bluuebunny/crossref_metadata_2025 huggingface dataset:
Single-cell transcriptome revealed dysregulated RNA-binding protein expression patterns and functions in human ankylosing spondylitis
Authors: Ren Zheng , Li Chenyang , Wang Jing , Sui Jiangtao , Ma Yuan
Published: May 2024

Objective

To explore the expression characteristics and regulatory patterns of RBPs in different immune cell types of AS, and to clarify the potential key role of RBPs in the occurrence and development of AS disease.

Methods

PBMC sample data from scRNA-seq (HC*29, AS*10) and bulk RNA-seq (NC*3, AS*5) were selected for correlation analysis.

Results

(1) Compared with the HC group, the numbers of B, DC (dendritic cells), CD14+ Mono and CD8+ T cells were increased in AS group, while the numbers of platelet (platelets), CD8+ NKT, CD16+ Mono (non-classical monocytes), Native CD4+ T and NK were decreased. (2) Through the analysis of RBP genes in B cells, some RBPs were found to play an important role in B cell differentiation and function, such as DDX3X, SFPQ, SRRM1, UPF2. (3) It may be related to B-cell receptor, IgA immunity, NOD-like receptor and other signaling pathways; Through the analysis of RBP genes in CD8+ T cells, some RBPs that play an important role in the immune regulation of CD8+ T were found, such as EIF2S3, EIF4B, HSPA5, MSL3, PABPC1 and SRSF7; It may be related to T cell receptor, TNF, IL17 and other signaling pathways. (4) Based on bulk RNA-seq, it was found that compared with HC and AS patients, differentially expressed variable splicing genes (RASGs) may play an important role in the occurrence and development of AS by participating in transcriptional regulation, protein phosphorylation and ubiquitination, DNA replication, angiogenesis, intracellular signal transduction and other related pathways.

Conclusion

RBPs has specific expression characteristics in different immune cell types of AS patients, and has important regulatory functions. Its abnormal expression and regulation may be closely related to the occurrence and development of AS.
Prospects of liquid biopsy in the prognosis and clinical management of gastrointestinal cancers
Authors: Mondal Deepankar , Shinde Sapnita , Sinha Vibha , Dixit Vineeta , Paul Souvik , Gupta Rakesh Kumar , Thakur Suresh , Vishvakarma Naveen Kumar , Shukla Dhananjay
Published: May 2024

Gastrointestinal (GI) cancers account for one-fourth of the global cancer incidence and are incriminated to cause one-third of cancer-related deaths. GI cancer includes esophageal, gastric, liver, pancreatic, and colorectal cancers, mostly diagnosed at advanced stages due to a lack of accurate markers for early stages. The invasiveness of diagnostic methods like colonoscopy for solid biopsy reduces patient compliance as it cannot be frequently used to screen patients. Therefore, minimally invasive approaches like liquid biopsy may be explored for screening and early identification of gastrointestinal cancers. Liquid biopsy involves the qualitative and quantitative determination of certain cancer-specific biomarkers in body fluids such as blood, serum, saliva, and urine to predict disease progression, therapeutic tolerance, toxicities, and recurrence by evaluating minimal residual disease and its correlation with other clinical features. In this review, we deliberate upon various tumor-specific cellular and molecular entities such as circulating tumor cells (CTCs), tumor-educated platelets (TEPs), circulating tumor DNA (ctDNA), cell-free DNA (cfDNA), exosomes, and exosome-derived biomolecules and cite recent advances pertaining to their use in predicting disease progression, therapy response, or risk of relapse. We also discuss the technical challenges associated with translating liquid biopsy into clinical settings for various clinical applications in gastrointestinal cancers.
The bioelectric mechanisms of local calcium dynamics in cancer cell proliferation: an extension of the A549 in silico cell model
Authors: Langthaler Sonja , Zumpf Christian , Rienmüller Theresa , Shrestha Niroj , Fuchs Julia , Zhou Rui , Pelzmann Brigitte , Zorn-Pauly Klaus , Fröhlich Eleonore , Weinberg Seth H. , Baumgartner Christian
Published: May 2024

Introduction

Advances in molecular targeting of ion channels may open up new avenues for therapeutic approaches in cancer based on the cells’ bioelectric properties. In addition to in-vitro or in-vivo models, in silico models can provide deeper insight into the complex role of electrophysiology in cancer and reveal the impact of altered ion channel expression and the membrane potential on malignant processes. The A549 in silico model is the first computational cancer whole-cell ion current model that simulates the bioelectric mechanisms of the human non-small cell lung cancer cell line A549 during the different phases of the cell cycle. This work extends the existing model with a detailed mathematical description of the store-operated Ca2+ entry (SOCE) and the complex local intracellular calcium dynamics, which significantly affect the entire electrophysiological properties of the cell and regulate cell cycle progression.

Methods

The initial model was extended by a multicompartmental approach, addressing the heterogenous calcium profile and dynamics in the ER-PM junction provoked by local calcium entry of store-operated calcium channels (SOCs) and uptake by SERCA pumps. Changes of cytosolic calcium levels due to diffusion from the ER-PM junction, release from the ER by RyR channels and IP3 receptors, as well as corresponding PM channels were simulated and the dynamics evaluated based on calcium imaging data. The model parameters were fitted to available data from two published experimental studies, showing the function of CRAC channels and indirectly of IP3R, RyR and PMCA via changes of the cytosolic calcium levels.

Results

The proposed calcium description accurately reproduces the dynamics of calcium imaging data and simulates the SOCE mechanisms. In addition, simulations of the combined A549-SOCE model in distinct phases of the cell cycle demonstrate how Ca2+ - dynamics influence responding channels such as KCa, and consequently modulate the membrane potential accordingly.

Discussion

Local calcium distribution and time evolution in microdomains of the cell significantly impact the overall electrophysiological properties and exert control over cell cycle progression. By providing a more profound description, the extended A549-SOCE model represents an important step on the route towards a valid model for oncological research and in silico supported development of novel therapeutic strategies.
Neuroimmunological effects of omega-3 fatty acids on migraine: a review
Authors: Chen Ting-Bin , Yang Cheng-Chia , Tsai I-Ju , Yang Hao-Wen , Hsu Yung-Chu , Chang Ching-Mao , Yang Chun-Pai
Published: May 2024

Migraine is a highly prevalent disease worldwide, imposing enormous clinical and economic burdens on individuals and societies. Current treatments exhibit limited efficacy and acceptability, highlighting the need for more effective and safety prophylactic approaches, including the use of nutraceuticals for migraine treatment. Migraine involves interactions within the central and peripheral nervous systems, with significant activation and sensitization of the trigeminovascular system (TVS) in pain generation and transmission. The condition is influenced by genetic predispositions and environmental factors, leading to altered sensory processing. The neuroinflammatory response is increasingly recognized as a key event underpinning the pathophysiology of migraine, involving a complex neuro-glio-vascular interplay. This interplay is partially mediated by neuropeptides such as calcitonin gene receptor peptide (CGRP), pituitary adenylate cyclase activating polypeptide (PACAP) and/or cortical spreading depression (CSD) and involves oxidative stress, mitochondrial dysfunction, nucleotide-binding domain-like receptor family pyrin domain containing-3 (NLRP3) inflammasome formation, activated microglia, and reactive astrocytes. Omega-3 polyunsaturated fatty acids (PUFAs), particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), crucial for the nervous system, mediate various physiological functions. Omega-3 PUFAs offer cardiovascular, neurological, and psychiatric benefits due to their potent anti-inflammatory, anti-nociceptive, antioxidant, and neuromodulatory properties, which modulate neuroinflammation, neurogenic inflammation, pain transmission, enhance mitochondrial stability, and mood regulation. Moreover, specialized pro-resolving mediators (SPMs), a class of PUFA-derived lipid mediators, regulate pro-inflammatory and resolution pathways, playing significant anti-inflammatory and neurological roles, which in turn may be beneficial in alleviating the symptomatology of migraine. Omega-3 PUFAs impact various neurobiological pathways and have demonstrated a lack of major adverse events, underscoring their multifaceted approach and safety in migraine management. Although not all omega-3 PUFAs trials have shown beneficial in reducing the symptomatology of migraine, further research is needed to fully establish their clinical efficacy and understand the precise molecular mechanisms underlying the effects of omega-3 PUFAs and PUFA-derived lipid mediators, SPMs on migraine pathophysiology and progression. This review highlights their potential in modulating brain functions, such as neuroimmunological effects, and suggests their promise as candidates for effective migraine prophylaxis.
The future in the litter bin – bioconversion of food waste as driver of a circular bioeconomy
Authors: Razouk Afraa , Tiganescu Eduard , von Glahn Anthea Julia , Abdin Ahmad Yaman , Nasim Muhammad Jawad , Jacob Claus
Published: May 2024

Bioconversion of organic waste requires the development and application of rather simple, yet robust technologies capable of transferring biomass into energy and sustainable materials for the future. Food waste plays a significant role in this process as its valorisation reduces waste and at the same time avoids additional exploitation of primary resources. Nonetheless, to literally become “litterate”. extensive research into such robust large-scale methods is required. Here, we highlight some promising avenues and materials which fulfill these “waste to value” requirements, from various types of food waste as sustainable sources for biogas, bioethanol and biodiesel to fertilizers and antioxidants from grape pomace, from old-fashioned fermentation to the magic of anaerobic digestion.
Activity of afatinib in patients with NSCLC harboring novel uncommon EGFR mutations with or without co-mutations: a case report
Authors: Christopoulos Petros , Herster Franziska , Hoffknecht Petra , Falk Markus , Tiemann Markus , Kopp Hans-Georg , Althoff Andre , Stammberger Anja , Laack Eckart
Published: May 2024

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) represent first-line standard of care in unresectable EGFR mutation-positive (EGFRm+) non-small cell lung cancer (NSCLC). However, 10–20% of patients with EGFRm+ NSCLC have uncommon EGFR variants, defined as mutations other than L858R substitutions or exon 19 deletions. NSCLC harboring uncommon EGFR mutations may demonstrate lower sensitivity to targeted agents than NSCLC with L858R or exon 19 deletion mutations. Prospective clinical trial data in patients with NSCLC uncommon EGFR mutations are lacking. Afatinib is a second-generation TKI and the only Food and Drug Administration-approved drug for some of the more prevalent uncommon EGFR mutations. We present a series of seven case reports describing clinical outcomes in afatinib-treated patients with NSCLC harboring a diverse range of extremely rare mutations with or without co-mutations affecting other genes. EGFR alterations included compound mutations, P-loop αC-helix compressing mutations, and novel substitution mutations. We also present a case with NSCLC harboring a novel EGFR::CCDC6 gene fusion. Overall, the patients responded well to afatinib, including radiologic partial responses in six patients during treatment. Responses were durable for three patients. The cases presented are in line with a growing body of clinical and preclinical evidence that indicating that NSCLC with various uncommon EGFR mutations, with or without co-mutations, may be sensitive to afatinib.
Design of a system for detection of non-ferromagnetic metallic foreign bodies based in eddy currents and GMI magnetometer
Authors: Seixas Vinícius Tostes , Barbosa Carlos Roberto Hall , Costa Monteiro Elisabeth
Published: May 2024

A portable magnetic mapping system was designed to determine the three-dimensional location of non-ferromagnetic metallic foreign bodies to ensure fast and successful surgical procedures for their removal. The system is based on the induction of eddy currents in the foreign body by an excitation stage and the measurement of the magnetic field generated by these currents employing a commercially available high-resolution magnetometer based on the Giant Magneto-Impedance effect. The instrument topology is based on decoupling the excitation and measurement stages with a configuration that produces a high primary magnetic field in the foreign body region and a weak one in the GMI sensor region. This feature allows increasing the primary excitation magnetic field without saturating the GMI magnetometer, making it feasible to overcome relevant limitations evidenced in a previously developed instrument proposal. Computational simulations were built considering four possible configurations, with two models of excitation and two options for the magnetometer GMI sensitivity axis orientations. International guidelines for exposure limits to non-ionizing radiation and the principles of biometrology, besides constructive and electrical aspects, were also considered in the system design. The performance analysis of the most promising settings confirmed the viability of the proposed measuring instrument, optimizing the linear operation of the magnetometer during the measurement procedure and contributing to the construction of a complete measurement system prototype, with performance and safety characteristics ensured for the intended biomedical application.
High efficiency continuous-wave Ho: LSO laser wing-pumped by the laser diode at 1.91 μm
Authors: Cui Zheng , Yu Yong , Pan Chao
Published: May 2024

We present a high-efficiency continuous-wave Ho: LSO laser wing-pumped by a 1.91 μm laser diode. The impact of different output transmittances on the laser output power is compared and analyzed. The optimal result was achieved with a −500-mm radius curvature and a 6% transmission output coupler. The maximum output power of the Ho: LSO laser is 7.81 W, with a slope efficiency of 44.7%, a center wavelength of 2,106.6 nm, and beam quality factors of 1.4 in the x-direction and 1.3 in the y-direction.
Walking to a number: is there affective involvement in generating the SNARC effect in numerical cognition?
Authors: Segal Hanna , Tzelgov Joseph , Algom Daniel
Published: May 2024

The effect known as the spatial-numerical association of response codes (SNARC) documents fast reaction to small numbers with a response at the left and to large numbers with a response at the right. The common explanation appeals to a hypothetical mental number line of a left-to-right orientation with the numerical magnitudes on the line activated in an automatic fashion. To explore the possibility of emotional involvement in processing, we employed prototypical affective behaviors for responses in lieu of the usual spatial-numerical ones (i.e., of pressing lateralized keys). In the present series of experiments, the participants walked toward a number or walked away from a number (in a physical approach-avoidance setup) or said “good” or “bad” in response to a number. We recorded strong SNARC effects with affective responding. For example, it took participants longer to say “good” than “bad” to small numbers, but it took them longer to say “bad” than “good” to larger numbers. Although each particular outcome can still be accounted for by a spatial interpretation, the cumulative results are suggestive of the possibly of affective involvement in generating the effect.
Development of an assessment tool for designated medical institutions in China——Based on the application of an online assessment system
Authors: Wang Qian , Dai Ruiming , Yu Qianqian , Zhang Tiantian , Wu Bin
Published: May 2024

Background

Due to the expanding coverage of medical insurance and the growth of medical expenses, the ability to assess the performance of designated medical institutions (DMIs) in supporting the delivery of high-quality patient care and the standardized use of funds represents a priority in China. Despite such interest, there has yet to be an operable standard and labor-saving method for assessing DMIs in China.

Objective

The main objectives include two aspects: (1) establishing an evaluation index system for DMIs based on contracts; (2) designing and developing an online evaluation platform.

Methods

A group of 20 experts with theoretical and practical expertise in medical insurance regulation and performance evaluation were invited to select available indicators. A combination weighting method based on analytic hierarchy process and entropy method was used to determine the weight coefficient. Shanghai was taken as the sample area, and 760 DMIs were included in the empirical research. The test-retest reliability method and criterion-related validity method was used to test the reliability and the validity of the evaluation result.

Results

An assessment index system that included 6 domains and 56 indicators was established in this study. Furthermore, we developed an online platform to assist in the implementation of the assessment. The results showed that the average score of assessment was 94.39, the median was 96.92. The test-retest reliability value was 0.96 (P ≤ 0.01), which indicated high stability of the assessment. In addition, there was a significant negative relationship between assessment score and the penalty amount of DMIs (R = −0.133, P < 0.001). After adjusting for the basic characteristics of medical institutions, the number of visits and revenue, the negative relationship was still significant (B = −0.080, P < 0.05). These results are consistent with expectations, indicating that the assessment had good criterion-related validity.

Conclusions

This study established an operable assessment measure and developed an online platform to assess the performance of DMIs. The results showed good feasibility and reliability in empirical research. Our research findings provided an operable Chinese solution for DMI assessment that saves manpower and time, which would have good enlightening significance in other regions of China and in low-income and middle-income countries internationally.
The effect of continuous geomagnetic storms on enhancements of ultrarelativistic electrons in the Earth’s outer radiation belt
Authors: Chen Jingrun , Tang Chaoling , Chu Xinxin
Published: May 2024

Ultrarelativistic electrons (Ek > 3 MeV) are the most energetic electrons in the Earth’s outer radiation belt, which can cause serious damage to equipments on satellites. The evolutions of ultrarelativistic electrons during geomagnetic storm have been well understood, but the effects of continuous geomagnetic storm on ultrarelativistic electrons are still unclear. Using the data of the Van Allen Probes, we study the evolutions of ultrarelativistic electrons in the Earth’s outer radiation belt during the three continuous geomagnetic storm events. These continuous geomagnetic storm events include the two geomagnetic storms. During the recovery phase of the first geomagnetic storm, enhanced relativistic and ultrarelativistic electrons with lower energies (≥ 3.4 MeV) are observed. These enhanced relativistic electrons could be the source of ultrarelativistic electrons and contribute to ultrarelativistic electron acceleration during the second geomagnetic storm. While 3.4 MeV electrons could be further enhanced during the second geomagnetic storm. During the recovery phase of the second small or moderate geomagnetic storm, ultrarelativistic electrons with higher cutoff energies (≥ 5.2 MeV) and higher fluxes are observed. Compared to an isolated geomagnetic storm with similar solar wind and geomagnetic conditions, ultrarelativistic electrons with higher cutoff energies and higher fluxes are observed during the recovery phase of the second geomagnetic storm. We also find that continuous geomagnetic storm events may contribute even more to enhancements of ultrarelativistic electrons in the outer radiation belt if the second geomagnetic storm is a small or moderate storm with a low solar wind dynamic pressure and short-duration main phase. These can help us to further understand the evolutions of ultrarelativistic electrons in the Earth’s outer radiation belt during geomagnetic storms.
The role, readiness to change and training needs of the Athlete Health and Performance team members to safeguard athletes from interpersonal violence in sport: a mini review
Authors: Gillard Allyson , Mountjoy Margo , Vertommen Tine , Radziszewski Stephanie , Boudreault Véronique , Durand-Bush Natalie , Parent Sylvie
Published: May 2024

Safeguarding athletes from interpersonal violence (IV) in sport is an important topic of concern. Athlete Health and Performance (AHP) team members working with athletes have a professional, ethical, and moral duty to protect the health of athletes, prevent IV, and intervene when it occurs. However, little is known on their respective roles regarding IV in sport and their needs to fulfill their responsibility of safeguarding athletes. The aim of this review is to synthesize knowledge about the roles, readiness to change and training needs of AHP team members to navigate IV in sport. A total of 43 articles are included in the review. Results show that all AHP team members have a role to play in safeguarding athletes and should therefore be trained in the area of IV in sport. Overall, very little research has directly assessed AHP team members' needs to positively foster safety and eliminate IV in sport. There are common training needs for all types of AHP team members such as the ability to recognize signs and symptoms of IV in sport. However, there are also specific needs based on the role of the AHP team members such as ways of facilitating behavioural change for sport managers. Findings from this review are mostly experts' recommendations and should therefore be interpreted as such. The results of the review can guide the development of future research and recommendations.
Sexual and Gender Minority Status and Suicide Mortality: An Explainable Artificial Intelligence Analysis
Authors: Yin Ying , Workman T. Elizabeth , Blosnich John R. , Brandt Cynthia A. , Skanderson Melissa , Shao Yijun , Goulet Joseph L. , Zeng-Treitler Qing
Published: May 2024

Objectives: Suicide risk is elevated in lesbian, gay, bisexual, and transgender (LGBT) individuals. Limited data on LGBT status in healthcare systems hinder our understanding of this risk. This study used natural language processing to extract LGBT status and a deep neural network (DNN) to examine suicidal death risk factors among US Veterans.

Methods: Data on 8.8 million veterans with visits between 2010 and 2017 was used. A case-control study was performed, and suicide death risk was analyzed by a DNN. Feature impacts and interactions on the outcome were evaluated.

Results: The crude suicide mortality rate was higher in LGBT patients. However, after adjusting for over 200 risk and protective factors, known LGBT status was associated with reduced risk compared to LGBT-Unknown status. Among LGBT patients, black, female, married, and older Veterans have a higher risk, while Veterans of various religions have a lower risk.

Conclusion: Our results suggest that disclosed LGBT status is not directly associated with an increase suicide death risk, however, other factors (e.g., depression and anxiety caused by stigma) are associated with suicide death risks.
An Enhanced Particle Swarm Optimization (PSO) Algorithm Employing Quasi-Random Numbers
Authors: Kannan Shiva Kumar , Diwekar Urmila
Published: May 2024

This paper introduces an innovative Particle Swarm Optimization (PSO) Algorithm incorporating Sobol and Halton random number samplings. It evaluates the enhanced PSO’s performance against conventional PSO employing Monte Carlo random number samplings. The comparison involves assessing the algorithms across nine benchmark problems and the renowned Travelling Salesman Problem (TSP). The results reveal consistent enhancements achieved by the enhanced PSO utilizing Sobol/Halton samplings across the benchmark problems. Particularly noteworthy are the Sobol-based PSO improvements in iterations and the computational times for the benchmark problems. These findings underscore the efficacy of employing Sobol and Halton random number generation methods to enhance algorithm efficiency.
A Numerical Investigation of Film Cooling under the Effects of Different Adverse Pressure Gradients
Authors: Shi Jingwei , Hui Zhonghao , Zhou Li , Wang Zhanxue , Liu Yongquan
Published: May 2024

Film cooling needs to be applied to serpentine nozzles due to an increase in thermal load. Adverse pressure gradients (APGs) near the upper wall of such nozzles hinder the forward flow of the coolant, and they may even induce a recirculation zone that complicates the cooling of the film in serpentine nozzles under different APGs. In this study, the film cooling characteristics of a serpentine nozzle under various APGs are investigated through numerical simulations. The studied pressure gradients include strong, moderate, and weak APGs. The results show that the APG weakened the adhesion of the coolant to the surface, thereby reducing the film cooling effectiveness (FCE) and the convective heat transfer coefficient (CHTC). The stronger the APG, the greater its obstructive effect. However, the recirculation zone induced by the strong APG was composed of the coolant, and it adhered tightly to the wall, thereby significantly strengthening the FCE and CHTC. The CHTC under the moderate APG significantly increased due to the convergence of two jets ejected from different holes. For the four blowing ratios, the area-averaged FCE under the strong APG was 29.8% and 24.5% higher than that under the moderate and weak APGs, while the area-averaged ratios of the CHTC under the moderate APG were 1.6% and 16.7% higher than those under the strong and weak APGs. Therefore, more holes should be arranged on the film in the zones of moderate and weak APGs.
Transformative Landscape of Anesthesia Education: Simulation, AI Integration, and Learner-Centric Reforms: A Narrative Review
Authors: Komasawa Nobuyasu
Published: May 2024

This article examines the intersection of simulation-based education and the AI revolution in anesthesia medicine. With AI technologies reshaping perioperative management, simulation education faces both challenges and opportunities. The integration of AI into anesthesia practice offers personalized management possibilities, particularly in preoperative assessment and monitoring. However, the ethical, legal, and social implications necessitate careful navigation, emphasizing patient data privacy and accountability. Anesthesiologists must develop non-technical skills, including ethical decision-making and effective AI management, to adapt to the AI era. The experience-based medical education (EXPBME) framework underscores reflective learning and AI literacy acquisition, fostering lifelong learning and adaptation. Learner-centered approaches are pivotal in anesthesia education, promoting active engagement and self-regulated learning. Simulation-based learning, augmented by AI technologies, provides a dynamic platform for technical and non-technical skills development. Ultimately, by prioritizing non-technical skills, embracing learner-centered education, and responsibly leveraging AI technologies, anesthesiologists can contribute to enhanced patient care and safety in the evolving perioperative landscape.
Antioxidants and Mechanistic Insights for Managing Dry Age-Related Macular Degeneration
Authors: Basyal Deepak , Lee Sooyeun , Kim Hye Jin
Published: May 2024

Age-related macular degeneration (AMD) severely affects central vision due to progressive macular degeneration and its staggering prevalence is rising globally, especially in the elderly population above 55 years. Increased oxidative stress with aging is considered an important contributor to AMD pathogenesis despite multifaceted risk factors including genetic predisposition and environmental agents. Wet AMD can be managed with routine intra-vitreal injection of angiogenesis inhibitors, but no satisfactory medicine has been approved for the successful management of the dry form. The toxic carbonyls due to photo-oxidative degradation of accumulated bisretinoids within lysosomes initiate a series of events including protein adduct formation, impaired autophagy flux, complement activation, and chronic inflammation, which is implicated in dry AMD. Therapy based on antioxidants has been extensively studied for its promising effect in reducing the impact of oxidative stress. This paper reviews the dry AMD pathogenesis, delineates the effectiveness of dietary and nutrition supplements in clinical studies, and explores pre-clinical studies of antioxidant molecules, extracts, and formulations with their mechanistic insights.
Roles of O-GlcNAcylation in Mitochondrial Homeostasis and Cardiovascular Diseases
Authors: Qiu Zhen , Cui Jiahui , Huang Qin , Qi Biao , Xia Zhongyuan
Published: May 2024

Protein posttranslational modifications are important factors that mediate the fine regulation of signaling molecules. O-linked β-N-acetylglucosamine-modification (O-GlcNAcylation) is a monosaccharide modification on N-acetylglucosamine linked to the hydroxyl terminus of serine and threonine of proteins. O-GlcNAcylation is responsive to cellular stress as a reversible and posttranslational modification of nuclear, mitochondrial and cytoplasmic proteins. Mitochondrial proteins are the main targets of O-GlcNAcylation and O-GlcNAcylation is a key regulator of mitochondrial homeostasis by directly regulating the mitochondrial proteome or protein activity and function. Disruption of O-GlcNAcylation is closely related to mitochondrial dysfunction. More importantly, the O-GlcNAcylation of cardiac proteins has been proven to be protective or harmful to cardiac function. Mitochondrial homeostasis is crucial for cardiac contractile function and myocardial cell metabolism, and the imbalance of mitochondrial homeostasis plays a crucial role in the pathogenesis of cardiovascular diseases (CVDs). In this review, we will focus on the interactions between protein O-GlcNAcylation and mitochondrial homeostasis and provide insights on the role of mitochondrial protein O-GlcNAcylation in CVDs.
Evaluation of Antimutagenic and Antioxidant Properties in Fomes fomentarius L.: Potential Development as Functional Food
Authors: Park Chang-Gyun , Lim Heung-Bin
Published: May 2024

Numerous studies derived from medicinal herbs have been conducted to explore bioactive compounds as potential alternatives to synthetic drugs, aiming to mitigate harmful side effects and alleviate economic burdens. In this study, we assessed the safety and potential biological activities of extracts from Fomes fomentarius L. (FFL). The FFL extracts were obtained through various ethanol concentrations, as follows: 0%, 30%, 50%, 70%, and 100%, respectively. All extracts did not induce mutagenicity even up to 5 mg/plate concentration. In the assessment of antioxidant activity, only the hot water extract exhibited weaker antioxidant activity than the other ethanol extracts. Notably, all extracts exhibited significant antimutagenetic effects only with a metabolically active enzyme system (S9 mix). The condition of 70% ethanol extract displayed the most robust antimutagenic activity; thus, the extract was sequentially fractionated with solvents of varying polarities to isolate inhibitory components. After the fractionization, the diethyl ether and butanol fractions effectively suppressed the growth of mutated colonies, suggesting that those such as essential oils, vitamins, alkaloids, and flavonoids can be considered major active compounds. Overall, our study demonstrated that FFL extracts induce potent antioxidant and antimutagenic effects. Further investigations are warranted to verify specific active compounds which induce an antimutagenic effect. Our findings provide valuable insights into FFL as a promising source for potential functional food development.
Antimicrobial Activity of Fungal Endophytes Associated with Peperomia argyreia (Piperaceae)
Authors: Barolo Melisa Isabel , Castelli María Victoria , López Silvia Noelí
Published: May 2024

The endophytic fungal biodiversity of unique plants like Peperomia argyreia (Miq.) É. Morren (Piperaceae) has antimicrobial properties and can be employed for infection treatment. Fungal isolates were obtained from appropriately treated plant tissues cultured in solid media, characterized by morphology, and identified by molecular biology using ITS and NL primers. The antimicrobial properties of fungal extracts were analyzed by combining microdilution and bioautographic assays complemented with metabolic profiling by automated thin-layer chromatography and 1H NMR techniques. Thirty-one filamentous fungi were isolated and characterized by ITS and/or D1/D2 region amplification of rDNA, identified as Thermothielavioides, Trichoderma, Cyphellophora, Cladosporium, Arcopilus, Plectosphaerella; Chaetomium, Sporothrix, Alboefibula, and Penicillium. Thermothielavioides spp. inhibited Staphylococcus aureus ATCC 25923; moreover, Penicillium westlingii P4 showed inhibitory activity on Ascochyta rabiei AR2. The bioactivity-guided fractionation of the EtOAc extract (MIC = 62.5 μg/mL) of P. westlingii P4 allowed the purification of citrinin as the main inhibitory compound (MIC = 62.5 μg/mL). Peperomia argyreia harbors a rich and diverse endophytic community able to produce bioactive molecules. Citrinin, with a minor influence of volatile compounds biosynthesized by P. westlingii P4, was responsible for the inhibition of A. rabiei AR2.
Revolutionizing Sustainable Nonwoven Fabrics: The Potential Use of Agricultural Waste and Natural Fibres for Nonwoven Fabric
Authors: Gaminian Hamdam , Ahvazi Behzad , Vidmar J. John , Ekuere Usukuma , Regan Sharon
Published: May 2024

There has been a growing interest in recycling and upcycling different waste streams due to concerns for environmental protection. This has prompted the desire to develop circular economies and optimize the utilization of bioresources for different industrial sectors. Turning agricultural and forestry waste streams into high-performance materials is a promising and meaningful strategy for creating value-added materials. Lignocellulose fibres from plants are emerging as a potential candidate for eco-friendly feedstock in the textile industry. Nonwoven fabric is one of the most innovative and promising categories for the textile industry since it currently utilizes about 66% synthetic materials. In the upcoming wave of nonwoven products, we can expect an increased utilization of natural and renewable materials, particularly with a focus on incorporating lignocellulosic materials as both binders and fibre components. The introduction of low-cost fibres from waste residue materials to produce high-performance nonwoven fabrics represents a shift towards more environmentally sustainable paradigms in various applications and they represent ecological and inexpensive alternatives to conventional petroleum-derived materials. Here, we review potential technologies for using agricultural waste fibres in nonwoven products.
The Intrarenal Reflux Diagnosed by Contrast-Enhanced Voiding Urosonography (ceVUS): A Reason for the Reclassification of Vesicoureteral Reflux and New Therapeutic Approach?
Authors: Saraga Marijan , Saraga-Babić Mirna , Arapović Adela , Vukojević Katarina , Pogorelić Zenon , Simičić Majce Ana
Published: May 2024

Vesicoureteral reflux (VUR) is defined as the urine backflow from the urinary bladder to the pyelo-caliceal system. In contrast, intrarenal reflux (IRR) is the backflow of urine from the renal calyces into the tubulointerstitial space. VURs, particularly those associated with IRR can result in reflux nephropathy when accompanied by urinary tract infection (UTI). The prevalence of IRR in patients with diagnosed VUR is 1–11% when using voiding cystourethrography (VCUG), while 11.9–61% when applying the contrast-enhanced voiding urosonography (ceVUS). The presence of IRR diagnosed by VCUG often correlates with parenchymal scars, when diagnosed by a 99mTc dimercaptosuccinic acid scan (DMSA scan), mostly in kidneys with high-grade VURs, and when diagnosed by ceVUS, it correlates with the wide spectrum of parenchymal changes on DMSA scan. The study performed by both ceVUS and DMSA scans showed IRRs associated with non-dilated VURs in 21% of all detected VURs. A significant difference regarding the existence of parenchymal damage was disclosed between the IRR-associated and IRR-non-associated VURs. A higher portion of parenchymal changes existed in the IRR-associated VURs, regardless of the VUR grade. That means that kidneys with IRR-associated VURs represent the high-risk group of VURs, which must be considered in the future classification of VURs. When using ceVUS, 62% of places where IRR was found were still unaffected by parenchymal changes. That was the basis for our recommendation of preventive use of long-term antibiotic prophylaxis until the IRR disappearance, regardless of the VUR grade. We propose a new classification of VURs using the ceVUS method, in which each VUR grade is subdivided based on the presence of an IRR.
On the Mechanical Properties and Fracture Patterns of Biphenylene-Based Nanotubes: A Reactive Molecular Dynamics Study
Authors: Armando Hudson Rodrigues , Giozza Wiliam Ferreira , Ribeiro Junior Luiz Antonio , Pereira Junior Marcelo Lopes
Published: May 2024

Carbon-based materials have garnered significant attention since the groundbreaking synthesis of graphene. The exploration of novel 2D carbon allotropes has led to the discovery of materials with intrinsic properties distinct from graphene. Within this context, the biphenylene network (BPN) was successfully synthesized. In this study, we used molecular dynamics (MD) simulations with the Reactive Force Field (ReaxFF) to delve into the thermomechanical properties and fracture patterns of biphenylene-based nanotubes (BPN-NTs) exhibiting armchair (AC-BPN-NT) and zigzag (ZZ-BPN-NT) chiralities. Throughout the longitudinal deformation process, we observed significant morphological transformations preceding the structural fracture of the system. These transformations unfolded in distinct inelastic phases. In both cases, AC- and ZZ-BPN-NT, stress accumulation in four-membered rings led to the creation of octagonal structures; however, in AC, this occurs in the fracture region, subsequently causing the presence of nanopores. On the other hand, for ZZ-BPN-NT, stress accumulation in the rectangular rings occurred in bonds parallel to the deformation, with elongated octagonal structures. The Young’s modulus of these nanotubes ranged from 746 to 1259 GPa, with a melting point of around 4000 K. Our results also explore the influence of diameter and curvature, drawing comparisons with BPN monolayers.
Macrophages Orchestrate the Liver Tumor Microenvironment
Authors: Quaranta Valeria , Ballarò Costanza , Giannelli Gianluigi
Published: May 2024

Liver cancer is one of the leading causes of cancer-related mortality. Hepatocellular carcinoma and cholangiocarcinoma are the most common types, and despite numerous advances, therapeutic options still remain poor for these cancer patients. Tumor development and progression strictly depend on a supportive tumor microenvironment (TME). Tumor-associated macrophages (TAMs) are the most abundant immune cells population within a tumorigenic liver; they sustain cancer cells’ growth and invasiveness, and their presence is correlated with a poor prognosis. Furthermore, TAM cross-talk with cells and components of the TME promotes immunosuppression, a desmoplastic response, and angiogenesis. In this review, we summarize the latest advances in understanding TAM heterogeneity and function, with a particular focus on TAM modulation of the TME. We also discuss the potential of targeting macrophage subpopulations and how this is now being exploited in current clinical trials for the treatment of liver cancer.
Effects on the Physical Functioning of Two Exercise Interventions in Patients with Multiple Myeloma: A Pilot Feasibility Study
Authors: Hillengass Jens , Hillengass Michaela , Joseph Janine M. , Attwood Kristopher , Cannioto Rikki , Jacobson Hillary , Miller Carolyn , Wittmeyer Bryan , Moysich Kirsten
Published: May 2024

Because of the high prevalence of bone destruction in patients with multiple myeloma (MM), physical exercise is oftentimes discouraged by healthcare providers. The goal of this prospective trial was to investigate the feasibility of two six-month exercise interventions in patients with MM (N = 42): a remotely prompted home-based walking intervention or a supervised strength training intervention. Physical function and pain were assessed with the Activity Measure for Post-Acute Care (AM-PAC) Basic Mobility Short Form raw score, a six-minute walk test (6 MWT), a 30-second sit-to-stand test (30 SST), a timed up-and-go (TUG) test, a visual analog scale (VAS) for pain, handheld dynamometer tests, heart rate at rest, blood oxygen saturation at rest, and body mass index. No intervention-related serious adverse events were observed. Adverse events mostly affected the musculoskeletal system. In the resistance training group (n = 24), patients showed significant improvements in AM-PAC, TUG, 6 MWT, and 30 SST, with all effects but the 6 MWT sustained six months after the intervention. The walking group (n = 18) saw improvements in the AM-PAC, TUG, 6 MWT, and 30 SST, with a sustained change in the AM-PAC and TUG. This trial shows the feasibility of both exercise interventions with a sustained beneficial effect on the physical functioning of a six-month strength training intervention and, to a lesser extent, a six-month unsupervised walking intervention. A larger study building on these findings is currently underway.
The Diagnostic Performance of 2-[18F]FDG PET/CT in Identifying Richter Transformation in Chronic Lymphocytic Leukemia: An Updated Systematic Review and Bivariate Meta-Analysis
Authors: Albano Domenico , Rizzo Alessio , Racca Manuela , Muoio Barbara , Bertagna Francesco , Treglia Giorgio
Published: May 2024

Richter transformation is a rare phenomenon characterized by the transformation of cell chronic lymphocytic leukemia (CLL) into a more aggressive lymphoma variant. The early identification of CLLs with a high risk of RT is fundamental. In this field, 2-deoxy-2-[18F]-fluoro-D-glucose positron emission tomography/computed tomography (2-[18F]FDG PET/CT) has been shown to be a non-invasive and promising tool, but apparently, unclear data seem to be present in the literature. This systematic review and bivariate meta-analysis aimed to investigate the diagnostic performance of 2-[18F]FDG PET/CT and its parameters in predicting RT. Between 2006 and 2024, 15 studies were published on this topic, including 1593 CLL patients. Among semiquantitative variables, SUVmax was the most investigated, and the best threshold derived for detecting RT was five. With this cut-off value, a pooled sensitivity of 86.8% (95% CI: 78.5–93.3), a pooled specificity of 48.1% (95% CI: 27–69.9), a pooled negative predictive value of 90.5% (95% CI: 88.4–92.4), a pooled negative likelihood ratio of 0.35 (95% CI: 0.17–0.70), a pooled positive likelihood ratio of 1.8 (95% CI: 1.3–2.4), and a pooled diagnostic odds ratio of 6.7 (3.5–12.5) were obtained. With a higher cut-off (SUVmax = 10), the specificity increased while the sensitivity reduced. The other metabolic features, like metabolic tumor volume, total lesion glycolysis, and radiomic features, were only marginally investigated with controversial evidence.
Amplification of Hippo Signaling Pathway Genes Is Governed and Implicated in the Serous Subtype-Specific Ovarian Carcino-Genesis
Authors: Balakrishnan Karthik , Chen Yuanhong , Dong Jixin
Published: May 2024

Among women, ovarian cancer ranks as the fifth most common cause of cancer-related deaths. This study examined the impact of Hippo signaling pathway on ovarian carcinogenesis. Therefore, the signatures related to Hippo signaling pathway were derived from the molecular signatures database (MSigDB) and were used for further analysis. The Z score-based pathway activation scoring method was employed to investigate the expression patterns of these signatures in the mRNA expression profiles of ovarian cancer cohorts. Compared to other subtype tumors, the results of this study show that the Hippo signaling pathway signatures are dysregulated prominently in serous subtype-specific ovarian carcinogenesis. A receiver operating characteristic (ROC) curve-based results of the Hippo gene set, yes-associated protein 1 (YAP1), and mammalian sterile 20-like kinases 1 (MST1) genes can predict the serous subtype tumors by higher specificity and sensitivity with significant areas under the curve values also further reconfirmed these signaling dysregulations. Moreover, these gene sets were studied further for mutation analysis in the profile of high-grade serous ovarian adenocarcinoma in the cBioPortal database. The OncoPrint results reveal that these Hippo signaling pathway genes are amplified highly during the grade three and stage third or fourth of serous type ovarian tumors. In addition, the results of the Dependency Map (DepMap) plot also clearly show that these genes are amplified significantly across the ovarian cancer cell lines. Finally, overall survival (OS) curve plot investigations also revealed that these gene expressions show poor survival patterns linked to highly expressed conditions in serous subtypes of ovarian cancer patients with significant p-values (p < 0.05). Thus, the current finding would help to develop the targeted therapies treatment for serous subtype ovarian carcinogenesis.
Expression of Potential Antibody–Drug Conjugate Targets in Cervical Cancer
Authors: Mallmann Michael R. , Tamir Sina , Alfter Katharina , Ratiu Dominik , Quaas Alexander , Domroese Christian M.
Published: May 2024

(1) Background: There is a huge unmet clinical need for novel treatment strategies in advanced and recurrent cervical cancer. Several cell membrane-bound molecules are up-regulated in cancer cells as compared to normal tissue and have revived interest with the introduction of antibody–drug conjugates (ADCs). (2) Methods: In this study, we characterize the expression of 10 potential ADC targets, TROP2, mesotheline, CEACAM5, DLL3, folate receptor alpha, guanylatcyclase, glycoprotein NMB, CD56, CD70 and CD138, on the gene expression level. Of these, the three ADC targets TROP2, CEACAM5 and CD138 were further analyzed on the protein level. (3) Results: TROP2 shows expression in 98.5% (66/67) of cervical cancer samples. CEACAM5 shows a stable gene expression profile and overall, 68.7% (46/67) of cervical cancer samples are CEACAM-positive with 34.3% (23/67) of cervical cancer samples showing at least moderate or high expression. Overall, 73.1% (49/67) of cervical cancer samples are CD138-positive with 38.8% (26/67) of cervical cancer samples showing at least moderate or high expression. (4) Conclusions: TROP2, CEACAM5 or CD138 do seem suitable for further clinical research and the data presented here might be used to guide further clinical trials with ADCs in advanced and recurrent cervical cancer patients.