bluuebunny/crossref_metadata_2025_split huggingface dataset:
Upregulation of CRISP3 and its clinical values in adult sepsis: a comprehensive analysis based on microarrays and a two-retrospective-cohort study
Authors: Zhang An-qiang , Wen Da-lin , Ma Xin-xin , Zhang Fei , Chen Guo-sheng , Maimaiti Kelimu , Xu Gang , Jiang Jian-xin , Lu Hong-xiang 
Published: November 2024

BackgroundCurrent lines of evidence indicate that cysteine-rich secretory protein 3 (CRISP3) is an immunoregulatory factor. Nevertheless, no study has explored the relationships between the values of CRISP3 and sepsis.MethodsWe conducted a comprehensive literature search and meta-analysis from the Gene Expression Omnibus (GEO) and ArrayExpress to determine the expression of CRISP3 in sepsis patients. Then, we explored whether plasma CRISP3 could serve as a potential biomarker to predict the risk of sepsis via two retrospective trauma cohorts. We evaluated the prediction power using the area under the curve (AUC).ResultsA total of 23 datasets were recruited for the comprehensive meta-analysis, and the combined standardized mean difference (SMD) of CRISP3 was 0.90 (0.50–1.30) (p &lt; 0.001), suggesting that CRISP3 was overexpressed in sepsis patients. Meanwhile, sepsis patients had higher CRISP3 concentrations than non-sepsis patients in 54 trauma patients (p &lt; 0.001). Plasma CRISP3 on admission was significantly associated with the incidence of sepsis [OR = 1.004 (1.002–1.006), p &lt; 0.001]. As a predictive biomarker, CRISP3 obtained a better AUC [0.811 (0.681–0.905)] than C-reactive protein (CRP) [0.605 (0.463–0.735)], procalcitonin (PCT) [0.554 (0.412–0.689)], and Sequential Organ Failure Assessment (SOFA) [0.754 (0.618–0.861)]. Additionally, the clinical relationships between plasma CRISP3 and sepsis were verified in another trauma cohort with 166 patients [OR = 1.002 (1.001–1.003), p &lt; 0.001]. The AUC of CRISP3 was 0.772 (0.701–0.834), which was better than that of CRP [0.521 (0.442–0.599)] and PCT [0.531 (0.452–0.609)], but not SOFA [0.791 (0.717–0.853)].ConclusionOur study indicated and validated that CRISP3 was highly expressed in sepsis. More importantly, CRISP3 may serve as a latent biomarker to predict the risk of sepsis.
Porcine non-conventional B-1-like cells are a potent source of Streptococcus suis-binding IgM
Authors: Seidel Anne-Marie , Kauffold Johannes , Protschka Martina , Baums Christoph G. , Alber Gottfried , Eschke Maria 
Published: November 2024

IntroductionStreptococcus suis serotype (cps) 2 is an important bacterial pathogen in piglet nurseries and an emerging zoonotic agent without effective vaccines available. Immunoglobulin (Ig)M plays an essential role in host defense against S. suis. In mice, non-conventional B-1 cells are a major source of protective IgM against encapsulated bacterial pathogens, such as S. pneumoniae. Two IgM+CD21− B-1-like cell subpopulations, distinguishable by CD11R1 expression, were described in pigs, but their properties and functions are poorly understood. This study aimed at a first characterization of the porcine early IgM B cell response against S. suis cps 2.MethodsWe analyzed the same healthy pigs, naturally colonized by different S. suis serotypes, including cps 2, at four and eight weeks of age serologically and determined the frequency of different peripheral B cell subpopulations by flow cytometry. Furthermore, we isolated conventional IgM+CD21+ B-2 cells as well as non-conventional B-1-like cell subpopulations from peripheral blood of eight-weeks-old pigs to evaluate their potential of IgM secretion in response to innate and adaptive stimuli in vitro.ResultsBetween the fourth and eighth week of life, a characteristic increase of S. suis cps 2-binding serum IgM antibodies, restricting bacterial growth, was observed. Moreover, we show for the first time that the significant increase of anti-S. suis serum IgM is associated with a relative increase of peripheral non-conventional IgM+CD21− B-1-like cells in vivo, particularly of the IgM+CD21− CD11R1− subpopulation. Noteworthy, sorted IgM+CD21− CD11R1− B-1-like cells from eight-weeks-old pigs spontaneously secreted IgM in vitro. In addition, both non-conventional IgM+CD21− B cell subpopulations, in contrast to conventional IgM+CD21+ B-2 cells, produced anti-S. suis IgM upon toll-like receptor (TLR) stimulation underlining their innate-like characteristics. We furthermore observed that both B-1-like subpopulations secrete S. suis cps 2-binding IgM upon stimulation with T cell-associated factors with highest amounts in IgM+CD21−CD11R1− B-1-like cells even exceeding anti-S. suis IgM levels produced by B-2 cells.ConclusionPorcine non-conventional B-1-like cells are a potent source of S. suis-binding IgM indicating a role in immunity during a critical phase of piglet rearing.
GVHD after CAR T-cell therapy post allogeneic hematopoietic cell transplantation — successfully treated by extracorporeal photopheresis
Authors: Farid Kiavasch Mohammad Nejad , Bug Gesine , Schmitt Anita , Lang Fabian , Schubert Maria-Luisa , Haberkorn Uwe , Müller-Tidow Carsten , Dreger Peter , Schmitt Michael 
Published: November 2024

IntroductionCAR T-cell therapy is highly effective, but also associated with unique toxicities. Because of the origin of T cells in patients who previously underwent allogeneic hematopoietic cell transplantation (alloHCT), graft-versus-host disease (GVHD) in the post-CAR T-cell setting poses a relevant concern but is only scarcely studied. Potential risk factors and mitigation strategies (from CAR T-cell modifications to clinical management) are yet to be determined.MethodsSharing our retrospective experience and a mini-review of the literature, our aim is to better understand the frequency and risk of the potential occurrence of GVHD after CAR T cells, which are most likely underestimated. ResultsHere, we present a cohort of 11 patients with symptoms suggestive of GVHD out of 25 allografted patients treated with CAR T cells, of whom 3 patients (12%) had GVHD most likely triggered by the preceding CAR T-cell treatment. Severe chronic pulmonary GVHD occurred in a patient after CD19-directed CAR T-cell therapy. Extracorporeal photopheresis (ECP) mediated successful long-term control of GVHD without causing relapse of the underlying disease. Discussion/ConclusionIn conclusion, CD19-directed CAR T-cell therapy seems to be feasible in patients after alloHCT but might comprise the potential risk of triggering GVHD, most likely depending on the T-cell source, donor compatibility, and the specific CAR construct used.
Reorganized brain functional network topology in stable and progressive mild cognitive impairment
Authors: Xue Chen , Zheng Darui , Ruan Yiming , Cao Xuan , Zhang Xulian , Qi Wenzhang , Yuan Qianqian , Liang Xuhong , Huang Qingling 
Published: November 2024

AIMMild cognitive impairment (MCI) includes two distinct subtypes, namely progressive MCI (pMCI) and stable MCI (sMCI). The objective of this study was to identify the topological reorganization of brain functional networks in patients with pMCI and sMCI.MethodsResting-state functional magnetic resonance imaging (rs-fMRI) was applied to patients with pMCI, sMCI and healthy controls. Graph theory was applied to study the topological characteristics of the brain’s functional networks, examining global and nodal metrics, modularity, and rich-club organization. Analysis of covariance and two sample t-tests were applied to assess differences in topological attributes between patient groups, alongside correlation analysis, which examined the value of changing topological attributes in predicting various clinical outcomes.ResultsSignificant differences between each group with regard to network metrics were observed. These included clustering coefficients and small-worldness. At the nodal level, several nodes with an abnormal degree centrality and nodal efficiency were detected. In rich club, pMCI and sMCI patients showed declined connectivity compared with HC. Significant differences were observed in the intra- and inter-module connections among the three groups. Particularly noteworthy was the irreplaceable role of the cerebellar module in network interactions.ConclusionOur study revealed significant differences in network topological properties among sMCI, pMCI and HC patients, which were significantly correlated with cognitive function. Most notably, the cerebellar module played a crucial role in the overall network interactions. In conclusion, these findings could aid in the development of imaging markers used to expedite diagnosis and intervention prior to Alzheimer’s disease onset.
Silymarin administration after cerebral ischemia improves survival of obese mice by increasing cortical BDNF and IGF1 levels
Authors: Rodríguez-Cortés Yesica María , Ramírez-Carreto Ricardo Jair , Rodríguez-Barrena Julia Isabel , Salazar-Castro Marelly , Chavarría Anahí 
Published: November 2024

BackgroundObesity is associated with a systemic inflammatory state that contributes to neuroinflammation and increases the risk of stroke at an early age. Stroke is the third leading cause of death worldwide and the leading cause of permanent disability. This work aimed to assess whether obesity-induced neuroinflammation can be a prognostic stroke factor that can be improved with oral administration of silymarin, an anti-inflammatory and neuroprotective drug.MethodsMale C57/Bl6 mice were used to establish an obesity model through a high-fat diet (HFD) for 12 weeks. Cerebral ischemia was performed with photothrombosis in the left motor cortex at the end of the diet. Following the induction of ischemia, silymarin (100 mg/kg) was administered orally for 14 days. Levels of pro-inflammatory (IL1β, TNFα, and MCP1) and anti-inflammatory markers (IL4, IL10), neurotrophic factors (IGF1, BDNF), and CX3CL1 were assessed in the cortex and striatum using ELISA.ResultsMice on the HFD gained significantly more weight than control subjects and exhibited altered glucose metabolism, which was improved after silymarin treatment. The survival rate was significantly lower in HFD mice (52.2%) compared to control mice (86%). Silymarin treatment improved survival in both ischemic groups (non-diet control: 95.7%, HFD: 78.3%). Silymarin raised cortical TNFα, IL4, IL10, IGF1, BDNF, and CX3CL1 levels in the HFD group with stroke, while the striatum did not present relevant differences.ConclusionOur findings suggest that silymarin improves glucose metabolism, possibly impacting post-stroke survival in obese mice. The increased levels of neurotrophic factors BDNF and IGF1, along with microglial regulatory factor CX3CL1, may contribute to the improved survival observed. These results indicate that silymarin could be a potential therapeutic option for managing neuroinflammation and enhancing post-stroke outcomes in obese individuals.
Accuracy of diagnostic tests for perilymphatic fistula: protocol for a systematic review
Authors: Situkho Maksym , Ikezono Tetsuo , Myhrum Marte , Rødvik Arne Kirkhorn , Maeda Yukihide , Matsuda Han , Sawada Masafumi , Jablonski Greg Eigner 
Published: November 2024

Perilymphatic fistula (PLF) is a challenging inner ear condition, characterized by the abnormal connection between inner and middle ear and subsequent leakage of inner ear liquid (perilymph) into the middle ear. Early surgical intervention for PLF might lead to favorable audiological and vestibular outcomes. The conventional reference standard of PLF detection is the intraoperative visualization of perilymph leakage during explorative tympanotomy or endoscopic inspection; the specificity and sensitivity of this method is unknown. Systematic reviews assessing the accuracy of diagnostic tests for PLF are not available.ObjectiveTo systematically review the literature for qualitative evidence exploring the diagnostic tests for the PLF diagnosis. The proposed systematic review will answer the following question: What is the accuracy of diagnostic tests in detecting perilymphatic fistula in humans?MethodsEligibility criteria: original peer-reviewed articles regarding studies on humans of any age containing data with diagnostic test accuracy estimation (sensitivity and specificity) for PLF diagnosis or in which diagnostic test accuracy could be calculated based on data provided, without language, study design or study date limits. MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, Scopus, and Web of Science will be searched for eligible articles. Additional manual searches will be performed. Covidence software will be used for title and abstract screening, full text review and data extraction. The risk of bias assessment will be conducted using the Quality Assessment of Diagnostic Test Accuracy 2 (QUADAS-2) tool. If two or more high-quality articles evaluating the same diagnostic test will be identified, their findings will be quantitatively synthesized; if a quantitative synthesis is not feasible, the results will be described in a narrative summary. Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework will be used to evaluate evidence strength. Study funded by Oslo University Hospital.
Exploration of the value of concurrent chemotherapy for T2N1 nasopharyngeal carcinoma under intensity modulated radiotherapy mode
Authors: Liao Kai , Zhang Jian , Qiu Wenze , Zheng Ronghui 
Published: November 2024

ProblemIn the era of intensity-modulated radiation therapy (IMRT), the status of concurrent chemoradiotherapy(CCRT) for stage II nasopharyngeal carcinoma(NPC), particularly for patients in T2N1 subtype, remains controversial nowadays.AimThis study exclusively aims to explore the value of concurrent chemotherapy in the treatment of T2N1 NPC under IMRT mode.MethodsA retrospective analysis was conducted on 218 cases of T2N1 NPC patients treated at our hospital from January 2015 to December 2020, comprising 75 cases treated with IMRT and 143 cases treated with CCRT. The study compared therapeutic outcomes and side effects between the two groups.ResultsThe 5-year progression-free survival (PFS), overall survival (OS), locoregional relapse-free survival (LRRFS) and,distant metastasis-free survival (DMFS) estimated by the K-M method for the IMRT vs. CCRT groups were 86.1% vs. 85.1%,89.3% vs. 87.9%, 95.9% vs. 94.9%,and 90.2% vs. 89.1%, respectively, with no statistically significant differences (Log-rank P&gt;0.05 for all comparisons). Cox regression analysis identified Epstein-Barr virus (EBV) DNA copy level (≥1000 vs. &lt;1000 copies/ml)(the cutoff value was determined through the ROC curve), lymph node necrosis (yes vs. no) and extra-nodal extension (yes vs. no) as independent prognostic factors for PFS(P&lt;0.05 for all comparisons). Subgroup analysis indicated an interaction effect between lymph node necrosis (yes vs. no) and treatment modality (IMRT vs. CCRT) regarding PFS (P for interaction&lt;0.05). In the subgroup with lymph node necrosis, IMRT compared to CCRT had a poorer prognosis (HR: 1.85,95% CI: 1.02-3.50). CCRT was noted to increase acute hematological, gastrointestinal and other toxicities.ConclusionsThis study provides a reference for clinical treatment decisions in T2N1 NPC. For the entire population of T2N1 NPC, the therapeutic effects of IMRT and CCRT are comparable, with increased acute toxicities in the latter. However, for patients with EBV-DNA copy level ≥1000 copies/ml, lymph node necrosis and extra-nodal extension, CCRT may be considered as appropriate. Particularly, patients with lymph node necrosis may be potential beneficiaries for CCRT.
Efficacy and safety of angiogenesis inhibitors combined with poly ADP ribose polymerase inhibitors in the maintenance treatment of advanced ovarian cancer: a meta-analysis
Authors: Huang Renming , Ji Feng , Huang Leyi , Qin Yueying , Liang Zhiyu , Huang Miaoyan , Li Chunyan , Ban Jian 
Published: November 2024

IntroductionThis meta-analysis was performed to evaluate the efficacy and safety of angiogenesis inhibitors (Ais) combined with poly ADP ribose polymerase inhibitors (PARPi) in the maintenance treatment of advanced ovarian cancer (OC).Materials and methodsA systematic search was conducted in four databases (Pubmed, Embase, Web of Science, and Cochrane) for articles published from the inception of the databases until January 15, 2024. The focus of the search was on articles investigating the combination of Ais with PARPi in the maintenance treatment of ovarian cancer. Meta-analyses were conducted to assess the objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and the risk of Grade ≥ 3 adverse events (Grade≥ 3 AEs).ResultsTotally nine studies were included for meta-analysis. The overall pooled ORR of Ais combined with PARPi was 57% (95% CI, 35% to 77%). Subgroup analyses showed that the ORR for patients with platinum-resistant recurrent ovarian cancer, platinum-sensitive recurrent ovarian cancer and newly diagnosed advanced ovarian cancer were 30% (95% CI, 12% to 52%), 70% (95% CI, 61% to 78%) and 59% (95% CI, 55% to 63%), respectively. The median PFS was 5.8 months (95% CI, 5.3 to 7.1), 12.4 months (95% CI, 10.6 to 13.2) and 22.4 months (95% CI, 21.5 to 24.2), respectively. The median OS was 15.5 months (95% CI, 12.3 to 24.8), 40.8 months (95% CI, 33.4 to 45.2) and 56.3 months (95% CI, 49.0 to 62.0), respectively. The rate Grade≥ 3 TRAEs rate was found to be 0.22 (95% CI, 0.13 to 0.33).ConclusionsOur results confirmed that PARPi plus Ais was a feasible and safe option for the maintenance treatment of advanced ovarian cancer. The combination therapy should be recommended as the first-line maintenance treatment for patients with advanced ovarian cancer. PARPi plus Ais yielded more favorable oncological prognosis for patients with platinum-sensitive recurrent ovarian cancer, compared to patients with platinum-resistant recurrent ovarian cancer.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024543590, identifier CRD42024543590.
Protocol of REACH-01: a single-arm, open label, prospective study of HAIC sequential TAE combined with tislelizumab and surufatinib in unresectable intrahepatic cholangiocarcinoma
Authors: Li Kang-shuai , Liu Yi , Zhang Tie-zhong , Xu Yun-fei , Zhang Zong-li 
Published: November 2024

IntroductionGemcitabine and cisplatin remain the cornerstone for the treatment of advanced or unresectable biliary tract cancers, but the incidence rate of the grade 3 or 4 toxic effects is high (70.7%). In recent years, significant progress has been achieved in the systemic treatment of cholangiocarcinoma with immune checkpoint inhibitors (ICIs), targeted therapy, and hepatic artery infusion chemotherapy (HAIC). HAIC may elevate the local drug concentration in the liver to 10–100 times the drug plasma concentration; therefore, it may enhance tumor cytotoxicity while minimizing systemic adverse effects. HAIC combined with immunotherapy and targeted therapy resulted in acceptable tumor responses and tolerable toxic effects in the treatment of hepatocellular carcinoma (HCC). However, whether this combination strategy can benefit patients with unresectable intrahepatic cholangiocarcinoma remains unclear.Methods and AnalysisWe describe a single-arm, open label, prospective clinical trial of HAIC sequential transcatheter arterial embolization (TAE) combined with tislelizumab and surufatinib in patients with unresectable intrahepatic cholangiocarcinoma. TAE + HAIC was performed at an interval of at least 3 weeks, and oxaliplatin (85 mg/m2) and rituximab (3 mg/m2) were infused. TAE was performed using undrugged microspheres. Tislelizumab was infused every 3 weeks and surufatinib was administered orally once a day, with 3-5 capsules (50 mg/capsule) each time. We plan to enroll 28 participants in this study. The primary study endpoint was objective response rate (ORR). The secondary endpoints were progression-free survival (PFS), conversion to surgical resection rate, overall survival (OS), 1-year OS rate, disease control rate (DCR), quality of life (QoL), and incidence of adverse events.Trial registration numberNCT06239532.
Maslinic acid induces autophagy and ferroptosis via transcriptomic and metabolomic reprogramming in prostate cancer cells
Authors: Hu Fen , Sun Yuxi , Zhang Yunfeng , Chen Jiaxin , Deng Yingzi , Li Yifei , Li Ruobing , Zhang Juan , Liang Yongping , Liu Yan , Wang Shuqing , Li Mi , Zhao Lina , Liu Yuwei , Gong Xiaodong , Cai Haifeng , Gu Shouqin 
Published: November 2024

Prostate cancer has the second highest incidence among male malignancies. Only a few studies exist on the inhibitory effects of maslinic acid (MA) on prostate cancer. Herein we found that MA inhibits prostate cancer cell proliferation by decreasing CDK2, CDK4, and CDK6 expression and concurrently increasing p27, Rb, p-Rb expression. Further, MA was observed to induce prostate cancer cell autophagy by increasing the expression of p53, p-p53, ULK1, Beclin1, Atg7, and Atg5 and the ratio of LC3-II/I and concurrently decreasing the expression of ERK1/2 and mTOR. In addition, MA induced RM-1 cell ferroptosis by regulating glutathione, glutamate, and oxidized glutathione concentrations, inhibiting SLC7A11 activity, and downregulating GPX4 expression. Integrated metabolome and transcriptome analysis led to the identification of key pathways (e.g., pathways in cancer and glutathione metabolism). Real-time quantitative PCR confirmed that MA regulates the expression of ABCA1, JUN, and NFKBIA. In vivo, we demonstrated that 50 mg/kg MA significantly inhibited the growth of tumors established using RM-1 cells. To summarize, we report that MA inhibits prostate cancer cell growth both in vitro and in vivo by inducing autophagy and ferroptosis via transcriptomic and metabolomic reprogramming.