bluuebunny/crossref_metadata_2025 huggingface dataset:
Mathematical modeling of a MoSe₂-based SPR biosensor for detecting SARS-CoV-2 at nM concentrations
Authors: Tene Talia , Bonilla García Nataly , Marcatoma Tixi Jessica Alexandra , Dávalos Villegas Martha Ximena , Vacacela Gomez Cristian , Bellucci Stefano
Published: February 2025

The rapid and accurate detection of SARS-CoV-2 remains a critical challenge in biosensing technology, necessitating the development of highly sensitive and selective platforms. In this study, we present a mathematical modeling approach to optimize a MoSe₂-based Surface Plasmon Resonance (SPR) biosensor for detecting the novel coronavirus at nM scale. Using the Transfer Matrix Method (TMM), we systematically optimize the biosensor’s structural parameters, including silver (Ag), silicon nitride (Si₃N₄), molybdenum diselenide (MoSe₂), and thiol-tethered single-stranded DNA (ssDNA) layers, to enhance sensitivity, detection accuracy, and optical performance. The results indicate that an optimized 45 nm Ag layer, 10 nm Si₃N₄ layer, and monolayer MoSe₂ configuration achieves a resonance shift (Δθ) of 0.3° at 100 nM, with a sensitivity of 197.70°/RIU and a detection accuracy of 5.24 × 10⁻2. Additionally, the incorporation of a 10 nm ssDNA functionalization layer significantly enhances molecular recognition, lowering the limit of detection (LoD) to 2.53 × 10⁻5 and improving overall biosensing efficiency. Sys₅ (MoSe₂ + ssDNA) outperforms Sys₄ (MoSe₂ without ssDNA) in terms of specificity and reliability, making it more suitable for practical applications. These findings establish the MoSe₂-based SPR biosensor as a highly promising candidate for SARS-CoV-2 detection, offering a balance between high sensitivity, optical stability, and molecular selectivity, crucial for effective viral diagnostics.
Overview of distinct 8-oxoguanine profiles of messenger RNA in normal and senescent cancer cells
Authors: Huang Jingwen , Lin Yu , Zhao Yingying , Wei Lingbo
Published: February 2025

Background

Cellular senescence plays a key role in the development of cancer, but the underlying mechanisms are unknown. Recently, several recent studies have shown that RNA methylation is closely related to cancer cell aging. 8-Oxoguanine (o8G) is an important and widely distributed methylation modification whose role in cancer cell senescence is far from elucidated.

Methods

In this study, senescent cancer cell models (CaCO2 cells) were constructed by knocking down the ADAR1 gene. RNA immunoprecipitation sequencing was used to identify the o8G peaks on messenger RNA (mRNA) of normal CaCO2 cells and senescent CaCO2 cells, and the distribution characteristics of mRNA o8G modification were identified. Further bioinformatics analysis of the sequencing data was performed to preliminarily elucidate the potential function of the o8G-modified mRNA.

Results

There were significant differences in mRNA o8G modification distribution between normal and senescent CaCO2 cells. It is suggested that o8G modification may play a key role in inducing cancer cells or promoting cancer cell senescence. Gene ontology (GO) enrichment analysis showed that the mRNAs modified by o8G were enriched in Cellular component organization or biogenesis, Focal adhesion, and RNA binding. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the genes modified by o8G are concentrated in Focal adhesion signaling pathway, Small cell lung cancer signaling pathway and Proteoglycans in cancer signaling pathway.

Conclusion

This study preliminarily revealed the different distribution patterns of o8G modification between normal CaCO2 cells and senescent CaCO2 cells. Our study established the link between o8G modification and cancer cell senescence, which provides a new insight into the mechanism of cancer cell senescence and a potential therapeutic target for subsequent cancer treatment.
Multifaceted roles of STING in tumors: from molecular mechanisms to therapeutic strategies
Authors: Hussain Aashiq , Wen Linchun , Wang Rui
Published: February 2025

Since the discovery of Stimulator of Interferon Genes (STING) as a key element in recognizing cytosolic DNA and initiating interferon (IFN) production, substantial research has been conducted to comprehend the precise molecular process of its activation for the treatment of tumor and immune-related diseases. However, new research has enhanced our understanding of STING biology and shown additional major functions of STING that go beyond its capacity to stimulate (Interferon-Stimulated Genes)(ISGs). This mini-review article highlights important details of the established STING biology, including TBK1-IRF3 activation, the NF-κB and MAPK pathway, endoplasmic reticulum (ER) stress and autophagy, and lysosome-induced degradation. We also provide an overview of the independent functions of cGAS and STING, unresolved questions that need to be addressed, and directions for future research.
Long-chain unsaturated free fatty acids reduce the host cell invasion of Listeria monocytogenes outbreak strains
Authors: Borreby Caroline , Hvidtfeldt Thea Amalie , Jespersen Magnus Ganer , T. dos Santos Patricia , Houborg Sofie Dam , Lillebæk Eva Maria Sternkopf , Kemp Michael , Kallipolitis Birgitte H.
Published: February 2025

The Gram-positive bacterium Listeria monocytogenes is a highly adaptable pathogen capable of causing severe foodborne infections, particularly in vulnerable populations. During infection, L. monocytogenes uses a variety of virulence factors to invade and multiply within host cells. The transcriptional regulator PrfA controls the expression of these virulence factors and is essential for the intracellular lifestyle of L. monocytogenes. Long-chain unsaturated free fatty acids (FFAs) have long been recognized for their antimicrobial activity and were recently shown to inhibit PrfA-dependent virulence gene expression in L. monocytogenes. To date, the antimicrobial and anti-virulent activities of FFAs have been primarily studied in laboratory strains. However, to fully evaluate their potential as anti-infective agents, it is essential to assess the effects of long-chain FFAs on clinically relevant isolates, including outbreak strains associated with high-fat food products. Here, we demonstrate that five different clinically relevant L. monocytogenes isolates are sensitive to the antimicrobial activity of long-chain unsaturated FFAs. Furthermore, at subinhibitory concentrations, these FFAs inhibit PrfA-regulated expression of virulence factors across all tested strains and reduce their invasive potential in non-phagocytic cells. These findings underscore the potential of long-chain unsaturated FFAs in developing new preventive strategies against L. monocytogenes strains associated with severe foodborne infections.
Neonatal hypoxia: impacts on the developing mind and brain
Authors: Shabani Nafiseh , Proverbio Alice Mado
Published: February 2025

This review examines the cognitive, emotional, and neurofunctional effects of neonatal hypoxia in both the short and long term. Neonatal hypoxic-ischemic encephalopathy (NHIE) is a critical condition with profound and lasting effects on brain development and function. This mini review examines the structural, cognitive, behavioral, and psychopathological outcomes associated with NHIE, highlighting its impact on neurodevelopment. NHIE is linked to structural abnormalities such as reduced white matter integrity, ventricular enlargement, and damage to key regions including the basal ganglia, hippocampus, and corpus callosum. These changes correlate with long-term impairments in cognition, memory, and motor skills, alongside elevated risks of neurodevelopmental disorders such as autism spectrum disorder (ASD) and attention deficit/hyperactivity disorder (ADHD). Behavioral and emotional challenges, including anxiety, depression, and mood instability, are also prevalent. This review underscores the significant and multifaceted impact of NHIE on neurodevelopmental and behavioral health, emphasizing the importance of developing methodologies to eliminate or minimize neonatal hypoxic states as much as possible.
Two loess landslide at the same hillslope triggered by the Mw 5.9 Minxian-Zhangxian earthquake in China (July 22, 2013): a comparative analysis of landslide mechanisms
Authors: Liu Kun , Wang Lanmin , Sun Junjie , Xu Shunhua , Lu Yuxia , Tian Wentong , Lu Fucun
Published: February 2025

Strong earthquakes and heavy rainfall are recognized as significant triggers of landslides, where the failure characteristics are intricately controlled by internal geological conditions of the slope. This study focuses on the investigation of two landslides triggered by the 2013 Minxian-Zhangye earthquake (Mw = 5.9, USGS). These landslides occurred on the Wamuchi slope, located approximately 22 km east of the epicenter in Minxian County, Gansu Province. Despite being less than 100 m apart, the two landslides exhibited significantly different flow sliding characteristics.The western landslide had a sliding distance of approximately 1.124 km, resulting in 12 fatalities, while the eastern landslide covered a distance of about 340 m.To further analyze the mechanisms of the two landslides and the reasons behind the differences in their flow sliding characteristics, we conducted field investigations and laboratory tests, including drilling, high-density electrical testing, unmanned aerial vehicle photography, and dynamic triaxial testing. A comparative analysis was performed on the landslide morphology, hydrogeological conditions, topography, and site-specific factors for both landslides.The results indicate that both landslides were triggered by a combination of seismic activity and rainfall. However, differing geological, hydrological, and topographical conditions, as well as site-specific influences, led to distinct mechanisms for each landslide, resulting in significant variations in their sliding characteristics.Understanding the initiation and movement mechanisms of such flowslides on slopes is crucial for effective landslide hazard analysis and mitigation strategies.
Swedish medical students’ attitudes toward artificial intelligence and effects on career plans: a survey
Authors: Neittaanmäki Noora
Published: February 2025

Background

The implementation of artificial intelligence (AI), and especially generative AI, is transforming many medical fields, while medical education faces new challenges in integrating AI into the curriculum and is facing challenges with the rise of generative AI chatbots.

Objective

This survey study aimed to assess medical students’ attitudes toward AI in medicine in general, effects of AI in students’ career plans, and students’ use of generative AI in medical studies.

Methods

An anonymous and voluntary online survey was designed using SurveyMonkey and was sent out to medical students at Gothenburg University. It consisted of 25 questions divided into various sections aiming to evaluate the students’ prior knowledge of AI, their use of generative AI during medical studies, their attitude toward AI in medicine in general, and the effect of AI on their career plans.

Results

Of the 172 students who completed the survey, 74% were aware of AI in medicine, and 71% agreed or strongly agreed that AI will improve medicine. One-third were frightened of the increased use of AI in medicine. Radiologists and pathologists were perceived as most likely to be replaced by AI. Interestingly, 37% of the responders agreed or strongly agreed that they will exclude some field of medicine because of AI. More than half argued that AI should be part of medical training. Almost all responders (99%) were aware of generative AI chatbots, and 64% had taken advantage of these in their medical studies. Fifty-eight percent agreed or strongly agreed that the use of AI is supporting their learning as medical students.

Conclusion

Medical students show high expectations for AI’s impact on medicine, yet they express concerns about their future careers. Over a third would avoid fields threatened by AI. These findings underscore the need to educate students, particularly in radiology and pathology, about optimizing human-AI collaboration rather than viewing it as a threat. There is an obvious need to integrate AI into the medical curriculum. Furthermore, the medical students rely on AI chatbots in their studies, which should be taken into consideration while restructuring medical education.
Mapping the global research on project-based learning: a bibliometric and network analysis (2014–2024)
Authors: Mota Fabio Batista , Cabral Bernardo Pereira , Braga Luiza Amara Maciel , Lopes Renato Matos
Published: February 2025

Background

Project-based learning (PjBL) is a widely adopted educational approach known for fostering critical skills such as collaboration, problem-solving, and self-regulated learning. Despite its global implementation across various educational levels and disciplines, there has been limited comprehensive analysis of global research trends in PjBL.

Objective

This study maps the global research on PjBL.

Methods

We used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, bibliometrics, and network analyses to analyze 2,273 peer-reviewed articles indexed in the Web of Science Core Collection and published between January 2014 and August 2024.

Results

Our findings show a significant increase in PjBL research over time, with an 800% growth in publications since 2014. The most frequent keywords are engineering education, higher education, and STEM, and the main research areas are Education and Educational Research, Engineering, and Computer Science. The United States of America, Spain, and China are the leading countries in publications. Additionally, the network analysis shows strong collaborations, particularly between organizations in the USA and Asia.

Conclusion

This study offers a broad understanding of the global research landscape on PjBL, delivering key insights for future studies and promoting collaborative research among organizations worldwide.
Art, music, and play as a teaching aid: applying creative uses of Universal Design for Learning in a prison science class
Authors: Heron Philip J. , Crameri Fabio , Canaletti Elisabetta Febe , Harrison Dalton , Hashemi Sara , Leigh Phoenix , Narayan Sophia , Osowski Kiona , Rantanen Rosa , Williams James A.
Published: February 2025

Science, technology, engineering, and mathematics (STEM) subjects can be rigid in their teaching structure, creating barriers to education for students with more complex learning needs. As a result, there has been an increased need for compassionate pedagogy and adaptive education practices to provide multi-modal learning experiences—often referred to as Universal Design for Learning (UDL). Here, we outline our work in teaching science in prison that applies UDL principles to create different educational access points which are not solely focused on rote learning and reading text (which some students struggle with). We use creative practices, including art, music, and play, as a teaching aid for science subjects such as climate change, sleep, and space exploration. The key findings here being that the application of UDL principles combined to produce a positive classroom experience in a science class—with students feeling more that science is for everyone of every neurotype. Although our work here is tailored to the restrictive prison environment, the application of its core principles to education are fundamental practices that could be beneficial to a wide audience.
Atherogenic Index of Plasma mediates the association between Life’s Crucial 9 with overactive bladder: a secondary data analysis from NHANES
Authors: Gong Hongyang , Lin Xiaomei , Huang Shaoqun
Published: February 2025

Background

Some studies suggest a potential link between cardiovascular health, lipid, and overactive bladder (OAB). Life’s Crucial 9 (LC9) is a recently developed method for assessing cardiovascular health, while the Atherogenic Index of Plasma (AIP) represents a novel marker of atherosclerotic lipid profiles. However, the relationship between Life’s Crucial 9 and overactive bladder and the role of Atherogenic Index of Plasma in the relationship between Life’s Crucial 9 and overactive bladder is unclear. This study investigates the relationship between Life’s Crucial 9 and overactive bladder and evaluates whether Atherogenic Index of Plasma influences this association.

Methods

This study conducted a cross-sectional analysis of 25,628 U.S. participants in the NHANES database from 2005-2018. Firstly, we used multivariate logistic regression to investigate the relationship between Life’s Crucial 9 and overactive bladder. Subsequently, subgroup analysis and restricted cubic splines (RCS) were further used to verify their relationship. Additionally, mediation analysis was conducted to explore the potential role of Atherogenic Index of Plasma levels in the association between Life’s Crucial 9 and overactive bladder.

Results

A total of 25,628 participants were included in this study, among whom 5,150 reported overactive bladder events. After using multivariate logistic regression to adjust for age, sex, race, marital status, education level, poverty-to-income ratio (PIR), smoking, alcohol consumption, hypertension, diabetes, and hypercholesterolemia, a 10-unit increase in Life’s Crucial 9 was associated with a 28% reduction in overactive bladder incidence (OR = 0.72, 95% CI: 0.69-0.76), while a 1-unit increase in Atherogenic Index of Plasma was associated with a 7% increase in overactive bladder incidence (OR = 1.07, 95% CI: 1.01-1.14). Similar results were obtained when Life’s Crucial 9 and Atherogenic Index of Plasma were categorized into tertiles, with a significant trend (P for trend < 0.05). Restricted cubic spline analysis revealed a linear negative correlation between Life’s Crucial 9 and overactive bladder incidence. Mediation analysis further indicated that 6.49% of the relationship between Life’s Crucial 9 and overactive bladder was mediated by Atherogenic Index of Plasma (P = 0.014).

Conclusion

This study found a significant negative correlation between Life’s Crucial 9 and overactive bladder, with Atherogenic Index of Plasma partially mediating this relationship. These findings highlight the potential link between cardiovascular health and overactive bladder, underscoring the role of Life’s Crucial 9 in reducing overactive bladder incidence, possibly through its effects on lowering lipid levels.
Deciphering the drivers of CO2 emissions in Haryana: a comprehensive analysis from 2005 to 2023
Authors: Kumar Parveen , Fatima Nudrat , Khan Muhammad Kamran , Alnafisah Hind
Published: February 2025

This study investigates the key factors influencing CO2 emissions in the state of Haryana from 2005 to 2023, focusing on economic and demographic determinants. Understanding the relationship between economic growth, population dynamics, and environmental impact is crucial for formulating effective sustainable development policies. The study employs a comprehensive dataset where CO2 emissions serve as the dependent variable, while Net State Domestic Product (NSDP) at constant prices, the square of NSDP, population growth, and life expectancy act as independent variables. To ensure robust analysis, stationarity tests are conducted to assess the data properties, followed by Dynamic Ordinary Least Squares (DOLS) and Canonical Cointegration Regression to explore long-run relationships among these variables. Empirical findings indicate a positive and statistically significant relationship between CO2 emissions, NSDP, and population growth, suggesting that economic expansion and population increase drive higher emissions. Conversely, life expectancy exhibits a negative association with CO2 emissions, implying that improvements in public health and longevity may contribute to reduced emissions. The results highlight the environmental challenges posed by economic and demographic growth, emphasizing the need for balanced policy measures that align economic progress with sustainability goals. The unexpected negative relationship between life expectancy and emissions underscores the complex interplay between socioeconomic development and environmental sustainability, warranting further investigation.
How does trade freedom affect the development of clean energy? based on the moderating effect of carbon emissions
Authors: Wu Yan
Published: February 2025

Changes in trade freedom affect national economic development and energy demand, which in turn affects clean energy development. This study assesses the impact of trade freedom on clean energy development in 114 countries from 2006 to 2020. Empirical testing shows that trade freedom significantly inhibits clean energy development in a linear manner. The results also indicate that higher GDP per capita and increased governmental capacity to control corruption are both important factors contributing to clean energy development. In addition, by incorporating mediating mechanisms, this study finds that trade freedom inhibits clean energy development by increasing a country’s innovation and trade openness. Finally, by exploring possible moderating effects, the results show that carbon emissions and bank lending weaken the negative effect of trade freedom on clean energy development, while globalization and government expenditure strengthen this effect. This study offers vital insights to policymakers in balancing the advancement of national trade liberalization policies with clean energy development.
Case Report: A case of progressive encephalopathy with or without lipodystrophy caused by BSCL2 variant and literature review
Authors: Wang Yao , Guo Jing , Zhang Peiqi , Liu Fang , Li Hua
Published: February 2025

Objectives

To describe a case of Progressive Encephalopathy with or without Lipodystrophy (PELD), characterized by a late onset of neurological regression at 9 years old, due to a homozygous c.974dupG variant in the BSCL2 gene.

Methods

An 11-year, 9-month-old girl with repeated seizures over 2 years underwent clinical assessment and genetic investigation. We also reviewed the published literature.

Results

The patient exhibited mild intellectual disability, a lipodystrophic appearance, precocious puberty, voracious appetite, elevated transaminase levels, hyperlipidemia, hypercortisolism, hepatomegaly, fatty liver, and splenomegaly. Motor and cognitive regression occurred at 9 years. A homozygous pathogenic variant c.974dup (p.Ile326HisfsTer12) in exon 7 of BSCL2 (NM_001122955.4) was identified. Despite multiple antiseizure medications, seizures were refractory, leading to status epilepticus and rapid death after genetic diagnosis.

Conclusion

We confirm that the BSCL2 c.974dupG variant is a cause of PELD. Regression may occur later than previously reported. Literature review suggests that the c.974dupG variant may present a milder phenotype compared to the classic c.985C>T variant. Early genetic testing and diagnosis are crucial for improving outcomes in rare neurodegenerative disorders like PELD.
Mixed methods in promoting contraceptive decision-making after voluntary-termination-of-pregnancy
Authors: Palma Sara , São-João Ricardo , Antunes Mónica , Presado Helena
Published: February 2025

Aim

Contraception aims to protect women from unplanned and unwanted pregnancies. The number of voluntary-terminations-of-pregnancy is an indicator that highlights issues such as difficulty accessing health services and women's lack of knowledge about contraceptives. These factors complicate choosing, adhering to, continuing, and achieving satisfaction with a contraceptive method. Mixed studies have gained prominence in health research with significant implications for care quality, particularly in nursing.

Objectives

Analyze the applicability of mixed-method research in promoting contraceptive decision-making for women undergoing voluntary termination of pregnancy.

Methods

A theoretical-reflective essay based on a theoretical framework guiding reflections on mixed research. This reflection explores the basic theoretical constructs of mixed methods and their applicability in promoting contraceptive decision-making for women in the process of voluntary pregnancy termination.

Results

Categories emerging from qualitative study participants' statements were consolidated with quantitative data from women's responses to questionnaires. Integrating these two data types facilitated a robust analysis, discussion, and inference of results, leading to proposals for future interventions.

Conclusions

Due to the advantages of the multimethod approach, we aim to disseminate its use in health research, demonstrating that combining quantitative and qualitative approaches provides greater insights into research phenomena and problems compared to using each method in isolation. This ultimately enhances care quality and contributes to scientific knowledge development.
Crosstalk between ferroptosis and innate immune in diabetic kidney disease: mechanisms and therapeutic implications
Authors: Wang Jinyang , Shi Haonan , Yang Ye , Gong Xueli
Published: February 2025

Diabetic kidney disease (DKD) is a prevalent complication of diabetes mellitus (DM), and its incidence is increasing alongside the number of diabetes cases. Effective treatment and long-term management of DKD present significant challenges; thus, a deeper understanding of its pathogenesis is essential to address this issue. Chronic inflammation and abnormal cell death in the kidney closely associate with DKD development. Recently, there has been considerable attention focused on immune cell infiltration into renal tissues and its inflammatory response’s role in disease progression. Concurrently, ferroptosis—a novel form of cell death—has emerged as a critical factor in DKD pathogenesis, leading to increased glomerular filtration permeability, proteinuria, tubular injury, interstitial fibrosis, and other pathological processes. The cardiorenal benefits of SGLT2 inhibitors (SGLT2-i) in DKD patients have been demonstrated through numerous large clinical trials. Moreover, further exploratory experiments indicate these drugs may ameliorate serum and urinary markers of inflammation, such as TNF-α, and inhibit ferroptosis in DKD models. Consequently, investigating the interplay between ferroptosis and innate immune and inflammatory responses in DKD is essential for guiding future drug development. This review presents an overview of ferroptosis within the context of DKD, beginning with its core mechanisms and delving into its potential roles in DKD progression. We will also analyze how aberrant innate immune cells, molecules, and signaling pathways contribute to disease progression. Finally, we discuss the interactions between ferroptosis and immune responses, as well as targeted therapeutic agents, based on current evidence. By analyzing the interplay between ferroptosis and innate immunity alongside its inflammatory responses in DKD, we aim to provide insights for clinical management and drug development in this area.
T cell receptor usage and epitope specificity amongst CD8+ and CD4+ SARS-CoV-2-specific T cells
Authors: Fahnøe Ulrik , Feng Shan , Underwood Alexander P. , Jacobsen Kivin , Ameri Amir , Blicher Thomas H. , Sølund Christina S. , Rosenberg Brad R. , Brix Liselotte , Weis Nina , Bukh Jens
Published: February 2025

Introduction

The coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has highlighted the critical importance of understanding protective long-lasting immune responses. This study investigates the epitope specificity, T cell receptor (TCR) usage, and phenotypic changes in SARS-CoV-2-specfic CD8+ and CD4+ T cells over time in convalescent individuals with COVID-19.

Methods

Peripheral blood mononuclear cells (PBMCs) were collected from 28 unvaccinated individuals with primary SARS-CoV-2 infection (6 identified as the D614G variant, clade 20C) and analyzed up to 12 months post-symptom onset. Antigen-specific CD8+ and CD4+ T cells were analyzed using flow cytometry and single-cell RNA sequencing (scRNAseq) using specific dextramer and antibody reagents. TCR clonotypes and activation markers were characterized to explore T cell dynamics.

Results

SARS-CoV-2-specific CD8+ T cells exhibited waning frequencies long-term, transitioning from memory-like to a naïve-like state. scRNAseq revealed specificity against both spike and non-spike antigens with increased CD95 and CD127 expression over time, indicating that naïve-like T cells may represent stem cell memory T cells, which are multipotent and self-renewing, likely important for long-lived immunity. TCR clonal expansion was observed mainly in memory T cells, with overlapping TCR beta chain (TRB)-complementary determining region 3 (CDR3) sequences between participants, suggesting shared public TCR epitope-specific repertoires against SARS-CoV-2. Further, unique spike-specific CD4+ T cells with high CD95 and CD127 expression were identified, which may play a crucial role in long-term protection.

Discussion

This study highlights epitope-specificity heterogeneity, with some immunodominant responses, and suggests a potential role for long-lived SARS-CoV-2-specific T cell immunity. Shared TCR repertoires offers insights into cross-reactive and protective T cell clones, providing valuable information for optimizing vaccine strategies against emerging SARS-CoV-2 variants. The findings underscore the critical role of cellular immunity in long-term protection against SARS-CoV-2 and emphasizes the importance of understanding T cell dynamics.
Digital remote monitoring of people with multiple sclerosis
Authors: Dini Michelangelo , Comi Giancarlo , Leocani Letizia
Published: February 2025

Introduction

Multiple sclerosis (MS) is a chronic neurodegenerative disease that affects over 2.8 million people globally, leading to significant motor and non-motor symptoms. Effective disease monitoring is critical for improving patient outcomes but is often hindered by the limitations of infrequent clinical assessments. Digital remote monitoring tools leveraging big data and AI offer new opportunities to track symptoms in real time and detect disease progression.

Methods

This narrative review explores recent advancements in digital remote monitoring of motor and non-motor symptoms in MS. We conducted a PubMed search to collect original studies aimed at evaluating the use of AI and/or big data for digital remote monitoring of pwMS. We focus on tools and techniques applied to data from wearable sensors, smartphones, and other connected devices, as well as AI-based methods for the analysis of big data.

Results

Wearable sensors and machine learning algorithms show significant promise in monitoring motor symptoms, such as fall risk and gait disturbances. Many studies have demonstrated their reliability not only in clinical settings and for independent execution of motor assessments by patients, but also for passive monitoring during everyday life. Cognitive monitoring, although less developed, has seen progress with AI-driven tools that automate the scoring of neuropsychological tests and analyse passive keystroke dynamics. However, passive cognitive monitoring is still underdeveloped, compared to monitoring of motor symptoms. Some preliminary evidence suggests that application of AI and big data to other understudied aspects of MS (namely sleep and circadian autonomic patterns) may provide novel insights.

Conclusion

Advances in AI and big data offer exciting possibilities for improving disease management and patient outcomes in MS. Digital remote monitoring has the potential to revolutionize MS care by providing continuous, long-term granular data on both motor and non-motor symptoms. While promising results have been demonstrated, larger-scale studies and more robust validation are needed to fully integrate these tools into clinical practice and generalise their results to the wider MS population.
A comprehensive prognostic and immune analysis of LAPTM4B in pan-cancer and Philadelphia chromosome-positive acute lymphoblastic leukemia
Authors: Zhou Hui , Yi Yuyao , He Wei , Zheng Li , Hu Yiguo , Niu Ting
Published: February 2025

Introduction

Lysosomal-associated protein transmembrane-4 beta (LAPTM4B) protein expression was increased in solid tumors, whereas few studies were performed in hematologic malignancies. We aimed to study the effect of the LAPTM4B gene in pan-cancer and Philadelphia chromosome-positive acute B cell lymphoblastic leukemia (Ph+ B-ALL).

Methods

The differential expression, diagnosis, prognosis, genetic and epigenetic alterations, tumor microenvironment, stemness, immune infiltration cells, function enrichment, single-cell analysis, and drug response across cancers were conducted based on multiple computational tools. Additionally, Ph+ B-ALL transgenic mouse model with Laptm4b knockout was used to analyze the function of LAPTM4B in vivo. BrdU incorporation method, flow cytometry, and Witte-lock Witte culture were used to evaluate the roles of LAPTM4B in vitro.

Results

We identified that LAPTM4B expression was increased in various cancers, with significant associations with clinical outcomes. LAPTM4B expression correlated with DNA and RNA methylation patterns and was associated with drug resistance. It also influenced the tumor immune microenvironment, with implications for immunotherapy response. In leukemia, LAPTM4B was expressed in stem cells and associated with specific subtypes. Knockout of LAPTM4B impeded B-ALL progression in mice and reduced cell proliferation and caused G0/G1 arrest in vitro.

Discussion

Our study elucidated the role LAPTM4B that promoted the development and progression in Ph+ B-ALL. Furthermore, LAPTM4B played a diagnostic, prognostic, and immunological factor.
Pig jejunal single-cell RNA landscapes revealing breed-specific immunology differentiation at various domestication stages
Authors: Fu Wenyu , Xie Qinqin , Yu Pengfei , Liu Shuang , Xu Lingyao , Ye Xiaowei , Zhao Wei , Wang Qishan , Pan Yuchun , Zhang Zhe , Wang Zhen
Published: February 2025

Background

Domestication of wild boars into local and intensive pig breeds has driven adaptive genomic changes, resulting in significant phenotypic differences in intestinal immune function. The intestine relies on diverse immune cells, but their evolutionary changes during domestication remain poorly understood at single-cell resolution.

Methods

We performed single-cell RNA sequencing (scRNA-seq) and marker gene analysis on jejunal tissues from wild boars, a Chinese local breed (Jinhua), and an intensive breed (Duroc). Then, we developed an immune cell evaluation system that includes immune scoring, gene identification, and cell communication analysis. Additionally, we mapped domestication-related clustering relationships, highlighting changes in gene expression and immune function.

Results

We generated a single-cell atlas of jejunal tissues, analyzing 26,246 cells and identifying 11 distinct cell lineages, including epithelial and plasma cells, and discovered shared and unique patterns in intestinal nutrition and immunity across breeds. Immune cell evaluation analysis confirmed the conservation and heterogeneity of immune cells, manifested by highly conserved functions of immune cell subgroups, but wild boars possess stronger immune capabilities than domesticated breeds. We also discovered four patterns of domestication-related breed-specific genes related to metabolism, immune surveillance, and cytotoxic functions. Lastly, we identified a unique population of plasma cells with distinctive antibody production in Jinhua pig population.

Conclusions

Our findings provide valuable single-cell insights into the cellular heterogeneity and immune function evolution in the jejunum during pig at various domestication stages. The single-cell atlas also serves as a resource for comparative studies and supports breeding programs aimed at enhancing immune traits in pigs.
The distinct functions of MIF in inflammatory cardiomyopathy
Authors: Pressley Kyle R. , Naseem Yashfa , Nalawade Saisha , Forsthuber Thomas G.
Published: February 2025

The immune system plays a crucial role in cardiac homeostasis and disease, and the innate and adaptive immune systems can be beneficial or detrimental in cardiac injury. The pleiotropic proinflammatory cytokine macrophage migration inhibitory factor (MIF) is involved in the pathogenesis of many human disease conditions, including heart diseases and inflammatory cardiomyopathies. Inflammatory cardiomyopathies are frequently observed after microbial infection but can also be caused by systemic immune-mediated diseases, drugs, and toxic substances. Immune cells and MIF are implicated in many of these conditions and may affect progression of inflammatory cardiomyopathy (ICM) to myocardial remodeling and dilated cardiomyopathy (DCM). The potential for targeting MIF therapeutically in patients with inflammatory diseases is an active area of investigation. Here we review the current literature supporting the role(s) of MIF in ICM and cardiac dysfunction. We posit that future research to further elucidate the underlying functions of MIF in cardiac pathologies is warranted.
Suppression of NLRP3 inflammasome by a small molecule targeting CK1α–β-catenin–NF-κB and CK1α–NRF2–mitochondrial OXPHOS pathways during mycobacterial infection
Authors: Guan Qing , Xiong Huan , Song Xiangyu , Liu Sheng , Guang Yuanjun , Nie Qi , Xie Yan , Zhang Xiao-Lian
Published: February 2025

Introduction

Pyroptosis is an important inflammatory form of cell death and Mycobacterium tuberculosis (M.tb) chronic infection triggers excessive inflammatory pyroptosis of macrophages. Our previous research has confirmed that a small compound pyrvinium pamoate (PP) could inhibit inflammatory pathological changes and mycobacterial burden in M.tb-infected mice, but the potential mechanism of PP for inhibiting M.tb-induced inflammation remains unexplored.

Methods

The effects of PP on the NLRP3-ASC-Casp1 inflammasome assembly and activation, gasdermin D (GSDMD) mediated pyroptosis and inflammatory cytokines expression were assessed in human THP-1-derived macrophages after M.tb H37Rv/H37Ra/ Salmonella typhimurium (S. typhimurium) infection or LPS treatment by Transcriptome sequencing, RT-qPCR, Co-immunoprecipitation and Western Blot (WB) analysis. The lactate dehydrogenase (LDH) release assay was used to evaluate the CC50 of PP in M.tb-infected THP-1 cells.

Results

We found that M.tb/S. typhimurium infection and LPS treatment significantly activate NLRP3-ASC-Casp1 inflammasome activation, GSDMD-mediated pyroptosis and inflammatory cytokines (IL-1β and IL-18) expression in macrophages, whereas PP could suppress these inflammatory effects in a dose dependent manner. Regarding the PP-inhibition mechanism, we further found that this inhibitory activity is mediated through the PP-targeting casein kinase 1A1 (CK1α)–β-catenin–NF-κB pathway and CK1α–NRF2–mitochondrial oxidative phosphorylation (OXPHOS) pathway. In addition, a CK1α specific inhibitor D4476 or CK1α siRNA could reverse these inhibitory effects of PP on bacteria-induced inflammatory responses in macrophages.

Conclusions

This study reveals a previously unreported mechanism that pyrvinium can inhibit NLRP3 inflammasome and GSDMD–IL-1β inflammatory pyroptosis via targeting suppressing CK1α–β-catenin–NF-κB and CK1α–NRF2–mitochondrial OXPHOS pathways, suggesting that pyrvinium pamoate holds great promise as a host directed therapy (HDT) drug for mycobacterial-induced excessive inflammatory response.
Beyond CCR7: dendritic cell migration in type 2 inflammation
Authors: Meloun Audrey , León Beatriz
Published: February 2025

Conventional dendritic cells (cDCs) are crucial antigen-presenting cells that initiate and regulate T cell responses, thereby shaping immunity against pathogens, innocuous antigens, tumors, and self-antigens. The migration of cDCs from peripheral tissues to draining lymph nodes (dLNs) is essential for their function in immune surveillance. This migration allows cDCs to convey the conditions of peripheral tissues to antigen-specific T cells in the dLNs, facilitating effective immune responses. Migration is primarily mediated by chemokine receptor CCR7, which is upregulated in response to homeostatic and inflammatory cues, guiding cDCs to dLNs. However, during type 2 immune responses, such as those triggered by parasites or allergens, a paradox arises—cDCs exhibit robust migration to dLNs despite low CCR7 expression. This review discusses how type 2 inflammation relies on additional signaling pathways, including those induced by membrane-derived bioactive lipid mediators like eicosanoids, sphingolipids, and oxysterols, which cooperate with CCR7 to enhance cDC migration and T helper 2 (Th2) differentiation. We explore the potential regulatory mechanisms of cDC migration in type 2 immunity, offering insights into the differential control of cDC trafficking in diverse immune contexts and its impact on immune responses.
Redefining CRP in tissue injury and repair: more than an acute pro-inflammatory mediator
Authors: Potempa Marc , Hart Peter C. , Rajab Ibraheem M. , Potempa Lawrence A.
Published: February 2025

Most early studies investigating the role of C-reactive protein (CRP) in tissue damage determined it supported pro-hemostatic and pro-inflammatory activities. However, these findings were not universal, as other data suggested CRP inhibited these same processes. A potential explanation for these disparate observations finally emerged with the recognition that CRP undergoes context-dependent conformational changes in vivo, and each of its three isoforms – pentameric CRP (pCRP), modified pentameric CRP (pCRP*), and monomeric CRP (mCRP) – have different effects. In this review, we consider this new paradigm and re-evaluate the role of CRP and its isoforms in the tissue repair process. Indeed, a growing body of evidence points toward the involvement of CRP not just in hemostasis and inflammation, but also in the resolution of inflammation and in tissue regeneration. Additionally, we briefly discuss the shortcomings of the currently available diagnostic tests for CRP and highlight the need for change in how CRP is currently utilized in clinical practice.
Neural network-based performance prediction of marine UHPC with coarse aggregates
Authors: Luan Yunhao , Cai Dongbo , Wang Deming , Luo Changqing , Wang Anni , Wang Chao , Kong Degao , Xu Chaohui , Huang Sining
Published: February 2025

In order to improve bearing capacity and service life of marine structure using marine UHPC with coarse aggregate (UHPC-CA), it is necessary to reasonably predict the performance of UHPC-CA. The performance of UHPC-CA was predicted in this paper based on five prediction models: multiple linear regression, multiple nonlinear regression, traditional neural network (T-BP), principal component approach neural network (PCA-BP), and improved neural network based on genetic algorithm (GA-BP). Seven influencing factors were taken as input, such as coarse aggregate type, coarse aggregate content, steel fiber type, steel fiber content, water-binder ratio, rubber particle sand replacement rate and curing system. Mechanical and long-term performance of UHPC-CA were taken as outputs. The results show that artificial neural network can be applied to predict performance of UHPC-CA with multi-parameter input and multi-index output. In terms of the prediction accuracy of mechanical properties and long-term performance of UHPC-CA, the order is GA-BP > PCA-BP > T-BP > multiple nonlinear regression > multiple linear regression. The GA-BP neural network has the highest goodness of fit for the prediction of mechanical properties and long-term performance of UHPC-CA, which is 93.87%, 37.34%, 5.13% and 3.21% averagely higher than that of multiple linear regression, multiple nonlinear regression, T-BP and PCA-BP, respectively. Furthermore, GA-BP neural network has the lowest error index for each performance prediction. MAE, MSE and RMSE are 18.13%, 77.26% and 52.31% lower than PCA-BP on average.
A transdisciplinary dual degree curriculum yields novel and successful learning outcomes: early lessons from training physicianeers
Authors: Wells Gregg B. , Baxter Douglas A. , Day Leslie J. , Boone Timothy B. , Moreno Michael R. , Gibson Jeremy L. , Peterson Thomas V. , Martinez-Moczygemba Margarita , Greene Ericka P. , Sears Nicholas , Paolini Michael A. , Pettigrew Roderic I.
Published: February 2025

The evolving needs in healthcare education and delivery have led to diverse MD-based dual degree programs offering trainees broader experiences and credential-based credibility after graduation. Medical schools typically implement multidisciplinary or interdisciplinary dual degree training with designs that separate the contributing disciplines chronologically and experientially. As a result, these designs fail to maximize the cohesive learning environment and outcomes possible with a transdisciplinary dual degree design, which integrates the contributing disciplines chronologically, experientially, and conceptually. Though rare, transdisciplinary dual degrees promise transformative educational outcomes and discipline convergence by dissolving traditional discipline boundaries and fostering a new learning environment and professional identity. Therefore, we hypothesize that a transdisciplinary dual degree curriculum yields novel—and potentially better—learning outcomes. ENMED, a transdisciplinary dual degree program collaboratively developed, sponsored, and implemented by Texas A&M University and Houston Methodist Hospital, is testing this hypothesis by training “physicianeers.” This new type of healthcare professional trains simultaneously for the MD and Master of Engineering degrees, thereby integrating medical and engineering expertise to advance health system innovations. Supporting the hypothesis, ENMED’s early experiences suggest its transdisciplinary dual-degree model leads physicianeer trainees to novel perspectives with the potential to transform healthcare systemically.
Evaluation of pathogenicity variation between two Erwinia species in apples and their population using a duplex real-time PCR method
Authors: Lee Mi-Hyun , Balaraju Kotnala , Choi Hyo-Won , Lee Yong Hwan
Published: February 2025

Fire blight and black shoot blight diseases, caused by Erwinia amylovora and Erwinia pyrifoliae, respectively, continue to spread several areas in Korea, despite intensive efforts by the government to control diseases. The distribution pattern of fire blight and black shoot blight is different from each other in Korea. Consequently, it is required to investigate the pathogenicity of E. amylovora and E. pyrifoliae in apple trees. The disease severity of fire blight and black shoot blight was compared in this study by an artificial inoculation of E. amylovora and E. pyrifoliae suspensions into the abaxial veins of apple leaves and measuring their pathogenicity at varying temperatures. Furthermore, disease severity was assessed by inoculating E. amylovora and E. pyrifoliae in apple flowers and assessing their pathogenicity at various temperatures. The E. amylovora-inoculated flowers displayed greater disease index than E. pyrifoliae-inoculated flowers at temperatures ranging from 18°C to 25°C. Upon examining the population sizes of E amylovora and E. pyrifoliae in flowers using a real-time polymerase chain reaction (PCR), the Ct value of E. amylovora was found to be lower in the style including stigma and hypanthium than the Ct value of E. pyrifoliae, except at 18°C. Hypanthium contained E. amylovora TS3128 and E. pyrifoliae YKB12327 at >107 and 105 CFU/mL, respectively at 15°C. Furthermore, in this study, we investigated the population size of E. amylovora and E. pyrifoliae in apple flowers in relation to temperature in order to clarify the differences in their pathogenicity.