bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of key miRNAs and target genes in extracellular vesicles derived from low-intensity pulsed ultrasound-treated stem cells
Authors: Yin Xin , Yi Jialian , Mao Fugang , Tang Qisheng , Zhang Xinyu , Yang Xiaoyu , Xie Hongqing , Wang Linping , Sun Shuifen , Yu Xin , Liu Jie , Jiang Lihong
Published: January 2025

Objectives

This study aimed to investigate the impact of low-intensity pulsed ultrasound (LIPUS) treatment on the miRNA and mRNA profiles of stem cell-derived extracellular vesicles (EVs). Specifically, it sought to identify key miRNAs and their target mRNAs associated with enhanced therapeutic efficacy in LIPUS-treated stem cell-derived EVs.

Methods

Utilizing miRNA deep-sequencing data from the Gene Expression Omnibus database, differential gene analysis was performed. MiRNA-mRNA target analysis, functional and pathway enrichment analysis, protein-protein interaction network construction, and hub gene identification were conducted. Validation of differentially expressed miRNAs was performed via RT-qPCR in human umbilical cord mesenchymal stem cells (hUC-MSCs) treated with LIPUS.

Results

Ten differentially expressed miRNAs were identified, with six upregulated and four downregulated miRNAs in LIPUS-treated stem cell-derived EVs. Functional enrichment analysis revealed involvement in biological processes such as regulation of metabolic processes, cellular component organization, and response to stress, as well as signaling pathways like cell cycle, MAPK signaling, and Hippo signaling. Protein-protein interaction network analysis identified key hub genes including MYC, GAPDH, HSP90AA1, EP300, JUN, PTEN, DAC1, STAT3, HSPA8, and HIF1A associated with LIPUS treatment. RT-qPCR validation confirmed differential expression of selected miRNAs (hsa-miR-933, hsa-miR-3943, hsa-miR-4633-5p, hsa-miR-592, hsa-miR-659-5p, hsa-miR-4766-3p) in LIPUS-treated hUC-MSCs.

Conclusion

This study sheds light on the potential therapeutic mechanisms underlying LIPUS-treated stem cell-derived EVs. The identified differentially expressed miRNAs and their potential target mRNAs offer valuable insights into the biological processes influenced by LIPUS treatment. While further investigation is necessary to validate their roles as therapeutic targets, this study lays the groundwork for future research on optimizing SC-EV therapy with LIPUS preconditioning.
Alloreactive-free CAR-VST therapy: a step forward in long-term tumor control in viral context
Authors: Wang Valentine , Savoldo Barbara , Guimaraes José-Arthur , Dotti Gianpietro , Reppel Loïc , Bensoussan Danièle
Published: January 2025

CAR-T cell therapy has revolutionized immunotherapy but its allogeneic application, using various strategies, faces significant challenges including graft-versus-host disease and graft rejection. Recent advances using Virus Specific T cells to generate CAR-VST have demonstrated potential for enhanced persistence and antitumor efficacy, positioning CAR-VSTs as a promising alternative to conventional CAR-T cells in an allogeneic setting. This review provides a comprehensive overview of CAR-VST development, emphasizing strategies to mitigate immunogenicity, such as using a specialized TCR, and approaches to improve therapeutic persistence against host immune responses. In this review, we discuss the production methods of CAR-VSTs and explore optimization strategies to enhance their functionality, activation profiles, memory persistence, and exhaustion resistance. Emphasis is placed on their unique dual specificity for both antitumor and antiviral responses, along with an in-depth examination of preclinical and clinical outcomes. We highlight how these advances contribute to the efficacy and durability of CAR-VSTs in therapeutic settings, offering new perspectives for broad clinical applications. By focusing on the key mechanisms that enable CAR-VSTs to address autologous CAR-T cell challenges, this review highlights their potential as a promising strategy for developing effective allogeneic CAR-T therapies.
Analysis of the spatio-temporal variability of spawning mackerel in the Northeast Atlantic
Authors: Costas Gersom
Published: January 2025

The northeast Atlantic (NEA) mackerel (Scomber scombrus) is a commercially significant species, with expansive spawning migrations occurring along the continental shelf of northwestern Europe. To identify the main variables influencing the spatial distribution of mackerel eggs, this study analyzed data from egg surveys conducted by the Working Group on Mackerel and Horse Mackerel Egg Surveys (WGMEGS) of the International Council for the Exploration of the Sea (ICES). To achieve this objective, a Random Forest model was used to predict the presence of mackerel eggs based on temporal, geographical, and environmental variables. Applying the Random Forest model to the survey data revealed that the main variables affecting mackerel spawning were the bottom depth, latitude, temperature, and salinity. Subsequently, Quotient Analysis was used to determine the optimal ranges of the key variables identified as influencing mackerel spawning. The results demonstrated a clear preference for spawning at depths between 100 m and 200 m, as well as a consistent preference for the area between 43° and 44° North, corresponding to the Cantabrian Sea. Furthermore, the results indicated that mackerel exhibited a considerable range of temperature tolerance throughout the spawning process, with a preference for cooler waters in the Western area in recent years. Salinity seems to have an effect on spawning at salinities between 35.0 ppm to 35.5 ppm, but results were imprecise. These results contribute to our understanding of how environmental and geographical variables influence the spawning behavior of NEA mackerel.
Constructing sports facilities using environment-friendly materials
Authors: Li Rui , Zhai Chenxi
Published: January 2025

This study is focused on applying environment-friendly materials (EFM) to construct sports facilities for sustainability. The current status and future potential of using EFM in sports facility construction are concretely discussed with a thorough literature review and analysis. First, we discuss the concept and significance of EFM, especially in terms of its advantages in reducing carbon emissions and conserving resources: e.g., Europe carries out the EU Horizon 2020 plan, which invests 3.018 billion euros for studying climate action, environment, resource efficiency, and rare materials for green manufacturing. Second, the application of EFM in venue construction, e.g., sports stadiums, is comprehensively reviewed and evaluated, including using renewable materials, energy-saving technologies, and eco-friendly architectural designs. Third, the challenges and future developing trends of applying EFM in sports facility construction are discussed by considering constructional design and material selection. We find that EFM shows great potential in constructing sports facilities, playing a key role in promoting the sustainable development of sports facilities and a low-carbon economy.
Difference between estimated glomerular filtration rate based on cystatin C versus creatinine and cardiovascular–kidney–metabolic health
Authors: Wu Xiaoyan , Hu Wuming , Xu Jian , Shen Jiayi , Lin Li , Zhu Jingshuai , Wei Tiemin , Lv Lingchun
Published: January 2025

Background

The difference between the estimated glomerular filtration rate (eGFR) calculated from cystatin C and creatinine (eGFRdiff) serves as a biomarker of kidney function impairment. However, the role of eGFRdiff in cardiovascular–kidney–metabolic (CKM) health and its impact on mortality in CKM syndrome patients has not yet been studied.

Methods

This study included 3,622 participants from the National Health and Nutrition Examination Survey (NHANES) conducted between 1999 and 2004. Weighted ordinal logistic regression was used to explore the link between eGFRdiff and CKM health, while weighted Cox regression was used to examine the relationship between eGFRdiff and mortality in CKM syndrome patients. Restricted cubic splines (RCSs) were used to analyze the dose–response relationship.

Results

The common odds ratio (cOR) per 10 mL/min/1.73m2 increase in eGFRdiff was 0.86 [95% confidence interval (CI), 0.81 to 0.91]. Compared to the midrange eGFRdiff, the cOR values for the negative and positive eGFRdiff were 1.88 [95% CI, 1.23 to 2.88] and 0.69 [95% CI, 0.58 to 0.83], respectively. During a median follow-up of 201 months, 853 participants died from all causes, while 265 died due to cardiovascular causes. The hazard ratios (HRs) per 10 mL/min/1.73m2 increase in eGFRdiff were 0.88 [95% CI, 0.83 to 0.93] for all-cause mortality and 0.90 [95% CI, 0.81 to 1.00] for cardiovascular mortality cases. Compared to the participants with a midrange eGFRdiff, those with negative eGFRdiff had a 48% higher risk of all-cause mortality, while those with positive eGFRdiff had a 30% lower risk. No significant non-linear associations were found in these regression analyses.

Conclusion

Our study found that eGFRdiff is associated with CKM health and stratified mortality risk in CKM syndrome patients.
Association between self-reported eye conditions in patients at rural federally qualified health centers and vision-targeted health-related quality of life: the AL-SIGHT study
Authors: Swain Thomas A. , McGwin Gerald , Rhodes Lindsay A. , Girkin Christopher A. , Owsley Cynthia
Published: January 2025

Background

Federally Qualified Health Centers (FQHCs) are safety-net primary health care clinics in the US serving medically underserved areas and populations. We administered the National Eye Institute Visual Function Questionnaire – 9 (VFQ-9), a vision-targeted, health-related quality of life questionnaire, to patients in 3 FQHCs in rural Alabama at risk for glaucoma. We examined demographic factors and self-reported eye conditions associated with VFQ-9 scores.

Methods

The VFQ-9 (score range 0–100) was administered to patients at-risk for glaucoma including African Americans or Hispanics ≥40 years, white persons ≥50 years, persons with diabetes ≥18 years, ≥18 years with glaucoma or glaucoma suspect, and/or ≥ 18 years with a family history of glaucoma. Demographic variables were collected -- age, gender, race/ethnicity, employment, marital status, health insurance, education, and driving status. Patients reported the presence of eye conditions including glaucoma and many other eye conditions. Stepwise linear regression modeled which variables accounted for the greatest variance of the VFQ-9 score.

Results

Composite VFQ-9 scores averaged 82.4. The best fitting model for VFQ-9 scores included being a driver, insurance type/status, self-reported glaucoma or glaucoma suspect, blurry vision, and double vision.

Conclusion

Patients at-risk for glaucoma seeking care at FQHCs in rural Alabama have moderate impairment in quality of life as assessed by the VFQ-9. Factors negatively influencing scores are self-reported glaucoma or glaucoma suspect, blurry vision, double vision, not being a driver, and having no health insurance. The VFQ-9 is a good candidate as a vision-targeted quality of life outcome for eye health interventions at rural FQHCs in those with glaucoma.
Angelica sinensis polysaccharide as potential protectants against recurrent spontaneous abortion: focus on autophagy regulation
Authors: Sun Yeli , Li Guohua , Kong Mengwen , Li Junyuan , Wang Shuyun , Tan Yuan
Published: January 2025

Introduction

Recurrent spontaneous abortion (RSA) represents a significant clinical challenge, with its underlying mechanisms yet to be fully elucidated. Despite advances in understanding, the precise pathophysiology driving RSA remains unclear. Angelica sinensis, a traditional herbal remedy, is frequently used as an adjunctive treatment for miscarriage. However, it remains uncertain whether its primary active component, Angelica sinensis polysaccharide (ASP), plays a definitive role in its therapeutic effects. The specific function and mechanism of ASP in the context of RSA require further investigation.

Methods

In this study, we sought to evaluate autophagy levels at the maternal-fetal interface in RSA patients and in an RSA mouse model treated with ASP, complemented by a comprehensive metabolomic analysis. Autophagy flux in the decidua was compared between eight RSA patients and eight healthy pregnant women. Additionally, changes in autophagy flux were assessed in an RSA mouse model following ASP treatment, with embryos and placental tissues collected for subsequent metabolomic profiling.

Results

Our results revealed a significant reduction in Beclin 1 protein levels in the decidua of RSA patients compared to the normal pregnancy group. Conversely, ASP treatment in the RSA mouse model restored autophagy-related protein expression, including ATG7, ATG16L, and Beclin 1, to levels higher than those observed in the untreated RSA group. Metabolomic analyses further identified significant changes in phosphatidylethanolamine levels between ASP-treated and control groups, with differential metabolites enriched in pathways related to glycolysis/gluconeogenesis, glycerolipid metabolism, and glycine, serine, and threonine metabolism. Functional assays revealed that ASP enhances trophoblast cell proliferation, migration, and invasion.

Conclusion

In summary, our findings demonstrate diminished autophagy activity in RSA patients, while ASP appears to restore autophagy and regulate key metabolic pathways, including glycolysis/gluconeogenesis. These results provide new insights into the protective mechanisms of ASP in RSA, suggesting its potential as a therapeutic intervention for this condition.
Acute stress triggers sex-dependent rapid alterations in the human small intestine microbiota composition
Authors: Rodiño-Janeiro Bruno K. , Khannous-Lleiffe Olfat , Pigrau Marc , Willis Jesse R. , Salvo-Romero Eloísa , Nieto Adoración , Expósito Elba , Fortea Marina , Pardo-Camacho Cristina , Albert-Bayo Mercé , González-Castro Ana María , Guagnozzi Danila , Martínez Cristina , Lobo Beatriz , Vicario María , Santos Javier , Gabaldón Toni , Alonso-Cotoner Carmen
Published: January 2025

Background/aims

Digestive disorders of gut-brain interaction (DGBI) are very common, predominant in females, and usually associated with intestinal barrier dysfunction, dysbiosis, and stress. We previously found that females have increased susceptibility to intestinal barrier dysfunction in response to acute stress. However, whether this is associated with changes in the small bowel microbiota remains unknown. We have evaluated changes in the small intestinal microbiota in response to acute stress to better understand stress-induced intestinal barrier dysfunction.

Methods

Jejunal biopsies were obtained at baseline and 90 min after cold pain or sham stress. Autonomic (blood pressure and heart rate), hormonal (plasma cortisol and adrenocorticotropic hormone) and psychological (Subjective Stress Rating Scale) responses to cold pain and sham stress were monitored. Microbial DNA from the biopsies was analyzed using a 16S metabarcoding approach before and after cold pain stress and sham stress. Differences in diversity and relative abundance of microbial taxa were examined.

Results

Cold pain stress was associated with a significant decrease in alpha diversity (P = 0.015), which was more pronounced in females, along with significant sex differences in the abundance of specific taxa and the overall microbiota composition. Microbiota alterations significantly correlated with changes in psychological responses, hormones, and gene expression in the intestinal mucosal. Cold pain stress was also associated with activation of autonomic, hormonal and psychological response, with no differences between sexes.

Conclusions

Acute stress elicits rapid alterations in bacterial composition in the jejunum of healthy subjects and these changes are more pronounced in females. Our results may contribute to the understanding of female predominance in DGBI.
Resistance to medically important antimicrobials in broiler and layer farms in Cameroon and its relation with biosecurity and antimicrobial use
Authors: Vougat Ngom Ronald , Laconi Andrea , Tolosi Roberta , Akoussa Adonis M. M. , Ziebe Stephane D. , Kouyabe Vincent M. , Piccirillo Alessandra
Published: January 2025

Introduction

Poultry production accounts for 42% of Cameroonian meat production. However, infectious diseases represent the main hindrance in this sector, resulting in overuse and misuse of antimicrobials that can contribute to the emergence and dissemination of antimicrobial resistance (AMR). This study aimed to evaluate the prevalence of antimicrobial resistance genes (ARGs) conferring resistance to carbapenems (blaVIM-2 and blaNDM), (fluoro) quinolones (qnrS, qnrA, and qnrB), polymyxins (mcr1 to mcr5), and macrolides (ermA and ermB) in the poultry farm environment. Additionally, the study examined the relationship between these ARGs and biosecurity implementation, as well as farmers’ knowledge, attitudes, and practices toward antimicrobial use (AMU) and AMR, including their perception of AMR risk.

Materials and methods

Fecal, drinking water, and biofilm samples from drinking water pipelines were collected from 15 poultry farms and subsequently analyzed by real-time PCR and 16S rRNA NGS.

Results

All samples tested positive for genes conferring resistance to (fluoro) quinolones, 97.8% to macrolides, 64.4% to polymyxins, and 11.1% to carbapenems. Of concern, more than half of the samples (64.4%) showed a multi-drug resistance (MDR) pattern (i.e., resistance to ≥3 antimicrobial classes). Drinking water and biofilm microbial communities significantly differed from the one of the fecal samples, both in term of diversity (α-diversity) and composition (β-diversity). Furthermore, opportunistic pathogens (i.e., Comamonadaceae and Sphingomonadaceae) were among the most abundant bacteria in drinking water and biofilm. The level of biosecurity implementation was intermediate, while the knowledge and attitude of poultry farmers toward AMU were insufficient and unsuitable, respectively. Good practices toward AMU were found to be correlated with a reduction in polymyxins and MDR.

Discussion

This study provides valuable information on resistance to medically important antimicrobials in poultry production in Cameroon and highlights their potential impact on human and environmental health.
Development of a colloidal gold immunochromatographic assay utilizing dual-antibody sandwich method for detecting Orientia tsutsugamushi
Authors: Lu Qingyu , Yu Shiyin , Wang Sibo , Cao Min , Li Liuxin , Xin Miao , Tan Weilong , Qi Yong , Lu Yichen , Xiong Xiaohui
Published: January 2025

A colloidal gold immunochromatographic assay (ICA) based on a dual-antibody sandwich method was developed for the rapid and convenient detection of Orientia tsutsugamushi (O. tsutsugamushi) antigens in the early stages of infection. Monoclonal antibodies designed as 5B3 targeting the conserved region of 56 kDa outer membrane protein in various strains of O. tsutsugamushi were generated through cell fusion and screening techniques and combined with previously prepared polyclonal antibodies as detection antibodies to establish the ICA. Colloidal gold and polyclonal antibody-colloidal gold complexes were synthesized under optimized conditions. The nitrocellulose membrane was treated with 5B3 monoclonal antibody and goat anti-mouse antibody as the test and control lines, respectively. The ICA demonstrated robust sensitivity, with a minimum detection limit of 70.5 ng for the 56 kDa recombinant of the Gilliam strain. Furthermore, a detection limit of 1 × 106 copies/μL DNA of O. tsutsugamushi was determined for both PT and SJ infected cell strains by constructing a relationship between cell number and copy number of the pathogen using a quantitative PCR-based standard curve. The assay also exhibited exceptional specificity, with no false positives observed against other bacterial species, including Escherichia coli, Salmonella, Staphylococcus aureus, and Listeria monocytogenes. In summary, an ICA which is sensitive, specific, and easy to operate was successfully established for the detection of O. tsutsugamushi in scrub typhus, potentially enabling early rapid point-of-care diagnosis of scrub typhus.
Predicting patient outcomes with gene-expression biomarkers from colorectal cancer organoids and cell lines
Authors: Razumovskaya Alexandra , Silkina Mariia , Poloznikov Andrey , Kulagin Timur , Raigorodskaya Maria , Gorban Nina , Kudryavtseva Anna , Fedorova Maria , Alekseev Boris , Tonevitsky Alexander , Nikulin Sergey
Published: January 2025

Introduction

Colorectal cancer (CRC) is characterized by an extremely high mortality rate, mainly caused by the high metastatic potential of this type of cancer. To date, chemotherapy remains the backbone of the treatment of metastatic colorectal cancer. Three main chemotherapeutic drugs used for the treatment of metastatic colorectal cancer are 5-fluorouracil, oxaliplatin and irinotecan which is metabolized to an active compound SN-38. The main goal of this study was to find the genes connected to the resistance to the aforementioned drugs and to construct a predictive gene expression-based classifier to separate responders and non-responders.

Methods

In this study, we analyzed gene expression profiles of seven patient-derived CRC organoids and performed correlation analyses between gene expression and IC50 values for the three standard-of-care chemotherapeutic drugs. We also included in the study publicly available datasets of colorectal cancer cell lines, thus combining two different in vitro models relevant to cancer research. Logistic regression was used to build gene expression-based classifiers for metastatic Stage IV and non-metastatic Stage II/III CRC patients. Prognostic performance was evaluated through Kaplan-Meier survival analysis and log-rank tests, while independent prognostic significance was assessed using multivariate Cox proportional hazards modeling.

Results

A small set of genes showed consistent correlation with resistance to chemotherapy across different datasets. While some genes were previously implicated in cancer prognosis and drug response, several were linked to drug resistance for the first time. The resulting gene expression signatures successfully stratified Stage II/III and Stage IV CRC patients, with potential clinical utility for improving treatment outcomes after further validation.

Discussion

This study highlights the advantages of integrating diverse experimental models, such as organoids and cell lines, to identify novel prognostic biomarkers and enhance the understanding of chemotherapy resistance in CRC.
Cognitive trajectories and their relationships with education and diets among older adults: a network-based 10-year cohort study
Authors: Wang Xuchun , Qiao Yuchao , Zhang Yudong , Cui Yu , Ren Hao , Hao Chongqi , Qiu Lixia
Published: January 2025

Objectives

Few studies have examined the underlying mechanisms of education, diets, and cognitive function in older adults. This study analyses the relationship between cognitive trajectories, education, and different dietary patterns in older adults from a network perspective, and further explores their longitudinal associations and mediation effects.

Methods

Data on cognitive trajectories were derived from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) between 2008 and 2018. Group-Based Trajectory Model (GBTM) was used to identify potential heterogeneity in the longitudinal changes in cognitive function. Multinomial logistic regression and network analysis were then applied to examine the relationships between different cognitive trajectories and years of education, food variety (FV), and plant-based dietary patterns. Cross-lagged panel model was used to examine the longitudinal associations between education, FV, and plant-based diet patterns. Furthermore, we constructed a mediation model based on categorical variables for cognitive trajectories to investigate the mediating effect of FV and plant-based diet index on education and cognitive.

Results

A total of 2,115 older adults were included in this study, revealing three distinct cognitive function trajectories. After controlling for potential confounders, education and dietary-related variables were associated with a cognitive stable decline trajectory (OR: 0.857/0.929/1.027) and a cognitive rapid decline trajectory (OR: 0.859/0.914, 95% CI: 0.775–0.882) compared to the cognitive stable trajectory. In the education, diet, and cognition network model, overall Plant-Based Diet Index (PDI) [expected influence (EI) = 1.82] and years of education (EI = 0.54) were the most central domains. There were longitudinal associations between education, FV, and plant-based dietary patterns, which were significant only in the slow decline group. FV acting as a mediator between education and cognitive trajectories.

Conclusion

Years of education are longitudinally associated with the diet of older adults in the slow cognitive decline group. Food diversity partially mediates the relationship between years of education and cognitive trajectories. Interventions targeting education and dietary behaviors may help alleviate cognitive decline in older adults.
Sex in aging matters: exercise and chronic stress differentially impact females and males across the lifespan
Authors: Sullens D. Gregory , Gilley Kayla , Moraglia Luke E. , Dison Sarah , Hoffman Jessica T. , Wiffler Madison B. , Barnes Robert C. , Ginty Annie T. , Sekeres Melanie J.
Published: January 2025

Assessing sex as a biological variable is critical to determining the influence of environmental and lifestyle risks and protective factors mediating behavior and neuroplasticity across the lifespan. We investigated sex differences in affective behavior, memory, and hippocampal neurogenesis following short- or long-term exposure to exercise or chronic mild stress in young and aged mice. Male and female mice were assigned control, running, or chronic stress rearing conditions for 1 month (young) or for 15 months (aged), then underwent a behavioral test battery to assess activity, affective behavior, and memory. Stress exposure into late-adulthood increased hyperactivity in both sexes, and enhanced anxiety-like and depressive-like behavior in aged female, but not male, mice. One month of stress or running had no differential effects on behavior in young males and females. Running increased survival of BrdU-labelled hippocampal cells in both young and aged mice, and enhanced spatial memory in aged mice. These findings highlight the importance of considering sex when determining how aging is differently impacted by modifiable lifestyle factors across the lifespan.
Advanced techniques and nanotechnologies for point-of-care testing
Authors: Secchi Valeria , Armanni Alice , Barbieri Linda , Bruno Antonia , Colombo Alessandro , Fumagalli Sara , Kukushkina Ekaterina A. , Lorenzi Roberto , Marchesi Letizia , Moukham Hind , Paleari Alberto , Ronchi Alessandra , Tomaino Giulia , Tripodi Farida , Colombo Miriam , Sironi Laura , Monguzzi Angelo
Published: January 2025

Hospitals and other healthcare facilities harbor a complex interplay of microbial pathogens. The correct understanding of pathogens distribution and evolution is therefore crucial for infections control and for the design of effective prevention strategies. In parallel, the integration of cutting-edge nanotechnologies for the early detection and monitoring of these specific target pathogens is considered the most effective approach to face nosocomial infections. In this context, point-of-care (POC) testing, also known as near-patient testing, is becoming increasingly important. In this review we provide a systematic insight into the recent scientific and technological advances in pathogen detection that explore advanced nanotechnologies to realize devices and nanobiosensors, with improved selectivity and sensitivity. In particular, we report on the most diffused and affordable nanotechnologies developed and still developing for POC testing, with the aim to increase the sensitivity, speed and accuracy of pathogens detection in different environments, from intensive care units to outside the laboratory and hospital settings. The text is sub-divided in several sections, each one focused on different type of nanomaterials and techniques actually employed.
Current virtual reality-based rehabilitation interventions in neuro-developmental disorders at developmental ages
Authors: Capobianco Micaela , Puzzo Concetto , Di Matteo Chiara , Costa Alberto , Adriani Walter
Published: January 2025

This mini-review examines the available papers about virtual reality (VR) as a tool for the diagnosis or therapy of neurodevelopmental disorders, focusing on Attention Deficit Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD), and Specific Learning Disorders (SLD). Through a search on literature, we selected 62 studies published between 1998 and 2024. After exclusion criteria, our synoptic table includes 32 studies on ADHD (17 were on diagnostic evaluation and 15 were on therapeutic interventions), 2 on pure ASD, and 2 on pure SLD. These cover a total of 8,139 participants with ADHD (ages 3–19), 458 with ASD (ages 4–19), and 162 with SLD (ages 7–11). Results show that VR offers high ecological validity and enables improvements in cognitive and social skills. Specifically, in individuals with ADHD, VR showed benefits in attention and executive function, with optimal results when combined with pharmacological treatments. For ASD kids, VR proved effective in enhancing social skills and emotional regulation through personalized virtual scenarios. However, the literature on SLD remains limited, suggesting an evolving area of research. Despite limitations related to small sample sizes and technology costs, VR presents a promising outlook for clinical intervention in neuro-developmental disorders, supporting enhanced skills in a safe and controlled environment. We conclude that both immersive and non-immersive VR represents a valuable supplement to traditional therapies, allowing for personalized approaches.
The global research of magnetic resonance imaging in Alzheimer’s disease: a bibliometric analysis from 2004 to 2023
Authors: Sun Xiaoyu , Zhu Jianghua , Li Ruowei , Peng Yun , Gong Lianggeng
Published: January 2025

Background

Alzheimer’s disease (AD) is a common neurodegenerative disorder worldwide and the using of magnetic resonance imaging (MRI) in the management of AD is increasing. The present study aims to summarize MRI in AD researches via bibliometric analysis and predict future research hotspots.

Methods

We searched for records related to MRI studies in AD patients from 2004 to 2023 in the Web of Science Core Collection (WoSCC) database. CiteSpace was applied to analyze institutions, references and keywords. VOSviewer was used for the analysis of countries, authors and journals.

Results

A total of 13,659 articles were obtained in this study. The number of published articles showed overall exponential growth from 2004 to 2023. The top country and institution were the United States and the University of California System, accounting for 40.30% and 9.88% of the total studies, respectively. Jack CR from the United States was the most productive author. The most productive journal was the Journal of Alzheimers Disease. Keyword burst analysis revealed that “machine learning” and “deep learning” were the keywords that frequently appeared in the past 6 years. Timeline views of the references revealed that “#0 tau pathology” and “#1 deep learning” are currently the latest research focuses.

Conclusion

This study provides an in-depth overview of publications on MRI studies in AD. The United States is the leading country in this field with a concentration of highly productive researchers and high-level institutions. The current research hotspot is deep learning, which is being applied to develop noninvasive diagnosis and safer treatment of AD.
Using cortical organoids to understand the pathogenesis of malformations of cortical development
Authors: Winden Kellen D. , Gisser Isabel , Sahin Mustafa
Published: January 2025

Malformations of cortical development encompass a broad range of disorders associated with abnormalities in corticogenesis. Widespread abnormalities in neuronal formation or migration can lead to small head size or microcephaly with disorganized placement of cell types. Specific, localized malformations are termed focal cortical dysplasias (FCD). Neurodevelopmental disorders are common in all types of malformations of cortical development with the most prominent being refractory epilepsy, behavioral disorders such as autism spectrum disorder (ASD), and learning disorders. Several genetic pathways have been associated with these disorders from control of cell cycle and cytoskeletal dynamics in global malformations to variants in growth factor signaling pathways, especially those interacting with the mechanistic target of rapamycin (mTOR), in FCDs. Despite advances in understanding these disorders, the underlying developmental pathways that lead to lesion formation and mechanisms through which defects in cortical development cause specific neurological symptoms often remains unclear. One limitation is the difficulty in modeling these disorders, as animal models frequently do not faithfully mirror the human phenotype. To circumvent this obstacle, many investigators have turned to three-dimensional human stem cell models of the brain, known as organoids, because they recapitulate early neurodevelopmental processes. High throughput analysis of these organoids presents a promising opportunity to model pathophysiological processes across the breadth of malformations of cortical development. In this review, we highlight advances in understanding the pathophysiology of brain malformations using organoid models.
Uncovering novel KCC2 regulatory motifs through a comprehensive transposon-based mutant library
Authors: Uvarov Pavel , Fudo Satoshi , Karakus Cem , Golubtsov Andrey , Rotondo Federico , Sukhanova Tatiana , Soni Shetal , Di Scala Coralie , Kajander Tommi , Rivera Claudio , Ludwig Anastasia
Published: January 2025

Introduction

The neuron-specific K-Cl cotransporter KCC2 maintains low intracellular chloride levels, which are crucial for fast GABAergic and glycinergic neurotransmission. KCC2 also plays a pivotal role in the development of excitatory glutamatergic neurotransmission by promoting dendritic spine maturation. The cytoplasmic C-terminal domain (KCC2-CTD) plays a critical regulatory role in the molecular mechanisms controlling the cotransporter activity through dimerization, phosphorylation, and protein interaction.

Methods

To identify novel CTD regulatory motifs, we used the Mu transposon-based mutagenesis system to generate a library of KCC2 mutants with 5 amino acid insertions randomly distributed within the KCC2-CTD. We determined the insertion positions in 288 mutants by restriction analysis and selected clones with a single insertion site outside known KCC2 regulatory motifs. We analyzed the subcellular distribution of KCC2-CTD mutants in cultured cortical neurons using immunocytochemistry and selected ten mutants with ectopic expression patterns for detailed characterization.

Results

A fluorescent Cl−-transport assay in HEK293 cells revealed mutants with both reduced and enhanced Cl−-extrusion activity, which overall correlated with their glycosylation patterns. Live-cell immunostaining analysis of plasma membrane expression of KCC2-CTD mutants in cultured cortical neurons corroborated the glycosylation data. Furthermore, the somatodendritic chloride gradient in neurons transfected with the KCC2-CTD mutants correlated with their Cl−-extrusion activity in HEK293 cells. Gain- and loss-of-function mutant positions were analyzed using available KCC2 cryo-EM structures.

Discussion

Two groups of mutants were identified based on 3D structural analysis. The first group, located near the interface of transmembrane and cytoplasmic domains, may affect interactions with the N-terminal inhibitory peptide regulating KCC2 activity. The second group, situated on the external surface of the cytoplasmic domain, may disrupt interactions with regulatory proteins. Analyzing CTD mutations that modulate KCC2 activity enhances our understanding of its function and is essential for developing novel anti-seizure therapies.
Pre-treatment nutrition-related indicators and the prognosis of patients with newly diagnosed epithelial ovarian cancer: an ambispective cohort study
Authors: Wang Shirui , Zhu Jingyu , Wu Ningjuan , Wang Nannan , Dang Xiaohe , Zhao Minyi , Zhao Juan , Ma Ding , Yang Xiaofeng
Published: January 2025

Background

Few studies have explored the link between nutritional status and prognosis in patients with epithelial ovarian cancer (EOC), and existing findings are controversial. Thus, this study aimed to explore the effects of pre-treatment nutrition-related indicators on the prognosis of patients with newly diagnosed EOC.

Methods

In this ambispective cohort study, 1,020 patients with EOC diagnosed by pathology examination were enrolled and followed-up until December 31, 2023. Univariate and multivariable analyses were conducted on nutrition-related indicators, including body mass index (BMI), albumin (ALB), hemoglobin (Hb), diabetes mellitus (DM), and hyperlipidemia, along with clinicopathological characteristics that might affect patients’ first-line chemotherapy response, progression-free survival (PFS), and overall survival (OS). Survival curves were created using the Kaplan–Meier method. A Cox proportional hazards model was established to obtain hazard ratios (HRs) and 95% confidence intervals (CIs).

Results

The median follow-up duration was 48 months. Compared with patients having normal nutritional indicators, those with hypoalbuminemia had poorer first-line chemotherapy responses. The proportions of those with complete response (CR), partial response (PR), and stable disease or progressive disease (SD/PD) for the ≤30 g/L, 30 < ALB<35 g/L and normal ALB groups were 57.2, 20.6, and 22.2% vs. 62.0, 22.5, and 15.5% vs.79.5, 13.6, and 6.9%. Patients with hypoalbuminemia had shorter median PFS (mPFS): 15 vs. 19 vs. 57 months in the three groups, respectively; and shorter median OS (mOS): 36 vs. 51 vs. 124 months. Patients with hyperlipidemia also exhibited poorer first-line chemotherapy responses; CR, PR, and SD/PD rates for the hyperlipidemia and non-hyperlipidemia groups were 68.9, 19.5, and 11.6% vs. 76.4, 14.7, and 8.9%, respectively, and shorter mPFS (17 vs. 57 months) and mOS (40 vs. 119 months). Patients with anemia had poorer first-line chemotherapy responses; CR, PR, and SD/PD rates for the anemia and non-anemia groups were 68.4, 19.7, and 11.9% vs. 76.2, 14.9, and 8.9%, respectively. All differences were statistically significant (p < 0.05). Multivariable analysis identified hyperlipidemia as an independent risk factor for PFS (hazard ratio [HR] = 2.083; 95% CI:1.726–2.514; p < 0.001) and OS (HR = 2.158; 95% CI:1.746–2.666; p < 0.001), whereas hypoalbuminemia and anemia were not confirmed as independent prognostic factors. This study found no effect of BMI or DM on patient prognosis.

Conclusion

Pre-treatment hypoalbuminemia, hyperlipidemia, and anemia negatively affected the prognosis of patients with newly diagnosed EOC, with hyperlipidemia being an independent risk factor for shorter survival.
Association between oxidative balance score and glaucoma in the National Health and Nutrition Examination Survey
Authors: Huang Jun , Zhang Yulan , Wu Chao , Wu Yifan , Wang Feiran , Ning Yunxuan , Shi Lu
Published: January 2025

Objective

To investigate the association between Oxidative Balance Score (OBS) and glaucoma risk.

Methods

Using data from the National Health and Nutrition Examination Survey (2005–2008), we analyzed 2,615 participants aged ≥40 years. OBS was calculated from 15 antioxidant and 5 pro-oxidant components, including dietary nutrients and lifestyle factors. Glaucoma was identified through self-reported diagnosis and retinal imaging. Survey-weighted logistic regression and restricted cubic splines (RCS) were used to assess associations.

Results

Higher OBS was associated with lower glaucoma risk (adjusted OR = 0.97, 95% CI: 0.94–1.00). Participants in the highest OBS quartile showed 51% lower odds of glaucoma compared to the lowest quartile (adjusted OR = 0.49, 95% CI: 0.27–0.90). The protective effect was more pronounced among middle-aged adults (40–60 years; OR = 0.90, 95% CI: 0.86–0.95) and males (OR = 0.93, 95% CI: 0.90–0.97).

Conclusion

Higher OBS were associated with lower glaucoma prevalence, particularly among middle-aged adults and males, suggesting potential benefits of maintaining oxidative balance in glaucoma prevention.
MRI-based intratumoral and peritumoral radiomics for assessing deep myometrial invasion in patients with early-stage endometrioid adenocarcinoma
Authors: Yang Jing , Liu Yang , Liu Xiaolong , Wang Yaoxin , Wang Xianhong , Ai Conghui , Bi Qiu , Zhao Ying
Published: January 2025

Purpose

To evaluate the effectiveness of magnetic resonance imaging (MRI)-based intratumoral and peritumoral radiomics models for predicting deep myometrial invasion (DMI) of early-stage endometrioid adenocarcinoma (EAC).

Methods

The data of 459 EAC patients from three centers were retrospectively collected. Radiomics features were extracted separately from the intratumoral and peritumoral regions expanded by 0 mm, 5 mm, and 10 mm on unimodal and multimodal MRI. Then, various radiomics models were developed and validated, and the optimal model was confirmed. Integrated models were constructed by ensemble and stacking algorithms based on the above radiomics models. The models’ performance was evaluated using the area under the curve (AUC).

Results

The multimodal MRI-based radiomics model, which included both intratumoral and peritumoral regions expanded by 5 mm, was the optimal radiomics model, with an AUC of 0.74 in the validation group. When the same integrated algorithm was utilized, the integrated models with 5-mm expansion presented higher AUCs than those with 0-mm and 10-mm expansion in the validation group. The performance of the stacking model and ensemble model with 5-mm expansion was similar, and their AUCs were 0.74 and 0.75, respectively.

Conclusion

The multimodal radiomics model from the intratumoral and peritumoral regions expanded by 5 mm has the potential to improve the performance for detecting DMI of early-stage EAC. The integrated models are of little value in increasing the prediction.
Case Report: Respiratory outcome in a preterm infant following previable rupture of membranes and persistent oligohydramnios
Authors: Subramanian Akila , Zhi Ong Kai , Pugalenthi Arun Kumar , Rajadurai Victor Samuel , Tan Lay Kok , Chandran Suresh
Published: January 2025

Mid-trimester preterm premature rupture of membranes is a rare complication of pregnancy associated with significant maternal and fetal risks. The ensuing prolonged oligohydramnios can lead to fetal pulmonary hypoplasia. In addition, there is an increased risk of miscarriage, preterm birth, and chorioamnionitis, contributing to septic morbidity in the mother–baby dyad. This case report describes the management and outcomes of an infant born at 32 weeks following the rupture of membranes at 16 weeks of gestation, resulting in severe oligohydramnios. Soon after birth, the infant had respiratory compromise, requiring high-frequency oscillatory ventilation and nitric oxide. Despite the initial poor prognosis, the infant remained stable with various ventilation modalities managed by a multidisciplinary team. He was discharged home after 108 days in the hospital and remained on non-invasive ventilatory support until 8 months of age while the home care and hospital specialty teams monitored him. The favorable respiratory outcome of this case is a rarity for cases with similar clinical circumstances, in which the managing team counsels parents about poor fetal outcomes and many proceed to terminate the pregnancies. In this reported case, we highlight the importance of multidisciplinary and interprofessional team management from antepartum monitoring and planning delivery time to subsequent short- and long-term postnatal care involving maternal-fetal medicine specialists, neonatologists, pediatric cardiology and respiratory specialists, and home care teams.
Case Report: Hypercalcemia, subcutaneous fat necrosis and nephrocalcinosis in neonates who undergo therapeutic hypothermia: a not so rare association, with different onset time
Authors: De Rose Domenico Umberto , Maddaloni Chiara , Salvatori Guglielmo , Campi Francesca , Gatto Antonio , Martini Ludovica , Savarese Immacolata , Bersani Iliana , Ubertini Graziamaria , Serrao Francesca , Costa Simonetta , Braguglia Annabella , Gallini Francesca , Vento Giovanni , Dotta Andrea
Published: January 2025

Subcutaneous fat necrosis (SCFN) in newborns is an uncommon and self-limiting non-infectious panniculitis. It can occur in the first weeks of life in full-term newborns with hypoxic-ischemic encephalopathy who underwent therapeutic hypothermia. Hypercalcemia may develop and has been implicated as the cause of several complications as nephrocalcinosis. Hypercalcemia has been previously reported to appear only after resolution of skin lesions. Herein, we report how hypercalcemia can be evident already at diagnosis of subcutaneous fat necrosis after therapeutic hypothermia and can be associated with an early onset developing nephrocalcinosis. We compare two cases of these uncommon findings and review the recent literature.
Case Report: Diagnosis and treatment of incontinentia pigmenti with central nervous system anomalies in one patient
Authors: Li Yun , Hong Junbin , Xu Shangge , Zhou Tong , Xiao Xiaolan , Yang Jinghua , Chen Yiting
Published: January 2025

Introduction

This article reports a detailed case of a patient with incontinentia pigmenti who exhibited epileptic status and dermatologic symptoms.

Case presentation

A 5-month-old female patient was brought to our hospital due to status epilepticus, with erythematous vesicular skin lesions on her trunk and extremities. Routine magnetic resonance imaging revealed infarction, ischemia, and encephalomalacia. Skin biopsy pathology indicated pigmentation disorder. Molecular genetic testing was conducted to identify IKBKG mutations, and the case was finally diagnosed with incontinentia pigmenti complicated by central nervous system anomalies. She was treated with oral levetiracetam (10 mg/kg/day, administered every 12 h) to control her recurrent seizures, and prednisone (1 mg/kg/day, once a day) for anti-inflammatory effects.

Conclusion

After nine months, her skin lesions have resolved, with only a few newly developed erythematous papules and areas of hyperpigmentation being evident. There were no recurrent epilepsy symptoms, developmental impairments, or other associated symptoms.