bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tau mediates the reshaping of the transcriptional landscape toward intermediate Alzheimer’s disease stages
Authors: Siano Giacomo , Varisco Martina , Terrigno Marco , Wang Congwei , Scarlatti Arianna , Iannone Vincenzo , Groth Marco , Galas Marie-Christine , Hoozemans Jeroen J. M. , Cellerino Alessandro , Cattaneo Antonino , Di Primio Cristina 
Published: January 2025

IntroductionRecent research revealed that Tau plays critical roles in various neuronal functions. We previously demonstrated that destabilization and nuclear delocalization of Tau alter the expression of glutamatergic genes, mediating early neuronal damage.MethodsIn this study, we discovered that changes in Tau availability are linked to global alterations in gene expression that affect multiple neuronal pathways. Comparison with the human temporal region showed that the Tau-dependent modulation of gene expression closely resembles the intermediate stages of Alzheimer’s disease (AD) that precede the definitive pathological condition.ResultsFurthermore, we identified the chromatin remodeling pathway as being significantly affected by Tau in both our cellular model and AD brains, with reductions in heterochromatin markers. Our findings indicate that Tau is able to globally affect the neuronal transcriptome and that its subcellular unbalance changes gene expression in the intermediate stages of AD development. In addition, we found that the chromatin architecture is affected by Tau during the progression of AD.DiscussionThese results provide new insights into the molecular mechanisms underlying early stages of AD development and highlight the central role of Tau and the contribution of nuclear Tau in this process.
Clinical efficacy of antibiotic-loaded bone cement and negative pressure wound therapy in multidrug-resistant organisms diabetic foot ulcers: a retrospective analysis
Authors: Guo Huihui , Xue Zhenqiang , Mei Siwei , Li Tengfei , Yu Haiyang , Ning Tao , Fu Yongbin 
Published: January 2025

ObjectiveThe purpose of this study was to investigate the clinical efficacy of antibiotic-loaded bone cement (ALBC) combined with Negative pressure wound therapy (NPWT) aspiration technique in the treatment of multidrug-resistant diabetic foot ulcers (MDRO-DFUs).MethodsA retrospective analysis of the clinical data of 80 patients with MDROs-DFU who were used Vacuum sealing drainage (VSD) as NPWT excipient and met the inclusion criteria from January 2019 to January 2024 at our hospital. Patients were divided into an experimental group and a control group, with 40 cases in each. The control group received conventional treatment, routine debridement, and NPWT treatment, while the experimental group received ALBC treatment in addition to the treatment plan of the control group. Measurements of blood inflammatory indicators, foot hemodynamic indicators, wound bacterial clearance time, wound healing time, and hospital stay were taken before and after treatment for both groups.ResultsInflammatory indexes, Vascular endothelial growth factor(VEGF), and internal diameter of dorsalis pedis arteriosus of both groups after treatment were significantly better than those before treatment, and the improvement of the experimental group was more obvious than that of the control group; the experimental group had a significantly shorter time of trauma bacterial turnover, healing time of trauma, and hospitalization time compared with that of the control group (P&lt;0.05).
Validation of an MPS-based intestinal cell culture model for the evaluation of drug-induced toxicity
Authors: Hoffmann Stefanie , Hewitt Philip , Koscielski Isabel , Kurek Dorota , Strijker Wouter , Kosim Kinga 
Published: January 2025

IntroductionThe potential for drug-induced gastrointestinal (GI) toxicity is significant, since the GI tract is one of the first barriers which come in to contact with oral drugs. In pharmaceutical research, the complex behavior of human intestinal cells is traditionally investigated using 2D cultures, in which one cell type grows under static conditions. With the development of advanced microphysiological systems (MPS) more in vivo like conditions can be generated which increase the physiological nature and also the predictive validity of these models. Caco-2 cells are known for their capability to build tight junctions. These connections are responsible for the maintenance of intestinal homeostasis and can be used as a specific safety endpoint, by measuring the Trans Epithelial Electrical Resistance (TEER), for the investigation of drug-induced GI toxicity. Compared to a widely used Caco-2 cell 2D Transwell model, the advanced MPS model (Mimetas OrganoPlate®) allows for the recapitulation of the enterocyte cell layer of the intestinal barrier as the Caco-2 cells grow in a tubular structure through which the medium continuously flows.MethodsThe OrganoPlate® intestinal model was qualified to be implemented as a routine test system for the early prediction of drug-induced GI toxicity based on the measurement of the tightness of the cell layer by measuring changes in the TEER. For this qualification 23 well known compounds as well as a positive, negative and solvent control were selected. The compounds were selected based on their known effect on the GI system (chemotherapeutics, tight junction disruptor, liver toxins, controls, NSAIDs and a mixed group of drugs).ResultsThe TEER values were measured 4 h and 24 h after treatment. In parallel the cell viability was determined after 24 h to be able to distinguish between an unspecific cytotoxic effect or direct tight junction damage. Overall, from the 23 tested compounds, 15 showed the expected outcome, i.e., the compound led to a decrease of the TEER for the positive control compounds, or the TEER value remained stable after treatment with non-GI-toxic compounds.ConclusionIn summary, this MPS model allowed the recapitulation of the human intestinal GI barrier and will enable a faster and more robust assessment of drug-induced damage in the GI tract.
The association between Vitamin D deficiency and clinical pregnancy rate in IVF patients with different age
Authors: Wang Keyan , Dong Fangli , Ma Shuxia , Bu Zhiqin 
Published: January 2025

BackgroundThe aim of the present study was to investigate the impact of serum VD status on IVF outcomes and to observe the effect of VD deficiency on the expression of the endometrial receptivity marker HOXA10.Materials and methodsPatients undergoing their first IVF cycles were divided into 3 groups according to VD levels (deficient: &lt;20 ng/mL, insufficient: 20-29.9 ng/mL), and replete ≥30 ng/mL). IVF laboratory parameters, implantation rate, and clinical pregnancy rate were compared among these groups according to patient age (≥ 35 years old and &lt; 35 years old). In addition, the expression of HOXA10 was analyzed using quantitative RT-PCR (qRT-PCR) and western blot in mRNA and protein levels, respectively.ResultsA total of 1459 patients were included. Clinical pregnancy outcomes were significantly worse in vitamin D-deficient patients of advanced age than in other patients. VD status was a predictor of clinical pregnancy according to the multivariate regression model (Deficient: OR = 0.74, 95% CI: 0.59-0.90, P = 0.022; Insufficient: OR = 0.85, 95% CI: 0.70-1.10, P = 0.104; Reference = Replete). However, clinical pregnancy outcomes were comparable among the three groups of young patients. Endometrial tissue was collected from a total of 35 women. HOXA10 expression was significantly lower only in young women in the vitamin D deficiency group. Furthermore, among patients of advanced age, HOXA10 levels were significantly decreased in both vitamin D-deficient and vitamin D-insufficient women.ConclusionVD deficiency appears to lead to poorer clinical pregnancy outcomes in patients of advanced age. In the future we can observe whether pregnancy outcomes can be improved in such patients with vitamin D supplementation. In addition, a possible explanation for the worse results may be the detrimental effect of reduced HOXA10 expression on endometrial receptivity.
Collagen deposition in lung parenchyma driven by depletion of interstitial Lyve-1+ macrophages prevents cigarette smoke-induced emphysema and loss of airway function
Authors: Dagnachew Yinebeb Mezgebu , Lim Hwee Ying , Wupeng Liao , Lim Sheau Yng , Lim Sheng Jie Natalie , Thiam Chung Hwee , Tan Shu Wen , Eng Joan Lau Joo , Mei Dan , Hazwany Mohammad Azhar Syaza , Ong Wei Siong , Tan Qi Hui Caris , Wong Wai-Shiu Fred , Angeli Veronique 
Published: January 2025

IntroductionCollagen is essential for maintaining lung structure and function and its remodeling has been associated with respiratory diseases including chronic obstructive pulmonary disease (COPD). However, the cellular mechanisms driving collagen remodeling and the functional implications of this process in the pathophysiology of pulmonary diseases remain poorly understood.MethodsTo address this question, we employed Lyve1wt/cre; Csf1rflox/flox mice with specific depletion of Lyve-1+ macrophages and assessed the content, types and organization of collagen in lung compartments at steady state and after chronic exposure to cigarette smoke (CS).ResultsUsing this mouse model, we found that the absence of this subpopulation of tissue resident macrophage led to the deposition of type I collagen fibers around the alveoli and bronchi at steady state. Further analysis by polarized light microscopy and Sircol collagen assay revealed that the collagen fibers accumulating in the lungs depleted of Lyve-1+ macrophages were thicker and crosslinked. A decrease in MMP-9 gene expression and proteolytic activity together with an increase in Col1a1, Timp-3 and Lox expression accompanied the collagen alterations. Next, we investigated the effect of the collagen remodeling on the pathophysiology of COPD and airway function in mice lacking Lyve-1+ macrophages exposed chronically to cigarette smoke (CS), a well-established animal model of COPD. We found that deposition of collagen prior CS exposure protected these mice against destruction of alveoli (emphysema), and bronchi thickening and prevented loss of airway function.DiscussionThus, we uncover that interstitial Lyve-1+ macrophages regulate the composition, amount, and architecture of collagen network in the lungs at steady state and that such collagen remodeling functionally impacts the development of COPD. This study further supports the potential of targeting collagen as promising approaches to treat respiratory diseases.
Identification of MYC and STAT3 for early diagnosis based on the long noncoding RNA-mRNA network and bioinformatics in colorectal cancer
Authors: Yao Kunhou , Fan Hao , Yang Tiancheng , Yang Can , Wang Guibin , Li Xingwang , Ji Xin-Ying , Wang Qun , Lv Shaojiang , Guo Shihao 
Published: January 2025

BackgroundColorectal cancer (CRC) ranks among the top three cancers globally in both incidence and mortality, posing a significant public health challenge. Most CRC cases are diagnosed at intermediate to advanced stages, and reliable biomarkers for early detection are lacking. Long non-coding RNAs (lncRNAs) have been implicated in various cancers, including CRC, playing key roles in tumor development, progression, and prognosis.MethodsA comprehensive search of the PubMed database was conducted to identify relevant studies on the early diagnosis of CRC. Bioinformatics analysis was performed to explore lncRNA-mRNA networks, leading to the identification of five potential blood biomarkers. Expression analysis was carried out using the GEPIA and GEO online databases, focusing on MYC and STAT3. Differential expression between normal and CRC tissues was assessed, followed by Receiver Operating Characteristic (ROC) analysis to evaluate the diagnostic potential of these markers. Quantitative Real-Time PCR (qRT-PCR) was performed to validate MYC and STAT3 expression levels, and findings were further confirmed using the Human Protein Atlas (HPA) database.ResultsDatabase analysis revealed significant differential expression of MYC and STAT3 between normal and CRC tissues. ROC analysis demonstrated the diagnostic potential of these markers. qRT-PCR validation confirmed the differential expression patterns observed in the databases. Validation through the HPA database further supported these findings, confirming the potential of MYC and STAT3 as diagnostic biomarkers for CRC.ConclusionOur results suggest that MYC and STAT3 are promising diagnostic biomarkers for CRC, offering new insights into its pathophysiology and potential for targeted therapies.
Whole blood ratio of CDK1/CX3CR1 mRNA expression combined to lactate refines the prediction of ICU mortality in septic patients in the Sepsis-3 era: a proof-of-concept study
Authors: Cazalis Marie-Angélique , Kreitmann Louis , Monneret Guillaume , Pachot Alexandre , Brengel-Pesce Karen , Llitjos Jean-François 
Published: January 2025

BackgroundTranscriptomics biomarkers have been widely used to predict mortality in patients with sepsis. However, the association between mRNA levels and outcomes shows substantial variability over the course of sepsis, limiting their predictive performance. We aimed to: (a) identify and validate an mRNA biomarker signature whose association with all-cause intensive care unit (ICU) mortality is consistent at several timepoints; and (b) evaluate how this mRNA signature could be used in association with lactate levels for predictive and prognostic enrichment in sepsis.MethodsWe conducted a gene expression analysis study at two timepoints (day 1 and day 2–3 following ICU admission) using microarray data from adult septic patients to identify candidate biomarkers predictive of all-cause ICU mortality. We validated mRNA biomarkers using reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) on an external validation cohort. The predictive performance of the mRNA biomarkers combination was assessed in association with lactate level to refine ICU mortality prediction.Main resultsAmong 180 chips from 100 septic patients, we identified 39 upregulated and 2 downregulated differentially expressed genes (DEGs) in survivors vs. non-survivors, both at day 1 and days 2–3 following ICU admission. We combined CDK1, the hub gene of upregulated DEGs, and CX3CR1 and IL1b to compute expression ratios. The CDK1/CX3CR1 ratio had the best performance to predict all-cause ICU mortality, with an area under the ROC curve (AUROC) of 0.77 (95% confidence interval [CI] 0.88–0.66) at day 1 and of 0.82 (95% CI 0.91–0.72) at days 2–3 after ICU admission. This performance was better than that of each individual mRNA biomarker. In the external validation cohort, the predictive performance of the CDK1/CX3CR1 ratio, measured using RT-qPCR, was similar to that of lactate when measure at day 1, and higher when measured at days 2–3. Combining lactate levels and the CDK1/CX3CR1 ratio, we identify 3 groups of patients with an increasing risk of ICU-mortality, ranging from 9 to 60% with an intermediate-risk group mortality rate of 28%.ConclusionWith stable predictive performance over the first 3 days following ICU admission, the CDK1/CX3CR1 ratio identifies three groups of septic patients with increasing ICU mortality risk. In combination with lactate, this novel biomarker strategy may be useful for sepsis patient stratification for personalized medicine trials and ICU management.
Marital status and risk of type 2 diabetes among middle-aged and elderly population: a systematic review and meta-analysis
Authors: Karimi Mohammad Amin , Binaei Sara , Hashemi Seyed Hadi , Refahi Pegah , Olama Ensiyeh , Olama Elnaz , Mohammadpour Aydin , Yonjali Reza Mostafaei , Poudineh Mohadeseh , Deravi Niloofar 
Published: January 2025

BackgroundMarital status is among the factors influencing type 2 diabetes mellitus (T2DM). However, the precise relationship remains incompletely understood. This meta-analysis aims to evaluate the association between marital status and the incidence of T2DM.MethodsA review and meta-analysis of observational studies were conducted to investigate the relationship between marital status and diabetes incidence. We searched three databases, including PubMed, Google Scholar, and Scopus, for relevant studies published up to August 16th, 2023. In our initial search, we identified a total of 358 articles. After a demanding screening process involving evaluating titles, abstracts, and full-text content, we ultimately included six studies for our meta-analysis.ResultComprising a total of 1,440,904 participants, our study found that in comparison to married individuals, unmarried participants exhibited a higher likelihood of developing diabetes [odds ratio (OR): 1.47, 95% confidence interval (CI): 0.88–2.45, I2: 91%, p-value = 0.14]. Divorced participants had a reduced likelihood of developing diabetes compared to married participants (OR: 0.84, 95% CI: 0.77–0.91, I2: 17%, p &lt; 0.001). Similarly, widowed participants showed a lower risk of developing diabetes compared to divorced participants (OR: 0.35, 95% CI: 0.26–0.46, I2: 83%, p &lt; 0.00001).ConclusionThis study provides strong evidence of links between marital status and type 2 diabetes risk. Unmarried individuals are more susceptible to T2DM, divorced individuals have a lower risk, and widowed individuals exhibit reduced T2DM risk. Further research should investigate underlying mechanisms and confounding factors.
Antiphospholipid antibodies positivity as a potential risk factor for restenosis following arteriovenous fistula stenting in hemodialysis patients: a pilot study
Authors: Taghavi Maxime , Lengelé Adrien , Laureys Marc , Jacobs Lucas , Kaysi Saleh , Collart Frédéric , Demulder Anne , Nortier Joëlle 
Published: January 2025

BackgroundThe arteriovenous fistula (AVF) is the preferred vascular access for hemodialysis. AVF stenosis is a common complication, often requiring balloon angioplasty. For recurrent stenosis, AVF stenting may be an option. Persistent antiphospholipid antibody (aPL) positivity is frequently observed in hemodialysis (HD) patients and is associated with AVF thrombosis and stenosis. This study aimed to evaluate AVF stent survival without stenosis in aPL-positive hemodialysis patients.MethodsA monocentric retrospective observational study was conducted on 35 patients who underwent AVF stenting between 1st January 2014 and 31st December 2023. The patients were divided into two groups: the aPL+ group [defined by a score of 3 or more based on the laboratory criteria of the 2023 ACR/EULAR for antiphospholipid syndrome (APS)] and the control group. Intrastent restenosis was defined as a chronic change in the AVFphysical examination or blood flow, confirmed by ultrasound (US) or angiography. Kaplan–Meier survival analysis was used to estimate the probability of stent survival without restenosis.ResultsThe prevalence of intrastent restenosis was significantly higher in the aPL+ group at 24 months. The Kaplan–Meier survival analysis showed a significantly lower probability of AVF stent survival without restenosis in the aPL+ group (age-adjusted Hazard Ratio, 2.13 [IC95%, 1.70–2.69]).ConclusionTo the best of our knowledge, we describe for the first time a statistically significant association between aPL+ and AVF intrastent restenosis. Intimal hyperplasia is a non-thrombotic lesion associated with aPL+ and is linked to the mammalian target of rapamycin (mTOR) signaling pathway. We hypothesize that aPL may contribute to intrastent restenosis by inducing intimal hyperplasia. Whether this phenomenon is mTOR-mediated and whether sirolimus-eluting stents or balloons could be a better option for aPL+ patients requires further study.
Traditional pediatric massage enhanced the skeletal muscle mass in OVA-exposed adolescent rats via regulating SCFAs-FFAR2-IGF-1/AKT pathway
Authors: Lin Lin , Li Siyuan , Liu Que , Zhang Xingxing , Xiong Ying , Zhao Shaoyun , Cao Liyue , Gong Jiaxuan , Liu Yaping , Wu Rong 
Published: January 2025

ObjectiveThis study aimed to investigate the potential relation between the retarded growth of skeletal muscle (SM) and dysbiosis of gut microbiota (GM) in children with asthma, and to explore the potential action mechanisms of traditional pediatric massage (TPM) from the perspective of regulating GM and short-chain fatty acids (SCFAs) production by using an adolescent rat model of asthma.MethodsMale Sprague-Dawley rats aged 3weeks were divided randomly into the 5 groups (n=6~7) of control, ovalbumin (OVA), OVA + TPM, OVA + methylprednisolone sodium succinate (MP) and OVA + SCFAs. Pulmonary function (PF) was detected by whole body plethysmograph, including enhanced pause and minute ventilation. Airway allergic inflammation (AAI) status was assessed by concentrations of OVA-specific immunoglobulin E in plasma, interleukin (IL)-4 and IL-1β in bronchoalveolar lavage fluid via ELISA assay. SM mass was assessed by using cross-sectional areas of diaphragm muscle and gastrocnemius via hematoxylin and eosin staining. GM and SCFAs production were detected by 16S rDNA sequencing and GC-MS, respectively. The protein and gene expressions of free fatty acid receptor 2 in SM were detected by using immunohistochemical staining and qRT-PCR, respectively. qRT-PCR was used to detect other relative gene expressions that were closely related with SM mass. The activity of insulin-like growth factor-1 (IGF-1)/protein kinase B (PKB/AKT) pathway in SM was detected by western blotting test.ResultsOVA exposure caused obvious AAI and poor PF in adolescent rats. OVA-exposed adolescent rats had a retarded growth of SM mass and inhibited activity of IGF-1/AKT pathway, which was related with GM dysbiosis, reduced SCFAs production and FFAR2 expressions in SM. TPM efficiently enhanced the SM mass, along with alleviating AAI and improving PF. TPM activated IGF-1/AKT pathway in SM, which was closely related with correcting GM dysbiosis, enhanced SCFAs production and FFAR2 expressions.ConclusionThe retarded growth of SM mass and inhibition of IGF-1/AKT pathway existed in OVA-exposed adolescent rats, which was related with GM dysbiosis, reduced SCFAs production and FFAR2 expressions in SM. TPM efficiently enhanced the SM mass, at least, partially via regulating GM, enhancing SCFAs production and activating FFAR2-IGF-1/AKT pathway.