bluuebunny/crossref_metadata_2025_split huggingface dataset:
Global research trends and hotspots on glioma stem cells
Authors: Song Sirong , Wu Haiyang , Wang Fanchen , Jiao Jiji , Xu Lixia , Wang Hongguang , Tong Xiaoguang , Yan Hua 
Published: September 2022

BackgroundGlioma stem cells (GSCs) are a sub-population of cancer stem cells with capacity of self-renewal and differentiation. Accumulated evidence has revealed that GSCs were shown to contribute to gliomagenesis, distant metastasis as well as the resistance to radiotherapy and chemotherapy. As a result, GSCs were regarded as a promising therapeutic target in human glioma. The purpose of our study is to identify current state and hotspots of GSCs research by analyzing scientific publications through bibliometric methods.MethodsAll relevant publications on GSCs during 2003-2021 were extracted from the Science Citation Index Expanded of Web of Science Core Collection (WoSCC), and related information was collected and analyzed using Microsoft Excel 2016, GraphPad Prism 8 and VOSviewer software.ResultsA total of 4990 papers were included. The United States accounted for the largest number of publications (1852), the second average citations per item (ACI) value (67.54) as well as the highest H-index (157). Cancer Research was the most influential journal in this field. The most contributive institution was League of European Research Universities. RICH JN was the author with the most publications (109) and the highest H-index (59). All studies were clustered into 3 groups: “glioma stem cell properties”, “cell biological properties” and “oncology therapy”. The keywords “identification”, “CD133” and “side population” appeared earlier with the smaller average appearing years (AAY), and the keywords”radiotherapy” and “chemotherapy” had the latest AAY. The analysis of top cited articles showed that “temozolomide”, “epithelial-mesenchymal transition”, and “immunotherapy” emerged as new focused issues.ConclusionThere has been a growing number of researches on GSCs. The United States has always been a leading player in this domain. In general, the research focus has gradually shifted from basic cellular biology to the solutions of clinical concerns. “Temozolomide resistance”, “epithelial-mesenchymal transition”, and “immunotherapy” should be given more attention in the future.
Clonal evolution characteristics and reduced dimension prognostic model for non-metastatic metachronous bilateral breast cancer
Authors: Li Lingyu , Li Jiaxuan , Jia Jiwei , He Hua , Li Mingyang , Yan Xu , Yu Qing , Guo Hanfei , Wang Hong , Lv Zheng , Sun Haishuang , Liao Guidong , Cui Jiuwei 
Published: September 2022

BackgroundHow to evaluate the prognosis and develop overall treatment strategies of metachronous bilateral breast cancer (MBBC) remains confused in clinical. Here, we investigated the correlation between clonal evolution and clinical characteristics of MBBC; we aim to establish a novel prognostic model in these patients.MethodsThe data from Surveillance, Epidemiology, and End Results (SEER) database and the First Hospital of Jilin University were analyzed for breast cancer–specific cumulative mortality (BCCM) by competing risk model. Meanwhile, whole-exome sequencing was applied for 10 lesions acquired at spatial–temporal distinct regions of five patients from our own hospital to reconstruct clonal evolutionary characteristics of MBBC. Then, dimensional-reduction (DR) cumulative incidence function (CIF) curves of MBBC features were established on different point in diagnostic interval time, to build a novel DR nomogram.ResultsSignificant heterogeneity in genome and clinical features of MBBC was widespread. The mutational diversity of contralateral BC (CBC) was significantly higher than that in primary BC (PBC), and the most effective prognostic MATH ratio was significantly correlated with interval time (R2 = 0.85, p&lt; 0.05). In SEER cohort study (n = 13,304), the interval time was not only significantly affected the BCCM by multivariate analysis (p&lt; 0.000) but determined the weight of clinical features (T/N stage, grade and ER status) on PBC and CBC in prognostic evaluation. Thus, clinical parameters after DR based on interval time were incorporated into the nomogram for prognostic predicting BCCM. Concordance index was 0.773 (95% CI, 0.769–0.776) in training cohort (n = 8,869), and 0.819 (95% CI, 0.813–0.826) in validation cohort (n = 4,435).ConclusionsBilateral heterogeneous characteristics and interval time were determinant prognostic factors of MBBC. The DR prognostic nomogram may help clinicians in prognostic evaluation and decision making.
Identification and validation of an immunological microenvironment signature and prediction model for epstein-barr virus positive lymphoma: Implications for immunotherapy
Authors: Yao Chenjiao , Xu Ruoyao , Li Qianyuan , Xiao Sheng , Hu Min , Xu Linyong , Zhuang Quan 
Published: September 2022

BackgroundEpstein-Barr virus (EBV) is considered a carcinogenic virus, which is associated with high risk for poor prognosis in lymphoma patients, and there has been especially no satisfying and effective treatment for EBV+ lymphoma. We aimed to identify the immunological microenvironment molecular signatures which lead to the poor prognosis of EBV+ lymphoma patients.MethodsDifferential genes were screened with microarray data from the GEO database (GSE38885, GSE34143 and GSE13996). The data of lymphoid neoplasm diffuse large B-cell lymphoma (DLBC) from the TCGA database and GSE4475 were used to identify the prognostic genes. The data of GSE38885, GSE34143, GSE132929, GSE58445 and GSE13996 were used to eluate the immune cell infiltration. Formalin-fixed, paraffin-embedded tissue was collected for Real Time Quantitative PCR from 30 clinical samples, including 15 EBV+ and 15 EBV- lymphoma patients.ResultsFour differential genes between EBV+ and EBV- lymphoma patients were screened out with the significance of the survival and prognosis of lymphoma, including CHIT1, SIGLEC15, PLA2G2D and TMEM163. Using CIBERSORT to evaluate immune cell infiltration, we found the infiltration level of macrophages was significantly different between EBV+ and EBV- groups and was closely related to different genes. Preliminary clinical specimen verification identified that the expression levels of CHIT1 and TMEM163 were different between EBV+ and EBV- groups.ConclusionsOur data suggest that differences in expression levels of CHIT1 and TMEM163 and macrophage infiltration levels may be important drivers of poor prognosis of EBV+ lymphoma patients. These hub genes may provide new insights into the prognosis and therapeutic target for EBV+ lymphoma.
Body composition as a predictor of chemotherapy-related toxicity in pancreatic cancer patients: A systematic review
Authors: Rizzo Stefania , Scala Isabel , Robayo Angela Rodriguez , Cefalì Marco , De Dosso Sara , Cappio Stefano , Xhepa Genti , Del Grande Filippo 
Published: September 2022

ObjectivesThe objective of this systematic review was to assess associations between quantitative body composition measures extracted from imaging examinations and chemotherapy-related toxicity in pancreatic cancer patients. A secondary objective was to evaluate the different definitions of sarcopenia across included studies.MethodsThis systematic review was conducted according to the PRISMA statement. A comprehensive literature search of three electronic databases was performed by two authors. For each eligible article, information was collected concerning the clinical setting; basic study; population characteristics; technical; body composition features evaluated; CA 19.9 tumor marker levels; chemotherapy drugs administered; toxicities (hematologic, nausea/vomiting, diarrhea, neuropathy, reduction of number of cycles, overall toxicity); association of body composition values with toxicities. The overall quality of the included studies was critically evaluated.ResultsAfter the initial retrieval of 1137 articles, the systematic review included 12 articles (1/12 in the neo-adjuvant setting; 2/12 in the adjuvant setting; 3/12 in the metastatic setting; 2/12 in the unresectable setting; the other 4/12 included more than one clinical setting). The number of patients included ranged between 17 and 251; mean/median age ranged between 63 and 77 years; the percentage of sarcopenic patients ranged between 23 and 76%. The most frequent body composition parameter evaluated was skeletal muscle index (11/12). Chemotherapy regimens included gemcitabine (as monotherapy or in combination with other drugs); FOLFIRINOX and S-1. Among the trials including gemcitabine, 2/9 demonstrated an association with toxicity, whereas 7/9 did not; among those including FOLFIRINOX, one demonstrated associated toxicity whereas the others did not. Altogether, 4/12 papers demonstrated an association between the body composition values and the development of chemotherapy-related toxicities.ConclusionsThere is a wide variability of results about the association of body composition and chemotherapy-related toxicity in PC patients. Furthermore, cut-off values to define sarcopenia in PC patients are not yet uniformly defined.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022337753, identifier CRD42022337753.
Intermittent MEK inhibition for the treatment of metastatic uveal melanoma
Authors: Khan Shaheer , Patel Sapna P. , Shoushtari Alexander N. , Ambrosini Grazia , Cremers Serge , Lee Shing , Franks Lauren , Singh-Kandah Shahnaz , Hernandez Susana , Sender Naomi , Vuolo Kristina , Nesson Alexandra , Mundi Prabhjot , Izar Benjamin , Schwartz Gary K. , Carvajal Richard D. 
Published: September 2022

IntroductionUveal melanoma (UM) is associated with poor outcomes in the metastatic setting and harbors activating mutations resulting in upregulation of MAPK signaling in almost all cases. The efficacy of selumetinib, an oral allosteric inhibitor of MEK1/2, was limited when administered at a continual dosing schedule of 75 mg BID. Preclinical studies demonstrate that intermittent MEK inhibition reduces compensatory pathway activation and promotes T cell activation. We hypothesized that intermittent dosing of selumetinib would reduce toxicity, allow for the administration of increased doses, and achieve more complete pathway inhibition, thus resulting in improved antitumor activity.MethodsWe conducted a phase Ib trial of selumetinib using an intermittent dosing schedule in patients with metastatic UM. The primary objective was to estimate the maximum tolerated dose (MTD) and assess safety and tolerability. Secondary objectives included assessment of the overall response rate (RR), progression-free survival (PFS) and overall survival (OS). Tumor biopsies were collected at baseline, on day 3 (on treatment), and between days 11-14 (off treatment) from 9 patients for pharmacodynamic (PD) assessments.Results29 patients were enrolled and received at least one dose of selumetinib across 4 dose levels (DL; DL1: 100 mg BID; DL2: 125 mg BID; DL3: 150 mg BID; DL4: 175 mg BID). All patients experienced a treatment-related adverse event (TRAE), with 5/29 (17%) developing a grade 3 or higher TRAE. Five dose limiting toxicities (DLT) were observed: 2/20 in DL2, 2/5 in DL3, 1/1 in DL4. The estimated MTD was 150 mg BID (DL3), with an estimated probability of toxicity of 29% (90% probability interval 16%-44%). No responses were observed; 11/29 patients achieved a best response of stable disease (SD). The median PFS and OS were 1.8 months (95% CI 1.7, 4.5) and 7.1 months (95% CI 5.3, 11.5). PD analysis demonstrated at least partial pathway inhibition in all samples at day 3, with reactivation between days 11-14 in 7 of those cases.ConclusionsWe identified 150 mg BID as the MTD of intermittent selumetinib, representing a 100% increase over the continuous dose MTD (75 mg BID). However, no significant clinical efficacy was observed using this dosing schedule.
The prognostic value of fibrinogen to albumin ratio in malignant tumor patients: A meta-analysis
Authors: Li Baibei , Deng Huachu , Lei Biao , Chen Leijie , Zhang Xinyuan , Sha Dingran 
Published: September 2022

BackgroundRecent studies have shown that the fibrinogen to albumin ratio (FAR) is closely related to the prognosis of various cancers. The aim of this systematic review and meta-analysis was to investigate the prognostic value of FAR in malignancies based on the available evidence.MethodTo systematically search the Cochrane Library, Embase, PubMed, Google Scholar, Baidu scholars, CNKI and VIP databases for relevant studies published before April 1, 2022, and to evaluate the fibrinogen-to-albumin ratio (FAR) and survival of patients with malignant tumors through a meta-analysis relationship between the results. Results. This meta-analysis included 19 eligible studies involving 5926 cancer patients. We found that high FAR was associated with poor overall survival (HR=2.25, 95%CI 1.86-2.74, p&lt;0.001), recurrence-free survival (HR=2.29, 95%CI 1.91-2.76, P&lt;0.001), progression-free survival (HR: 2.10, 95%CI 1.58-2.79, p&lt;0.001), disease-free survival (HR=1.52, 95%CI 1.17-1.96, p=0.001), and time to recurrence (HR: 1.555, 95%CI 1.031-2.346, P=0.035) was significantly correlated.ConclusionsHigh FAR is significantly associated with poor clinical outcomes in cancer, suggesting that it may be an important predictor of prognosis in patients with malignancies.
Identification of pyroptosis-related lncRNA signature and AC005253.1 as a pyroptosis-related oncogene in prostate cancer
Authors: Yu JiangFan , Tang Rui , Li JinYu 
Published: September 2022

BackgroundPyroptosis and prostate cancer (PCa) are closely related. The role of pyroptosis-related long non-coding RNAs (lncRNAs) (PRLs) in PCa remains elusive. This study aimed to explore the relationship between PRL and PCa prognosis.MethodsGene expression and clinical signatures were obtained from The Cancer Genome Atlas and Gene Expression Omnibus databases. A PRL risk prediction model was established by survival random forest analysis and least absolute shrinkage and selection operator regression. Functional enrichment, immune status, immune checkpoints, genetic mutations, and drug susceptibility analyses related to risk scores were performed by the single-sample gene set enrichment analysis, gene set variation analysis, and copy number variation analysis. PRL expression was verified in PCa cells. Cell Counting Kit-8, 5-ethynyl-2′-deoxyuridine, wound healing, transwell, and Western blotting assay were used to detect the proliferation, migration, invasion, and pyroptosis of PCa cells, respectively.ResultsPrognostic features based on six PRL (AC129507.1, AC005253.1, AC127502.2, AC068580.3, LIMD1-AS1, and LINC01852) were constructed, and patients in the high-score group had a worse prognosis than those in the low-score group. This feature was determined to be independent by Cox regression analysis, and the area under the curve of the 1-, 3-, and 5-year receiver operating characteristic curves in the testing cohort was 1, 0.93, and 0.92, respectively. Moreover, the external cohort validation confirmed the robustness of the PRL risk prediction model. There was a clear distinction between the immune status of the two groups. The expression of multiple immune checkpoints was also reduced in the high-score group. Gene mutation proportion in the high-score group increased, and the sensitivity to drugs increased significantly. Six PRLs were upregulated in PCa cells. Silencing of AC005253.1 inhibited cell proliferation, migration, and invasion in DU145 and PC-3 cells. Moreover, silencing of AC005253.1 promoted pyroptosis and inflammasome AIM2 expression.ConclusionsOverall, we constructed a prognostic model of PCa with six PRLs and identified their expression in PCa cells. The experimental verification showed that AC005253.1 could affect the proliferation, migration, and invasion abilities of PCa cells. Meanwhile, AC005253.1 may play an important role in PCa by affecting pyroptosis through the AIM2 inflammasome. This result requires further research for verification.
Perceptions and experiences of Congolese midwives implementing a low-cost battery-operated heart rate meter during newborn resuscitation
Authors: Thornton Madeline , Ishoso Daniel , Lokangaka Adrien , Berkelhamer Sara , Bauserman Melissa , Eilevstjønn Joar , Iyer Pooja , Kamath-Rayne Beena D. , Mafuta Eric , Myklebust Helge , Patterson Janna , Tshefu Antoinette , Bose Carl , Patterson Jackie K. 
Published: September 2022

Background900,000 newborns die from respiratory depression each year; nearly all of these deaths occur in low- and middle-income countries. Deaths from respiratory depression are reduced by evidence-based resuscitation. Electronic heart rate monitoring provides a sensitive indicator of the neonate's status to inform resuscitation care, but is infrequently used in low-resource settings. In a recent trial in the Democratic Republic of the Congo, midwives used a low-cost, battery-operated heart rate meter (NeoBeat) to continuously monitor heart rate during resuscitations. We explored midwives' perceptions of NeoBeat including its utility and barriers and facilitators to use.MethodsAfter a 20-month intervention in which midwives from three facilities used NeoBeat during resuscitations, we surveyed midwives and conducted focus group discussions (FGDs) regarding the incorporation of NeoBeat into clinical care. FGDs were conducted in Lingala, the native language, then transcribed and translated from Lingala to French to English. We analyzed data by: (1) coding of transcripts using Nvivo, (2) comparison of codes to identify patterns in the data, and (3) grouping of codes into categories by two independent reviewers, with final categories determined by consensus.ResultsEach midwife from Facility A used NeoBeat on an estimated 373 newborns, while each midwife at facilities B and C used NeoBeat an average 24 and 47 times, respectively. From FGDs with 30 midwives, we identified five main categories of perceptions and experiences regarding the use of NeoBeat: (1) Providers' initial skepticism evolved into pride and a belief that NeoBeat was essential to resuscitation care, (2) Providers viewed NeoBeat as enabling their resuscitation and increasing their capacity, (3) NeoBeat helped providers identify flaccid newborns as liveborn, leading to hope and the perception of saving of lives, (4) Challenges of use of NeoBeat included cleaning, charging, and insufficient quantity of devices, and (5) Providers desired to continue using the device and to expand its use beyond resuscitation and their own facilities.ConclusionMidwives perceived that NeoBeat enabled their resuscitation practices, including assisting them in identifying non-breathing newborns as liveborn. Increasing the quantity of devices per facility and developing systems to facilitate cleaning and charging may be critical for scale-up.
A population-based study on prevalence and predisposing risk factors of infant functional gastrointestinal disorders in a single center in Southern Fujian
Authors: Huang Huanhuan , Wang Caiyun , Lin Wei , Zeng Yongbin , Wu Bin 
Published: September 2022

Background and aimThe prevalence of infant functional gastrointestinal disorders (FGIDs) varies across different areas but is largely unknown in southern Fujian. The aim of this study is to evaluate the prevalence of infant FGIDs in southern Fujian according to Rome IV diagnostic criteria.MethodsA cross-sectional prospective questionnaire-based survey was conducted among healthy infants between 0 and 3 months of age in southern Fujian. A total of 1,006 infants who received a physical examination from October 2017 to October 2018 were recruited in this study. Parents or caregivers provided demographic information and completed the questionnaire on gastrointestinal symptoms for infants. Infants with FGIDs were diagnosed using the Rome IV criteria.ResultsBased on the Rome IV criteria, the prevalence of having a FGID in infants is 58.3% (586/1,006). The most common FGIDs in infants were regurgitation (45.7%, 460/1,006), followed by difficult defecation (3.6%, 36/1,006), functional constipation (3.2%, 32/1,006), and colic (2.4%, 24/1,006). No infants fulfilled diagnostic criteria for rumination syndrome and cyclic vomiting syndrome. Among the infants with FGIDs, 457 cases (78.0%, 457/586) were found with single FGID. Combined FGIDs were diagnosed in 129 (22.0%, 129/586) infants; of whom, 21.2% (124/586) had double disorders and 0.9% (5/586) had triple disorders. The most common combined FGIDs were regurgitation and difficult defecation (12.8%), followed by regurgitation and colic (2.4%). Risk factor analysis revealed that younger paternal age (B = 0.424, P = 0.004), paternal history of FGIDs (B = 0.821, P = 0.000), maternal history of FGIDs (B = 0.427, P = 0.012), and probiotics received in infant (B = 0.324, P = 0.032) were associated with an increased risk of infant FGIDs, whereas vitamin D supplementation after birth (B = −0.690, P = 0.000) can reduce the risk of developing FGIDs.ConclusionFGIDs are common in infants living in southern Fujian according to Rome IV diagnostic criteria. The most common FGIDs in infants were regurgitation, difficult defecation, and functional constipation. Factors including younger paternal age, parental history of FGIDs, and the probiotic supplementation in infant showed a significant association with infant FGIDs. Whereas, vitamin D supplementation in infant was found to be a protective factor against FGIDs.
Identification of cellular heterogeneity and immunogenicity of chondrocytes via single-cell RNA sequencing technique in human osteoarthritis
Authors: Hu Xinyue , Li Zhuang , Ji Mingliang , Lin Yucheng , Chen Yuzhi , Lu Jun 
Published: September 2022

Background: Osteoarthritis (OA) has placed a heavy burden to the economy and humanistics. To explore the biological functions and markers of chondrocytes contributes significantly to the accurate diagnosis and targeted treatment of OA.Methods: We systematically analyzed the immunogenicity and biological function of varied chondrocytes at single cell resolution, and identified the chondrocyte subtypes and biomarkers involved in the development of OA, which are verified in the bulk sequencing cohort.Results: Based on previous study, we defined eight subtypes of chondrocytes with different biological functions, finding out that effector chondrocytes (ECs) and fibrocartilage chondrocytes (FCs) may promote the development of OA. Compared with other chondrocytes, ECs and FCs show stronger immunogenicity. FCs mainly affects the degeneration of cartilage caused by fibrous degeneration, while ECs mainly exerts immune function and causes tissues inflammation. In addition, the canonical gene markers of EC and FC assist with the prediction of OA, which has been verified in Bulk RNA sequencing data from two GEO datasets.Conclusion: In summary, this study provides a new perspective for the exploration of cellular heterogeneity and pathophysiology in OA and will make contribution to the accurate diagnosis and targeted treatment of OA.