1, CACNA1E, CPEB4, DLGAP2, CCDC181, GCM2, ITPRIPL1, POM121L2, KCNQ1, and TIMP3. Significant differences in the validation set of samples were found for seven genes; the combination of the four genes GCM2, ITPRIPL1, CACNA1E, DLGAP2 (AUC = 0.99) showed the highest diagnostic value based on logistic regression for all breast cancer samples. Our modified MS–HRM method demonstrated that small breast cancer tumors have a specific DNA methylation profile that distinguishes them from healthy tissues and benign proliferative lesions.
Neuronal Death Caused by HMGB1-Evoked via Inflammasomes from Thrombin-Activated Microglia Cells
Authors: Sheu Meei-Ling , Pan Liang-Yi , Yang Cheng-Ning , Sheehan Jason , Pan Liang-Yu , You Weir-Chiang , Wang Chien-Chia , Chen Hong-Shiu , Pan Hung-Chuan
Published: August 2023

Microglial cells are a macrophage-like cell type residing within the CNS. These cells evoke pro-inflammatory responses following thrombin-induced brain damage. Inflammasomes, which are large caspase-1-activating protein complexes, play a critical role in mediating the extracellular release of HMGB1 in activated immune cells. The exact role of inflammasomes in microglia activated by thrombin remains unclear, particularly as it relates to the downstream functions of HMGB1. After receiving microinjections of thrombin, Sprague Dawley rats of 200 to 250 gm were studied in terms of behaviors and immunohistochemical staining. Primary culture of microglia cells and BV-2 cells were used for the assessment of signal pathways. In a water maze test and novel object recognition analysis, microinjections of thrombin impaired rats’ short-term and long-term memory, and such detrimental effects were alleviated by injecting anti-HMGB-1 antibodies. After thrombin microinjections, the increased oxidative stress of neurons was aggravated by HMGB1 injections but attenuated by anti-HMGB-1 antibodies. Such responses occurred in parallel with the volume of activated microglia cells, as well as their expressions of HMGB-1, IL-1β, IL-18, and caspase-I. In primary microglia cells and BV-2 cell lines, thrombin also induced NO release and mRNA expressions of iNOS, IL-1β, IL-18, and activated caspase-I. HMGB-1 aggravated these responses, which were abolished by anti-HMGB-1 antibodies. In conclusion, thrombin induced microglia activation through triggering inflammasomes to release HMGB1, contributing to neuronal death. Such an action was counteracted by the anti-HMGB-1 antibodies. The refinement of HMGB-1 modulated the neuro-inflammatory response, which was attenuated in thrombin-associated neurodegenerative disorder.
Integration of Metabolomic and Transcriptomic Provides Insights into Anti-Inflammatory Response to trans-10-Hydroxy-2-decenoic Acid on LPS-Stimulated RAW 264.7 Cells
Authors: Huang Minjie , Dong Jie , Tan Xiaodong , Yang Shuyuan , Xiao Minghui , Wang Deqian
Published: August 2023

Trans-10-hydroxy-2-decenoic acid (10-HDA) is a unique fatty acid found in royal jelly that possesses potential health benefits such as anti-inflammatory. However, further research is needed to fully understand its mechanisms of action and therapeutic potential for inflammation-associated diseases. In this present study, liquid chromatography–tandem mass spectrometry (LC-MS/MS) and RNA-seq analyses were conducted to comprehensively analyze the in vitro anti-inflammatory effects of 10-HDA on lipopolysaccharide (LPS)-stimulated RAW 264.7 cells. Our results demonstrated that 128 differentially expressed metabolites and 1721 differentially expressed genes were identified in the 10-HDA-treated groups compared to the LPS groups. Metabolites were significantly enriched in amino acid metabolism pathways, including methionine metabolism, glycine and serine metabolism, and tryptophan metabolism. The differentially expressed genes enrichment analysis indicated that antigen processing and presentation, NOD-like receptor signaling pathway, and arginine biosynthesis were enriched with the administration of 10-had. The correlation analysis revealed that glycerophospholipid metabolism and s-adenosylmethionine-dependent methylation processes might be involved in the response to the 10-HDA treatment. Overall, the findings from this study showed that 10-HDA might involve the modulation of certain signaling pathways involved in the inflammatory response, but further research is needed to determine the safety and efficacy as a therapeutic agent.
Cytoprotective, Cytotoxic and Cytostatic Roles of Autophagy in Response to BET Inhibitors
Authors: Elshazly Ahmed M. , Gewirtz David A.
Published: August 2023

The bromodomain and extra-terminal domain (BET) family inhibitors are small molecules that target the dysregulated epigenetic readers, BRD2, BRD3, BRD4 and BRDT, at various transcription-related sites, including super-enhancers. BET inhibitors are currently under investigation both in pre-clinical cell culture and tumor-bearing animal models, as well as in clinical trials. However, as is the case with other chemotherapeutic modalities, the development of resistance is likely to constrain the therapeutic benefits of this strategy. One tumor cell survival mechanism that has been studied for decades is autophagy. Although four different functions of autophagy have been identified in the literature (cytoprotective, cytotoxic, cytostatic and non-protective), primarily the cytoprotective and cytotoxic forms appear to function in different experimental models exposed to BET inhibitors (with some evidence for the cytostatic form). This review provides an overview of the cytoprotective, cytotoxic and cytostatic functions of autophagy in response to BET inhibitors in various tumor models. Our aim is to determine whether autophagy targeting or modulation could represent an effective therapeutic strategy to enhance the response to these modalities and also potentially overcome resistance to BET inhibition.
Diabetes Mellitus Secondary to Endocrine Diseases: An Update of Diagnostic and Treatment Particularities
Authors: Popoviciu Mihaela Simona , Paduraru Lorena , Nutas Raluca Marinela , Ujoc Alexandra Maria , Yahya Galal , Metwally Kamel , Cavalu Simona
Published: August 2023

Secondary diabetes mellitus is frequently ignored in specialized literature. In this narrative review, the main endocrinopathies accompanied by increased glycemic values are identified, as well as the mechanisms by which the excess or deficiency of certain hormones impact beta cell function or insulin resistance. The main endocrinopathies (acromegaly, Cushing’s syndrome, Basedow–Graves’ disease, pheochromocytoma, somatostatinoma and glucagonoma) and their characteristics are described along with the impact of hormone changes on blood sugar, body mass index and other parameters associated with diabetes. The overall information regarding the complex molecular mechanisms that cause the risk of secondary diabetes and metabolic syndrome is of crucial importance in order to prevent the development of the disease and its complications and particularly to reduce the cardiovascular risk of these patients. The purpose of this study is to highlight the particular features of endocrine pathologies accompanied by an increased risk of developing diabetes, in the context of personalized therapeutic decision making. The epidemiological, physiopathological, clinical and therapeutic approaches are presented along with the importance of screening for diabetes in endocrine diseases.
On the Value of In Vitro Cell Systems for Mechanobiology from the Perspective of Yes-Associated Protein/Transcriptional Co-Activator with a PDZ-Binding Motif and Focal Adhesion Kinase and Their Involvement in Wound Healing, Cancer, Aging, and Senescence
Authors: Steinberg Thorsten , Dieterle Martin Philipp , Ramminger Imke , Klein Charlotte , Brossette Julie , Husari Ayman , Tomakidi Pascal
Published: August 2023

Mechanobiology comprises how cells perceive different mechanical stimuli and integrate them into a process called mechanotransduction; therefore, the related mechanosignaling cascades are generally important for biomedical research. The ongoing discovery of key molecules and the subsequent elucidation of their roles in mechanobiology are fundamental to understanding cell responses and tissue conditions, such as homeostasis, aging, senescence, wound healing, and cancer. Regarding the available literature on these topics, it becomes abundantly clear that in vitro cell systems from different species and tissues have been and are extremely valuable tools for enabling the discovery and functional elucidation of key mechanobiological players. Therefore, this review aims to discuss the significant contributions of in vitro cell systems to the identification and characterization of three such key players using the selected examples of yes-associated protein (YAP), its paralog transcriptional co-activator with a PDZ-binding motif (TAZ), and focal adhesion kinase (FAK) and their involvement in wound healing, cancer, aging, and senescence. In addition, the reader is given suggestions as to which future prospects emerge from the in vitro studies discussed herein and which research questions still remain open.
Current Advances in the Biomedical Applications of Quantum Dots: Promises and Challenges
Authors: Le Nhi , Kim Kyoungtae
Published: August 2023

Quantum dots (QDs) are a type of nanoparticle with exceptional photobleaching-resistant fluorescence. They are highly sought after for their potential use in various optical-based biomedical applications. However, there are still concerns regarding the use of quantum dots. As such, much effort has been invested into understanding the mechanisms behind the behaviors of QDs, so as to develop safer and more biocompatible quantum dots. In this mini-review, we provide an update on the recent advancements regarding the use of QDs in various biomedical applications. In addition, we also discuss# the current challenges and limitations in the use of QDs and propose a few areas of interest for future research.
Localized Increased Permeability of Blood–Brain Barrier for Antibody Conjugates in the Cuprizone Model of Demyelination
Authors: Abakumova Tatiana , Kuzkina Anastasia , Koshkin Philipp , Pozdeeva Daria , Abakumov Maxim , Melnikov Pavel , Ionova Klavdia , Gubskii Ilia , Gurina Olga , Nukolova Natalia , Chekhonin Vladimir
Published: August 2023

The development of new neurotherapeutics depends on appropriate animal models being chosen in preclinical studies. The cuprizone model is an effective tool for studying demyelination and remyelination processes in the brain, but blood–brain barrier (BBB) integrity in the cuprizone model is still a topic for debate. Several publications claim that the BBB remains intact during cuprizone-induced demyelination; others demonstrate results that could explain the increased BBB permeability. In this study, we aim to analyze the permeability of the BBB for different macromolecules, particularly antibody conjugates, in a cuprizone-induced model of demyelination. We compared the traditional approach using Evans blue injection with subsequent dye extraction and detection of antibody conjugates using magnetic resonance imaging (MRI) and confocal microscopy to analyze BBB permeability in the cuprizone model. First, we validated our model of demyelination by performing T2-weighted MRI, diffusion tensor imaging, quantitative rt-PCR to detect changes in mRNA expression of myelin basic protein and proteolipid protein, and Luxol fast blue histological staining of myelin. Intraperitoneal injection of Evans blue did not result in any differences between the fluorescent signal in the brain of healthy and cuprizone-treated mice (IVIS analysis with subsequent dye extraction). In contrast, intravenous injection of antibody conjugates (anti-GFAP or non-specific IgG) after 4 weeks of a cuprizone diet demonstrated accumulation in the corpus callosum of cuprizone-treated mice both by contrast-enhanced MRI (for gadolinium-labeled antibodies) and by fluorescence microscopy (for Alexa488-labeled antibodies). Our results suggest that the methods with better sensitivity could detect the accumulation of macromolecules (such as fluorescent-labeled or gadolinium-labeled antibody conjugates) in the brain, suggesting a local BBB disruption in the demyelinating area. These findings support previous investigations that questioned BBB integrity in the cuprizone model and demonstrate the possibility of delivering antibody conjugates to the corpus callosum of cuprizone-treated mice.
Early and Late Transcriptomic and Metabolomic Responses of Rhododendron ‘Xiaotaohong’ Petals to Infection with Alternaria sp.
Authors: Zhang Xi-Min , Li Jie-Ting , Xia Ying , Shi Xiao-Qian , Liu Xian-Lun , Tang Ming , Tang Jing , Sun Wei , Yi Yin
Published: August 2023

In recent years, petal blight disease caused by pathogens has become increasingly epidemic in Rhododendron. Breeding disease-resistant rhododendron is considered to be a more environmentally friendly strategy than is the use of chemical reagents. In this study, we aimed to investigate the response mechanisms of rhododendron varieties to petal blight, using transcriptomics and metabolomics analyses. Specifically, we monitored changes in gene expression and metabolite accumulation in Rhododendron ‘Xiaotaohong’ petals infected with the Alternaria sp. strain (MR-9). The infection of MR-9 led to the development of petal blight and induced significant changes in gene transcription. Differentially expressed genes (DEGs) were predominantly enriched in the plant–pathogen interaction pathway. These DEGs were involved in carrying out stress responses, with genes associated with H2O2 production being up-regulated during the early and late stages of infection. Correspondingly, H2O2 accumulation was detected in the vicinity of the blight lesions. In addition, defense-related genes, including PR and FRK, exhibited significant up-regulated expression during the infection by MR-9. In the late stage of the infection, we also observed significant changes in differentially abundant metabolites (DAMs), including flavonoids, alkaloids, phenols, and terpenes. Notably, the levels of euscaphic acid, ganoderol A, (−)-cinchonidine, and theophylline in infected petals were 21.8, 8.5, 4.5, and 4.3 times higher, respectively, compared to the control. Our results suggest that H2O2, defense-related genes, and DAM accumulation are involved in the complex response mechanisms of Rhododendron ‘Xiaotaohong’ petals to MR-9 infection. These insights provide a deeper understanding of the pathogenesis of petal blight disease and may have practical implications for developing disease-resistant rhododendron varieties.
Genetic Mechanisms of Migraine: Insights from Monogenic Migraine Mutations
Authors: Gosalia Helin , Karsan Nazia , Goadsby Peter J.
Published: August 2023

Migraine is a disabling neurological disorder burdening patients globally. Through the increasing development of preclinical and clinical experimental migraine models, advancing appreciation of the extended clinical phenotype, and functional neuroimaging studies, we can further our understanding of the neurobiological basis of this highly disabling condition. Despite increasing understanding of the molecular and chemical architecture of migraine mechanisms, many areas require further investigation. Research over the last three decades has suggested that migraine has a strong genetic basis, based on the positive family history in most patients, and this has steered exploration into possibly implicated genes. In recent times, human genome-wide association studies and rodent genetic migraine models have facilitated our understanding, but most migraine seems polygenic, with the monogenic migraine mutations being considerably rarer, so further large-scale studies are required to elucidate fully the genetic underpinnings of migraine and the translation of these to clinical practice. The monogenic migraine mutations cause severe aura phenotypes, amongst other symptoms, and offer valuable insights into the biology of aura and the relationship between migraine and other conditions, such as vascular disease and sleep disorders. This review will provide an outlook of what is known about some monogenic migraine mutations, including familial hemiplegic migraine, familial advanced sleep-phase syndrome, and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.
Extra Virgin Olive Oil-Based Formulations: A “Green” Strategy against Chlamydia trachomatis
Authors: Di Pietro Marisa , Filardo Simone , Mattioli Roberto , Bozzuto Giuseppina , Molinari Agnese , Mosca Luciana , Sessa Rosa
Published: August 2023

In recent decades, antibiotic misuse has emerged as an important risk factor for the appearance of multi-drug-resistant bacteria, and, recently, antimicrobial resistance has also been described in Chlamydia trachomatis as the leading cause of bacterial sexually transmitted diseases worldwide. Herein, we investigated, for the first time, the antibacterial activity against C. trachomatis of a polyphenolic extract of extra virgin olive oil (EVOO), alongside purified oleocanthal and oleacein, two of its main components, in natural deep eutectic solvent (NaDES), a biocompatible solvent. The anti-chlamydial activity of olive-oil polyphenols (OOPs) was tested in the different phases of chlamydial developmental cycle by using an in vitro infection model. Transmission and scanning electron microscopy analysis were performed for investigating potential alterations of adhesion and invasion, as well as morphology, of chlamydial elementary bodies (EBs) to host cells. The main result of our study is the anti-bacterial activity of OOPs towards C. trachomatis EBs down to a total polyphenol concentration of 1.7 μg/mL, as shown by a statistically significant decrease (93.53%) of the total number of chlamydial-inclusion-forming units (p < 0.0001). Transmission and scanning electron microscopy analysis supported its anti-chlamydial effect, suggesting that OOP might damage the chlamydial outer layers, impairing their structural integrity and hindering EB capability to infect the host cell. In conclusion, OOPs may represent an interesting alternative therapeutic option toward C. trachomatis, although further studies are necessary for exploring its clinical applications.
Water-Soluble Alkali Lignin as a Natural Radical Scavenger and Anticancer Alternative
Authors: Ivanova Donika , Nikolova Galina , Karamalakova Yanka , Semkova Severina , Marutsova Vania , Yaneva Zvezdelina
Published: August 2023

Several phytochemicals, which display antioxidant activity and inhibit cancer cell phenotypes, could be used for cancer treatment and prevention. Lignin, as a part of plant biomass, is the second most abundant natural biopolymer worldwide, and represents approximately 30% of the total organic carbon content of the biosphere. Historically, lignin-based products have been viewed as waste materials of limited industrial usefulness, but modern technologies highlight the applicability of lignin in a variety of industrial branches, including biomedicine. The aims of our preliminary study were to compare the antioxidant properties of water-soluble alkali lignin solutions, before and after UV-B irradiation, as well as to clarify their effect on colon cancer cell viability (Colon 26), applied at low (tolerable) concentrations. The results showed a high antioxidant capacity of lignin solutions, compared to a water-soluble control antioxidant standard (Trolox) and remarkable radical scavenging activity was observed after their UV-B irradiation. Diminishment of cell viability as well as inhibition of the proliferative activity of the colon cancer cell line with an increase in alkali lignin concentrations were observed. Our results confirmed that, due to its biodegradable and biocompatible nature, lignin could be a potential agent for cancer therapy, especially in nanomedicine as a drug delivery system.