bluuebunny/crossref_metadata_2025_split huggingface dataset:
An immune risk score predicts progression-free survival of melanoma patients in South China receiving anti-PD-1 inhibitor therapy—a retrospective cohort study examining 66 circulating immune cell subsets
Authors: Chi Peidong , Jiang Hang , Li Dandan , Li Jingjing , Wen Xizhi , Ding Qiyue , Chen Linbin , Zhang Xiaoshi , Huang Junqi , Ding Ya 
Published: December 2022

IntroductionImmune checkpoint blockade inhibitor (ICI) therapy offers significant survival benefits for malignant melanoma. However, some patients were observed to be in disease progression after the first few treatment cycles. As such, it is urgent to find convenient and accessible indicators that assess whether patients can benefit from ICI therapy.MethodsIn the training cohort, flow cytometry was used to determine the absolute values of 66 immune cell subsets in the peripheral blood of melanoma patients (n=29) before treatment with anti-PD-1 inhibitors. The least absolute shrinkage and selection operator (LASSO) Cox regression model was followed for the efficacy of each subset in predicting progression-free survival. Then we validated the performance of the selected model in validation cohorts (n=20), and developed a nomogram for clinical use.ResultsA prognostic immune risk score composed of CD1c+ dendritic cells and three subsets of T cells (CD8+CD28+, CD3+TCRab+HLA-DR+, CD3+TCRgd+HLA-DR+) with a higher prognostic power than individual features (AUC = 0.825). Using this model, patients in the training cohort were divided into high- and low-risk groups with significant differences in mean progression-free survival (3.6 vs. 12.3 months), including disease control rate (41.2% vs. 91.7%), and objective response rate (17.6% vs. 41.6%). Integrating four-immune cell-subset based classifiers and three clinicopathologic risk factors can help to predict which patients might benefit from anti-PD-1 antibody inhibitors and remind potential non-responders to pursue effective treatment options in a timely way.ConclusionsThe prognostic immune risk score including the innate immune and adaptive immune cell populations could provide an accurate prediction efficacy in malignant melanoma patients with ICI therapy.
Inhibiting the inflammasome with MCC950 counteracts muscle pyroptosis and improves Duchenne muscular dystrophy
Authors: Dubuisson Nicolas , Davis-López de Carrizosa María A. , Versele Romain , Selvais Camille M. , Noel Laurence , Van den Bergh P. Y. D. , Brichard Sonia M. , Abou-Samra Michel 
Published: December 2022

BackgroundDuchenne muscular dystrophy (DMD) is the most common inherited human myopathy. Typically, the secondary process involving severe inflammation and necrosis exacerbate disease progression. Previously, we reported that the NLRP3 inflammasome complex plays a crucial role in this disorder. Moreover, pyroptosis, a form of programmed necrotic cell death, is triggered by NLRP3 via gasdermin D (GSDMD). So far, pyroptosis has never been described either in healthy muscle or in dystrophic muscle. The aim of this study was to unravel the role of NLRP3 inflammasome in DMD and explore a potentially promising treatment with MCC950 that selectively inhibits NLRP3.MethodsFour‐week‐old mdx mice (n=6 per group) were orally treated for 2 months with MCC950 (mdx‐T), a highly potent, specific, small-molecule inhibitor of NLRP3, and compared with untreated (mdx) and wild-type (WT) mice. In vivo functional tests were carried out to measure the global force and endurance of mice. Ex vivo biochemical and molecular analyses were performed to evaluate the pathophysiology of the skeletal muscle. Finally, in vitro tests were conducted on primary cultures of DMD human myotubes.ResultsAfter MCC950 treatment, mdx mice exhibited a significant reduction of inflammation, macrophage infiltration and oxidative stress (-20 to -65%, P&lt;0.05 vs untreated mdx). Mdx‐T mice displayed considerably less myonecrosis (-54%, P&lt;0.05 vs mdx) and fibrosis (-75%, P&lt;0.01 vs mdx). Moreover, a more mature myofibre phenotype, characterized by larger-sized fibres and higher expression of mature myosin heavy chains 1 and 7 was observed. Mdx-T also exhibited enhanced force and resistance to fatigue (+20 to 60%, P&lt;0.05 or less). These beneficial effects resulted from MCC950 inhibition of both active caspase-1 (-46%, P=0.075) and cleaved gasdermin D (N-GSDMD) (-42% in medium-sized-fibres, P&lt;0.001). Finally, the anti-inflammatory action and the anti-pyroptotic effect of MCC950 were also recapitulated in DMD human myotubes.ConclusionSpecific inhibition of the NLRP3 inflammasome can significantly attenuate the dystrophic phenotype. A novel finding of this study is the overactivation of GSDMD, which is hampered by MCC950. This ultimately leads to less inflammation and pyroptosis and to a better muscle maturation and function. Targeting NLRP3 might lead to an effective therapeutic approach for a better management of DMD.
Interaction between glycolysis‒cholesterol synthesis axis and tumor microenvironment reveal that gamma-glutamyl hydrolase suppresses glycolysis in colon cancer
Authors: Chen Yan-Jie , Guo Xi , Liu Meng-Ling , Yu Yi-Yi , Cui Yue-Hong , Shen Xi-Zhong , Liu Tian-Shu , Liang Li 
Published: December 2022

BackgroundMetabolic reprogramming is a feature of cancer. However, colon cancer subtypes based on the glycolysis‒cholesterol synthesis axis have not been identified, and little is known about connections between metabolic features and the tumor microenvironment.MethodsData for 430 colon cancer cases were extracted from The Cancer Genome Atlas, including transcriptome data, clinical information, and survival outcomes. Glycolysis and cholesterol synthesis-related gene sets were obtained from the Molecular Signatures Database for a gene set variation analysis. The relationship between the genomic landscape and immune landscape were investigated among four metabolic subtypes. Hub genes were determined. The clinical significance of candidate hub gene was evaluated in 264 clinical samples and potential functions were validated in vitro and in vivo.ResultsColon cancer cases were clustered into four metabolic subtypes: quiescent, glycolytic, cholesterogenic, and mixed. The metabolic subtypes differed with respect to the immune score, stromal score, and estimate score using the ESTIMATE algorithm, cancer-immunity cycle, immunomodulator signatures, and signatures of immunotherapy responses. Patients in the cholesterogenic group had better survival outcomes than those for other subtypes, especially glycolytic. The glycolytic subtype was related to unfavorable clinical characteristics, including high mutation rates in TTN, APC, and TP53, high mutation burden, vascular invasion, right colon cancer, and low-frequency microsatellite instability. GGH, CACNG4, MME, SLC30A2, CKMT2, SYN3, and SLC22A31 were identified as differentially expressed both in glycolytic-cholesterogenic subgroups as well as between colon cancers and healthy samples, and were involved in glycolysis‒cholesterol synthesis. GGH was upregulated in colon cancer; its high expression was correlated with CD4+ T cell infiltration and longer overall survival and it was identified as a favorable independent prognostic factor. The overexpression of GGH in colon cancer-derived cell lines (SW48 and SW480) inhibited PKM, GLUT1, and LDHA expression and decreased the extracellular lactate content and intracellular ATP level. The opposite effects were obtained by GGH silencing. The phenotype associated with GGH was also validated in a xenograft nude mouse model.ConclusionsOur results provide insight into the connection between metabolism and the tumor microenvironment in colon cancer and provides preliminary evidence for the role of GGH, providing a basis for subsequent studies.
Effect of dietary cholesterol on ovarian development of Chinese mitten crabs (Eriocheir sinensis)
Authors: Guo Huixing , Wang Mangmang , Wang Xi , Xiao Kang , Huang Yangyang , Hua Haokun , Xiong Wei , Liu Wenbin , Abasubong Kenneth Prudence , Qiang Wei , Chi Cheng , Jiang Guangzhen 
Published: December 2022

This study was conducted to evaluate the effect of cholesterol (CHO) on ovarian development of Eriocheir sinensis through a feeding trial. Crabs (average weight 43.35 ± 0.05 g) were randomly fed with one of three diets: 0% CHO, 0.4% CHO and 1.6% CHO for 16 weeks. Results indicated that the hepatosomatic index (HSI) and gonad index (GSI) of crabs fed with 0.4% CHO diet were significantly higher than those in the control group. (P &lt; 0.05). Meanwhile, 0.4% CHO can significantly increase the gene expression of vtg and vgr in ovary (P &lt; 0.05), thus promoting the accumulation of Vtg. The protein expression of MEK1/2, ERK, p-ERK1/2, Cyclin B and CDC2 were significantly increased in the 0.4% CHO group, therefore dietary CHO might promote oocyte maturation by activating MAPK signal pathway and cooperating with maturation promoting factor (MPF). Further exploration results showed that 0.4% CHO was able to significantly up-regulate the protein expression of STAR and SR-B1 to promote the transport of CHO to ovary, thereby providing sufficient substrates for estradiol (E2) synthesis. In addition, the results in vivo and in vitro shown that CHO could regulate the activities of enzymes such as CYP11A1 and CYP19A1 through the cAMP-PKA-CREB/SF-1 signal pathway and then affects the level of E2 in the organism. In summary, supplementing the appropriate amount of CHO in the diet can improve the E2 level of the organism, thus increasing the accumulation of nutrients in the ovary, promoting the completion of meiosis, and finally achieving the purpose of promoting ovarian maturation.
Gene expression profile analysis to discover molecular signatures for early diagnosis and therapies of triple-negative breast cancer
Authors: Alam Md Shahin , Sultana Adiba , Wang Guanghui , Haque Mollah Md Nurul 
Published: December 2022

Triple-negative breast cancer (TNBC) is one of the most lethal subtypes of breast cancer (BC), and it accounts for approximately 10%–20% of all invasive BCs diagnosed worldwide. The survival rate of TNBC in stages III and IV is very low, and a large number of patients are diagnosed in these stages. Therefore, the purpose of this study was to identify TNBC-causing molecular signatures and anti-TNBC drug agents for early diagnosis and therapies. Five microarray datasets that contained 304 TNBC and 109 control samples were collected from the Gene Expression Omnibus (GEO) database, and RNA-Seq data with 116 tumor and 124 normal samples were collected from TCGA database to identify differentially expressed genes (DEGs) between TNBC and control samples. A total of 64 DEGs were identified, of which 29 were upregulated and 35 were downregulated, by using the statistical limma R-package. Among them, seven key genes (KGs) were commonly selected from microarray and RNA-Seq data based on the high degree of connectivity through PPI (protein–protein interaction) and module analysis. Out of these seven KGs, six KGs (TOP2A, BIRC5, AURKB, ACTB, ASPM, and BUB1B) were upregulated and one (EGFR) was downregulated. We also investigated their differential expression patterns with different subtypes and progression stages of BC by the independent datasets of RNA-seq profiles from UALCAN database, which indicated that they may be potential biomarkers for early diagnosis. Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses with the proposed DEGs were performed using the online Enrichr database to investigate the pathogenetic processes of TNBC highlighting KGs. Then, we performed gene regulatory network analysis and identified three transcriptional (SOX2, E2F4, and KDM5B) and three post-transcriptional (hsa-mir-1-3p, hsa-mir-124-3p, and hsa-mir-34a-5p) regulators of KGs. Finally, we proposed five KG-guided repurposable drug molecules (imatinib, regorafenib, pazopanib, teniposide, and dexrazoxane) for TNBC through network pharmacology and molecular docking analyses. These drug molecules also showed significant binding performance with some cancer-related PTM-sites (phosphorylation, succinylation, and ubiquitination) of top-ranked four key proteins (EGFR, AURKB, BIRC5, and TOP2A). Therefore, the findings of this computational study may play a vital role in early diagnosis and therapies against TNBC by wet-lab validation.
Risk for intracranial hemorrhage in individuals after mild traumatic brain injury who are taking serotonergic antidepressants
Authors: Isokuortti Harri , Iverson Grant L. , Posti Jussi P. , Berghem Ksenia , Kotilainen Anna-Kerttu , Luoto Teemu M. 
Published: December 2022

BackgroundSerotonergic antidepressants may predispose to bleeding, but little is known of the risk for traumatic intracranial bleeding.MethodsThis was a prospective case-control study of 218 patients with mild traumatic brain injuries (TBI) who were treated at a Finnish tertiary trauma hospital. Injury-related information and clinical findings were prospectively collected in the emergency department. Detailed pre-injury health history was collected from electronic medical records. Information on the use of serotonergic antidepressants was attained from the Finnish national prescription registry. All head CT scans were reviewed by a neuroradiologist based on the Common Data Elements. Cases were patients with traumatic intracranial hemorrhage on head CT. Controls were patients from the same cohort, but without traumatic intracranial lesions on CT. The proportion with traumatic intracranial bleeding for patients on serotonergic antidepressant medication was compared to the proportion for patients not on serotonergic medication.ResultsThe study cohort consisted of 24 cases with traumatic intracranial bleeding and 194 injured controls. The median age of the sample was 70 years (interquartile range = 50–83). One fifth (21.6%) of all the patients were taking a serotonergic antidepressant. Of the patients on an antidepressant, 10.6% (5/47) had an acute hemorrhagic lesion compared to 11.1% (19/171) of those who were not on an antidepressant (p = 0.927). In the regression analysis, traumatic intracranial hemorrhage was not associated with antidepressant use.ConclusionSerotonergic antidepressant use was not associated with an increased risk of traumatic intracranial hemorrhage after a mild TBI. The patients in this relatively small cohort were mostly middle-aged and older adults. These factors limit the generalizability of the results in younger patients with mild TBI.
Effect of prebiotics, probiotics, and synbiotics on gastrointestinal outcomes in healthy adults and active adults at rest and in response to exercise—A systematic literature review
Authors: Rauch Christopher E. , Mika Alice S. , McCubbin Alan J. , Huschtscha Zoya , Costa Ricardo J. S. 
Published: December 2022

IntroductionA systematic literature search was undertaken to assess the impact of pre-, pro-, and syn-biotic supplementation on measures of gastrointestinal status at rest and in response to acute exercise.MethodsSix databases (Ovid MEDLINE, EMBASE, Cinahl, SportsDISCUS, Web of Science, and Scopus) were used. Included were human research studies in healthy sedentary adults, and healthy active adults, involving supplementation and control or placebo groups. Sedentary individuals with non-communicable disease risk or established gastrointestinal inflammatory or functional diseases/disorders were excluded.ResultsA total of n = 1,204 participants were included from n = 37 papers reported resting outcomes, and n = 13 reported exercise-induced gastrointestinal syndrome (EIGS) outcomes. No supplement improved gastrointestinal permeability or gastrointestinal symptoms (GIS), and systemic endotoxemia at rest. Only modest positive changes in inflammatory cytokine profiles were observed in n = 3/15 studies at rest. Prebiotic studies (n = 4/5) reported significantly increased resting fecal Bifidobacteria, but no consistent differences in other microbes. Probiotic studies (n = 4/9) increased the supplemented bacterial species-strain. Only arabinoxylan oligosaccharide supplementation increased total fecal short chain fatty acid (SCFA) and butyrate concentrations. In response to exercise, probiotics did not substantially influence epithelial injury and permeability, systemic endotoxin profile, or GIS. Two studies reported reduced systemic inflammatory cytokine responses to exercise. Probiotic supplementation did not substantially influence GIS during exercise.DiscussionSynbiotic outcomes resembled probiotics, likely due to the minimal dose of prebiotic included. Methodological issues and high risk of bias were identified in several studies, using the Cochrane Risk of Bias Assessment Tool. A major limitation in the majority of included studies was the lack of a comprehensive approach of well-validated biomarkers specific to gastrointestinal outcomes and many included studies featured small sample sizes. Prebiotic supplementation can influence gut microbial composition and SCFA concentration; whereas probiotics increase the supplemented species-strain, with minimal effect on SCFA, and no effect on any other gastrointestinal status marker at rest. Probiotic and synbiotic supplementation does not substantially reduce epithelial injury and permeability, systemic endotoxin and inflammatory cytokine profiles, or GIS in response to acute exercise.
Serum vitamin D status and circulating irisin levels in older adults with sarcopenia
Authors: Wang Yawen , Gu Yeqing , Huang Jian , Wu Hongmei , Meng Ge , Zhang Qing , Liu Li , Zhang Shunming , Wang Xuena , Zhang Juanjuan , Sun Shaomei , Wang Xing , Zhou Ming , Jia Qiyu , Song Kun , Huo Junsheng , Zhang Bing , Ding Gangqiang , Du Peng , Niu Kaijun 
Published: December 2022

BackgroundEmerging evidence suggests sarcopenia, which is involved in the serum vitamin D deficiency and development of abnormal muscle metabolism, is predominately centered in the general older population. In the present study, we aimed to explore the relationship between the level of serum vitamin D and irisin concentrations in the older adults with sarcopenia.MethodsA cross-sectional study was conducted which included 422 sarcopenia participants (146 males and 276 females). Sarcopenia was assessed according to the recommended diagnostic criteria of the Asia Working Group for Sarcopenia (AWGS). The levels of serum 25-hydroxyvitamin D (25(OH)D), 25-hydroxyvitamin D2 (25(OH)D2) and 25-hydroxyvitamin D3 (25(OH)D3) were determined by LC-MS/MS. Irisin levels were measured by enzyme-linked immunosorbent assay (ELISA). The relationship between serum concentration of vitamin D and irisin were determined using multiple linear regression analysis.ResultsAfter adjustment for potential confounding factors, a significant and positive relationship between changes in irisin across 25(OH)D, and 25(OH)D3 was observed (standard regression coefficients of 0.150 and 0.151, respectively, P &lt; 0.05). However, no significant relationship was observed between serum vitamin D concentrations and irisin levels in males.ConclusionsThis study demonstrated that a higher level of serum vitamin D is independently related to the increment of irisin in sarcopenia females, not in males. These investigations need to be verified in other large-scale prospective studies.
Gender-related differences in career development among gynecologic oncology surgeons in Europe. European Network of Young Gynecologic Oncologists’ Survey based data
Authors: Nikolova Tanja , Bossart Michaela , Kacperczyk-Bartnik Joanna , Razumova Zoia , Strojna Alexandra , Bizzarri Nicolò , Pletnev Andrei , Gómez-Hidalgo Natalia R. , Theofanakis Charalampos , Lanner Maximilian , Selcuk Ilker , Shushkevich Alexander , Anca Chelariu-Raicu , Nikolova Natasha , Concin Nicole , Zalewski Kamil 
Published: December 2022

IntroductionGender-related differences in career development are well known issues in various professions. An international survey on gender-related differences was performed among young gynecologic oncology surgeons in Europe to identify potential gender inequalities in career development.Material and methodsA survey on demographics, clinical and academic working environment, family/parenting, career development, salary and leadership was sent to all members of the European Network of Young Gynecologic Oncologists (ENYGO), which is a network within the European Society of Gynecologic Oncology (ESGO). Gynecologic oncology surgeons and obstetricians/gynecologists who actively work in this field in Europe were included in the study.ResultsResponses were analyzed from 192 gynecologic oncology surgeons of whom 65.1% (125/192) were female (median age 37, IQR: 34 - 42) and 34.9% (67/192) were male (median age 38, IQR: 36 - 41). Male reported to perform a median of 15 and female a median of 10 operations per month (p = .007). Among female, 24.8% had a leadership position vs. 44.8% among male, crude OR = 2.46, 95% CI 1.31-4.62, p&lt;.01. When stratifying for age under 41 and having children, 36.7% of male and 5.6% of female had a leadership position, adjusted OR 10.8, 95% CI 3.28-35.64, p&lt;.001. A significantly higher proportion of female compared to male believed they earned less than their gender counterparts at the same clinical position and with same qualifications (30.4% vs. 2.5%, p&lt;.001). There was not a statistically significant gender difference in the academic qualification PhD degree or professorship (p = .92 and p = .64, respectively). In the previous year, male published more peer-reviewed articles than female (median 3 vs. median 2; p = .017).ConclusionThis first comprehensive survey on gender-differences in gynecologic oncology in Europe revealed that there are gender gaps concerning several aspects during the critical time of career development in the young generation of gynecologic oncology surgeons. These gender gaps are particularly reflected by a lower rate of female leadership positions. ENYGO and ESGO are dedicated to work on solution to overcome the identified obstacles and to support closing gender gaps.
Development and validation of a new stage-specific nomogram model for predicting cancer-specific survival in patients in different stages of colon cancer: A SEER population-based study and external validation
Authors: Hu Chenhao , Shi Feiyu , Zhang Zhe , Zhang Lei , Liu Ruihan , Sun Xuejun , Zheng Liansheng , She Junjun 
Published: December 2022

BackgroundThe effects of laterality of the primary tumor on survival in patients in different stages of colon cancer are contradictory. We still lack a strictly evaluated and validated survival prediction tool, considering the different roles of tumor laterality in different stages.MethodsA total of 101,277 and 809 colon cancer cases were reviewed using the Surveillance, Epidemiology, and End Results database and the First Affiliated Hospital of Xi ‘an Jiaotong University database, respectively. We established training sets, internal validation sets and external validation sets. We developed and evaluated stage-specific prediction models and unified prediction models to predict cancer-specific survival and compared the prediction abilities of these models.ResultsCompared with right-sided colon cancers, the risk of cancer-specific death of left-sided colon cancer patients was significantly higher in stage I/II but was markedly lower in stage III patients. We established stage-specific prediction models for stage I/II and stage III separately and established a unified prediction model for all stages. By evaluating and validating the validation sets, we reported high prediction ability and generalizability of the models. Furthermore, the stage-specific prediction models had better predictive power and efficiency than the unified model.ConclusionsRight-sided colon cancer patients have better cancer-specific survival than left-sided colon cancer patients in stage I/II and worse cancer-specific survival in stage III. Using stage-specific prediction models can further improve the prediction of cancer-specific survival in colon cancer patients and guide clinical decisions.