bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endovascular treatment of postoperative aortic coarctation aneurysms—a single center experience
Authors: Dimitrova Iva N. , Simeonov Peyo 
Published: December 2024

BackgroundFormation of local type aortic aneurysm years after surgical repair of coarctation (CoA) occurs in 10% of patients independent of the surgical technique and is a potentially life-threatening condition if left untreated with a high risk of aortic rupture. Redo open surgery is associated with 14% in-hospital mortality and a high risk of complications. Endovascular treatment appears to be a feasible alternative with a high success rate and low morbidity and mortality, but data concerning long-term results is still mandatory. We describe the single center experience of a series of patients treated with endovascular stent grafting for large aneurysms after previous surgery for CoA.MethodsThis series involves 12 consecutive patients treated with endovascular stent grafting from April 2003 to January 2022 for late aneurysm at the site of previous surgical repair for CoA. Data on baseline characteristics, clinical, computed tomography (CT), procedural features, and in-hospital and long-term results were analyzed. All patients signed institutional informed consent for the procedure.ResultsA total of 12 patients (average age 38.5 ± 10.2 years) underwent endovascular repair. The average interval between the initial surgical intervention and the aneurysm repair was 24.1 ± 9.1 years and the majority (83.3%) underwent synthetic patch aortoplasty as previous intervention. All patients were symptomatic at presentation with an average maximum diameter of the aneurysm 67.2 mm (ranging from 44 to 110 mm). Stent-graft placement was successful in all cases without procedural, in-hospital, 30-day, and one-year mortality or major complications. The average hospital stay was 9.3 days (range 7–19 days). For a mean follow-up period of 87 months (range, 23–168 months), all patients demonstrated positive aneurysm remodeling with cavity thrombosis and aneurysm diameter reduction to 54.9 mm (±16,6). For the entire follow-up period, we observed one aneurysm-related death and three deaths of heart failure.ConclusionEndovascular stent-graft treatment of patients with thoracic aneurysms after repair of CoA is an acceptable treatment of choice. It has shown promising results with high technical success and low immediate, short—and mid-term morbidity and mortality. Still, randomised control trials (RCTs) are needed to define the long-term outcome of this approach. Routine surveillance and screening of patients with previous CoA repair are mandatory.
Transarterial therapy combined with bevacizumab plus immune checkpoint inhibitors as a neoadjuvant therapy for locally advanced HCC
Authors: Yang Zhenyun , Wang Qianyu , Hu Li , Sima Xiaoxian , Wang Juncheng , Hu Dandan , Zhou Zhongguo , Chen Minshan , Zhang Yaojun , Fu Yizhen 
Published: December 2024

BackgroundTransarterial therapy (TAT), bevacizumab (Bev), and immune checkpoint inhibitors (ICIs) have individually exhibited efficacy in treating advanced-stage hepatocellular carcinoma (HCC). This study aimed to assess the efficacy and safety of the combination of these three treatments as a neoadjuvant modality in patients with locally advanced HCC.MethodsThe primary endpoint is overall survival (OS). The second endpoint is progression free survival (PFS), objective response rate (ORR), pathological response rate and safety.ResultsA total of 54 patients received standard systemic therapy comprising Bev combined with ICIs (Bev-ICIs group), 113 patients received direct surgery (Surgery group), and 273 patients received neoadjuvant therapy of TAT combined Bev plus ICIs, among which 79 patients (28.9%) underwent surgical resection after successful tumor downstaging (Neo-surgery group) while the remaining 194 patients (71.1%) received maintenance systemic therapies (Neo-maintenance group). Neoadjuvant following surgery demonstrated a prolonged OS in contrast to direct surgery, with a median OS time not reached in the Neo-surgery group and 30.6 (95% CI: 26.4-34.7) months in the Surgery group (hazard ratio (HR)=0.29, P=0.0058). The median PFS time in the Neo-surgery and Surgery groups stood at 19.2 (95% CI: 16.1-22.2) and 6.3 (95% CI:4.7-8) months, respectively (HR=0.25, P&lt;0.0001). In patients failed to receiving resection after neoadjuvant therapy, the median OS was 22.8 (95% CI: 22.3-23.1) months, whereas that for the standard care population was 19.7 (95% CI: 15.9-24) month (HR=0.53, P=0.023). The median PFS time in Neo-maintenance group and Bev-ICIs groups was 11.2 (95% CI: 10.4-11.9) and 6.4 (95% CI: 4.4-8.5) months (HR=0.60, P=0.024). The ORR and disease control rate (DCR) across all patients received TAT-Bev-ICIs were 38.8% and 89.4%, respectively. Additionally, the pathological complete response (pCR) rate and the major pathological response (MPR) rate were 22.8% and 48.1% in the Neo-surgery group. As for safety, neoadjuvant therapy did not increase the perioperative complications when compared to direct surgery, and demonstrated similar incidences and severity of AEs when compared to the standard systemic therapy.ConclusionThe triple therapy regimen comprising TAT-Bev-ICIs emerged as a promising therapeutic strategy for locally advanced hepatocellular carcinoma (HCC) as a neoadjuvant intervention.
Identification and experimental validation of diagnostic and prognostic genes CX3CR1, PID1 and PTGDS in sepsis and ARDS using bulk and single-cell transcriptomic analysis and machine learning
Authors: Jiang Jijin , Chen Yan , Su Yue , Zhang Li , Qian Hao , Song Xinmiao , Xu Jin-Fu 
Published: December 2024

BackgroundSepsis is an uncontrolled reaction to infection that causes severe organ dysfunction and is a primary cause of ARDS. Patients suffering both sepsis and ARDS have a poor prognosis and high mortality. However, the mechanisms behind their simultaneous occurrence are unclear.MethodsWe acquired sepsis and ARDS datasets from GEO and Arrayexpress databases and screened hub genes by WGCNA and machine learning algorithm. For diagnosis and prognosis, ROC curve and survival analysis were used. We performed GO, KEGG, GSEA, immune cell infiltration, drug prediction, molecular docking, transcription factor prediction, and constructed PPI and ceRNA networks to explore these genes and the common mechanisms of sepsis and ARDS. Single-cell data analysis compared immune cell profiles and hub gene localization. Finally, RT-qPCR and H&amp;E staining confirmed the reliability of hub genes using PBMCs samples and mouse models.ResultsWe identified 242 common differentially expressed genes in sepsis and ARDS. WGCNA analysis showed that the turquoise module in GSE95233 is strongly linked to sepsis occurrence and poor prognosis, while the black module in GSE10474 is associated with ARDS. Using WGCNA and three machine learning methods (LASSO, random forest and Boruta), we identified three key genes CX3CR1, PID1 and PTGDS. Models built with them showed high AUC values in ROC curve evaluations and were validated by external datasets, accurately predicting the occurrence and mortality. We further explored the immunological landscape of these genes using immune infiltration and single-cell analysis. Then, the ceRNA, predicted drugs and molecular docking were analyzed. Ultimately, we demonstrated that these genes are expressed differently in human and mouse samples with sepsis and ARDS.ConclusionThis study identified three molecular signatures (CX3CR1, PID1 and PTGDS) linked to the diagnosis and poor prognosis of sepsis and ARDS, validated by RT-qPCR and H&amp;E staining in both patient and mouse samples. This research may be valuable for identifying shared biological mechanisms and potential treatment targets for both diseases.
Durvalumab and pembrolizumab in advanced biliary tract cancer: a reconstructed patient-level mimic head-to-head comparative analysis
Authors: Wang Bi-Cheng , Kuang Bo-Hua , Lin Guo-He , Fu Chen 
Published: December 2024

BackgroundThe addition of durvalumab or pembrolizumab to gemcitabine and cisplatin (GP) has been approved to statistically improve survival outcomes in patients with advanced biliary tract cancer. However, since the survival time was only prolonged by about two months, doubts have been raised. In this analysis, we aimed to evaluate the efficacy of combining durvalumab or pembrolizumab with GP chemotherapy.MethodsRecords were identified through a formal search of PubMed and Web of Science. The TOPAZ-1 and KEYNOTE-966 trials were definitively included. Patient-level overall survival (OS) and progression-free survival (PFS) data were reconstructed and analyzed using a one-stage approach.ResultsThe immunotherapy plus GP chemotherapy group showed superiority over the GP chemotherapy group (OS: HR 0.83, p &lt; 0.001; PFS: HR 0.88, p = 0.009). The survival outcomes were similar between the durvalumab and pembrolizumab groups (OS: HR 1.02, p = 0.83; PFS: HR 0.95, p = 0.53). In the subgroup analysis, the gemcitabine-maintenance group significantly prolonged the OS compared to the gemcitabine-limited-to-8-cycles group (OS: HR 0.86, p = 0.007). Neither the durvalumab nor pembrolizumab groups statistically improved the OS compared to the gemcitabine-maintenance group. In contrast, the durvalumab and pembrolizumab groups significantly improved OS compared to the gemcitabine-limited-to-8-cycles group.ConclusionsBased on this mimic head-to-head analysis, we are convinced that durvalumab and pembrolizumab benefit patients with biliary tract cancer. However, despite the statistically significant differences, the moderate progress made in OS and PFS might still be considered inadequate. It is crucial for clinicians to identify the precise subgroup population that could benefit most from immunotherapy and develop more strategies for those who might not respond well to immunotherapy.
SQLE-mediated squalene metabolism promotes tumor immune evasion in pancreatic cancer
Authors: Pan Junchen , Liang Haixi , Zhou Lin , Lu Wenhua , Huo Bitao , Liu Rui , Huang Peng 
Published: December 2024

BackgroundSqualene epoxidase (SQLE) is a key enzyme in cholesterol biosynthesis and has been shown to negatively affect tumor immunity and is associated with poor outcomes of immunotherapy in various cancers. While most research in this area has focused on the impact of cholesterol on immune functions, the influence of SQLE-mediated squalene metabolism within the tumor immune microenvironment (TIME) remains unexplored.MethodsWe established an immune-competent mouse model (C57BL/6) bearing mouse pancreatic cancer xenografts (KPC cells) with or without stable SQLE-knockdown (SQLE-KD) to evaluate the impact of SQLE-mediated metabolism on pancreatic cancer growth and immune functions. The effect of squalene on tumor growth and immune cells was tested by direct administration of squalene to C57BL/6 mice bearing KPC tumors. Flow cytometry analysis and immunohistochemical (IHC) staining of immune cells from the tumor tissues were performed to evaluate changes in immune function. We also employed RNA-sequencing to analyze the gene expression profiles in pancreatic cancer cells (PANC-1) treated with or without squalene. RT-PCR and Western blot analyses were used to investigate the relevant molecular mechanisms.ResultsWe show that SQLE is significantly overexpressed in pancreatic cancer, and abrogation of SQLE results in a significant increase in squalene accumulation within tumor cells. The elevated squalene inhibits CXCL1 transcription through its impact on the NF-κB pathway via p65, and thus reduces the recruitment of myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) into the tumor microenvironment. Silencing of SQLE also leads to an increased proportion of CD8+ T cells in the tumor tissues and suppresses tumor growth in vivo. Importantly, direct administration of squalene, the metabolic substrate of SQLE, to immune-competent mice bearing KPC pancreatic cancer tumors causes a substantial decrease in CD206+ TAMs and MDSCs, thus releasing immune suppression and inhibiting tumor growth.ConclusionOur study shows that squalene is an important immune-modulating metabolite that inhibits the infiltration of immune-suppressive cells in TIME, and that SQLE exerts its tumor immune evasion effect by metabolic removal of squalene. Thus, SQLE-mediated squalene metabolic pathway could be a potential target to enhance antitumor immunity in pancreatic cancer.
Reduced portal vein blood flow velocity in acute fatty liver of pregnancy
Authors: Zhao Yang , Zhang Er-ke , Li Dan-Hua , Zhou Yu-Jing , Jiang Hui , Jia Xiao-Chao , Qin Chuan 
Published: December 2024

PurposeAcute fatty liver of pregnancy (AFLP) is a severe complication that can occur in the third trimester or immediately postpartum, characterized by rapid hepatic failure. This study aims to explore the changes in portal vein blood flow velocity and liver function during pregnancy, which may assist in the early diagnosis and management of AFLP.MethodsThis longitudinal study was conducted at a tertiary healthcare center with participants recruited from routine antenatal check-ups. The study included healthy women aged 20–40 years with singleton pregnancies. Doppler ultrasonography was used to assess portal vein flow and velocity, complemented by standard laboratory tests to monitor liver function. A nomogram model integrating the clinical features and Doppler ultrasonography parameters was constructed using logistic regression analysis for differentiating AFLP from normal controls.ResultsA total of 135 women were enrolled, divided into control and AFLP groups. The AFLP group demonstrated a significant reduction in portal vein flow velocity and alterations in liver dimensions. Laboratory tests indicated elevated liver enzymes and altered lipid profiles in the AFLP group. Statistical analysis showed that portal vein flow velocity could be a sensitive marker for predicting liver dysfunction in AFLP. The area under the receiver operating characteristic (ROC) curves (AUC) of the nomogram model were 0.88 (95% confidence interval [CI]: 0.82–0.95) with specificity, sensitivity, negative predictive value, and positive predictive value of 67.8, 95.0, 95.0, and 67.8, respectively, in the training cohort and 0.86 (95% CI: 0.72–0.98) and 86.9, 75.0, 83.3, and 80.0 in the test cohort, respectively. The calibration curves demonstrated good agreement between the predicted and observed probability for predicting AFLP.ConclusionThe study underscores the potential of using portal vein flow velocity as an early diagnostic marker for AFLP in pregnant women. Further research is required to establish standardized diagnostic thresholds for portal vein flow measurements.
WhiA transcription factor provides feedback loop between translation and energy production in a genome-reduced bacterium
Authors: Fisunov Gleb Y. , Tsvetkov Vladimir B. , Tsoy Ekaterina A. , Evsyutina Daria V. , Vedyaykin Alexey D. , Garanina Irina A. , Semashko Tatiana A. , Manuvera Valentin A. , Varizhuk Anna M. , Kovalchuk Sergey I. , Zubov Alexander I. , Barinov Nicolay A. , Pobeguts Olga V. , Govorun Vadim M. 
Published: December 2024

IntroductionWhiA is a conserved protein found in numerous bacteria. It consists of an HTH DNA-binding domain linked with a homing endonuclease (HEN) domain. WhiA is one of the most conserved transcription factors in reduced bacteria of the class Mollicutes. Its function in Mollicutes is unknown, while it is well-characterized in Streptomyces. Here, we focused on WhiA protein from Mycoplasma gallisepticum.MethodsWe used a combination molecular dynamics, EMSA, MST and AFM to study the DNA-binding and ATP-binding properties of WhiA from M. gallisepticum. The transcriptional repressor function of WhiA was demonstrated using gene knockdown, reporter constructs and proteome analysis.ResultsWe demonstrate that WhiA homolog from M. gallisepticum binds a conserved sequence of the GAYACRCY core (Y = C or T, R = A or G), which is located in the promoter of an operon coding for ribosomal proteins and adenylate kinase (rpsJ operon). We show that WhiA in M. gallisepticum is a repressor of rpsJ operon and a sensor of ATP. HTH domain binds to the core motif and HEN domain binds to the auxiliary motif GTTGT that is located downstream to the core motif. We show that binding by both domains to DNA is required to fulfill the transcription repressor function. Knockdown of whiA does not affect actively growing M. gallisepticum, but leads to the growth retardation after freezing.DiscussionWe propose the following model for M. gallisepticum WhiA function. WhiA remains bound to the core motif at any conditions. At low ATP concentrations (starvation) HEN domain binds auxiliary motif and represses rpsJ operon transcription. At high ATP concentrations (nutrient-rich conditions) HEN domain binds ATP and releases auxiliary motif. It leads to the de-repression of rpsJ operon and increased production of ribosomal proteins.
Effect of conjugative transfer of antibiotic resistance genes mediated by plasmids on the microecology of different intestinal segments
Authors: Ding Chengshi , Yan Li , Zhang Kai , Liu Xiangxiang , Liu Ziyu , Hou Shaowei , Ma Jing , Wu Zhiping , Wei Hongfei 
Published: December 2024

IntroductionThe conjugative transfer of antibiotic resistance genes (ARGs) mediated by plasmids occurred in different intestinal segments of mice was explored.MethodsThe location of ARG donor bacteria and ARGs was investigated by qPCR, flow cytometry, and small animal imaging. The resistant microbiota was analyzed by 16S rRNA gene amplification sequencing.ResultsThe small intestine was the main site for the location of ARG donor bacteria and ARGs. The intestinal microbiota richness of the small intestine (duodenum and jejunum) and the large intestine (cecum, colon, and rectum) increased, and the ileum microbiota richness decreased under the action of donor bacteria. The differences in the number of bacteria in the small intestine and the large intestine, as well as the relative richness of Firmicutes from the small intestine to the large intestine, decreased. By contrast, the relative abundance of Proteobacteria increased. The intake of resistant plasmids alleviated the impact of antibiotics on intestinal microbiota, particularly increasing the proportion of Proteobacteria and Bacteroides, which were presumed to be susceptible to ARGs.DiscussionThe acquisition of ARGs by intestinal microbes is an important reason why infectious diseases are difficult to cure, which brings risks to human health and intestinal microecology.
Untargeted metabolomics profiling of gestational diabetes mellitus: insights into early diagnosis and metabolic pathway alterations
Authors: Aleidi Shereen M. , Al Fahmawi Hiba , AlMalki Reem H. , Al Mogren Maha , Alwahsh Mohammad , Mujammami Muhammad , Costanzo Michele , Abdel Rahman Anas 
Published: December 2024

IntroductionGestational Diabetes Mellitus (GDM) is a metabolic disorder marked by Q10 hyperglycemia that can negatively affect both mothers and newborns. The increasing prevalence of GDM and the limitations associated with the standard diagnostic test highlight the urgent need for early screening strategies that promote timely interventions.MethodsThis study aims to investigate the metabolic profile associated with GDM through an untargeted metabolomic analysis using mass spectrometry (MS)- based omics. Serum samples were collected from 40 pregnant women at weeks 24–28 of gestation based on the 2-h 75-g oral glucose tolerance test (OGTT); 50% were diagnosed with GDM (n = 20), and the remaining were considered a control group.Results and discussionThe results showed distinct metabolic differences between women with GDM and those without, with 222 significantly dysregulated metabolites, 120 up- and 102 downregulated in GDM compared to the control group. Key metabolic pathways, such as tryptophan, inositol phosphate, phenylalanine, and histidine metabolism, were notably dysregulated in GDM. The study also found that specific metabolites, like N-Acetylproline and Serylmethionine, with area under the curve (AUC) of 0.978 and 0.968, respectively, showed high accuracy in distinguishing between GDM and non-GDM women. This study would enhance our understanding of metabolic alterations in GDM and could contribute to early prediction and management strategies.
Adult neurogenesis in the ventral hippocampus decreased among animal models of neurodevelopmental disorders
Authors: Sun Lihao , Ohashi Nobuhiko , Mori Takuma , Mizuno Yuka , Zang Weichen , Guo Qi , Kouyama-Suzuki Emi , Shirai Yoshinori , Tabuchi Katsuhiko 
Published: December 2024

IntroductionAutism spectrum disorder (ASD) is a neurodevelopmental condition characterized by deficits in social interaction and communication, along with restricted and repetitive behaviors. Both genetic and environmental factors contribute to ASD, with prenatal exposure to valproic acid (VPA) and nicotine being linked to increased risk. Impaired adult hippocampal neurogenesis, particularly in the ventral region, is thought to play a role in the social deficits observed in ASD.MethodsIn this study, we investigated social behavior and adult hippocampal neurogenesis in C57BL/6J mice prenatally exposed to VPA or nicotine, as well as in genetically modified ASD models, including IQSEC2 knockout (KO) and NLGN3-R451C knock-in (KI) mice. Sociability and social novelty preference were evaluated using a three-chamber social interaction test. Adult hippocampal neurogenesis was assessed by BrdU and DCX immunofluorescence to identify newborn and immature neurons.ResultsVPA-exposed mice displayed significant deficits in social interaction, while nicotine-exposed mice exhibited mild impairment in social novelty preference. Both IQSEC2 KO and NLGN3-R451C KI mice demonstrated reduced adult neurogenesis, particularly in the ventral hippocampus, a region associated with social behavior and emotion. Across all ASD mouse models, a significant reduction in BrdU+/NeuN+ cells in the ventral hippocampus was observed, while dorsal hippocampal neurogenesis remained relatively unaffected. Similar reductions in DCX-positive cells were identified in VPA, nicotine, and NLGN3-R451C KI mice, indicating impaired proliferation or differentiation of neuronal progenitors.DiscussionThese findings suggest that impaired adult neurogenesis in the ventral hippocampus is a common hallmark across ASD mouse models and may underlie social behavior deficits. This study provides insight into region-specific neurogenic alterations linked to ASD pathophysiology and highlights potential targets for therapeutic interventions.