bluuebunny/crossref_metadata_2025 huggingface dataset:
Fear of hypoglycemia and sleep in children with type 1 diabetes and their parents
Authors: Schierloh Ulrike , Aguayo Gloria A. , Fichelle Muriel , De Melo Dias Cindy , Schritz Anna , Vaillant Michel , Barnard-Kelly Katharine , Cohen Ohad , Gies Inge , de Beaufort Carine
Published: December 2024

Aims

To compare impact of pump treatment and continuous glucose monitoring (CGM) with predictive low glucose suspend (SmartGuard) or user initiated CGM (iscCGM) on sleep and hypoglycemia fear in children with type 1 Diabetes and parents.

Methods

Secondary analysis of data from 5 weeks pump treatment with iscCGM (A) or SmartGuard (B) open label, single center, randomized cross-over study was performed. At baseline and end of treatment arms, sleep and fear of hypoglycemia were evaluated using ActiGraph and questionnaires.

Results

31 children (6-14 years, male: 50%) and 30 parents (28-55 years) participated. Total sleep minutes did not differ significantly for children (B vs. A: -9.27; 95% CI [-24.88; 6.34]; p 0.26) or parents (B vs. A: 5.49; 95% CI [-8.79; 19.77]; p 0.46). Neither daytime sleepiness nor hypoglycemia fear in children or parents differed significantly between the systems. Neither group met recommended sleep criteria.

Conclusion

Lack of sleep and fear of hypoglycemia remain a major burden for children with diabetes and their parents. Whilst no significant differences between the systems were found, future technology should consider psychosocial impacts of diabetes and related technologies on children and parents’ lived experience to ensure parity of esteem between physical and mental health outcomes.

Clinical Trial Registration

www.ClinicalTrials.gov, identifier NCT03103867.
Association of oxidative balance score with cardiovascular disease and all-cause and cardiovascular mortality in American adults with type 2 diabetes: data from the National Health and Nutrition examination survey 1999-2018
Authors: Fan Meilin , Song Shina , Chu Tingting , Li Ronghong , Yue Miao , Li Xiaofeng , Yang Jing
Published: December 2024

Background

Oxidative stress has an important role in type 2 diabetes (T2D). Oxidative balance score (OBS) is an emerging assessment of dietary and lifestyle oxidative balance. We aimed to explore the association of OBS with cardiovascular disease (CVD) and all-cause and CVD mortality in the T2D population through NHANES 1999-2018.

Methods

OBS integrated 16 dietary components and 4 lifestyle components. T2D was diagnosed according to the American Diabetes Association criteria. Multivariate logistic regression and multivariate Cox proportional hazards regression analyses were used to explore the association of OBS with CVD and mortality in T2D, respectively.

Results

3801 adult T2D participants were included. In fully adjusted models, OBS, dietary OBS, and lifestyle OBS were all negatively associated with the prevalence of CVD (odds ratios of 0.98, 0.98, and 0.85, respectively). Higher OBS and lifestyle OBS (p for trend 0.016 and <0.001, respectively) rather than dietary OBS (p for trend = 0.06) were associated with significantly lower odds of CVD. Higher OBS, dietary OBS, and lifestyle OBS were all negatively associated with all-cause mortality (hazard ratios [HR] of 0.98, 0.98, and 0.92, respectively; p for trend of 0.002, 0.009, and 0.035, respectively). Higher OBS and dietary OBS were negatively associated with CVD mortality (HR 0.96 and 0.95, respectively; p for trend both <0.001), whereas lifestyle OBS was not. Restricted cubic spline analysis suggested that most associations were linear. Stratified analyses showed that these associations were influenced by some demographic variables and disease status.

Conclusions

Adherence to higher OBS was associated with reduced CVD prevalence and mortality risk in T2D. Antioxidant diet and lifestyle had more significant associations with mortality and CVD prevalence, respectively. However, as these findings are merely associations and do not allow causal inferences to be drawn, future validation in high-quality randomized controlled trials is needed.
Evolutionary characteristics, regional differences and spatial effects of coupled coordination of rural revitalization, new-type urbanization and ecological environment in China
Authors: Zhang Ruijuan , Bao Qingfeng
Published: December 2024

Rural revitalization (R), new-type urbanization (U) and the ecological environment (E) are a unity of complementary advantages and mutual promotion and coexistence, the coupling and coordination of the three is the key to realizing the Chinese modernization and the harmonious coexistence of human beings and nature. Based on China’s provincial panel data from 2011 to 2022, this paper constructed a comprehensive evaluation index for the R-U-E system, using the entropy method, coupled coordination model, Dagum’s Gini coefficient, kernel density estimation, spatial correlation analysis, and spatial Durbin model to explore the level of comprehensive development, spatial-temporal evolutionary characteristics of coupled coordination, regional differences and spatial effects of the three systems. The following results were observed: (1) The comprehensive index of rural revitalizationand new-type urbanization exhibits a growing trend and significant regional differences, with East China outperforming other regions, but the average value of below 0.5 needs to be further improved. The ecological environment index exhibits a smoother growth trend, higher in South China than in other regions. (2) The level of R-U-E coupling coordination has increased year on year, from barely coordinated to primary coordination. (3) The spatial imbalance in coupling coordination has improved both nationally and in the seven regions, with the largest intra-regional differences in South China and the smallest intra-regional differences in Central China. The differences between the Northeast and Central China regions exhibit a widening trend, while the differences between all other regions exhibit a decreasing trend. Interregional variations are the main factor affecting overall variance, but their impact on the overall variance is gradually diminishing. (4) The level of coupling coordination has obvious spatial correlation, and the “high-high” and “low-low” cluster aggregation characteristics was evident. (5) Government behavior and the levels of economic growth, human capital, and digitization significantly contribute to the coupled and coordinated development of the region and, at the same time, have a significant spatial spillover effect on neighboring provinces; the degree of openness to the outside world contributed to the coordinated development of the region, while it had an inhibitory effect on the neighboring provinces; and the drive to innovate has only a certain contributing effect on the neighboring regions. Targeted policy measures in response to this paper’s empirical findings may provide policymakers with a reference point for achieving regional sustainable development goals.
Associations between breastfeeding and self-reported experience of the “10 Steps to Successful Breastfeeding”: a cross-sectional and longitudinal study of maternity clinic practices in Cyprus
Authors: Economou Mary , Kolokotroni Ourania , Paphiti-Demetriou Irene , Kouta Christiana , Lambrinou Ekaterini , Hadjigeorgiou Eleni , Hadjiona Vasiliki , Middleton Nicos
Published: December 2024

Objective

To assess the implementation of the “10 Steps for Successful Breastfeeding” and explore associations with any Breastfeeding (BF) and Exclusive Breastfeeding (EBF) initiation and continuation.

Methods

Implementation of the 10 Steps was assessed based on a consecutive sample of 568 mothers’ self-reported experience across all public (N = 5) and 29 (of 35) private maternity clinics using the WHO/UNICEF BFHI questionnaire (Section 4) within the first 24–48 h after birth. BF and EBF were estimated within 48 h after birth as well as at 1st, 4th and 6th month based on a self-reported current status method. Associations with initiation and continuation of any BF and EBF up to the 6th month were explored in logistic regression after adjusting for potential confounders. Associations were explored with individual steps as well as the overall experience, operationalized as the sum score of full, partial or no implementation of each item, with the exception of Step 6 (exclusive breastfeeding).

Results

At mean score 6.2 (SD = 2.7), the overall 10 Steps experience was low (theoretical range 0–14), even among those who breastfed exclusively (M = 7.7, SD = 2.0). EBF and BF initiation and continuation showed a stepwise association with self-reported experience of the 10 Steps. Across quartiles of increasing scores within 48 h after birth, the prevalence of EBF was 7.5%, 14.4%, 19.0%, and 34.2%. Mothers who experienced full or partial implementation of Step 4 (i.e., early initiation with skin-to-skin) were more likely to continue BF and EBF up to the 4th month, while use of pacifiers (Step 9) was more likely to have an adverse effect on breastfeeding continuation and exclusivity.

Conclusion

The BFIH's “10 Steps” are associated with BF initiation while certain practices seem to be more strongly associated with exclusivity and continuation of breastfeeding up to the sixth month. While breastfeeding intention may determine the experience of the 10 Steps, this also suggests that maternity care practices can have a supportive role for mothers to succeed their intentions to BF and EBF.
What are clinically significant anti-drug antibodies and why is it important to identify them
Authors: Swanson Steven James
Published: December 2024

The FDA has released new draft guidance to standardize how immunogenicity of protein therapeutics is described in product labels. A key aspect to this new guidance is that companies should describe anti-drug antibodies that have clinical significance in addition to reporting ADAs’ incidence. Factors to consider when determining clinical significance include if those antibodies have a significant effect on the drug’s pharmacokinetics, pharmacodynamics, efficacy, and/or safety. While in many instances, the humoral response to protein therapeutics does not have any clinical significance, there are cases where there is a clinically significant effect and it is important to communicate this information to physicians and patients. This new guidance also delineates where immunogenicity information should be listed in product labels which should provide consistency in how this information is listed. There are many factors that contribute to a therapeutic’s immunogenicity and determining clinical significance is both complex and challenging, requiring that companies perform thorough analyses with scientific rigor. The analysis that is now proposed to understand clinical significance of ADAs is a new concept and will require companies to develop a strategy for compliance. This manuscript sets forth some of the key considerations in answering this important question. One of the benefits that this new guidance will provide is a common approach for describing the immune response to therapeutics that will be located in a dedicated section of the label, providing valuable consistency across protein therapeutics. Section 12.6 in the Clinical Pharmacology portion of the label will contain the relevant immunogenicity information, which will make it much simpler to find immunogenicity information in product labels. This new guidance is currently being utilized for new protein therapeutics and companies are being requested to systematically revise the labels of previously approved drugs for compliance, although an absolute timeline for this has not been established as of this writing.
AKR1B10 and digestive tumors development: a review
Authors: Shen Yao , Qiu Ailin , Huang Xin , Wen Xiaosha , Shehzadi Sundar , He Yan , Hu Qian , Zhang Jian , Luo Dixian , Yang Shenghui
Published: December 2024

Aldo-keto reductase family 1 member B10 (AKR1B10) is a member of the AKR1B subfamily. It is mainly found in cytoplasm, and it is typically expressed in the stomach and intestines. Given that its expression is low or absent in other tissues, AKR1B10 is a potential diagnostic and therapeutic biomarker for various digestive system diseases. Here, we review recent research progress on AKR1B10 in digestive system tumors such as hepatocellular carcinoma, gastric carcinoma, colorectal carcinoma, pancreatic carcinoma, oral squamous cell carcinoma, laryngeal squamous cell carcinoma, cholangiocarcinoma, and nasopharyngeal carcinoma, over the last 5 years. We also discuss the current trends and future research directions for AKR1B10 in both oncological and non-oncological diseases to provide a scientific reference for further exploration of this gene.
CRP deposition in human abdominal aortic aneurysm is associated with transcriptome alterations toward aneurysmal pathogenesis: insights from in situ spatial whole transcriptomic analysis
Authors: Kim Eun Na , Seok Hee Young , Lim Joon Seo , Koh Jiwon , Bae Jeong Mo , Kim Chong Jai , Ryu Ga-Hyeon , Ok You Jung , Choi Jae-Sung , Cho Chung-Hyun , Oh Se Jin
Published: December 2024

Background

We investigated the effects of C-reactive protein (CRP) deposition on the vessel walls in abdominal aortic aneurysm (AAA) by analyzing spatially resolved changes in gene expression. Our aim was to elucidate the pathways that contribute to disease progression.

Methods

AAA specimens from surgically resected formalin-fixed paraffin-embedded tissues were categorized into the AAA–high CRP [serum CRP ≥ 0.1 mg/dL, diffuse and strong immunohistochemistry (IHC); n = 7 (12 cores)] and AAA–low-CRP [serum CRP < 0.1 mg/dL, weak IHC; n = 3 (5 cores)] groups. Normal aorta specimens obtained during heart transplantation were used as the control group [n = 3 (6 cores)]. Spatially resolved whole transcriptomic analysis was performed, focusing on CD68-positive macrophages, CD45-positive lymphocytes, and αSMA-positive vascular smooth muscle cells.

Results

Spatial whole transcriptomic analysis revealed significant differential expression of 1,086, 1,629, and 1,281 genes between high-CRP and low-CRP groups within CD68-, CD45-, and αSMA-positive cells, respectively. Gene ontology (GO) analysis of CD68-positive macrophages identified clusters related to inflammation, apoptosis, and immune response, with signal transducer and activator of transcription 3 implicated across three processes. Notably, genes involved in blood vessel diameter maintenance were significantly downregulated in the high-CRP group. GO analysis of lymphocytes showed upregulation of leukocyte rolling and the apoptosis pathway, whereas, in smooth muscle cells, genes associated with Nuclear factor kappa B (NF-κB) signaling and c-Jun N-terminal Kinase (JNK) pathway were upregulated, and those related to blood pressure regulation were downregulated in the high-CRP group.

Discussion

CRP deposition was associated with significant transcriptomic changes in macrophages, lymphocytes, and vascular smooth muscle cells in AAA, suggesting its potential role in promoting pro-inflammatory and apoptotic processes, as well as contributing to the degradation of vascular structure and elasticity.
Associations of NETs with inflammatory risk and clinical predictive value in large artery atherosclerosis stroke: a prospective cohort study
Authors: Li Jiang , Liu Lei , Zhang Ruxu , Pan Liqun , Tan Juanying , Ou Mingxin , Luo Xiuju , Peng Jun , Hu Zhongyang
Published: December 2024

Background and objective

Neutrophil extracellular traps (NETs) with inflammatory risk are important contributors to cardiovascular disease, but no definitive information is available in large artery atherosclerotic (LAA) stroke. This study aims to investigate the association between NETs with related inflammatory biomarkers and prognosis of LAA stroke in the Chinese population.

Methods

A prospective study involving 145 LAA stroke cases and 121 healthy controls was conducted. Serum levels of MPO-DNA, PAD4, HMGB1, C1q, AIM2, ASC, Caspase-1, IL-1β, IL-6, and IL-8 were determined in all participants. The biomarkers were detected at three time points after stroke onset (24 hours: T1, 48 hours: T2, 7 days: T3) for LAA stroke patients and once for controls. Patients were followed up for 2 years after the ischemic event.

Results

The serum MPO-DNA, PAD4, C1q, IL-1β, IL-6 and IL-8 reach their peak at 24 hours after stroke onset and show a decreasing trend during acute phase. MPO-DNA, AIM2 and IL-1β at baseline were associated with poor outcome at 3 months, further GMDR analysis revealed that the combination of MPO-DNA, AIM2 and IL-1β exert a synergistic effect on the prognosis of LAA stroke (OR: 8.75 95%CI (2.10-32.42)). For time-to-event analysis, MPO-DNA, Caspase-1 and IL-1β at baseline were predictors of MVEs after stroke (HR:4.04 (95%CI 1.28-12.70), 2.33 (95%CI 1.06-5.12) and 4.09 (95%CI 1.39-11.99), respectively).

Conclusions

NETs and related inflammatory biomarkers at baseline predicted outcome at 3 months and late major vascular events following LAA stroke, supporting a rationale of randomized trials for targeted therapy directed at high-risk patients with elevated baseline NETs and related inflammatory biomarkers.
Immunological characterization of pleural effusions in pediatric patients
Authors: Flögel Luca , Kaiser Elisabeth , Hans Muriel Charlotte , Goedicke-Fritz Sybelle , Bous Michelle , Abdul-Khaliq Hashim , Poryo Martin , Zemlin Michael , Weber Regine
Published: December 2024

Background

The pleural cavity represents a unique immunological compartment that can mount inflammatory reactions during infections, after surgery and in chronic immunological diseases. The connection between systemic immune reactions in the blood and local immune reactions in pleural effusions remains unclear. This study provides the first comprehensive immunological characterization of paired blood and pleural effusion samples, utilizing combined cell and cytokine analyses in pediatric patients undergoing cardiac surgery.

Methods

In 30 pediatric patients (median age: 22 months) with pleural effusion after cardiac surgery for congenital heart defects, corresponding peripheral blood and pleural effusion samples were analyzed for their immune response. We used flow cytometry and multiplex immunoassays to quantify 14 T cell subpopulations and 12 T cell associated cytokines in each biosample.

Results

IL-6, IL-8, IL-10, TNF (p<0.0001) levels were significantly higher in pleural effusion compared to plasma. In contrast, IFN-γ, GM-CSF, IL-17A levels were lower in pleural effusion than in plasma (p ≤ 0.0005). In comparison to peripheral blood, there was a significantly higher proportion of T helper cells 1 (Th1, p=0.0023), T helper cells 17 (Th17, p=0.0334) and memory effector cytotoxic T cells (CD3+CD8+CD45RO+CD62L-, p=0.0449) in pleural effusion and the same trend was observed for memory effector Th cells (CD3+CD4+CD45RO+CD62L-, p=0.0633) and double-negative T cells (CD3+CD4-CD8-) (p=0.1085). Naïve Th cells (CD3+CD4+CD45RO-CD62L+) and naïve cytotoxic T cells (CD3+CD8+CD45RO-CD62L+) were slightly reduced in pleural effusion compared to peripheral blood (not significant).

Conclusion

Immunological factors in pleural effusions differed significantly from the corresponding blood samples in pediatric patients after cardiac surgery. The results suggest localized production of specific cytokines within the pleural space, while the distribution of other cytokines in pleural effusions appears to be more reflective of the systemic immune response. We found evidence that on the cellular level, the surface marker CD62L may play a key role in navigating T cells between the blood and pleural effusion. This study confirms that the pleural cavity harbors a unique lymphatic compartment, the analysis of which may be useful for both diagnostic and therapeutic purposes.
Proteomic profiling of peripheral blood mononuclear cells reveals immune dysregulation and metabolic alterations in kidney transplant recipients with COVID-19
Authors: Leite Giuseppe G. F. , Sousa Mônica Bragança , Rodrigues Larissa de Oliveira C. P. , Brunialti Milena Karina Colo , Medina-Pestana José , Butler Joe M. , Peters-Sengers Hessel , Requião-Moura Lúcio , Salomão Reinaldo
Published: December 2024

The COVID-19 pandemic has significantly impacted global health, especially in vulnerable populations like kidney transplant recipients (KTRs). Recently, mass spectrometry-based proteomics has emerged as a powerful tool to shed light on a broad spectrum of dysregulated biological processes in KTRs with COVID-19. In this study, we prospectively collected blood samples from 17 COVID-19-positive KTRs and 10 non-infected KTRs between May and September 2020. Using tandem mass tag-based quantitative proteomics, we analyzed peripheral blood mononuclear cells (PBMCs), plasma protein biomarkers, and lymphocyte counts, followed by bioinformatics analysis. Our results revealed significant proteomic alterations in COVID-19-infected KTRs, particularly in pathways related to glycolysis, glucose metabolism, and neutrophil degranulation. Additionally, we observed an altered immune response characterized by elevated cytokines and decreased lymphocyte counts. Notably, KTRs with AKI exhibited worse clinical outcomes, including higher rates of ICU admission and mechanical ventilation. Comparative analysis of PBMC proteomic profiles between AKI and non-AKI patients identified distinct immune-related pathways, with AKI patients showing marked changes in innate immune responses, particularly neutrophil degranulation. Furthermore, we observed a negative correlation between T cell counts and neutrophil degranulation, suggesting a role for immune dysregulation in COVID-19. Our findings provide critical insights into the immune and metabolic responses in COVID-19-infected KTRs, especially those with AKI, highlighting the need for focused research and therapeutic strategies targeting immune dysregulation in this high-risk population.
A systematic review of the neuroprotective role and biomarker potential of GDF15 in neurodegeneration
Authors: Isik Finula I. , Thomson Shannon , Cueto John F. , Spathos Jessica , Breit Samuel N. , Tsai Vicky W. W. , Brown David A. , Finney Caitlin A.
Published: December 2024

Neurodegeneration is characteristically multifaceted, with limited therapeutic options. One of the chief pathophysiological mechanisms driving these conditions is neuroinflammation, prompting increasing clinical interest in immunomodulatory agents. Growth differentiation factor 15 (GDF15; previously also called macrophage inhibitory cytokine-1 or MIC-1), an anti-inflammatory cytokine with established neurotrophic properties, has emerged as a promising therapeutic agent in recent decades. However, methodological challenges and the delayed identification of its specific receptor GFRAL have hindered research progress. This review systematically examines literature about GDF15 in neurodegenerative diseases and neurotrauma. The evidence collated in this review indicates that GDF15 expression is upregulated in response to neurodegenerative pathophysiology and increasing its levels in preclinical models typically improves outcomes. Key knowledge gaps are addressed for future investigations to foster a more comprehensive understanding of the neuroprotective effects elicited by GDF15.
Enhancing bathymetric prediction by integrating gravity and gravity gradient data with deep learning
Authors: Li Junhui , Chao Nengfang , Li Houpu , Chen Gang , Bian Shaofeng , Wang Zhengtao , Ma Aoyu
Published: December 2024

This study aims to enhance the spatial resolution and accuracy of bathymetric prediction by integrating Gravity Anomaly (GA) and Vertical Gravity Gradient Anomaly (VGG) data with a dual-channel Backpropagation Neural Network (BPNN). The seafloor topography of the Izu-Ogasawara Trench in the Western Pacific will be constructed and evaluated using depth models and single-beam data. The BPNN improved the accuracy of seafloor topography prediction by 0.17% and 0.35% using the 1 arc-minute SIO and GEBCO depth models, respectively, in areas without in-situ data. When single-beam data was utilized, the BPNN improved prediction accuracy by 64.93%, 70.29%, and 68.78% compared to the Gravity Geological Method (GGM), SIO v25.1, and GEBCO 2023, respectively. When single-beam, GA, and VGG data were all combined, the root mean square error (RMSE) was reduced to 19.12 m, representing an improvement of 60.92% and 61.13% compared to using only GA or VGG data, respectively. Comparing bathymetric predictions at different depths, the BPNN achieved a mean relative error (MRE) as low as 0.5%. Across various terrains—such as trench areas, seamounts, and deep-sea plains—the accuracy of seafloor topography predicted by the BPNN improved by 88.36%, 87.42%, and 84.39% compared to GGM, SIO and GEBCO depth models, respectively. These findings demonstrate that BPNN can integrate GA and VGG data to enhance both the accuracy and spatial resolution of seafloor topography in regions with and without in-situ data, and across various depths and terrains. This study provides new data and methodological support for constructing high-precision global seafloor topography.
Effect of peripheral blood absolute monocyte count at admission on relapse-free survival in patients with idiopathic thrombotic thrombocytopenic purpura in remission
Authors: Yu Xiaomin , Zhong Mingzhu , Wang Chen , Shi Yifen , Xing Chongyun , Yu Kang , Lin Ying , Ou Rongying , Yang Junjun , Zhu Liqing
Published: December 2024

Introduction

Peripheral monocytes have been reported to correlate with clinical outcomes in various types of malignancies. Previous reports have also shown that acute-phase thrombotic thrombocytopenic purpura (TTP) plasma could induce the activation of monocytes. However, the significance of peripheral blood absolute monocyte count (AMC) in idiopathic TTP remains an unanswered question. The primary aim of this retrospective study was to evaluate the prognostic value of AMC at admission in idiopathic TTP patients in remission.

Methods

A total of 37 patients with idiopathic TTP who survived their first episode of the disease and achieved remission following treatment were eligible for inclusion in the study. SPSS and Stata were used to analysis.

Results

There were 1 patient (2.7%) with low AMC (< 0.12  × 109/L), 27 patients (73.0%) with normal AMC (0.12–0.80 × 109/L), and 9 patients (24.3%) with high AMC (> 0.80 × 109/L) at admission. Ten (27.0%) of 37 patients in our cohort subsequently relapsed (1 in the low AMC group and 9 in the normal AMC group). Survival analysis showed that there was a trend of higher relapse-free survival (RFS) rate in patients having increased A MC (log-rank test, p = 0.026). Univariate analysis revealed that increased AMC at admission was significantly associated with higher RFS (hazard ratio = 0.12, 95% confidence interval: 0.02–0.62, p = 0.011).

Discussion

Our results suggest that increased AMC at admission could represent a predictor of higher RFS in TTP patients having survived their first episode of the disease and achieved remission following treatment.
Long short-term-memory-based depth of anesthesia index computation for offline and real-time clinical application in pigs
Authors: Caillet Benjamin , Maître Gilbert , Devènes Steve , Hight Darren , Mirra Alessandro , Levionnois Olivier L. , Simalatsar Alena
Published: December 2024

We here present a deep-learning approach for computing depth of anesthesia (DoA) for pigs undergoing general anesthesia with propofol, integrated into a novel general anesthesia specialized MatLab-based graphical user interface (GAM-GUI) toolbox. This toolbox permits the collection of EEG signals from a BIOPAC MP160 device in real-time. They are analyzed using classical signal processing algorithms combined with pharmacokinetic and pharmacodynamic (PK/PD) predictions of anesthetic concentrations and their effects on DoA and the prediction of DoA using a novel deep learning-based algorithm. Integrating the DoA estimation algorithm into a supporting toolbox allows for the clinical validation of the prediction and its immediate application in veterinary practice. This novel, artificial-intelligence-driven, user-defined, open-access software tool offers a valuable resource for both researchers and clinicians in conducting EEG analysis in real-time and offline settings in pigs and, potentially, other animal species. Its open-source nature differentiates it from proprietary platforms like Sedline and BIS, providing greater flexibility and accessibility.
Analyzing gait data measured by wearable cyborg hybrid assistive limb during assisted walking: gait pattern clustering
Authors: Namikawa Yasuko , Kawamoto Hiroaki , Uehara Akira , Sankai Yoshiyuki
Published: December 2024

Introduction

The wearable cyborg Hybrid Assistive Limb (HAL) is a therapeutic exoskeletal device that provides voluntary gait assistance using kinematic/kinetic gait data and bioelectrical signals. By utilizing the gait data automatically measured by HAL, we are developing a system to analyze the wearer's gait during the intervention, unlike conventional evaluations that compare pre- and post-treatment gait test results. Despite the potential use of the gait data from the HAL's sensor information, there is still a lack of analysis using such gait data and knowledge of gait patterns during HAL use. This study aimed to cluster gait patterns into subgroups based on the gait data that the HAL automatically collected during treatment and to investigate their characteristics.

Methods

Gait data acquired by HAL, including ground reaction forces, joint angles, trunk angles, and HAL joint torques, were analyzed in individuals with progressive neuromuscular diseases. For each measured item, principal component analysis was applied to the gait time-series data to extract the features of the gait patterns, followed by hierarchical cluster analysis to generate subgroups based on the principal component scores. Bayesian regression analysis was conducted to identify the influence of the wearer's attributes on the clustered gait patterns.

Results

The gait patterns of 13,710 gait cycles from 457 treatments among 48 individuals were divided into 5–10 clusters for each measured item. The clusters revealed a variety of gait patterns when wearing the HAL and identified the characteristics of multiple sub-group types. Bayesian regression models explained the influence of the wearer's disease type and gait ability on the distribution of gait patterns to subgroups.

Discussion

These results revealed key differences in gait patterns related to the wearer's condition, demonstrating the importance of monitoring HAL-assisted walking to provide appropriate interventions. Furthermore, our approach highlights the usefulness of the gait data that HAL automatically measures during the intervention. We anticipate that the HAL, designed as a therapeutic device, will expand its role as a data measurement device for analysis and evaluation that provides gait data simultaneously with interventions, creating a novel cybernics treatment system that facilitates a multi-faceted understanding of the wearer's gait.
The changes of intestinal flora and metabolites in atopic dermatitis mice
Authors: Wang Feifei , Wang Zuding , Qu Liping
Published: December 2024

Introduction

Atopic dermatitis (AD) is an allergic disease caused by various factors that can affect an individual’s appearance and cause psychological stress. Therefore, it is necessary to investigate the underlying mechanisms and develop effective treatment strategies. The gut microbiota and bacterial metabolism play crucial roles in human diseases. However, their specific role in AD remains unclear.

Methods

In this study, we established a mouse model of AD and found that 2,4-dinitrofluorobenzene disrupted the skin barrier in mice. The species composition of intestinal bacteria was then analyzed by fecal 16s rRNA sequencing. The metabolic level of mice was analyzed by untargeted and targeted metabolomics in stool.

Results

The levels of filaggrin and aquaporin 3 proteins in the model mice and total superoxide dismutase, catalase and malondialdehyde levels were significantly altered. Additionally, inflammatory factors such as tumor necrosis factor-alpha showed a significant increase. Using 16S rRNA gene sequencing, we identified 270 bacterial species with altered abundances of Ruminococcaceae and Bifidobacteriaceae. The untargeted metabolomic analysis detected 1,299 metabolites. Targeted analysis of free fatty acids revealed 49 metabolites with notable increases in linoleic and linolenic acid levels. Fecal bacterial transplantation experiments have demonstrated that oxidative stress, inflammation, and skin barrier damage were alleviated after transplantation.

Discussion

These findings suggested that the metabolite linoleic acid negatively correlated with Ruminococcaceae and Bifidobacteriaceae may influence AD development. Perturbations in the intestinal bacteria and flora contributed to the development of AD, and the mouse model could serve as a valuable tool for further investigation of therapeutic approaches for managing ADS.
Electromyography findings in L5 radiculopathy are not associated with fatty infiltration of paraspinal muscles: a retrospective observational study
Authors: Seliverstova Ekaterina , Sinkin Mikhail , Grin Andrey
Published: December 2024

Introduction

Increased fatty infiltration of the paraspinal muscles (PM) has been recognized as a sign of decreased muscle quality in patients with degenerative disc disease. However, whether fatty infiltration is a consequence of a neurogenic process due to spinal nerve root compression has not yet been determined.

Objective

To investigate the correlation between fatty infiltration of the paraspinal muscles (PM) and neurogenic remodeling of motor unit action potentials (MUAPs) in patients with lumbar radiculopathy.

Materials and methods

58 adult patients (32 women) with L5 radiculopathy caused by an L4-L5 herniated disc were examined. We compared the neurological status, EMG data of the PM at the L5 level on the affected side and the L4 level on the opposite side of the spine, and the severity of fatty infiltration of the PM assessed on axial T2-weighted magnetic resonance imaging (MRI) scans.

Results

We did not find any correlation between the degree of fatty infiltration and neurogenic remodeling of MUAPs in the PM.

Conclusion

The lack of correlation between the degree of fatty infiltration and the presence of neurogenic remodeling of MUAPs in the PM suggests that fatty infiltration and neuropathic changes in muscles may be considered as separate processes requiring further research.
Vision transformer-equipped Convolutional Neural Networks for automated Alzheimer's disease diagnosis using 3D MRI scans
Authors: Zhao Zhen , Yeoh Pauline Shan Qing , Zuo Xiaowei , Chuah Joon Huang , Chow Chee-Onn , Wu Xiang , Lai Khin Wee
Published: December 2024

Alzheimer's disease (AD) is a neurodegenerative ailment that is becoming increasingly common, making it a major worldwide health concern. Effective care depends on an early and correct diagnosis, but traditional diagnostic techniques are frequently constrained by subjectivity and expensive costs. This study proposes a novel Vision Transformer-equipped Convolutional Neural Networks (VECNN) that uses three-dimensional magnetic resonance imaging to improve diagnosis accuracy. Utilizing the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset, which comprised 2,248 3D MRI images and diverse patient demographics, the proposed model achieved an accuracy of 92.14%, a precision of 86.84%, a sensitivity of 93.27%, and a specificity of 89.95% in distinguishing between AD, healthy controls (HC), and moderate cognitive impairment (MCI). The findings suggest that VECNN can be a valuable tool in clinical settings, providing a non-invasive, cost-effective, and objective diagnostic technique. This research opens the door for future advancements in early diagnosis and personalized therapy for Alzheimer's Disease.
Research hotspots and trends in diabetes and insulin resistance: a bibliometric analysis
Authors: Zhang Shaobo , Yan Huixin , Cao Di , Sun Weichen , Li Jingnan , Xu Jing , Song Bailin , Wu Xingquan
Published: December 2024

Background

Many previous studies explored the relationship between diabetes and insulin resistance (IR); however, addressing the research gap where no bibliometric analysis had been conducted to summarize and analyze these publications, we will undertake a comprehensive bibliometric analysis to investigate the current status and emerging trends in publications examining the association between diabetes and IR.

Methods

We retrieved publications related to the interaction between diabetes and IR from the Web of Science Core Collection (WoSCC). By utilizing software such as CiteSpace, VOSviewer, and Excel 2019, we analyzed and extracted relevant information from the literature to identify and delineate the research hotspots and directions in the study of diabetes and IR.

Results

From 1900 to 2024, a total of 2,698 publications were included in the bibliometric analysis, showing a steady annual increase in the number of publications. The USA led in this research field, with the Harvard University being a key research institution. The author Olefsky JM, published the most papers;Defronzo RA was the most cited author. DIABETES was the journal with the highest number of published papers and was also the most cited journal. The main discipline in the field of diabetes and IR research was Endocrinology and Metabolism. The most cited article was “Mechanisms linking obesity to insulin resistance and type 2 diabetes (2006)”;“The IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045(2018)” was the most cited reference. “insulin resistance” was the most frequently occurring keyword. The main research hotspots and frontier areas in diabetes and IR research were as follows: (1) The association between IR, diabetes, and obesity was a popular research topic; (2) Cardiovascular diseases secondary to diabetes and IR were another hot topic among researchers; (3) As a core pathological change in diabetes, IR was a major therapeutic target for improving diabetes.

Conclusion

This study summarized the research trends and hotspots in the field of diabetes and IR, provided valuable information and insights for scholars who focused on diabetes and IR scientific research, and offered a reference for future research directions.
Radiological features of basal ganglia germinoma: a case report and early-stage alerts
Authors: Nguyen Quyen Thi To , Nguyen Phuc Van , Ho Phuong Hoang , Le Khiem Tan , Le Thanh Anh , Nguyen Truc Thi Thuy
Published: December 2024

Basal ganglia germinomas are uncommon neoplasms. Basal ganglia germinomas exhibit high sensitivity to both radiation therapy and chemotherapy. In contrast, surgery is the standard treatment for most primary brain tumors (such as gliomas, which are the most common tumors in the pediatric basal ganglia region). A 21-year-old male patient was admitted to our hospital because of unexplained right-sided hemiparesis for two years. Biomarkers indicating germ cell tumors are typically negative. On the initial MRI, the abnormalities were nonspecific, causing no suspicion of a tumor. Therefore, the patient did not receive an earlier diagnosis or treatment. His brain MRI revealed a mass with more apparent features one year later. Based on the imaging characteristics of conventional and advanced MR images, the preoperative radiological diagnosis was highly likely to reveal germinomas. The patient then underwent a biopsy and received appropriate treatment. Despite treatment, his symptoms only partially improved. Accurate preoperative diagnosis is crucial for ensuring that patients receive appropriate treatment and to help avoid more invasive surgery. Additionally, early identification of germinomas is also important for improving long-term patient outcomes and preventing tumor spread due to delayed diagnosis. Therefore, we aim to review and report this case to assist radiologists in recognizing and becoming familiar with the early imaging signs of basal ganglia germinoma.
Transcriptomic analysis of ROS1+ non-small cell lung cancer reveals an upregulation of nucleotide synthesis and cell adhesion pathways
Authors: Terrones Marc , Op de Beeck Ken , Van Camp Guy , Vandeweyer Geert , Mateiu Ligia
Published: December 2024

Introduction

The transcriptomic characteristics of ROS1+ non-small cell lung cancer (NSCLC) represent a crucial aspect of its tumor biology. These features provide valuable insights into key dysregulated pathways, potentially leading to the discovery of novel targetable alterations or biomarkers.

Methods

From The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus (GEO) databases, all available ROS1+ (n = 10), ALK+ (n = 5) and RET+ (n = 5) NSCLC tumor and ROS1+ cell line (n = 7) RNA-sequencing files were collected. In addition, 10 healthy lung RNA-seq samples were included. Differential gene expression with DESeq2 (R package) and gene co-expression (WGCNA, R package) analyses were performed. Functional annotation was performed through Gene Set Enrichment Analysis (GSEA) using Webgestalt and RNAseqChef, Over-Representation Analysis (ORA) through Enrichr. iRegulon was used to identify enriched transcription factors that regulate a gene co-expression module.

Results

ROS1+ NSCLC samples were significantly enriched for the nucleotide synthesis and cell adhesion KEGG pathways compared to ALK+ and RET+ samples. Moreover, NOTCH1 was significantly downregulated in ROS1+ NSCLC and PD-L1 was weakly expressed. When comparing ROS1+ tumor versus cell line transcriptomes, an upregulation of MYC and MET was found in cell lines together with a significantly decreased expression of HER3, HER4 and BRAF. Within ROS1-tumors, GJB2 was overexpressed in the CD74- and CLTC-ROS1+ subgroups. The differential expression of IL20RB and GJB2 in cell lines was confirmed through RT-qPCR. Finally, the gene co-expression analysis unveils a gene cluster involving cell cycle-related genes which significantly correlates with the disease stage of patients. In addition, we propose TFDP1 and ISL1 as key ROS1-specific transcription factors.

Conclusion

This study highlights cell adhesion and nucleotide synthesis as crucial signatures in ROS1+ NSCLC. The upregulation of GJB2 may serve as a prognostic biomarker, along with IL20RB, a known mediator of bone metastases. Furthermore, TDFP1 and ISL1 were identified as relevant transcription factors that could potentially regulate the biological processes in ROS1-rearranged NSCLC.
Optimal exercise dose-response improves health-related quality of life in cancer survivors: a systematic review and Bayesian network meta-analysis of RCTs
Authors: Xiong Zhiyu , Yuan Yuan , Yang Yong , Qiu Bopeng , Bai Ying , Wang Tao , Wang Junyu , Zhang Lin , Li Yawen
Published: December 2024

Objective

Cancer survivors often face significant health-related quality of life (HRQoL) challenges. Although exercise has been proven to improve HRQoL in cancer survivors, the optimal dose and intensity of exercise for this population has not been fully determined. Adherence to exercise may vary based on exercise intensity, affecting results. This study explored the dose-response relationship of different exercise types and intensities to better understand their impact on HRQoL in cancer survivors.

Methods

We searched five databases—PubMed, Embase, the Cochrane Library, Web of Science, and Scopus—from their inception until 1 December 2023. Data analysis was performed using R software with the MBNMA and RJAGS packages. Due to combining data from different scales, effect sizes were reported as standardized mean differences (SMD) with 95% credible intervals (95% CrI). The risk of bias was assessed independently by three reviewers using the RoB2 tool.

Results

A total of 48 studies involving 3050 cancer survivors. Across all exercise types, the most beneficial exercise dose was identified to be 850 metabolic equivalents of task (METs)-min/week (SMD: 0.753, 95%Crl: 0.463 to 1.096), with diminishing returns observed beyond 1,100 METs-min/week. Among the various types of exercises, mixed training (MT) emerged as the optimal choice, demonstrating its efficacy at 970 METs-min/week (SMD: 0.883, 95% Crl: 0.455 to 1.345). Aerobic exercise (AE) at a dose of 430 METs-min/week (SMD: 0.681, 95% Crl: 0.206 to 1.099) and resistance training (RT) at 450 METs-min/week (SMD: 0.695, 95% Crl: 0.227 to 1.203) also showed significant benefits. Additionally, mind-body exercises, such as tai chi, qigong, or yoga, exhibited optimal effects at a dose of 390 METs-min/week (SMD: 0.672, 95% Crl: 0.259 to 1.087).

Conclusion

Our study sheds light on the intricate relationship between exercise interventions and health-related quality of life in cancer survivors, as elucidated through a systematic review and Bayesian network meta-analysis. The identified optimal exercise dose of 850 METs-min/week resulted in a significant improvement in health-related quality of life, underscoring the importance of regular exercise in cancer survivorship. MT emerged as the most effective modality, closely followed by RT, AE, and MBE.

Systematic review registration

https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=493328, identifier CRD42024493328.
Serum PD-1 regulation and PD-1 expression of CD4+Foxp3+ regulatory T cells in patients in thyroid eye disease associated with immunosuppression treatment
Authors: Sakai Atsushi , Tagami Mizuki , Misawa Norihiko , Haruna Yusuke , Tomita Mami , Honda Shigeru
Published: December 2024

Purpose

Thyroid eye disease (TED) primarily occurs in hyperthyroid patients, sometimes resulting in poor visual prognosis. Although other autoimmune diseases have been reported to be associated with serum programmed cell death 1 (PD-1), the relationship with TED remains unknown. This study investigated the relationship between TED and immune checkpoint molecules.

Methods

Serum immune checkpoint molecules were measured in TED and control patient blood samples. In TED patients, blood samples were compared before and 6 months after steroid pulse treatment. Cytometry analysis was additionally performed in TED and control patients to compare the expression of (PD-1) of T cells.

Results

Serum concentrations of PD-1 in TED and control patients were 163.49 ± 79.01 (pg/mL) and 123.58 ± 46.61 (pg/mL) (P = 0.03). Serum PD-L1 concentration in TED was 157.89 ± 55.34 (pg/mL), while 152.58 ± 22.70 (pg/mL) in control patients (P = 0.92). For flow cytometry analysis, the mean fluorescence intensity (MFI) ratio of PD-1 in Foxp3high CD45RA- of the CD4+ T cells and CD127-CD25high of the CD4+ T cells were higher in TED versus control patients (P = 0.04, P = 0.02). There was also a higher percentage of PD-1 expressions on CD4+ T cells and Foxp3high CD45- T cells in TED patients versus that for control patients (P < 0.001, P = 0.003).

Conclusions

PD-1 expression of CD4+Foxp3+ regulatory T cells appear to be associated with TED pathogenesis before and after treatment. Regulatory T cells expressed PD-1 have possibilities of clinical activity and autoimmune pathology of TED.