bluuebunny/crossref_metadata_2025_split huggingface dataset:
The XIAP inhibitor AZD5582 improves the treatment effect of microwave ablation on hepatocellular carcinoma
Authors: Wang Wenhui , Wu Fuyuan , Wu Zhe , Zhang Mengfan , Lu Qiang 
Published: January 2025

Background and purposeMicrowave ablation (MWA) is one of the first-line therapy recommended for early-stage hepatocellular carcinoma (HCC). However, the residual tumor, resulting from insufficient ablation, led to recurrence and metastasis of liver cancer. Novel combination strategies are urgently needed to enhance efficiency of MWA.MethodsWe detected the expression of XIAP protein after ablation in primary liver cancer patients using immunohistochemistry. Then, we established in vitro and in vivo IMWA models to further detect XIAP expression. We established an in vitro IMWA model by heating HCC cell lines and, at the same time, applied the XIAP inhibitor AZD5582 and verified the proliferation, migration, and pro-apoptotic ability of the XIAP inhibitor on tumor cells using CCK8, colony formation assay, cell scratch assay, and flow cytometry flow. The IMWA model of C57BL/6 and NTG mice were established, and AZD5582 was used in combination to evaluate the inhibitory and pro-apoptotic effects of different treatment regimens on tumor growth and to detect the local immune infiltration of C57BL/6 tumors. Finally, AZD5582 drug toxicity was detected to confirm its feasibility.ResultsXIAP protein expression is significantly increased in recurrent hepatocellular carcinoma tissues of patients who previously received microwave ablation therapy. In vitro experiments showed that the migration and proliferation ability of HCC cells was significantly reduced, and the level of apoptosis was increased after application of the XIAP inhibitor AZD5582. In vivo experiments further confirmed that ablation combined with the application of AZD5582 significantly reduced the proliferation ability of residual hepatocellular carcinoma. Concurrently, in C57 BL/6 mice with AZD5582 application, the level of local CD8+ T-cell infiltration in the tumor was increased, while the level of Foxp3+ regulatory T-cell infiltration was significantly reduced. The low toxicity of AZD5582 was further confirmed through hematological and pathological examinations of vital organs. These results provide new clues for hepatocellular carcinoma treatment, suggesting the potential role of XIAP inhibitors in hepatocellular carcinoma treatment and their impact in immunomodulation.ConclusionsIn this study, we found that the XIAP inhibitor AZD5582 modulates the immune microenvironment and inhibits the progression of post-ablation residual hepatocellular carcinoma.
Dual-release hydrocortisone treatment improves serum and peripheral blood mononuclear cell inflammatory and immune profiles in patients with autoimmune primary adrenal insufficiency
Authors: Tomasello Laura , Coppola Antonina , Pizzolanti Giuseppe , Giordano Carla , Arnaldi Giorgio , Guarnotta Valentina 
Published: January 2025

ObjectiveThe primary outcome was the evaluation of the T-cell phenotype in autoimmune primary adrenal insufficiency (PAI). Secondary outcomes included the evaluation of the CD4+CD25+Foxp3+ Treg population and the gene expression levels of IL-6, IL-17A, cyclooxygenase (COX)-2, heat shock proteins (HSP)-70, indoleamine-2,3-dioxygenase (IDO), programmed death-ligand 1 (PD-L1), inducible nitric oxide synthase (iNOS), and thioredoxin (TXN)-1.MethodsWe prospectively included 15 patients with PAI on conventional glucocorticoid (GC) replacement therapy, 15 switched to dual-release hydrocortisone (DR-HC), and 20 healthy controls. Serum inflammatory parameters and peripheral blood mononuclear cells (PBMCs) were evaluated at baseline and after 12 months of treatment.ResultAt baseline, significantly higher CD4+ and CD8+ (both p &lt; 0.001) T-cell percentages, a lower CD4+/CD8+ ratio (p &lt; 0.05), and higher CD25+ and CD4+/CD25+ T cells (both p &lt; 0.001) were observed in PAI compared to controls. After 12 months of DR-HC treatment, we found significantly lower IL-6 (p = 0.019), IL-17A (p = 0.046), COX-2 (p &lt; 0.001), HSP-70 (p = 0.006), and TXN-1 (p = 0.008) and higher PD-L1 (p &lt; 0.001) and IDO (p &lt; 0.001) mRNA values compared to baseline. After 12 months of DR-HC treatment, a significant increase in CD4+ T cells (p = 0.012), PD-L1 (p = 0.003), and IDO (p &lt; 0.001) and a decrease in CD8+ T cells (p &lt; 0.001), IL-6 (p = 0.003), IL-17A (p = 0.0014), COX-2 (p &lt; 0.001), HSP-70 (p = 0.005), and TXN-1 (p = 0.0008), as well as a significantly higher conversion in the CD4+/CD8+ ratio (p = 0.033), were observed compared to conventional GCs.ConclusionsThe switch from conventional GCs to DR-HC treatment altered the T lymphocyte phenotype and CD4+/CD8+ ratio in a Treg-independent manner, inducing significant improvements in the immune and inflammatory profile in PAI.
The real-world safety of Ofatumumab: a pharmacovigilance analysis based on the FDA adverse event reporting system
Authors: Zhou Yue , Wu Yutong , Zhao Xiao , Xu Lingxu , Sun Mingguang , Meng Zhaoyou 
Published: January 2025

BackgroundOfatumumab is a humanized monoclonal antibody that targets CD20-positive B cells. It was approved by the FDA in 2020 for the treatment of relapsing multiple sclerosis (RMS) in adult patients, and in 2009 for the treatment of Chronic Lymphocytic Leukemia (CLL). With the escalating clinical application of Ofatumumab, comprehending its safety profile within actual healthcare environments is of considerable importance.MethodsThis study compiled a dataset derived from the FAERS database, which included real-world safety data on Ofatumumab from Q4 2009 to Q2 2024. We applied four distinct methodologies, including ROR, PRR, MGPS, and BCPNN, to perform a disproportionality analysis of adverse events (AEs) associated with Ofatumumab. Furthermore, we utilized the Weibull distribution model to estimate the temporal risk pattern of AEs.ResultsThe investigation incorporated a total of 24,468 case reports pertaining to AEs associated with Ofatumumab. The commonly observed AEs encompass Fatigue, Headache, Chills, Pyrexia, Pain, Nausea, Nasopharyngitis, Vomiting, Urinary tract infection, and Pneumonia. Additionally, we identified potential AEs not specified on the drug label, such as Asthenia, Hypoesthesia, Dizziness, Malaise, Injection site pain, Paresthesia, and Diarrhea.ConclusionsThis investigation has identified several AEs associated with Ofatumumab and revealed previously unacknowledged potential adverse reaction signals. Healthcare providers can refer to these adverse reaction signals to more comprehensively consider the possible conditions that patients may present with during actual clinical practice.
Emerging applications of NLP and large language models in gastroenterology and hepatology: a systematic review
Authors: Omar Mahmud , Nassar Salih , SharIf Kassem , Glicksberg Benjamin S. , Nadkarni Girish N. , Klang Eyal 
Published: January 2025

Background and aimIn the last years, natural language processing (NLP) has transformed significantly with the introduction of large language models (LLM). This review updates on NLP and LLM applications and challenges in gastroenterology and hepatology.MethodsRegistered with PROSPERO (CRD42024542275) and adhering to PRISMA guidelines, we searched six databases for relevant studies published from 2003 to 2024, ultimately including 57 studies.ResultsOur review of 57 studies notes an increase in relevant publications in 2023–2024 compared to previous years, reflecting growing interest in newer models such as GPT-3 and GPT-4. The results demonstrate that NLP models have enhanced data extraction from electronic health records and other unstructured medical data sources. Key findings include high precision in identifying disease characteristics from unstructured reports and ongoing improvement in clinical decision-making. Risk of bias assessments using ROBINS-I, QUADAS-2, and PROBAST tools confirmed the methodological robustness of the included studies.ConclusionNLP and LLMs can enhance diagnosis and treatment in gastroenterology and hepatology. They enable extraction of data from unstructured medical records, such as endoscopy reports and patient notes, and for enhancing clinical decision-making. Despite these advancements, integrating these tools into routine practice is still challenging. Future work should prospectively demonstrate real-world value.
Inflammatory lipid biomarkers and transplant-free mortality risk in hepatitis B-related cirrhosis and hepatic encephalopathy
Authors: Shi Ke , Wang Xiaojing , Yi Zhang , Li Yanqiu , Feng Ying , Wang Xianbo 
Published: January 2025

ObjectiveInflammatory reactions and dyslipidemia are associated with the pathogenesis and prognosis of hepatitis B virus-related cirrhosis. We aimed to assess the predictive ability of these parameters in patients with hepatitis B virus-related cirrhosis and overt hepatic encephalopathy (HBV-related OHE).DesignWe conducted an analysis of 1,404 participants diagnosed with HBV-related OHE between January 2008 and July 2023. The prognostic significance of the neutrophil-to-high-density lipoprotein cholesterol (HDL-C) ratio (NHR), lymphocyte-to-HDL-C ratio (LHR), and monocyte-to-HDL-C ratio (MHR) was evaluated using the area under the receiver operating characteristic curve (AUC). Restrictive cubic splines (RCS) were employed to explore the relationship between NHR and 12-month transplant-free (TF) mortality. This study included a prospective test cohort of 328 patients.ResultsNHR was identified as an independent risk factor for 12-month TF mortality. The AUC for NHR (0.776) was similar to that of the model end-stage liver disease (MELD) score (AUC: 0.777). In the test cohort, NHR demonstrated AUC values comparable to MELD, with significantly higher AUCs than LHR and MHR (both p &lt; 0.05). Based on cutoff values for NHR and MELD, patients were classified into four risk subgroups: very-low (NHR &lt; 10 and MELD &lt;18), low (NHR ≥ 10 and MELD &lt;18), moderate (NHR &lt; 10 and MELD ≥18), and high (NHR ≥ 10 and MELD ≥18). The 12-month TF mortality rates in the training cohort were 7.2, 23.5, 30.8, and 51.4%, respectively, for these subgroups, while in the test cohort, the rates were 8.7, 20.5, 30.7, and 46.0%.ConclusionNHR is a valuable and accessible prognostic indicator for 12-month TF mortality in patients with HBV-related OHE. Patients with both NHR ≥ 10 and MELD ≥18 are at the highest risk of mortality.
Poly-ADP ribose polymerase (PARP) inhibitor regimens for platinum-sensitive ovarian cancer in randomized, double-blind, phase III controlled trials: protocol for a systematic review and network meta-analysis
Authors: Peng Xiaolian , Liu Jie 
Published: January 2025

IntroductionClinical trials have shown that PARP inhibitors are effective in treating patients with platinum-sensitive ovarian cancer. They have been indicated to improve progression-free survival or overall survival in patients with patients with platinum-sensitive ovarian cancer. However, there is insufficient comprehensive evidence regarding the comparison of different agents. To evaluate and compare the efficacy and side effects of various PARP inhibitors.MethodsWe plan to conduct a network meta-analysis that includes randomized, double-blind, controlled phase III trials of Niraparib, Rucaparib, Olaparib, or Veliparib in patients with Platinum-sensitive ovarian cancer. The primary outcomes will be progression-free survival or overall survival. The secondary outcome will be grade ≥ 3 of treatment-emergent adverse events. Published and unpublished studies will be retrieved through PubMed, Embase, the Cochrane Library, ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform from 1990 to 2023. We will use STATA V.14.0 to perform all analyses, and the RevMan software to report the risk of bias in the included studies. We will determine the quality of evidence using the GRADEpro GDT software online version. This is a protocol description only. Results and conclusions are subject to completion. This study will be based on published studies, since no primary data collection will be carried out, no formal ethical assessment is required. The network graph and meta-analysis will be used to compare all PARP inhibitors. Their ranking will employ a rankogram, surface under the cumulative ranking curves, and mean ranks.DiscussionOur study will answer the most important question in platinum-sensitive ovarian cancer: which PARPi should be preferred regarding efficacy and side effects? Trials of platinum-resistant or refractory ovarian cancer will be excluded. The limitation is that the results of network meta-analyses do not yet have the same level of evidence as direct head-to-head trials. However, it is a useful complementary method when direct comparative studies cannot be performed. We plan to publish the results of this systematic review and network meta-analysis in peer-reviewed scientific journals, conferences, and the mass media.Systematic review registrationPROSPERO, CRD42024511248, available from: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024511248.
Predatory bacteria can intensify lung-injury in a multidrug-resistant Acinetobacter baumannii pneumonia model in rat
Authors: Mohsenipour Zeinab , Kianian Farzaneh , Jahanbin Behnaz , Abtahi Hamid Reza , Ghazanfari Tooba , Edalatifard Maryam , Amanpour Saeid , Skurnik Mikael , Arazi Parya , Feizabadi Mohammad Mehdi 
Published: January 2025

IntroductionRespiratory tract infection caused by antibiotic-resistant bacteria are one of the most important causes of death worldwide. Therefore, in this study, we investigated the possibility of using predatory bacteria to improve the Acinetobacter baumannii pneumonia model in rat.MethodsMultidrug-resistant (MDR) A. baumannii clinical strain was used to induce pneumonia. In addition to the sham and predator control group, three treatment groups (n = 5) were studied with colistin, Bdellovibrio bacteriovorus HD100, and combination of predator and antibiotics. Also, the colistin MIC value for B. bacteriovorus HD100 (8 μg/mL) was determined for the first time to our knowledge. Removal of excess endotoxin from the predator suspension was performed with the help of organic solvents before inoculation of rats.ResultsThe most successful treatment was observed in the group treated with colistin followed by combined treatment. In the predator treatment group, the systemic spread of A. baumannii was lower than other treatment groups. However, treatment with predatory bacteria not only failed to reduce the pathogen load in the lungs to the same extent as the antibiotic treatment group, but also induced acute pulmonary and systemic inflammatory responses. Therefore, the rats showed the highest septic score (21.4 at 48 h) and did not survive more than 48 h.DiscussionThis is the first report of systemic complications of using B. bacteriovorus HD100 for infection control. According to our results, the effects of predatory bacteria in the in vivo environment are complex and many questions need to be answered before it can be introduced as a live antibiotic.
Whole genome sequencing of a novel carrageenan-degrading bacterium Photobacterium rosenbergii and oligosaccharide preparation
Authors: Chen Jing , Chen Runmin , Cheong Kit-Leong , Wang Zhuo , Li Rui , Jia Xuejing , Zhao Qiaoli , Liu Xiaofei , Song Bingbing , Zhong Saiyi 
Published: January 2025

IntroductionCarrageenan oligosaccharides are of significant interest due to their diverse bioactivities, necessitating efficient methods for their production. To this day, the discovery and isolation of microorganisms capable of effectively degrading carrageenan is still crucial for the production of carrageenan oligosaccharides. In addition, there are no current reports of bacteria of the genus Photobacterium capable of secreting κ-carrageenanase or degrading carrageenan.MethodsIn the current study, strain GDSX-4 was obtained from Gracilaria coronopifolia after enrichment culture, primary screening and rescreening and was initially characterized by morphology and 16SrDNA. The pure culture of strain GDSX-4 was further subjected to bacterial genome sequencing assembly and bioinformatic analysis. Specifically, homology group cluster (COG) annotation, CAZy (carbohydrate-active enzyme) database annotation and CAZyme genome clusters (CGCs) annotation were utilized to identify potential polysaccharide degradation functions. Enzymatic activity was assessed under different conditions, including substrate, temperature, pH, and the presence of metal ions. Hydrolysis products were analyzed using thin-layer chromatography (TLC) and electrospray ionization mass spectrometry (ESI-MS).ResultsPhotobacterium rosenbergii GDSX-4 is a Gram-negative bacterium isolated from the red algae, capable of degrading several polysaccharides. The draft genome was predicted to have 6,407,375 bp, 47.55% G+C content and 6,749 genes. Among them, 214 genes encoding carbohydrate enzymes were annotated, including carrageenase, agarose, alginate lyase, and chitinase. GDSX-4 exhibited remarkable carrageenan-degrading activity, with a specific enzyme activity of 46.94 U/mg. Optimal hydrolysis conditions were determined to be 40°C and pH 7.0, with the enzyme retaining 80% of its activity below 30°C and across a pH range of 4.0–10.0. Metal ions such as as K+, Na+, and Ba2+ enhanced enzymatic activity, while Ni2+, Mn2+, and Cu2+ had inhibitory effects. kappa-carrageenan was totally hydrolyzed into oligosaccharides with degrees of polymerization ranging from 2 to 6.DiscussionThese findings highlight the potential of GDSX-4 for the efficient production of carrageenan oligosaccharides, paving the way for applications in the food and agricultural industries. Future studies may focus on the efficient expression of κ-carrageenase and expand its industrial application in the preparation of oligosaccharides.
Global trends in migraine and anxiety over the past 10 years: a bibliometric analysis
Authors: Huang Biao , Chen Weining , Peng Chunmei , Wang Yu , Shen Xiuli , Zhang Qi , Yang Liu , Wu Jun 
Published: January 2025

BackgroundRecent studies have shown that migraine significantly increases the incidence of anxiety and is positively correlated with the severity and frequency of migraine. The relationship between migraine and anxiety has attracted extensive attention. This study focused on the association between migraine and anxiety, aiming to predict potential future research trends.MethodsA bibliometric analysis was conducted using publications from the Core Collection of Web of Science. We utilized CiteSpace.5.8.R3 and VOSviewer 1.6.17 to evaluate the value of articles over the past 10 years.ResultsThe number of publications has increased significantly over the past 10 years. The cooperative network analysis shows that the United States is the most collaborative country. Additionally, Harvard University is the institution and Richard B. Lipton the individual with the highest number of studies on migraine. The analysis of keyword outbreaks indicates that the strong citation burst words are closely related to sex differences, activation, allodynia, and preventive treatment, which represent emerging new research areas and potential hotspots for future research.ConclusionAn overall upward trend in the research of migraine and anxiety was observed. Sex differences, functional magnetic resonance imaging (fMRI), activation, allodynia, and preventive treatment are predicted to be hotspots in the future.
Children with autistic spectrum disorder can imagine actions— what can this reveal about the Broken Mirror Hypothesis?
Authors: Galli Jessica , Dusi Laura , Garofalo Gioacchino , Brizzi Alessandra , Gritti Michela , Polo Federica , Fazzi Elisa , Buccino Giovanni 
Published: January 2025

ObjectiveThis study investigated whether children with Autistic Spectrum Disorder (ASD) can imagine object directed actions similarly to their typically developed (TD) peers.Study designWe tested the ability to imagine goal directed actions in children with ASD (n = 18) and TD (n = 18) peers by means of VMIQ-2 questionnaire and a novel behavioral task, in which children were requested to imagine some daily actions, after seeing them through videoclips presented on a computer screen. Observed actions lasted 4 s and children were requested to follow the same time course during imagination. During this motor imagery (MI) task, children were interrupted at a specific timepoint (e.g., at 1.5 s) from the beginning of the task. Afterwards, they had to select one of two frames extracted from the videoclips: one showed the correct timepoint at which the imagined action was stopped, the other depicted an earlier or later timepoint. Children had to press the key associated to the correct frame to provide their responses.ResultsBoth groups performed similarly in the questionnaire and in the novel MI task, where they showed the same error rate. Errors distribution suggests that all children exploited a similar strategy to solve the task, being errors mainly distributed in judging the later frame.ConclusionThese findings support the view that children with ASD can imagine actions similarly to their TD peers. These results do not fully support the Broken Mirror Hypothesis and may encourage the use of MI as a cognitive strategy in the rehabilitation of autism.