bluuebunny/crossref_metadata_2025_split huggingface dataset:
TACE plus lenvatinib and tislelizumab for intermediate-stage hepatocellular carcinoma beyond up-to-11 criteria: a multicenter cohort study
Authors: Chen Song , Shuangyan Tang , Shi Feng , Cai Hongjie , Wu Zhiqiang , Wang Liguang , Ma Ping , Zhou Yuanmin , Mai Qicong , Wang Fan , Lai Jiaming , Chen Xiaoming , Chen Huanwei , Guo Wenbo 
Published: July 2024

BackgroundIntermediate-stage (BCLC-B) hepatocellular carcinoma (HCC) beyond the up-to-11 criteria represent a significant therapeutic challenge due to high and heterogeneous tumor burden. This study evaluated the effectiveness and safety of transarterial chemoembolization (TACE) in combination with lenvatinib and tislelizumab for these patients.MethodsIn this retrospective cohort study, patients with unresectable intermediate-stage HCC beyond the up-to-11 criteria were enrolled and divided into TACE monotherapy (T), TACE combined with lenvatinib (TL), or TACE plus lenvatinib and tislelizumab (TLT) group based on the first-line treatment, respectively. The primary endpoint was overall survival (OS). The secondary outcomes included progression-free survival (PFS), tumor response according to RESIST1.1 and modified RECIST, and adverse events (AEs).ResultsThere were 38, 45, and 66 patients in the T, TL, and TLT groups, respectively. The TLT group exhibited significantly higher ORR and DCR than the other two groups, as assessed by either mRECIST or RECIST 1.1 (all P&lt;0.05). Median PFS and OS were significantly longer in the TLT group compared with the T group (PFS: 8.5 vs. 4.4 months; OS: 31.5 vs. 18.5 months; all P&lt;0.001) and TL group (PFS: 8.5 vs. 5.5 months; OS: 31.5 vs. 20.5 months; all P&lt;0.05). The incidence of TRAEs was slightly higher in the TLT and TL groups than in the T group, while all the toxicities were tolerable. No treatment-related death occurred in all groups.ConclusionsTACE combined with lenvatinib and tislelizumab significantly improved the survival benefit compared with TACE monotherapy and TACE plus lenvatinib in patients with intermediate-stage HCC beyond the up-to-11 criteria, with an acceptable safety profile.
Effective debriefings in the clinical setting: a pilot study to test the impact of an evidence based debriefing app on anesthesia care providers’ performance
Authors: Seelandt Julia C , Schneider Jeannine , Kolbe Michaela , Grande Bastian 
Published: July 2024

BackgroundDebriefing enhances team learning, performance, and patient safety. Despite its benefits, it’s underused. To address this, we developed an evidence-based debriefing app.MethodsThis pilot study, conducted at a Swiss hospital, evaluated team performance during two anesthesia inductions using the Team Performance Scale (TPS). Following the first induction, teams engaged with the Zurich Debriefing App, with debriefing sessions meticulously recorded for subsequent evaluation. To mitigate bias, raters underwent comprehensive TPS training. The debriefings were analyzed through the DE-CODE framework. We utilized paired t-tests to examine performance improvements and linear regressions to assess the impact of reflective statements on performance, moderated by psychological safety.ResultsTeam performance significantly improved from the first to the second induction (t (9) = −2.512, p = 0.033). Senior physicians’ (n = 8) reflective statements predicted post-assessment TPS scores (R2 = 0.732, p = 0.061), while consultants (n = 7) and nurse anesthetists (n = 10) did not. Interaction analysis revealed no moderation effects, but a main effect indicated the significance of senior physicians’ reflective statements.ConclusionThis pilot study confirms the efficacy of the evidence-based debriefing app in enhancing anesthesia team performance. Senior physicians’ reflective statements positively influenced performance; however, no moderation effects were observed. The study highlights the potential of debriefing apps to streamline and enhance team debriefing processes, with significant implications for improving clinical practice and patient safety. Further research is needed to validate these findings on a larger scale and optimize the integration of debriefing into routine clinical practice.
Multi-omics analysis of the biological mechanism of the pathogenesis of non-alcoholic fatty liver disease
Authors: Lin Jie , Zhang Ruyi , Liu Huaie , Zhu Yunzhen , Dong Ningling , Qu Qiu , Bi Hongyan , Zhang Lihua , Luo Ou , Sun Lei , Ma Mengjuan , You Jing 
Published: July 2024

BackgroundNon-alcoholic fatty liver disease (NAFLD) is a type of liver metabolic syndrome. Employing multi-omics analyses encompassing the microbiome, metabolome and transcriptome is crucial for comprehensively elucidating the biological processes underlying NAFLD.MethodsHepatic tissue, blood and fecal samples were obtained from 9 NAFLD model mice and 8 normal control mice. Total fecal microbiota DNA was extracted, and 16S rRNA was amplified, to analyze alterations in the gut microbiota (GM) induced by NAFLD. Subsequently, diagnostic strains for NAFLD were screened, and their functional aspects were examined. Differential metabolites and differentially expressed genes were also screened, followed by enrichment analysis. Correlations between the differential microbiota and metabolites, as well as between the DEGs and differential metabolites were studied. A collinear network involving key genes-, microbiota-and metabolites was constructed.ResultsIleibacterium and Ruminococcaceae, both belonging to Firmicutes; Olsenella, Duncaniella and Paramuribaculum from Bacteroidota; and Bifidobacterium, Coriobacteriaceae_UCG_002 and Olsenella from Actinobacteriota were identified as characteristic strains associated with NAFLD. Additionally, differentially expressed metabolites were predominantly enriched in tryptophan, linoleic acid and methylhistidine metabolism pathways. The functions of 2,510 differentially expressed genes were found to be associated with disease occurrence. Furthermore, a network comprising 8 key strains, 14 key genes and 83 key metabolites was constructed.ConclusionThrough this study, we conducted a comprehensive analysis of NAFLD alterations, exploring the gut microbiota, genes and metabolites of the results offer insights into the speculated biological mechanisms underlying NAFLD.
Frontier and hotspot evolution in cerebrotendinous xanthomatosis: a bibliometric analysis from 1993 to 2023
Authors: Luo Fei , Ding Yali , Zhang Shanyun , Diao Juanjuan , Yuan Bin 
Published: July 2024

BackgroundCerebrotendinous xanthomatosis (CTX) is an autosomal recessive disease associated with lipid metabolic disorders. Because of its clinical diversity and rarity, the diagnosis is often unclear. However, there is still a lack of reports on bibliometric analysis of CTX. The aim of this study was to assess the progress and research developments of CTX over the past three decades, identify emerging trends, and establish novel directions for future research.MethodsThe eligible literature were screened from the Web of Science Core Collection (WoSCC) database. The annual publication, countries, institutions, authors, journals, keywords and references were visually analyzed by Microsoft Excel 2019, CiteSpace 6.2.R4, VOSviewer 1.6.18 and online bibliometrics website (https://bibliometric.com/).ResultsA total of 561 publications from WoSCC were included in this study. The United States is the country with the largest number of publications, and Karolinska Institutet is the institution with the largest number of publications. Björkhem I. ranks as the most published and cited author in the last three decades. Journal of Lipid Research is the most widely published and cited journal. The strongest burst of keywords is “diagnosis.”ConclusionUnraveling the pathogenesis of CTX and improving its diagnosis and treatment continue to be critical challenges that require urgent attention. Future research endeavors will be centered on enhancing the efficiency and accuracy of early diagnosis and intervention.
Association between psychiatric disorders and intracranial aneurysms: evidence from Mendelian randomization analysis
Authors: Bao Sichen , Xing Zhenqiu , He Shengkai , Hu Xiaowei , Yang Jianjing , Zhou Bingqing 
Published: July 2024

ObjectiveSeveral studies have explored the relationship between intracranial aneurysms and psychiatric disorders; nevertheless, the causal connection remains ambiguous. This study aimed to evaluate the causal link between intracranial aneurysms and specific psychiatric disorders.MethodsA two-sample Mendelian randomization (MR) analysis was conducted utilizing aggregated genome-wide association study (GWAS) data from the International Stroke Genetics Association for Intracranial Aneurysms (IAs), unruptured Intracranial Aneurysm (uIA), and aneurysmal Subarachnoid Hemorrhage (aSAH). Psychiatric disorder data, encompassing Schizophrenia (SCZ), Bipolar Disorder (BD), and Panic Disorder (PD), were sourced from the Psychiatric Genomics Consortium (PGC), while Cognitive Impairment (CI) data, comprising Cognitive Function (CF) and Cognitive Performance (CP), were obtained from IEU OpenGWAS publications. Causal effects were evaluated using inverse variance weighted (IVW), MR-Egger, and weighted median methods, with the robustness of findings assessed via sensitivity analyses employing diverse methodological approaches.ResultsOur MR analysis indicated no discernible causal link between intracranial aneurysm (IA) and an elevated susceptibility to psychiatric disorders. However, among individuals with genetically predisposed unruptured intracranial aneurysms (uIA), there was a modest reduction in the risk of SCZ (IVW odds ratio [OR] = 0.95, 95% confidence interval [CI] 0.92–0.98, p = 0.0002). Similarly, IAs also exhibited a moderate reduction in SCZ risk (OR = 0.92, 95% CI 0.86–0.99, p = 0.02). Nevertheless, limited evidence was found to support a causal association between intracranial aneurysms and the risk of the other three psychiatric disorders.ConclusionOur findings furnish compelling evidence suggesting a causal influence of intracranial aneurysms on psychiatric disorders, specifically, both IAs and uIA exhibit a negative causal association with SCZ.
Emerging biomarkers for non-invasive diagnosis and treatment of cancer: a systematic review
Authors: Zakari Suleiman , Niels Nguedia K. , Olagunju Grace V. , Nnaji Precious C. , Ogunniyi Oluwabusayo , Tebamifor Mercy , Israel Emmanuel N. , Atawodi Sunday E. , Ogunlana Olubanke Olujoke 
Published: July 2024

Cancer remains a global health challenge, necessitating continuous advancements in diagnostic and treatment strategies. This review focuses on the utility of non-invasive biomarkers in cancer diagnosis and treatment, their role in early detection, disease monitoring, and personalized therapeutic interventions. Through a systematic review of the literature, we identified 45 relevant studies that highlight the potential of these biomarkers across various cancer types, such as breast, prostate, lung, and colorectal cancers. The non-invasive biomarkers discussed include liquid biopsies, epigenetic markers, non-coding RNAs, exosomal cargo, and metabolites. Notably, liquid biopsies, particularly those based on circulating tumour DNA (ctDNA), have emerged as the most promising method for early, non-invasive cancer detection due to their ability to provide comprehensive genetic and epigenetic information from easily accessible blood samples. This review demonstrates how non-invasive biomarkers can facilitate early cancer detection, accurate subtyping, and tailored treatment strategies, thereby improving patient outcomes. It underscores the transformative potential of non-invasive biomarkers in oncology, highlighting their application for enhancing early detection, survival rates, and treatment precision in cancer care.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42023474749 PROSPERO, identifier CRD42023474749.
Construction and validation of prognostic signatures related to mitochondria and macrophage polarization in gastric cancer
Authors: Zhang Yan , Cao Jian , Yuan Zhen , Zuo Hao , Yao Jiacong , Tu Xiaodie , Gu Xinhua 
Published: July 2024

BackgroundIncreasing evidence reveals the involvement of mitochondria and macrophage polarisation in tumourigenesis and progression. This study aimed to establish mitochondria and macrophage polarisation-associated molecular signatures to predict prognosis in gastric cancer (GC) by single-cell and transcriptional data.MethodsInitially, candidate genes associated with mitochondria and macrophage polarisation were identified by differential expression analysis and weighted gene co-expression network analysis. Subsequently, candidate genes were incorporated in univariateCox analysis and LASSO to acquire prognostic genes in GC, and risk model was created. Furthermore, independent prognostic indicators were screened by combining risk score with clinical characteristics, and a nomogram was created to forecast survival in GC patients. Further, in single-cell data analysis, cell clusters and cell subpopulations were yielded, followed by the completion of pseudo-time analysis. Furthermore, a more comprehensive immunological analysis was executed to uncover the relationship between GC and immunological characteristics. Ultimately, expression level of prognostic genes was validated through public datasets and qRT-PCR.ResultsA risk model including six prognostic genes (GPX3, GJA1, VCAN, RGS2, LOX, and CTHRC1) associated with mitochondria and macrophage polarisation was developed, which was efficient in forecasting the survival of GC patients. The GC patients were categorized into high-/low-risk subgroups in accordance with median risk score, with the high-risk subgroup having lower survival rates. Afterwards, a nomogram incorporating risk score and age was generated, and it had significant predictive value for predicting GC survival with higher predictive accuracy than risk model. Immunological analyses revealed showed higher levels of M2 macrophage infiltration in high-risk subgroup and the strongest positive correlation between risk score and M2 macrophages. Besides, further analyses demonstrated a better outcome for immunotherapy in low-risk patients. In single-cell and pseudo-time analyses, stromal cells were identified as key cells, and a relatively complete developmental trajectory existed for stromal C1 in three subclasses. Ultimately, expression analysis revealed that the expression trend of RGS2, GJA1, GPX3, and VCAN was consistent with the results of the TCGA-GC dataset.ConclusionOur findings demonstrated that a novel prognostic model constructed in accordance with six prognostic genes might facilitate the improvement of personalised prognosis and treatment of GC patients.
A network meta-analysis of efficacy and safety for first-line and maintenance therapies in patients with unresectable colorectal liver metastases
Authors: Jiang Yunlin , Shao Taihang , Zhao Mingye , Xue Yahong , Zheng Xueping 
Published: July 2024

Background: Evidence comparing the efficacy of different treatments for patients with unresectable colorectal liver metastases (CRLM) receiving first-line or maintenance therapy is sparse. We aimed to assess the efficacy and safety of these treatments, with a distinct focus on evaluating first-line and maintenance treatments separately.Methods: We conducted Bayesian network meta-analyses, sourcing English-language randomized controlled trials (RCTs) published through July 2023 from databases including PubMed, Embase, the Cochrane Library, ClinicalTrials.gov, and key conference proceedings. Phase Ⅱ or Ⅲ trials that assessed two or more therapeutic regimens were included. Primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), objective response rate (ORR), adverse events graded as 3 or above (SAE), and R0 liver resection rate. Hazards Ratios (HRs) and 95% confidence intervals (CI) were used as effect size for OS and PFS, Odds Ratios (ORs) and 95% CI were used for ORR, SAEs and R0 resection rate. Subgroup and sensitive analyses were conducted to analysis the model uncertainty (PROSPERO: CRD42023420498).Results: 56 RCTs were included (50 for first-line treatment, six for maintenance therapies), with a total of 21,323 patients. Regarding first-line, for OS, the top three mechanisms were: local treatment + single-drug chemotherapy (SingleCT), Targeted therapy (TAR)+SingleCT, and TAR + multi-drug chemotherapy (MultiCT). Resection or ablation (R/A)+SingleCT, S1, and Cetuximab + intensified fluorouracil-based combination chemotherapy (ICTFU) were identified as the best treatments. For PFS, the top three mechanisms were: Immune therapy + TAR + MultiCT, multi-targeted therapy (MultiTAR), TAR + SingleCT. The top three treatments were: Atezolizumab + Bevacizumab + fluorouracil-based combination chemotherapy (CTFU), TAS-102+bevacizumab, Bevacizumab + ICTFU. Cetuximab + CTFU was the best choice for RAS/RAF wild-type patients. Regarding maintenance treatment, Bevacizumab + SingleCT and Adavosertib were the best options for OS and PFS, respectively. For safety, MultiCT was the safest, followed by local treatment + MultiCT, TAR + MultiCT caused the most SAEs. Bevacizumab plus chemotherapy was found to be the safest among all targeted combination therapies.Conclusion: In first-line, local treatment or targeted therapsy plus chemotherapy are the best mechanisms. R/A + SingleCT or CTFU performed the best for OS, Atezolizumab + Bevacizumab + ICTFU was the best option regarding PFS. For RAS/RAF wild-type patients, Cetuximab + CTFU was the optimal option. Monotherapy may be preferred choice for maintenance treatment. Combination therapy resulted in more SAEs when compared to standard chemotherapy.
LSD1 inhibition by tranylcypromine hydrochloride reduces alkali burn-induced corneal neovascularization and ferroptosis by suppressing HIF-1α pathway
Authors: Deng Qian , Gao Yuelan , Wang Yujin , Mao Jiewen , Yan Yulin , Yang Zixian , Cong Yuyu , Yang Yanning , Wan Shanshan 
Published: July 2024

BackgroundCorneal neovascularization (CNV) is a sight-threatening condition that necessitates epigenetic control. The role of lysine-specific demethylase 1 (LSD1) in CNV remains unclear, despite its established significance in tumor angiogenesis regulation.MethodsAn alkali burn-induced CNV mouse model was used in vivo. The effects of LSD1 inhibitor tranylcypromine hydrochloride (TCP) were examined through slit lamp, histological staining, and immunofluorescence. The expression of malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione (GSH) levels were assessed in corneal tissues. Oxidative stress and ferrous ion expression during CNV were determined using 4-HNE, GPX4, and FerroOrange staining. In vitro, a hypoxia-reoxygenation (H/R) model was established using human umbilical vein endothelial cells (HUVECs) to study LSD1 or hypoxia-inducible factor (HIF-1α) knockdown and lentiviral overexpression of HIF-1α. The effects on HUVECs migration, invasion, and angiogenesis were evaluated through cell scratching assay, transwell migration assay and tube formation assay. The role of ferroptosis was investigated using ROS staining, FerroOrange staining, and key ferroptosis proteins. Further, The JAK2/STAT3 pathway’s involvement in CNV regulation was explored through in vivo experiments with subconjunctival injection of AG490.ResultsThe results showed a substantial correlation between corneal damage and LSD1 levels. In addition, HIF-1α expression was also elevated after alkali burns, and subconjunctival injection of TCP reduced corneal inflammation and neovascularization. Corneal alkali burns increased ROS levels and reduced antioxidative stress indicators, accompanied by elevated ferrous ion levels, which were reversed by TCP injection. In vitro, TCP or siRNAs inhibited H/R-induced ferroptosis and angiogenesis in HUVECs by affecting specific protein expressions and MDA, SOD, and GSH levels. HIF-1α levels, associated with ROS production, ferroptosis, and angiogenesis, increased during H/R, but were reversed by TCP or siRNA administration. HIF-1α overexpression counteracted the effects of LSD1 inhibition. Additionally, AG490 injection effectively reduced HIF-1α and VEGFA expression in the CNV model.DiscussionThese findings suggest that LSD1 inhibition via the HIF-1α-driven pathway prevents angiogenesis, oxidative stress, and ferroptosis in corneal alkali burn-induced CNV, highlighting LSD1 as a potential therapeutic target.
Safety profiles of doxycycline, minocycline, and tigecycline in pediatric patients: a real-world pharmacovigilance analysis based on the FAERS database
Authors: Qiao Yanli , Chen Yechao , Wang Qiaoyun , Liu Jingrui , Guo Xiaohui , Gu Qiaoling , Ding Peng , Zhang Haixia , Mei Hongliang 
Published: July 2024

IntroductionRecently, the rise of antibiotic resistance has prompted a reconsideration of tetracyclines. However, existing studies are inadequate in assessing the pediatric safety of this class of antibiotics. To address the gap, our study aims to comprehensively assess the safety of tetracyclines in children.MethodsAdverse event (AE) reports from January 2005 to September 2023 were obtained from the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) database, and reporting odds ratio (ROR) was performed to identify potential risk signals in children under 18 years old who were administered any of the three tetracyclines: doxycycline, minocycline, and tigecycline.ResultsA total of 1903 AE cases were included in our study: 782 for doxycycline, 981 for minocycline, and 140 for tigecycline. Doxycycline and tigecycline were predominantly associated with “general disorders and administration site conditions” and “gastrointestinal disorders,” while minocycline was more frequently linked to “skin and subcutaneous tissue disorders” and “gastrointestinal disorders.” Psychiatric risks predominantly included depression, suicidal ideation, and suicide attempt. In the category of skin and subcutaneous tissues, 30.88% of the minocycline-induced drug reaction with eosinophilia and systemic symptoms (DRESS) cases resulted in death, alongside a high occurrence of co-occurring AEs such as multiple organ dysfunction syndrome, Type 1 Diabetes Mellitus (T1DM), and autoimmune thyroiditis. As for the endocrine system, both doxycycline and minocycline were found to potentially increase the risk of thyroid dysfunction. For children under the age of 8, doxycycline was associated with tooth discoloration (N = 7, ROR = 20.11%, 95% CI: 9.48–42.67), although it remained unclear whether the discoloration was permanent.ConclusionOur findings indicated that for pediatric patients, the majority of results were in line with the prescribing information and previous studies, and minocycline tended to cause more frequent and severe AEs than doxycycline. However, it is noteworthy that exceptions were found for psychiatric disorders and thyroid dysfunction associated with doxycycline, which are not mentioned in its FDA prescribing information. Additionally, further safety studies on tigecycline are still needed for children. When prescribing tetracyclines to pediatric patients, a careful risk-benefit assessment is crucial.