bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of a wearable device to improve sleep quality
Authors: Moore Susan L. , Carey Evan P. , Finikiotis Kristyna , Ford Kelsey L. , Zane Richard D. , Green Katherine K.
Published: February 2025

Objectives

The present study aimed to analyze the effects of the use of a digital wellness device on improving sleep through reducing environmental noise.

Methods

Fifty-five self-reported light or moderate sleepers with difficulty falling or staying asleep due to environmental noise participated in the study. Objective sleep architecture data were collected via a wireless electroencephalogram (EEG) sleep monitor and subjective data were obtained through analysis of daily sleep diaries and responses to study-specific user experience surveys. Four primary outcomes specified a priori were analyzed for statistical significance: objectively measured sleep onset latency (SOL), wake after sleep onset (WASO), number of awakenings, and perceived SOL. Exploratory analysis through descriptive statistics was conducted for an additional 36 secondary outcomes.

Results

Use of the digital wellness device was associated with reduced SOL both objectively and subjectively. Perceived SOL was 32.5% reduced (p < 0.001, difference in means 7.5 min, 95% CI 22.3%–41.4% faster), and objectively measured SOL was 13.3% reduced (p = 0.030, difference in means 2.7 min, 95% CI = 1.4%–23.8% faster). No statistically significant differences were found for other primary outcomes. Among the subjective secondary outcomes, 100% of participants felt the device blocked environmental noise, 86% reported falling asleep more easily, 76% felt they stayed asleep longer, and 82% felt overall sleep quality was improved. No differences were observed among objectively measured secondary outcomes.

Conclusions

Participants fell asleep faster when using the wearable wellness device. Participants also perceived sleep quality improvements with the intervention, although no objective differences were measured. These findings show promise for using noise-masking digital wellness devices in noisy environments to improve sleep quality.
The externalization of internal experiences in psychotherapy through generative artificial intelligence: a theoretical, clinical, and ethical analysis
Authors: Haber Yuval , Hadar Shoval Dorit , Levkovich Inbar , Yinon Dror , Gigi Karny , Pen Oori , Angert Tal , Elyoseph Zohar
Published: February 2025

Introduction

Externalization techniques are well established in psychotherapy approaches, including narrative therapy and cognitive behavioral therapy. These methods elicit internal experiences such as emotions and make them tangible through external representations. Recent advances in generative artificial intelligence (GenAI), specifically large language models (LLMs), present new possibilities for therapeutic interventions; however, their integration into core psychotherapy practices remains largely unexplored. This study aimed to examine the clinical, ethical, and theoretical implications of integrating GenAI into the therapeutic space through a proof-of-concept (POC) of AI-driven externalization techniques, while emphasizing the essential role of the human therapist.

Methods

To this end, we developed two customized GPTs agents: VIVI (visual externalization), which uses DALL-E 3 to create images reflecting patients' internal experiences (e.g., depression or hope), and DIVI (dialogic role-play-based externalization), which simulates conversations with aspects of patients' internal content. These tools were implemented and evaluated through a clinical case study under professional psychological guidance.

Results

The integration of VIVI and DIVI demonstrated that GenAI can serve as an “artificial third”, creating a Winnicottian playful space that enhances, rather than supplants, the dyadic therapist-patient relationship. The tools successfully externalized complex internal dynamics, offering new therapeutic avenues, while also revealing challenges such as empathic failures and cultural biases.

Discussion

These findings highlight both the promise and the ethical complexities of AI-enhanced therapy, including concerns about data security, representation accuracy, and the balance of clinical authority. To address these challenges, we propose the SAFE-AI protocol, offering clinicians structured guidelines for responsible AI integration in therapy. Future research should systematically evaluate the generalizability, efficacy, and ethical implications of these tools across diverse populations and therapeutic contexts.
Navigating the landscape of remote patient monitoring in Canada: trends, challenges, and future directions
Authors: Bouabida Khayreddine , Chaves Breitner Gomes , Anane Enoch , Jagram Navaal
Published: February 2025

Remote Patient Monitoring (RPM) has driven significant advancements in Canadian healthcare, especially during the transformative period from 2018 to 2023. This perspective article explores the state of play and examines the current landscape of RPM platforms adopted across Canada, detailing their functionalities and measurable impacts on healthcare outcomes, particularly in chronic disease management and hospital readmission reduction. We explore the regulatory, technical, and operational challenges that RPM faces, including critical issues around data privacy, security, and interoperability, factors essential for sustainable integration. Additionally, this article provides a balanced analysis of RPM's potential for continued growth within Canadian healthcare, highlighting its strengths and limitations in the post-2023 context and offering strategic recommendations to guide its future development. Keywords: Remote Patient Monitoring, Digital Health, Virtual Care, Canadian Healthcare, Healthcare Technology, AI, Perspectives.
Thyroid function during COVID-19 and post-COVID complications in adults: a systematic review
Authors: Panesar Anisha , Gharanei Palma , Khovanova Natasha , Young Lawrence , Grammatopoulos Dimitris
Published: February 2025

The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus, has presented multifaceted health challenges. COVID-19 primarily targets the respiratory system but also affects multiple organ systems, including the endocrine system. Emerging evidence suggests interactions between thyroid function, the acute phase of COVID-19, and the prolonged symptoms known as post-COVID sequalae or long COVID. Several studies have reported that COVID-19 can induce thyroid dysfunction, leading to conditions such as thyroiditis and alterations in thyroid hormone levels. The mechanisms through which SARS-CoV-2 affects the thyroid include direct viral infection of thyroid cells, leading to viral thyroiditis, which causes inflammation and transient or sustained thyroid dysfunction, as well as an excessive systemic immune response (cytokine storm). This is associated with elevated levels of cytokines, such as IL-6, that disrupt thyroid function and lead to nonthyroidal illness syndrome (NTIS). Medications administered during the acute illness phase, such as corticosteroids and antiviral drugs, can also impact thyroid hormone actions. The involvement of the thyroid gland in long COVID, or postacute sequelae of SARS-CoV-2 infection, is an area not well defined, with potential implications for understanding and managing this condition. Persistent low-grade inflammation affecting thyroid function over time can lead to ongoing thyroiditis or exacerbate pre-existing thyroid conditions. Viral infections, including SARS-CoV-2, can trigger or worsen autoimmune thyroid diseases, such as Hashimoto’s thyroiditis and Graves’ disease. Long COVID may disrupt the hypothalamic–pituitary–adrenal (HPA) axis, which can, in turn, affect the hypothalamic-pituitary-thyroid (HPT) axis, leading to abnormal thyroid function. This review was designed to systematically capture recent literature on COVID-19-related thyroid dysfunction in the adult population, the prognostic consequences of thyroid dysfunction during COVID-19, and the effects of thyroid dysfunction on patients with long COVID. A comprehensive search of PubMed and EMBASE databases was conducted. The systematic review was performed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Study quality was assessed using the Critical Appraisal Skills Programme (CASP). A total of 53 studies met the inclusion criteria. The review summarises recent findings and provides an update of the current understanding of thyroid dysfunction in COVID-19-related spectrum of disorders, underscoring the complex nature of SARS-CoV-2 infection and its far-reaching impacts on human health.
Research on master-slave game theory-based demand response strategies for renewable energy integration
Authors: Hu Wei , Li Yining , Du Puliang , Li Jiyu
Published: February 2025

As renewable energy sources are extensively incorporated into electrical grids, the necessity for enhanced flexibility and stability within the power system has significantly grown., Demand Response (DR) has attracted widespread attention as an effective load management tool. This study delves into the master-slave game theory-based demand response strategy integrated with renewable energy, aiming to optimize the interaction mechanism between grid operators and users participating in demand response through a game-theoretic framework, thereby enhancing the system’s economic efficiency and reliability. In this research, we first constructed a power system model that includes renewable energy sources such as wind and solar power. A master-slave game theory-based demand response strategy framework was proposed, where the energy suppliers act as the leader by setting demand response policies, while energy operators who act as followers decide their consumption behaviors to maximize their own interests. The strategy allows participants to adjust their strategies based on real-time market information and changes in renewable energy output so as to realize optimal scheduling of demand response resources. Through theoretical analysis and simulation experiments, the results illustrate that the demand response strategy affects the respective revenues of energy operators and energy suppliers by dispatching electricity purchases in four different modes. The effectiveness of the demand response strategy was verified in reducing operational costs of the grid, enhancing the system’s adaptability to fluctuations in renewable energy, and encouraging active user participation in demand response. In summary, the master-slave game theory-based demand response strategy for renewable energy integration proposed in this study not only promotes the economic and efficient operation of the power grid but also provides important theoretical support and technical references for the development of future smart grids.
Effects of water level changes on the hydrological connectivity and water quality of a lake-type wetland
Authors: Lin Yemiao , Dai Junfeng , Peng Xinyue , Li Zheqing , Wan Zupeng
Published: February 2025

Introduction

Understanding the effects of water level fluctuations on wetland ecosystems is crucial for water resource management and ecological conservation. While there have been some studies on this topic, comprehensive analyses of how water level changes affect the hydrological connectivity and water quality of complex lake-type wetlands remain relatively limited. This work aims to explore the effects of water level changes on the connectivity and water quality of lake-type water bodies in the Huixian Karst Wetland, Guilin.

Methods

Water quality data for Mudong Lake from January 2021 to December 2022 were obtained by collecting monthly water samples and conducting laboratory tests for six common water quality parameters. Through a combination of remote sensing image data, drone image data and actual measured data on the Mudong Lake water level, the comprehensive ecological-hydrological connectivity index and comprehensive water quality index were used to evaluate the water level changes in Mudong Lake, water body connectivity, and water quality. The correlations between them were then analysed.

Results

The results show that as the water level increases, the degree of landscape fragmentation decreases, and the water connectivity index increases by 262%. In addition, as the water level increases, the comprehensive water quality pollution index shows an overall downward trend.

Discussion

However, the factors affecting lake water quality are complex and changeable. Future research could consider increasing the monitoring frequency during critical periods of rapid hydrological change, such as rainfall-runoff events, to capture more precise and detailed hydrological and water quality data. This study provides an important example of the effects of changes in water level and wetland connectivity on the water quality of a lake ecosystem.
A structural genomics approach to investigate Dystrophin mutations and their impact on the molecular pathways of Duchenne muscular dystrophy
Authors: Elasbali Abdelbaset Mohamed , Anjum Farah , AlKhamees Osama A. , Abu Al-Soud Waleed , Adnan Mohd , Shamsi Anas , Hassan Md. Imtaiyaz
Published: February 2025

Background

Dystrophin is a key protein encoded by the DMD gene, serves as a scaffold linking the cytoskeleton to the extracellular matrix that plays a critical role in muscle contraction, relaxation, and structural integrity. Mutations, particularly single-point amino acid substitutions, can lead to dysfunctional Dystrophin, causing muscular dystrophies, with Duchenne muscular dystrophy (DMD) being the most severe form.

Objective

This study aimed to evaluate the effects of 184 single-point amino acid substitutions on the structure and function of Dystrophin using computational approaches.

Methods

Many computational tools were used to predict the impact of amino acid substitutions on protein stability, solubility, and function. Pathogenic potential was assessed using disease phenotype predictors and CADD scores, while allele frequency data from gnomAD contextualized mutation prevalence. Additionally, aggregation propensity, frustration analysis, and post-translational modification sites were analyzed for functional disruptions.

Results

Of the 184 substitutions analyzed, 50 were identified as deleterious, with 41 predicted to be pathogenic. Seventeen mutations were localized in the Calponin-homology (CH) 1 domain, a critical functional region of Dystrophin. Six substitutions (N26H, N26K, G47W, D98G, G109A, and G109R) were predicted to decrease protein solubility and were located in minimally frustrated regions, potentially compromising Dystrophin functionality and contributing to DMD pathogenesis.

Conclusion

This study provides novel insights into the molecular mechanisms of DMD, highlighting specific mutations that disrupt Dystrophin’s solubility and function. These findings could inform future therapeutic strategies targeting Dystrophin mutations to address DMD pathogenesis.
Genome-wide identification of oat TCP gene family and expression patterns under abiotic stress
Authors: Nie Jiaming , Zhao Hongbin , Guo Xiaodong , Zhang Tao , Han Bing , Liu Huiyan
Published: February 2025

TCP transcription factors are a unique class of transcription factors that play important roles in alleviating abiotic stresses such as drought and salt. In this study, the whole-genome data of three cultivated varieties, namely, “SFS”, “Sang” and “OT3098v2”, were utilized to identify and analyze the members of the TCP gene family in oats, and their responses to two abiotic stresses, drought and salt, were also investigated. Results showed that there are 83, 65, and 30 non-redundant TCP genes in the three oats, with the highest number of TCP genes specific to the “SFS”, reaching 22 genes. The oat TCP genes can be classified into three subfamilies: PCF, CIN, and CYC/TB1. Most AsTCP genes have important motifs, Motif 1 and Motif 2, which are part of the bHLH domain. Additionally, various cis-acting elements related to hormone response, abiotic stress, light response, and growth and development were found in the promoters of AsTCP genes. The main amplification mechanism of the oat TCP gene family is fragment duplication. Two tandem duplications, AsTCP058/AsTCP059 and AsTCP023/AsTCP025, are stably present in the three oats. The highest number of AsTCP collinear relationships exist in the “SFS” with 89 pairs. After drought and salt stress treatments, significant differences in gene expression were observed among different oat cultivars and treatment periods. Genes that showed significant expression changes under both treatments (AsTCP021, AsTCP033, AsTCP044, AsTCP053, and AsTCP058) may play important roles in oat’s response to abiotic stresses. Notably, AsTCP053 gene was significantly upregulated at 24 h of stress treatment and showed a more sensitive response to salt stress. This study provides insights into the functional characterization of the oat TCP gene family and its molecular mechanisms underlying stress tolerance.
Detection of viral antigen and inflammatory mediators in fatal pediatric dengue: a study on lung immunopathogenesis
Authors: Moragas Leandro Junqueira , Arruda Laíza Vianna , Oliveira Lucca de Lima Siqueira , Alves Felipe de Andrade Vieira , Salomão Natália Gedeão , da Silva Jemima Fuentes Ribeiro , Basílio-de-Oliveira Carlos Alberto , Basílio-de-Oliveira Rodrigo Panno , Mohana-Borges Ronaldo , Azevedo Caio Gonçalves , Oliveira Gabriela Xavier de , Carvalho Jorge José de , Rosman Fernando Colonna , Paes Marciano Viana , Rabelo Kíssila
Published: February 2025

Introduction

The dengue virus (DENV) is the etiological agent that causes dengue fever illness, an arbovirus with a major endemic potential that has become increasingly prevalent in Brazil and has already been associated with fatal cases in children. DENV has tropism for several organs, including lungs causing pulmonary complications. The aim of this article was to evaluate the inflammatory and histopathological profile of the lung tissue of three fatal cases of children infected with DENV, which represents a group more susceptible to fatality due to its incomplete development.

Methods

Histopathological analysis was carried out using Hematoxylin and Eosin staining and special stains. While the characterization of the inflammatory response and cellular expression was done by marking the viral protein, macrophages, lymphocytes and pro-inflammatory cytokines.

Results and discussion

The results confirm that vascular dysfunctions such as hemorrhage, vascular congestion and edema associated with a mononuclear infiltrate were observed in all three cases. In addition, the presence of viral replication and increased expression of inflammatory markers were also observed. Such findings contribute to the study and description of dengue, especially its effects on lung tissue.
Haploidentical stem cell transplantation with posttransplant cyclophosphamide in children with Wiskott–Aldrich syndrome: a case report
Authors: Nguyen Ngoc Quynh Le , Nguyen Thanh Binh , Luong Thi Lien , Nguyen Thi Dieu Thuy , Dang Anh Duong , P. Lee Pamela , Cao Viet Tung , Tran Minh Dien
Published: February 2025

Wiskott–Aldrich syndrome (WAS) is a condition characterized by a low platelet count, eczema, and a weakened immune system. Hematopoietic stem cell transplantation (HSCT) is the only curative treatment option. Haploidentical HSCT with posttransplant cyclophosphamide (PTCy) is an emerging approach for children with noncancerous conditions. This case describes a WAS patient who was early diagnosed and successfully treated with haploidentical HSCT. A 3-month-old boy presented with widespread eczema, a low platelet count, and severe infections in infancy. The diagnosis of WAS was quickly confirmed by genetic test. He received immunoglobulin replacement therapy and antimicrobial prophylaxis and underwent HSCT at 4 years 3 months of age. After failed unrelated cord blood HSCT, second rescue haploidentical HSCT had been performed using the patient’s mother as the donor, with stem cells collected from peripheral blood. The conditioning regimen included anti-thymocyte globulin, melphalan, and fludarabine. The stem cell dose was 2.63 × 106 CD34+ cells/kg. GVHD prevention included PTCy, mycophenolat mofetil, and tacrolimus. The patient had no significant complications after the transplant. Neutrophil and platelet engraftment occurred promptly. At 32 months post-HSCT, the patient had complete hematological and immune reconstitution, with full donor chimerism and no GVHD. In conclusion, the PTCy approach to haploidentical HSCT was a safe and effective treatment for this WAS patient.
T-regulatory cells for the treatment of autoimmune diseases
Authors: Fisher Marina S. , Sennikov Sergey V.
Published: February 2025

Autoimmune diseases result from imbalances in the immune system and disturbances in the mechanisms of immune tolerance. T-regulatory cells (Treg) are key factors in the formation of immune tolerance. Tregs modulate immune responses and repair processes, controlling the innate and adaptive immune system. The use of Tregs in the treatment of autoimmune diseases began with the manipulation of endogenous Tregs using immunomodulatory drugs. Then, a method of adoptive transfer of Tregs grown in vitro was developed. Adoptive transfer of Tregs includes polyclonal Tregs with non-specific effects and antigen-specific Tregs in the form of CAR-Treg and TCR-Treg. This review discusses non-specific and antigen-specific approaches to the use of Tregs, their advantages, disadvantages, gaps in development, and future prospects.
Case report: Exploring efficacy of tofacitinib in modulating interferon response in five case of anti-MDA5+ dermatomyositis with interstitial lung disease
Authors: Zhao Jie , Bao Yan , Gao Ying , Xie Keliang
Published: February 2025

A case report highlights the challenges faced in managing a 66-year-old Chinese woman diagnosed with anti-MDA5 antibody-positive dermatomyositis (MDA5-DM) complicated by rapidly progressive interstitial lung disease (RP-ILD). Despite aggressive therapeutic interventions, her condition rapidly deteriorated, emphasizing the severity and devastating nature of this subtype of DM. A salient feature of her clinical presentation was the marked elevation of interferon (IFN)-γ and IFN-α levels, underscoring the pivotal role that IFNs play in driving the pathogenesis and progression of MDA5-DM-related RP-ILD. In an attempt to stem the relentless progression, tofacitinib, a Janus kinase (JAK) inhibitor, was applied into her treatment regimen. This therapeutic intervention led to a transient decrease in IFN-related cytokines, offering a glimpse of hope that JAK inhibition could modulate the exaggerated IFN response implicated in the disease. Other four similar cases underscore the critical importance of early and aggressive intervention in MDA5-DM patients, as well as the potential therapeutic avenues involving IFN blockers by JAK inhibitors. Urgent and well-designed clinical trials are imperative to unravel the intricate interplay between RP-ILD and the IFN signature in MDA5-DM, and to evaluate novel therapeutic targets that promise long-term efficacy and safety.
Intricating connections: the role of ferroptosis in systemic lupus erythematosus
Authors: Zhao Guowang , Li Xinghai , Zhang Ying , Wang Xingzi , Deng Li , Xu Juan , Jin Shumei , Zuo Zan , Xun Linting , Luo Mei , Yang Fan , Qi Jialong , Fu Ping
Published: February 2025

Systemic lupus erythematosus (SLE) is a chronic inflammatory and autoimmune disease with multiple tissue damage. However, the pathology remains elusive, and effective treatments are lacking. Multiple types of programmed cell death (PCD) implicated in SLE progression have recently been identified. Although ferroptosis, an iron-dependent form of cell death, has numerous pathophysiological features similar to those of SLE, such as intracellular iron accumulation, mitochondrial dysfunction, lipid metabolism disorders and concentration of damage associated-molecular patterns (DAMPs), only a few reports have demonstrated that ferroptosis is involved in SLE progression and that the role of ferroptosis in SLE pathogenesis continues to be neglected. Therefore, this review elucidates the potential intricate relationship between SLE and ferroptosis to provide a reliable theoretical basis for further research on ferroptosis in the pathogenesis of SLE.
Carbon emissions reduction in shipping based on four-party evolutionary game
Authors: Zhang Suyong , Song Xiyan
Published: February 2025

In order to realize a win-win situation between economic development and environmental benefits, this paper constructs a four-party evolutionary game model including the government, two homogeneous ports and shipping companies based on evolutionary game theory. By calculating the payoff matrices of the four parties and replicating the dynamic equations, according to the Jacobi matrix, we study and discuss the possible stabilization points of the model under five different scenarios. The game is simulated using MATLAB and the relevant parameters are selected for sensitivity analysis. The results show that the environmental benefits are maximized when the government does not implement the policy and the port and shipping companies use the shore electricty system (i.e., the stability point E12 (0,1,1,1)). Meanwhile, by analyzing the port size sensitivity, when t=1.116, the large-scale port evolution tends to 0, while the small-scale port fluctuates up and down, which leads to the conclusion that the small-scale ports have more potential to implement shore electricty and are able to gain benefits faster. This study provides theoretical support for the implementation of shore electricty systems, while pointing out the key role of the government in promoting the development of shore electricty. It provides a reference for effectively promoting the use of shore electricty in the context of carbon emission reduction, which is especially important for the implementation of shore electricty in small-scale ports and helps to maximize the environmental benefits of port operations.
Study of interfacial bonding properties and shrinkage deformation of cement-alkali activated gradient-structured composite in complex environments with temperature-humidity changes
Authors: Li Xinzhe , Jiang Ganyou , Wang Naishuang , Wei Yisong , Chen Zheng , Li Jing , Chen Ben , Yu Jiamin
Published: February 2025

The early shrinkage-deformation and mechanical property evolution of gradient-structured composites in extreme environments are still insufficient. The paper prepared ordinary Portland cement-alkali-activated slag (OPC-AAS) and ordinary Portland cement-alkali-activated metakaolin (OPC-AAMK) gradient-structured composite by stacking cement and alkali-activated materials together. The effects of temperature difference cycling and wetdry cycling extremes on the early shrinkage strain and splitting strength of OPC-AAS and OPC-AAMK composites, as well as the structure of the bond interface and the micromorphology of the hydration products, were comparatively analyzed. The results demonstrated that the temperature difference cycling affected the early deformation and bond strength of the gradient-structured composite interfaces more significantly than the dry-wet cycling. The maximum expansion strains of OPC-AAS and OPC-AAMK were 1,130.88 μm and 1,399.25 μm, respectively, under the effect of temperature difference cycling; the splitting strengths of OPC-AAS and OPC-AAMK after three cycles of temperature difference cycling were reduced by 26.37% and 31.32%, respectively, compared with that after three cycles of wet-dry cycling. In addition, the OPC-AAS composites showed better interfacial bonding properties after extreme environmental cycling compared to the OPC-AAMK composites. The early splitting strengths under the two extreme environmental effects increased and then decreased, and the maximum splitting strengths of OPCAAS were 2.66 MPa and 3.65 MPa under the temperature difference cycling and dry-wet cycling, respectively, which were 5.14% and 35.69% higher than those of OPC-AAMK, respectively. Scanning electron microscopy (SEM) characterization analysis showed that the temperature difference cycling resulted in more severe product decomposition of the AAMK cementitious material, and obvious cracks and holes appeared at the bonding interface of OPC-AAMK. This study provides some references for the optimal design of the early shrinkage-deformation properties and mechanical properties of gradient-structured composites under extreme environments as well as the assessment of service life.
Infarct volume as a predictor and therapeutic target in post-stroke cognitive impairment
Authors: Xu Lingjia , Shan Dan , Wu Danling
Published: February 2025

Post-stroke cognitive impairment is one of the most common consequences of stroke, affecting more than half of stroke patients, especially in the geriatric population. Post-ischemic stroke cognitive impairment (PISCI) is particularly detrimental, as it can exacerbate a patient’s disability. Given that the severe consequences of adverse life outcomes are major contributors to disability and death among survivors of ischemic stroke, preventing stroke and PISCI remains a fundamental strategy for maintaining optimal brain health. Recent studies have extensively investigated the epidemiology, diagnosis, and management of PISCI. Nevertheless, significant gaps persist in our understanding of its pathophysiological mechanisms and potential therapeutic targets, which warrants further research. Factors such as baseline brain health, cerebral small vessel disease, and stroke characteristics (e.g., infarct location, severity, and morphology) have been associated with PISCI. However, its pathophysiology remains inadequately understood. Recent research suggests that infarct volume may serve as a novel indicator for predicting and managing PISCI. Thus, this review aims to expand our understanding of factors influencing PISCI and to elucidate its pathophysiological mechanisms. In particular, infarct volume has been proposed as a potential target and may play a critical role in predicting and managing PISCI. We advocate for improved and timely predictions of PISCI to enhance the quality of life for patients and reduce the economic and emotional burden on caregivers.
Responses of a soil-inhabiting collembolan (Entomobrya proxima Folsom) to organic fertilizer addition illustrated by functional traits and gut bacterial community
Authors: Yang Xinyue , Li Gang , Xiu Weiming
Published: February 2025

Introduction

Organic fertilizer offers significant advantages for sustainable agricultural development compared to inorganic fertilizers and is increasingly becoming the predominant fertilizer strategy. Functional traits and gut microbiota of soil fauna are recognized as potential indicators of environmental changes. However, there is a dearth of research examining the correlation between functional traits and intestinal microorganisms in response to organic fertilizer.

Methods

In this study, we selected Entomobrya proxima Folsom, a predominant soil collembolan species found in cropland across North China, as our subject of study. We set treatments with no organic fertilizer (CK) and three different concentrations of organic fertilizer at 1% (O1), 6% (O2), and 10% (O3). Stereomicroscopy and high-throughput amplicon sequencing were employed to elucidate the response of soil fauna to organic fertilizer through host functional traits and associated gut microbial communities.

Results

The results indicated that the impact of organic fertilizer on the functional traits of collembolans was closely linked to the input concentration. Specifically, low input concentrations positively influenced all functional traits of Entomobrya proxima Folsom; conversely, higher input concentrations exerted an overall detrimental effect. For the gut bacterial community, the addition of organic fertilizer resulted in a significant decrease in abundance, adversely affected α-diversity, and significantly altered the structure of the gut bacterial community compared to CK. However, there was no significant effect of fertilizer concentration on these three parameters. The composition of the gut bacterial community varied due to the addition of organic fertilizer, with significant changes observed in the relative abundances of six phyla and three genera. Furthermore, body length and foreleg length may serve as potential indicators for characterizing the proportions of Alcanivorax and Sphingobacterium of gut bacterial community. Additionally, the assembly process of the gut bacterial community was strongly influenced by the amount of organic fertilizer added; this led to a narrowing niche width that is believed to contribute to an increase in species richness.

Discussion

In conclusion, adding organic fertilizer exerted multiple impacts on soil fauna, with effect sizes related to its concentration. These findings provide insights for conserving soil animals while maximizing their ecological functions and offer perspectives on optimizing sustainable agricultural management practices.
Transcriptome analysis of 3D4/21 cells expressing CSFV NS4B
Authors: Dong Wang , Lv Huifang , Song Yuzhen , Lv Yujin , Xu Xiapeng , Jing Huiyuan , Peng Zhifeng , Song Xinghui , Guo Yongbin
Published: February 2025

Classical swine fever (CSF) caused by classical swine fever virus (CSFV) has resulted in severe losses to the pig industry worldwide. CSFV non-structural protein 4B (NS4B) plays a crucial role in CSFV replication and pathogenicity. However, the function of NS4B is still limited during CSFV infection. In this study, the RNA-seq was used to investigate differentially expressed genes (DEGs) in 3D4/21 cells expressing CSFV NS4B. 4397 DEGs were identified in 3D4/21 cells expressing NS4B compared to cells expressing the empty vector (NC). Twelve DEGs were selected and further verified by RT-qPCR. Enrichment analyses of GO annotations and KEGG pathways revealed that these DEGs were associated with endocytosis, autophagy, cell adhesion, transport, immune response, apoptosis and so on. The expression of endocytosis-related genes, including CAV1/2, CAVIN2, Rab1B, CHMP2B/4C, VPS35, SNX2, Rab11B, CHMP6, MVB12B and VPS28, were found to be regulated. In addition, some genes associated with host immune defense, such as USP15, DHX29, DDX3, RIG-I and MDA5, were downregulated and the genes associated with host autophagy, such as WIPI2, ATG16L2, SMCR8, RPTOR and MLST8, were upregulated. Therefore, CSFV NS4B involved in virus invasion and intracellular trafficking, the induction of autophagy and the inhibition of antiviral response. Taken together, this study provides useful information for further understanding the function of NS4B during CSFV infection.
The co-occurrence patterns and assembly mechanisms of microeukaryotic communities in geothermal ecosystems of the Qinghai-Tibet Plateau
Authors: Yan Bingjie , Li Xiaodong , Qiao Nanqian , Da Zhen , Xu Jiajie , Jiang Chuanqi , Ba Sang
Published: February 2025

Geothermal spring ecosystems, as extreme habitats, exert significant environmental pressure on their microeukaryotic communities. However, existing studies on the stability of microeukaryotic communities in geothermal ecosystems across different habitats and temperature gradients are still limited. In this study, we used high-throughput 18S rDNA sequencing in combination with environmental factor analysis to investigate the co-occurrence patterns, assembly mechanisms, and responses to environmental changes of microeukaryotic communities in sediment and water samples from 36 geothermal springs across different temperature gradients in southern Tibet. The results show that with increasing temperature, the network stability of microeukaryotic communities in sediments significantly improved, while the stability in water communities decreased. The assembly mechanisms of microeukaryotic communities in both sediment and water were primarily driven by undominant processes within stochastic processes. Latitude and longitude were the key factors influencing changes in sediment community composition, while water temperature and electrical conductivity were the major environmental factors affecting water community composition. Additionally, the stability of the geothermal community network was closely related to its response to external disturbances: sediment communities, being in relatively stable environments, demonstrated higher resistance to disturbances, whereas water communities, influenced by environmental changes such as water flow and precipitation, exhibited greater dynamic variability. These findings not only enhance our understanding of the ecological adaptability of microeukaryotic communities in geothermal springs but also provide valuable insights into how microorganisms in extreme environments respond to external disturbances. This is especially significant for understanding how microeukaryotic communities maintain ecological stability under highly dynamic and stressful environmental conditions.
Transcriptomic and metabolomic analysis of recalcitrant phosphorus solubilization mechanisms in Trametes gibbosa
Authors: Chen Yulan , Farooq Akasha , Wei XieLuyao , Qin Leitao , Wang Yong , Zhang Lingzi , Xiang Quanju , Zhao Ke , Yu Xiumei , Chen Qiang , Gao Xue , Nyima Tashi , Penttinen Petri , Gu Yunfu
Published: February 2025

Introduction

Phosphorus (P) is a crucial growth-limiting nutrient in soil, much of which remains challenging for plants to absorb and use. Unlike chemical phosphate fertilizers, phosphate-solubilizing microorganisms (PSMs) offer a means to address available phosphorus deficiency without causing environmental harm. PSMs possess multiple mechanisms for phosphorus solubilization. Although the phosphorus-solubilizing mechanisms of phosphate-solubilizing bacteria (PSB) have been well characterized, the mechanisms utilized by phosphate-solubilizing fungi (PSF) remain largely unexplored.

Methods

This study isolated a PSF strain, Trametes gibbosa T-41, from soil and evaluated its phosphorus solubilizing capacity with organic (calcium phytin; Phytin-P) and inorganic (tricalcium phosphate; Ca-P) phosphorus sources. The phosphorus solubilization, enzyme activity, and organic acid production of T-41 were measured. And the P-solubilizing mechanism conducted by transcriptomic and metabolomic analyses.

Results and discussion

T-41 exhibited varying phosphorus solubilizing capacity when grown with organic (calcium phytin; Phytin-P) and inorganic (tricalcium phosphate; Ca-P) phosphorus sources (109.80 ± 8.9 mg/L vs. 57.5 ± 7.9 mg/L, p < 0.05). Compared with the Ca-P treatment, T-41 demonstrated a stronger alkaline phosphatase (ALP) production capacity under Phytin-P treatment (34.5 ± 1.2 μmol/L/h vs. 19.8 ± 0.8 μmol/L/h, p < 0.05). Meanwhile, the production of oxalic acid, maleic acid, and succinic acid was higher under Phytin-P treatment (p < 0.05). Transcriptomic and metabolomic analysis revealed that different phosphorus sources altered metabolic pathways such as galactose metabolism, glyoxylate and dicarboxylic acid metabolism, and ascorbate and aldolate metabolism. Key metabolites like myo-inositol, 2-oxoglutarate, and pyruvate were found to impact the performance of T. gibbosa T-41 differently under the two P sources. Notably, synthesis in Ca-P vs. Pytin-P, T-41 upregulated genes involved in myo-inositol synthesis, potentially enhancing its P-solubilizing ability. These results provide new insights into the molecular mechanisms of PSF at the transcriptomic and metabolomic levels, laying a theoretical foundation for the broader application of PSF as bio-phosphorus fertilizers in the future.
Cecum microbiota composition, fermentation characteristics, and immunometabolic biomarkers of Yunshang black goat fed varying dietary energy and protein levels
Authors: Fu Binlong , Zhao Xiaoqi , Khan Muhammad , Jiang Yanting , Li Weijuan , Mushtaq Maida , Danzeng Baiji , Ni Xiaojun , Azeem Zobia , Shao Qingyong , Xue Bai , Ouyang Yina
Published: February 2025

Introduction

Ruminants including goats have diverse microcosms of microbiota involved in diet digestion, absorption, and assimilation. Moreover, it is well known that changes in dietary regimens including nutrient levels result in varied gut microbiota composition, and ultimately, the performance and health of these animals.

Methods

The current study examined the effects of varying dietary energy and protein levels on the cecal fermentation, immune biomarkers, and microbiota characteristics of 80 male Yunshan Black Goats (6 months, ~35.82 ± 2.79 kg), divided into four diets: 1) High Energy-High Protein (HEHP), 2) High Energy-Low Protein (HELP), 3) Low Energy-High Protein (LEHP), and 4) Low Energy-Low Protein (LELP). Twenty goats (five from each treatment group) were randomly slaughtered after a 50-day feeding trial, and cecal digesta and tissue were sampled for microbial analysis.

Results

The cecal content revealed that the high-energy groups (HEHP, HELP) had lower pH levels than the LEHP group (p < 0.05) and significantly higher valeric and isovaleric acid concentrations in HEHP. Although species richness (Chao1 index) remained consistent, the HEHP group showed higher diversity (Shannon and Simpson indices) than LEHP (p < 0.05). Dominant phyla included Bacteroidetes and Firmicutes; LEHP and LELP had significantly higher Bacteroidetes abundance than HELP, while HELP had higher Firmicutes abundance than LEHP (p < 0.05). Verrucomicrobia abundance was lower in LEHP than in HELP and LELP (p < 0.05). At the genus level, 311 genera were identified, with Clostridium, Prevotella, unidentified_BS11, and others showing significant variation. The HELP group had lower unidentified_BS11 than LEHP and LELP, and higher unidentified_Ruminococcaceae, Clostridium, and Lachnospiraceae than LEHP (p < 0.05). VFA metabolism, absorption, cytokine expression, and tight junction protein mRNA in cecal tissue were also analyzed. Genes like MCT-1 and SLC16A4, linked to VFA absorption, positively correlated with Paludibacter, which was associated with immune markers (TLR-3, TLR-4, IFN-γ) and Occludin expression. In contrast, VFA-related genes and tight junction proteins negatively correlated with unidentified Fibrobacterales, suggesting a microbial role in adaptive immunity.

Conclusion

This study demonstrated that dietary energy and protein levels significantly influenced cecal fermentation, immune biomarkers, and microbiota composition in Yunshan Black Goats.
Age-related immune response disparities between adults and children with severe COVID-19: a case–control study in China
Authors: Chen Hongliang , Li Yuan , Yuan Liping , Liu Fen , Sun Qian , Luo Qingkai , Lei Yefei , Hou Yinglan , Li Jiayan , Cai Liang , Tang Shixing
Published: February 2025

Background

Elucidation of immune response differences is critical for uncovering underlying mechanisms and developing potential intervention measures among adults and children with COVID-19.

Methods

In this retrospective study, we analyzed serum biochemical markers and cytokine profiles among adults and children with COVID-19 in the First People’s Hospital of Chenzhou in Hunan, China from 1 December 2022 to 13 February 2023. A case–control study was conducted using propensity score matching (PSM) to mitigate possible confounding factors.

Results

The significant differences observed included lymphocyte exhaustion, an increased neutrophil-to-lymphocyte (NEU/LYM) ratio, high levels of C-reactive protein (CRP), and a cytokine storm, characterized by high levels of Th1 proinflammatory cytokines, including interleukin 1β (IL-1β), IL-6, IL-8, interferon type I (IFN-γ), and tumor necrosis factor (TNF-α) in the lung among severe adult COVID-19 patients. Additionally, systemic immune responses were observed in children with COVID-19.

Conclusion

Significant differences in immune responses between adults and children with COVID-19 highlight the different mechanisms and potential intervention measures of COVID-19.
Identification of Parkinson’s disease using MRI and genetic data from the PPMI cohort: an improved machine learning fusion approach
Authors: Yang Yifeng , Hu Liangyun , Chen Yang , Gu Weidong , Lin Guangwu , Xie YuanZhong , Nie Shengdong
Published: February 2025

Objective

This study aim to leverage advanced machine learning techniques to develop and validate novel MRI imaging features and single nucleotide polymorphism (SNP) gene data fusion methodologies to enhance the early identification and diagnosis of Parkinson’s disease (PD).

Methods

We leveraged a comprehensive dataset from the Parkinson’s Progression Markers Initiative (PPMI), which includes high-resolution neuroimaging data, genetic single-nucleotide polymorphism (SNP) profiles, and detailed clinical information from individuals with early-stage PD and healthy controls. Two multi-modal fusion strategies were used: feature-level fusion, where we employed a hybrid feature selection algorithm combining Fisher discriminant analysis, an ensemble Lasso (EnLasso) method, and partial least squares (PLS) regression to identify and integrate the most informative features from neuroimaging and genetic data; and decision-level fusion, where we developed an adaptive ensemble stacking (AE_Stacking) model to synergistically integrate the predictions from multiple base classifiers trained on individual modalities.

Results

The AE_Stacking model achieving the highest average balanced accuracy of 95.36% and an area under the receiver operating characteristic curve (AUC) of 0.974, significantly outperforming feature-level fusion and single-modal models (p < 0.05). Furthermore, by analyzing the features selected across multiple iterations of our models, we identified stable brain region features [lh 6r (FD) and rh 46 (GI)] and key genetic markers (rs356181 and rs2736990 SNPs within the SNCA gene region; rs213202 SNP within the VPS52 gene region), highlighting their potential as reliable early diagnostic indicators for the disease.

Conclusion

The AE_Stacking model, trained on MRI and genetic data, demonstrates potential in distinguishing individuals with PD. Our findings enhance understanding of the disease and advance us toward the goal of precision medicine for neurodegenerative disorder.
Auditory steady state response can predict declining EF in healthy elderly individuals
Authors: Mao Xiaopeng , Shenton Nelly , Puthusserypady Sadasivan , Lauritzen Martin Johannes , Benedek Krisztina
Published: February 2025

Background

The aging population imposes significant economic and societal challenges, underscoring the need for early detection of individuals at risk of cognitive decline prior to the onset of clinical symptoms. This study explores the association between gamma-band Auditory Steady-State Responses (ASSRs) and subclinical cognitive decline using longitudinal data from healthy volunteers in the Metropolit Birth Cohort (MBC).

Methods

Longitudinal recordings of cognitive test results and ASSRs at 40 Hz stimulation were analyzed. Generalized Linear Models (GLMs) were employed to determine the association between ASSR characteristics and cognitive performance with an emphasis on Executive Function (EF) at ages 61–68. Additionally, Vision Transformers (ViTs) were trained to distinguish between individuals with declining and stable cognitive performance.

Results

Subjects with declining cognitive performance through midlife showed a larger area of entrainment and delayed neural assembly of ASSRs compared to those with stable cognitive performance. These neurophysiological changes were correlated with poorer EF, as measured by the Stockings of Cambridge (SOC) task. The ViTs trained and cross-validated on time-frequency-transformed Electroencephalograms (EEGs) achieved an average cross-subject accuracy of 51.8% in identifying cognitive decline.

Conclusion

Gamma-band ASSR characteristics are linked to early cognitive decline in middle-aged individuals, offering potential as biomarkers. However, the limited predictive accuracy of ML models emphasizes the need for further refinement to enhance their clinical applicability.