bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of an α-calcium sulfate hemihydrate/treated dentin matrix composite to regenerate bone in critically sized SD rat calvarial defects
Authors: Wang Mengmeng , Li Bingyan , Li Wenshuai , Hu Zelong , Fu Haojie , Li Rui
Published: December 2024

Introduction

α-Calcium sulfate hemihydrate (α-CSH) is a widely used artificial bone graft material, but it suffers from rapid deterioration and limited osteoinductivity. This study aims to develop composite cements by combining treated dentin matrix (TDM) with α-CSH to enhance osteogenic properties for the healing of bone deformities.

Methods

The composite cements were prepared by mixing treated dentin matrix (TDM) with α-calcium sulfate hemihydrate (α-CSH) and characterized for their mechanical, morphological, and chemical properties using a universal mechanical testing machine, scanning electron microscopy (SEM), X-ray diffraction (XRD), and Fourier-transform infrared (FTIR) spectroscopy. The biological performance was assessed by measuring osteoblast proliferation using the CCK-8 test and evaluating new bone formation in a calvarial bone defect model in rats.

Results

The compressive strength of the TDM/α-CSH cements decreased with increasing TDM mass ratio, while SEM analysis revealed a distinct three-dimensional porous network structure and increased surface roughness upon thorough mixing. XRD and FTIR studies confirmed the physical mixture of the two materials without phase changes. The TDM/α-CSH composites significantly stimulated osteoblast proliferation, which was dependent on the TDM content, and demonstrated superior enhancement in new bone formation as confirmed by X-ray examination and micro-CT analysis.

Discussion

The findings suggest that TDM/α-CSH composite cements have promising potential as an alternative for repairing bone defects due to their improved mechanical properties, osteoblast proliferation, and enhanced new bone formation in vivo.

Conclusion

TDM/α-CSH composite cements show potential as a novel bone graft material, offering advantages in terms of mechanical strength, osteoconductivity, and osteoinductivity, making them a viable option for bone repair applications.
Innovative approaches in lung tissue engineering: the role of exosome-loaded bioscaffolds in regenerative medicine
Authors: Torkashvand Mohammad , Rezakhani Leila , Habibi Zahra , Mikaeili Abdolhamid , Rahmati Shima
Published: December 2024

Lung diseases account for over four million premature deaths every year, and experts predict that this number will increase in the future. The top cause of death globally is diseases which include conditions like lung cancer asthma and COPD. Treating severe acute lung injury is a complex task because lungs struggle to heal themselves in the presence of swelling inflammation and scarring caused by damage, to the lung tissues. Though achieving lung regeneration, in controlled environments is still an ambition; ongoing studies are concentrating on notable progress, in the field of lung tissue engineering and methods for repairing lung damage. This review delves into methods, for regenerating lungs with a focus on exosome carry bioscaffolds and mesenchymal stem cells among others. It talks about how these new techniques can help repair lung tissue and improve lung function in cases of damage. Also noted is the significance of ex vivo lung perfusion (EVLP), for rejuvenating donor lungs and the healing properties of exosomes in supporting lung regeneration.
Status of diabetes mellitus in different regions of KSA and update on its management
Authors: AL-Rasheedi Mabrouk , Alhazmi Yasir , AlDaiji Lamees Abdullah , AlDaiji Lamya Abdullah , Mobarki Fatimah Ismail , Almuhaysini Khuzama Mohammed , Alshammari Jawza Salem , Almistadi Nouf Awadh , Yoldash Saeed Adnan , Almaqwashi Nouf , Al Abdulgader Rawabi Saleh , Mashyakhi Mohammed Yahya , Alamro Sadin , Walbi Ismail A. , Haider Khawaja Husnain
Published: December 2024

Background

Complications of diabetes and its associated comorbidities can cause rapid progression of type II diabetes mellitus (T2DM). It comes at high costs and affects a patient’s quality of life. We aim to assess T2DM in KSA, including the demographics, medications, complications, and comorbidities, as it remains an integral part of Vision 2030.

Methods

Observational retrospective study was designed spanning five administrative regions of KSA. A total of 638 patients’ records were randomly selected from general hospitals and diabetes centers from 2017 to 2020, and the collected were statistically analyzed.

Results

Most (77%) selected patients had uncontrolled diabetes, showing a statistically significant correlation between regions and diabetes control. The Northern, Central, and Southern regions had the highest uncontrolled percentage with less than 20% control, while Western and Eastern regions’ control percentages were around 40% of subjects. Eighty percent of the uncontrolled BP patients had uncontrolled diabetes contrasting the 68% of the BP-controlled patients. Biguanides, DPP-4 inhibitors, GLP-1 agonists, Insulin, and SGLT-2 inhibitors are the most common diabetes medications. Metformin was the most prescribed in all regions, followed by DPP4. Results showed that patients used one to four non-diabetes drugs on average. Dispensing of vitamin B complex and statins were higher in diabetes centers than in hospitals. Retinopathy and peripheral neuropathy were the most common complications, while hypertension and ASCVD were the most common comorbidities.

Conclusion

Results showed a poor glycemic control situation in the kingdom that necessitates implementing stricter measures to hinder disease progression and reduce complications and comorbidities. Increasing awareness, training, and monitoring programs with larger sample sizes and broader distribution is highly recommended nationally.
Cysteine-rich zinc finger proteins and the nuclear factor kappa-B pathway
Authors: Stoltzfus Andrew T. , Michel Sarah L. J.
Published: December 2024

Inflammation-related disorders, such as autoimmune diseases and cancer, impose a significant global health burden. Zinc finger proteins (ZFs) are ubiquitous metalloproteins which regulate inflammation and many biological signaling pathways related to growth, development, and immune function. Numerous ZFs are involved in the nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB) pathway, associating them with inflammation-related diseases that feature chronically elevated pro-inflammatory cytokines. This review highlights the predominance of ZFs in NFκB-related signaling and summarizes the breadth of functions that these proteins perform. The cysteine-specific post-translational modification (PTM) of persulfidation is also discussed in the context of these cysteine-rich ZFs, including what is known from the few available reports on the functional implications of ZF persulfidation. Persulfidation, mediated by endogenously produced hydrogen sulfide (H2S), has a recently established role in signaling inflammation. This work will summarize the known connections between ZFs and persulfidation and has the potential to inform on the development of related therapies.
ASEAN’s climate change mitigation and adaptation measures: abandoning stagnant policy responses
Authors: Putra Bama Andika
Published: December 2024

Southeast Asia is one of the most at-risk regions when it comes to the impacts of climate change. Densely populated cities and the increasing dependency of the Southeast Asian population on coastal areas make the risk of sea-level rise more prominent for the region. The Association of Southeast Asian Nations (ASEAN) has not been able to match this growing threat with the lack of ideal collective action in terms of mitigating and adapting to climate change. The reliance on the ASEAN State of Climate Change Report and vast ASEAN sectoral bodies have shown stagnant progress. This policy brief recommends (1) imposing adaptation and mitigation measures for ASEAN member states to adopt and (2) elevation of the “climate change’ discourse within ASEAN’s bodies into the category of “existential threat” to abandon ASEAN’s current risk-based perception vis-à-vis climate change. The actionable recommendation for ASEAN would be dependent upon whether the proposed mechanism ensures an alignment with the ASEAN Way (non-interference and consensus in decision-making).
Revisiting Southern Gallo-Romance from a complexity theory standpoint: Occitan
Authors: Léonard Jean Léo
Published: December 2024

In this paper, the inner structure of the Occitan dialect network is revisited in the light of a range of cumulative (Ward’s method) vs. reductive (Complete linkage, Groupe Average, Weighted Average) hierarchical algorithms provided by Gabmap, an Online dialectometric application for calculating distance/similarities by edit distance (Levenshtein algorithm). Reticularity of the Occitan geolinguistic space is addressed through connectograms using Gephi, and Multidimensional Scaling is also used to some extent. After sketching the canonical classifications of the Occitan geolinguistic space (Bec, Ronjat), providing the “eponymous dialects”, we explore the deep patterns of this diasystem, bringing to light a hierarchy of systemic entities constituting an array of “invisible dialects”, corresponding to entities of various size and functions (macrodialects, dialects, subdialects, varieties, hubs, small worlds, buffer zones, default dialects). The approach is based on concrete linguistic data from the THESOC database (Université de Nice/CNRS), contrasting the major isoglosses (macrodialectal features) with the “intricate variables”, i.e., segmental nexi, extracting data relating to strategic points in the complex dialectal network from reductionist algorithms.
Prognostic value of the derived inflammatory marker SIRI in postmenopausal women with coronary artery disease
Authors: Yang Pengli , Xue Rui , Wei Yuhang , Cao Chenxi , Yu Songcheng , Peng Shanling , Zhang Wenjing , Wang Yunzhe , Zheng Yingying , Liu Gangqiong
Published: December 2024

Objective

The aim of this study was to explore the predictive value of the Systemic Inflammatory Response Index (SIRI) for the prognosis of older postmenopausal women with coronary artery disease (CAD).

Patients and methods

This retrospective cohort study included 617 postmenopausal female patients aged 50 years or older with a CAD diagnosis confirmed by coronary angiography seen at the First Affiliated Hospital of Zhengzhou University from January 2019 to December 2020. Patients were divided into three groups based on SIRI tertiles. Primary endpoints were all-cause mortality (ACM) and cardiac mortality (CM), and secondary endpoints were major adverse cardiovascular events (MACEs) and major adverse cardiovascular and cerebrovascular events (MACCEs).

Results

The frequencies of all adverse outcomes were greater in the high level (third tertile) SIRI group than in the low level (first tertile) SIRI group. Multivariable regression analysis showed that compared to the low level SIRI group, the high level SIRI group had a 1.581-fold greater risk of ACM [hazard ratio (HR) = 2.581, 95% confidence interval (CI): 1.045–6.373, p = 0.040) and a 1.798-fold greater risk of CM (HR = 2.798, 95% CI: 0.972–8.060, p = 0.057). In addition, the risks of MACEs and MACCEs were 62.3% (HR = 1.623, 95% CI: 1.123–2.346, p = 0.01) and 55.8% (HR = 1.558, 95% CI: 1.100–2.207, p = 0.012) greater in the high level SIRI group compared with the low level SIRI group. Kaplan–Meier survival analyses confirmed that the high SIRI level was associated with increased risks of ACM (p = 0.001), CM (p = 0.005), MACEs (p = 0.003), and MACCEs (p = 0.005).

Conclusion

This retrospective study demonstrates that the novel derived inflammatory index SIRI can effectively predict the risk of multiple adverse outcomes in postmenopausal women with CAD.
The early and mid-term outcomes of acute type A aortic dissection patients with ECMO
Authors: Meng Qingqing , Jiang Hongkai , Li Tianbao , Pang Shanwen , Zhou Chengbin , Huang Huanlei , Sun Tucheng , Wu Jinlin
Published: December 2024

Background

Acute type A aortic dissection (ATAAD) poses significant challenges in cardiovascular management due to its high morbidity and mortality rates. Postcardiotomy cardiogenic shock (PCS) is a severe complication following ATAAD repair that complicates postoperative recovery. Extracorporeal membrane oxygenation (ECMO) has emerged as a potential life-saving intervention in this context, yet the specific outcomes related to ECMO in ATAAD patients remain insufficiently studied.

Methods

This retrospective single-center study reviewed the medical records of 479 patients who underwent ATAAD surgery from September 2017 to June 2021. Patients were stratified into those requiring postoperative ECMO support and those who did not. Data collected included demographics, operative details, and postoperative outcomes.

Results

Of the cohort, 19 patients (4.0%) required ECMO support. The ECMO group exhibited significantly higher mortality rates (57.9% vs. 5.4%, p < 0.001) and increased complications, including a higher rate of continuous renal replacement therapy (84.2% vs. 24.3%, p < 0.001) and prolonged ICU stays (14.5 days vs. 7.6 days, p = 0.009). Survival analysis demonstrated a stark contrast in 3-year survival rates, with 36.8% for the ECMO group vs. 92.8% for non-ECMO patients (p < 0.001).

Conclusions

ECMO can be a crucial intervention for ATAAD patients suffering from PCS; however, it is associated with significantly higher mortality and complications. Despite lower long-term survival rates compared to non-ECMO patients, ECMO may offer a survival benefit as a salvage therapy. Interpretation is limited by the retrospective single-center design, small ECMO cohort size, and lack of post-discharge quality-of-life data.
Relations of the use of out-of-school suspensions in U.S. public pre-kindergarten programs to neighborhood opportunity
Authors: Fabes Richard A. , Shen Zuchao , Catherine Evandra , McDonald Ashley , Low Sabina , Xie Fuzhe
Published: December 2024

A key goal of the U.S. and its citizens is to promote positive development for young children and their families, particularly those who are marginalized and vulnerable. However, suspending young children from pre-kindergarten (Pre-K) undermines this goal. The primary purpose of the present research was to document the extent to which young children are suspended from Pre-K and how these suspensions are related to the quality of the Pre-K neighborhood. To do this, we used national data from the 26,122 public Pre-K schools in the 2017-2018 Civil Rights Data Collection and examined how the quality of neighborhood resources related to the use of out-of-school suspensions (OSS) for all children, as well as separately for Black and white children, and male and female students. We found that children living in low-opportunity neighborhoods tended to be enrolled in U.S. Pre-K public school programs that had high rates of OSS. We also found that disparities in the rates of use of OSS were greater for Black relative to white students and male relative to female students in Pre-K schools that resided in relatively low-resourced neighborhoods. The findings highlight that one of the ways that neighborhoods influence children's health and well-being is through the disciplinary culture of its schools. The present findings also highlight that disparities in the use of OSS are tied to these neighborhood opportunities and conditions.
Insights into agricultural practices at the Phoenician site of Castro Marim between 7th-5th century BCE
Authors: Paladugu Roshan , Celant Alessandra , Jha Gopesh , Di Rita Federico , de Sousa Elisa , Arruda Ana Margarida , Maurer Anne-France , Magri Donatella , Barrocas Dias Cristina
Published: December 2024

Castro Marim is an Iron Age site from the Algarve region, Portugal. The earliest evidence of settlement, from the Late Bronze Age, dates to the 9th century BCE, with the Phoenician-Punic period dating from the 7th to the 3rd century BCE. This study focuses on the stable isotope analysis of plant and collagen of faunal remains to reconstruct cultivation and husbandry practices. Barley was the most abundantly cultivated cereal crop. The stable isotope results of barley indicate that the primary source of water was natural precipitation and the soil nitrogen was enriched through manuring. Δ13C and δ15N isotope values of stone pine support the previously suggested human management hypothesis. The differences from stable isotope data of domesticated fauna indicate a diverse management strategy for different species based on their economic importance to capitalize from the animal by-products such as wool and dairy products.
Enrichment characteristics and genesis mechanism of critical elements (Nb-Ta-Zr-Hf-REE-Y) in coals: a case study of Late Permian coalfield in Northeastern Guizhou, China
Authors: Ye Ziyi , Li Baoqing , Cao Jialiang
Published: December 2024

The discovery of coal-type beneficial metal deposits and corresponding genesis mechanisms are cutting-edge issues in current sedimentary environment research. Based on industrial analysis, mineralogy, and geochemical measurement of seven typical mines in the Late Permian coalfield of northeastern Guizhou, the enrichment characteristics and mineralization mechanisms of critical metal elements in coal rocks have been revealed in this study. The chemical composition of coal from the Late Permian Wujiaping Formation in northeastern Guizhou is mainly characterized by ultra-low moisture content, medium ash and medium volatile matter yield, and medium high sulfur content. The content of coal-hosted critical metal elements is very high. There are significant differences in elemental composition of coalbeds from different mines, and they are mostly enriched vertically in the coal between and near tonsteins. For example, the K1 coalbed of XX Mine is characterized by Se-Nb-Ta-Zr-Hf enrichment, while the K3 coalbed only has Se enrichment characteristics. TDY Mine has the characteristics of Zr-Nb-Be-Se-Hf-Ta and rare earth element (REE) -Y enrichment. The differences in assemblage type and abundance of critical metal elements in coal rock are mainly controlled by the input of terrestrial detrital materials, environmental conditions, seawater, and hydrothermal fluids. The weathering products of acidic volcanic ash, basalt, and intermediate acidic rocks in the Kangdian Upland provide material sources for the enrichment of critical metal elements. Specifically, the input of intermediate acidic volcanic ash is the main factor for the enrichment of Nb-Ta-Zr-Hf-REY (REE plus Y) in most coal mines. The coastal swamp environment in marine-continental transitional zone, periodic seawater transgression, and hydrothermal fluids control the alteration, transformation, and formation of detrital minerals, affecting the activation and migration of some critical metal elements.
Analyzing click data with AI: implications for student performance prediction and learning assessment
Authors: Borna Mahdi-Reza , Saadat Hanan , Hojjati Aref Tavassoli , Akbari Elham
Published: December 2024

Background

As the intersection of artificial intelligence (AI) and education deepens, predictive analytics using machine learning (ML) and deep learning (DL) models offer novel approaches to assessing student performance in online environments. However, challenges remain in accurately predicting high achievers and identifying students at risk due to limitations in traditional assessment models. This study explores the capabilities of these models in predicting academic achievement and highlights their potential role in reshaping educational assessment paradigms.

Objectives

To evaluate the efficacy of various AI models—including Random Forest, XGBoost, and recurrent neural networks (RNNs)—in identifying at-risk students and differentiating levels of academic achievement, with an emphasis on inclusive and adaptive educational assessments. A key focus is on leveraging these models to create more inclusive and adaptive educational assessments.

Methods

We analyzed a dataset comprising interaction data from the Open University Learning Analytics Dataset (OULAD), which includes clickstream data on student interactions with course materials from over 32,000 students. The models were trained and evaluated using performance metrics such as accuracy, precision, recall, and F1-scores, specifically targeting predictions of student withdrawals and distinctions.

Results

The models effectively identified students at risk of withdrawing, with the Random Forest model achieving an accuracy of 78.68% and deep learning models approximately 77%. However, accurately predicting high achievers posed challenges, suggesting a complex relationship between interaction data and academic success. This limitation underscores the need for more nuanced modeling approaches to improve predictions for top-performing students.

Conclusion

This research demonstrates the promise of AI-driven models in enhancing educational assessments while also highlighting current limitations in capturing academic excellence. Our findings indicate a need for ongoing development of AI tools that are ethically designed and capable of supporting dynamic, inclusive assessment strategies. Future research should focus on incorporating additional factors, such as student motivation and study behaviors, to enhance predictive accuracy, particularly for high achievers. Such advancements can contribute to a more equitable and effective educational landscape.
The who and what of inclusive education—Profiles of student teachers' attitudes toward inclusive education
Authors: Selisko Tom Jannick , Eckert Christine , Perels Franziska
Published: December 2024

The present study investigated the relationship between different attitudes toward inclusive education. It draws from the Framework of Inclusive Education by assuming a reciprocal relationship between learning theory beliefs, models of disability, and the assessment of joined education, resulting in consistent attitudes toward inclusion. The study investigated attitudes toward inclusion by applying a person-centered approach (latent profile analysis; LPA) to a sample of N = 138 student teachers. The results suggest a two-class solution: firstly, a consistent exclusive profile combining higher transmissive beliefs of learning and teaching and a preference for exclusion; secondly, a general inclusive profile that combines support for functional and full inclusion, relational and social models of disability, and a cognitive, constructivist learning theory. The profile distribution appeared to be related to teacher self-efficacy, but not to gender or the educational stage of prospective teaching practice.
Unveiling two decades of forest transition in Anamur, Türkiye: a remote sensing and GIS-driven intensity analysis (2000–2020)
Authors: Aksoy Hasan , Kaptan Sinan , Keçecioğlu Dağli Pelin , Atar Davut
Published: December 2024

Introduction

Monitoring LULC changes is crucial for developing strategies for natural resource management, assessing the current potential of a region, and addressing global environmental issues. In this context, this study examines land use and land cover (LULC) changes in forest and non-forest areas of Anamur district, located in the Mediterranean Region of Türkiye, between 2000 and 2020.

Methods

Using the intensity analysis method, which offers a detailed and efficient approach to understanding LULC changes, the study analyzes transitions at interval, category, and transition levels. LULC maps were generated through supervised classification of Landsat satellite images, focusing on seven classes: Coniferous, Broad-Leaved, Mixed, Treeless Gap, Settlement, Agriculture, and Water. The analysis evaluated changes within and between these categories, interpreting the results through graphical outputs. The driving forces behind these changes were also explored, and their underlying causes were discussed.

Results and Discussion

Results at the interval level revealed that the most significant changes occurred during the 2000-2010 period. At the category level, the Coniferous category exhibited the highest degree of change in both intervals. During 2000-2010, Coniferous gains predominantly replaced non-forest areas (Agriculture, Settlement, and Water), while this pattern was less evident in 2010-2020. In contrast, Treeless Gap gains primarily replaced Coniferous areas during 2010-2020, while no significant losses in Treeless Gap were targeted by other categories. Broad-Leaved species were found to heavily target Water losses, likely due to their higher water demands compared to Coniferous species, as supported by prior studies. This research highlights the advantages of intensity analysis in LULC studies, offering insights into spatial changes and their intensity across categories. It aims to promote its adoption and underscores the importance of targeted conservation and land management strategies to mitigate the impacts of forest loss, land use changes, and water resource pressures.
Subgroup specific transcriptional regulation of salmonid non-classical MHC class I L lineage genes following viral challenges and interferon stimulations
Authors: Imam Maryam , Kianian Atefeh , Bhat Shripathi , Fure Lukes Viktoria Erika , Greiner-Tollersrud Linn , Edholm Eva-Stina
Published: December 2024

Non-classical MHC class I genes which, compared to classical MHC class I, are typically less polymorphic and have more restricted expression patterns are attracting interest because of their potential to regulate immune responses to various pathogens. In salmonids, among the numerous non-classical MHC class I genes identified to date, L lineage genes, including Sasa-LIA and Sasa-LGA1, are differentially induced in response to microbial challenges. In the present study, we show that while transcription of both Sasa-LIA and Sasa-LGA1 are induced in response to SAV3 infection the transcriptional induction patterns are distinct for each gene. While elevated Sasa-LGA1 expression is maintained long-term following in vivo SAV3 infection Sasa-LIA expression is transient, returning to near baseline weeks prior to viral clearance. Furthermore, by contrasting L lineage transcriptional induction potential of SAV3 with that of IPNV we show that Sasa-LIA and Sasa-LGA1 transcriptional induction is tightly interconnected with select type I and type II interferon induction. Both type I and type II interferon stimulation, to varying degrees, induce Sasa-LIA and Sasa-LGA1 expression. Compared to IFNa1 and IFNc, IFN-gamma was a more effective inducer of both Sasa-LIA and Sasa-LGA1 while IFNb showed no activity. Furthermore, IFNa was a more potent inducer of Sasa-LIA compared to IFNc. The involvement of type I IFN and IFN gamma in regulation of Sasa-LIA and Sasa-LGA1 expression was further substantiated by analysis of their respective promoter regions which indicate that ISRE and GAS like elements most likely cooperatively regulate Sasa-LIA expression while IFN gamma induced expression of Sasa-LGA1 is critically dependent on a single, proximally located ISRE element. Together, these findings imply that Sasa-LIA and Sasa-LGA1 play important but likely functionally distinct roles in the anti-viral response of salmonids and that these two molecules may serve as immune regulators promoting more effective antiviral states.
Assessing immunotherapy response: going beyond RECIST by integrating early tumor growth kinetics
Authors: Felfli Mehdi , Thinnes Alexandre , Jacques Sebastien , Liu Yan , Iannessi Antoine
Published: December 2024

Objective

Assess the contribution of early tumor growth dynamics modeling to predict clinical outcomes in non-small cell lung cancer patients receiving immunotherapy, alongside standard RECIST 1.1 criteria.

Methods

Our retrospective studies used data from 861 patients with advanced NSCLC enrolled in three randomized Phase III trials evaluating immunotherapy plus chemotherapy were analyzed. Tumor size measurements up to two follow-up time points were used to fit a novel Gompertz model and estimate growth rate (GR) and kinetic parameters representing depth of response (A), speed of response (B), and long-term modulation (M). Correlations between these early tumor growth parameters and clinical outcomes such as progression-free survival (PFS) and time to response (TTR) were assessed. Descriptive and discriminative analyses were performed to delineate tumor growth dynamics across various response profiles based on RECIST 1.1 criteria.

Results

The novel Gompertz model accurately described early tumor growth kinetics in 861 non-small cell lung cancer patients treated with immunotherapy. Lower growth rate (GR) and model parameter M were associated with longer progression-free survival (PFS) (HR=0.897 and 7.47x10^-7, respectively). Higher GR and parameter A correlated with shorter time to response (HR=0.575 and 0.696, respectively). Responders had significantly lower A (p=1.51e-53) and higher GR (p=0.4e-12) than non-responders. Non-durable stable disease patients had higher GR (p=0.0001) and parameter B (p=0.0002) compared to late responders. Early tumor growth parameters showed potential for predicting long-term outcomes and treatment response patterns.
Evaluation of link between COVID-19 adjacent spike in hydroxychloroquine use and increased reports of pemphigus: a disproportionality analysis of the FDA Adverse Event Reporting System
Authors: Baroukhian Justin , Seiffert-Sinha Kristina , Attwood Kristopher , Sinha Animesh A.
Published: December 2024

Importance

Identifying environmental factors that contribute to disease onset/activity in PV stands to improve clinical outcomes and patient quality of life by strategies aimed at reducing specific disease promoting exposures and promoting personalized clinical management strategies.

Objective

To evaluate the association between hydroxychloroquine use and the development of pemphigus using population level, publicly available, FDA-generated data.

Design

Observational, retrospective, case-control, pharmacovigilance analysis.

Setting

Population based.

Participants

Individuals who either independently or via their healthcare provider submitted a voluntary report of a drug related adverse event to the FDA from Q4 of 2003 to Q2 of 2023.

Exposure

Cases were identified by the presence of adverse events described by the MedDRA preferred term (PT) of “pemphigus” (10034280) and then sorted based on exposure to the drug of interest, hydroxychloroquine, or lack thereof.

Main outcomes and measures

Frequency of hydroxychloroquine exposure among those individuals who reported an adverse event of pemphigus to the FDA; quantification of the reporting odds ratio (ROR).

Results

We identified a total of 2,548 reports that included the adverse event pemphigus; among these, 1,545 (n=706 (41.92%) age 18-64, n=1 age 65-85 years, and n=977 (58.02%) with no age specified; n=1,366 (81.12%) females, n=4 (0.24%) males, and n=314 (18.65%) with no gender specified) included exposure to hydroxychloroquine (ROR, 282.647; 95% CI, 260.951-306.148). We then stratified those reports that included the combination of pemphigus and hydroxychloroquine by gender and found that while the association between the exposure and adverse event remained significant across genders, the magnitude of the effect sizes differed significantly (p<0.001), being over 100-fold greater among females (ROR, 378.7; 95% CI, 339.0-423.1) compared to males (ROR, 3.6; 95% CI, 1.4-9.8).

Conclusions and relevance

The frequency of reports containing the combination of the adverse event pemphigus and exposure to the drug hydroxychloroquine was disproportionately elevated across all genders in the years since the start of the COVID-19 pandemic. The disproportionately elevated frequency of reports of the combination of pemphigus and hydroxychloroquine supports an association between the two, corroborates previous case-report based evidence for such an association, suggests that hydroxychloroquine represents a possible trigger factor for the development of pemphigus, and paves the way for future research that is capable of establishing causality.
Unveiling sialoglycans’ immune mastery in pregnancy and their intersection with tumor biology
Authors: Huang Jianmei , Feng Lu , Huang Jianming , Zhang Guonan , Liao Shixiu
Published: December 2024

Sialylation is a typical final step of glycosylation, which is a prevalent post-translational modification of proteins. Sialoglycans, the products of sialylation, are located on the outmost of cells and participate in pivotal biological processes. They have been identified as glyco-immune checkpoints and are currently under rigorous investigation in the field of tumor research. It is noteworthy that the exploration of sialoglycans in tumor and pregnancy contexts was both initiated in the 1960s. Mechanisms in these two conditions exhibit similarities. Trophoblast infiltration during pregnancy gets controlled, while tumor invasion is uncontrolled. The maternal-fetal immunotolerance balances acceptance of the semiallogeneic fetus and resistance against “non-self” antigen attack simultaneously. Tumors mask themselves with sialoglycans as “don’t eat me” signals to escape immune surveillance. The trophoblastic epithelium is covered with sialoglycans, which have been demonstrated to play an immune regulatory role throughout the entire pregnancy. Immune abnormalities are commonly recognized as an important reason for miscarriages. Therapeutic strategies that desialylation and targeting receptors of sialoglycans have been studied in tumors, while agents that target glyco-immune checkpoints have not been studied in pregnancy. Thus, investigating the roles of sialoglycans in pregnancy and their intersection with tumors may facilitate the development of novel therapies targeting glyco-immune checkpoints for the treatment of pregnancy-related diseases, such as miscarriage and preeclampsia.
Exploration of molecular biomarkers in ankylosing spondylitis transcriptomics
Authors: Ni Yuanpiao , Zhong Linrui , Li Yanhui , Zhang Zeng , Ming Bin , Qing Yufeng , Zhang Quanbo
Published: December 2024

Background

Inflammation of the spine and sacroiliac joints is a hallmark of the chronic, progressive inflammatory illness known as ankylosing spondylitis (AS). The insidious onset and non-specific early symptoms of AS often lead to delays in diagnosis and treatment, which may result in the onset of disability. It is therefore imperative to identify new biomarkers.

Methods

In this study, datasets GSE73754 and GSE25101 were derived from the Gene Expression Omnibus (GEO). Key genes were identified through differential expression analysis and weighted gene co-expression network analysis (WGCNA). A model was then established using LASSO regression, and then it was subjected to the receiver operating characteristic (ROC) curve analysis for evaluation of the diagnostic accuracy of the genes. Subsequently, immune infiltration analysis was conducted to demonstrate the immune infiltration status of the samples and the correlation between key genes and immune infiltration. Finally, the expression levels of key genes in peripheral blood mononuclear cells (PBMCs) and their correlation with clinical indicators were validated via RT-qPCR assay.

Results

Through WGCNA and differential expression analysis, 6 genes were identified. Ultimately, five key genes (ACSL1, SLC40A1, GZMM, TRIB1, XBP1) were determined using LASSO regression. The area under the ROC curve (AUC) for these genes was greater than 0.7, indicating favorable diagnostic performance. Immune infiltration analysis showed that AS was associated with infiltration levels of various immune cells. RT-qPCR validated that the expression of ACSL1, SLC40A1, GZMM, and XBP1 was consistent with the predictive model, whereas TRIB1 expression was contrary to the predictive model. Clinical correlation analysis of key genes revealed that ACSL1 was positively linked to hsCRP levels, GZMM was negatively linked to, hsCRP levels, and neutrophil absolute values, SLC40A1 was positively linked to ESR, hsCRP levels and neutrophil absolute values, and XBP1 was negatively linked to ESR, hsCRP levels, and neutrophil absolute values.

Conclusion

This study identified key genes that may reveal a potential association between AS and ferroptosis, demonstrating high diagnostic value. Furthermore, the expression levels of these genes in peripheral blood mononuclear cells (PBMCs) are strongly correlated with disease activity. These findings not only suggest potential biomarkers for the diagnosis of AS but also offer important references for exploring new therapeutic targets, highlighting their substantial clinical applicability.
A comprehensive overview of tolerogenic vaccine adjuvants and their modes of action
Authors: Arve-Butler Sabine , Moorman Cody Deumont
Published: December 2024

Tolerogenic vaccines represent a therapeutic approach to induce antigen-specific immune tolerance to disease-relevant antigens. As general immunosuppression comes with significant side effects, including heightened risk of infections and reduced anti-tumor immunity, antigen-specific tolerance by vaccination would be game changing in the treatment of immunological conditions such as autoimmunity, anti-drug antibody responses, transplantation rejection, and hypersensitivity. Tolerogenic vaccines induce antigen-specific tolerance by promoting tolerogenic antigen presenting cells, regulatory T cells, and regulatory B cells, or by suppressing or depleting antigen-specific pathogenic T and B cells. The design of tolerogenic vaccines vary greatly, but they all deliver a disease-relevant antigen with or without a tolerogenic adjuvant. Tolerogenic adjuvants are molecules which mediate anti-inflammatory or immunoregulatory effects and enhance vaccine efficacy by modulating the immune environment to favor a tolerogenic immune response to the vaccine antigen. Tolerogenic adjuvants act through several mechanisms, including immunosuppression, modulation of cytokine signaling, vitamin signaling, and modulation of immunological synapse signaling. This review seeks to provide a comprehensive examination of tolerogenic adjuvants currently utilized in tolerogenic vaccines, describing their mechanism of action and examples of their use in human clinical trials and animal models of disease.
Advancements in nanoparticle-based vaccine development against Japanese encephalitis virus: a systematic review
Authors: Adugna Takele , Niu Qingli , Guan Guiquan , Du Junzheng , Yang Jifei , Tian Zhancheng , Yin Hong
Published: December 2024

Vaccination remains the sole effective strategy for combating Japanese encephalitis (JE). Both inactivated and live attenuated vaccines exhibit robust immunogenicity. However, the production of these conventional vaccine modalities necessitates extensive cultivation of the pathogen, incurring substantial costs and presenting significant biosafety risks. Moreover, the administration of live pathogens poses potential hazards for individuals or animals with compromised immune systems or other health vulnerabilities. Subsequently, ongoing research endeavors are focused on the development of next-generation JE vaccines utilizing nanoparticle (NP) platforms. This systematic review seeks to aggregate the research findings pertaining to NP-based vaccine development against JE. A thorough literature search was conducted across established English-language databases for research articles on JE NP vaccine development published between 2000 and 2023. A total of twenty-eight published studies were selected for detailed analysis in this review. Of these, 16 studies (57.14%) concentrated on virus-like particles (VLPs) employing various structural proteins. Other approaches, including sub-viral particles (SVPs), biopolymers, and both synthetic and inorganic NP platforms, were utilized to a lesser extent. The results of these investigations indicated that, despite variations in the usage of adjuvants, dosages, NP types, antigenic proteins, and animal models employed across different studies, the candidate NP vaccines developed were capable of eliciting enhanced humoral and cellular adaptive immune responses, providing effective protection (70–100%) for immunized mice against lethal challenges posed by virulent Japanese encephalitis virus (JEV). In conclusion, prospective next-generation JE vaccines for humans and animals may emerge from these candidate formulations following further evaluation in subsequent vaccine development phases.
Melittin as a therapeutic agent for rheumatoid arthritis: mechanistic insights, advanced delivery systems, and future perspectives
Authors: Pareek Ashutosh , Mehlawat Khushbu , Tripathi Kritika , Pareek Aaushi , Chaudhary Simran , Ratan Yashumati , Apostolopoulos Vasso , Chuturgoon Anil
Published: December 2024

Rheumatoid arthritis (RA), a condition characterized by joint deterioration through the action of matrix metalloproteinases (MMPs), is prevalent worldwide. Bee venom (BV) has traditionally been used in Chinese medicine for pain, arthritis, rheumatism, skin diseases, etc. BV is enriched with active substances, notably melittin and phospholipase A2 (PLA2), offering significant therapeutic potential. Hence, the review summarizes current insights into BV’s composition, antiarthritic mechanism and pharmacological benefits, focusing on melittin. Constituting 50-60% of BV, melittin notably downregulates nuclear factor Kappa B (NF-κB) activity, inhibits MMP-1 and MMP-8, and diminishes tumor necrosis factor (TNF-α), all of which contribute to the mitigation of type 2 collagen degradation. Despite its potential, melittin exhibits hemolytic activity and can significantly affect cell membranes, limiting its application, which poses a challenge to its therapeutic use. To overcome these challenges, delivery techniques utilizing nanocarriers and modifications in amino acid sequencing have been developed. Recent advancements in delivery systems, including nanocarriers, transdermal patches, and nanoemulsions, aim to minimize toxicity, expanding its therapeutic utility for RA. This article explores these novel strategies, underlining the evolving role of melittin in RA management.
Insights into the effects of environmental factors on phytoplankton and microzooplankton at a basin scale: diversity, assembly mechanisms, and co-occurrence networks
Authors: Shen Yanjun , Zhou Xinxin , Zhang Jiaming , Li Qinghua , Zhang Yufeng , Zuo Qing
Published: December 2024

Mastering the characteristics of planktonic microbial communities under the influence of basin-scale environmental factors can provide scientific basis to develop more targeted protection and restoration measures. Here, an environmental DNA metabarcoding technology was applied to investigate the phytoplankton and microzooplankton simultaneously along the whole basin of Jialing River, one of the most important rivers in Southwest China with large scale altitude gradient and water temperature discrepancy. Along the river-way from upper to lower reach, an upward trend in richness of both phytoplankton and microzooplankton was observed with significant positive and negative correlations to water temperature and altitude (Spearman correlation, p < 0.05), respectively. Significant variations in their compositions along the river were also uncovered with Chrysophyta and Foraminifera was potential keystones recognized by the co-occurrence network analysis. Additionally, exponential distance-decay of similarities were detected for both phytoplankton and microzooplankton, which were stronger for phytoplankton. Based on the results of variation partitioning analysis and null model, variations in phytoplankton communities were more governed by environmental selection than those in microzooplankton. Furthermore, the co-occurrence network showed a declining trend in the complexity and stability from the upper to lower reaches. These findings could serve to establish a basis for the investigation of phytoplankton and microzooplankton communities in rivers with multiple artificial modifications.
Effects of dietary lipid levels on growth, antioxidant capacity, intestinal and liver structure of juvenile giant salamander (Andrias davidianus)
Authors: Yan Xiaolu , Pan Lingcheng , Yu Junqi , Wang Shuang , Li Yong , Zhao Min , Zhai Xuliang , Xue Yang , Luo Li
Published: December 2024

This research was to assess how varying dietary lipid levels influence the growth, body composition, antioxidant capacity of the liver, and the structure of liver and intestine in A. davidianus. The juvenile A. davidianus (initial weight of 34.20 ± 0.27g) were given isonitrogenous diets (crude protein 57%) that contained six different levels of lipid (5.02%, 8.96%, 12.90%, 16.21%, 19.46%, and 22.80%, respectively) for 105 days. The results revealed that WGR, SGR, PRR and muscle RNA/DNA ratio were significantly enhanced by dietary lipid level up to 16.21%, beyond which these parameters declined; FCR exhibited an inverse trend(P<0.05). The maximum activity of intestinal digestive enzymes and superoxide dismutase (SOD) were observed at the 16.21% dietary lipid level, accompanied by a significant reduction in liver malondialdehyde (MDA) concentration (P<0.05). With the increase in dietary lipid level, the lipid content of both the whole body and liver, along with skin collagen content, initially improved before subsequently declining(P<0.05). At the 16.21% dietary lipid level, the height, number, and width of intestinal mucosal folds significantly increase (P<0.05), and intestinal microvilli were more orderly arranged. At the 22.80% dietary lipid level, the liver cells exhibited degradation of the cell membrane, alongside an increased presence of autophagosomes; additionally, the mitochondria demonstrated significant swelling and rounding. Optimal lipid level could enhance feed utilization efficiency and promote both intestinal and liver health in A. davidianus. In contrast, high dietary lipid level has a detrimental effect on the health of A. davidianus. According to WGR, skin collagen content, muscle RNA/DNA ratio, total cholesterol (TCHO) and lipase activity, it has been determined through quadratic curve model analysis that the optimal dietary lipid level for juvenile A. davidianus ranges from 13.3% to 17.5%.