bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of novel biomarkers, shared molecular signatures and immune cell infiltration in heart and kidney failure by transcriptomics
Authors: Long Qingqing , Zhang Xinlong , Ren Fangyuan , Wu Xinyu , Wang Ze-Mu 
Published: September 2024

IntroductionHeart failure (HF) and kidney failure (KF) are closely related conditions that often coexist, posing a complex clinical challenge. Understanding the shared mechanisms between these two conditions is crucial for developing effective therapies.MethodsThis study employed transcriptomic analysis to unveil molecular signatures and novel biomarkers for both HF and KF. A total of 2869 shared differentially expressed genes (DEGs) were identified in patients with HF and KF compared to healthy controls. Functional enrichment analysis was performed to explore the common mechanisms underlying these conditions. A protein-protein interaction (PPI) network was constructed, and machine learning algorithms, including Random Forest (RF), Support Vector Machine-Recursive Feature Elimination (SVM-RFE), and Least Absolute Shrinkage and Selection Operator (LASSO), were used to identify key signature genes. These genes were further analyzed using Gene Set Variation Analysis (GSVA) and Gene Set Enrichment Analysis (GSEA), with their diagnostic values validated in both training and validation sets. Molecular docking studies were conducted. Additionally, immune cell infiltration and correlation analyses were performed to assess the relationship between immune responses and the identified biomarkers.ResultsThe functional enrichment analysis indicated that the common mechanisms are associated with cellular homeostasis, cell communication, cellular replication, inflammation, and extracellular matrix (ECM) production, with the PI3K-Akt signaling pathway being notably enriched. The PPI network revealed two key protein clusters related to the cell cycle and inflammation. CDK2 and CCND1 were identified as signature genes for both HF and KF. Their diagnostic value was validated in both training and validation sets. Additionally, docking studies with CDK2 and CCND1 were performed to evaluate potential drug candidates. Immune cell infiltration and correlation analyses highlighted the immune microenvironment, and that CDK2 and CCND1 are associated with immune responses in HF and KF.DiscussionThis study identifies CDK2 and CCND1 as novel biomarkers linking cell cycle regulation and inflammation in heart and kidney failure. These findings offer new insights into the molecular mechanisms of HF and KF and present potential targets for diagnosis and therapy.
Efficacy and safety of chemoradiotherapy plus immune checkpoint inhibitors for the treatment of locally advanced cervical cancer: a systematic review and meta-analysis
Authors: Zhao Zhihong , Ruan Jian , Fang Minjie , Liu Jingwen , Liao Guixiang 
Published: September 2024

BackgroundRadiotherapy plus concurrent chemotherapy is a standard method for treating locally advanced cervical cancer (LACC). Immune checkpoint inhibitors (ICIs) are widely applied in the treatment of recurrent cervical cancer, metastatic cervical cancer or LACC. The efficacy and safety of radiotherapy plus immunotherapy for LACC require further investigation. The objective of this review and meta-analysis was to analyze the efficacy and safety of concurrent chemoradiotherapy (CCRT) combined with ICIs for treating LACC on the basis of the results of randomized controlled trials (RCTs).MethodsWe comprehensively searched electronic databases to identify RCTs that focused on CCRT plus ICIs for LACC treatment. The outcomes included the objective response rate (ORR) and progression-free survival (PFS), overall survival (OS) and adverse events (AEs). A standard method for systematic review and meta-analysis was used. Review Manager 5.4 was used for data combination and analyses.ResultsThree RCTs involving 1882 participants with LACC were identified and included in the systematic review and meta-analysis. CCRT plus ICIs improved the rates of PFS (hazard ratio [HR]: 0.76, 95% confidence interval [CI]: CI: 0.64, 0.91, P = 0.002) and OS (HR: 0.7695% CI (95% CI 0.58–0.99, P = 0.04) in patients with LACC. Compared with the control group, the CCRT plus immunotherapy group had an increased ORR (OR: 1.37, 95% CI: 1.02,1.85, P=0.04). The two methods had similar rates (HR=1.99, 95% CI: 0.99, 1.43; P=0.07) of treatment-related grade 3 or higher AEs. The CCRT plus immunotherapy group had a higher rate than did the control group (HR: 2.68, 95% CI: 1.38, 5.21; P=0.004) in terms of any grade immunotherapy-related AEs.ConclusionsCCRT plus ICIs is efficacious and safe for the management of LACC. The addition of ICIs to CCRT improved the rates of PFS and OS in patients with LACC. The adverse effects of immunotherapy-related AEs should be strictly examined and managed in a timely manner.
Urolithin A alleviates cell senescence by inhibiting ferroptosis and enhances corneal epithelial wound healing
Authors: Guo Xiao-Xiao , Chang Xue-Jiao , Pu Qi , Li Ao-Ling , Li Jing , Li Xin-Yu 
Published: September 2024

PurposeTo analyze the therapeutic effect and mechanism of Urolithin A (UA) on delayed corneal epithelial wound healing.MethodsThe C57BL/6 mice were continuously exposed to hyperosmotic stress (HS) for 7 days followed by the removal of central corneal epithelium to establish a delayed corneal epithelial wound healing model in vivo. In vitro, the human corneal epithelial cell line (HCE-T) was also incubated under HS. UA was administered in vivo and in vitro to study its effects on corneal epithelial cells. Senescence-associated β-galactosidase (SA-β-gal) staining was performed to detect the level of cell senescence. Transcriptome sequencing (RNA-seq) was conducted to elucidate the molecular mechanism underlying the effect of UA on corneal epithelial repair. Additionally, the expression of senescence-related and ferroptosis-related genes and the levels of lipid peroxides (LPO) and malondialdehyde (MDA) were measured.ResultsHyperosmotic stress (HS) significantly increased the proportion of SA-β-gal staining positive cells in corneal epithelial cells and upregulated the expression of p16 and p21 (p &lt; 0.0001). Topical application of UA decreased the accumulation of senescent cells in corneal epithelial wounds and promoted epithelial wound healing. The results of RNA-seq of HS-induced corneal epithelial cells showed that the ferroptosis pathway was significantly dysregulated. Further investigation revealed that UA decreased the level of oxidative stress in HCE-T cells, including the levels of LPO and MDA (p &lt; 0.05). Inhibition of ferroptosis significantly prevented cellular senescence in HS-induced HCE-T cells.ConclusionIn this study, UA promoted HS-induced delayed epithelial wound healing by reducing the senescence of corneal epithelial cells through the inhibition of ferroptosis.
Analysis of soft rot Pectobacteriaceae population diversity in US potato growing regions between 2015 and 2022
Authors: Ma Xing , Zhang Xiuyan , Stodghill Paul , Rioux Renee , Shrestha Smita , Babler Brooke , Rivedal Hannah , Frost Kenneth , Hao Jianjun , Secor Gary , Swingle Bryan 
Published: September 2024

IntroductionSoft rot Pectobacteriaceae (SRP) bacteria are globally dispersed pathogens that cause significant economic loss in potato and other crops. Our understanding of the SRP species diversity has expanded in recent years due to advances and adoption of whole-genome sequence technologies. There are currently 34 recognized SRP species that belong to the Dickeya and Pectobacterium genera.MethodsWe used whole-genome sequencing based analysis to describe the current distribution and epidemiology of SRP isolated from diseased potato samples obtained from commercial potato cropping systems in the United States. Our primary objectives in the present study were to: (1) identify the species of these SRP isolates recovered from potato samples across 14 states in the US, (2) describe the variation among SRP isolates from various US locations and track their temporal changes, and (3) evaluate the evolutionary relationships among these SRP isolates to deduce their source. We collected 118 SRP strains from diseased potato plants and tubers in 14 states between 2015 and 2022.ResultsWe identified three Dickeya and eight Pectobacterium species from diseased potato samples. Dickeya dianthicola, Pectobacterium parmentieri, P. carotovorum, and P. versatile appeared to be the predominant species, constituting 83% of the isolates. Furthermore, all D. dianthicola strains studied here as well as 90% of US D. dianthicola isolates sequenced to date exhibit significant clonality.DiscussionThe prevalence of this specific group of D. dianthicola, temporally and geographically, aligns with the occurrence of blackleg and soft rot outbreaks in the northeastern US after 2014. The genomic diversity observed in P. parmentieri implies multiple introductions to the US from at least four distinct sources, earlier than the arrival of the predominant group of D. dianthicola. In contrast, P. carotovorum and P. versatile appear to be widespread, long-term endemic strains in the US.
Subthreshold amyloid deposition, cerebral small vessel disease, and functional brain network disruption in delayed cognitive decline after stroke
Authors: Lim Jae-Sung , Lee Jae-Joong , Kim Geon Ha , Kim Hang-Rai , Shin Dong Woo , Lee Keon-Joo , Baek Min Jae , Ko Eunvin , Kim Beom Joon , Kim SangYun , Ryu Wi-Sun , Chung Jinyong , Kim Dong-Eog , Gorelick Philip B. , Woo Choong-Wan , Bae Hee-Joon 
Published: September 2024

BackgroundAlthough its incidence is relatively low, delayed-onset post-stroke cognitive decline (PSCD) may offer valuable insights into the “vascular contributions to cognitive impairment and dementia,” particularly concerning the roles of vascular and neurodegenerative mechanisms. We postulated that the functional segregation observed during post-stroke compensation could be disrupted by underlying amyloid pathology or cerebral small vessel disease (cSVD), leading to delayed-onset PSCD.MethodsUsing a prospective stroke registry, we identified patients who displayed normal cognitive function at baseline evaluation within a year post-stroke and received at least one subsequent assessment. Patients suspected of pre-stroke cognitive decline were excluded. Decliners [defined by a decrease of ≥3 Mini-Mental State Examination (MMSE) points annually or an absolute drop of ≥5 points between evaluations, confirmed with detailed neuropsychological tests] were compared with age- and stroke severity-matched non-decliners. Index-stroke MRI, resting-state functional MRI, and 18F-florbetaben PET were used to identify cSVD, functional network attributes, and amyloid deposits, respectively. PET data from age-, sex-, education-, and apolipoprotein E-matched stroke-free controls within a community-dwelling cohort were used to benchmark amyloid deposition.ResultsAmong 208 eligible patients, 11 decliners and 10 matched non-decliners were identified over an average follow-up of 5.7 years. No significant differences in cSVD markers were noted between the groups, except for white matter hyperintensities (WMHs), which were strongly linked with MMSE scores among decliners (rho = −0.85, p &lt; 0.01). Only one decliner was amyloid-positive, yet subthreshold PET standardized uptake value ratios (SUVR) in amyloid-negative decliners inversely correlated with final MMSE scores (rho = −0.67, p = 0.04). Decliners exhibited disrupted modular structures and more intermingled canonical networks compared to non-decliners. Notably, the somato-motor network’s system segregation corresponded with the decliners’ final MMSE (rho = 0.67, p = 0.03) and was associated with WMH volume and amyloid SUVR.ConclusionDisruptions in modular structures, system segregation, and inter-network communication in the brain may be the pathophysiological underpinnings of delayed-onset PSCD. WMHs and subthreshold amyloid deposition could contribute to these disruptions in functional brain networks. Given the limited number of patients and potential residual confounding, our results should be considered hypothesis-generating and need replication in larger cohorts in the future.
Mapping the research of mitochondria and Parkinson’s disease: a bibliometric analysis
Authors: Chen Yan-Jun , Xie Ming-Rong , Zhou Sheng-Qiang , Liu Fang 
Published: September 2024

BackgroundParkinson’s disease (PD) is a chronic, progressive neurodegenerative disorder primarily affecting the elderly. Relevant studies suggest a significant connection between the mitochondria and PD. Publications exploring this connection have steadily increased in recent years. This study employs a bibliometric approach to comprehensively analyze the current status and future directions of the research on mitochondria and PD.MethodWe retrieved data from the Web of Science database and used CiteSpace, VOSviewer, and “Bibliometrix” software to visually analyze various aspects of the research field. These aspects included the number of published papers, contributing countries and institutions, authors, publishing journals, cited references, and keywords.ResultsOur analysis identified a total of 3,291 publications involving 14,670 authors from 2,836 organizations across 78 countries. The publication volume exhibited a continuous upward trend from 1999 to 2023. The United States emerged as the leading force in this research area, contributing the highest number of high-quality publications. Notably, the United States collaborated extensively with Germany and the United Kingdom. The University of Pittsburgh stood out as the most prolific institution. Harvard University had the highest academic influence and closely cooperated with the University of Pittsburgh, Juntendo University, and McGill University. Dr. Hattori Nobutaka was identified as the most prolific author, while Dr. Youle, Richard J emerged as the most influential author based on the highest average citation frequency. The Journal of Neurochemistry was the most published journal. The most co-cited paper was titled “Hereditary early-onset Parkinson’s disease caused by mutations in PINK1.” The major keywords included oxidative stress, alpha-synuclein, pink1, mitophagy, and mitochondrial dysfunction. Mitofusin 2, ubiquitin, and mitochondrial quality control have been identified as new research hotspots in recent years.ConclusionMitochondria-PD research is experiencing a steady increase in activity, fueled by increasing close collaboration between countries and different institutions. However, there is a need to further strengthen collaboration and communication between developed and developing nations. Current research has focused on the specific mechanisms of mitochondrial dysfunction and their relationship with PD. Mitofusin 2, ubiquitin, and mitochondrial quality control are positioned to be the hotspots and future research directions.
Cognitive function in dyslipidemia patients: exploring the impact of statins
Authors: Wang Wenxiao , Li Xin 
Published: September 2024

BackgroundEvidence regarding the relationship between the use of statins and cognitive outcomes presents varying findings. This study aims to analyze the relationship between sustained statin use and cognitive performance in dyslipidemia patients.MethodsThis study presents findings from the Beijing Ageing Brain Rejuvenation Initiative (BABRI) study, in which a cohort of community-dwelling dyslipidemia patients (Entire sample, N = 1,062, aged 50–86) was recruited. Participants were divided into two groups based on their sustained use statins (Statins group, N = 677) or not use any lipid-lowering agents (Untreated group, N = 385). Furthermore, the entire sample was stratified by age into the middle-aged sample (N = 451) and the older people sample (N = 611), following a similar categorization based on statin application. ANCOVA was used to evaluate the relationship between sustained statin use and cognitive function.ResultsOverall, in the total sample, the statins group demonstrated better cognition in overall cognition, memory, visuospatial ability, attention, executive function, and language domains compared to the untreated group. Moreover, the statins group only showed better performance in attention among the middle-aged sample. In the older people sample, statins group exhibited superior cognitive performance across various cognitive domains compared to untreated group.ConclusionAmong dyslipidemia patients in Beijing community, sustained statin users exhibited superior cognitive function across all domains compared to untreated individuals, with particularly noticeable improvements among those aged 65 and above. These findings underscore the protective effect of statins on cognitive function in dyslipidemia patients, highlighting significant benefits for the older people population.
Clinical significance of the modified Naples prognostic score in patients with stage II-III colon cancer undergoing curative resection: a retrospective study from the real world
Authors: Li Xiaopeng , Cheng Chen , Huo Xiongwei , Zhao Chenye , Yuan Hang , Chen Gang , Yu Junhui , Mu Mingchao , Sun Xuejun 
Published: September 2024

BackgroundThe Naples prognostic score (NPS) determined by the nutritional and inflammatory condition of an individual is attracting growing attention for predicting postoperative outcomes in a variety of malignancies. The study aimed to assess the clinical significance of a modified NPS (M-NPS) and establish and validate nomograms incorporating M-NPS in curative stage II-III colon cancer patients.MethodsWe retrospectively analyzed 328 stage II-III colon cancer patients receiving radical surgical resection at our hospital from January 2011 to December 2016. Kaplan–Meier (KM) survival analysis and Cox regression analysis were executed for overall survival (OS) and cancer-specific survival (CSS). Independent predictive indicators were applied to develop nomograms. The model’s performance was evaluated using many different methods.ResultsOf a total of 328 cases, 153 cases were in group 0, 145 in group 1, and 30 in group 2. In terms of OS or CSS, there were obvious differences between groups 0 and 1, and between groups 0 and 2. Age, obstruction, N stage, gross tumor type, and M-NPS group were independent prognostic indicators for OS, while obstruction, gross tumor type, M-NPS group, and N stage were independent predictive parameters for CSS. Furthermore, the training and validation sets were randomly allocated among a cohort of 328 patients. OS and CSS prediction nomograms were developed. In the training and validation cohort, the C-index and ROC analysis showed good discrimination, calibration curves exhibited an excellent level of consistency between model-predicted survival and actual survival outcomes, and DCA curves demonstrated good clinical performance.ConclusionM-NPS is a reliable survival predictor in patients with curative stage II-III colon cancer. Nomograms incorporating M-NPS for OS and CSS have good predictive performance and clinical utility.
Correlating dermatoscopic features with immunohistochemical markers in basal cell carcinoma: a comprehensive analysis of 100 cases in Caucasian population
Authors: Calik Jacek , Sauer Natalia , Giedziun Piotr , Piotrowska Aleksandra , Tumiłowicz Maciej , Wojnar Andrzej , Dzięgiel Piotr 
Published: September 2024

BackgroundBasal Cell Carcinoma (BCC) is the most common form of skin cancer, characterized by its low metastatic potential yet considerable diversity in clinical and dermatoscopic presentation. Advances in dermatoscopy have significantly improved the early detection of BCC, revealing specific patterns that guide diagnosis and management. Parallelly, immunohistochemical markers have been explored for their potential to elucidate the underlying tumor biology and prognosis, with particular focus on angiogenesis, melanocytic activity, and lymphangiogenesis.ObjectiveThis study aims to investigate the correlations between dermatoscopic features and the immunohistochemical expressions of CD34, CD31, Melan-A, and D2-40 in BCC, through a comprehensive analysis of 100 cases We sought to determine whether visual dermatoscopic patterns correlate with the molecular characteristics defined by immunohistochemical staining, potentially enhancing diagnostic accuracy.MethodsA total of 100 cases of clinically and histopathologically confirmed BCC were prospectively analyzed, employing standard dermatoscopic techniques for lesion evaluation and immunohistochemical staining for CD34, CD31, Melan-A, and D2-40 to assess tumor angiogenic potential, melanocytic activity, and lymphangiogenesis. The study was conducted with adherence to ethical standards and informed consent from all participants.ResultsDermatoscopic examination revealed a variety of vascular patterns and pigmented features across different BCC anatomical locations. However, the comprehensive correlation analysis predominantly found a lack of significant associations between dermatoscopic appearances and expressions of the targeted immunohistochemical markers, with the notable exception of a correlation between observed hemorrhage and the Melan-A marker.ConclusionsThe lack of significant correlations between dermatoscopic features and immunohistochemical marker expressions in BCC suggests that the biological behavior and angiogenic, melanocytic, and lymphangiogenic activities within BCC lesions may be influenced by factors beyond those assessed in this study. Despite the exploratory nature of these findings, they underscore the complexity of BCC biology and highlight the need for further research incorporating additional markers and advanced imaging techniques.
Novel multitarget analgesic candidate SZV-1287 demonstrates potential disease-modifying effects in the monoiodoacetate-induced osteoarthritis mouse model
Authors: Horváth Ádám István , Bölcskei Kata , Szentes Nikolett , Borbély Éva , Tékus Valéria , Botz Bálint , Rusznák Kitti , Futácsi Anett , Czéh Boldizsár , Mátyus Péter , Helyes Zsuzsanna 
Published: September 2024

IntroductionMonoiodoacetate (MIA)-induced osteoarthritis (OA) is the most commonly used rodent model for testing anti-OA drug candidates. Herein, we investigated the effects of our patented multitarget drug candidate SZV-1287 (3-(4,5-diphenyl-1,3-oxazol-2-yl) propanal oxime) that is currently under clinical development for neuropathic pain and characterized the mouse model through complex functional, in vivo imaging, and morphological techniques.MethodsKnee OA was induced by intraarticular MIA injection (0.5 and 0.8 mg). Spontaneous pain was assessed based on weight distribution, referred pain by paw mechanonociception (esthesiometry), edema by caliper, neutrophil myeloperoxidase activity by luminescence, matrix metalloproteinase activity, vascular leakage and bone remodeling by fluorescence imaging, bone morphology by micro-CT, histopathological alterations by semiquantitative scoring, and glia activation by immunohistochemistry. Then, SZV-1287 (20 mg/kg/day) or its vehicle was injected intraperitoneally over a 21-day period.ResultsMIA induced remarkably decreased thresholds of weight bearing and paw withdrawal, alterations in the tibial and femoral structures (reactive sclerosis, increased trabeculation, and cortical erosions), histopathological damage (disorganized cartilage structure, hypocellularity, decreased matrix staining and tidemark integrity, and increased synovial hyperplasia and osteophyte formation), and changes in the astrocyte and microglia density in the lumbar spinal cord. There were no major differences between the two MIA doses in most outcome measures. SZV-1287 inhibited MIA-induced weight bearing reduction, hyperalgesia, edema, myeloperoxidase activity, histopathological damage, and astrocyte and microglia density.ConclusionSZV-1287 may have disease-modifying potential through analgesic, anti-inflammatory, and chondroprotective effects. The MIA mouse model is valuable for investigating OA-related mechanisms and testing compounds in mice at an optimal dose of 0.5 mg.