bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differences in dementia prevention knowledge by educational attainment: an analysis of a household survey from Great Britain
Authors: Nafilyan Vahe , Eley Sarah , Courtin Emilie 
Published: November 2024

BackgroundHigher levels of education are associated with slower cognitive decline and a lower risk of dementia, with some evidence of a causal relationship. However, the mechanisms explaining these associations are not well established.MethodsWe collected data on dementia knowledge using a cross-sectional household survey representative of the population of Great Britain. Dementia knowledge was assessed using a self-reported measure and a question measuring the knowledge of key risk factors. We examined whether dementia knowledge varied by levels of education (as measured by the level of the highest qualification) by fitting logistic regressions adjusted for confounding factors.FindingsOut of the 5036 respondents aged 25 or over (46.6% male; average age 63.8), 9.3% reported knowing a great deal about dementia, and 32.2% quite a lot. We found a strong educational gradient in dementia prevention knowledge. For people with a degree qualification compared with people with no formal qualification, the ORs of reporting having quite a lot or a great deal of knowledge about dementia were 2.54 (95% CIs 1.81 to 3.56). The ORs were 3.58 (2.61 to 4.91) for mentioning all risk factors. The difference in awareness by educational level was largest for some risk factors such as lack of physical and mental activity, alcohol consumption and poor mental health.InterpretationThe protective effect of higher levels of education against the risk of dementia may partly be driven by differences in dementia prevention knowledge. Health education efforts on dementia prevention should target people with lower levels of education to reduce inequalities in dementia prevalence.
Camrelizumab plus carboplatin and pemetrexed as first-line therapy for advanced non-squamous non-small-cell lung cancer: 5-year outcomes of the CameL randomized phase 3 study
Authors: Zhou Caicun , Chen Gongyan , Huang Yunchao , Zhou Jianying , Lin LiZhu , Feng Jifeng , Wang Zhehai , Shu Yongqian , Shi Jianhua , Hu Yi , Wang QiMing , Cheng Ying , Wu Fengying , Chen Jianhua , Lin Xiaoyan , Wang Yongsheng , Huang Jianan , Cui Jiuwei , Cao Lejie , Liu Yunpeng , Zhang Yiping , Pan Yueyin , Zhao Jun , Wang LiPing , Chang Jianhua , Chen Qun , Ren Xiubao , Zhang Wei , Fan Yun , He Zhiyong , Fang Jian , Gu Kangsheng , Dong XiaoRong , Jin Faguang , Gao Hongjun , An Guangyu , Ding Cuimin , Jiang Xiaodong , Xiong Jianping , Zhou Xiangdong , Hu Sheng , Lu Ping , Liu Anwen , Guo Shuliang , Huang Jianjin , Zhu Chengchu , Zhao Jian , Gao Beili , Chen Yinglan , Hu Chengping , Zhang Jian , Zhang Hongmei , Zhao Hui , Wang Zhigao , Ma Xinjing , Shi Wei 
Published: November 2024

BackgroundCameL phase 3 study demonstrated the superiority of camrelizumab plus chemotherapy over chemotherapy alone for progression-free survival in patients with previously untreated advanced non-squamous non-small-cell lung cancer (NSCLC) withoutEGFR/ALKalterations. Here, we present the 5-year outcomes.MethodsPatients were randomized (1:1) and received 4–6 cycles of camrelizumab plus carboplatin and pemetrexed (n=205) or carboplatin and pemetrexed (n=207) every 3 weeks, followed by maintenance camrelizumab plus pemetrexed or pemetrexed only. Crossover from chemotherapy group to camrelizumab monotherapy was permitted after disease progression.ResultsMedian time from randomization to data cut-off was 65.2 months (range, 59.7–72.2). HR for overall survival (OS) was 0.74 (95% CI 0.58 to 0.93; one-sided p=0.0043), and was 0.62 (95% CI 0.49 to 0.79; one-sided p<0.0001) after adjustment for crossover. Five-year OS rates were 31.2% (95% CI 24.7% to 37.9%) with camrelizumab plus chemotherapy versus 19.3% (95% CI 13.9% to 25.3%) with chemotherapy alone. Among the 33 patients who completed 2 years of camrelizumab, 5-year OS rate was 84.3% (95% CI 66.4% to 93.2%), and 5-year duration of response rate was 46.5% (95% CI 24.9% to 65.6%) in the 32 responders. No new safety signals were noted.ConclusionsCamrelizumab plus carboplatin and pemetrexed as first-line therapy continued to demonstrate long-term OS benefit over carboplatin and pemetrexed, with manageable toxicity. Patients who completed 2 years of camrelizumab had enduring response and impressive OS. Current 5-year updated analysis further supports camrelizumab plus carboplatin and pemetrexed as a standard-of-care for previously untreated advanced non-squamous NSCLC withoutEGFR/ALKalterations.Trial registration numberNCT03134872.
B cell c-Maf signaling promotes tumor progression in animal models of pancreatic cancer and melanoma
Authors: Zhong Qian , Hao Hongying , Li Shu , Ning Yongling , Li Hong , Hu Xiaoling , McMasters Kelly M , Yan Jun , Ding Chuanlin 
Published: November 2024

BackgroundThe role of B cells in antitumor immunity remains controversial, with studies suggesting the protumor and antitumor activity. This controversy may be due to the heterogeneity in B cell populations, as the balance among the subtypes may impact tumor progression. The immunosuppressive regulatory B cells (Breg) release interleukin 10 (IL-10) but only represent a minor population. Additionally, tumor-specific antibodies (Abs) also exhibit antitumor and protumor functions dependent on the Ab isotype. Transcription factor c-Maf has been suggested to contribute to the regulation of IL-10 in Breg, but the role of B cell c-Maf signaling in antitumor immunity and regulating Ab responses remains unknown.MethodsConditional B cell c-Maf knockout (KO) and control mice were used to establish a KPC pancreatic cancer model and B16.F10 melanoma model. Tumor progression was evaluated. B cell and T cell phenotypes were determined by flow cytometry, mass cytometry, and cytokine/chemokine profiling. Differentially expressed genes in B cells were examined by using RNA sequencing (RNA-seq). Peripheral blood samples were collected from healthy donors and patients with melanoma for B cell phenotyping.ResultsCompared with B cells from the spleen and lymph nodes (LN), B cells in the pancreas exhibited significantly less follicular phenotype and higher IL-10 production in naïve mice. c-Maf deficiency resulted in a significant reduction of CD9+IL-10-producing Breg in the pancreas. Pancreatic ductal adenocarcinoma (PDAC) progression resulted in the accumulation of circulating B cells with the follicular phenotype and less IL-10 production in the pancreas. Notably, B cell c-Maf deficiency delayed PDAC tumor progression and resulted in proinflammatory B cells. Further, tumor volume reduction and increased effective T cells in the tumor-draining LN were observed in B cell c-Maf KO mice in the B16.F10 melanoma model. RNA-seq analysis of isolated B cells revealed that B cell c-Maf signaling modulates immunoglobulin-associated genes and tumor-specific Ab production. We furthermore demonstrated c-Maf-positive B cell subsets and an increase of IL-10-producing B cells after incubation with IL-4 and CD40L in the peripheral blood of patients with melanoma.ConclusionOur study highlights that B cell c-Maf signaling drives tumor progression through the modulation of Breg, inflammatory responses, and tumor-specific Ab responses.
Genetic and therapeutic heterogeneity shape the baseline and longitudinal immune ecosystem of ovarian clear cell carcinoma
Authors: Xia Siyu , Chen Lihua , Yu Min , Li Jiana , Chen Jiaxin , Xu Fei , Ni Mengdong , Liu Chaohua , Wu Xiaohua , Chen Xiaojun , Li Jiajia 
Published: November 2024

BackgroundOvarian clear cell carcinoma (OCCC) is a rare and chemo-resistant subtype of ovarian cancer. While immunotherapy has demonstrated effectiveness in some OCCC cases, the mechanisms for heterogeneous immunoreactivity and potential combinatory strategies remain unclear.MethodsTumor samples from 13 patients with OCCC underwent single-cell mRNA-seq and TCR-seq to generate 1 40 683 cells transcriptome, while additionally 31 formalin-fixed paraffin-embedded samples were used for immunohistochemistry. Spatial transcriptomics of two OCCC samples and bulk RNA-seq of 58 patients were incorporated for spatial and interpatient level explorations. Serum tumor markers and radiologic images of three patients with OCCC who received combinatory VEGF and PD-1 inhibition were retrospectively analyzed.ResultsOCCC exhibited a dynamic immune architecture shaped by genetic and therapeutic pressure.ARID1Amutation linked to baseline immune activation, correlated with an enrichment of neoantigen-reactive CXCL13+CTLA4+CD8+T cells (p<0.001) and enhanced FASLG–FAS interactions. Recurrent OCCC was fibrotic, angiogenic, and immunosuppressive, exhibiting metabolic reprogramming towards activated activity in fatty acid metabolism. High CD36 (log-rank p=0.012, HR: 4.515) and CD47 expression (log-rank p=0.037, HR: 3.246) indicated worse progression-free survival. Treatment with bevacizumab increased intratumoral T cell infiltration and activated T cell interferon-γ signaling. Retrospective analysis of clinical cases revealed that combination therapy with anti-VEGF (vascular endothelial growth factor) and anti-PD-1 agents exerted clinical benefits in patients with OCCC with persistent, recurrent, and metastatic disease.ConclusionsARID1Amutation correlated with OCCC baseline immune activation. Stromal reconstruction and tumor metabolic reprogramming functioned as key processes of OCCC dynamic progression. VEGF inhibition remodeled OCCC stroma, restored T cell function and potentiated immunotherapy. CD36 and CD47 might be potential therapeutic targets for recurrent OCCC.
Degradation of PARP1 by MARCHF3 in tumor cells triggers cCAS-STING activation in dendritic cells to regulate antitumor immunity in hepatocellular carcinoma
Authors: Cao Jun , Su Bingbing , Zhang Chi , Peng Rui , Tu Daoyuan , Deng Qiangwei , Jiang Guoqing , Jin Shengjie , Wang Qian , Bai Dou-Sheng 
Published: November 2024

BackgroundResistance to immune checkpoint inhibitors (ICIs) significantly limits the efficacy of immunotherapy in patients with hepatocellular carcinoma (HCC). However, the mechanisms underlying immunotherapy resistance remain poorly understood. Our aim was to clarify the role of membrane-associated ring-CH-type finger 3 (MARCHF3) in HCC within the framework of anti-programmed cell death protein-1 (PD-1) therapy.MethodsMARCHF3 was identified in the transcriptomic profiles of HCC tumors exhibiting different responses to ICIs. In humans, the correlation between MARCHF3 expression and the tumor microenvironment (TME) was assessed via multiplex immunohistochemistry. In addition, MARCHF3 expression in tumor cells and immune cell infiltration were assessed by flow cytometry.ResultsMARCHF3 was significantly upregulated in tumors from patients who responded to ICIs. Increased MARCHF3 expression in HCC cells promoted dendritic cell (DC) maturation and stimulated CD8+T-cell activation, thereby augmenting tumor control. Mechanistically, we identified MARCHF3 as a pivotal regulator of the DNA damage response. It directly interacted with Poly(ADP-Ribose) Polymerase 1 (PARP1) via K48-linked ubiquitination, leading to PARP1 degradation. This process promoted the release of double-strand DNA and activated cCAS-STING in DCs, thereby initiating DC-mediated antigen cross-presentation and CD8+T-cell activation. Additionally, ATF4 transcriptionally regulated MARCHF3 expression. Notably, the PARP1 inhibitor olaparib augmented the efficacy of anti-PD-1 immunotherapy in both subcutaneous and orthotopic HCC mouse models.ConclusionsMARCHF3 has emerged as a pivotal regulator of the immune landscape in the HCC TME and is a potent predictive biomarker for HCC. Combining interventions targeting the DNA damage response with ICIs is a promising treatment strategy for HCC.
HNF-1β alleviates podocyte injury in lupus nephritis by maintaining endoplasmic reticulum homeostasis
Authors: Zou Hui-mei , Yu Jie , Ruan Yuan-yuan , Xie Ying , An Xiao-min , Chen Pei-lei , Luo Ying-qin , Shi Ming-jun , Liu Miao , Xu Li-fen , Liu Jun , Guo Bing , Zhang Fan 
Published: November 2024

ObjectiveThe current study aims to elucidate the critical function of hepatocyte nuclear factor 1-beta (HNF1-β) in lupus nephritis (LN) by investigating its modulation of the Derlin-1/valosin-containing protein (VCP)/VCP-interacting membrane selenoprotein (VIMP) complex, endoplasmic reticulum (ER) stress and podocyte apoptosis.MethodsIn vitro and in vivo models of LN were established using glomerular podocytes treated with LN serum and MRL/lpr mice, respectively. The expression levels of HNF1-β were analysed in kidney tissues from patients with LN and MRL/lpr mice. To assess the effects of HNF1-β inhibition, an adeno-associated virus vector carrying HNF1-β short hairpin was administered to MRL/lpr mice. In vitro, glomerular podocytes were transfected with HNF1-β small interfering RNA (siRNA) or HNF1-β overexpression plasmids to explore their regulatory effects on the Derlin-1/VCP/VIMP complex and podocyte apoptosis. Dual-luciferase reporter assays and chromatin immunoprecipitation (ChIP) assays were performed to investigate the transcriptional activation of Derlin-1 and VCP promoters by HNF1-β.ResultsA significant decrease in HNF1-β levels was observed in kidney tissues from patients with LN while MRL/lpr mice exhibited an initial compensatory increase followed by a subsequent decrease in renal HNF1-β expression. Overexpression of HNF1-β transcriptionally upregulated Derlin-1 and VCP mitigating LN serum-induced ER stress and podocyte apoptosis. In contrast, HNF1-β inhibition exacerbated renal dysfunction and structural damage in MRL/lpr mice. Interestingly, HNF1-β inhibition transcriptionally repressed ERP44, leading to calcium ions (Ca²+) release-mediated disruption and inactivation of the Derlin-1/VCP/VIMP complex. This finding suggests that HNF1-β not only regulates the expression of key proteins in the Derlin-1/VCP/VIMP complex but also influences their assembly through Ca²+release regulation.ConclusionThis study provides novel insights into the regulatory mechanisms of HNF1-β in LN emphasising its impact on the Derlin-1/VCP/VIMP complex, ER stress and podocyte apoptosis. These findings have the potential to inform the development of new diagnostic tools and therapeutic strategies for LN.
Performance of the EULAR Systemic sclerosis Impact of Disease (ScleroID) questionnaire as a patient-reported outcome measure for patients with diffuse systemic sclerosis
Authors: Dobrota Rucsandra , Garaiman Alexandru , Fligelstone Kim , Tyrrell Kennedy Ann , Roennow Annelise , Allanore Yannick , Carreira Patricia E , Czirják László , Denton Chris , Hesselstrand Roger , Sandqvist Gunnel , Kowal-Bielecka Otylia , Bruni Cosimo , Matucci-Cerinic Marco , Mihai Carina , Gherghe Ana Maria , Mueller-Ladner Ulf , Kvien Tore , Heiberg Turid , Distler Oliver , Becker Mike Oliver 
Published: November 2024

ObjectiveSystemic sclerosis Impact of Disease (ScleroID) is the first comprehensive patient-reported outcome measure (PROM) specifically developed for systemic sclerosis (SSc). We investigated the performance of ScleroID in patients with diffuse cutaneous SSc (dcSSc), as a prerequisite for its use in randomised controlled trials (RCTs) testing potentially disease-modifying drugs.MethodsAll patients with dcSSc from the large, multicentric, ScleroID cohort were included. SSc-Health Assessment Questionnaire (HAQ), EuroQol-5 Dimensions and 36-item Short Form Health Survey (SF-36) were used as comparators. The study includes a longitudinal arm with a reliability visit at 7±3 days and a 12 months follow-up visit. The performance of ScleroID in dcSSc was assessed according to the Outcome Measures in Rheumatology filter.ResultsIn total, 152 dcSSc patients were analysed (29% male, median age 54 years). ScleroID reflected well the disease impact of dcSSc, showing a good construct validity with high Spearman’s correlation coefficients with comparators (SSc-HAQ, 0.79, 95% CI (0.69, 0.86); HAQ-Disability Index, 0.72 95% CI (0.60, 0.80); SF-36 physical score, −0.69 95% CI (−0.77, –0.60)). The internal consistency was strong (Cronbach’s alpha 0.87, split-half reliability coefficient 0.88).In the longitudinal arm, 44 patients had a reliability visit and 113 had a follow-up visit, of whom 19/113 (17%) reported a significant change (11 improved, 8 worsened). ScleroID showed a good consistency and discriminative ability with excellent test–retest reliability (intraclass correlation coefficient 0.89, 95% CI (0.84, 0.92)) and moderate sensitivity to change (standardised response mean −0.63 in the improved subgroup and 0.48 in the worsened subgroup), but superior to the comparators.ConclusionThe European Alliance of Associations for Rheumatology (EULAR) ScleroID performs well for patients with dcSSc. This supports its inclusion and regular assessment as PROM in RCTs.
Courts and judicial transformation in modern China
Authors: Han Tao , Chen Li 
Published: November 2024

Summary
The Daliyuan and the local courts in the late Qing dynasty served as the loci of judicial power in the early days of modern China. Following the doctrine of separation of powers, these judicial organs emerged during the preparation for constitutionalism and the quest for judicial independence in the late Qing dynasty. The government brushed aside the standard design of the government office, drawing inspiration from the designs of the highest courts in constitutional states in the East and West. Despite the financial constraints, significant funding was allocated to the construction of the Daliyuan premises. The grand and majestic Western-style structure was designed for high purposes. In addition to its customary functions, it was also entrusted with a political mission – impressing the world writ large with the successes of judicial reform and the image of China’s new-fangled judiciary. Due to a lack of funding, the local courts had downsized architecture, yet they still incorporated Western styles, mirroring the design of the Daliyuan. The transformed style of these courts offers insight into the prevailing philosophy of the reform and the new regime. It also illuminates the tension and fusion of legal culture that contributed to the modernization of the Chinese legal system.
Deciphering the role of probiotics in mental health: a systematic literature review of psychobiotics
Authors: Hussain A. , Koser N. , Aun S.M. , Siddiqui M.F. , Malik S. , Ali S.A. 
Published: November 2024

Abstract
Probiotics are live microorganisms that, when administered in adequate amounts, confer a health benefit to the host. The selection criteria for probiotics include strain safety, viability, tolerance, metabolite production and/or the ability to modulate the immune system. Probiotics are commonly used in industries, such as food, agriculture, medicine, biotechnology, pharmaceuticals, and aquaculture. Recently, the medicinal applications of probiotics have gained attention and are being explored for the prevention and treatment of various diseases. One emerging area of interest is their potential role in psychological disorders. Mental illnesses, characterised by disturbances in behaviour, mood, thinking, and emotions, affect over one billion people globally. While various preventive and treatment options for mental disorders exists, each is associated with certain limitations. A new avenue being explored is the gut-brain axis, a complex bi-directional communication between the gut and the brain, that is facilitated by hormonal, neuronal, humoral, and immunological pathways. This system plays an important role in mental health. Probiotics, as a key modulator of the gut microbiome, could play a vital role in this communication. However, the underlying mechanisms remain to be explored. Probiotics may act through the production of metabolites and neuroactive substances, as well as through immunomodulation and cytokine production. Current data shows promising effects on stress, mood, and depression, presenting probiotics as a potential natural treatment option for psychological disorders. Nevertheless, major limitations in the existing research include insufficient clinical outcomes, limited sample sizes, and variable dosing. Future advancements may be achieved through stratifications based on gut microbiota, the use of next-generation probiotic strains, and the conduct of comprehensive validation studies.
The Holy Horizon: The Early 18th Dynasty Royal Necropolis at Deir el-Bahari
Authors: Niwiński Andrzej 
Published: November 2024

In 2019 the Polish Cliff Mission cleaning the slopes above the temple of Thutmose III at Deir el-Bahari discovered a foundation deposit of Thutmose II perhaps related to an unfinished rock tomb of an inverted T-shape, or to a simple rock sanctuary nearby. Further works in front of this have revealed a huge man-made accumulation of stones and debris topped with a platform. The excavated place is axially connected with the cult chapel devoted to Thutmose I and II within the temple precinct of Thutmose III. The existence of the tomb of Thutmose II nearby seemed not to be excluded, and indeed a tomb was planned there, with an (only begun) entrance situated just behind this chapel. Other hints suggest that the tomb of Amenhotep I may have also been located in the area of this temple called ‘Holy Horizon’. A common cult place of Amenhotep I and Thutmose III is attested there, too. [Formula: see text]
Quantitative elemental sensitive imaging based on K-edge subtraction tomography
Authors: Zhang Yichi , Tao Fen , Gao Ruoyang , Zhang Ling , Wang Jun , Du Guohao , Xiao Tiqiao , Deng Biao 
Published: November 2024

Background K-edge subtraction (KES) tomography has been extensively utilized in the field of elemental sensitive imaging due to its high spatial resolution, rapid acquisition, and three-dimensional (3D) imaging capabilities. However, previous studies have primarily focused on the qualitative analysis of element contents, rather than quantitative assessment. Objective The current study proposes a novel method for quantitative elemental analysis based on K-edge subtraction tomography. Methods The linear correlation between the slice grayscale of standard samples and the difference in their linear absorption coefficients is confirmed. This finding suggests that the grayscale data from slices may be employed to perform quantitative estimations of elemental compositions. Results In order to verify the accuracy and validity of this method, the target element contents in standard and actual samples are quantitatively analyzed, respectively. The results demonstrate that the method is capable of achieving nanometer-resolved quantitative elemental sensitive imaging with a relative error of less than 3% in the target elemental content. Conclusions The method described in this paper is expected to expand the scope of applications for K-edge subtraction tomography and provide a novel approach to achieve more precise and convenient quantitative elemental analysis.