bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genotypic and phenotypic characteristics of 12 chinese children with glycogen storage diseases
Authors: Dong Rui , Wei Xuxia , Zhang Kaihui , Song Fengling , Lv Yuqiang , Gao Min , Wang Dong , Ma Jian , Gai Zhongtao , Liu Yi 
Published: August 2022

Background: Glycogen storage diseases (GSDs) are known as a group of disorders characterized by genetic errors leading to accumulation of glycogen in various tissues. Since different types of GSD can sometimes be clinically indistinguishable, next generation sequencing is becoming a powerful tool for clinical diagnosis.Methods: 12 patients with suspected GSDs and their parents were enrolled in this study. The clinical and laboratory data of the patients were reviewed. Causative gene variants were identified in the patients using whole exome sequencing (WES) and verified by Sanger sequencing.Results: Genetic testing and analysis showed that 7 patients were diagnosed with GSD II (Pompe disease), 2 patients with GSD III, 1 patient with GSD VI, and 2 patients with GSD IXα. A total number of 18 variants were identified in 12 patients including 11 variants in GAA gene, 3 variants in AGL gene, 2 variants in PYGL gene and 2 variants in PHKA2 gene, of which 9 variants were reported and 9 variants were novel. SIFT, Polyphen-2, Mutation Taster, and REVEL predicted the novel variants (except GAA c.1052_1075 + 47del) to be disease-causing. The 3D structures of wild/mutant type GAA protein were predicted indicating that variants p. Trp621Gly, p. Pro541Leu, p. Ser800Ile and p. Gly293Trp might affect the proteins function via destroying hydrogen bonds or conformational constraints. Neither liver size nor laboratory findings allow for a differentiation among GSD III, GSD VI and GSD IXα.Conclusion: Our study expanded the variation spectrum of genes associated with GSDs. WES, in combination with clinical, biochemical, and pathological hallmarks, could provide accurate results for diagnosing and sub-typing GSD and related diseases in clinical setting.
Identification of N7-methylguanosine-related IncRNA signature as a potential predictive biomarker for colon adenocarcinoma
Authors: Ma Xiaomei , Yang Baoshun , Yang Yuan , Wu Guozhi , Ma Xiaoli , Yu Xiao , Li Yingwen , Wang Yuping , Guo Qinghong 
Published: August 2022

N7-Methylguanosine (m7G) is an RNA modification serving as a key part of colon cancer development. Thus, a comprehensive analysis was executed to explore prognostic roles and associations with the immune status of the m7G-related lncRNA (m7G-RNAs) in colon adenocarcinoma (COAD). Identification of m7G-RNAs was achieved via Pearson’s correlation analysis of lncRNAs in the TCGA-COAD dataset and m7G regulators. A prognostic signature was developed via LASSO analyses. ESTIMATE, CIBERSORT, and ssGSEA algorithms were utilized to assess immune infiltration between different risk groups. Survival analysis suggested the high-risk group possesses poor outcomes compared with the low-risk group. According to the ROC curves, the m7G-RNAs signature exhibited a reliable capability of prediction (AUCs at 1, 3, and 5 years were 0.770, 0.766, and 0.849, respectively). Multivariate hazard analysis proved that the signature was an independent predictive indicator for OS. Moreover, the risk score was related to infiltration levels of naïve B cells, CD4+ memory T cells, and resting NK cells. The result revealed the prognostic value of m7G modification in COAD and provided a novel perspective on personalized immunotherapy strategies.
Construction and validation of a novel coagulation-related 7-gene prognostic signature for gastric cancer
Authors: Wang Bofang , Zou Dan , Wang Na , Wang Haotian , Zhang Tao , Gao Lei , Ma Chenhui , Zheng Peng , Gu Baohong , Li Xuemei , Wang Yunpeng , He Puyi , Ma Yanling , Wang Xueyan , Chen Hao 
Published: August 2022

Background: Gastric cancer (GC) is the most common malignant tumor. Due to the lack of practical molecular markers, the prognosis of patients with advanced gastric cancer is still poor. A number of studies have confirmed that the coagulation system is closely related to tumor progression. Therefore, the purpose of this study was to construct a coagulation-related gene signature and prognostic model for GC by bioinformatics methods.Methods: We downloaded the gene expression and clinical data of GC patients from the TCGA and GEO databases. In total, 216 coagulation-related genes (CRGs) were obtained from AmiGO 2. Weighted gene co-expression network analysis (WGCNA) was used to identify coagulation-related genes associated with the clinical features of GC. Last absolute shrinkage and selection operator (LASSO) Cox regression was utilized to shrink the relevant predictors of the coagulation system, and a Coag-Score prognostic model was constructed based on the coefficients. According to this risk model, GC patients were divided into high-risk and low-risk groups, and overall survival (OS) curves and receiver operating characteristic (ROC) curves were drawn in the training and validation sets, respectively. We also constructed nomograms for predicting 1-, 2-, and 3-year survival in GC patients. Single-sample gene set enrichment analysis (ssGSEA) was exploited to explore immune cells’ underlying mechanisms and correlations. The expression levels of coagulation-related genes were verified by real-time quantitative polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC).Results: We identified seven CRGs employed to construct a Coag-Score risk model using WGCNA combined with LASSO regression. In both training and validation sets, GC patients in the high-risk group had worse OS than those in the low-risk group, and Coag-Score was identified as an independent predictor of OS, and the nomogram provided a quantitative method to predict the 1-, 2-, and 3-year survival rates of GC patients. Functional analysis showed that Coag-Score was mainly related to the MAPK signaling pathway, complement and coagulation cascades, angiogenesis, epithelial–mesenchymal transition (EMT), and KRAS signaling pathway. In addition, the high-risk group had a significantly higher infiltration enrichment score and was positively associated with immune checkpoint gene expression. Conclusion: Coagulation-related gene models provide new insights and targets for the diagnosis, prognosis prediction, and treatment management of GC patients.
Implementation of a biochemical, clinical, and genetic screening programme for familial hypercholesterolemia in 26 centres in Spain: The ARIAN study
Authors: Arrobas Velilla Teresa , Brea Ángel , Valdivielso Pedro 
Published: August 2022

Background: Familial hypercholesterolemia (FH) is clearly underdiagnosed and undertreated. The aim of this present study is to assess the benefits of FH screening through a joint national program implemented between clinical laboratories and lipid units.Methods: All clinical laboratory tests from 1 January 2017 to 31 December 2018 were reviewed, and those with LDL cholesterol (LDL-C) levels &gt;250 mg/dl were identified in subjects &gt;18 years of age of both sexes. Once secondary causes had been ruled out, the treating physician was contacted and advised to refer the patient to an LU to perform the Dutch Lipid Clinic Network score and to request genetic testing if the score was ≥6 points. Next Generation Sequencing was used to analyse the promoter and coding DNA sequences of four genes associated with FH (LDLR, APOB, PCSK9, APOE) and two genes that have a clinical overlap with FH characteristics (LDLRAP1 and LIPA). A polygenic risk score based on 12 variants was also obtained.Results: Of the 3,827,513 patients analyzed in 26 centers, 6,765 had LDL-C levels &gt;250 mg/dl. Having ruled out secondary causes and known cases of FH, 3,015 subjects were included, although only 1,205 treating physicians could be contacted. 635 patients were referred to an LU and genetic testing was requested for 153 of them. This resulted in a finding of sixty-seven pathogenic variants for FH, 66 in the LDLR gene and one in APOB. The polygenic risk score was found higher in those who had no pathogenic variant compared to those with a pathogenic variant.Conclusion: Despite its limitations, systematic collaboration between clinical laboratories and lipid units allows for the identification of large numbers of patients with a phenotypic or genetic diagnosis of FH, which will reduce their vascular risk. This activity should be part of the clinical routine.
Efficacy and safety of concomitant immunotherapy and denosumab in patients with advanced non-small cell lung cancer carrying bone metastases: A retrospective chart review
Authors: Li Hong-Shuai , Lei Si-Yu , Li Jun-Ling , Xing Pu-Yuan , Hao Xue-Zhi , Xu Fei , Xu Hai-Yan , Wang Yan 
Published: August 2022

BackgroundSynergistic anti-tumor effects were observed in vivo and in vitro when immune checkpoint inhibitors (ICIs) were combined with denosumab. However, the clinical benefit and safety of this synergy have not been adequately evaluated in non-small cell lung cancer (NSCLC).MethodsConsecutive charts of NSCLC patients with bone metastases between December 2020 and December 2021 in the Chinese National Cancer Center were reviewed. The entire cohort was divided into one experimental group (denosumab + ICIs [DI]) and three control groups (denosumab + non-ICIs [DnI], phosphates + ICIs [PI], phosphates + non-ICIs [PnI]). Real-world objective response rates (ORRs), median progression-free survival (mPFS), skeletal-related events (SREs), and adverse events (AEs) were compared between groups.ResultsA total of 171/410 (41.7%) patients with advanced or recurrent NSCLC carrying bone metastases who received bone-targeted therapy were eligible for analysis. Although the DI group showed a better benefit trend, differences were not statistically significant concerning the therapeutic efficacy among the DI group (n = 40), PI group (n = 74), DnI group (n = 15), and PnI group (n = 42) (ORRs: 47.5%, 43.2%, 33.3%, and 40.5%, respectively, p = 0.799; and mPFS: 378, 190, 170, and 172 days, respectively, p = 0.115; SREs: 5%, 10.8%, 13.3%, and 11.9%, respectively, p = 0.733). Nevertheless, further analysis in the NON-DRIVER cohort revealed a greater benefit for the DI group (p = 0.045). Additionally, the AEs of the DI group were not significantly different from those of the PI, DnI, and PnI groups (AEs: 27.5%, 39.2%, 26.7%, and 28.6%, respectively, p = 0.742). Furthermore, the multivariate analysis revealed the independent prognostic role of DI treatment for PFS in the overall cohort. Within the DI group, we did not observe differences in benefit among different mutational subgroups (p = 0.814), but patients with single-site bone metastasis (p = 0.319) and high PD-L1 expression (p = 0.100) appeared to benefit more, though no significant differences were observed.ConclusionsDenosumab exhibited synergistic antitumor efficacy without increasing toxicity when used concomitantly with ICIs in patients with advanced non-small cell lung cancer carrying bone metastases.
IGF1R signalling is a guardian of self-tolerance restricting autoantibody production
Authors: Erlandsson Malin C. , Erdogan Seval , Wasén Caroline , Andersson Karin M. E. , Silfverswärd Sofia T. , Pullerits Rille , Bemark Mats , Bokarewa Maria I. 
Published: August 2022

ObjectiveInsulin-like growth factor 1 receptor (IGF1R) acts at the crossroad between immunity and cancer, being an attractive therapeutic target in these areas. IGF1R is broadly expressed by antigen-presenting cells (APC). Using mice immunised with the methylated albumin from bovine serum (BSA-immunised mice) and human CD14+ APCs, we investigated the role that IGF1R plays during adaptive immune responses.MethodsThe mBSA-immunised mice were treated with synthetic inhibitor NT157 or short hairpin RNA to inhibit IGF1R signalling, and spleens were analysed by immunohistology and flow cytometry. The levels of autoantibody and cytokine production were measured by microarray or conventional ELISA. The transcriptional profile of CD14+ cells from blood of 55 patients with rheumatoid arthritis (RA) was analysed with RNA-sequencing.ResultsInhibition of IGF1R resulted in perifollicular infiltration of functionally compromised S256-phosphorylated FoxO1+ APCs, and an increased frequency of IgM+CD21+ B cells, which enlarged the marginal zone (MZ). Enlargement of MHCII+CD11b+ APCs ensured favourable conditions for their communication with IgM+ B cells in the MZ. The reduced expression of ICOSL and CXCR5 by APCs after IGF1R inhibition led to impaired T cell control, which resulted in autoreactivity of extra-follicular B cells and autoantibody production. In the clinical setting, the low expression of IGF1R on CD14+ APCs was associated with an involuted FOXO pathway, non-inflammatory cell metabolism and a high IL10 production characteristic for tolerogenic macrophages. Furthermore, autoantibody positivity was associated with low IGF1R signalling in CD14+ APCs.ConclusionsIn experimental model and in patient material, this study demonstrates that IGF1R plays an important role in preventing autoimmunity. The study raises awareness of that immune tolerance may be broken during therapeutic IGF1R targeting.
Nano-architectured cobalt selenide spheres anchored on graphene oxide sheets for sodium ion battery anode
Authors: Ali Zeeshan , Ali Muhammad , Mehmood Ahtisam , Ishfaq Ayesha , Akram Muhammad Aftab , Zeb Akif , Lin Xiaoming 
Published: August 2022

Aimed at commercializing the technology of sodium-ion batteries (SIBs), researchers have been trying to produce electrode materials with optimally high charge storage capacity, superior rate capability, extended life, and cost-effective components. Herein, we synthesized an electrode of cobalt selenides loaded in carbon spheres and anchored on reduced graphene (CSSs@rGO) for high-performance SIBs. This improved structure of CSSs@rGO permits the pseudocapacitive storage of charge, thus enhancing the electrical characteristics. It was discovered that the diameter of the carbon sphere had a significant impact on the charge storage capacities of the developed electrode materials, suggesting the probable depth of sodium-ion (Na-ion) movement in the electrode materials during charge and discharge. For instance, CSSs@rGO with an average diameter of ∼70 nm presented the best electrochemical performance as an anode of SIBs. The nano-architecture CSSs@rGO exhibits excellent ion storage capability with a reversible capacity of 600 mA h g-1 at a discharge rate of 100 mA g−1 after 50 cycles. However, at a higher discharge rate (e.g., 1,000 mA g−1), a storage capacity as high as 380 mA h g−1 was achieved. In addition to higher charge storage capability and efficient charge storage at higher discharge rates, the developed CSSs@rGO exhibited stable cycling performance for over 3,000 cycles, which clearly shows the feasibility of our products. This work will open new approaches for developing advanced electrode materials for high-performance sodium-ion batteries.
The role of long noncoding RNAs as regulators of the epithelial–Mesenchymal transition process in oral squamous cell carcinoma cells
Authors: Shao Zifei , Wang Xiang , Li Yiyang , Hu Yanjia , Li Kun 
Published: August 2022

Oral squamous cell carcinoma (OSCC) is a highly invasive and relatively prevalent cancer, accounting for around 3% of all cancers diagnosed. OSCC is associated with bad outcomes, with only 50% overall survival (OS) after five years. The ability of OSCC to invade local and distant tissues relies on the induction of the epithelial–mesenchymal transition (EMT), wherein epithelial cells shed their polarity and cell-to-cell contacts and acquire mesenchymal characteristics. Consequently, a comprehensive understanding of how tumor cell EMT induction is regulated has the potential of direct attempts to prevent tumor progression and metastasis, resulting in better patient outcomes. Several recent studies have established the significance of particular long noncoding RNAs (lncRNAs) in the context of EMT induction. Moreover, lncRNAs regulate a vast array of oncogenic pathways. With a focus on the mechanisms by which the underlined lncRNAs shape the metastatic process and a discussion of their potential utility as clinical biomarkers or targets for therapeutic intervention in patients with OSCC, the present review thus provides an overview of the EMT-related lncRNAs that are dysregulated in OSCC.
Effect of hypoalbuminemia on short-term outcomes after colorectal cancer surgery: A propensity score matching analysis
Authors: Kang Bing , Zhao Zhi-Qiang , Liu Xiao-Yu , Cheng Yu-Xi , Tao Wei , Wei Zheng-Qiang , Peng Dong 
Published: August 2022

PurposeThe purpose of our study was to investigate the effect of pre-operative hypoalbuminemia on the short-term outcomes after primary colorectal cancer (CRC) surgery.Materials and methodsThe retrospective study enrolled CRC patients who underwent primary surgery from January 2011 to December 2021 in a single teaching hospital. The short-term outcomes were compared between the hypoalbuminemia group and the normal group using propensity score matching (PSM). Univariate and multivariate logistic regression analyses were used for analyzing independent predictors of overall complications and major complications.ResultsA total of 7,072 patients from a single center were enrolled in this study. There were 1,078 (15.2%) patients in the pre-operative hypoalbuminemia group and 5,994 (84.8%) patients in the normal pre-operative albumin group. After 1:1 PSM, there were 1,028 patients in the hypoalbuminemia group and 1,028 patients in the normal group. No significant differences were found in baseline information between the two groups after PSM. In terms of short-term outcomes, the hypoalbuminemia group had a longer operation time (p = 0.003), greater volume of blood loss (p = 0.036), longer hospital stays (p &lt; 0.01), higher proportion of overall complications (p = 0.003), major complications (p = 0.016), higher incidence of pneumonia and abdominal infection (p = 0.001) than the normal group after PSM. Furthermore, hypoalbuminemia was an independent predictor for overall complications (p = 0.008) and major complications (p = 0.016).ConclusionPre-operative hypoalbuminemia increased overall complications and major complications after primary CRC surgery. Furthermore, hypoalbuminemia was an independent predictor for overall complications and major complications.
Robust treatment planning in scanned carbon-ion radiotherapy for pancreatic cancer: Clinical verification using in-room computed tomography images
Authors: Kusano Yohsuke , Katoh Hiroyuki , Minohara Shinichi , Fujii Hajime , Miyasaka Yuya , Takayama Yoshiki , Imura Koh , Kusunoki Terufumi , Miyakawa Shin , Kamada Tadashi , Serizawa Itsuko , Takakusagi Yosuke , Mizoguchi Nobutaka , Tsuchida Keisuke , Yoshida Daisaku 
Published: August 2022

PurposeCarbon-ion beam (C-beam) has a sharp dose distribution called the Bragg peak. Carbon-ion radiation therapy, such as stereotactic body radiotherapy in photon radiotherapy, can be completed in a short period by concentrating the radiation dose on the tumor while minimizing the dose to organs at-risk. However, the stopping position of C-beam is sensitive to density variations along the beam path and such variations can lower the tumor dose as well as cause the delivery of an unexpectedly high dose to the organs at risk. We evaluated the clinical efficacy of a robust planning technique considering gastrointestinal gas (G-gas) to deliver accurate radiation doses in carbon-ion radiotherapy for pancreatic cancer.Materials and methodsWe focused on the computed tomography (CT) value replacement method. Replacement signifies the overwriting of CT values in the CT images. The most effective replacement method for robust treatment planning was determined by verifying the effects of the three replacement patterns. We selected 10 consecutive patients. Pattern 1 replaces the CT value of the G-gas contours with the value of the region without G-gas (P1). This condition indicates a no-gas state. Pattern 2 replaces each gastrointestinal contour using the mean CT value of each contour (P2). The effect of G-gas was included in the replacement value. Pattern 3 indicates no replacement (P3). We analyzed variations in the target coverage (TC) and homogeneity index (HI) from the initial plan using in-room CT images. We then performed correlation analysis on the variations in G-gas, TC, and HI to evaluate the robustness against G-gas.ResultsAnalysis of variations in TC and HI revealed a significant difference between P1 and P3 and between P2 and P3. Although no statistically significant difference was observed between P1 and P2, variations, including the median, tended to be fewer in P2. The correlation analyses for G-gas, TC, and HI showed that P2 was less likely to be affected by G-gas.ConclusionFor a treatment plan that is robust to G-gas, P2 mean replacement method should be used. This method does not necessitate any particular software or equipment, and is convenient to implement in clinical practice.
Time to death and its predictors among neonates who were admitted to the neonatal intensive care unit at tertiary hospital, Addis Ababa, Ethiopia: Retrospective follow up study
Authors: Menalu Mulat Mossie , Gebremichael Bereket , Desta Kalkidan Wondwossen , Kebede Worku Misganaw , Tarekegn Fetene Nigussie , Mulu Getaneh Baye , Atinafu Bantalem Tilaye 
Published: August 2022

BackgroundsNeonatal death is the major problem in developing world. Burden and predictors of neonatal mortality vary across countries and even among regions of a country, so understanding the problem concerning these factors is essential to overcome the problem. Therefore, this study aimed to determine time to death and its predictors of neonatal mortality among neonates who were admitted to the neonatal intensive care unit of Tertiary Hospital, Addis Ababa, Ethiopia.MethodsA hospital-based retrospective cohort study was employed among 434 neonates admitted in Tertiary hospital, Addis Ababa, Ethiopia. A Kaplan Meier curve and a log-rank test were used to estimate the survival time and compare survival curves between variables. The cox proportional hazard model was also fitted to identify predictors.ResultsA total of 434 neonates included in the study, 11.1% of which were died, and the incidence rate was 19.2 per 1000 live births. The time to death of neonates was 17 days. Independent predictors of neonatal mortality were incomplete maternal antenatal follow up[AHR: 3.7 (95% CI:1.86,7.60)], low(Appearance, Pulse, Grimily, Activity, and Respiration(APGAR)score[AHR:5.0 (95%CI:1.51–15.04)], perinatal asphyxia [AHR:5.2 (95%CI:1.92–14.30)], preterm 4.2 (95%CI: 1.32–8.83)]. Moreover, small for gestational age [AHR:4.8 (95%CI:2.33–9.72)], respiratory distress[AHR: 2.5 (95%CI: 1.24–5.09)], sepsis [AHR: 3.4 (95%CI: 1.71–4.01)], low birth weight[AHR: 7.3 (95%CI:2.69,1.91)], and tracheoesophageal fistula [AHR: 2.2 (95%CI: 1.13–4.32)].ConclusionThe overall incidence rate was 19.2 deaths per 1,000 live births. Emphasis should be given to incomplete Antenatal care follow up, small for gestation, preterm, low birth weight, low 5th min APGAR score, neonatal sepsis, respiratory distress, perinatal asphyxia, and tracheoesophageal fistula.