bluuebunny/crossref_metadata_2025_split huggingface dataset:
EIF2S2 is a novel independent prognostic biomarker and correlated with immune infiltrates in hepatocellular carcinoma
Authors: Liu Jing , Liu Tongyu , Zhang Chuanhao , He Jiabei , Zhou Dong , Wang Zhe , Wang Ruoyu 
Published: October 2022

Background: Hepatocellular carcinoma (HCC) is a highly malignant disease with poor prognosis. It is urgent to find effective biomarkers. Eukaryotic Translation Initiation Factor 2 Subunit Beta (EIF2S2) is a subunit of heterotrimeric G protein EIF2, and its function is still unclear. We studied the role of EIF2S2 in the malignant progression of liver cancer and its relationship with immune infiltration.Methods: Download the RNA expression and clinical information of EIF2S2 from the Cancer Genome Atlas (TCGA) database, analyze the relationship between the expression of EIF2S2 and the prognosis and clinicopathological characteristics of HCC, analyze the differential genes by Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and tumor related immune infiltrating cells. The Protein expression level of EIF2S2 was obtained from Human Protein Atlas (HPA) databases. The relationship between EIF2S2 expression and immune infiltrates in HCC was analyzed on TIMER 2.0. The data processing analysis based on R language. Drug Sensitivity data from Genomics of Drug Sensitivity in Cancer (GDSC).Results: EIF2S2 is highly expressed in HCC patients and is associated with poor prognosis. The expression of EIF2S2 was also correlated with age, clinical stage and pathological grade. Univariate and multivariate COX regression analysis showed that EIF2S2 was an independent risk factor for survival. The receiver operating characteristic (ROC) curve of EIF2S2 also confirmed the diagnostic value of EIF2S2 in HCC patients. Through GO and KEGG enrichment analysis, EIF2S2 expression was found to be closely related to some immune pathways. The expression of EIF2S2 was correlated with memory B cell, plasma B cell, CD8+ T cell, CD4+ resting memory T cell and the expression of some immune checkpoints, such as PDCD1, TIGIT and CTLA-4. It is also more sensitive to paclitaxel, sunitinib and other drugs.Conclusion: This study shows that EIF2S2 can be used as a prognostic factor for HCC, which is closely related to immune infiltration and immune checkpoints, and may play a potential regulatory role in predicting drug sensitivity.
Case report: CD19-directed CAR-T cell therapy combined with BTK inhibitor and PD-1 antibody against secondary central nervous system lymphoma
Authors: Zhang Wenqi , Huang Chen , Liu Ruixia , Zhang Huichao , Li Weijing , Yin Shaoning , Wang Lianjing , Liu Wei , Liu Lihong 
Published: October 2022

Current therapeutic strategies for central nervous system (CNS) relapse of diffuse large B-cell lymphoma (DLBCL) are extremely limited. Secondary central nervous system lymphoma (SCNSL) also shows a grave prognosis and high mortality. This report describes a young female patient with DLBCL and CNS relapse who received low-dose CD19-directed chimeric antigen receptor T (CAR-T) cell therapy followed with Bruton’s tyrosine kinase inhibitor and programmed cell death protein 1 antibody after several lines of chemotherapy. However, limited reports on CAR-T cell therapy are applied for SCNSL, particularly those in combination with targeted agents. The current treatment combination for this case provides a new regimen for CNS relapse from DLBCL.Clinical Trial RegistrationClinicalTrials.gov number, NCT04666168.
Identification and characterization of aging/senescence-induced genes in osteosarcoma and predicting clinical prognosis
Authors: Lv Yigang , Wu Liyuan , Jian Huan , Zhang Chi , Lou Yongfu , Kang Yi , Hou Mengfan , Li Zhen , Li Xueying , Sun Baofa , Zhou Hengxing 
Published: October 2022

BackgroundAging is an influential risk factor for progression of both degenerative and oncological diseases of the bone. Osteosarcoma, considered the most common primary mesenchymal tumor of the bone, is a worldwide disease with poor 5-year survival. This study investigated the role of aging-/senescence-induced genes (ASIGs) in contributing to osteosarcoma diagnosis, prognosis, and therapeutic agent prediction.MethodsTherapeutically Applicable Research to Generate Effective Treatments (TARGET), Gene Expression Omnibus (GEO), and The Cancer Genome Atlas (TCGA) were used to collect relevant gene expression and clinical data of osteosarcoma and paracancerous tissues. Patients were clustered by consensus using prognosis-related ASIGs. ssGSEA, ESTIMATE, and TIMER were used to determine the tumor immune microenvironment (TIME) of subgroups. Functional analysis of differentially expressed genes between subgroups, including Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene set variation analyses (GSVAs), was performed to clarify functional status. Prognostic risk models were constructed by univariate Cox regression and least absolute shrinkage and selection operator (LASSO) regression. SCISSOR was used to identify relevant cells in osteosarcoma single-cell data for different risk groups. The effect of immunotherapy was predicted based on TIDE scores and chemotherapy drug sensitivity using CTRP and PRISM.ResultsThree molecular subgroups were identified based on prognostic differentially expressed ASIGs. Immunological infiltration levels of the three groups differed significantly. Based on GO and KEGG analyses, differentially expressed genes between the three subgroups mainly relate to immune and aging regulation pathways; GSVA showed substantial variations in multiple Hallmark pathways among the subgroups. The ASIG risk score built based on differentially expressed genes can predict patient survival and immune status. We also developed a nomogram graph to accurately predict prognosis in combination with clinical characteristics. The correlation between the immune activation profile of patients and the risk score is discussed. Through single-cell analysis of the tumor microenvironment, we identified distinct risk-group-associated cells with significant differences in immune signaling pathways. Immunotherapeutic efficacy and chemotherapeutic agent screening were evaluated based on risk score.ConclusionAging-related prognostic genes can distinguish osteosarcoma molecular subgroups. Our novel aging-associated gene signature risk score can be used to predict the osteosarcoma immune landscape and prognosis. Moreover, the risk score correlates with the TIME and provides a reference for immunotherapy and chemotherapy in terms of osteosarcoma.
Study on mineral composition design and mechanical properties improvement mechanism of high ferrite oil well cement
Authors: Fan Baitao , Huang Kun , Yang Xiangqian , Wu Zhiqiang , Ni Xiucheng , Cheng Xiaowei 
Published: October 2022

In shale gas production, secondary fracturing technology is often used to improve shale gas production capacity. However, the toughness of cement stone used in Class G oil wells is poor, and the cement sheath is easily damaged by impact load during fracturing, resulting in cement sheath sealing failure. To solve this problem, this paper proposes to improve the strength and toughness of cement paste by optimizing the mineral composition of Class G oil well cement. The cement clinker is burned in the laboratory, and the microstructure differences of clinker under different mineral composition ratios are observed by reflection microscope. The mechanical properties of cement paste before and after optimization are analyzed, and the best mineral composition ratio is obtained. The petrographic structure, hydration products and microstructure of high ferrite oil well cement were analyzed by petrography, X-ray diffraction analysis (XRD), thermal analysis (TG/DTG) and scanning electron microscopy (SEM), analyzed and explored its enhancement mechanism. The results show that the best mineral composition mass ratios of C3S, C2S, C3A and C4AF in high ferrite oil well cement are 58.34%, 16.39%, 1.51% and 17.94% respectively. Compared with grade G oil well cement, the compressive strength and flexural strength of curing 28 days are increased by 14.11% and 19.51%, respectively. The stress-strain results show that high ferrite oil well cement has better toughness. The petrographic results show that the lithofacies structure of high ferrite oil well cement is evenly distributed and the particle size is moderate; XRD, TG/DTG and microanalysis show that there are more hydration products in high ferrite oil well cement, the hydration products are closely combined, the hydration degree is more thorough, and the structure of cement paste is more compact. High ferrite oil well cement has the advantages of high strength and good toughness, which has potential advantages for shale gas cementing.
Gestational weight gain in the REVAMP pregnancy cohort in Western India: Comparison with international and national references
Authors: Dangat Kamini , Gupte Sanjay , Wagh Girija , Lalwani Sanjay , Randhir Karuna , Madiwale Shweta , Pisal Hemlata , Kadam Vrushali , Gundu Shridevi , Chandhiok Nomita , Kulkarni Bharati , Joshi Sadhana , Fall Caroline , Sachdev Harshpal Singh 
Published: October 2022

ObjectiveTo determine the trimester specific gestational weight gain (GWG) in a population of pregnant women from Western India and compare it with the Intergrowth–21st international and an Indian reference (GARBH–Ini cohort—Group for Advanced Research on BirtH outcomes).Study designA prospective longitudinal observational study was undertaken in Pune, West India and data for gestational weight gain was collected [the REVAMP study (Research Exploring Various Aspects and Mechanisms in Preeclampsia)]. Generalized Additive Models for Location, Scale and Shape method (GAMLSS model) were used to create GWG centile curves according to gestational age, stratified by BMI at recruitment (n = 640) and compared with Intergrowth-21st reference and GARBH–Ini cohort. Multivariable regression analysis was used to evaluate the relationship between GWG and antenatal risk factors.ResultsThe median GWG was 1.68, 5.80, 7.06, and 11.56 kg at gestational ages 18, 26, 30, and 40 weeks, respectively. In our study, pregnant women gained less weight throughout pregnancy compared to Intergrowth-21st study, but more weight compared to the GARBH–Ini cohort centile curves in all the BMI categories. GWG in overweight/obese women (BMI ≥ 25) was significantly lower (&lt;0.001) as compared to underweight (BMI &lt; 18.5), or normal weight women (BMI ≥ 18.5 and &lt;25). The median GWG at 40 weeks in underweight, normal and overweight/obese women was 13.18, 11.74, and 10.48 kg, respectively. Higher maternal BMI, older maternal age, higher parity and higher hemoglobin concentrations were associated with lower GWG, while taller maternal height was associated with greater GWG.ConclusionGWG of Indian women is lower than the prescriptive standards of the Intergrowth charts.
Prognostic effect of pulmonary hypertension in patients with chronic kidney disease: Univariate and multivariate analyses of factors associated with survival
Authors: Wang Lei , Zhang Wei , Zhang Cailian , Yan Zhe , Li Shaomei , Zhang Chunxia , Chen Yakun , Pan Qing , Liang Xuzhi , Chen Xian 
Published: October 2022

BackgroundPrognostic effect of pulmonary hypertension (PH) in patients with chronic kidney disease (CKD) is not fully clear yet, this study was designed to elucidate baseline characteristics of CKD patients with different severities of PH, the association between kidney indicators and PH severity, and survival factors in CKD patients with PH.MethodsWe extracted clinical data from electronic medical records of all patients diagnosed with PH in CKD from Jan 2016 to Dec 2020, and those with comorbid conditions causing PH were excluded. CKD stages were defined by estimated glomerular filtration rate thresholds. PH was defined as a systolic pulmonary artery pressure (sPAP) &gt;35 mmHg estimated using echocardiograms. Demographics, clinical data, and test results were analyzed, and all-cause mortality data were obtained.ResultsA total of 137 patients were included in the study. The mean age of the participants was 60 (42.5, 67) years, the mean sPAP was 58 (51, 69.5) mmHg, and 40.9% of the patients were women. Moderate PH group had more patients undergoing dialysis and higher frequency of coronary heart disease. Moderate-severe PH group had higher parathyroid hormone levels and lower low-density lipoprotein levels. Severe PH group had better kidney function parameters and lower serum phosphorus levels. PH severity had no direct relationship with CKD stages. In the univariate analysis, age and PH severity influenced survival. Multivariate analysis also showed independent prognostic effects for age and sPAP. Kaplan-Meyer curve intuitively displayed the survival differences among CKD patients with different PH severity. Predictor values of nomogram identified from survival analyses enabled calculation of death probabilities for CKD with PH patients. Nomogram was validated by ROC analysis.ConclusionsPH begins with early-stage CKD, and PH severity is not related to CKD progression. A higher pulmonary artery pressure and an older age are associated with an increased risk of death.
Noncovalent hyaluronan crosslinking by TSG-6: Modulation by heparin, heparan sulfate, and PRG4
Authors: Sin Yun Jin Ashley , MacLeod Rebecca , Tanguay Adam P. , Wang Andrew , Braender-Carr Olivia , Vitelli Teraesa M. , Jay Gregory D. , Schmidt Tannin A. , Cowman Mary K. 
Published: October 2022

The size, conformation, and organization of the glycosaminoglycan hyaluronan (HA) affect its interactions with soluble and cell surface-bound proteins. HA that is induced to form stable networks has unique biological properties relative to unmodified soluble HA. AlphaLISA assay technology offers a facile and general experimental approach to assay protein-mediated networking of HA in solution. Connections formed between two end-biotinylated 50 kDa HA (bHA) chains can be detected by signal arising from streptavidin-coated donor and acceptor beads being brought into close proximity when the bHA chains are bridged by proteins. We observed that incubation of bHA with the protein TSG-6 (tumor necrosis factor alpha stimulated gene/protein 6, TNFAIP/TSG-6) leads to dimerization or higher order multimerization of HA chains in solution. We compared two different heparin (HP) samples and two heparan sulfate (HS) samples for the ability to disrupt HA crosslinking by TSG-6. Both HP samples had approximately three sulfates per disaccharide, and both were effective in inhibiting HA crosslinking by TSG-6. HS with a relatively high degree of sulfation (1.75 per disaccharide) also inhibited TSG-6 mediated HA networking, while HS with a lower degree of sulfation (0.75 per disaccharide) was less effective. We further identified Proteoglycan 4 (PRG4, lubricin) as a TSG-6 ligand, and found it to inhibit TSG-6-mediated HA crosslinking. The effects of HP, HS, and PRG4 on HA crosslinking by TSG-6 were shown to be due to HP/HS/PRG4 inhibition of HA binding to the Link domain of TSG-6. Using the AlphaLISA platform, we also tested other HA-binding proteins for ability to create HA networks. The G1 domain of versican (VG1) effectively networked bHA in solution but required a higher concentration than TSG-6. Cartilage link protein (HAPLN1) and the HA binding protein segment of aggrecan (HABP, G1-IGD-G2) showed only low and variable magnitude HA networking effects. This study unambiguously demonstrates HA crosslinking in solution by TSG-6 and VG1 proteins, and establishes PRG4, HP and highly sulfated HS as modulators of TSG-6 mediated HA crosslinking.
Neurological disorders associated with glutamic acid decarboxylase 65 antibodies: Clinical spectrum and prognosis of a cohort from China
Authors: Bai Lin , Ren Haitao , Liang Menglin , Lu Qiang , Lin Nan , Liu Mange , Fan Siyuan , Cui Ruixue , Guan Hongzhi 
Published: October 2022

ObjectiveTo describe clinical phenotypes and prognosis of neurological autoimmunity related to glutamic acid decarboxylase 65 (GAD65) antibodies in China.MethodIn this retrospective observational study from Peking Union Medical College Hospital, we identified patients with neurological disorders related to GAD65 antibodies (cell-based assay) from May 2015 to September 2021. Clinical manifestations, immunotherapy responsiveness, and outcomes were collected after obtaining informed consent from all patients.ResultsFifty-five patients were included: 40 (72.73%) were women and initial neurological symptoms developed at 42(34-55) years of age. The median time to the nadir of the disease was 5 months (range from 1 day to 48 months). The clinical syndromes included limbic encephalitis (LE) or epilepsy (Ep) (n= 34, 61.82%), stiff-person syndromes (SPS) (n= 18, 32.73%), autoimmune cerebellar ataxia (ACA) (n= 11, 20%), and overlap syndrome in eight (14.55%) patients. Thirty-two (58.2%) patients had comorbidities of other autoimmune diseases, including Hashimoto thyroiditis (n= 17, 53.13%), T1DM (n= 11, 34.78%), vitiligo (n= 6, 18.75%), and others (n=5, 15.63%). Two (3.64%) patients had tumors, including thymoma and small cell lung cancer. Fifty-one (92.7%) patients received first-line immunotherapy (glucocorticoids and/or IV immunoglobulin), and 4 (7.3%) received second-line immunotherapy (rituximab). Long-term immunotherapy (mycophenolate mofetil) was administered to 23 (41.8%) patients. At the median time of 15 months (IQR 6–33.75 month, range 3–96 month) of follow-up, the patients' median modified Rankin Score (mRS) had declined from 2 to 1. Thirty-eight (70.4%) patients experienced clinical improvement (mRS declined ≥1), 47 (87%) had favorable clinical outcomes (mRS ≤2), and nine were symptom-free (16.7%). The sustained response to immunotherapy ranged from 7/15 (63.63%) in ACA patients and 22/34 (64.7%) in LE/Ep patients to 14/17 (82.35%) in SPS patients.ConclusionsLE/Ep was the most common neurological phenotype of GAD65 antibody neurological autoimmunity in our cohort. Most patients had comorbidities of other autoimmune diseases, but underlying tumors were rare. Most patients responded to immunotherapy. However, the long-term prognosis varied among different clinical phenotypes.
Identification of bromodomain-containing proteins prognostic value and expression significance based on a genomic landscape analysis of ovarian serous cystadenocarcinoma
Authors: Zhang Juan , Li Yan , Fan Ting-yu , Liu Dan , Zou Wen-da , Li Hui , Li Yu-kun 
Published: October 2022

BackgroundOvarian serous cystadenocarcinoma (OSC), a common gynecologic tumor, is characterized by high mortality worldwide. Bromodomain (BRD)-containing proteins are a series of evolutionarily conserved proteins that bind to acetylated Lys residues of histones to regulate the transcription of multiple genes. The ectopic expression of BRDs is often observed in multiple cancer types, but the role of BRDs in OSC is still unclear.MethodsWe performed the differential expression, GO enrichment, GSEA, immune infiltration, risk model, subtype classification, stemness feature, DNA alteration, and epigenetic modification analysis for these BRDs based on multiple public databases.ResultsMost BRDs were dysregulated in OSC tissues compared to normal ovary tissues. These BRDs were positively correlated with each other in OSC patients. Gene alteration and epigenetic modification were significant for the dysregulation of BRDs in OSC patients. GO enrichment suggested that BRDs played key roles in histone acetylation, viral carcinogenesis, and transcription coactivator activity. Two molecular subtypes were classified by BRDs for OSC, which were significantly correlated with stemness features, m6A methylation, ferroptosis, drug sensitivity, and immune infiltration. The risk model constructed by LASSO regression with BRDs performed moderately well in prognostic predictions for OSC patients. Moreover, BRPF1 plays a significant role in these BRDs for the development and progression of OSC patients.ConclusionBRDs are potential targets and biomarkers for OSC patients, especially BRPF1.
A comparative study of robotics and laparoscopic in minimally invasive pancreatoduodenectomy: A single-center experience
Authors: Zong Ke , Luo Kai , Chen Kunlun , Ye Jianwen , Liu Wentao , Zhai Wenlong 
Published: October 2022

ObjectiveTo retrospectively compare the short-term benefits of robotic surgery and laparoscopic in the perioperative period of minimally invasive pancreatoduodenectomy (MIPD).MethodsThis retrospective analysis evaluated patients who underwent laparoscopic pancreatoduodenectomy (LPD) or robotic pancreatoduodenectomy (RPD) from March 2018 to January 2022 in the First Affiliated Hospital of Zhengzhou University (Zhengzhou, China). Perioperative data, including operating time, complications, morbidity and mortality, estimated blood loss (EBL), and postoperative length of stay, were analysed.ResultA total of 190 cases of MIPD were included, of which 114 were LPD and 76 were RPD. There was no significant difference between the two groups in gender, age, previous history of upper abdominal operation, jaundice (&gt;150 µmol/L), or diabetes (P &gt; 0.05). The conversion rate to laparotomy was similar in the LPD and RPD groups (5.3% vs. 6.6%, P = 0.969). A total of 179 cases of minimally invasive pancreatoduodenectomy were successfully performed, including 108 cases of LPD and 71 cases of RPD. There were significant differences between the laparoscopic and robotic groups in operation time [mean, 5.97 h vs. 5.42 h, P &lt; 0.05] and postoperative length of stay [mean, 15.3 vs. 14.6 day, P &lt; 0.05]. No significant difference was observed between the two groups in terms of EBL, intraoperative transfusion, complication rate, mortality rate, or reoperation rate (P &gt; 0.05). There were no significant differences in pathological type, number of lymph nodes harvested, or positive lymph node rate (P &gt; 0.05).ConclusionRPD had an advantage compared to LPD in reduced operation time and postoperative length of stay, technical feasibility, and safety.