bluuebunny/crossref_metadata_2025 huggingface dataset:
Conditional diffusion-generated super-resolution for myocardial perfusion MRI
Authors: Sun Changyu , Goyal Neha , Wang Yu , Tharp Darla L. , Kumar Senthil , Altes Talissa A.
Published: January 2025

Introduction

Myocardial perfusion MRI is important for diagnosing coronary artery disease, but current clinical methods face challenges in balancing spatial resolution, temporal resolution, and slice coverage. Achieving broader slice coverage and higher temporal resolution is essential for accurately detecting abnormalities across different slice locations but remains difficult due to constraints in acquisition speed and heart rate variability. While techniques like parallel imaging and compressed sensing have significantly advanced perfusion imaging, they still suffer from noise amplification, residual artifacts, and potential temporal blurring due to the rapid transit of dynamic contrast vs. the temporal constraints of the reconstruction.

Methods

This study introduces a conditional diffusion-based generative model for myocardial perfusion MRI super resolution, addressing the trade-offs between spatiotemporal resolution and slice coverage. We adapted Denoising Diffusion Probabilistic Models (DDPM) to enhance low-resolution perfusion images into high-resolution outputs without requiring temporal regularization. The forward diffusion process introduces Gaussian noise incrementally, while the reverse process employs a U-Net architecture to progressively denoise the images, conditioned on the low-resolution input image.

Results

We trained and validated the model on a retrospective dataset of dynamic contrast-enhanced (DCE) perfusion MRI, consisting of both stress and rest images from 47 patients with heart disease. Our results showed significant image quality improvements, with a 5.1% reduction in nRMSE, a 1.1% increase in PSNR, and a 2.2% boost in SSIM compared to GAN-based super-resolution method (P < 0.05 for all metrics using paired t-test) in retrospective study. For the 9 prospective subjects, we achieved a total nominal acceleration of 8.5-fold across 5–6 slices through a combination of low-resolution acquisition and GRAPPA. PerfGen outperformed GAN-based approach in sharpness (4.36 ± 0.38 vs. 4.89 ± 0.22) and overall image quality (4.14 ± 0.28 vs. 4.89 ± 0.22), as assessed by two experts in a blinded evaluation (P < 0.05) in prospective study.

Discussion

This work demonstrates the capability of diffusion-based generative models in generating high-resolution myocardial perfusion MRI from conditional low-resolution images. This approach has shown the potentials to accelerate myocardial perfusion MRI while enhancing slice coverage and temporal resolution, offering a promising alternative to existing methods.
The plight of Ukrainian refugees staying in Sweden under EU:s mass refugee directive: a brief trauma-focused, participatory, online intervention as a pilot feasibility study
Authors: Ekblad Solvig , Gramatik Oksana , Suprun Yuliia
Published: January 2025

Background

Ukrainians staying in Sweden under the EU mass refugee directive may face challenges due to traumas caused by the invasion that started on February 24, 2022. Part of an European Social Fund (ESF) project, our study showed that a brief trauma-focused group intervention onsite helped to increase health and mental-health literacy. The intervention has not yet been adapted online.

Methods

This pilot study during six months aimed to investigate the feasibility, acceptability and outcome in perceived trust, anxiety/stress, and perceived health after this brief trauma-focused group intervention online. A second aim was to observe perceived acceptability of the group intervention with different ways of online intervention. Local coaches, interpreters, the authors, and local experts participated. A mixed-methods design with participatory methodology and evaluation were used. Data was collected with a short questionnaire in Ukrainian. Additionally, at the end of each set, we orally asked about perceived trust and integrity. There were six sets of five group sessions per set, a total of 30 sessions. Each group met online five times for 2 h, a total of 10 h excluding pre- and post-assessment. Breathing exercises sought to reduce stress among the participants.

Results

The group intervention had both strengths and limitations. Baseline data were obtained from 136 participants, mostly females (75.7%). Answers to pre- and post-questionnaires showed that perceived anxiety/stress was significantly reduced (N = 91, chi-2 20.648, df = 6, p < .02). Perceived health significantly improved between pre- (mean 63.6) and post (77.2) (N = 77, t = −8.08, df = 66, p < .001). Older participants were vulnerable with higher stress and lower mean perceived health after the intervention. Four out of ten needed individual psychosocial support online.The participants' open questions were analyzed with qualitative content analysis, giving five general categories and 25 sub-categories and the theme “Strong efforts to cope with Swedish system”.

Conclusion

Trust and reduced anxiety level changed after the intervention and a combination online of small, closed group meetings with the possibility of personal acquaintance, trust and individual follow-up psychosocial support for those in need to be paid attention to for future refugee support services, particular an online format.
Norwegian higher education teachers’ beliefs about teaching, motivation, and approaches to researching and developing teaching
Authors: Ferguson Leila E.
Published: January 2025

Quality teaching in higher education is enjoying renewed political and scholarly interest in Norway. Building on extant research on teachers at primary and secondary levels, and budding research at the tertiary level, the present investigation focuses on higher education teachers’ beliefs about teaching, motivation, and beliefs about researching and developing teaching. Using data from the Teaching in Higher Education (THE) Survey that was subjected to factor and regression analyses, we found that participants (n = 56) preferred alternative and personal sources of teaching knowledge over formal sources and those offered by academic developers. On the whole, the participants were motivated to teach. Relations were found between beliefs about sources of teaching knowledge and motivation, respectively, and beliefs about research and development of teaching. Implications in terms of the Scholarship of Teaching and Learning and academic development, including the need for increased focus on teacher beliefs and evidence-based practice in higher education, are discussed.
What do I need from myself as a student but also from others to reduce the impact of stress on academic performance? Self-efficacy and social support
Authors: Pǎduraru Ancuţa Elena , Soponaru Camelia , Dîrţu Cǎtǎlin , Gavrilovici Ovidiu , Bucuţǎ Mihaela Dana
Published: January 2025

Introduction

The literature emphasizes the link between academic stress and academic performance and the fact that the most vulnerable students are first-year students, but we still need to understand the underlying mechanism for forming targeted intervention strategies and the protective factors. The main objective of the present study was to test the mediating effect of self-efficacy and social support on the relationship between academic stress and academic performance. We also aimed to identify the main sources of stress and their significant sources of support.

Methods

Data were collected via an online survey platform in January 2024, with 436 students, with a mean age of 19.99 ± 3.72, responding affirmatively to our invitation. Thus, in this cross-sectional study, the sample was a convenience sample.

Results

The highest source of stress was the pressure to perform, followed by time restraints, perceptions of workload and examinations, and self-perceptions. The highest level of support is obtained from significant others, followed by family support and, last, friends' support. Both self-efficacy and social support partially mediate the effect of academic stress on academic performance.

Conclusions

Our results suggest that one way to improve students' performance, even when they experience academic stress, is to increase their levels of social support, especially from family, as well as their self-efficacy. These results can be used by services that provide psychological support to students in order to design and implement intervention programs.
Interpretative phenomenological analysis of guidance advocates’ online counseling experiences
Authors: Tangco-Siason Amabel , Paulino Rex S.
Published: January 2025

Introduction

In order to document and understand the lived experiences of guidance advocates navigating transactional distance in education, this phenomenological study examined the experiences of advocates in the Philippines.

Methods

This study examined how clients and guidance advocates interact in online learning environments, with a particular emphasis on the experiences of eight individuals who underwent online counseling (OC). These individuals provided firsthand experiences that elaborated the phenomenon.

Results

The study, which has its roots in Transactional Distance Theory (TDT), finds interesting connections between the variables and the experiences of the individuals. Among these variables are: (i) discourse that mirrors the exchanges between a counselor and a client; (ii) framework, which includes OC dynamics and changing communication requirements; and (iii) learner autonomy, which stands for the involvement of clients in online learning.

Discussion

A community-based framework for developing students is formed by these variables. The data shared by participants reveal complex issues as they struggle with the limitations and realities of applying standards in multimodal counseling sessions. This change emphasizes how important it is for students to have a strong support system. The study, which focused on guidance advocate-client relations, took inspiration from the eight participants’ OC experiences. The mechanisms that promote a reciprocal, technology-mediated kind of communication are central to this emerging structure.
Language-mixing in Content and Language Integrated Learning: benefit or burden? An auditory recall perspective
Authors: Caira Thomas , Declerck Mathieu , Struys Esli
Published: January 2025

Recent pedagogical trends have seen a revival in language-mixing in CLIL contexts, thereby challenging the traditional ‘one subject-one language’ approach. From a cognitive standpoint, recent research indicates that the disadvantages of language mixing may not be as significant as previously thought. This is further supported by studies showing no negative effects of language-mixing on immediate memory recall in CLIL pupils. Using an Old/New recognition task design, participants in the present study had to differentiate between previously defined concepts and new ones in three different language contexts (i.e., single-language L1; single-language L2 and a mixed context). We also accounted for delayed recall with a second test phase 36 hours after the first one. Response times and accurate recall scores were retained for further analysis. Our findings reveal a nuanced picture: we found that mixed-language input negatively impacts immediate and delayed recall of information compared to L1 input. However, mixed-language input also brings about better recall of information compared to L2 input. It seems that language-mixing thus partly mitigates the disadvantage in auditory recall that occurs in a single-language L2 context. Overall, these results suggest a need to reconsider the effects of language-mixing on memory and, consequently, nuance its role in CLIL practices.
Empowering marginalized communities through the digital transformation course
Authors: Yüksel-Arslan Pelin , Plant Claudia , Kayali Fares
Published: January 2025

This article examines a project dedicated to comprehensively addressing the social impact of digital transformation. The project also emphasizes the effects of digital transformation on marginalized populations, especially forced migrants and individuals with special needs. The project involves the development of open-access course materials titled “Digital Life 1–2–3-4,” which are shared as open-access resources through four MOOCs on the iMooX platform. The primary goal is to increase awareness of the effects of digital transformation in daily life, such as algorithmic bias, inaccessibility, robots and digital divide, digital inclusion, and digital discrimination. By integrating ethical considerations, promoting digital literacy, and considering bringing users into the design process, the course mitigates the impact of digital transformation and promotes an equitable and empowering digital environment for the everyday use of technology, particularly for marginalized communities. In this article, we discuss specific course content, including digital inclusion, algorithmic bias, and emerging inequalities. The key goals are to understand and mitigate the risks of algorithmic bias, inaccessibility, and digital discrimination in educational technologies affecting diverse and vulnerable populations, and to promote digital literacy, access, and motivational design to encourage forced migrants’ active and safe participation in technology-enabled education. We conclude that it is essential to prioritize ethical principles in their design and application, elevate underrepresented voices, and foster a more equitable and inclusive digital landscape.
Case report: Persistent syndrome of inappropriate antidiuresis after traumatic brain injury: spontaneous resolution and impact on RAAS and bone metabolism over five years
Authors: Liu Yaoxia , Tang Jiao , Zhou Mingwei , Huang Haotian , Wang Tao , Zhang Min
Published: January 2025

The syndrome of Inappropriate Antidiuresis (SIAD) is a well-known cause of hyponatremia and can be associated with various etiologies, including traumatic brain injury (TBI). Most cases of SIAD following TBI exhibit a pattern in which hyponatremia develops several days to weeks after the trauma and resolves within a few weeks. Here, we present a rare case of persistent SIAD caused by TBI that resolved spontaneously after five years. The patient experienced prolonged hyponatremia for several years and was ultimately diagnosed with post-traumatic SIAD after excluding other potential causes. Notably, the patient exhibited an unusual sensitivity to tolvaptan, accompanied by decreased renin levels and increased bone turnover markers. The condition resolved spontaneously after five years, with renin, aldosterone, and bone turnover markers returning to normal upon re-evaluation.
Household level fuelwood use and carbon dioxide emissions in Delanta district, Northeastern Ethiopia
Authors: Sintayehu Eshetu Abebaw
Published: January 2025

Introduction

Ethiopian rural households primarily rely on fuelwood as their main energy Q7 source, yet the country lacks precise data on fuelwood harvesting and its economic significance. Consequently, there is limited understanding of CO2 emissions resulting from fuelwood use.

Methods

This study aimed to estimate the annual amount of fuelwood collected and the associated CO2 and carbon (C) emissions. Using simple random sampling for household selection, data were analyzed with Excel and Stata.

Results

The results reveal that fuelwood dependency is a major driver of deforestation and CO2 emissions, with households consuming approximately 2,725 kg of firewood and 26 kg of charcoal annually. Each household also extracts an average of 3,909.3 kg of firewood and 516.5 kg of charcoal annually for sale. Among sampled households, fuelwood constitutes 904,261 kg of energy, with 51% used for household consumption and 96% allocated for income generation. The inefficient burning of this fuel results in significant emissions, adding 974,000 kg of CO2 or 265,600 kg of carbon annually to the household carbon footprint. On average, each household emits 7,740 kg of CO2 and 1,960 kg of carbon per year.

Discussion

The study emphasizes that, while fuelwood plays a critical role in household energy and income, its unsustainable use accelerates emissions and deforestation. To mitigate these effects, the adoption of alternative energy sources like electricity and forest conservation through local plantations is essential for climate resilience.
Identification of key genes underlying radiosensitivity and radioresistance in endometrial cancer through integrated bioinformatics analysis
Authors: Wan Chunhui , Zhang Lei , Yu Ting , Lu Hui , Xiao Han , Du Juan
Published: January 2025

Introduction

Radiation therapy is crucial in the treatment of endometrial cancer (UCEC). Patients exhibit significant variability in radiosensitivity, affecting therapeutic effect. Scarcity of studies exploring the gene-radiosensitivity relationship based on clinical data. Underlying molecular mechanisms of radiosensitivity and radioresistance require further investigation.

Methods

Study aimed to reveal molecular mechanisms underlying radiosensitivity and radioresistance in UCEC patients. Included 12 radiosensitive and 20 radioresistant UCEC samples. Conducted differential expression analysis to screen for significantly different genes between groups. Applied Lasso regression and randomized survival forest model to identify key genes. Performed functional annotation, correlation analysis, and survival analysis on key genes.

Results

Key genes positively correlated with UCEC tumorigenesis-related genes in the radioresistant group. Reduction in the proportion of Macrophages.M0 observed in the radioresistant group, associated with poor prognosis. GO and GSVA analyses revealed biological processes and signaling pathways involved in key genes. High expression of MARCKS, MACC1, and GRB10 correlated with poorer survival rates. High expression of NINJ2 correlated with higher survival rates and higher sensitivity to radiation therapy.

Discussion

Study contributes to a deeper understanding of UCEC radiosensitivity. Provides theoretical support for the development of personalized radiotherapy regimens in clinical practice. Potential to improve prognosis and quality of life of patients.
Prevalence and characteristics of gastrointestinal disorders, medication use, and diagnostic interventions in pediatric patients with cystic fibrosis: a nested case–control analysis from the TriNetX EMR-derived global research network real-world dataset
Authors: Trocchia Carolena , Mosha Maua , Hamner Bailey , Goldenberg Neil , Khalaf Racha
Published: January 2025

Background

Gastrointestinal (GI) disease in pediatric patients with cystic fibrosis (CF) is a growing concern in the era of improved lung disease; however, the true prevalence of GI diagnoses, medical therapies, and frequency of diagnostic and therapeutic interventions in this population have yet to be explored on a multisystem scale. The aim of the present study was to describe, among pediatric patients with CF (PwCF) compared to a large cohort of healthy controls, the prevalence and types of 1) GI disorders; 2) GI medication use; and 3) GI procedural interventions.

Methods

This was a multicenter case-control analysis using the TriNetX electronic medical record (EMR) global anonymized data platform. Patients were included if they had an ICD9/10 diagnosis code and were between the age of zero to ≤ 21 years between January 1st, 2010, and January 1st, 2020. Those with a history of solid organ transplants were excluded.

Results

The cohort was comprised of 7,649 patients with a diagnosis of CF (cases) and 22,516,240 patients without CF (controls). The prevalence of any GI disorder was greater in pediatric PwCF compared to those without CF (73% versus <1%). The prevalence of diseases of the biliary tract and pancreas (43% vs. <1%; p<.0001), hepatic disease (8.8% vs. <1%; p<.0001), disease of the esophagus to duodenum (34% vs. <1%; p<.0001), and intestinal disease (43% vs. <1%; p<.0001) were each significantly greater in PwCF (p<0.0001). Furthermore, the frequencies of esophagogastroduodenoscopy (EGD), colonoscopy and endoscopic retrograde cholangiopancreatography (ERCP) were significantly higher among PwCF than controls (9.5% vs. <1%; 2.8%% vs. <1%; and 0.3% vs <.001% respectively; p<0.0001 for all comparisons).

Conclusion

The prevalence of GI diagnoses, use of GI medications, and frequency of GI procedures are all higher among pediatric patients PwCF. Prospective multicenter studies are warranted to substantiate these findings, further investigate risk factors for GI disorders, and to describe potential changes in GI disorders with novel CF disease-modifying therapies.
Deciphering the role of metal ion transport-related genes in T2D pathogenesis and immune cell infiltration via scRNA-seq and machine learning
Authors: Pu Zuhui , Wang Tony Bowei , Lu Ying , Wu Zijing , Chen Yuxian , Luo Ziqi , Wang Xinyu , Mou Lisha
Published: January 2025

Introduction

Type 2 diabetes (T2D) is a complex metabolic disorder with significant global health implications. Understanding the molecular mechanisms underlying T2D is crucial for developing effective therapeutic strategies. This study employs single-cell RNA sequencing (scRNA-seq) and machine learning to explore the the pathogenesis of T2D, with a particular focus on immune cell infiltration.

Methods

We analyzed scRNA-seq data from islet cells of T2D and nondiabetic (ND) patients, identifying differentially expressed genes (DEGs), especially those related to metal ion transport (RMITRGs). We employed 12 machine learning algorithms to develop predictive models and assessed immune cell infiltration using single-sample gene set enrichment analysis (ssGSEA). Correlations between immune cells and key RMITRGs were investigated, and the interactions among these genes were explored through protein-protein interaction (PPI) network analysis. Additionally, we performed a detailed cell-cell communication analysis to identify significant signaling pathways in T2D.

Results

Our analysis identified 1953 DEGs between T2D and ND patients, with the Stepglm[backward] plus GBM model demonstrating high predictive accuracy and identifying 13 hub RMITRGs. Twelve protein structures were predicted using AlphaFold 3, revealing potential functional conformations. We observed a strong correlation between hub RMITRGs and immune cells, and PPI network analysis revealed key interactions. Cell-cell communication analysis highlighted 16 active signaling pathways, with CXCL, MIF, and COMPLEMENT linked to immune and inflammatory responses, and WNT, KIT, LIFR, and HGF pathways uniquely activated in T2D.

Conclusion

Our analysis identified genes crucial for T2D, emphasizing ion transport, signaling, and immune cell interactions. These findings suggest therapeutic potential to enhance T2D management. The identified pathways and genes provide valuable insights into the disease mechanisms and potential targets for intervention.
MUC2 expression modulates immune infiltration in colorectal cancer
Authors: Raynaud Christophe M. , Jabeen Ayesha , Ahmed Eiman I. , Hubrack Satanay , Sanchez Apryl , Sherif Shimaa , Al-Shaibi Ahmad A. , Lo Bernice , Roelands Jessica , Bedognetti Davide , Hendrickx Wouter
Published: January 2025

Introduction

Colorectal cancer (CRC) is a prevalent malignancy with significant morbidity and mortality worldwide. A deeper understanding of the interaction of cancer cells with other cells in the tumor microenvironment is crucial to devise effective therapeutic strategies. MUC2, a major component of the protective mucus layer in the gastrointestinal tract, has been implicated in CRC progression and immune response regulation.

Method

In this study, we sought to elucidate the relationship between MUC2 expression and immune infiltration within CRC using in vitro models involving two well-established cell lines, HT-29 and LS-174T. By employing CRISPR-mediated MUC2 knockout, we investigated the influence of MUC2 on tumor immune infiltration and its interplay with T cells and NK cells enriched peripheral blood mononuclear cells (PBMCs) in 3D spheroid cultures.

Results

While MUC2 was more abundant in LS-174T cell line compared to HT-29, its knockout resulted in increased immune infiltration solely in the HT-29 cell line, but not in the LS-174T cell line. We revealed that the removal of MUC2 protein was compensated in LS-174T by the expression of other gel-forming mucin proteins (MUC6, MUC5B) commonly expressed in the gastrointestinal epithelium, while this was not observed in HT-29 cell line.

Conclusion

Our study is the first to demonstrate that MUC2 functions as a physical barrier to immune infiltration in colorectal cancer (CRC) in vitro. In HT-29 cells, MUC2 knockout increased immune infiltration, while in LS-174T cells, compensatory expression of other mucins (MUC6, MUC5B) maintained the barrier. These findings reveal the complexity of mucin biology in CRC and suggest that targeting mucin pathways could be a novel therapeutic approach.
Novel immunochromatographic test for rapid detection of anti-factor H autoantibodies with an assessment of its clinical relevance
Authors: Rodríguez de Córdoba Santiago , Reparaz Andrea , Sanchez Daniel , Pinto Sheila , Juana Lopez Lucia , Martin Merinero Héctor , Calvete Iria , Perez-Perez Julian , Jellison Sydney S. , Zhang Yuzhou , Smith Richard J. H. , Moreno Inmaculada , Dominguez Mercedes
Published: January 2025

Factor H (FH) is a crucial complement regulator that prevents complement-mediated injury to healthy cells and tissues. This regulatory function can be disrupted by Factor H autoantibodies (FHAA), which then leads to diseases such as atypical hemolytic uremic syndrome (aHUS) and C3 Glomerulopathy (C3G). In pediatric aHUS, the FHAA incidence is ~10-15%, although in the Indian population, it rises to ~50%. The specific regions of FH targeted by FHAAs correlate with the pathogenic mechanism of the associated disease. In aHUS, FHAAs target the C-terminus, thereby impacting FH ability to recognize cell surfaces. In C3G, in contrast, FHAAs often target the N-terminus, generating an acquired functional FH deficiency. Detection and monitoring FHAAs are decisive for effectively treating patients. Current FHAA analysis normally identify free FHAAs that bind surface-bound FH using ELISA techniques. These methods require well-equipped laboratories and qualified staff, and do not measure FH-FHAA complexes, which can make it difficult to correlate titers with clinical outcomes. The visually-based immunochromatographic test (ICT) described herein allows for quick detection and quantification of IgG and IgM FH-FHAA complexes in human EDTA-plasma or serum. This ICT offers improved detection of FHAAs compared to ELISA as demonstrated by cases where the ICT identifies FH-FHAA complexes in samples that tested negative with the free FHAA ELISA. Importantly, the ICT indirectly informs on the amount of FH that is complexed with FHAAs, thus assessing the significance of the FHAA in disrupting the regulatory function of FH. Overall, this novel assay offers a simple, fast, cost-effective, and, likely, more clinically relevant alternative for diagnosing FHAAs in at-risk populations.
Mycobacterium spp. exposure, childhood vaccinations, and early childhood brain and CNS cancers
Authors: Singh Samer , Singh Rakesh K.
Published: January 2025

Globally, with improvements in general hygiene, the incidence of early childhood (0-4Y-olds/<5Y-olds) brain and central nervous system (BCNS) cancers is increasing. Although immunological underpinning is suspected, the identification of protective variables for the majority of BCNS cancer cases remains elusive. Extant hypotheses suggest a role for progressively diminishing exposure to common microbes/pathogens in the rise of childhood cancers in industrialized countries with improved hygiene. Natural exposure to common microbes/pathogens and childhood vaccinations help train the developing immune system of children to respond appropriately to future infections and maintain a healthy immune system. Considering the established role of childhood vaccinations in augmenting immunity, including “trained immunity," their protective role in pediatric cancers may be surmised. However, a lack of definitive theoretical and practical frameworks to explain conflicting observations has impaired progress. When we analyze the epidemiological data of European region countries with different childhood vaccination policies but more similar socioeconomic conditions, access to medical services, and genetic makeup as compared to other parts of the world, the coverage of seven major childhood (0-1Y-olds) vaccines does not significantly associate with BCNS cancer incidences in the same cohort of 0-4Y-olds (2020). However, interestingly, prevailing tuberculin immunoreactivity, a surrogate for the existence of heterologous cell-mediated immunity resulting from exposure to Mycobacterium spp., including Bacille Calmette-Guérin (BCG) vaccination, for these populations, is found consistently negatively correlated with the BCNS cancer incidence in 0-4Y-olds for countries mandating neonatal BCG vaccination [r(24): -0.7226, p-value:<0.0001]. Seemingly, neonatal immune-system priming by BCG and boosting by exposure to environmental Mycobacterium spp. appear protective in 0-4Y-olds. Exploration of BCNS cancer incidence and prevailing immune correlates in matched cohorts, along with prospective randomized controlled trials, may be warranted to conclusively ascertain the impact of childhood vaccinations and boosters (including natural exposure) on early childhood BCNS cancer incidence.
Time-restricted feeding improves metabolic syndrome by activating thermogenesis in brown adipose tissue and reducing inflammatory markers
Authors: Gong Yueling , Zhang Honghui , Feng Jiang , Ying Li , Ji Mengmeng , Wei Shiyin , Ma Qiming
Published: January 2025

Background

Obesity and metabolic syndrome (MetS) have become increasingly significant global health issues. Time-restricted feeding (TRF), as a novel dietary intervention, has garnered attention in recent years. However, there is limited research focusing on the effects of TRF on energy expenditure and systemic low-grade inflammation. This study aims to investigate the impact of TRF on weight management, glucose metabolism, insulin resistance, and lipid metabolism in male C57BL/6J mice, particularly in the context of metabolic disorders induced by a high-fat diet (HFD).

Methods

C57BL/6J mice were divided into two groups: a normal diet (ND) group and a high-fat diet (HFD) group. The study duration was 12 weeks. Key parameters observed included body weight, glucose tolerance (via glucose tolerance tests), insulin resistance (HOMA-IR), and insulin secretion under glucose stimulation. Additionally, liver tissue was subjected to Oil Red O staining to assess lipid accumulation, and white and brown adipose tissues were stained with hematoxylin and eosin (HE) to evaluate adipocyte size. The expression of hepatic lipogenesis-related genes (Srebp-c, Chrebp, Fasn, and Acc1) and thermogenic genes in brown adipose tissue (UCP1 and PGC-1α) were also measured. Furthermore, temperature changes in the interscapular brown adipose tissue (BAT) were monitored.

Results

In the ND group: TRF improved insulin resistance and reduced circulating levels of the pro-inflammatory cytokine IL-6, with a slight reduction in body weight.In the HFD group: TRF significantly mitigated weight gain, improved glucose tolerance and insulin resistance, and enhanced insulin secretion under glucose stimulation. Additionally, TRF reduced hepatic steatosis by downregulating the expression of lipogenesis-related genes in the liver. TRF also increased thermogenesis by upregulating the expression of thermogenic genes (UCP1 and PGC-1α) in BAT, while lowering serum levels of pro-inflammatory cytokines IL-6 and TNF-α, though IL-1β levels remained unchanged.

Conclusion

This study demonstrates that TRF can activate thermogenesis in brown adipose tissue and reduce inflammation maker, leading to an improvement in hepatic steatosis and a reduction in white adipose tissue accumulation. These findings suggest that TRF may be a promising intervention for mitigating metabolic disturbances associated with obesity and metabolic syndrome. The study provides mechanistic insights into the beneficial effects of TRF, highlighting its potential in modulating lipid metabolism and exerting anti-inflammatory effects.
Evaluation of B cell related markers and autoantibodies in rheumatoid arthritis patients treated with abatacept
Authors: Wang Ting , Giltiay Natalia V. , Lood Christian , Wang Ning , Han Bobby Kwanghoon
Published: January 2025

Objectives

To investigate whether biomarkers related to B cell activation and autoantibody production are associated with the response to abatacept in rheumatoid arthritis (RA) patients.

Methods

Twenty-five patients with RA were enrolled in this study. Responders (n=10) to abatacept were subjects who achieved ACR50 response at week 24. Serum levels of soluble biomarkers were measured with ProcartaPlex by Luminex or ELISA. Peripheral blood mononuclear cells were isolated and analysed for T cell and B cell subsets by flow cytometry. Patients were genotyped for human leukocyte antigen (HLA)-DRB1 shared epitope (SE) alleles. Baseline levels and longitudinal changes of markers were assessed between responders and nonresponders.

Results

Baseline levels of anti-cyclic citrullinated peptide (anti-CCP) antibodies (p=0.01), IgM rheumatoid factor (RF) (p=0.02), CXC chemokine ligand 13 (CXCL13, p=0.02), sCD23 (p<0.05), as well as frequencies of CD19+CD11c+IgD-CD27- B cells (p=0.04), were higher in responders than nonresponders. Among them, anti-CCP and frequencies of CD19+CD11c+IgD-CD27- B cells were independently associated with response to abatacept. The presence of two alleles of SE was associated with responders (p=0.04). Patients with 2 alleles of SE had higher levels of anti-CCP (p=0.02) and IgM RF (p=0.04) compared to patients with 0 or 1 allele. Further, IgM RF and CXCL13 levels decreased only in responders (p=0.02 and 0.004 respectively, at week 24), while anti-CCP levels did not decrease significantly in either responders or nonresponders.

Conclusion

Markers of B cell activation including anti-CCP and frequencies of CD19+CD11c+IgD-CD27- B cells in RA were associated with response to abatacept. IgM RF and CXCL13 decreased only in responders and could be potentially used as pharmacodynamic markers.
From actinic keratosis to cutaneous squamous cell carcinoma: the key pathogenesis and treatments
Authors: Li Zhenlin , Lu Fangqi , Zhou Fujin , Song Dekun , Chang Lunhui , Liu Weiying , Yan Guorong , Zhang Guolong
Published: January 2025

Cutaneous squamous cell carcinoma (cSCC) is the second most common non-melanoma skin cancer, among which 82% arise from actinic keratosis (AK) characterized by lesions of epidermal keratinocyte dysplasia. It is of great significance to uncover the progression mechanisms from AK to cSCC, which will facilitate the early therapeutic intervention of AK before malignant transformation. Thus, more and more studies are trying to ascertain the potential transformation mechanisms through multi-omics, including genetics, transcriptomics, and epigenetics. In this review, we gave an overview of the specific biomarkers and signaling pathways that may be involved in the pathogenesis from AK to cSCC, pointing out future possible molecular therapies for the early intervention of AK and cSCC. We also discussed current interventions on AK and cSCC, together with future perspectives.
Active ingredients of traditional Chinese medicine inhibit NOD-like receptor protein 3 inflammasome: a novel strategy for preventing and treating heart failure
Authors: Lin Ruifang , Yu Yunfeng , Du Lixin , Ding Zehui , Wang Ziyan , Wei Jiaming , Guo Zhihua
Published: January 2025

Heart failure (HF) has emerged as a significant global public health challenge owing to its high rates of morbidity and mortality. Activation of the NOD-like receptor protein 3 (NLRP3) inflammasome is regarded as a pivotal factor in the onset and progression of HF. Therefore, inhibiting the activation of the NLRP3 inflammasome may represent a promising therapeutic approach for preventing and treating HF. The active ingredients serve as the foundation for the therapeutic effects of traditional Chinese medicine (TCM). Recent research has revealed significant advantages of TCM active ingredients in inhibiting the activation of the NLRP3 inflammasome and enhancing cardiac structure and function in HF. The study aimed to explore the impact of NLRP3 inflammasome activation on the onset and progression of HF, and to review the current advancements in utilizing TCM active ingredients to inhibit the NLRP3 inflammasome for preventing and treating HF. This provides a novel perspective for the future development of precise intervention strategies targeting the NLRP3 inflammasome to prevent and treat HF.
Comprehensive single-cell pan-cancer atlas unveils IFI30+ macrophages as key modulators of intra-tumoral immune dynamics
Authors: Jiang Lihe , Wang Peili , Hou Yixuan , Chen Jingying , Li Hua
Published: January 2025

Background

The convergence of macrophage-targeted strategies with immune checkpoint blockade therapies defines a pivotal avenue in contemporary tumor therapy. Identifying robust genetic regulators in this context is imperative.

Methods

This study elucidates IFI30's role in enhancing Major Histocompatibility Complex II (MHC-II) restriction antigen processing. Despite its recognition in cancer immunotherapy, IFI30 remains a nascent focus. Our approach involves a multi-omics analysis of IFI30 tumor immunological profile in the macrophage-mediated Tumor Microenvironment (TME), spanning various cancers and bolstered by rigorous co-culture laboratory work.

Results

IFI30 predominantly localizes in monocyte/macrophage populations, correlating strongly with immune cell infiltration. Substantiated by single-cell analysis, IFI30 exhibits significant functional enrichment in immune-related pathways. Co-expression with immune-related genes, including MHC elements and immune checkpoints, further validates its relevance.

Conclusion

Our study positions IFI30 as a promising immunotherapeutic target. Pan-cancer analyses and glioblastoma multiforme (GBM) investigations collectively underscore IFI30's potential as a TME modulator, particularly in its interaction with M2-macrophages. IFI30 emerges as a prospective intervention point in the immunotherapeutic landscape.
Exhaustion of CD8pos central memory regulatory T cell differentiation is involved in renal allograft rejection
Authors: Kälble Florian , Leonhard Jonas , Zeier Martin , Zivanovic Oliver , Schaier Matthias , Steinborn Andrea
Published: January 2025

Background

The role of regulatory CD8pos T cells (CD8pos Tregs) and cytotoxic CD8pos responder T cells (CD8pos Tresps) in maintaining stable graft function in kidney transplant recipients (KTR) remains largely unclear. The pathogenesis of graft deterioration in case of rejection involves the exhaustive differentiation of both CD8pos T cell subsets, but the causal mechanisms have not yet been identified.

Methods

In this study, we separately investigated the differentiation of CD8posTregs/Tresps in 134 stable KTR with no evidence of renal graft rejection, in 41 KTR diagnosed with biopsy-confirmed rejection at enrolment and in 5 patients who were unremarkable at enrolment, but developed rejection within three years of enrolment. We were investigating whether changed differentiation of CCR7posCD45RAposCD31pos recent thymic emigrant (RTE) cells via CD45RAnegCD31pos memory (CD31pos memory) cells (pathway 1), via direct proliferation (pathway 2), or via CCR7posCD45RA+CD31neg resting mature naïve (MN) cells (pathway 3) into CD45RAnegCD31neg memory (CD31neg memory) cells affects the CD8pos Treg/Tresp ratio or identifies a CD8pos Treg/Tresp subset that predicts or confirms renal allograft rejection.

Results

We found that RTE Treg differentiation via pathway 1 was age-independently increased in KTR, who developed graft rejection during the follow-up period, leading to abundant MN Treg and central memory Treg (CM Treg) production and favoring a strongly increased CD8pos Treg/Tresp ratio. In KTR with biopsy-confirmed rejection at the time of enrolment, an increased differentiation of RTE Tregs into CCR7negCD45RAposCD31neg terminally differentiated effector memory (CD31neg TEMRA Tregs) and CD31pos memory Tregs was observed. CD31neg memory Treg production was maintained by alternative differentiation of resting MN Tregs, resulting in increased effector memory Treg (EM Treg) production, while the CD8pos Treg/Treg ratio was unaffected. An altered differentiation of CD8pos Tresps was not observed, shifting the Treg/Tresp ratio in favor of Tregs.

Conclusions

Our results show that exhaustive CD8pos Treg differentiation into CM Tregs may lead to future rejection, with a shift towards EM Treg production and an accumulation of CD31neg TEMRA Tregs in KTR with current rejection.
Ochratoxin A induces immunotoxicity by targeting Annexin A1 mediated neutrophil apoptosis in zebrafish
Authors: Zheng Yihong , Liu Yinuo , Tian Jin , Liu Shuhong , Ma Gaowei , Xie Yupeng , Zheng Chenhua , Wu Zekai
Published: January 2025

Introduction

Ochratoxin A (OTA) is a toxic secondary metabolite produced by Aspergillus and Penicillium species, posing a significant threat to global food safety. Previous studies have demonstrated the diverse toxic effects of OTA, including hepatotoxicity, nephrotoxicity, and carcinogenicity. However, limited understanding exists regarding its immunotoxicity and the underlying mechanisms, particularly in relation to innate immunity.

Methods

Zebrafish embryos were exposed to varying concentrations of OTA to assess its impact on embryonic development, innate immune cell formation, and immune response. Transcriptome sequencing analysis was performed to identify changes in gene expression. Additionally, the potential therapeutic effect of aesculetin was evaluated.

Results

Our results demonstrated that exposure to OTA inhibited embryonic development and induced malformations in a concentration-dependent manner. Additionally, OTA exposure led to a significant reduction in the number of neutrophils and macrophages, indicating compromised formation of innate immune cells. Furthermore, OTA exposure hampered the immune response during zebrafish fin regeneration, as evidenced by the diminished migration of neutrophils and macrophages to the wound area. Transcriptome sequencing analysis identified significant up-regulation of the anxa1a and anxa1d-mediated apoptosis signaling pathway in neutrophils following OTA treatment. Notably, administration of aesculetin, known for its anti-apoptosis activity, effectively attenuated the immunotoxic effects induced by OTA.

Discussion

These findings provide valuable insights into the immunotoxicity of OTA while highlight the potential therapeutic strategy using aesculetin for mitigating immune dysfunction caused by OTA.
Short distances dominate connectivity patterns of coral communities in the North-West Arabian Sea
Authors: Claereboudt Michel R. , Bruss Gerd
Published: January 2025

Larval connectivity relies on the ability of coral larvae to disperse into the environment following ocean currents. At short timescales, larval connectivity plays a key role in the resilience of coral reefs, as it determines their capacity to regain structure and function after major disturbances. At longer time scales, larval connectivity controls the distribution and, ultimately, the biogeography of species. We used a Lagrangian stochastic model to simulate the transport routes of coral larvae released from the major reef communities of the Arabian Sea and Gulf of Oman. The model used surface currents from two independent global circulation models, and we simulated 120 scenarios, covering four years and three larval competency models. Additionally we determine mean flow fields and LCS structures based on 20 years of reanalysis data from a third model. Connectivity values—the proportion of larvae successfully transported from their natal reef to another reef—varied significantly across reefs and years due to mesoscale variability in ocean currents, yet both circulation models produced similar overall patterns of connectivity. The general flow of larvae was from northwest to southeast in the Gulf of Oman, and from southwest to northeast in the Arabian Sea. The exchange of larvae across Ras Al-Hadd between the coral communities of the Arabian Sea and those of the Gulf of Oman is very low. Local retention (self-seeding) was the most important larval source for most reefs (mean = 32.3% for spawning corals and 70.8% for brooding corals). All reefs received larvae from at least one other reef and several received larvae from as many as five other reefs. ANOVA indicated significant differences between brooding and spawning coral larvae, and between reefs. Differences between years depended on the reef or reproduction type. Some reefs (Daymaniyat Islands in the Gulf of Oman and Mirbat in the Arabian Sea) could be considered sources of larvae, as they proportionally produced more larvae that later settled successfully than the other reefs. The limited connectivity between the Gulf of Oman and Arabian Sea supports their biogeographic distinction based on species distribution.
The evolution and morphodynamic characteristics of shoals and troughs in Lingdingyang Bay of the Pearl River Estuary
Authors: Fu Linxi , Zhong Yuhang , Zhang Ping , Niu Lixia , Zhang Xiaohe , Lin Jianliang , Cai Huayang , Yang Qingshu
Published: January 2025

Shoals and troughs are the fundamental geomorphological units of estuarine systems. However, their definition and morphodynamic characteristics, influenced by the complex dynamic environment, remain a critical challenge. This work introduces a depth–area spatial function as a quantitative criterion for the definition of shoals and troughs, while simultaneously elucidating their geodynamic implications. The Lingdingyang Bay (LDB) of the Pearl River Estuary serves as a case study. From 1901 to 2018, the LDB consisted of the West Shoal, Middle Shoal, and East Shoal and the West Trough and East Trough. The threshold depth of the LDB shifted from −5.75 m in 1901 to −4.75 m between 1964 and 2018. The depth–area distribution curve of the LDB exhibits two dominant peak depths (approximately 0 m and −2 m) within the shoal stable state, which categorizes shallow areas into high, medium and low tidal flats. The shoal–trough area ratio in the LDB, relative to the threshold depths, increased from 1901 to 1998, followed by a decline between 2008 and 2018, and culminated in a restoration to the level seen in 1901 (65% shoals and 35% troughs). Regional variations in dominant forces influencing shoal formation and evolution were observed by the vertical classification of the shoal state. The West Shoal is river dominated, the East Shoal is tide dominated, and the Middle Shoal reflects an interaction between riverine inflows and tides. Stabilized curves observed between 2008 and 2018 indicate that this estuary is progressively achieving new equilibrium states. The depth–area spatial function is useful for identifying shoals and troughs within various estuaries, which also provides a geomorphological framework for understanding the estuarine evolution and sediment dynamics.