bluuebunny/crossref_metadata_2025 huggingface dataset:
Multitasking muscle: engineering iPSC-derived myogenic progenitors to do more
Authors: Hamer Mark Stephen , Rossi Fabio M. V.
Published: January 2025

The generation of myogenic progenitors from iPSCs (iMPs) with therapeutic potential for in vivo tissue regeneration has long been a goal in the skeletal muscle community. Today, protocols enable the production of potent, albeit immature, iMPs that resemble Pax7+ adult muscle stem cells. While muscular dystrophies are often the primary therapeutic target for these cells, an underexplored application is their use in treating traumatic muscle injuries. Notably absent from recent reviews on iMPs is the concept of engineering these cells to perform functions post-transplantation that non-transgenic cells cannot. Here, we highlight protocols to enhance the generation, purification, and maturation of iMPs, and introduce the idea of engineering these cells to perform functions beyond their normal capacities, envisioning novel therapeutic applications.
Discovery of paradoxical genes: reevaluating the prognostic impact of overexpressed genes in cancer
Authors: Liu Dequan , Liu Lei , Che Xiangyu , Wu Guangzhen
Published: January 2025

Oncogenes are typically overexpressed in tumor tissues and often linked to poor prognosis. However, recent advancements in bioinformatics have revealed that many highly expressed genes in tumors are associated with better patient outcomes. These genes, which act as tumor suppressors, are referred to as “paradoxical genes.” Analyzing The Cancer Genome Atlas (TCGA) confirmed the widespread presence of paradoxical genes, and KEGG analysis revealed their role in regulating tumor metabolism. Mechanistically, discrepancies between gene and protein expression-affected by pre- and post-transcriptional modifications-may drive this phenomenon. Mechanisms like upstream open reading frames and alternative splicing contribute to these inconsistencies. Many paradoxical genes modulate the tumor immune microenvironment, exerting tumor-suppressive effects. Further analysis shows that the stage- and tumor-specific expression of these genes, along with their environmental sensitivity, influence their dual roles in various signaling pathways. These findings highlight the importance of paradoxical genes in resisting tumor progression and maintaining cellular homeostasis, offering new avenues for targeted cancer therapy.
Hydroxyurea mitigates diabetic kidney disease through mTOR-S6K signaling pathway in STZ-induced diabetic mice
Authors: Cheng Wanying , Wang Cenzhu , Ma Meican , Zhou Yu
Published: January 2025

Background

Diabetic kidney disease (DKD) is the leading risk factor for end-stage renal disease (ESRD). Hydroxyurea (HU), a sickle cell disease (SCD) drug approved by FDA, shows protective effect in nephropathy. This study aims to understand whether the application of HU could be effective to treat DKD.

Methods

The streptozotocin (STZ)-induced diabetic mice, and high glucose (HG)-treated human renal mesangial cells (HRMCs) were used to investigate the effect of HU on DKD. Serum creatinine and blood urea nitrogen levels reflecting renal function were evaluated. Histology was used to evaluate pathological changes. Indicators of inflammation and apoptosis were detected. Lastly, the mTOR-S6K pathway was explored by detecting the protein expression of S6K and phosphorylated S6K.

Results

In STZ-induced diabetic mice, administration of HU (20 mg/kg) in drinking water for 16 weeks resulted in significant reductions in creatinine and urea nitrogen levels, alongside mitigating histopathological damage. Additionally, HU effectively suppressed the inflammatory response and apoptosis within the kidneys. HRMC cells were cultivated in HG conditions, and HU effectively attenuated the HG-induced inflammation and apoptosis. Moreover, HU treatment significantly inhibited the mTOR signaling pathway in both in both in vivo and in vitro experiments.

Conclusion

This study unveils a new role of HU in alleviating diabetic kidney disease by modulating inflammation and apoptosis through the mTOR-S6K pathway. However, since HU did not significantly affect blood glucose levels, its therapeutic potential may be best realized when used in combination with standard antidiabetic therapies. Such a combination approach could simultaneously address hyperglycemia and renal dysfunction, offering a more comprehensive management strategy for DKD.
Salivary miRNAs and cytokines associated with diagnosis and prognosis of oral squamous cell carcinoma
Authors: Qin Yuxiao , Dong Xiaodan , Li Bo
Published: January 2025

Oral squamous cell carcinoma (OSCC) is the most common malignant tumour in the oral and maxillofacial region. Early diagnosis can significantly improve the 5-year survival rate of patients with OSCC. Therefore, it is extremely important to differentiate OSCC patients early, easily and quickly. Human saliva contains a variety of components that can be used as biomarkers for the diagnosis and prognosis of OSCC. Studies have shown that salivary microRNAs (miRNAs) and cytokines are closely associated with the progression of OSCC. The aim of this review is to summarize the research progress of salivary biomarkers (miRNAs and cytokines) in the past 3 years, and to explore the possibility of using miRNAs and cytokines to improve the diagnosis and prognosis of OSCC.
3D convective flow in a hybrid nanofluid filled bi-truncated-pyramid equipped with adiabatic cylinders
Authors: Almeshaal Mohammed A.
Published: January 2025

This study consists of an investigation of the 3D convective flow of hybrid nanofluids (HNFs) within a bi-truncated pyramid equipped with adiabatic cylinders, with a focus on the enhancement of natural convection (NC) heat transfer (HT). The use of HNFs, which is based on the combination of two different nanoparticles (NPs), provides improved thermal conductivity and stability, and leads to significant advantages in thermal management systems. Numerical simulations based of the FEM were performed to analyze the effects of Rayleigh number (Ra), nanoparticle volume fraction (φ), and cylinders size (D) on the heat transfer and fluid flow (FF) within the pyramid. The results showed that at higher Ra and nanoparticle concentrations a significant enhancement of the HT occurs, and the average Nusselt number (Nua) was increased by up to 23% at a Ra = 106 and φ = 0.045. Concerning the adiabatic cylinders, it was found that the optimal cylinder diameter is D = 0.15, (balance between flow disturbance and heat transfer rate). The outputs of the current study are valuable in the optimization of the hybrid nanofluid applications for advanced thermal management solutions.
Prevalence of the oral pathogen Filifactor alocis and its FtxA toxin related to clinical parameters and presence of Aggregatibacter actinomycetemcomitans
Authors: Razooqi Zeinab , Khzam Nabil , L’Hostis Mahina , Belibasakis Georgios N. , Johansson Anders , Oscarsson Jan
Published: January 2025

The Gram-positive organism Filifactor alocis is implicated in multiple oral diseases including periodontitis, and approximately 50% of known strains encode and produce a recently identified repeat-in-toxin (RTX) protein, FtxA, partly homologous to the Aggregatibacter actinomycetemcomitans leukotoxin. By assessing a longitudinal Ghanaian study population of adolescents, we recently identified a possible correlation between F. alocis levels, ftxA gene carriage, and progression of clinical attachment loss (CAL). To extend knowledge on the possible significance of F. alocis and its FtxA in periodontal disease, we have in the present work analyzed saliva samples in an independent cohort of periodontitis (n=156), collected at two private periodontal specialist practices in Perth, Western Australia. The present results corroborate that high loads of F. alocis and the presence of its ftxA gene together are associated with parameters of periodontal tissue destruction and severity. Moreover, among the individuals carrying A. actinomycetemcomitans, a majority also exhibited an ftxA-positive F. alocis, supporting the notion of the synergistic behavior of these two species. This emphasizes that F. alocis and its ftxA are involved in the pathogenesis of periodontitis and may have ecological roles, with diagnostic and prognostic implications for the disease.
Attitudes of Turkish academics towards the effects of digital journalism on shaping the political image
Authors: Malkawi Omar Suleiman Saleh
Published: January 2025

This study aimed to know the nature of the effects of digital journalism in shaping the political mental image of Turkish university professors. It also aimed to know the motives and reasons for their follow-up to digital journalism while following political events around the world. To achieve the objective of the study, the researcher relied on descriptive studies, and within its framework, he used the survey method, by applying the method of a public opinion poll with the sample, and distributed the electronic questionnaire to the study sample, which numbered (103) academic professors working in the universities according to the appropriate sample method. The study reached a set of results, the most important of which was that Most Turkish professors use digital journalism to follow current political events (42.7%). The reason for following political events through digital journalism is that it displays political events quickly (29.0%). Concerning the most prominent digital arts that contribute to the formation of the political mental image, Turkish professors pointed out that the technology of “news” (AVT = 4.01) followed by video technology where “video” (AVT = 3.91) is the most prominent digital arts in forming a political mental image. As for the most prominent element that digital journalism contributes to the formation of its image, the answer was “the image of political events” (Ort. 3.99) and the “parliament” (Org = 3.40) was the lesser victory. On the effects side, “cognitive effects” came first with an average (mean = 2.42), and the item with the highest average cognitive effects “gave me detailed information about the candidates” (AVT = 2.65). The least at all was to “give me different information about MPs” (mean = 1.96). The highest average emotional impact, according to Turkish academics involved in the study, was “saturate my cognitive curiosity about political issues and events” (AVT = 2.11). The statement with the highest average behavioral influences was “It enabled me to follow the speeches and reactions of heads of state in all activities and areas” (AVT = 2.40). Finally, a low positive correlation (0.307**) was found between the effects of the general political mental image and the image of the electoral candidate (p < 0.05), in addition to a low positive correlation between the digital journalism arts and the elements of the general political mental image, where the value of (p < 0.05) was found.
Toward improving precision and complexity of transformer-based cost-sensitive learning models for plant disease detection
Authors: Do Manh-Tuan , Ha Manh-Hung , Nguyen Duc-Chinh , Tzyh-Chiang Chen Oscal
Published: January 2025

Early and accurate detection of plant diseases is crucial for making informed decisions to increase the yield and quality of crops through the decision of appropriate treatments. This study introduces an automated system for early disease detection in plants that enhanced a lightweight model based on the robust machine learning algorithm. In particular, we introduced a transformer module, a fusion of the SPP and C3TR modules, to synthesize features in various sizes and handle uneven input image sizes. The proposed model combined with transformer-based long-term dependency modeling and convolution-based visual feature extraction to improve object detection performance. To optimize a model to a lightweight version, we integrated the proposed transformer model with the Ghost module. Such an integration acted as regular convolutional layers that subsequently substituted for the original layers to cut computational costs. Furthermore, we adopted the SIoU loss function, a modified version of CIoU, applied to the YOLOv8s model, demonstrating a substantial improvement in accuracy. We implemented quantization to the YOLOv8 model using ONNX Runtime to enhance to facilitate real-time disease detection on strawberries. Through an experiment with our dataset, the proposed model demonstrated mAP@.5 characteristics of 80.30%, marking an 8% improvement compared to the original YOLOv8 model. In addition, the parameters and complexity were reduced to approximately one-third of the initial model. These findings demonstrate notable improvements in accuracy and complexity reduction, making it suitable for detecting strawberry diseases in diverse conditions.
Prognostic value of inflammatory markers for all-cause mortality in patients with acute myocardial infarction in the coronary care unit: a retrospective study based on MIMIC-IV database
Authors: Cao Fen , Jiang Jun-jun , Zhang Gui , Liu Jun , Xiao Ping , Tian Yang , Zhang Wei , Zhang Sheng , Hou Feng , Bao Zhong-Wu , Wu Kun , Zhu Yong-zhi
Published: January 2025

Background

Acute myocardial infarction (AMI) is prevalent and perilous, leading to mortality and disability in the coronary care unit (CCU). This paper was to verify the correlation of neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), platelet-to-lymphocyte ratio (PLR), and systemic inflammation response index (SIRI) with all-cause mortality for AMI patients in the CCU.

Methods

Adult patients diagnosed with AMI and admitted to CCU were selected from the MIMIC-IV database. Various clinical and laboratory data were extracted. Logistic regression models were employed to determine the correlation between NLR and in-hospital mortality, 30-day mortality, and 90-day mortality. Confounding factors were adjusted to validate the result robustness. Restricted cubic spline (RCS) curves were adopted to analyze the potential correlation between NLR and all-cause mortality. Meanwhile, the area under the receiver operating characteristic (ROC) curve (AUC) was utilized to compare the prediction ability of NLR, SII, PLR, and SIRI in all-cause mortality. Subsequently, subgroup analyses of gender and comorbidities were performed.

Results

1,386 AMI patients in the CCU were enrolled. The NLR was non-linearly and positively associated with in-hospital mortality [Q4: OR (95%CI) 2.61; (1.261–5.626), p = 0.012], 30-day mortality [Q4: OR (95%CI) 2.005; (1.048–3.925); p = 0.038], 90-day mortality [Q4: OR (95%CI) 2.191; (1.235–3.948); p = 0.008] with Q1 as the reference group. The NLR had the highest AUC for in-hospital mortality, 30-day mortality, and 90-day mortality among four inflammatory markers (NLR, SII, PLR, SIRI). Stratified analyses based on gender and comorbidities showed that the risk of death was significantly increased in male and female patients, with or without diabetes, without cerebral infarction, chronic obstructive pulmonary disease, liver disease, and renal disease in the Q4 group when compared to the Q1 group.

Conclusions

NLR is nonlinearly and positively associated with all-cause mortality of AMI patients in the CCU. The predictive ability of NLR in in-hospital mortality, 30-day mortality, and 90-day mortality is superior to that of SII, PLR, and SIRI.
Grading evaluation methods for lacustrine shale oil resources developed by in-situ heating conversion technology
Authors: Lin Senhu , Luo Xia , Zhao Zhongying , Hou Lianhua , Li Shixiang , Li Hui , Pang Zhenglian , Zhang Lijun
Published: January 2025

In-situ conversion technology is a sustainable and effective method of recovering medium-low maturity shale, which can be produced with oil resources expected to exceed global total proven oil reserves. Nevertheless, criteria and procedures for grading such shale oil resources are lacking. We present a combination of distinct faceis and theoretical economic index (Ie) to grade the in-situ conversion shale oil resources of Chang 7 Member in the Ordos Basin and Nenjiang Formation in the Songliao Basin. This shale oil resource was categorized into four classes: invalid, valid, sweet-spot and core resource. For the shale dominated by type II kerogen (Chang 7), total organic carbon (TOC) values at 6%, 9%, and 12%, hydrocarbon generation potential (S1+S2) values at 15 mg/g, 30 mg/g, and 50 mg/g, and Ie at 2, 3, and 4, respectively, represent the boundary of the four resource grades. For the shale dominated by type Ⅰ kerogen (Nenjiang), TOC values at 4%, 6%, and 8%, S1+S2 values at 19 mg/g, 32 mg/g, 48 mg/g, and Ie at 2, 3, and 4, respectively, represent the boundary of the four resource grades. Our research provides a feasible practical strategy for evaluating and predicting in-situ conversion shale oil resources in lacustrine basins.
Identifying sources of preservice teachers’ dyslexia knowledge to guide teacher education
Authors: Chambre Susan J. , Anderson Alida
Published: January 2025

This paper presents findings from an exploratory descriptive qualitative inquiry of preservice teachers’ (PSTs’) self-reported dyslexia knowledge sources. The purpose of this research is to provide a baseline understanding of how and where PSTs’ understandings of dyslexia originate to inform teacher educators about sources of misconceptions and to support PSTs’ conceptual growth about dyslexia. Seventy-six PSTs in the United States completed written responses to online learning module questions about dyslexia knowledge sources. Sources of PSTs’ dyslexia knowledge were identified via thematic coding, to include popular media, friends or acquaintances, college coursework, and family. Findings indicate PSTs’ dyslexia knowledge as stemming from sources that perpetuate misconceptions of dyslexia. Discussion centers on the implications of identifying PSTs’ initial knowledge sources for teacher preparation research and practice by guiding PSTs’ conceptual growth regarding dyslexia.
A study on the carbon emission reduction pathways of China’s digital economy from multiple perspectives
Authors: Shi Xiaoyan , Zhu Zhenhua , Wu Jiaxin , Li Zhijiang
Published: January 2025

As the share of the digital economy’s output continues to rise each year, the emergence of new industries such as e-commerce, mobile payments, and cloud computing has opened new avenues for carbon emission reduction (CER). Based on panel data from 30 provinces in China, this article systematically analyzes the CER pathways of China’s digital economy (DE) from the perspectives of direct effects, indirect effects, threshold effects, and heterogeneity analysis. The main conclusions are as follows: (1) China’s DE has a significant CER effect. (2) The DE can indirectly reduce regional carbon emissions (CE) by industrial structures and technological innovation, with the mediating effect of technological innovation being more significant than that of industrial structure. (3) Urbanization has threshold effects on the CER effect of China’s DE. Under the influence of urbanization, there is an inverted U-shaped relationship between DE and CE. (4) Heterogeneity analysis finds that, compared to other types of provinces, the CER effect of DE is stronger in non-resource-based and economically developed provinces. (5) We propose five tailored recommendations for CER: fostering the synergistic development of the DE and industrial structure, strengthening the role of technological innovation, advancing urbanization and carbon reduction in a differentiated manner, formulating distinct policies for resource-based and non-resource-based provinces, and enhancing the construction of digital infrastructure in less-developed regions. This article not only establishes a more comprehensive connection between the DE and CER, but also reveals the differences in the role of technological innovation, industrial structure optimization, urbanization and other factors in the carbon reduction effect of the DE through the comparison of different paths and mechanisms.
Restoration of phosphate mined lands: literature review with insights from Morocco
Authors: Bourazza Anass , Hassane Sidikou Abdel Aziz , Fenta Berhanu Amsalu , Hirich Abdelaziz
Published: January 2025

Phosphate mining is essential for global agriculture but poses significant environmental challenges, particularly in landscape degradation. This study reviews the current state and trends of phosphate mining, highlighting economic importance, environmental impacts, and sustainability issues. It evaluates restoration techniques, focusing on the effectiveness of various plant species in restoring mined areas. Key factors influencing successful rehabilitation include topsoil management, physico-chemical site characteristics, nutrient bioavailability, topography, and water availability. The study advocates for integrated land management strategies that combine tailored nutrient management plans, erosion control, and water conservation, particularly in arid climates. Strengthening and enforcing regulatory frameworks is crucial to ensure accountability in land rehabilitation, with a focus on sustainability. Recent legal advancements in Morocco aim to modernize mining operations and enhance environmental accountability. The findings recommend increased investment in research to develop innovative rehabilitation techniques and long-term monitoring programs to ensure adaptive management and continuous improvement of restoration outcomes.
DNA-loaded targeted nanoparticles as a safe platform to produce exogenous proteins in tumor B cells
Authors: Grimaldi Maria Cristina , Bozzer Sara , Sjöström Dick J. , Andersson Linnea I. , Mollnes Tom Eirik , Nilsson Per H. , De Maso Luca , Riccardi Federico , Dal Bo Michele , Sblattero Daniele , Macor Paolo
Published: January 2025

Introduction

The functionalization of nanoparticles (NPs) with an antiCD19 targeting mechanism represents a promising approach for the selective delivery of drugs and nucleic acids into normal and tumor B cells. This strategy has the advantage of minimizing off-target effects by restricting gene delivery to the desired cell population. However, the nanoplatform must guarantee both the local production of the protein and the safety of the treatment to allow an effective therapy with reduced systemic toxicity.

Methods

In order to ensure a selective delivery of nucleic acids, we developed poly(lactic-co-glycolic acid) (PLGA)-poly(vinyl alcohol) (PVA) NPs loaded with an Enhanced Green Fluorescent Protein (EGFP)-coding plasmid and covalently coated with antiCD19 recombinant antibody as a targeting mechanism. To assess the functionality of the NPs, physicochemical characterization, safety tests, and transfection assay were employed to evaluate the NPs’ behavior in vitro and in vivo, in a human/zebrafish lymphoma xenograft model.

Results

The results demonstrated that the PLGA-PVA nanoplatform was capable of efficiently encapsulating and releasing the payload. These nanostructures demonstrated a favorable safety profile, as evidenced by the absence of significant cell cytotoxicity, coagulation activation, complement system activation, and the slight activation of endothelial cells and leukocytes. The targeting mechanism facilitated the interaction of NPs with target cells, thereby enhancing their internalization and subsequent exogenous plasmid DNA (pDNA) translation and protein expression. In the human/zebrafish lymphoma xenograft model, no evidence of toxicity was observed, and targeted NPs demonstrated the capacity to enhance exogenous pDNA expression.

Conclusion

Our findings provide a rationale for the use of targeted NPs as a DNA delivery system for the local expression of therapeutic proteins.
Human inborn errors of immunity underlying Talaromyces marneffei infections: a multicenter, retrospective cohort study
Authors: Fan Huifeng , Yang Zhiyong , Wu Yuhui , Lu Xiulan , Li Tian , Lu Xuyang , Lu Gen , He Liming , Lu Guoping , Huang Li
Published: January 2025

Introduction

Talaromyces marneffei (T. marneffei) infections in children can occur secondary to inborn errors of immunity (IEIs). We aimed to investigate the clinical and genetic features of T. marneffei infection in Chinese pediatric patients.

Materials and methods

We retrospectively reviewed 18 pediatric patients with IEIs who were diagnosed with T. marneffei infections at five public hospitals in China from January 2015 to January 2023.

Results

The common clinical features among the patients were fever, cough, and hepatomegaly. The most common severe complications included septic shock, hemophagocytic lymphohistiocytosis (HLH), and acute respiratory distress syndrome (ARDS). Three cases presented with pan-hypogammaglobulinemia, while three other cases showed heightened levels of IgM. Elevated levels of IgE were detected in five cases, and six cases exhibited decreased T lymphocyte absolute counts. Four children were diagnosed with hyperimmunoglobulin M syndrome (HIGM) due to CD40LG mutations, three cases had severe combined immunodeficiency (SCID), and five were diagnosed with hyper-IgE syndrome (HIES). Gain-of-function (GOF) mutations in STAT1 led to STAT1 GOF in four cases. One patient was diagnosed with caspase-recruitment domain (CARD9) deficiency due to a compound mutation in the CARD9 gene, while another patient was confirmed with adenosine deaminase (ADA) deficiency.

Conclusion

T. marneffei infections in children with IEIs induced severe systemic complications. These children commonly exhibited abnormal immunoglobulin levels in peripheral blood, and underlying IEIs associated with T. marneffei infections have enhanced our understanding of the disease.
Cardiovascular toxicity of tisagenlecleucel in children and adolescents: analysis of spontaneous reports submitted to FAERS
Authors: Wang Ganggang , Su Lin , Liu Yanjun , Yang Xiaohan , Li Yi , Mei Qi , Gao Wen
Published: January 2025

Background

The advent of tisagenlecleucel has been a major advance in the pharmacological treatment of relapsed/refractory B-cell acute lymphoblastic leukemia in children and adolescents. However, further research is required to better define its safety profile.

Objectives

To determine the cardiovascular toxicity of tisagenlecleucel in children and adolescents.

Methods

The US Food and Drug Administration’s Adverse Event Reporting System was searched to identify cardiovascular adverse events (CVAEs) related to tisagenlecleucel in pediatric patients up to the age of 18 years.

Results

The median time to onset of tisagenlecleucel-associated CVAEs was shorter than that of tisagenlecleucel-associated non-CVAEs (3 days [interquartile range (IQR) 1, 6] vs. 7 days [IQR 2, 54]). The median time to onset was longer in patients with fatal CVAEs than in those with non-fatal CVAEs (4 days [IQR 1, 12.5] vs. 2 days [IQR 1, 4]). The most frequently reported CVAEs were mitral valve disease, hypotension, and capillary leak syndrome. Patients who developed shock had the highest mortality rate (66.67%). Concomitant use of medication for a neurological disorder was an independent risk factor for CVAEs, and concomitant use of medication for a respiratory disease was an independent risk factor for fatal CVAEs. Most CVAEs were associated with cytokine release syndrome, and older patients had a more favorable prognosis.

Conclusions

Children and adolescents who receive tisagenlecleucel should be closely monitored for CVAEs, particularly during the first week of treatment.
PDL1 inhibitors may be associated with a lower risk of allograft rejection than PD1 and CTLA4 inhibitors: analysis of the WHO pharmacovigilance database
Authors: Gérard Alexandre O. , Merino Diane , Benzaquen Jonathan , Destere Alexandre , Borchiellini Delphine , Gosset Clément , Rocher Fanny , Andreani Marine , Marquette Charles-Hugo , Montaudié Henri , Drici Milou-Daniel , Sicard Antoine
Published: January 2025

Background

Transplant recipients face increased cancer mortality due to immunosuppressive treatments. Immune checkpoint inhibitors (ICI) have improved survival rates, but data on the use of these agents in transplant recipients is scarce. ICI may trigger allograft rejection, but the absolute risk of AR between the different ICI classes remains to be defined.

Methods

VigiBase® (WHO’s pharmacovigilance database) was queried for reports of AR involving CTLA4, PD1, or PDL1 inhibitors. Disproportionality analysis compares the proportion of reports with a specific adverse drug reaction (ADR) and a given drug to the proportion of reports with the same ADR and other drugs. A lower 95% confidence interval for the Information Component (IC) >0 suggests a signal. The comparative Reporting Odds Ratios (ROR) for AR, between PD1 and PDL1 inhibitors, was calculated.

Results

We gathered 159 AR involving an ICI, especially nivolumab (73, 45.9%), mostly affecting kidneys (87, 54.7%). Median time to onset: 28 days. Fatal outcome: 36 reports (22.6%). ICI were significantly associated with AR: IC=1.7 [1.4;1.9]. Specifically, PD1 inhibitors yielded an IC of 2.0 [1.7;2.2] (152 reports observed compared to 38 expected). By contrast, the IC of PDL1 inhibitors was negative: -2.6 [-6.4;-1.0] (1 observed, 9 expected). The comparative ROR of PD1 compared to PDL1 inhibitors was 33.7 [4.7;240.9] (p=0.0005).

Conclusions

We confirm the association between ICI treatment and AR. Notably, PDL1 inhibitors showed surprisingly low AR reports compared to CTLA4 and PD1 inhibitors. Further prospective studies are warranted to confirm whether PDL1 inhibitors indeed reduce AR risk compared to other ICI.
Current status and future prospects of molecular imaging in targeting the tumor immune microenvironment
Authors: Wang Xiang , Shen Weifen , Yao Lingjun , Li Chao , You Huiming , Guo Duancheng
Published: January 2025

Molecular imaging technologies have significantly transformed cancer research and clinical practice, offering valuable tools for visualizing and understanding the complex tumor immune microenvironment. These technologies allow for the non-invasive examination of key components within the tumor immune microenvironment, including immune cells, cytokines, and stromal cells, providing crucial insights into tumor biology and treatment responses. This paper reviews the latest advancements in molecular imaging, with a focus on its applications in assessing interactions within the tumor immune microenvironment. Additionally, the challenges faced by molecular imaging technologies are discussed, such as the need for highly sensitive and specific imaging agents, issues with data integration, and difficulties in clinical translation. The future outlook emphasizes the potential of molecular imaging to enhance personalized cancer treatment through the integration of artificial intelligence and the development of novel imaging probes. Addressing these challenges is essential to fully realizing the potential of molecular imaging in improving cancer diagnosis, treatment, and patient outcomes.
Prodrug-based bispecific antibodies for cancer therapy: advances and future directions
Authors: Ai Zhijuan , Wang Bing , Song Yunlong , Cheng Panpan , Liu Xinlin , Sun Peng
Published: January 2025

Bispecific antibodies represent an innovative paradigm in cancer therapy, offering broader therapeutic potential compared to conventional monoclonal antibodies. To increase tumor selectivity while mitigating off-target effects in normal tissues, the concept of prodrug-based bispecific antibodies has emerged. This review delineates the various mechanisms underlying the action of prodrug-based bispecific antibodies, including protease-mediated activation, steric hindrance release via proteolytic processing, activation by soluble factors, conditional assembly, and chain exchange-mediated activation. We also address the critical challenges that must be overcome to optimize the development and clinical application of these sophisticated therapeutic agents.
The gut microbiome, immune modulation, and cognitive decline: insights on the gut-brain axis
Authors: Zhang Ruyi , Ding Ning , Feng Xicui , Liao Wenli
Published: January 2025

The gut microbiome has emerged as a pivotal area of research due to its significant influence on the immune system and cognitive functions. Cognitive disorders, including dementia and Parkinson’s disease, represent substantial global health challenges. This review explores the relationship between gut microbiota, immune modulation, and cognitive decline, with a particular focus on the gut-brain axis. Research indicates that gut bacteria produce metabolites, including short-chain fatty acids (SCFAs), which affect mucosal immunity, antigen presentation, and immune responses, thereby influencing cognitive functions. A noteworthy correlation has been identified between imbalances in the gut microbiome and cognitive impairments, suggesting novel pathways for the treatment of cognitive disorders. Additionally, factors such as diet, environment, and pharmaceuticals play a role in shaping the composition of the gut microbiome, subsequently impacting both immune and cognitive health. This article aims to clarify the complex interactions among gut microbiota, immune regulation, and cognitive disorders, evaluating their potential as therapeutic targets. The goal is to promote microbiome-based treatments and lay the groundwork for future research in this field.
Applications of cell penetrating peptide-based drug delivery system in immunotherapy
Authors: Du Jing-Jing , Zhang Ru-Yan , Jiang Shangchi , Xiao Shanshan , Liu Yiting , Niu Yongheng , Zhao Wen-Xiang , Wang Dongyuan , Ma XianShi
Published: January 2025

Cell penetrating peptides (CPPs) are usually positive charged peptides and have good cell membrane permeability. Meanwhile, CPPs are facile to synthesize, and can be functionalized to satisfy different demands, such as cyclization, incorporating unnatural amino acids, and lipid conjugation. These properties have made them as efficient drug-delivery tools to deliver therapeutic molecules to cells and tissues in a nontoxic manner, including small molecules, DNA, siRNA, therapeutic proteins and other various nanoparticles. However, the poor serum stability and low tumor targeting ability also hindered their broad application. Besides, inappropriate chemical modification can lead to membrane disruption and nonspecific toxicity. In this paper, we first reviewed recent advances in the CPP applications for cancer therapy via covalent or non-covalent manners. We carefully analyzed the advantages and disadvantages of each CPP modifications for drug delivery. Then, we concluded the recent progress of their clinical trials for different diseases. Finally, we discussed the challenges and opportunities CPPs met to translate into clinical applications. This review presented a new insight into CPPs for drug delivery, which could provide advice on the design of clinically effective systemic delivery systems using CPPs.
Progress in immune microenvironment, immunotherapy and prognostic biomarkers in pediatric osteosarcoma
Authors: Zhang Lin , Jiang Haoming , Ma Haichao
Published: January 2025

Pediatric osteosarcoma, the most prevalent primary malignant bone tumor in children, is marked by aggressive progression and a generally poor prognosis. Despite advances in treatment, including multi-agent chemotherapy, survival rates remain suboptimal, with metastasis, particularly to the lungs, contributing significantly to mortality. The tumor microenvironment plays a crucial role in osteosarcoma progression, with immune cells such as tumor-associated macrophages and T lymphocytes significantly influencing tumor behavior. The immunosuppressive environment, dominated by M2 macrophages, contributes to immune evasion and poor therapeutic outcomes, though recent findings suggest the potential for reprogramming these cells to enhance immune responses. This review provides a comprehensive overview of the immune landscape in pediatric osteosarcoma, with a focus on the role of immune cells and their interactions within the tumor microenvironment (TME). It examines the impact of immune checkpoints, genetic mutations, and inflammatory pathways on osteosarcoma progression, highlighting their contribution to tumor immune evasion and disease advancement. Additionally, emerging immunotherapeutic strategies, such as immune checkpoint inhibitors, macrophage reprogramming, and antibody-based therapies, are summarized in detail, showcasing their potential to improve therapeutic outcomes.
Observed upper-ocean structure and seasonal production in the southern Kerguelen Plateau region, 1994-2021
Authors: Liang Man , Foppert Annie , Westwood Karen J. , Bestley Sophie
Published: January 2025

In the Indian sector of the Southern Ocean, 80°E marks an important transition in ocean circulation between the greater Prydz Bay gyre to the west and the Australian Antarctic gyre to the east. Here, the submarine Kerguelen Plateau impedes the eastward flow of the Antarctic Circumpolar Current (ACC), topographically steering the flow. Enhanced biological productivity associated with the southern plateau supports an important marine ecosystem with many foraging marine predators. We collate ship-based hydrographic data on the vertical structure of the upper water column near 80°E from eight voyages spanning 1994 to 2021, from 58°S towards the Antarctic continent. The study aims to investigate the mixed layer oceanography, the implications for nutrient supply from deep to near-surface waters, and associated biological production. Our results show that the major oceanographic fronts are constrained within the narrow Princess Elizabeth Trough, between the southern Kerguelen Plateau and the Antarctic slope. Therefore, the Southern Boundary and the Southern ACC Front (SACCF) are often co-located, albeit with some interannual variability, with the location of the SACCF ranging from roughly 63°S to 65°S. The average depth of the seasonal mixed layer ranges from 34-49 m, typically deepening from south to north, in association with longer time since sea-ice melt. Below the mixed layer, Winter Water (WW) characteristics also vary across the observed latitudinal range; typically the temperature and thickness of the WW layer are inversely related, with warmer WW layers being thinner. Subsurface nitrate concentrations range from 20-40 µM, while silicate concentrations reach 100 µM. Nutrient drawdown is calculated based on mean concentrations in the mixed layer and WW layer, with drawdown values at individual stations reaching nearly 12 µM and 60 µM for nitrate and silicate, respectively, and a positive correlation between the two. Nutrient drawdown was higher in association with longer time since sea-ice melt and with thinner WW layers, while higher nitrate-based production was associated with deeper mixed layers. Observed relationships between upper water column characteristics and biological processes are discussed in terms of likely nutrient supply mechanisms and seasonal patterns of utilization.
Effectiveness rehabilitative therapy and Pridinol Mesylate in low back pain
Authors: Lauricella Lorenza , Calabrese Noemi , Scaturro Dalila , Migliorino Domenico , Vecchio Michele , Letizia Mauro Giulia
Published: January 2025

Background

Spondylarthritis is a degenerative disease involving the intervertebral disc, vertebral bodies, and adjacent soft tissues. Treatment aims to slow disease progression and manage symptoms through an interdisciplinary approach. It can be conservative and rarely chirurgic.

Objective

This study aimed to evaluate the effectiveness of a rehabilitation combined with Pridinol Mesylate in the treatment of Spondylarthritis in elderly patients in terms of pain resolution, improving disability, and quality of life.

Materials and methods

We conducted a retrospective study on patients with Spondylarthritis. The patients recruited (n = 86) were divided into three groups: the Combined Group (CG:28), who received a rehabilitation combined with Pridinol Mesylate (16 women and 12 men, age 66.4 ± 3.99); the Rehabilitation Group (RG, n = 26), who received only rehabilitation (14 women and 12 men, age 66.2 ± 3.84); and the Drug Group (DG: 32), who received only the administration of the Pridinol(18 women and 14 men, age of 66.3 ± 3.9).

Results

The results show, at T1 (20 days after treatment) in the CG, statistically significant improvements for the NRS and QBPDS. In the RG, statistically significant improvements were observed only for the QBPDS scale. In the DG group, only pain improvement. At T2 (90 days after treatment), the CG showed improvements in NRS, QBPDS, and (SF-36). The RG and DG showed improvements for NRS and for QBPDS. By Bonferroni method, obtained statistically significant values for CG versus RG and for CG versus DG. No statistical significance was found between RG versus DG.

Conclusion

Targeted rehabilitation treatment, combined with Pridinol Mesylate, reduced pain and improved disability in lumbar Spondylarthritis both in the short and medium term, with improved quality of life in elderly patients.
The amplitude of low frequency fluctuation and spontaneous brain activity alterations in age-related macular degeneration
Authors: Zhang Yan Yan , Hu Jin Yu , Ling Qian , Xu San Hua , Kang Min , Wei Hong , Zou Jie , Yi Quanyong , Tan Gang , Shao Yi
Published: January 2025

Background

Wet age-related macular degeneration (wAMD) is a vision-threatening eye disease worldwide. The amplitude of low-frequency fluctuation (ALFF) method was used to observe changes in spontaneous brain activity, which may help to investigate the underlying pathological mechanism of AMD.

Methods

Eighteen patients with wAMD and 18 age- and gender-matched healthy controls (HCs) were recruited. The ALFF method was used on each subject and mean ALFF values were compared between groups. The receiver operating characteristic (ROC) curve was used to compare the two groups.

Results

ALFF values in the temporal lobe and limbic lobe/parahippocampal gyrus were significantly higher than controls, while values in the postcentral gyrus were significantly lower. The under the curve of the ROC (AUC) of the three regions shows high accuracy of the diagnosis.

Conclusion

The abnormal spontaneous brain activity of patients with AMD suggests scope for the use of ALFF in the diagnosis or prognosis in AMD.
Risk factors for new vertebral fractures after percutaneous vertebroplasty or percutaneous kyphoplasty in the treatment of osteoporotic vertebral compression fractures
Authors: Yang Wencheng , Zou Kaiwei , Lin Xuping , Yang Yanfang , Chen Tianpei , Wu Xiuming , Wang Xiaomeng , Liu Qingjun , Huang Chunhui , Su Wanhan
Published: January 2025

Object

This study aims to conduct a prospective analysis of patients with osteoporotic vertebral compression fractures (OVCF) who underwent percutaneous vertebroplasty (PVP) or percutaneous kyphoplasty (PKP), and further analyze the risk factors for new vertebral fracture following treatment.

Methods

A prospective study was conducted from November 2020 to March 2022 at the First Hospital of Longyan City to select patients with OVCF who underwent treatment in the Department of Spinal Surgery. Data collection during the follow-up period focused on various factors that could potentially be associated with new vertebral fractures after PVP/PKP procedures. Patients were divided into two groups based on whether they experienced new vertebral fractures within two years after discharge: the new fracture group (n = 186) and the non-fracture group (n = 64), and statistical analysis was conducted accordingly.

Results

All cases were followed up for 12 to 24 months, with an average of 14.7 months. Differential analysis revealed that age, diabetes, hemoglobin (HB), total protein (TP), serum albumin (ALB), b-C-terminal telopeptide of type I collage (β-CTX), 25-hydroxyvitamin D (25-OH-D3), number of fractured vertebrae, bone mineral density (BMD), regular exercise after discharge, anti-osteoporosis treatment after discharge, cross-sectional area (CSA), and fatty degeneration ratio (FDR) were associated with new vertebral fractures (all P < 0.05). Multivariate analysis showed that age (OR = 1.519, P = 0.032), diabetes (OR = 3.273, P = 0.048), and FDR (OR = 1.571, P = 0.027) were positively associated with the occurrence of new vertebral fractures, while bone mineral density (OR = 0.108, P = 0.044), 25-OH-D3 (OR = 0.871, P = 0.032), CSA (OR = 0.564, P = 0.009), regular postoperative exercise (OR = 0.259, P = 0.025), and osteoporosis treatment (OR = 0.291, P = 0.045) were negatively associated with the occurrence of new vertebral fractures.

Conclusion

Patients with osteoporosis fractures who are older, have poor glycemic control, lower bone mineral density, lower levels of 25-OH-D3, weaker paraspinal muscles, and higher fat infiltration are at increased risk of new vertebral fractures after undergoing PKP/PVP. On the other hand, maintaining regular physical activity and adhering to osteoporosis treatment can help prevent new vertebral fractures.
Perceptions and future perspectives of medical students on the use of artificial intelligence based chatbots: an exploratory analysis
Authors: Gualda-Gea Juan José , Barón-Miras Lourdes Estefanía , Bertran Maria Jesús , Vilella Anna , Torá-Rocamora Isabel , Prat Andres
Published: January 2025

Background

Artificial Intelligence (AI) has made a strong entrance into different fields such as healthcare, but currently, medical degree curricula are not adapted to the changes that adopting these types of tools entitles. It is important to understand the future needs of students to provide the most comprehensive education possible.

Objective

The aim of this teaching improvement project is to describe the knowledge, attitudes, and perspectives of medical students regarding the application of AI and chatbots with patients, also considering their ethical perceptions.

Methods

Descriptive cross-sectional analysis in which the participants were students enrolled in the subject “Preventive Medicine, Public Health and Applied Statistics” during the second semester of the 2023/24 academic year, corresponding to the fifth year of the Degree in Medicine at the University of Barcelona. The students were invited to complete a specific questionnaire anonymously and voluntarily, which they could respond to using their mobile devices by scanning a QR code projected on the classroom screen, we used Microsoft Forms to perform the survey.

Results

Out of the 61 students enrolled in the subject, 34 (56%) attended the seminar, of whom 29 (85%) completed the questionnaire correctly. Of those completing the questionnaire, 20 (69%) had never used chatbots for medical information, 19 (66%) expressed a strong interest in the practical applications of AI in medicine, 14 (48%) indicated elevated concern about the ethical aspects, 17 (59%) acknowledged potential biases in these tools, and 17 (59%) expressed at least moderate confidence in chatbot-provided information. Notably, 24 (83%) agreed that acquiring AI-related knowledge will be essential to effectively perform their future professional roles.

Conclusion

Surveyed medical students demonstrated limited exposure to AI-based tools and showed a mid-level of awareness about ethical concerns, but they recognized the importance of AI knowledge for their careers, emphasizing the need for AI integration in medical education.