bluuebunny/crossref_metadata_2025 huggingface dataset:
Insight on intrusion behavior of compacted bentonite with accessory-mineral ring: a modelling approach
Authors: Xu Libo , Ye Junneng , Yao Yanming
Published: January 2025

Investigating the intrusion behavior of buffer/backfill materials is a critical aspect in the design of high-level radioactive waste (HLW) disposal repositories. This study proposes an intrusion model that accounts for the influence of the accessory-mineral ring and refines it by incorporating the specimen saturation process. The results show that the model demonstrated good agreement with the measured values after 30 days, but less accurate prior to this time. After incorporating a correction for the specimen’s saturation process, the model could well predict the measured values throughout the whole intrusion process. Additionally, the study suggests that predictions under parallel montmorillonite plates may be lower compared to non-parallel plates. The accessory-mineral ring significantly inhibits bentonite intrusion, and its restraining effect increases with the ring’s width. Compared to the smooth acrylic fissures, the irregular fractures in actual disposal repositories further limit bentonite intrusion. Fracture water seepage restricts bentonite intrusion in the upper part of the specimen while promoting it in the lower part, and also enhances the inhibiting effect of the accessory-mineral ring. The extent of this effect depends on the water flow velocity. Furthermore, increasing temperature promotes bentonite intrusion.
Exploration of policy feedback mechanism for healthcare improvement in China: a grounded theory model
Authors: Zhu Tuo-Dong , Yang Ming-Jin , Wu Hao
Published: January 2025

Background

Despite increasing governments’ endeavors to improve the quality of medical services focused on patient experience, it has been difficult due to a lack of systematic and replicable theories to guide healthcare improvement. This study aimed to construct a theoretical model of a policy feedback mechanism for guiding healthcare improvement based on healthcare improvement in China’s context.

Methods

We constructed a theoretical model of policy feedback mechanism for improving healthcare using a grounded theory approach to collect and analyze textual data on healthcare improvement in China.

Results

In this study, the theoretical model of policy feedback mechanism for healthcare improvement contained five core modules: multi-level objects, policy context, policy tools driven, policy feedback process, and policy feedback results. At the theoretical level, we innovatively constructed the module of “patient feelings,” including “patient sense of gain,” “patient happiness,” and “patient sense of safety.” Practically, we generated a list of ways through the “medical organization behavior” module to enhance patient feelings.

Conclusion

This model elaborated a policy feedback mechanism for healthcare improvement. This research provided theoretical and practical support for health authorities to formulate and apply various policies or initiatives to improve healthcare. Theoretically, the model innovated the development of patient feelings in the policy feedback for healthcare improvement. On the practical level, we generated specific strategies for hospitals to enhance healthcare and patient experience.
Tuberculosis menace: a case report of disseminated tuberculosis presenting as tubercular meningitis and long-segment cervical tuberculous myelitis in a 32-year-old man from rural India
Authors: Toshniwal Saket Satyasham , Kinkar Jiwan S. , Toshniwal Amit , Sood Anshul , Kumar Sunil , Acharya Sourya
Published: January 2025

This case report discusses an uncommon presentation of miliary tuberculosis as tubercular meningitis (TBM) and long-segment cervical tuberculous myelitis in a 32-year-old man from rural India. The patient presented with symptoms of fever, headache, neck stiffness, and gradual weakness in all four limbs. Hydrocephalic changes secondary to meningitis and involvement of the spinal cord were observed on neuroimaging and were correlated with clinical findings of cervical myelitis, confirming the diagnosis of TBM with cervical myelitis. TBM, together with cervical myelitis in patients with miliary tuberculosis (TB), is a rare manifestation in tubercular endemic countries, such as India. It is crucial to confirm the diagnosis and initiate antitubercular therapy (ATT) promptly in order to prevent neurological complications. In this context, the present case highlights the importance of considering TB in patients with neurological manifestations that are not characteristic of the most common diseases. This report also emphasizes the need to raise awareness and improve the management of tuberculosis in rural areas where there are few opportunities to access tertiary centers.
Profiling of small RNAs derived from tomato brown rugose fruit virus in infected Solanum lycopersicum plants by deep sequencing
Authors: Chen Mangle , Wang Donghai , Yang Jiali , Cao Yuhao , Song Xuemei , Lu Yuwen , Zheng Hongying , Peng Jiejun , Wu Guanwei , Wu Jian , Li Junmin , Chen Jianping , Yan Fei , Rao Shaofei
Published: January 2025

Tomato brown rugose fruit virus (ToBRFV) is an emerging, rapidly spreading virus belonging to the genus Tobamovirus which seriously decreases tomato yields. RNA silencing is an evolutionarily conserved antiviral mechanism. In virus-infected plants, virus-derived small interfering RNAs (vsiRNAs) are one of the key components involved in the RNA silencing-based antiviral activity in plants. The main function of vsiRNAs is to target and degrade viral RNA. Studies have found that some vsiRNAs can also target host transcripts, further regulating host responses and symptoms and promoting viral survival and spread. In this study, the vsiRNA profiles of ToBRFV-infected tomato plants were obtained by deep sequencing. VsiRNAs were mainly 21 and 22 nucleotides in length and had a U-bias at the 5′ end. The single-nucleotide resolution profile shows that vsiRNAs exhibit a heterogeneous continuous distribution in the ToBRFV genomic RNA, with hotspot regions on the antisense strand located at the 5′ end of the RdRP and in the coding regions of MP and CP. The presence of vsiRNAs was confirmed in tomato plants infected with ToBRFV through RT-PCR, and GO and KEGG enrichment analyses were performed on the predicted vsiRNA target genes (with an expectation value less than or equal to 2.5). Seven potential target genes were selected for qRT-PCR analysis, confirming that their transcript accumulation significantly decreased in the leaves of tomato plants infected with ToBRFV. These genes may play an important role in the process of viral infection in tomatoes. Our results suggest a role for vsiRNAs in the ToBRFV–tomato interaction.
A scientometric visualization analysis of the gut microbiota and gestational diabetes mellitus
Authors: Su Zehao , Liu Lina , Zhang Jian , Guo Jingjing , Wang Guan , Zeng Xiaoxi
Published: January 2025

Background

The prevalence of gestational diabetes mellitus (GDM), a condition that is widespread globally, is increasing. The relationship between the gut microbiota and GDM has been a subject of research for nearly two decades, yet there has been no bibliometric analysis of this correlation. This study aimed to use bibliometrics to explore the relationship between the gut microbiota and GDM, highlighting emerging trends and current research hotspots in this field.

Results

A total of 394 papers were included in the analysis. China emerged as the preeminent nation in terms of the number of publications on the subject, with 128 papers (32.49%), whereas the United States had the most significant impact, with 4,874 citations. The University of Queensland emerged as the most prolific institution, contributing 18 publications. Marloes Dekker Nitert was the most active author with 16 publications, and Omry Koren garnered the most citations, totaling 154. The journal Nutrients published the most studies (28 publications, 7.11%), whereas PLoS One was the most commonly co-cited journal, with a total of 805 citations. With respect to keywords, research focuses can be divided into 4 clusters, namely, “the interrelationship between the gut microbiota and pregnancy, childbirth,” “the relationship between adverse metabolic outcomes and GDM,” “the gut microbiota composition and metabolic mechanisms” and “microbiota and ecological imbalance.” Key areas of focus include the interactions between the gut microbiota and individuals with GDM, as well as the formation and inheritance of the gut microbiota. Increasing attention has been given to the impact of probiotic supplementation on metabolism and pregnancy outcomes in GDM patients. Moreover, ongoing research is exploring the potential of the gut microbiota as a biomarker for GDM. These topics represent both current and future directions in this field.

Conclusion

This study provides a comprehensive knowledge map of the gut microbiota and GDM, highlights key research areas, and outlines potential future directions.
Pediatric kidney transplant recipients are at an increased risk for dysbiosis
Authors: Yılmaz Gizem , Saygılı Seha , Ağbaş Ayşe , Karabağ Yılmaz Esra , Variş Ahmet , Canpolat Nur
Published: January 2025

Introduction

This study aimed to compare the gut microbiota composition in pediatric kidney transplant (KTx) recipient with that of healthy children.

Methods

This cross-sectional observational study included 30 pediatric KTx recipients aged between 7 and 21 years and 25 healthy children. The gut microbiota was assessed using 16S rRNA gene sequencing, with alpha and beta diversity, as well as all statistical analyses, conducted using the Phyloseq library in the R programming language. Taxonomic profiles were evaluated with QIIME2, and differences in gut microbiota profiles were compared using linear discriminant analysis effect size (LEFSe) with an LDA threshold of >2 and p < 0.05.

Results

No significant differences were found in alpha and beta diversity between the KTx recipients and healthy controls. However, KTx recipients exhibited significant alterations in microbiota composition, including higher relative abundances of Verrucomicrobiota at the phylum level, and Akkermansia and Neisseria at the genus level (p < 0.05 for all). Conversely, there was a decrease in bacterial genera belonging to the phylum Firmicutes. In addition, KTx recipients with a history of frequent urinary tract infections, diarrhea and reduced GFR showed significant increases in bacterial abundance (p < 0.05 for all).

Discussion

Pediatric KTx recipients demonstrated significant alterarions in gut microbiota composition, indicating dysbiosis. Further studies are needed to elucidate the cause-and-effect relationships of these changes and their impact on clinical consequencies and long-term prognosis.
A novel two-component system contributing the catabolism of c-di-GMP influences virulence in Aeromonas veronii
Authors: Liu Chaolun , Shao Jia , Ma Xiang , Tang Yanqiong , Li Juanjuan , Li Hong , Chi Xue , Liu Zhu
Published: January 2025

Introduction

Response regulators from diverse two-component systems often function as diguanylate cyclases or phosphodiesterases, thereby enabling precise regulation of intracellular c-di-GMP levels to control bacterial virulence and motility. However, the regulatory mechanisms of c-di-GMP require further elucidation.

Methods

This study confirmed that ArrS and ArrR form a two-component system via structural analysis, two-hybrid, and phosphodiesterase activity detection. To evaluate the impact of ArrS/ArrR on intracellular c-di-GMP levels, biofilm detection, motility detection, fluorescence reporter plasmids, and LC-MS/MS analysis were employed. One-hybrid, EMSA, and RT-qPCR were used to demonstrate the function of ArgR on arrSR promoter. The roles of ArrS/ArrR in Aeromonas veronii were investigated using RT-qPCR, murine model, and proteomics.

Results

ArrS and ArrR constituted a two-component system in Aeromonas veronii and were transcriptionally repressed by ArgR. ArrR exhibited phosphodiesterase activity, which is inhibited through phosphorylation mediated by ArrS. In Aeromonas veronii, ArrS/ArrR significantly altered the intracellular c-di-GMP levels. In a murine model, ΔarrS exhibited increased pathogenicity, leading to elevated TNF-α and IFN-γ levels in serum, and severer toxicity to spleen and kidney. These effects might be elucidated by the upregulated inflammation-associated proteins in ΔarrS. Moreover, the exonuclease RecB was also up-regulated in ΔarrS.

Discussion

We elucidated the regulatory mechanism of ArrS/ArrR on intracellular c-di-GMP levels and its impact on the virulence in Aeromonas veronii, and discussed the intricate relationship between c-di-GMP metabolism and arginine metabolism.
The effects of Bifidobacterium animalis QC08 on reducing uric acid level and providing renal protection in mice with hyperuricemia
Authors: Mao Huijia , Fan Yang , Tan Fang , Long Xingyao
Published: January 2025

Objective

The present study aimed to investigate the uric acid-lowering effects of Bifidobacterium animalis QC08 and explore its underlying mechanisms.

Methods

Hyperuricemia (HUA) model in mice was established using potassium oxonate (250 mg/kg) and yeast extract (15 g/kg). The serum levels of uric acid (UA), blood urea nitrogen (BUN), creatinine (Cr), and liver xanthine oxidase (XO) were measured in four groups, including normal group, control group, allopurinol group (5 mg/kg), and Bifidobacterium animalis QC08 group (1010 CFU/kg) using enzyme colorimetry. Additionally, serum tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels were assessed using enzyme-linked immunosorbent assay (ELISA). Pathological changes in renal tissue were examined through hematoxylin–eosin (HE) staining.

Results

In vivo experimental results indicated that compared with the normal group, the serum UA, Cr, and BUN levels, as well as the levels of inflammatory factors (TNF-α and IL-1β), and the activities of hepatic xanthine oxidase (XOD) and adenosine deaminase (ADA) were significantly elevated in the control group (p < 0.05). The expression levels of uric acid transport-related genes (UAT, ABCG2, and OAT1) in kidney tissue were significantly downregulated (p < 0.05), and evident kidney damage was found. In contrast, compared with the control group, the Bifidobacterium animalis QC08 group exhibited a significant decrease in serum UA, BUN, Cr, TNF-α, and IL-6 levels, along with reduced hepatic XOD and ADA activities (p < 0.05). Additionally, Bifidobacterium animalis QC08 was found to regulate the mRNA transcription of renal uric acid transporters, leading to significantly upregulation of the expression levels of UAT, ABCG2, and OAT1 genes (p < 0.05).

Conclusion

Bifidobacterium animalis QC08 demonstrates certain uric acid-lowering, anti-inflammatory, and renal protective effects, which are associated with the inhibition of XOD activity and the modulation of the expression levels of uric acid transporter genes (UAT, ABCG2, and OAT1).
Sotorasib resistance triggers epithelial-mesenchymal transition and activates AKT and P38-mediated signaling
Authors: Megid Raquel Arantes , Ribeiro Guilherme Gomes , Gomes Izabela Natalia Faria , Laus Ana Carolina , Ferro Leal Letícia , Sussuchi da Silva Luciane , Ariwoola Abu-Bakr Adetayo , Dias Josiane Mourão , Reis Rui Manuel , Jose da Silva-Oliveira Renato
Published: January 2025

Background

The molecular non-genetic changes of resistance to sotorasib are currently uncertain. The aim of this study was to generate a sotorasib-resistant cell line via selective pressure and systematically examine the molecular and phenotypic alterations caused by resistance.

Methods

Mutant NCI-H358 (KRASG12C) were exposed to incremental doses (2–512 nM) of sotorasib. Then, resistant clones were separated by single-cell sorting. Proliferation was analyzed in real-time by xCELLigence; protein profiles were quantified by protein arrays; and mRNA expression profile was measured using the PanCancer Pathways panel by NanoString. In silico analyses were conducted from a database comprising patient-derived xenograft (PDX) models and cell lines resistant to sotorasib. AKT and p38. The synergistic effect of combining AKT, p38, and EGFR inhibitors was assessed using the SynergyFinder platform. Additionally, AKT and p38 genes were silenced using esiRNA.

Results

Sotorasib-resistant H358-R cell line displayed markers of the mesenchymal-epithelial transition and loss of cell adhesion. Were identified 30 overexpressed genes in the resistance model, implicating in signaling pathways that leads to AKT activation and heightened protein expression levels of phosphorylated AKT and p38. To identify potential therapeutic strategies for overcoming sotorasib resistance, we investigated the combination of AKT and p38 inhibitors. Notably, combined inhibition of AKT (MK2206) and p38 (adezmapimod) restored sensitivity to sotorasib in resistant cell lines, as did silencing AKT expression.

Conclusion

These findings underscore the importance of adaptive mechanisms in sotorasib resistance in NSCLC cells contributing by EMT activation and demonstrates synergic combination with AKT and p38 inhibitors to restore sotorasib sensitivity in KRASG12C cells.
Evidence from NHANES 2011–2014: a correlation between the weight-adjusted-waist index and cognitive abilities in the United States
Authors: Zhao Chan , Xu Xintian , Hao Chunyan
Published: January 2025

Background

Obesity exerts a significant detrimental impact on cognitive function. The weight-adjusted waist index (WWI) serves as a more precise indicator of visceral obesity that is independent of weight, in contrast to body mass index (BMI). Still, little research has been conducted on the interrelation between WWI and cognitive abilities. This investigation explored the link between WWI and older Americans’ cognitive function.

Methods

Utilizing data from the 2011–2014 National Health and Nutrition Examination Cross-Sectional Survey, multiple linear regression analysis was used to assess the influence of WWI on cognitive abilities in those over 60. Three cognitive assessments were administered: the Animal Fluency Test (AFT), the Digit Symbol Substitution Test (DSST), and the Word Learning and Recall Module from the Coalition to Establish a Registry for Alzheimer’s Disease (CERAD). We implemented threshold effects analysis and smoothed curve fitting to elucidate the nonlinear relationship. Additionally, we analyzed subgroups to check for variability.

Results

There were 2,762 participants, including1,504 (54.45%) females and 1,258 (45.55%) males. 53.77% of them had completed high school or above, and their average age was 69.05 ± 6.62. After controlling for confounding variables, the improved model predicted a negative connection between WWI and CERAD-Total, AFT, and DSST scores (all p < 0.05). Furthermore, we performed a smoothenable curve fitting between WWI and cognitive function scores, resulting in a nonlinear connection and a threshold saturation effect. We also executed subgroup analyses and interaction tests based on gender, race, educational background, marital status, diabetes, body mass index, alcohol consumption, hypertension, smoking habits, stroke, depression, and sleep quality to assess whether the relationship between WWI and cognitive function was affected by heterogeneity across different population segments. The subgroup analysis found no significant differences in cognitive performance associated with WWI across the various subgroups.

Conclusion

Higher WWI levels are associated with impaired cognitive function in Americans aged 60 and older.
Estimation of extreme temperatures in direct solar methane pyrolysis within a porous medium
Authors: Xu Hengrui , Abuseada Mostafa , Ju Y. Sungtaek , Spearrin R. Mitchell , Fisher Timothy S.
Published: January 2025

Porous media have wide application in renewable energy conversion processes, such as solar-thermal fuels production and decarbonization. Heat transport mechanisms within porous media can be highly complex, particularly under extreme conditions encountered in concentrated solar thermal reactors in which direct measurement of temperature is challenging. Here, we implement and report an inverse heat conduction model to estimate the temperature distribution throughout a porous substrate domain in a direct solar methane pyrolysis process. By solving a two-dimensional heat transfer problem and applying an inverse optimization algorithm, we estimate the quasi-steady state spatial temperature distribution in a fibrous porous carbon substrate. The results are validated indirectly by experimentally measured graphite deposition and a simplified reaction kinetic model.
Critical review on the relationship between design variables and performance of dexterous hands: a quantitative analysis
Authors: Jiang Lei , Fu Chaojie , Liang Yanhong , Jin Yongbin , Wang Hongtao
Published: January 2025

Dexterous hands play vital roles in tasks performed by humanoid robots. For the first time, we quantify the correlation between design variables and the performance of 65 dexterous hands using Cramér’s V. Comprehensive cross-correlation analysis quantitatively reveals how the performance, such as speed, weight, fingertip force, and compactness are related to the design variables including degrees of freedom (DOF), structural form, driving form, and transmission mode. This study shows how various design parameters are coupled inherently, leading to compromise in performance metrics. These findings provide a theoretical basis for the design of dexterous hands in various application scenarios and offer new insights for performance optimization.
Area postrema syndrome in patients with autoimmune glial fibrillary acidic protein astrocytopathy
Authors: Li Qingchen , Teng Junfang
Published: January 2025

Objective

Area postrema syndrome (APS) is a relatively rare symptom of autoimmune glial fibrillary acidic protein astrocytopathy (A-GFAP-A). This study aimed to report the APS in GFAP-immunoglobulin G (GFAP-IgG) positive patients.

Methods

We retrospectively analyzed the clinical data of APS in GFAP-IgG positive patients and reviewed relevant literature. Moreover, we compared these data with APS patients in aquaporin-4-IgG-positive neuromyelitis optica spectrum disorders (AQP4-IgG+ NMOSD).

Results

7 of 75 (9.3%) GFAP-IgG positive patients experienced APS, including 4 females and 3 males. The median age of onset was 42 years (range, 12–71 years). All patients presented with APS as their initial manifestation. Nausea and vomiting were observed in all 7 patients, while hiccups occurred in 5 patients. The median duration of APS episodes was 12 days (range, 6–40 days). None of the patients experienced isolated APS episodes during their illness. AQP4-IgG was positive in 2 patients. 5 patients had dorsal medulla oblongata lesions, while 3 patients showed an “inverted V” sign on axial images. In addition, 5 patients presented with longitudinally extensive linear or patchy lesions in cervical spinal cord extending to area postrema on sagittal images. All APS attacks completely disappeared after immunotherapy. Compared with the APS in AQP4 + NMOSD, APS in A-GFAP-A had a lower proportion of females (33.3% vs. 80%, p = 0.003), more hiccups (81% vs. 50%, p = 0.037), more leptomeningeal enhancement (61.9% vs. 5%, p = 0.000), higher CSF white blood cell count (median 120 vs. 10 cells/mm3, p = 0.000) and protein (median 0.949 vs. 0.407 g/L, p = 0.000). Furthermore, fewer patients with A-GFAP-A received long-term immunotherapy (19% vs. 65%, p = 0.003).

Conclusion

APS often occurs as an initial manifestation of A-GFAP-A. MRI examination and antibody testing should be performed in suspected patients to avoid misdiagnosis.
Research status and trends of functional magnetic resonance imaging technology in the field of acupuncture: a bibliometric analysis over the past two decades
Authors: Wang Zhongke , Chen Lu , Jiang Tianyu , Zhang Qi , Zhao Jinying , Wang Fuchun
Published: January 2025

Objective

Although fMRI has been widely used in the field of acupuncture. However, the literature analysis in this field still has significant differences. This study summarizes the current status of functional magnetic resonance imaging (fMRI) in the field of acupuncture and moxibustion and predicts its future trends through Web of Science bibliometric analysis.

Methods

This study uses “fMRI” and “acupuncture” as keywords to search for literature related to functional magnetic resonance imaging (fMRI) in acupuncture research in the Web of Science Core Collection database from January 1, 2004, to April 30, 2024. Visualization analyses were conducted using Citespace (version 6.3 R1) and VOSviewer (version 1.6.20). Citespace was employed to analyze annual publications, countries, institutions, keywords, and co-cited references. VOSviewer was used to analyze authors and co-cited authors, as well as journals and co-cited journals.

Results

From 2004 to 2024, a total of 967 publications were retrieved, of which 557 were included after screening. Despite annual fluctuations, the overall trend shows an increase. China and the Chinese Academy of Sciences are the countries and institutions with the highest number of publications, with Tian, J being the author with the most publications, and Kong, J having the highest Co-citation frequency. The article by Dhond, RP, published in 2008, has the highest Co-citation frequency among the co-cited literature. Evidence-based Complementary and Alternative Medicine is the journal with the most publications, while Neuroimage is the co-cited journal with the highest citation frequency. Keyword co-occurrence and burst reveal the main research hotspots, including the diversity of intervention methods, cortical activation, mechanisms related to pain-associated diseases, and brain-related diseases. Keyword burst detection reflects emerging trends, including meta-analysis and systematic reviews, the relationship between ischemic stroke and women, and the connection between mild cognitive impairment and prevention.

Conclusion

This study employs bibliometric methods to explore the current status, research hotspots, and frontier issues regarding the application of functional magnetic resonance imaging (fMRI) technology in the field of acupuncture, providing new perspectives and directions for acupuncture fMRI research.
Effects of apple cider vinegar on glycemic control and insulin sensitivity in patients with type 2 diabetes: A GRADE-assessed systematic review and dose–response meta-analysis of controlled clinical trials
Authors: Arjmandfard Donya , Behzadi Mehrdad , Sohrabi Zahra , Mohammadi Sartang Mohsen
Published: January 2025

Background and aims

Diabetes mellitus (DM) is a multifactorial metabolic disorder that affects the body’s ability to regulate blood sugar levels. Apple cider vinegar (ACV) could possibly improve diabetes; nevertheless, evidences provide conflicting results. This study aimed to evaluate the effects of ACV on glycemic profile in type 2 diabetes patients (T2DM) in controlled trials (CTs) by systematically reviewing and dose–response meta-analysis.

Methods

The Scopus, PubMed, and Web of Science databases were searched until November 2024 according to a systematic approach. All CTs investigating ACV’s effects on glycemic factors were included. We used a random-effects model to calculate WMDs and 95% confidence intervals (CIs). The present study assessed publication bias, sensitivity analysis, meta-regression, and heterogeneity based on standard methods. We assessed the bias risk of the included studies using Cochrane quality assessments and used GRADE (Grading of Recommendations Assessment, Development, and Evaluation) to calculate evidence certainty. We registered the study protocol at Prospero (no. CRD42023457493).

Results

Overall, we included seven studies in this meta-analysis. ACV significantly reduced fasting blood sugar (FBS) (WMD: −21.929 mg/dL, 95% CI: −29.19, −14.67, p < 0.001) and HbA1c (WMD: −1.53, 95% CI: −2.65, −0.41, p = 0.008) and increased insulin (WMD: 2.059 μu/ml, 95% CI: 0.26, 3.86, p = 0.025), while it did not affect hemostatic model assessment for insulin resistance (HOMA-IR). We observed linear and non-linear associations between ACV consumption and FBS levels (p < 0.001). Each 1 mL/day increase in ACV consumption was associated with a-1.255 mg/dL reduction in FBS. Moreover, greater effects on FBS were in dosages >10.

Conclusion

ACV had positive effects on FBS and HbA1c in T2DM patients.

Systematic Review Registration

The study protocol was registered at Prospero (no. CRD42023457493).
Bifidobacterium breve BB05 alleviates depressive symptoms in mice via the AKT/mTOR pathway
Authors: Pan Yanni , Huang Qingling , Liang Yuan , Xie Yuwuqi , Tan Fang , Long Xingyao
Published: January 2025

Introduction

This study investigates the potential of Bifidobacterium breve BB05 (BB05) in mitigating depressive symptoms in a mouse model of Chronic Unpredictable Mild Stress (CUMS), with fluoxetine as a positive control.

Methods and Results

High-dose BB05 (1.0 × 109 CFU/kg, BB05H) significantly reduced anxiety- and depression-like behaviors in CUMS mice, as measured by the open field test, tail suspension test, and forced swim test. BB05 treatment also reduced pathological ileal damage, alleviated inflammation, and lowered serum levels of pro-inflammatory cytokines IL-6 and TNF-α. Additionally, BB05 increased serum 5-HT levels and decreased ACTH concentrations. Mechanistic analysis revealed that BB05 exerts antidepressant effects by activating the AKT/mTOR signaling pathway in the prefrontal cortex, promoting neuroprotection, neurogenesis, and synaptic plasticity.

Discussion

These findings suggest that BB05, particularly at higher doses, effectively alleviates CUMS-induced depressive behaviors and improves physiological outcomes, supporting the use of probiotics as a potential treatment for depression by targeting the AKT/mTOR pathway.
Unraveling the pathogenesis of Barrett’s esophagus and esophageal adenocarcinoma: the “omics” era
Authors: Barchi Alberto , Dell’Anna Giuseppe , Massimino Luca , Mandarino Francesco Vito , Vespa Edoardo , Viale Edi , Passaretti Sandro , Annese Vito , Malesci Alberto , Danese Silvio , Ungaro Federica
Published: January 2025

Barrett’s esophagus (BE) represents a pre-cancerous condition that is characterized by the metaplastic conversion of the squamous esophageal epithelium to a columnar intestinal-like phenotype. BE is the consequence of chronic reflux disease and has a potential progression burden to esophageal adenocarcinoma (EAC). The pathogenesis of BE and EAC has been extensively studied but not completely understood, and it is based on two main hypotheses: “transdifferentiation” and “transcommitment”. Omics technologies, thanks to the potentiality of managing huge amounts of genetic and epigenetic data, sequencing the whole genome, have revolutionized the understanding of BE carcinogenesis, paving the way for biomarker development helpful in early diagnosis and risk progression assessment. Genomics and transcriptomics studies, implemented with the most advanced bioinformatics technologies, have brought to light many new risk loci and genomic alterations connected to BE and its progression to EAC, further exploring the complex pathogenesis of the disease. Early mutations of the TP53 gene, together with late aberrations of other oncosuppressor genes (SMAD4 or CKND2A), represent a genetic driving force behind BE. Genomic instability, nonetheless, is the central core of the disease. The implementation of transcriptomic and proteomic analysis, even at the single-cell level, has widened the horizons, complementing the genomic alterations with their transcriptional and translational bond. Increasing interest has been gathered around small circulating genetic traces (circulating-free DNA and micro-RNAs) with a potential role as blood biomarkers. Epigenetic alterations (such as hyper or hypo-methylation) play a meaningful role in esophageal carcinogenesis as well as the study of the tumor micro-environment, which has led to the development of novel immunological therapeutic options. Finally, the esophageal microbiome could be the protagonist to be investigated, deepening our understanding of the subtle association between the host microbiota and tumor development.
Prostate cancer incidence and mortality linked to metalworking fluid exposure: a systematic review and meta-analysis
Authors: Moradpour Zahra , Barik Amin , Jorjani Goljamal , Taherian Mohammad Reza , Tousizadeh Sepideh , Halimi Aram , Soleimani Yaser , Karimian Mobina , Khavari Tina , Kalankari Fateme Azizi , Asadipour Fatemeh , Azari Mojtaba , Shakouri Niloofar Yousefzadeh , Karamian Saeideh , Bahari Nasser , Mosavi Jarrahi Alireza
Published: January 2025

Background

Prostate cancer is the second most diagnosed cancer in men globally, with high prevalence in North America, Europe, and Australia. Occupational exposures, including metalworking fluids (MWFs), have emerged as a potential risk factor for prostate cancer, yet comprehensive studies on this association are limited.

Objective

This study aims to systematically review and conduct a meta-analysis to examine the incidence and mortality of prostate cancer linked to MWF exposure.

Methods

A systematic review and meta-analysis were conducted following the PRISMA guidelines. A comprehensive search strategy was developed to identify relevant studies from PubMed, Scopus, Embase, and Web of Science. Inclusion criteria encompassed studies reporting on the association between MWF exposure and prostate cancer incidence or mortality. Data extraction and risk of bias assessment were performed independently by two reviewers, with discrepancies resolved by a third reviewer. Statistical analyses were conducted using STATA version 17.

Results

The search identified 1376 unique references, with 5 studies meeting the inclusion criteria for the meta-analysis. These studies, conducted in the USA, primarily involved auto workers and reported Standardized Mortality Ratio (SMR), Relative Risk (RR) and 95% Confidence Interval (95%CI) measures. Meta-analysis revealed an overall RR of 1.06 (95% CI: 1.01-1.11) for prostate cancer incidence and an overall SMR of 1.20 (95% CI: 1.09-1.31) for prostate cancer mortality, indicating a statistically significant increased risk and mortality among MWF-exposed workers.

Conclusions

These findings carry significant implications for workplace safety regulations. Given the observed association between MWF exposure and prostate cancer risk, it is imperative to minimize occupational exposure through the implementation of effective engineering controls, personal protective equipment, and substitution of less hazardous fluids. Regular health surveillance and education programs for workers in industries utilizing MWFs are also essential to mitigate risk. Additionally, regulatory agencies should consider revising exposure limits and safety guidelines to account for emerging evidence on the carcinogenic potential of newer MWF formulations.
Triptolide suppresses IL-1β-induced expression of interleukin-8 by inhibiting ROS-Mediated ERK, AP-1, and NF-κB molecules in human gastric cancer AGS cells
Authors: Li Shinan , Sah Dhiraj Kumar , Arjunan Archana , Ameer Mohamed Yazeer , Lee Bora , Jung Young-Do
Published: January 2025

Triptolide, the major component of Chinese herbal medicine Tripterygium wilfordii Hook F, possesses potent anticancer and anti-inflammatory effects. IL-8, a proinflammatory cytokine, is associated with cancer cell proliferation and angiogenesis. Here, we found that Triptolide has an inhibitory effect on IL-1β-induced IL-8 expression in human gastric cancer cells, via the suppression of reactive oxygen species (ROS) production, AP-1, and NF-κB activation, which in turn affects human endothelial cell angiogenetic activity in tumor microenvironments. Human gastric AGS cells were treated with IL-1β (10 ng/mL) and Triptolide (0–20 nM), and the ROS generation, ERK, AP-1, and NF-κB signaling were all investigated. These results demonstrate that Triptolide inhibits the IL-1β-induced IL-8 expression in gastric cancer cells by inhibiting ROS production and angiogenesis, via the dose-dependent attenuation of ERK, AP-1, and NF-κB activation. In this study, we showed that Triptolid inhibits ROS/ERK-mediated AP-1 and ROS-mediated NF-κB axes potentially leading to an improved treatment outcome for gastric cancer and its associated tumor microenvironment.
Enhancing glioblastoma therapy: unveiling synergistic anticancer effects of Onalespib - radiotherapy combination therapy
Authors: Uffenorde Julia , Hariri Mehran , Papalanis Eleftherios , Staffas Annika , Berg Josefine , Stenerlöw Bo , Berglund Hanna , Malmberg Christer , Spiegelberg Diana
Published: January 2025

Background

Glioblastoma (GBM) is the deadliest form of brain cancer, impacting both adults and children, marked by exceptionally high morbidity and mortality rates, even with current standard treatments such as surgery, radiation therapy, and chemotherapy. Therefore, there is a pressing need for new therapeutic strategies to improve survival and reduce treatment side effects. In this study, we investigated the effect of HSP90 inhibition in combination with radiotherapy in established and patient-derived glioblastoma cell lines.

Methods

Potential radiosensitizing effects of the HSP90 inhibitor Onalespib were studied in XTT and clonogenic survival assays as well as in tumor-mimicking multicellular spheroid models. Further, migration capacity and effects on protein expression were studied after exposure to Onalespib and radiation using Proximity Extension Assay analysis.

Results

HSP90 inhibition with Onalespib synergistically enhanced the radiosensitivity of glioblastoma cells grown in 2D and 3D models, resulting in increased cell death, reduced migration capacity and activation of the apoptotic signaling pathway. The proteomic analysis of glioblastoma cells treated with Onalespib, radiation, and their combination revealed significant alterations in protein expression profiles, involved in growth signaling, immune modulation pathways and angiogenesis. Moreover, the combination treatment indicated potential for enhancing cell cycle arrest and apoptosis, suggesting promising anti-tumor effects.

Conclusion

These findings demonstrate that HSP90 inhibition may be a promising strategy to enhance the efficacy of radiotherapy in the treatment of GBM, potentially leading to improved outcomes for patients battling this challenging disease.
Understanding cellular proliferation activity in breast cancer using multi-compartment model of transverse relaxation time mapping on 3T MRI
Authors: Nkonde Kangwa Alex , Cheung Sai Man , Senn Nicholas , He Jiabao
Published: January 2025

Introduction

Precise understanding of proliferative activity in breast cancer holds significant value in the monitoring of neoadjuvant treatment, while current immunostaining of Ki-67 from biopsy or resected tumour suffers from partial sampling error. Multi-compartment model of transverse relaxation time has been proposed to differentiate intra- and extra-cellular space and biochemical environment but susceptible to noise, with recent development of Bayesian algorithm suggested to improve robustness. We hence hypothesise that intra- and extra-cellular transverse relaxation times using Bayesian algorithm might be sensitive to proliferative activity.

Materials and methods

Twenty whole tumour specimens freshly excised from patients with invasive ductal carcinoma were scanned on a 3 T clinical scanner. The overall transverse relaxation time was computed using a single-compartment model with the non-linear least squares algorithm, while intra- and extra-cellular transverse relaxation times were computed using a multi-compartment model with the Bayesian algorithm. Immunostaining of Ki-67 was conducted, yielding 9 and 11 cases with high and low proliferating activities respectively.

Results

For single-compartment model, there was a significant higher overall transverse relaxation time (p = 0.031) in high (83.55 ± 7.38 ms) against low (73.30 ± 11.30 ms) proliferating tumours. For multi-compartment model, there was a significant higher intra-cellular transverse relaxation time (p = 0.047) in high (73.52 ± 10.92 ms) against low (61.30 ± 14.01 ms) proliferating tumours. There was no significant difference in extra-cellular transverse relaxation time (p = 0.203) between high and low proliferating tumours.

Conclusions

Overall and Bayesian intra-cellular transverse relaxation times are associated with proliferative activities in breast tumours, potentially serving as a non-invasive imaging marker for neoadjuvant treatment monitoring.
Diffuse panbronchiolitis as a rare complication of thymectomy and radiation therapy in a patient with thymoma: a case report
Authors: Lu Ye , Qi Qi , Qu Dan , Chen Yu
Published: January 2025

Background

Diffuse panbronchiolitis (DPB) is an uncommon respiratory disorder characterized by the presence of respiratory bronchiolitis and persistent inflammation in adjacent tissues, which can be effectively treated with early diagnosis and intervention. DPB is a rare complication associated with thymoma that remains poorly understood, especially when it occurs in conjunction with acquired cellular immune deficiency.

Case presentation

We present a case of DPB in a patient with thymoma following thymectomy and radiation therapy. A 47-year-old Chinese man underwent thymectomy due to the presence of a mediastinal mass, and pathological examination confirmed a type B2 thymoma. He also underwent 25 sessions of radiation therapy. The patient’s respiratory symptoms, including cough, expectoration, and shortness of breath, worsened significantly after radiation treatment. Immune dysfunction, marked by CD4+ T cell immunodeficiency with normal immunoglobulin levels, was observed. Chest computed tomography revealed diffuse nodules with tree-in-bud signs and new consolidation within the irradiated area, leading to a diagnosis of combined DPB and radiation pneumonitis. The patient’s symptoms and lung imaging findings significantly improved after the initiation of low-dose oral azithromycin for DPB and low-dose glucocorticoid therapy for radiation pneumonitis.

Conclusions

Clinicians should consider DPB in patients with thymoma and cellular immunodeficiency. Both thymectomy and radiation therapy can contribute to the development of DPB. Early treatment with macrolides can improve patient prognosis.
Case report: Complete response of recurrent locally advanced basal cell carcinoma following addition of vismodegib to neoadjuvant cemiplimab therapy
Authors: Lambert-Swainston Chalette , Samlowski Wolfram , Reynolds Brandon , Hedayat Amin
Published: January 2025

Locally advanced basal cell carcinoma (laBCC) remains a significant management challenge. Historically, surgery or radiotherapy represented the major treatment options. Recently, hedgehog inhibitors and checkpoint inhibitors have demonstrated significant activity. The optimal sequencing of these approaches is not yet known. We describe a case of laBCC that recurred after definitive radiotherapy. This patient was treated with neoadjuvant cemiplimab with minimal response. Cautious addition of vismodegib with ongoing cemiplimab treatment was well tolerated and resulted in significant tumor regression. A wide excision demonstrated a pathologic complete response. Further evaluation of cemiplimab and hedgehog inhibitor combination therapy in la BCC appears warranted.
Case report: A case report and literature review on the efficacy of high-dose aumolertinib combined intrathecal pemetrexed by Ommaya reservoir for EGFR-mutated NSCLC with leptomeningeal metastasis as the initial symptoms
Authors: Zhong Maoxi , Zhou Li , Guo Jing , Chen Chuan , Wang Wei , Huang Xiaoping , Liu Yi
Published: January 2025

Leptomeningeal metastasis (LM) is a significant complication of advanced non-small cell lung cancer (NSCLC), occurring in only 3-5% of patients and exceedingly rare in newly diagnosed NSCLC patients. This also indicates that the tumor is highly malignant and aggressive, which brings great challenges to treatment. Here we present a case report of an EGFR-mutated NSCLC patient who presented with LM as the primary clinical manifestation, and review the latest advances in existing studies on LM-related treatment. The patient underwent multiple cycles of high-dose aumolertinib in combination with intrathecal pemetrexed administered via Ommaya reservoir. As of the submission date, the patient achieved significant remission and a LM Progression-Free Survival (PFS) exceeding 20 months. This case highlights the positive impact of high-dose aumolertinib combined with intrathecal pemetrexed on NSCLC patients presenting with severe meningeal symptoms as the initial manifestation, offering a viable therapeutic approach for managing severe meningeal symptoms associated with LM, such as headache, nausea, neck stiffness, and vomiting.
Advances in non-apoptotic regulated cell death: implications for malignant tumor treatment
Authors: Zhang Yizheng , Yi Shiqi , Luan Mingyuan
Published: January 2025

Cell death mechanisms are broadly classified into accidental cell death (ACD) and regulated cell death (RCD). ACD such as necrosis, is an uncontrolled, accidental process, while RCD is tightly regulated by specific signaling pathways and molecular mechanisms. Tumor cells are characterized by their ability to evade cell death and sustain uncontrolled proliferation. The failure of programmed cell death is a key contributor to tumor initiation, progression, and resistance to cancer therapies. Traditionally, research has focused primarily on apoptosis as the dominant form of RCD in cancer. However, emerging evidence highlights the importance of other non-apoptotic forms of RCD, such as pyroptosis, ferroptosis, necroptosis, and parthanatos, in tumorigenesis and treatment response. These pathways are gaining attention for their potential roles in overcoming therapy resistance. In this review, we will discuss the recent advances in the study of non-apoptotic cell death pathways in malignant tumors and explore their therapeutic implications, offering insights into new targets for cancer treatment strategies.