bluuebunny/crossref_metadata_2025 huggingface dataset:
Large-scale analysis highlights obesity as a risk factor for chronic, non-communicable inflammatory diseases
Authors: Mousavi Sadegh , Bieber Katja , Zirpel Henner , Vorobyev Artem , Olbrich Henning , Papara Cristian , De Luca David A. , Thaci Diamant , Schmidt Enno , Riemekasten Gabriele , Lamprecht Peter , Laudes Matthias , Kridin Khalaf , Ludwig Ralf J.
Published: February 2025

Background

Overweight and obesity are a global pandemic, contributing to death and disability-adjusted life-years. Obesity is a major factor in the onset of chronic inflammatory diseases (CIDs). Yet, several knowledge gaps remain: For several CIDs, inconsistent results have been reported, relating to their obesity-imposed risk, data on most rare CIDs remain unavailable, sex differences and racial disparities remain mostly unaddressed.

Methods

A large-scale cohort study compared the risk of developing 46 CIDs in individuals with overweight/obesity (n=3,101,824) to an equal number of non-overweight/obese individuals. Propensity score matching optimized between-group comparability, and sensitivity analyses assessed study robustness.

Results

The risk of developing any CID was 28.48% in overweight/obese individuals versus 17.55% in non-overweight/obese controls, with a hazard ratio (95%-confidence interval) of 1.52 (1.509-1.521, p<0.0001). This risk was consistent across all sensitivity, sex-, and race-stratified analyses. Overweight and obesity were associated with an increased risk for 24 of 46 CIDs in the primary analysis and all sensitivity analyses. For 12 diseases, increased risks were confirmed to one of the two sensitivity analyses, while for 10 diseases, results were discordant. No increased risk was observed for one disease. In sex-stratified analysis, overweight and obesity posed a more pronounced risk for four CIDs in female individuals. In race-stratified analysis, overweight and obesity were linked to a higher risk for seven CIDs in White individuals and to one CID in “Black or African American” individuals.

Conclusion

Overweight and obesity increase the risk for the majority of CIDs in a sex- and race-specific manner.
Offset or harmonious coexistence: untangling the interrelationship between green finance and rural revitalisation
Authors: Gao Yi , Hua Xiang , Sokolov Boris Ivanovich , Zhao Fangfei , Shen Simin
Published: February 2025

Examining the relationship and its dynamics between green finance and rural revitalisation is crucial for achieving an equitable, sustainable economy and low-carbon transition. This paper develops a comprehensive evaluation system for green finance and rural revitalisation, utilising data from 31 provinces in China from 2000 to 2020, and reveals the coordinated relationship and spatial characteristics. From the system theory, the coordinated and interacting relationship between green finance and rural revitalisation and its geographic features are also described in this paper. The results show that green finance levels have significantly increased across 31 provinces in China. The rural revitalisation process is also moving forward, and there is mutual reinforcement that creates a balance of harmonious symbiosis and positive interaction between green finance and rural revitalization. The relationship between the two also exhibits distinct stages and notable regional disparities, resulting in a spatial and temporal pattern characterised by ‘high east, sluggish middle, and delayed in the west.’ At the same time, a pattern of green finance development has appeared in the demonstrative unit of development. However, to enable the revitalisation of rural areas through green policies, it must accelerate the development of rural revitalisation and provide more robust and focused policy support.
Integrated analysis of M2 macrophage-related gene prognostic model and single-cell sequence to predict immunotherapy response in lung adenocarcinoma
Authors: Li Meifang , Wang Zhiping , Huang Bin , Lai Yanyun , Zhang Meng , Lin Cheng
Published: February 2025

Background

Lung adenocarcinoma (LUAD) patients have high heterogeneity. The significance and clinical value of M2 macrophage-related genes in LUAD require further exploration. We aimed to construct a prognostic signature to predict the immunotherapy efficacy and prognosis in LUAD.

Methods

GSE26939 and GSE19188 chips were downloaded from the Gene Expression Omnibus (GEO). Weighted gene co-expression network analysis (WGCNA) and least absolute shrinkage and selection operator (LASSO) analysis were used to screen M2 macrophage-related prognostic genes. A signature based on M2 macrophage-related prognostic genes was established and used to predict the prognosis and immunotherapy efficacy in LUAD.

Results

Twenty-two M2 macrophage-related genes associated with the prognosis of LUAD were confirmed using WGCNA, and then two molecular subtypes were identified with significantly different survival, gene expressions, and clinic characteristics were classified. LASSO analysis identified nine M2 macrophage-related prognostic genes to establish a risk signature, classifying patients into low- and high-risk groups. Data indicated that low-risk patients had better survival. Moreover, the signature was an independent prognostic factor for LUAD and a potential biomarker for patients receiving immunotherapy. Single-cell transcriptome analysis may provide important information on molecular subtypes and heterogeneity.

Conclusion

Risk signature based on M2 macrophage-related genes is a valuable tool for predicting prognosis and immunotherapy response in patients with LUAD.
Fresh-cut watermelon: postharvest physiology, technology, and opportunities for quality improvement
Authors: Quandoh Ebenezer , Albornoz Karin
Published: February 2025

Watermelon (Citrullus lanatus L.) fruit is widely consumed for its sweetness, flavor, nutrition and health-promoting properties. It is commonly commercialized in fresh-cut format, satisfying consumer demand for freshness and convenience, but its shelf-life is limited. Despite the potential for growth in fresh-cut watermelon sales, the industry faces the challenge of maintaining quality attributes during storage. Fresh-cut processing induces a series of physiological and biochemical events that lead to alterations in sensory, nutritional and microbiological quality. A signal transduction cascade involving increases in respiration and ethylene production rates and elevated activities of cell wall and membrane-degrading enzymes compromise cellular and tissue integrity. These responses contribute to the development of quality defects like juice leakage, firmness loss and water-soaked appearance. They also drive the loss of bioactive compounds like lycopene, affecting flesh color and reducing nutritional value, ultimately culminating in consumer rejection, food losses and waste. Although great research progress has been achieved in the past decades, knowledge gaps about the physiological, biochemical and molecular bases of quality loss persist. This review article summarizes the advances in the study of physicochemical, microbiological, nutritional, and sensory changes linked to the deterioration of watermelon after processing and during storage. Different technological approaches for quality improvement and shelf-life extension are summarized: pre- and postharvest, physical, and chemical. We also discuss the advantages, disadvantages and challenges of these interventions and propose alternative directions for future research aiming to reduce qualitative and quantitative fresh-cut watermelon losses.
Health care provider's perceived factors for the increased practice of caesarean delivery in North West Amhara referral hospitals, Ethiopia, 2022: a qualitative study
Authors: Ayele Mulat , Berta Marta , Zewudie Amare , Shitie Lake Eyob , Yilak Gizachew , Tilahun Befkad Derese , Aklil Mastewal Belayneh
Published: February 2025

Background

Caesarean delivery is an essential obstetric intervention to reduce maternal and newborn mortality in emergencies. However, in Ethiopia, there is a high prevalence of caesarean deliveries. Therefore, this study aimed to explore the factors perceived by healthcare providers that contribute to the excessive rates of caesarean deliveries in North West Amhara referral hospitals, Ethiopia, in 2022.

Methods

A phenomenological study design was employed, utilizing semi-structured interview guide for data collection. Fifteen healthcare providers working in referral hospitals in the north-western region of Amhara were interviewed using a heterogeneous purposive sampling approach until data was saturated. Transcribed interviews were translated coded and finally thematic analyses were employed using Open Code 4.0 software.

Results

Healthcare providers observed a significant increase in the frequency of caesarean deliveries. Multiple factors were identified as contributing to this rise, including the involvement of medical students, the use of cardiotocography, a decline in instrumental deliveries, inadequate trial of labor after previous caesarean deliveries, and the absence of clear indications for performing caesarean deliveries for social or maternal requests. Notably, patients who had received care in private clinics were more likely to undergo caesarean deliveries.

Conclusion

Caesarean deliveries were observed to be performed based on subjective or approximate indications, rather than clear obstetric indications. Encouraging greater emphasis on trial of labor, instrumental delivery, and performing caesarean deliveries only when there are definitive obstetric indications, rather than for social or maternal requests, can contribute to reducing the prevalence of caesarean delivery rates.
Vision transformers for automated detection of diabetic peripheral neuropathy in corneal confocal microscopy images
Authors: Ben Rabah Chaima , Petropoulos Ioannis N. , Malik Rayaz A. , Serag Ahmed
Published: February 2025

Early detection and management of diabetic peripheral neuropathy (DPN) are critical to reducing associated morbidity and mortality. Corneal Confocal Microscopy (CCM) facilitates the imaging of corneal nerves to detect early and progressive nerve damage in DPN. However, its wider adoption has been limited by the subjectivity and time-intensive nature of manual nerve fiber quantification. This study investigates the diagnostic utility of state-of-the-art Vision Transformer (ViT) models for the binary classification of CCM images to distinguish between healthy controls and individuals with DPN. The ViT model's performance was also compared to ResNet50, a convolutional neural network (CNN) previously applied for DPN detection using CCM images. Using a dataset of approximately 700 CCM images, the ViT model achieved an AUC of 0.99, a sensitivity of 98%, a specificity of 92%, and an F1-score of 95%, outperforming previously reported methods. These findings highlight the potential of the ViT model as a reliable tool for CCM-based DPN diagnosis, eliminating the need for time-consuming manual image segmentation. Moreover, the results reinforce CCM's value as a non-invasive and precise imaging modality for detecting nerve damage, particularly in neuropathy-related conditions such as DPN.
Recent advances in adipose-derived mesenchymal stem cell-derived exosomes for regulating macrophage polarization
Authors: Dong Zhewei , Fu Yingli , Cai Zhongming , Dai Hao , He Yucang
Published: February 2025

Adipose-derived mesenchymal stem cells (ADSCs) exhibit superior immunomodulatory properties and have broad therapeutic applications. They induce macrophage M2 polarization for anti-inflammatory responses. Exosomes derived from ADSCs (ADSC-EXOs) exhibit biological functions similar to those of ADSCs but can circumvent the limitations associated with cellular injection therapies. Potent anti-inflammatory substances contained in exosomes include the glycoprotein MFGE8, the cytokines such as prostaglandin E2, IL-6, and IGF, as well as non-coding nucleotides (miR-451a, miR-23, miR-30d-5p, let-7, lncRNA DLEU2, circRps5, Circ-Ptpn4, and mmu_ circ_0001359). The anti-inflammatory and immunomodulatory properties of these exosomes provide new perspectives for therapeutic approaches for graft inflammation, bone healing, acute lung injury, kidney stones, myocardial infarction, and diabetes-related diseases. This review summarizes the contents and functions of ADSC-EXOs, outlines their properties and the characteristics of macrophage phenotypes, and emphasizes their impact on macrophage polarization and their contribution to immune-related diseases.
Insights into CSF-1/CSF-1R signaling: the role of macrophage in radiotherapy
Authors: Shang Qingchao , Zhang Pei , Lei Xiao , Du Lehui , Qu Baolin
Published: February 2025

Macrophage plays an important role in homeostasis and immunity, and dysfunctional macrophage polarization is believed to be associated with the pathogenesis of tissue fibrosis and tumor progression. Colony stimulating factor-1 (CSF-1), a polypeptide chain cytokine, through its receptor (CSF-1R) regulates the differentiation of macrophages. Recently, the promising therapeutic potential of CSF-1/CSF-1R signaling pathway inhibition in cancer treatment is widely used. Furthermore, inhibition of CSF-1/CSF-1R signaling combined with radiotherapy has been extensively studied to reduce immunosuppression and promote abscopal effect. In addition, cumulative evidence demonstrated that M2 phenotype macrophage is dominant in tissue fibrosis and the inhibition of CSF-1/CSF-1R signaling pathway ameliorated pulmonary fibrosis, including radiation-induced lung fibrosis. Herein, we provide a comprehensive review of the CSF-1/CSF-1R signaling pathway in radiotherapy, with a focus on advances in macrophage-targeted strategies in the treatment of cancer and pulmonary fibrosis.
An integrative analysis of ASCL1 in breast cancer and inhibition of ASCL1 increases paclitaxel sensitivity by activating ferroptosis via the CREB1/GPX4 axis
Authors: Yang Xiaolu , Li Yilun , Peng Yaqi , Chang Yuan , He Binglu , Zhang Tianqi , Zhang Shiyu , Geng Cuizhi , Liu Yunjiang , Li Xiaolong , Hao Jun , Ma Li
Published: February 2025

Objective

Our previous study found that Achaete-scute complex homolog 1 (ASCL1) is involved in classifying BC subtypes with different prognostic and pathological characteristics. However, the biological role of ASCL1 in BC still remains largely unexplored. This study aims to elucidate the function of ASCL1 in BC using bioinformatics analyses, as well as in vitro and in vivo experimental approaches.

Methods

Data from the TCGA, GEO, and Human Protein Atlas databases were utilized to evaluate ASCL1 expression in BC and its association with patient prognosis. Genetic alterations in ASCL1 were assessed through the COSMIC and cBioPortal databases, while the TIMER2.0 database provided insights into the relationship between ASCL1 expression and key gene mutations in BC. The GDSC database was used to examine correlations between ASCL1 levels and sensitivity to standard chemotherapeutic agents. Associations between ASCL1 expression and cytokines, immunomodulatory factors, MHC molecules, and receptors were analyzed using Pearson and Spearman correlation methods. The TIP database was employed to investigate the connection between ASCL1 expression and immunoreactivity scores, and six computational approaches were applied to evaluate immune cell infiltration. Functional assays were conducted on BC cell lines MCF-7 and MDA-MB-231, and nude mouse models were used for in vivo studies.

Results

ASCL1 was found to be upregulated in BC and correlated with unfavorable prognosis and mutations in key oncogenes. Its expression was linked to immunomodulatory factors, immune cell infiltration, and immunoreactivity scores in the tumor microenvironment. Additionally, ASCL1 influenced tumor immune dynamics and chemosensitivity in BC. Overexpression of ASCL1 enhanced BC cell proliferation, migration and invasion, while its knockdown had the opposite effect. Notably, inhibition of ASCL1 increased BC cell sensitivity to paclitaxel both in vitro and in vivo. In addition, inhibition of ASCL1 activated ferroptosis in BC, including altered mitochondrial morphology, increased MDA and ROS levels, decreased GSH levels and reduced GSH/GSSG ratio. Mechanistically, inhibition of ASCL1 decreases the phosphorylation of CREB1, thus reducing the expression of GPX4. In summary, inhibition of ASCL1 increases paclitaxel sensitivity by activating ferroptosis via the CREB1/GPX4 axis.

Conclusions

ASCL1 exerts oncogenic effects in BC and represents a potential therapeutic target for intervention.
Linking interannual variability of turbidity fronts in the Eastern China Seas to local processes and ocean warming
Authors: Du Yunfei , Fan Daidu , Zhang Jicai
Published: February 2025

The turbidity front is susceptible to rapid changes in ocean hydrodynamics. Understanding its variability is crucial for elucidating material transport on continental shelves in light of evolving land-ocean interactions. However, the long-term frontal variability and its controlling mechanism over the shelf sea scale still need further study. Using a decade of satellite observations, this study assesses the interannual variability of turbidity fronts in the Eastern China Seas and their responses to local processes and rapid ocean warming. A gradient-based front detection algorithm and frontal probability are used to identify the geographical locations of turbidity fronts and their variability at the interannual scale, respectively. Regional heterogeneities in interannual variations and controlling mechanisms of frontal activity are observed. Specifically, the significant (p<0.05) and strongest correlations show that wind wave, horizontal temperature gradient, and mixed layer depth are identified as the most important drivers of interannual variations in frontal activity in the Bohai, Yellow, and East China Seas, respectively. The El Niño-Southern Oscillation influences frontal anomalies through a delayed wind-response mechanism (>=4 months). Notably, the recent increase in frontal probability (+0.07%/year) in offshore areas of the Yellow and East China Seas is primarily attributed to an intensified horizontal temperature (density) gradient (+0.0005 °C/km/year) resulting from ocean warming. As ocean warming continues, the offshore transport of terrigenous materials is expected to increase, potentially enhancing ocean primary productivity and carbon sequestration, and altering ecosystem function and fisheries.
A multi-source data-driven approach for navigation safety integrating computational intelligence and Bayesian networks
Authors: Qu Xiaotong , Wang Chengbo
Published: February 2025

Ships often face various risks when sailing at sea, ranging from harsh natural environments to complex traffic conditions. To reduce the impact of these risks on ships and crews, this paper proposes a navigation risk assessment method that integrates computational intelligence (CI) techniques, such as fuzzy logic, with Bayesian networks (BNs) and utility theory. Firstly, a navigation risk assessment system is established using maritime data and expert knowledge, which evaluates risks from a spatial perspective by considering factors such as safeguard and accident conditions across different regions. Secondly, a fuzzy logic-based numerical and expert data transformation method is proposed to derive the prior probabilities of risk factors in BNs. The weighted fuzzy rule base is used to capture the dependencies among the risk factors. Finally, the probability distribution of navigation risk is determined by combining the prior probability and the dependencies, which are converted into risk index values through utility theory. Taking the grid-based navigation risk assessment of the South China Sea as an example, the effectiveness of this method is verified. The results of the study provide theoretical support for navigation risk assessment based on multi-source data and provide a reference for formulate maritime regulatory policies.
Toxic epidermal necrolysis induced by moxifloxacin and exacerbated by clindamycin in an elderly patient: A case report
Authors: Wang Yongguang , Guo Qizheng , Li Zhenyang , Gan Guifen , Pan Chun
Published: February 2025

Toxic Epidermal Necrolysis (TEN) is a severe skin-mucosal reaction induced by medications, commonly characterized by blister formation and widespread epidermal detachment. Typical causative agents include allopurinol, antibiotics, anticonvulsants, and non-steroidal anti-inflammatory drugs (NSAIDs), with trimethoprim/sulfamethoxazole and penicillin being the most frequently implicated among antibiotics. However, lincosamide antibiotics as the cause of aggravation are rarely reported in clinical settings. This case report presents a patient with TEN induced by quinolone antibiotics, who experienced rapid progression of the condition after combining with lincomycin antibiotics. Clinical remission was achieved through a combination of corticosteroids, intravenous immunoglobulin, and plasma exchange therapy. This report aims to enhance clinicians’ understanding of TEN by providing a detailed case presentation and discussion.
Survey of Notified Bodies reveals very limited use of conditional certification for high-risk medical devices
Authors: Dobrzynska A. , Rejon-Parrilla J. C. , Epstein D. , Aranda-López J. , Fraser A. G. , Blasco-Amaro J. A.
Published: February 2025

The aim was to identify the experiences of Notified Bodies (NBs) in Europe in applying restrictions or limitations to certificates for high-risk medical devices. A survey examining NB practices regarding restrictions or limitations applied to Class III and IIb implantable medical devices was conducted as part of the CORE-MD Horizon 2020 project. Thirteen NBs responded; three had issued certificates of conformity with restrictions or limitations. NBs reported challenges in collecting and providing data on conditional certification, which would likely increase their workload. Enhancing clarity of regulatory standards, improving data transparency, fostering stakeholders' collaboration, and providing targeted training are essential to ensure uniform and homogeneous application of conditional certifications across the EU.
Persistent functional and taxonomic groups dominate an 8,000-year sedimentary sequence from Lake Cadagno, Switzerland
Authors: Rodriguez Paula , Berg Jasmine S. , Deng Longhui , Vogel Hendrik , Okoniewski Michal , Lever Mark A. , Magnabosco Cara
Published: February 2025

Most of our knowledge of deep sedimentary life comes from marine environments; however, despite their relatively small volume, lacustrine sediments constitute one of the largest global carbon sinks and their deep sediments are largely unexplored. Here, we reconstruct the microbial functional and taxonomic composition of an 8,000-year Holocene sedimentary succession from meromictic Lake Cadagno (Switzerland) using shotgun metagenomics and 16S rRNA gene amplicon sequencing. While younger sediments (<1,000 years) are dominated by typical anaerobic surface sedimentary bacterial taxa (Deltaproteobacteria, Acidobacteria, and Firmicutes), older layers with lower organic matter concentrations and reduced terminal electron acceptor availability are dominated by taxa previously identified as “persistent populations” within deep anoxic marine sediments (Candidatus Bathyarchaeia, Chloroflexi, and Atribacteria). Despite these dramatic changes in taxonomic community composition and sediment geochemistry throughout the sediment core, higher-order functional categories and metabolic marker gene abundances remain relatively consistent and indicate a microbial community capable of carbon fixation, fermentation, dissimilatory sulfate reduction and dissimilatory nitrate reduction to ammonium. As the conservation of these metabolic pathways through changes in microbial community compositions helps preserve the metabolic pathway connectivity required for nutrient cycling, we hypothesize that the persistence of these functional groups helps enable the Lake Cadagno sedimentary communities persist amidst changing environmental conditions.
Introduction of Panax notoginseng into pine forests significantly enhances the diversity, stochastic processes, and network complexity of nitrogen-fixing bacteria in the soil
Authors: Zhao Xiaoyan , He Shu , Rui Rui , Hei Jingying , He Xiahong , Wang Shu
Published: February 2025

Introduction

Nitrogen-fixing bacteria (NFB) have a pivotal impact on the nitrogen cycle within agroforestry systems. The organic management of the Panax notoginseng (sanqi)-Pinus armandii agroforestry (SPA) system resulted in nitrogen deficiency because of the lack of application of chemical fertilizers. Therefore, assessing the variability in NFB due to the cultivation of sanqi in the SPA system becomes crucial.

Methods

The seasonal dynamics in the abundance, diversity, and community structure of NFB in the soil of monocropping pine (MP) and SPA systems were assessed using real-time quantitative polymerase chain reaction and high-throughput sequencing technology.

Results and discussion

Sanqi cultivation triggered a decrease in the abundance of NFB but increased α diversity. Additionally, significant differences in the community structure of NFB were noted between the MP and SPA systems. Moreover, the abundance of Bradyrhizobium and Azospirillum increased in the soil after sanqi was cultivated. Furthermore, the cultivation of sanqi broadened the ecological niche breadth of NFB and increased the stochasticity in its community structure assembly (i.e., dispersal limitation). Additionally, the SPA system increased the network complexity but not the stability of NFB. The structural equation model (SEM) revealed that pH directly impacted the network complexity and stability of NFB in the SPA system. Sanqi cultivation positively influences the community characteristics of NFB in the soil in the SPA system. Our study provides new insights into nitrogen cycling and utilization in the SPA system.
Established Pseudomonas syringae pv. tomato infection disrupts immigration of leaf surface bacteria to the apoplast
Authors: Cowles Kimberly N. , Iyer Arjun S. , McConnell Iain , Guillemette Ellie G. , Nellore Dharshita , Zaacks Sonia C. , Barak Jeri D.
Published: February 2025

Bacterial disease alters the infection court creating new niches. The apoplast is an oasis from the hardships of the leaf surface and is generally inaccessible to nonpathogenic members of the phyllosphere bacterial community. Previously, we demonstrated that Salmonella enterica serovar Typhimurium (S. Typhimurium) immigrants to the leaf surface can both enter the apoplast and replicate due to conditions created by an established Xanthomonas hortorum pv. gardneri (Xhg) infection in tomato. Here, we have expanded our investigation of how infection changes the host by examining the effects of another water-soaking pathogen, Pseudomonas syringae pv. tomato (Pst), on immigrating bacteria. We discovered that, despite causing macroscopically similar symptoms as Xhg, Pst infection disrupts S. Typhimurium colonization of the apoplast. To determine if these effects were broadly applicable to phyllosphere bacteria, we examined the fates of immigrant Xhg and Pst arriving on an infected leaf. We found that this effect is not specific to S. Typhimurium, but that immigrating Xhg or Pst also struggled to fully join the infecting Pst population established in the apoplast. To identify the mechanisms underlying these results, we quantified macroscopic infection symptoms, examined stomata as a pinch point of bacterial entry, and characterized aspects of interbacterial competition. While it may be considered common knowledge that hosts are fundamentally altered following infection, the mechanisms that drive these changes remain poorly understood. Here, we investigated these pathogens to reach a deeper understanding of how infection alters a host from a rarely accessible, inhabitable environment to an obtainable, habitable niche.
Tight junction proteins in glial tumors development and progression
Authors: Moskal Jakub , Michalak Slawomir
Published: February 2025

Tight junctions form a paracellular barrier in epithelial and endothelial cells, and they regulate the diffusion of fluids, molecules, and the penetration of cells across tissue compartments. Tight junctions are composed of a group of integral membrane proteins, which include the claudin family, tight junction-associated Marvel protein family, junctional adhesion molecule family, and proteins that anchor the cytoskeleton, such as zonula occludens proteins and the cingulin family. Several factors, such as neurotransmitters or cytokines, and processes like ischemia/hypoxia, inflammation, tumorigenesis, phosphorylation/dephosphorylation, ubiquitination, and palmitoylation, regulate tight junction proteins. Claudins are involved in tumorigenesis processes that lead to glioma formation. In gliomas, there is a noticeable dysregulation of claudins, occludin, and zonula occludens-1 abundance, and their dislocation has been observed. The weakening of intercellular adhesion and cell detachment is responsible for glioma infiltration into surrounding tissues. Furthermore, the paracellular permeability of the blood–brain barrier, formed with the involvement of tight junction proteins, influences the development of peritumoral edema – and, simultaneously, the rate of drug delivery to the glial tumor. Understanding the junctional and paracellular environments in brain tumors is crucial to predicting glial tumor progression and the feasibility of chemotherapeutic drug delivery. This knowledge may also illuminate differences between high and low-grade gliomas.
Exploring cerebellar transcranial magnetic stimulation in post-stroke limb dysfunction rehabilitation: a narrative review
Authors: Wang Zhan , Wang Likai , Gao Fei , Dai Yongli , Liu Chunqiao , Wu Jingyi , Wang Mengchun , Yan Qinjie , Chen Yaning , Wang Chengbin , Wang Litong
Published: February 2025

This review delves into the emerging field of cerebellar Transcranial Magnetic Stimulation (TMS) in the rehabilitation of limb dysfunction following a stroke. It synthesizes findings from randomized controlled trials and case studies, examining the efficacy, safety, and underlying mechanisms of cerebellar TMS. The review outlines advancements in TMS technologies, such as low-frequency repetitive TMS, intermittent Theta Burst Stimulation, and Cerebello-Motor Paired Associative Stimulation, and their integration with physiotherapy. The role of the cerebellum in motor control, the theoretical underpinnings of cerebellar stimulation on motor cortex excitability, and the indirect effects on cognition and motor learning are explored. Additionally, the review discusses current challenges, including coil types, safety, and optimal timing and modes of stimulation, and suggests future research directions. This comprehensive analysis highlights cerebellar TMS as a promising, though complex, approach in stroke rehabilitation, offering insights for its clinical optimization.
The inhibitory effect of intraspinal microstimulation of the sacral spinal cord on nonlinear bladder reflex dynamics in cats
Authors: Qasemi Amirhossein , Aminian Alireza , Erfanian Abbas
Published: February 2025

Objective

Electrical stimulation of the pudendal nerve, pelvic nerve, sacral dorsal root ganglion (DRG), and spinal cord has been explored to treat urinary incontinence and overactive bladder (OAB). This study introduces sacral intraspinal microstimulation (ISMS) as a novel method to inhibit spontaneous bladder reflexes in anesthetized cats. In addition, we investigated the effects of intermittent and switching stimulation patterns on bladder inhibition.

Methods

The electrode was implanted in the dorsal horn of the S2 spinal cord. Bladder pressure was recorded under isovolumetric conditions, and the stimulation parameters were adjusted to inhibit spontaneous bladder contractions. Nonlinear dynamic methods, including chaos theory, were employed to analyze the complexity of bladder reflexes.

Results

Results demonstrated that ISMS targeting the dorsal horn of the S2 spinal segment effectively suppressed high-amplitude spontaneous contractions. Furthermore, bladder reflexes exhibited complex dynamics, ranging from regular to chaotic patterns, with transitions between these states. Importantly, ISMS was able to stabilize these chaotic dynamics, leading to more controlled bladder behavior.

Conclusion

These findings suggest that sacral ISMS offers a promising, targeted alternative to traditional stimulation therapies, potentially providing a new therapeutic approach for managing OAB and urinary incontinence by regulating chaotic bladder activity.
Association of a novel nutritional index with cognitive impairment in middle-aged and elderly Chinese adults: a cross-sectional analysis from the China Health and Retirement Longitudinal Study
Authors: Liu Guotao , Zhang Jianyuan
Published: February 2025

Purpose

The triglyceride-cholesterol-body weight index (TCBI), a novel and easily computable nutritional index, incorporates serum triglyceride (TG), total cholesterol (TC), and body weight (BW). This study explored the association between TCBI and cognitive impairment in middle-aged and elderly Chinese populations.

Patients and methods

This cross-sectional study employed data from the China Health and Retirement Longitudinal Study (CHARLS) baseline survey, including 7,145 participants. TCBI was calculated as TG (mg/dL) × TC (mg/dL) × BW (kg)/1,000. Cognitive function was assessed based on mental status and episodic memory, with a total score below 11 indicating cognitive impairment. The relationship between TCBI and cognitive impairment was examined using multiple logistic regression, smooth curve fitting, and subgroup analyses.

Results

After full adjustment, each 1-unit increase in log-transformed TCBI (Lg TCBI) was associated with a 29.7% reduction in cognitive impairment risk [odds ratio (OR) = 0.703, 95% confidence interval (CI): 0.529–0.933; p = 0.015]. When Lg TCBI was categorized into quartiles, the Q2, Q3, and Q4 groups exhibited a reduced risk of cognitive impairment by 19.9, 16.3, and 22.9%, respectively (p for trend = 0.043), compared to the Q1 group. Smooth curve fitting revealed a consistent decrease in cognitive impairment risk with higher Lg TCBI levels. Subgroup analysis indicated that the association was stronger among participants aged ≥60 years (OR = 0.655, 95% CI: 0.438–0.979), non-current drinkers (OR = 0.643, 95% CI: 0.451–0.917), and those who engaged in socializing (OR = 0.568, 95% CI: 0.371–0.871).

Conclusion

TCBI was significantly and negatively associated with cognitive impairment in Chinese middle-aged and elderly individuals, with the effect more pronounced in those aged ≥60 years, non-current drinkers, and socially active participants.
Tacrolimus and mycophenolate mofetil in corticosteroid-resistant hepatitis secondary to tislelizumab: a case report
Authors: Jiang Chang , Guo Shanxian
Published: February 2025

Tislelizumab is a monoclonal antibody with high binding affinity for programmed death-1 (PD-1) receptors. In patients with extensive-stage small-cell lung cancer (ES-SCLC), the first-line use of tislelizumab combined with chemotherapy has shown significant efficacy. However, with the widespread use of PD-1 inhibitors, there are increasing reports of immune-related adverse events (irAEs) in clinical practice, with immune-related hepatitis (IRH) being particularly common. This article reports a case of an ES-SCLC patient (cT3N3M0 cStage IIIB) who developed corticosteroid-resistant hepatitis and recovered through dual immunosuppressant therapy. The patient was a 67-year-old male, diagnosed with ES-SCLC, who received a combination therapy of etoposide, cisplatin, and tislelizumab. Three weeks after the fourth treatment cycle, the patient experienced symptoms, such as decreased appetite, itching, yellow urine, and jaundice, and was diagnosed with IRH, manifested as “Grade 3 total bilirubin increase,” “Grade 3 alanine transaminase increase,” and “Grade 3 aspartate transaminase increase.” Despite intravenous injection of methylprednisolone (MP) 100 mg/day (2 mg/kg) and oral administration of mycophenolate mofetil (MMF) 1 g twice daily, liver function continued to be impaired. In this context, tacrolimus (TAC) (5 mg, twice daily) was added to the therapy, and the IRH level was reduced from Grade 3 to normal. Subsequently, TAC and MMF were gradually reduced and eventually discontinued. Unfortunately, after discontinuing immunosuppressants, IRH recurred. Although the patient still responded to TAC combined with MMF, liver function recovery took a longer time. Due to persistent liver dysfunction, the patient failed to receive second-line chemotherapy and ultimately passed away due to disease progression. Through this case, we hope to emphasize the importance of reasonably extending the use of immunosuppressants to avoid the recurrence of IRH and reduce the premature discontinuation of immunosuppressants. Besides, when tumor progression and IRH recurrence occur simultaneously, providing effective immunosuppressive therapy and reasonably arranging systemic anti-tumor therapy may bring clinical benefits to patients.
The effect of locomotive syndrome on the trajectory of sleep disturbance in geriatric oncology inpatients
Authors: Yang Yu-Ling , Su Hui , Lu Hui , Wang Jing , Zhou Yu-Qing , Li Ling , Yu Hui , Lv Yan , Chen Ying
Published: February 2025

Objective

To explore the developmental trajectory of sleep disturbance in geriatric oncology inpatients and assess the impact of locomotive syndrome (LS) on this trajectory.

Methods

This longitudinal study enrolled 284 geriatric oncology inpatients through convenience sampling from August 2023 to February 2024 at the Oncology Center of the Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu Province, China. Sleep quality was monitored for seven days following admission (T0-T6) using a wrist motion analyzer. The developmental trajectory of sleep disturbance was analyzed using the latent category growth model (LCGM). Patients were categorized into the LS group (n=177) and the non-LS group (n=107) based on the 25-question Geriatric Locomotive Function Scale (GLFS-25). Comparisons were made between the two groups regarding the distribution of sleep disturbance trajectories.

Results

Three potential categories for the development trajectory of sleep disturbance in inpatients were identified: non-sleep disturbance, sleep disturbance improvement, and sleep disturbance persistence. The lowest sleep quality was observed on the second day after admission (T2). In the non-LS group, 40 cases (37.4%) experienced no sleep disturbance, 45 cases (42.1%) showed improvement, and 22 cases (20.6%) showed persistence of sleep disturbance. In the LS group, 32 cases (18.1%) experienced no sleep disturbance, 50 cases (28.2%) showed improvement, and 95 cases (53.7%) exhibited persistent sleep disturbance. Significant differences were found in the trajectory distribution of sleep disturbance between the two groups (P<0.001).

Conclusions

Sleep disturbance is prevalent in geriatric oncology inpatients, with an incidence of 74.6% (212/284), and is most severe on the third day after admission. Patients with LS exhibit lower overall sleep quality and a higher likelihood of persistent sleep disturbances.
MicroRNA155 in non-small cell lung cancer: a potential therapeutic target
Authors: Wei Xiangju , Xiong Xianmin , Chen Ze , Chen Bi , Zhang Cantang , Zhang Wenhui
Published: February 2025

Lung cancer (LC) is the second most commonly diagnosed cancer among both men and women, and it stands as the leading cause of cancer-related mortality, characterized by high rates of morbidity and mortality. Among its subtypes, non-small cell lung cancer (NSCLC) is the most prevalent and one of the most challenging malignant tumors to treat. To date, various therapeutic approaches, including surgery, radiotherapy, and chemotherapy, have been employed in the management of lung cancer; however, due to its aggressive nature, the survival rates remain low. Consequently, exploring novel treatment strategies is of paramount importance. MicroRNAs (miRNAs), a large family of non-coding RNAs, play crucial roles in regulating several key biological processes, including cell proliferation, differentiation, inflammation, and apoptosis. Among these, microRNA155(miR-155) is one of the most conserved and versatile miRNAs, predominantly overexpressed in various diseases, including malignant tumors. This review elucidates the biological functions and roles of miR-155 in NSCLC and discusses its potential significance as a therapeutic target for future research directions and clinical applications.
Development and validation of a nomogram to predict recurrence in epithelial ovarian cancer using complete blood count and lipid profiles
Authors: Tang Xi , He Jingke , Huang Qin , Chen Yi , Chen Ke , Liu Jing , Tian Yingyu , Wang Hui
Published: February 2025

Objective

Ovarian cancer is one of the most lethal gynecological malignancies. This study aimed to evaluate the prognostic significance of complete blood count (CBC) and lipid profile in patients with optimally debulked epithelial ovarian cancer (EOC) and develop a nomogram model to predict recurrence-free survival (RFS).

Methods

This retrospective study analyzed patients diagnosed with EOC between January 2018 and June 2022.

Results

A total of 307 patients were randomly divided into training and validation sets in a ratio of 7:3. Grade, International Federation of Gynecology and Obstetrics (FIGO) stage, platelet-to-lymphocyte ratio, red blood cell distribution width-coefficient of variation, triglycerides, and human epididymal protein 4 were identified as independent prognostic factors. The novel nomogram displayed a good predictive performance, with a concordance index (C-index) of 0.787 in the training group and 0.807 in the validation group. The areas under the curve for 1-, 3-, and 5-year RFS were 0.770, 0.881, and 0.904, respectively, in the training group, and 0.667, 0.906, and 0.886, respectively, in the validation group. The calibration curves exhibited good concordance between the predicted survival probabilities and actual observations. Time-dependent C-index curves, integrated discrimination improvement, net reclassification index, and decision curve analysis showed that the nomogram outperformed FIGO staging.

Conclusion

This study established and validated a nomogram combining CBC and lipid profiles to predict RFS in patients with optimally debulked EOC, which is expected to aid gynecologists in individualized prognosis assessment and clinical management.
Postpartum changes in maternal physiology and milk composition: a comprehensive database for developing lactation physiologically-based pharmacokinetic models
Authors: Deferm Neel , Dinh Jean , Pansari Amita , Jamei Masoud , Abduljalil Khaled
Published: February 2025

Introduction

Pharmacotherapy during lactation often lacks reliable drug safety data, resulting in delayed treatment or early cessation of breastfeeding. In silico tools, such as physiologically-based pharmacokinetic (PBPK) models, can help to bridge this knowledge gap. To increase the accuracy of these models, it is essential to account for the physiological changes that occur throughout the postpartum period.

Methods

This study aimed to collect and analyze data on the longitudinal changes in various physiological parameters that can affect drug distribution into breast milk during lactation. Following meta-analysis of the collated data, mathematical functions were fitted to the available data for each parameter. The best-performing functions were selected through numerical and visual diagnostics.

Results and Discussion

The literature search identified 230 studies, yielding a dataset of 36,689 data points from 20,801 postpartum women, covering data from immediately after childbirth to 12 months postpartum. Sufficient data were obtained to describe postpartum changes in maternal plasma volume, breast volume, cardiac output, glomerular filtration rate, haematocrit, human serum albumin, alpha-1-acid glycoprotein, milk pH, milk volume, milk fat, milk protein, milk water content, and daily infant milk intake. Although data beyond 7 months postpartum were limited for some parameters, mathematical functions were generated for all parameters. These functions can be integrated into lactation PBPK models to increase their predictive power and better inform medication efficacy and safety for breastfeeding women.
Natural products targeting AMPK signaling pathway therapy, diabetes mellitus and its complications
Authors: Li Min , Ding Lu , Cao Liyan , Zhang Zepeng , Li Xueyan , Li Zirui , Xia Qinjing , Yin Kai , Song Siyu , Wang Zihan , Du Haijian , Zhao Daqing , Li Xiangyan , Wang Zeyu
Published: February 2025

Diabetes mellitus (DM) ranks among the most prevalent chronic metabolic diseases, characterized primarily by a persistent elevation in blood glucose levels. This condition typically stems from either insufficient insulin secretion or a functional defect in the insulin itself. Clinically, diabetes is primarily classified into type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM), with T2DM comprising nearly 90% of all diagnosed cases. Notably, the global incidence of T2DM has surged dramatically over recent decades. The adenylate-activated protein kinase (AMPK) signaling pathway is crucial in regulating cellular energy metabolism, marking it as a significant therapeutic target for diabetes and related complications. Natural products, characterized by their diverse origins, multifaceted bioactivities, and relative safety, hold considerable promise in modulating the AMPK pathway. This review article explores the advances in research on natural products that target the AMPK signaling pathway, aiming to inform the development of innovative antidiabetic therapies.
Rutaecarpine alleviates hepatic ischemia‒reperfusion injury in liver transplantation by inhibiting inflammatory response and oxidative stress
Authors: Liu Yan , Qi Feng , Xiang Lun-Jian , Yi Zhu-Jun , Li Sheng-Wei
Published: February 2025

Background

Donation after circulatory death (DCD) livers are limited by mandatory warm ischemia and are more susceptible to ischemia‒reperfusion injury (IRI). Inflammation and oxidative stress play key roles in the development of hepatic IRI, and Rutaecarpine (Rut) has anti-inflammatory and anti-oxidative stress effects. The aim of this study was to investigate whether Rut can alleviate hepatic IRI in liver transplantation (LT) and to explore the underlying mechanisms.

Methods

Rat DCD LT and oxygen-glucose deprivation/reoxygenation (OGD/R) cell models were established to clarify the effect of Rut on hepatic IRI. The key molecules involved in the hepatoprotective effects of Rut were identified through joint analysis of data from LT patients and drug targets. The target was further validated by in silico, in vivo and in vitro experiments.

Results

Rut significantly alleviated liver dysfunction, pathological injury, and apoptosis and improved the survival rate of the rats subjected to LT. In addition, Rut significantly inhibited inflammatory response and oxidative stress. Rut also had similar effects on OGD/R-induced hepatocyte injury. Mechanistically, bioinformatics analysis and in vivo and in vitro experiments revealed that PDE4B may be a key target by which Rut exerts its protective effect, and molecular docking and cellular thermal shift assay confirmed this result. The function of PDE4B was studied via gene intervention technology, and the results showed that PDE4B can aggravate hepatic IRI. Furthermore, PDE4B overexpression abrogated the protective effect of Rut on the liver in LT.

Conclusion

Rut alleviates hepatic IRI by targeting PDE4B to inhibit inflammation and oxidative stress. These findings highlight the potential of Rut as a drug candidate for the treatment of patients undergoing LT.