bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differences of macrophages in the tumor microenvironment as an underlying key factor in glioma patients
Authors: Wang Yangyang , Liu Yan , Zhang Chengkai , Zhang Chuanbao , Guan Xiudong , Jia Wang 
Published: October 2022

BackgroundMacrophages, the major immune cells in glioma microenvironment, are closely related to tumor prognosis. Further studies are needed to investigate macrophages, which will be helpful to fully understand the role of it and early achieve clinical translation.MethodsA total of 1334 glioma cases were enrolled in this study from 3 databases. In our works, the single cell cohorts from GSE89567, GSE84465, and the Chinese Glioma Genome Atlas (CGGA) datasets were used to analyze the key genes of macrophage. The bulk sequencing data from the Cancer Genome Atlas (TCGA) and CGGA datasets were respectively divided into the training set and validation set to test prognostic value of the key genes from single cell analysis.ResultsQuantitative and functional differences significantly emerge in macrophage clusters between LGG and GBM. Firstly, we used the Seurat R package to identify 281 genes differentially expressed genes in macrophage clusters between LGG and GBM. Furthermore, based on these genes, we developed a predictive risk model to predict prognosis and reflect the immune microenvironment in glioma. The risk score calculation formula was yielded as follows: Risk score = (0.11 × EXPMACC1) + (−0.31 × EXPOTUD1) + (−0.09 × EXPTCHH) + (0.26 × EXPADPRH) + (-0.40× EXPABCG2) + (0.21 × EXPPLBD1) + (0.12 × EXPANG) + (0.29 × EXPQPCT). The risk score was independently related to prognosis. Further, significant differences existed in immunological characteristics between the low- and high-risk score groups. What is more, mutation analysis found different genomic patterns associated with the risk score.ConclusionThis study further confirms that the proportion of macrophage infiltration is not only significantly different, but the function of them is also different. The signature, identified from the differentially expressed macrophage-related genes impacts poor prognosis and short overall survival and may act as therapeutic targets in the future.
Sepsis causes neutrophil infiltration in muscle leading to muscle atrophy and weakness in mice
Authors: Nakanishi Nobuto , Ono Yuko , Miyazaki Yusuke , Moriyama Naoki , Fujioka Kazumichi , Yamashita Kimihiro , Inoue Shigeaki , Kotani Joji 
Published: October 2022

BackgroundSepsis-induced muscle atrophy leads to prolonged physical dysfunction. Although the interaction of muscle atrophy and macrophage has been reported in sepsis, the role of neutrophils in muscle atrophy has not been thoroughly investigated. This study sought to investigate the long-term changes in muscle-localized neutrophils after sepsis induction and their possible role in sepsis.MethodsSepsis was induced in seven-week-old male C57BL/6J mice 8-12 (cecal slurry [CS] model) via intraperitoneal injection of 1 mg/g cecal slurry. The percentage change in body weight and grip strength was evaluated. The tibialis anterior muscles were dissected for microscopic examination of the cross-sectional area of myofibers or Fluorescence-activated cell sorting (FACS) analysis of immune cells. These changes were evaluated in the following conditions: (1) Longitudinal change until day 61, (2) CS concentration-dependent change on day 14 at the low (0.3 mg/g), middle (1.0 mg/g), and high (2.0 mg/g) concentrations, and (3) CS mice on day 14 treated with an anti-Ly6G antibody that depletes neutrophils.ResultsBody weight and grip strength were significantly lower in the CS model until day 61 (body weight: 123.1% ± 1.8% vs. 130.3% ± 2.5%, p = 0.04; grip strength: 104.5% ± 3.8% vs. 119.3% ± 5.3%, p = 0.04). Likewise, cross-sectional muscle area gradually decreased until day 61 from the CS induction (895.6 [606.0–1304.9] μm2 vs. 718.8 [536.2–937.0] μm2, p &lt; 0.01). The number of muscle-localized neutrophils increased from 2.3 ± 0.6 cell/mg on day 0 to 22.2 ± 13.0 cell/mg on day 14, and decreased thereafter. In terms of CS concentration–dependent change, cross-sectional area was smaller (484.4 ± 221.2 vs. 825.8 ± 436.2 μm2 [p &lt; 0.001]) and grip strength was lower (71.4% ± 12.8% vs. 116.3% ± 7.4%, p = 0.01) in the CS High group compared with the control, with increased neutrophils (p = 0.03). Ly6G-depleted mice demonstrated significant increase of muscle cross-sectional area and grip strength compared with control mice (p &lt; 0.01).ConclusionsSepsis causes infiltration of neutrophils in muscles, leading to muscle atrophy and weakness. Depletion of neutrophils in muscle reverses sepsis-induced muscle atrophy and weakness. These results suggest that neutrophils may play a critical role in sepsis-induced muscle atrophy and weakness.
The efficacy and safety analysis of first-line immune checkpoint inhibitors in pulmonary sarcomatoid carcinoma
Authors: Zeng Zhimin , Qian Xiaoying , Liu Fanrong , Wang Yong , Yuan Yong , Fang Chen , Zhang Xinwei , Yuan Shangkun , Chen Renfang , Yu Biao , Wang Tong , Yin Yan , Li Yong , Liu Anwen 
Published: October 2022

BackgroundPulmonary sarcomatoid carcinoma (PSC) is a rare and aggressive disease without standardized treatment strategies. The efficacy of second-line or beyond immune checkpoint inhibitors (ICIs) has been proven in recent studies, whereas the evidence for first-line immunotherapy for PSC is still limited to case reports and remains poorly understood.Materials and methodsThis was a multicenter, retrospective analysis of 21 patients with a histological diagnosis of PSC who received ICI as first-line therapy from January 2019 to March 2022. The expression of PD-L1 was evaluated by immunohistochemistry (IHC) using the monoclonal antibody 22C3. Low and high PD-L1 expressions were defined using the tumor proportion score (TPS), with cutoffs of 1 and 50%, respectively.ResultsAll eight patients had PD-L1 positivity who underwent PD-L1 expression assessment, and six patients (6/8, 75.0%) had high PD-L1 expression. Among the 21 PSC patients, seven received tislelizumab, six received camrelizumab, four received sintilimab, three received pembrolizumab, and one received durvalumab. Among them, 18 PSCs received combination therapy, whereas another three PSCs received immunotherapy alone. Out of the 21 PSC patients, 12 (57.1%) achieved a partial response (PR), and five patients had stable disease (SD) as the best response, whereas four PSCs experienced dramatic progressive disease (PD). The median progression-free survival (PFS) was 9.2 (95% CI [4.3, 14.1]) months, and the median OS was 22.8 (95% CI [4.0, 41.5]) months. Among the three treatment groups (immunotherapy alone, immunotherapy combined with anlotinib, and chemoimmunotherapy), the median PFS was 8.0, 9.4, and 9.6 months, and the median OS was 19.0, 22.8, and 30.6 months, respectively. There was no difference in PFS and OS between the three treatment regimen groups (P = 0.86 and P = 0.34, respectively) and different immunotherapies (P = 0.10 and P = 0.23, respectively). No serious adverse events (grade ≥ 3) were noted.ConclusionFirst-line immunotherapy has promising therapeutic potential in the treatment of PSC. More studies are warranted to confirm these findings.
Single-cell RNA-sequencing uncovers compound kushen injection synergistically improves the efficacy of chemotherapy by modulating the tumor environment of breast cancer
Authors: Liu Xinkui , Bai Meirong , Li Huiying , Ye Peizhi , Duan Xiaoxia , Wu Chao , Huang Zhihong , Lu Shan , Zhang Jingyuan , Zhao Zihan , Guo Fengying , You Rongli , Qin Wenjie , Wang Wei , Han Aiqing , Shen Liangliang , Wang Yitao , Zhao Zheng , Luo Hua , Wu Jiarui 
Published: October 2022

BackgroundDue to lack of enough specific targets and the immunosuppressive tumor microenvironment (TME) of triple-negative breast cancer (TNBC), TNBC patients often cannot benefit from a single treatment option. This study aims to explore the regulatory effects of Compound kushen injection (CKI) plus chemotherapy on the TME of TNBC from a single cell level.MethodsA mouse TNBC model in BALB/c mice was established to evaluate the antitumor efficacy and toxicity of CKI combined with chemotherapy. Flow cytometry was used to observe the influence of CKI on the lymphocyte populations in the tumor bearing mice. Both bulk RNA sequencing (RNA-seq) and single-cell RNA-seq (scRNA-seq) were applied to portray the modulation of CKI combined with chemotherapy on the TME of TNBC mice.ResultsCKI significantly enhanced the anticancer activity of chemotherapy in vivo with no obvious side effects. Flow cytometry results revealed a significantly higher activation of CD8+ T lymphocytes in the spleens and tumors of the mice with combination therapy. Bulk RNA-seq indicated that CKI could promote the cytotoxic immune cell infiltrating into tumor tissues. Meanwhile, scRNA-seq further revealed that CKI combined with chemotherapy could enhance the percentage of tumor-infiltrating CD8+ T cells, inhibit tumor-promoting signaling pathways, and promote T cell activation and positive regulation of immune response. In addition, CKI showed obvious anticancer activity against MDA-MB-231 breast tumor cells in vitro.ConclusionsThe combination of CKI and chemotherapy might provide a higher efficiency and lower toxicity strategy than a single chemotherapy drug for TNBC. CKI potentiates the anti-TNBC effects of chemotherapy by activating anti-tumor immune response in mice.
The role of benthic habitat mapping for science and managers: A multi-design approach in the Southeast Brazilian Shelf after a major man-induced disaster
Authors: Menandro Pedro S. , Lavagnino Ana Carolina , Vieira Fernanda V. , Boni Geandré C. , Franco Tarcila , Bastos Alex C. 
Published: October 2022

Seabed mapping is currently the baseline information for ocean management and conservation, and is an indispensable item within research and Marine Spatial Planning. Here, we use a case study and published data along the southeast Brazilian continental shelf to illustrate the concepts and ideas of potential benthic habitat mapping and the importance of having maps on different scales and the potential for using a multi-design approach. The case analysis presented here uses a regional map and distinct criteria (seabed geodiversity and biodiversity, and potential influence of a tailings plume) to define three areas along the continental shelf to be mapped in a high-resolution, as part of a marine monitoring program. The background of the case study is a tailing dam failure disaster that led to the input of iron ore tailings in the ocean, leading to a major environmental disaster. Three areas were chosen, including: a Marine Protected Area (MPA Costa das Algas), a major fishing ground (the Doce River prodelta/depocenter), and an understudied reef area (Forgotten Reefs). Potential benthic habitat mapping was carried out using acoustic surveys (multibeam echosounder acquiring bathymetry and backscatter) and ground-truthing (sediment samples and seafloor image). Results detailed the potential habitats throughout the three areas, providing primary information for the study of benthic habitats and their distribution. The multi-design approach indicated that although a regional analysis can indicate potential vulnerability as a first assessment approach, high-resolution potential habitat mapping (herein, 20 m or finer) is beneficial to evaluate and produce a higher-confidence level for decision-makers. Having an overall view of what and where to collect new and finer data would be best to identify vulnerable areas that, in this case study, could be threatened by plume dispersion and tailings accumulation. Our results support the delineation of priority areas aiming for monitoring, protection and guiding for other studies, besides the consolidation of habitat importance and the integration of various datasets through a hierarchical classification scheme. Although Brazil has never produced a regional or national habitat map for the entire continental margin, there are already conditions to plan, execute and maintain a habitat mapping program, partnering with Universities, Government Institutions (e.g., the Brazilian Navy), and the private sector. In the context of the UN Decade of Ocean Science targets, it is urgent to plan and implement a national database capable of supporting a habitat classification effort on a broader national scale, with the flexibility to support a multi-design or a multi-scale approach.
Revealing the prognostic and clinicopathological significance of systemic immune-inflammation index in patients with different stage prostate cancer: A systematic review and meta-analysis
Authors: Qi Wenqiang , Zhou Yongheng , Liu Zhifeng , Wang Jian , Lv Guangda , Zhong Minglei , Wang Wenfu , Li Rongyang , Chen Shouzhen , Shi Benkang , Zhu Yaofeng 
Published: October 2022

BackgroundA novel inflammatory marker called the systemic immune-inflammation index (SII) was applied to predict the prognosis of different cancers. However, the role of SII in prostate cancer (PCa) remains unclear. This systematic review aims to explore the prognostic role of SII in different stage PCa.MethodsWe comprehensively searched three public databases: PubMed, EMBASE, and the Cochrane Library. The hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were extracted to evaluate the association between SII and the prognosis and clinicopathological characteristics in different stage PCa patients.ResultsTen studies and 7,986 patients were enrolled in our meta-analysis, 1,442 patients were diagnosed with metastatic-castration resistant prostate cancer (mCRPC), and 6544 patients were diagnosed with non-metastatic prostate cancer (nmPCa). According to the pooled results, we found that a high SII was associated with worse overall survival (OS) in mCRPC patients (HR = 1.94, 95% CI: 1.26–3.01, p = 0.003), and a high SII was associated with biochemical recurrence-free survival (BFS) in nmPCa patients (HR = 1.85, 95% CI: 1.06–3.24, p = 0.031). But there was no significant association observed between SII and progression-free survival (PFS) in mCRPC patients (HR = 1.90, 95% CI: 0.87–4.14, p = 0.107). And we found that the high SII was associated with advanced tumor stage of PCa (OR = 2.19, 95% CI: 1.11–4.33, p = 0.024), presence of lymph node involvement (OR = 2.72, 95% CI: 1.96–3.76, p &lt; 0.001) and Gleason score (OR = 1.27, 95% CI: 1.13–1.44, p &lt; 0.001).ConclusionHigh SII was associated with bad OS in mCRPC patients, and associated with bad BFS and some adverse pathological features in nmPCa patients. We think SII can be a prognostic predictor for PCa patients. The application of SII will advance the diagnosis and treatment of different stage prostate cancer.
Improving the prognostic value of multimorbidity through the integration of selected biomarkers to the comprehensive geriatric assessment: An observational retrospective monocentric study
Authors: Piacenza Francesco , Di Rosa Mirko , Fedecostante Massimiliano , Madotto Fabiana , Montesanto Alberto , Corsonello Andrea , Cherubini Antonio , Provinciali Mauro , Soraci Luca , Lisa Rosamaria , Bustacchini Silvia , Bonfigli Anna Rita , Lattanzio Fabrizia 
Published: October 2022

BackgroundMultimorbidity (MM) burdens individuals and healthcare systems, since it increases polypharmacy, dependency, hospital admissions, healthcare costs, and mortality. Several attempts have been made to determine an operational definition of MM and to quantify its severity. However, the lack of knowledge regarding its pathophysiology prevented the estimation of its severity in terms of outcomes. Polypharmacy and functional impairment are associated with MM. However, it is unclear how inappropriate drug decision-making could affect both conditions. In this context, promising circulating biomarkers and DNA methylation tools have been proposed as potential mortality predictors for multiple age-related diseases. We hypothesize that a comprehensive characterization of patients with MM that includes the measure of epigenetic and selected circulating biomarkers in the medical history, in addition to the functional capacity, could improve the prognosis of their long-term mortality.MethodsThis monocentric retrospective observational study was conducted as part of a project funded by the Italian Ministry of Health titled “imProving the pROgnostic value of MultimOrbidity through the inTegration of selected biomarkErs to the comprehensive geRiatric Assessment (PROMOTERA).” This study will examine the methylation levels of thousands of CpG sites and the levels of selected circulating biomarkers in the blood and plasma samples of older hospitalized patients with MM (n = 1,070, age ≥ 65 years) recruited by the Reportage Project between 2011 and 2019. Multiple statistical approaches will be utilized to integrate newly measured biomarkers into clinical, demographic, and functional data, thus improving the prediction of mortality for up to 10 years.DiscussionThis study's results are expected to: (i) identify the clinical, biological, demographic, and functional factors associated with distinct patterns of MM; (ii) improve the prognostic accuracy of MM patterns in relation to death, hospitalization-related outcomes, and onset of new comorbidities; (iii) define the epigenetic signatures of MM; (iv) construct multidimensional algorithms to predict negative health outcomes in both the overall population and specific disease and functional patterns; and (v) expand our understanding of the mechanisms underlying the pathophysiology of MM.
Multi-omics studies reveal ameliorating effects of physical exercise on neurodegenerative diseases
Authors: Guo Yuhuai , Wang Shouli , Chao Xiaowen , Li Ding , Wang Ying , Guo Qihao , Chen Tianlu 
Published: October 2022

IntroductionNeurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease, amyotrophic lateral sclerosis, and Huntington’s disease, are heavy burdens to global health and economic development worldwide. Mounting evidence suggests that exercise, a type of non-invasive intervention, has a positive impact on the life quality of elderly with neurodegenerative diseases. X-omics are powerful tools for mapping global biochemical changes in disease and treatment.MethodThree major databases were searched related to current studies in exercise intervention on neurodegenerative diseases using omics tools, including metabolomics, metagenomics, genomics, transcriptomics, and proteomics.ResultWe summarized the omics features and potential mechanisms associated with exercise and neurodegenerative diseases in the current studies. Three main mechanisms by which exercise affects neurodegenerative diseases were summed up, including adult neurogenesis, brain-derived neurotrophic factor (BDNF) signaling, and short-chain fatty acids (SCFAs) metabolism.ConclusionOverall, there is compelling evidence that exercise intervention is a feasible way of preventing the onset and alleviating the severity of neurodegenerative diseases. These studies highlight the importance of exercise as a complementary approach to the treatment and intervention of neurodegenerative diseases in addition to traditional treatments. More mechanisms on exercise interventions for neurodegenerative diseases, the specification of exercise prescriptions, and differentiated exercise programs should be explored so that they can actually be applied to the clinic.
Neuroanatomical correlates of screening for aphasia in NeuroDegeneration (SAND) battery in non-fluent/agrammatic variant of primary progressive aphasia
Authors: Premi Enrico , Cotelli Maria , Gobbi Elena , Pagnoni Ilaria , Binetti Giuliano , Gadola Yasmine , Libri Ilenia , Mattioli Irene , Pengo Marta , Iraji Armin , Calhoun Vince D. , Alberici Antonella , Borroni Barbara , Manenti Rosa 
Published: October 2022

BackgroundNon-fluent/agrammatic variant of Primary Progressive Aphasia (avPPA) is primarily characterized by language impairment due to atrophy of the inferior frontal gyrus and the insula cortex in the dominant hemisphere. The Screening for Aphasia in NeuroDegeneration (SAND) battery has been recently proposed as a screening tool for PPA, with several tasks designed to be specific for different language features. Applying multivariate approaches to neuroimaging data and verbal fluency tasks, Aachener Aphasie Test (AAT) naming subtest and SAND data may help in elucidating the neuroanatomical correlates of language deficits in avPPA.ObjectiveTo investigate the neuroanatomical correlates of language deficits in avPPA using verbal fluency tasks, AAT naming subtest and SAND scores as proxies of brain structural imaging abnormalities.MethodsThirty-one avPPA patients were consecutively enrolled and underwent extensive neuropsychological assessment and MRI scan. Raw scores of verbal fluency tasks, AAT naming subtest, and SAND subtests, namely living and non-living picture naming, auditory sentence comprehension, single-word comprehension, words and non-words repetition and sentence repetition, were used as proxies to explore structural (gray matter volume) neuroanatomical correlates. We assessed univariate (voxel-based morphometry, VBM) as well as multivariate (source-based morphometry, SBM) approaches. Age, gender, educational level, and disease severity were considered nuisance variables.ResultsSAND picture naming (total, living and non-living scores) and AAT naming scores showed a direct correlation with the left temporal network derived from SBM. At univariate analysis, the left middle temporal gyrus was directly correlated with SAND picture naming (total and non-living scores) and AAT naming score. When words and non-words repetition (total score) was considered, a direct correlation with the left temporal network (SBM) and with the left fusiform gyrus (VBM) was also evident.ConclusionNaming impairments that characterize avPPA are related to specific network-based involvement of the left temporal network, potentially expanding our knowledge on the neuroanatomical basis of this neurodegenerative condition.