bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interplay between reactive oxygen species and ERK activation in cervical cancer cells
Authors: Larrauri-Rodríguez Karen Andrea , Leon-Chavez Bertha Alicia , Vallejo-Ruiz Verónica , Peña Lourdes Millán-Perez , Maycotte Paola 
Published: November 2024

IntroductionAmong the types of cancer affecting women, cervical cancer (CC) is a public health problem with high global incidence and mortality rates. It is currently classified into three main histological types: squamous cell carcinoma (SCC), adenocarcinoma (AC), and adenosquamous (ASC) carcinoma. All of them lack a targeted therapy. The primary risk factor for CC is Human Papilloma Virus (HPV) infection, which is known to increase reactive oxygen species (ROS), contributing to malignant transformation and tumor progression. At basal levels, ROS can function as second messengers in signaling pathways, and elevated concentrations have been linked to their overactivation. One of these, the ERK pathway, is implicated in both cell proliferation and differentiation and is often dysregulated in cancer, promoting malignant transformation. Several studies have proposed antioxidant supplementation or ERK inhibitors as potential therapies.MethodsIn vitro studies were performed using CC cell lines. ROS levels were evaluated by flow cytometry; cellular proliferation, death and migration were evaluated using real-time microscopy; cell viability was evaluated with crystal violet staining, and phosphorylated ERK levels were evaluated by Western Blot. A bioinformatic analysis was done in a cervical cancer database.ResultsWe elucidate part of the complex interplay between ROS and ERK pathway in CC pro-tumorigenic characteristics. Through bioinformatic analysis, we found distinct ROS and ERK activation patterns across CC tumor samples from different histological types. However, in vitro, ROS regulated migration and viability in CC, with no discernible variance based on histological classification. ERK activation, however, differed according to the histological type with SCC displaying increased ERK activation compared to AC and regulating cellular migration in SCC cells.DiscussionOur study identifies a potential synergistic interaction between ROS and ERK inhibitors, highlighting the therapeutic promise of combinatorial targeting for CC treatment. These findings underscore the importance of personalized approaches aimed at improving the outcomes of CC patients.
The correlation between severe asymptomatic carotid artery stenosis and severe multi-organ dysfunction after off-pump coronary artery bypass grafting
Authors: Wang Tong , Zhao Chang , Cao Jian , Zhang Kui , Wang Rui , Xiao Yu , Dong Ran , Wang Jiayang 
Published: November 2024

BackgroundThe current research aimed to demonstrate the independent association between preoperative severe asymptomatic carotid artery stenosis (ACAS) and severe multi-organ dysfunction after off-pump coronary artery bypass grafting (OPCAB), which may further indicate the relationship between severe ACAS and adverse 30-day postoperative outcomes of patients undergoing OPCAB.MethodsThis was a single-center, retrospective observational study including patients without a history of stroke or Transient Ischemic Attacks (TIA) (asymptomatic), who underwent for an isolated OPCAB in the center for operative treatment of coronary artery disease of Beijing Anzhen Hospital from January 2020 to December 2021. All enrolled patients underwent carotid artery ultrasound prior to OPCAB. The information was extracted independently by two authors of the study from the medical records. Both univariate and multivariate analyses were conducted.ResultsA total of 562 patients met the inclusion criteria for the current study. 63 (11.2%) suffered from severe ACAS. The Sequential Organ Failure Assessment (SOFA) maximum in the severe ACAS group was significantly higher than that in the non-severe ACAS group (9.76 ± 3.03 vs. 7.75 ± 2.96, p &lt; 0.0001), and a higher proportion of patients in the severe ACAS group exhibited severe multi-organ dysfunction (44.4% vs. 14.0%, p &lt; 0.0001). In addition, severe ACAS was related to an increased rate of 30-day postoperative major adverse cardiovascular and cerebral events (MACCEs), including a 30-day postoperative stroke. Severe ACAS was associated with an elevated risk of delirium, and acute kidney injury (AKI). The results of the multivariate analysis demonstrated that severe ACAS may be independently associated with severe multi-organ dysfunction (OR, 7.37, 95% CI 4.80–14.30, p &lt; 0.0001) after OPCAB. Also, severe ACAS may be independently associated with 30-day postoperative stroke (OR, 2.83, 95% CI 1.03–7.75, p = 0,043).ConclusionsSevere ACAS was independently associated with severe multi-organ dysfunction after OPCAB, which may be associated further with an increased rate of 30-day postoperative mortality and complications. This study highlights: (1) the importance of personalized assessment for potential advantages and disadvantages in prognosis of severe ACAS patients undergoing OPCAB with carotid endarterectomy; (2) the role of multi-organ parameters, especially cardio-cerebral factors, should be emphasized during the process of severe ACAS management.
Efficacy and safety of atezolizumab–bevacizumab vs pembrolizumab-lenvatinib in unresectable hepatocellular carcinoma: a retrospective, cohort study
Authors: Hu Zili , Yang Zhoutian , Fu Zibo , Fu Yizhen , Ma Zeliang , Zhou Zhongguo , Chen Minshan , Zhang Yaojun 
Published: November 2024

BackgroundThe relative superiority of atezolizumab–bevacizumab versus pembrolizumab-lenvatinib in treatment of unresectable hepatocellular carcinoma (HCC) remains uncertain. This study aims to compare the efficacy of atezolizumab–bevacizumab and pembrolizumab-lenvatinib in first-line treatments for unresectable HCC.MethodsA total of 72 patients receiving pembrolizumab-lenvatinib (PL group) and 92 patients receiving atezolizumab-bevacizumab (AB group) between January 2019 and June 2023 were included in this study. By employing propensity score matching (PSM), we compared the overall survival (OS) and progression-free survival (PFS) between the two groups.ResultsAfter PSM, the 1-, 2-, and 3-year OS rates were 70.4%, 54.5%, and 40.0% in the PL group, and 88.4%, 44.2%, and 44.2% in the AB group, respectively. The 6-, 12-, and 18-month PFS rates were 56.9%, 43.0%, and 32.1% in the PL group, and 74.2%, 40.9%, and 30.7% in the AB group, respectively. No significant differences were observed in both OS (HR, 0.498; 95% CI, 0.217-1.143; P = 0.1) and PFS (HR, 0.913; 95% CI, 0.512-0.1.629; P = 0.758) between the two groups. Through subgroup analysis, we developed a Cirrhosis-Portal vein invasion-ALBI (CPA) score and identified that the AB group exhibited significantly longer OS than the PL group in the CPA high population (HR, 0.219; 95% CI, 0.075–0.637; P = 0.005). The treatment-related adverse events between the PL group and the AB group were comparable.ConclusionsThis study suggests that the efficacy of pembrolizumab-lenvatinib and atezolizumab-bevacizumab is comparable in first-line treatment of unresectable HCC, the atezolizumab-bevacizumab combination may confer additional benefits for patients with high CPA scores compared to pembrolizumab-lenvatinib.
Machine learning-informed liquid-liquid phase separation for personalized breast cancer treatment assessment
Authors: Wang Tao , Wang Shu , Li Zhuolin , Xie Jie , Chen Huan , Hou Jing 
Published: November 2024

BackgroundBreast cancer, characterized by its heterogeneity, is a leading cause of mortality among women. The study aims to develop a Machine Learning-Derived Liquid-Liquid Phase Separation (MDLS) model to enhance the prognostic accuracy and personalized treatment strategies for breast cancer patients.MethodsThe study employed ten machine learning algorithms to construct 108 algorithm combinations for the MDLS model. The robustness of the model was evaluated using multi-omics and single-cell data across 14 breast cancer cohorts, involving 9,723 patients. Genetic mutation, copy number alterations, and single-cell RNA sequencing were analyzed to understand the molecular mechanisms and predictive capabilities of the MDLS model. Immunotherapy targets were predicted by evaluating immune cell infiltration and immune checkpoint expression. Chemotherapy targets were identified through correlation analysis and drug responsiveness prediction.ResultsThe MDLS model demonstrated superior prognostic power, with a mean C-index of 0.649, outperforming 69 published signatures across ten cohorts. High-MDLS patients exhibited higher tumor mutation burden and distinct genomic alterations, including significant gene amplifications and deletions. Single-cell analysis revealed higher MDLS activity in tumor-aneuploid cells and identified key regulatory factors involved in MDLS progression. Cell-cell communication analysis indicated stronger interactions in high-MDLS groups, and immunotherapy response evaluation showed better outcomes for low-MDLS patients.ConclusionThe MDLS model offers a robust and precise tool for predicting breast cancer prognosis and tailoring personalized treatment strategies. Its integration of multi-omics and machine learning highlights its potential clinical applications, particularly in improving the effectiveness of immunotherapy and identifying therapeutic targets for high-MDLS patients.
Protective effect of Shenqi Wenfei Formula against lipopolysaccharide/cigarette smoke-induced COPD in Rat based on gut microbiota and network pharmacology analysis
Authors: Shi Mengyao , Xue Qian , Xie Jinghui , Yang Qinjun , Tong Jiabing , Zhu Jie , Gao Yating , Ma Xiao , Wu Di , Li Zegeng 
Published: November 2024

IntroductionThe incidence of chronic obstructive pulmonary disease (COPD) appears to be increasing and evidence suggests that the intestinal flora may play a causative role in its development. Previous studies found that the Shenqi Wenfei Formula (SQWF) can regulate pyroptosis via the NLRP3/GSDMD pathway, thereby reducing the inflammatory response in the lungs of COPD model rats. However, there is no information on whether the drug's effects are associated with intestinal flora. Therefore, this study investigates whether the effects of SQWF are mediated through the regulation of intestinal flora, aiming to elucidate the underlying mechanisms of its therapeutic impact on COPD.MethodsCOPD was induced in rats using lipopolysaccharide and cigarette smoke, followed by intragastric administration of SQWF or physiological saline The targets of SQWF, associated signaling pathways, and key bacterial groups were investigated using 16S rRNA sequencing, network pharmacology, and bioinformatics techniques. The prediction results were validated using quantitative reverse transcription PCR, western blotting, and immunofluorescence, among other methods.ResultsSQWF treatment was found to alleviate COPD in model rats. Treatment was also observed to restore the balance of the intestinal flora in the rats, especially by reducing the abundance of g_Parabacteroides. Bioinformatics predictions identified g_Parabacteroides metabolites, RelA, HDAC1, and enriched neutrophil extracellular trap formation pathways as core targets of SQWF in COPD. qRT-PCR and Western blotting results showed that SQWF treatment reduced ReLA and HDAC1 mRNA and protein expression, along with decreased myeloperoxidase and neutrophil elastase levels in the nucleus.ConclusionTreatment with SQWF was found to restore the imbalance of intestinal g_Parabacteroides in COPD and also regulate the expression of the ReLA and HDAC1 genes, thereby reducing pulmonary neutrophil extracellular traps and alleviating lung inflammation.
Clinical efficacy of washed microbiota transplantation on metabolic syndrome and metabolic profile of donor outer membrane vesicles
Authors: Hu Xuan , Wu Qingting , Huang Lingui , Xu Jiating , He Xingxiang , Wu Lei 
Published: November 2024

ObjectTo clarify the clinical efficacy of washed microbiota transplantation (WMT) for metabolic syndrome (MetS), and explore the differences in the metabolic profile of bacterial outer membrane vesicles (OMVs) in donor fecal bacteria suspension received by MetS patients with good and poor outcomes, and to construct a predictive model for the efficacy of WMT for MetS using differential metabolites.MethodsMedical data 65 MetS patients who had completed at least 2 courses of WMT from 2017.05 to 2023.07 were collected. Fecal bacteria suspension of WMT donors were collected, and the clinical data of MetS patients treated with WMT during this period were collected as well. The changes of BMI, blood glucose, blood lipids, blood pressure and other indicators before and after WMT were compared. OMVs were isolated from donor fecal bacteria suspension and off-target metabolomic sequencing was performed by Liquid Chromatograph Mass Spectrometer (LC–MS).ResultsCompared with baseline, Body mass index (BMI), Systolic blood pressure (SBP) and Diastolic blood pressure (DBP) of MetS patients showed significant decreases after the 1st (short-term) and 2nd (medium-term) courses, and fasting blood glucose (FBG) also showed significant decreases after the 1st session. There was a significant difference between the Marked Response OMVs and the Moderate Response OMVs. It was showed that 960 metabolites were significantly up-regulated in Marked Response OMVs and 439 metabolites that were significantly down-regulated. The ROC model suggested that 9-carboxymethoxymethylguanine, AUC = 0.8127, 95% CI [0.6885, 0.9369], was the most potent metabolite predicting the most available metabolite for efficacy.ConclusionWMT had significant short-term and medium-term clinical efficacy in MetS. There were differences in the structure of metabolites between Marked Response OMVs and Moderate Response OMVs. The level of 9-Carboxy methoxy methylguanine in Marked Response OMVs can be a good predictor of the efficacy of WMT in the treatment of MetS.
Novel approach to assess sarcopenia in children with inflammatory bowel disease
Authors: Boros Kriszta Katinka , Veres Gábor , Pintér Hajnalka Krisztina , Richter Éva , Cseh Áron , Dezsőfi Antal , Arató András , Reusz George S. , Dohos Dóra , Müller Katalin E. , Cseprekál Orsolya 
Published: November 2024

IntroductionSarcopenia is associated with poor clinical outcomes in chronic diseases. Our study aimed to characterize body composition (BC) parameters in patients with inflammatory bowel disease (IBD) and compare skeletal muscle mass (SMM) parameters with the healthy pediatric population.MethodsBC of healthy controls (HC) and of patients with IBD were measured via multifrequency bioelectrical impedance (InBody 720 device) in a cross-sectional manner. The effect of sex, age, height, weight, and body mass index (BMI) on BC parameters, with a special attention to SMM, was assessed. Reference tables from SMM were generated using a maximum-likelihood curve-fitting technique for calculating Z scores.ResultsBC parameters were associated with age, body size, and sex. SMM was lower in patients with IBD (n = 57, aged 6.71 ± 8.7 years) compared to unadjusted HC (n = 307, aged 9.9–19.3 years; 143 males; SMM: 22.34 ± 8.38 vs. 24.4 ± 6.3 kg; p = 0.03). SMM showed a moderately strong correlation with age, weight, height, and BMI (R = 0.65, 0.9, 0.87, and 0.66; p &lt; 0.05 for each) in HC. In multivariate stepwise, ridge regression analysis, age, sex, and BMI remained the significant predictors of SMM (age β = 0.47, −0.31, and 0.38, respectively; p &lt; 0.05). SMM of sex-, age-, and BMI-adjusted HC did not differ from IBD. Therefore, BMI Z score–based references were plotted for normalizing SMM, and SMM Z score was calculated and found to be similar to that of HC.ConclusionsBC is supposed to be an easy-to-measure and objective marker of sarcopenia in children with IBD. Adjustment of SMM for BMI Z score might be needed to avoid the overestimation of sarcopenia in this patient population.
Impact of camel milk lactoferrin peptides against breast cancer cells: in silico and in vitro study
Authors: Baothman Othman , Ali Ehab M. M. , Alguridi Hassan , Hosawi Salman , Konozy Emadeldin Hassan E. , Abu Zeid Isam M. , Ahmad Abrar , Altayb Hisham N. 
Published: November 2024

Background and AimsBreast cancer remains a significant global health concern, necessitating the exploration of novel therapeutic strategies. Despite advancements in cancer therapeutics, effective treatments with minimal side effects remain elusive. Natural sources, such as camel milk, harbor bioactive compounds such as lactoferrin peptides, which hold promise as anticancer agents. This study investigated the potential of camel milk-derived lactoferrin peptides against breast cancer cells through a combined in silico and in vitro approach. By integrating computational modeling with experimental assays, we aimed to elucidate the anticancer mechanisms of these peptides and provide insights for their optimization as anticancer therapeutics.MethodsIn silico analysis involving pepetid design, and validation, then molecular docking and molecular dynamics (MD) simulations was used to explore peptide-protein interactions and stability. Peptides were synthesized and tested for anticancer activity using MTT assays on MCF-7 cells, with HDFa normal cells used as controls.ResultsResults of this study showed that camel milk-derived lactoferrin peptides, particularly PEP66, exhibited strong anticancer activity against MCF-7 breast cancer cells, with the lowest IC50 value (52.82 μg/mL) compared to other peptides. In silico molecular docking and dynamics simulations revealed that PEP66 formed stable interactions with key residues in the HER2 catalytic site, indicating its potential as an effective anticancer agent. The selectivity index (SI) of PEP66 (3.19) also suggested lower toxicity to normal cells compared to cancer cells, reinforcing its therapeutic potential. Hydrogen bonding analysis highlighted key residues involved in stabilizing peptide-protein complexes, while molecular dynamics simulations demonstrated the stability of these interactions over time. Notably, PEP66 exhibited the highest stability and formed significant interactions with essential residues in the HER2 catalytic site, suggesting its potential as an effective anticancer agent.ConclusionCamel milk-derived lactoferrin peptides show promise as anticancer agents against breast cancer cells. The multidisciplinary approach employed in this study provides valuable insights into the mechanisms underlying their activity, paving the way for rational design strategies to enhance their efficacy. Further experimental validation is warranted to validate the anticancer potential of these peptides and advance their development as novel therapeutic agents for breast cancer treatment.
Temporal atrophy together with verbal encoding impairment is highly predictive for cognitive decline in typical Alzheimer’s dementia – a retrospective follow-up study
Authors: Doganyigit Burak , Defrancesco Michaela , Schurr Timo , Steiger Ruth , Gizewski Elke R. , Mangesius Stephanie , Galijasevic Malik , Hofer Alex , Tuovinen Noora 
Published: November 2024

IntroductionThe increasing prevalence of Alzheimer’s disease (AD) has created an urgent need for rapid and cost-effective methods to diagnose and monitor people at all stages of the disease. Progressive memory impairment and hippocampal atrophy are key features of the most common so-called typical variant of AD. However, studies evaluating detailed cognitive measures combined with region of interest (ROI)-based imaging markers of progression over the long term in the AD dementia (ADD) stage are rare.MethodWe conducted a retrospective longitudinal follow-up study in patients with mild to moderate ADD (aged 60-92 years). They underwent magnetic resonance imaging (MRI; 3 Tesla, MPRAGE) as well as clinical and neuropsychological examination (Consortium to Establish a Registry for Alzheimer’s Disease [CERAD] -Plus test battery) at baseline and at least one follow-up visit. ROI-based brain structural analysis of baseline MRIs was performed using the Computational Anatomy Toolbox (CAT) 12. Clinical dementia progression (progression index [PI]) was measured by the annual decline in the Mini Mental State Examination (MMSE) scores. MRI, demographic, and neuropsychological data were included in univariate and multiple linear regression models to predict the PI.Results104 ADD patients (age 63 to 90 years, 73% female, mean MMSE score 22.63 ± 3.77, mean follow-up 4.27 ± 2.15 years) and 32 age- and gender-matched cognitively intact controls were included. The pattern of gray matter (GM) atrophy and the cognitive profile were consistent with the amnestic/typical variant of ADD in all patients. Deficits in word list learning together with temporal lobe GM atrophy had the highest predictive value for rapid cognitive decline in the multiple linear regression model, accounting for 25.4% of the PI variance.DiscussionOur results show that temporal atrophy together with deficits in the encoding of verbal material, rather than in immediate or delayed recall, is highly predictive for rapid cognitive decline in patients with mild to moderate amnestic/typical ADD. These findings point to the relevance of combining detailed cognitive and automated structural imaging analyses to predict clinical progression in patients with ADD.
Health-related quality of life of HIV patients with comorbidities of hypertension or diabetes in Ghana
Authors: Owusu Richmond , Kwarteng Emmanuel Bugyei , Bawua Serwaa Akoto , Otoo Desmond Dzidzornu , Nonvignon Justice 
Published: November 2024

BackgroundClinical studies, particularly in the context of HIV/AIDS, have utilized health-related quality of life (HRQoL) and health state utility values to assess both clinical and economic implications. Improvement in HIV management with antiretroviral therapy (ART) has coincided with an increased morbidity of chronic conditions such as diabetes and hypertension among people living with HIV. The study offers empirical evidence establishing a link between HIV, comorbidities like hypertension and diabetes, and their collective impact on HRQoL.MethodsA cross-sectional quantitative study among 418 HIV patients in three regions of Ghana in the Savannah, Middle Belt, and Coastal belt. Face-to-face interviews were conducted using EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) in combination with EuroQol-Visual Analog Scales (EQ-VAS). Ugandan EQ-5D-5L value set was used for computing the utility values. Patients' socio-demographic and clinical data were obtained from medical records and analyzed descriptively. Mann-Whitney U and Kruskal Wallis tests were used to evaluate the relationship between patient socio-demographic and clinical variables and health status.ResultsOverall median utility value was 0.93(IQR=0.79, 1.00) from the EQ-5D index and 90 (IQR = 80, 100) from the EQ-VAS scores. Prevalence of hypertension and diabetes were 9.1% and 2.4% respectively. There was significant difference in EQ-VAS score between HIV patients with hypertension and those without hypertension (z = 2.146 p = 0.032). There was also a significant difference in the EQ-VAS scores (z = 2.381, p = 0.017) of patients with diabetes and those without diabetes. Region, sex, age, education, marital status, employment status, place of residence, monthly income level, duration of infection, adherence to ART, and other illness were significantly associated with EQ-5D-5L utility and EQ-VAS scores at 0.05 significant level.ConclusionHRQoL among HIV positive individuals in Ghana was high. Comorbidities such as hypertension or diabetes had nuanced effects on perceived health status. A patient-centered, multidisciplinary approach to HIV care should be adopted considering regional differences and the presence of comorbidities.