bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrated analysis of circRNA-associated ceRNA network in ischemic stroke
Authors: Fan Rongli , Hu Die , Wang Maiqiu , Zheng Huilin , Zhou Yifeng , Zhang Lei 
Published: June 2023

Introduction: Stroke, of which ischemic stroke (IS) is the major type, is the second leading cause of disability and death worldwide. Circular RNAs (circRNAs) are reported to play important role in the physiology and pathology of IS. CircRNAs often act as competing endogenous RNA (ceRNA) to regulate gene expression by acting as miRNA sponges. However, whole transcriptome-wide screenings of circRNA-mediated ceRNA networks associated with IS are still lacking. In the present study, we constructed a circRNA-miRNA-mRNA ceRNA network by whole transcriptome-wide analysis.Methods: CircRNAs, miRNAs and mRNAs expression profiles were downloaded from the Gene Expression Omnibus (GEO) datasets. We identified differentially expressed (DE) circRNAs, miRNAs, and mRNAs in IS patients. StarBase and CircBank databases were used to predict the miRNA targets of DEcircRNAs, and mirDIP database was used to predict the mRNA targets of DEmiRNAs. CircRNA-miRNA pairs and miRNA-mRNA pairs were established. Then, we identified hub genes via protein-protein interaction analysis and constructed a core ceRNA sub-network.Results: In total, 276 DEcircRNAs, 43 DEmiRNAs, and 1926 DEmRNAs were explored. The ceRNA network included 69 circRNAs, 24 miRNAs, and 92 mRNAs. The core ceRNA subnetwork included hsa_circ_0011474, hsa_circ_0023110, CDKN1A, FHL2, RPS2, CDK19, KAT6A, CBX1, BRD4, and ZFHX3.Discussion: In conclusion, we established a novel hsa_circ_0011474 - hsa-miR-20a-5p/hsa-miR-17-5p - CDKN1A ceRNA regulatory axis associated with IS. Our findings provide new insights into the pathogenesis of IS and offer promising diagnostic and predictive biomarkers.
Enhancing genomic mutation data storage optimization based on the compression of asymmetry of sparsity
Authors: Ding Youde , Liao Yuan , He Ji , Ma Jianfeng , Wei Xu , Liu Xuemei , Zhang Guiying , Wang Jing 
Published: June 2023

Background: With the rapid development of high-throughput sequencing technology and the explosive growth of genomic data, storing, transmitting and processing massive amounts of data has become a new challenge. How to achieve fast lossless compression and decompression according to the characteristics of the data to speed up data transmission and processing requires research on relevant compression algorithms.Methods: In this paper, a compression algorithm for sparse asymmetric gene mutations (CA_SAGM) based on the characteristics of sparse genomic mutation data was proposed. The data was first sorted on a row-first basis so that neighboring non-zero elements were as close as possible to each other. The data were then renumbered using the reverse Cuthill-Mckee sorting technique. Finally the data were compressed into sparse row format (CSR) and stored. We had analyzed and compared the results of the CA_SAGM, coordinate format (COO) and compressed sparse column format (CSC) algorithms for sparse asymmetric genomic data. Nine types of single-nucleotide variation (SNV) data and six types of copy number variation (CNV) data from the TCGA database were used as the subjects of this study. Compression and decompression time, compression and decompression rate, compression memory and compression ratio were used as evaluation metrics. The correlation between each metric and the basic characteristics of the original data was further investigated.Results: The experimental results showed that the COO method had the shortest compression time, the fastest compression rate and the largest compression ratio, and had the best compression performance. CSC compression performance was the worst, and CA_SAGM compression performance was between the two. When decompressing the data, CA_SAGM performed the best, with the shortest decompression time and the fastest decompression rate. COO decompression performance was the worst. With increasing sparsity, the COO, CSC and CA_SAGM algorithms all exhibited longer compression and decompression times, lower compression and decompression rates, larger compression memory and lower compression ratios. When the sparsity was large, the compression memory and compression ratio of the three algorithms showed no difference characteristics, but the rest of the indexes were still different.Conclusion: CA_SAGM was an efficient compression algorithm that combines compression and decompression performance for sparse genomic mutation data.
The independent prognostic effect of marital status on non-small cell lung cancer patients: a population-based study
Authors: Zhao Dechang , Zhang Rusi , Yang Longjun , Huang Zirui , Lin Yongbin , Wen Yingsheng , Wang Gongming , Guo Guangran , Zhang Lanjun 
Published: June 2023

BackgroundPrevious studies had demonstrated that marital status was an independent prognostic factor in multiple cancers. However, the impact of marital status on non-small cell lung cancer (NSCLC) patients was still highly controversial.MethodAll NSCLC patients diagnosed between 2010–2016 were selected from the Surveillance, Epidemiology and End Results (SEER) database. To control the confounding effect of related clinicopathological characteristics, propensity score matching (PSM) was conducted between married and unmarried groups. In addition, independent prognostic clinicopathological factors were evaluated via Cox proportional hazard regression. Moreover, nomograms were established based on the clinicopathological characteristics, and the predictive accuracy was assessed by calibration curves. Furthermore, decision curve analysis (DCA) was used to determine the clinical benefits.ResultsIn total, 58,424 NSCLC patients were enrolled according to the selection criteria. After PSM, 20,148 patients were selected into each group for further analysis. The married group consistently demonstrated significantly better OS and CSS compared to unmarried group [OS median survival (95% CI): 25 (24–26) vs. 22 (21–23) months, p &lt; 0.001; CSS median survival (95% CI): 31 (30–32) vs. 27 (26–28) months, p &lt; 0.001]. Moreover, single patients were associated with the worst OS [median survival (95% CI): 20 (19–22) months] and CSS [median survival (95%CI): 24 (23–25) months] among unmarried subgroups. Besides, unmarried patients had a significantly worse prognosis compared to married patients in both univariate and multivariate Cox proportional hazard regressions. Furthermore, married group was associated with better survival in most subgroups. To predict the 1-, 3- and 5-year OS and CSS probabilities, nomograms were established based on age, race, sex, gender, marital status, histology, grade, TNM stage. The C-index for OS and CSS were 0.759 and 0.779. And the calibration curves showed significant agreement between predictive risk and the observed probability. DCA indicated nomograms had consistently better predict performance.ConclusionThis study demonstrated that unmarried NSCLC patients were associated with significantly worse OS and CSS compared to married NSCLC patients. Therefore, unmarried patients need not only closer surveillance, but also more social and family support, which may improve patients’ adherence and compliance, and eventually improve the survival.
Binocular imbalance in patients after implantable collamer lens V4c implantation or femtosecond laser-assisted in situ keratomileusis for myopia with presbyopia
Authors: Ye Yuhao , Zhang Zhe , Niu Lingling , Shi Wanru , Wang Xiaoying , Yan Li , Zhou Xingtao , Zhao Jing 
Published: June 2023

AimTo investigate the long-term safety, efficacy, and binocular balance of monovision surgery using Implantable Collamer Lens (ICL) V4c implantation and Femtosecond Laser-Assisted in situ Keratomileusis (FS-LASIK) for the treatment of myopic patients with presbyopia.MethodsThis case series study involved 90 eyes of 45 patients (male/female = 19/26; average age:46.27 ± 5.54 years; average follow-up time:48.73 ± 14.65 months) who underwent the aforementioned surgery to treat myopic presbyopes. Data on manifest refraction, corrected distance visual acuity, dominant eye, presbyopic addition, intraocular pressure, and anterior segment biometric parameters were collected. The visual outcomes and binocular balance at 0.4 m, 0.8 m, and 5 m were documented.ResultsThe safety index for the ICL V4c and FS-LASIK groups were 1.24 ± 0.27 and 1.04 ± 0.20 (p = 0.125), respectively. Binocular visual acuity (logmar) for 0.4 m, 0.8 m, and 5 m were −0.03 ± 0.05, −0.03 ± 0.02, and 0.10 ± 0.03 for the ICL V4c group, and −0.02 ± 0.09, −0.01 ± 0.02, and 0.06 ± 0.04 for the FS-LASIK group, respectively. The proportions of all patients with imbalanced vision at 0.4 m, 0.8 m, and 5 m distances were 68.89, 71.11, and 82.22%, respectively (all p &gt; 0.05 between the two groups). There were significant differences in refraction between the balanced and imbalanced vision for patients at 0.4 m distance (for non-dominant eye spherical equivalent [SE]: −1.14 ± 0.17D and −1.47 ± 0.13D, p &lt; 0.001), 0.8 m distance (for preoperative ADD:0.90 ± 0.17D and 1.05 ± 0.11D, p = 0.041), and 5 m distance (for non-dominant SE: −1.13 ± 0.33D and −1.42 ± 0.11D, p &lt; 0.001).ConclusionICL V4c implantation and FS-LASIK monovision treatment demonstrated good long-term safety and binocular visual acuity at various distances. After the procedure, the imbalanced patients’ vision is primarily related to the age-related presbyopia and anisometropia progression caused by the monovision design.
Plasma tRF-16-79MP9PD and tRF-28-OB1690PQR304 as potential biomarkers for 4- to 7-year-old children with obstructive sleep apnea-hypopnea syndrome
Authors: Wu Junhua , Cai Xiaohong , Lu Yanbo , Shen Yijing , Shen Zhisen , Lyv Qin 
Published: June 2023

BackgroundWe investigated the expression and the potential value of plasma transfer RNA-derived fragments (tRFs) of children with obstructive sleep apnea–hypopnea syndrome (OSAHS) as screening biomarkers.MethodsAt first, we randomly selected five plasma samples from the case group and the control group for high-throughput RNA sequencing. Secondly, we screened two tRFs with different expression between the two groups, amplified it by quantitative reverse transcription-PCR (qRT-PCR) on all samples. Then we analyzed the diagnostic value of the tRFs and their correlation with the clinical data.ResultsA total of 50 OSAHS children and 38 healthy controls were included. Our results demonstrated that the plasma levels of tRF-16-79MP9PD and tRF-28-OB1690PQR304 were significantly down-regulated in OSAHS children. Receiver operating characteristic curve (ROC) showed that the area under the curve (AUC) of tRF-16-79MP9PD and tRF-28-OB1690PQR304 was 0.7945 and 0.8276. In addition, the AUC of the combination reached 0.8303 with 73.46% and 76.42% sensitivity and specificity. Correlation analysis showed that the degree of tonsil enlargement, hemoglobin (Hb) and triglyceride (TG). were related to the expression levels of tRF-16-79MP9PD and tRF-28-OB1690PQR304. Multivariable linear regression analysis showed that degree of tonsil enlargement, Hb and TG related to tRF-16-79MP9PD while degree of tonsil enlargement and Hb related to tRF-28-OB1690PQR304.ConclusionsThe expression levels of tRF-16-79MP9PD and tRF-28-OB1690PQR304 in the plasma of OSAHS children decreased significantly which were closely related to the degree of tonsil enlargement, Hb and TG, may become novel biomarkers for the diagnosis of pediatric OSAHS.
Clinical characteristics and outcomes in febrile infants aged 29–90 days with urinary tract infections and cerebrospinal fluid pleocytosis
Authors: Moon Ga Won , Shin Donghyun , Kim Young Mi , Choi Soo-Han 
Published: June 2023

IntroductionFever without a focus is a common reason for medical evaluations, hospitalizations, and the antimicrobial treatment of infants younger than 90 days. The presence of cerebrospinal fluid (CSF) pleocytosis could be challenge for clinicians who treat febrile young infants with urinary tract infection (UTI). We evaluated the factors associated with sterile CSF pleocytosis and the clinical outcomes of the patients.MethodsA retrospective review of patients aged 29–90 days with febrile UTIs who underwent a non-traumatic lumbar puncture (LP) at Pusan National University Hospital from January 2010 to December 2020 was conducted. CSF pleocytosis was defined as white blood cell (WBC) counts ≥9/mm3.ResultsA total of 156 patients with UTI were eligible for this study. Four (2.6%) had concomitant bacteremia. However, no patients had culture-proven bacterial meningitis. In correlation analysis, although weak strength, CSF WBC counts were positively correlated with C-reactive protein (CRP) level (Spearman r = 0.234; P = 0.003). Thirty-three patients had CSF pleocytosis [21.2%; 95% confidential interval (CI), 15.5–28.2]. The time from fever onset to the hospital visit, peripheral blood platelet counts, and CRP level at admission were statistically significant in patients with sterile CSF pleocytosis compared to those without CSF pleocytosis. In the multiple logistic regression, only CRP was independently associated with sterile CSF pleocytosis (cutoff, 3.425 mg/dl; adjusted odds ratio, 2.77; 95% CI, 1.19–6.88). The proportion of fever defervescence by hospital day 2 was 87.9% in patients with CSF pleocytosis and 89.4% in those without CSF pleocytosis (P = 0.759). There was no statistical difference in the fever defervescence curves between the two patient groups (P = 0.567). No patients had neurological manifestations or complications.ConclusionsCoexisting sterile CSF pleocytosis among febrile infants with UTIs suggest a systemic inflammatory response. However, the clinical outcomes between the two groups were similar. A selective LP should be considered in young infants with evidence of UTI, and inappropriate antibiotic therapy for sterile CSF pleocytosis should be avoided.
Yiwei decoction promotes apoptosis of gastric cancer cells through spleen-derived exosomes
Authors: Chen Yingzhi , Li Yu , Wu Yue , Chen Shiyong , Jin Xiaoming , Chen Xuan , Fei Baoying , Xue Xiaomin , Wu Renzhao , Chai Kequn 
Published: June 2023

Yiwei decoction (YWD) is a formula of traditional Chinese medicine (TCM) that is clinically effective for the prevention and treatment of gastric cancer recurrence and metastasis. According to the theory of TCM, YWD tonifies the body and strengthens the body’s resistance to gastric cancer recurrence and metastasis potentially via the immune regulation of the spleen. The aims of the present study were to investigate whether YWD-treated spleen-derived exosomes in rats inhibit the proliferation of tumor cells, to elucidate the anticancer effects of YWD, and to provide evidence supporting the use of YWD as a new clinical treatment for gastric cancer. Spleen-derived exosomes were obtained by ultracentrifugation and identified by transmission electron microscopy, nanoparticle tracking analysis, and western blot analysis. The location of the exosomes in tumor cells was then determined by immunofluorescence staining. After tumor cells were treated with different concentrations of exosomes, the effect of exosomes on cell proliferation was determined by cell counting kit 8 (CCK8) and colony formation assays. Tumor cell apoptosis was detected by flow cytometry. Particle analysis and western blot analysis identified the material extracted from spleen tissue supernatant as exosomes. Immunofluorescence staining showed that spleen-derived exosomes were taken up by HGC-27 cells, and the CCK8 assay confirmed that the relative tumor inhibition rate of YWD-treated spleen-derived exosomes in the 30 μg/mL reached 70.78% compared to control exosomes in the 30 μg/mL (p &lt; 0.05). Compared to control exosomes in the 30 μg/mL, the colony formation assay indicated that YWD-treated spleen-derived exosomes in the 30 μg/mL colonies have decreased by 99.03% (p &lt; 0.01). Moreover, flow cytometry analysis showed that treatment with YWD-treated exosomes in the 30 μg/mL increased the apoptosis rate to 43.27%, which was significantly higher than that of the control group in the 30 μg/mL (25.91%) (p &lt; 0.05). In conclusion, spleen-derived exosomes from YWD-treated animals inhibit the proliferation of HGC-27 cells via inducing apoptosis, suggesting that spleen-derived exosomes are involved in mediating the antitumor effect of YWD. These results demonstrated a novel exosome-mediated anticancer effect of YWD as a TCM formula, thereby supporting the use of YWD-treated exosomes as a new approach for the clinical treatment of gastric cancer.
Triptolide enhances carboplatin-induced apoptosis by inhibiting nucleotide excision repair (NER) activity in melanoma
Authors: Wang Geng , Guo Hongmin , Ren Yan , Chen Weiyi , Wang Yixuan , Li Jianing , Liu Hua , Xing Jingjun , Zhang Yanru , Li Na 
Published: June 2023

Introduction:Carboplatin (CBP) is a DNA damaging drug used to treat various cancers, including advanced melanoma. Yet we still face low response rates and short survival due to resistance. Triptolide (TPL) is considered to have multifunctional antitumor effects and has been confirmed to enhance the cytotoxic effects of chemotherapeutic drugs. Herein, we aimed to investigate the knowledge about the effects and mechanisms for the combined application of TPL and CBP against melanoma.Methods:Melanoma cell lines and xenograft mouse model were used to uncover the antitumor effects and the underlying molecular mechanisms of the alone or combined treatment of TPL and CBP in melanoma. Cell viability, migration, invasion, apoptosis, and DNA damage were detected by conventional methods. The rate-limiting proteins of the NER pathway were quantitated using PCR and Western blot. Fluorescent reporter plasmids were used to test the NER repair capacity.Results:Our results showed that the presence of TPL in CBP treatment could selectively inhibit NER pathway activity, and TPL exerts a synergistic effect with CBP to inhibit viability, migration, invasion, and induce apoptosis of A375 and B16 cells. Moreover, combined treatment with TPL and CBP significantly inhibited tumor progression in nude mice by suppressing cell proliferation and inducing apoptosis.Discussion:This study reveals the NER inhibitor TPL which has great potential in treating melanoma, either alone or in combination with CBP.
Single-cell RNA sequencing revealed subclonal heterogeneity and gene signatures of gemcitabine sensitivity in pancreatic cancer
Authors: Hou Zelin , Lin Jiajing , Ma Yuan , Fang Haizhong , Wu Yuwei , Chen Zhijiang , Lin Xianchao , Lu Fengchun , Wen Shi , Yu Xunbin , Huang Heguang , Pan Yu 
Published: June 2023

Introduction: Resistance to gemcitabine is common and critically limits its therapeutic efficacy in pancreatic ductal adenocarcinoma (PDAC).Methods: We constructed 17 patient-derived xenograft (PDX) models from PDAC patient samples and identified the most notable responder to gemcitabine by screening the PDX sets in vivo. To analyze tumor evolution and microenvironmental changes pre- and post-chemotherapy, single-cell RNA sequencing (scRNA-seq) was performed.Results: ScRNA-seq revealed that gemcitabine promoted the expansion of subclones associated with drug resistance and recruited macrophages related to tumor progression and metastasis. We further investigated the particular drug-resistant subclone and established a gemcitabine sensitivity gene panel (GSGP) (SLC46A1, PCSK1N, KRT7, CAV2, and LDHA), dividing PDAC patients into two groups to predict the overall survival (OS) in The Cancer Genome Atlas (TCGA) training dataset. The signature was successfully validated in three independent datasets. We also found that 5-GSGP predicted the sensitivity to gemcitabine in PDAC patients in the TCGA training dataset who were treated with gemcitabine.Discussion and conclusion: Our study provides new insight into the natural selection of tumor cell subclones and remodeling of tumor microenvironment (TME) cells induced by gemcitabine. We revealed a specific drug resistance subclone, and based on the characteristics of this subclone, we constructed a GSGP that can robustly predict gemcitabine sensitivity and prognosis in pancreatic cancer, which provides a theoretical basis for individualized clinical treatment.
Immune cell status, cardiorespiratory fitness and body composition among breast cancer survivors and healthy women: a cross sectional study
Authors: Arana Echarri Ainhoa , Struszczak Lauren , Beresford Mark , Campbell John P. , Jones Robert H. , Thompson Dylan , Turner James E. 
Published: June 2023

Methods: We examined whether immune cell profiles differ between healthy women (n = 38) and breast cancer survivors (n = 27) within 2 years of treatment, and whether any group-differences were influenced by age, cytomegalovirus infection, cardiorespiratory fitness and body composition. Using flow cytometry, CD4+ and CD8+ T cell subsets, including naïve (NA), central memory (CM) and effector cells (EM and EMRA) were identified using CD27/CD45RA. Activation was measured by HLA-DR expression. Stem cell-like memory T cells (TSCMs) were identified using CD95/CD127. B cells, including plasmablasts, memory, immature and naïve cells were identified using CD19/CD27/CD38/CD10. Effector and regulatory Natural Killer cells were identified using CD56/CD16.Results: Compared to healthy women, CD4+ CM were +Δ21% higher among survivors (p = 0.028) and CD8+ NA were −Δ25% lower (p = 0.034). Across CD4+ and CD8+ subsets, the proportion of activated (HLA-DR+) cells was +Δ31% higher among survivors: CD4+ CM (+Δ25%), CD4+ EM (+Δ32%) and CD4+ EMRA (+Δ43%), total CD8+ (+Δ30%), CD8+ EM (+Δ30%) and CD8+ EMRA (+Δ25%) (p &lt; 0.046). The counts of immature B cells, NK cells and CD16+ NK effector cells were higher among survivors (+Δ100%, +Δ108% and +Δ143% respectively, p &lt; 0.04). Subsequent analyses examined whether statistically significant differences in participant characteristics, influenced immunological differences between groups. Compared to healthy women, survivors were older (56 ± 6 y vs. 45 ± 11 y), had lower cardiorespiratory fitness (V̇O2max mL kg−1 min−1: 28.8 ± 5.0 vs. 36.2 ± 8.5), lower lean mass (42.3 ± 5.0 kg vs. 48.4 ± 15.8 kg), higher body fat (36.3% ± 5.3% vs. 32.7% ± 6.4%) and higher fat mass index (FMI kg/m2: 9.5 ± 2.2 vs. 8.1 ± 2.7) (all p &lt; 0.033). Analysis of covariance revealed divergent moderating effects of age, CMV serostatus, cardiorespiratory fitness and body composition on the differences in immune cell profiles between groups, depending on the cell type examined. Moreover, across all participants, fat mass index was positively associated with the proportion of HLA-DR+ CD4+ EMRA and CD8+ EM/EMRA T cells (Pearson correlation: r &gt; 0.305, p &lt; 0.019). The association between fat mass index and HLA-DR+ CD8+ EMRA T cells withstood statistical adjustment for all variables, including age, CMV serostatus, lean mass and cardiorespiratory fitness, potentially implicating these cells as contributors to inflammatory/immune-dysfunction in overweight/obesity.