bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of Potential Novel Prognosis-Related Genes Through Transcriptome Sequencing, Bioinformatics Analysis, and Clinical Validation in Acute Myeloid Leukemia
Authors: Wang Jie , Uddin Md. Nazim , Hao Jian-ping , Chen Rong , Xiang Yun-xia , Xiong Dai-qin , Wu Yun 
Published: October 2021

Background: Acute Myeloid Leukemia (AML) is a complex and heterogeneous hematologic malignancy. However, the function of prognosis-related signature genes in AML remains unclear.Methods: In the current study, transcriptome sequencing was performed on 15 clinical samples, differentially expressed RNAs were identified using R software. The potential interactions network was constructed by using the common genes between target genes of differentially expressed miRNAs with transcriptome sequencing results. Functional and pathway enrichment analysis was performed to identify candidate gene-mediated aberrant signaling pathways. Hub genes were identified by the cytohubba plugin in Cytoscape software, which then expanded the potential interactions regulatory module for hub genes. TCGA-LAML clinical data were used for the prognostic analysis of the hub genes in the regulatory network, and GVSA analysis was used to identify the immune signature of prognosis-related hub genes. qRT-PCR was used to verify the expression of hub genes in independent clinical samples.Results: We obtained 1,610 differentially expressed lncRNAs, 233 differentially expressed miRNAs, and 2,217 differentially expressed mRNAs from transcriptome sequencing. The potential interactions network is constructed by 12 lncRNAs, 25 miRNAs, and 692 mRNAs. Subsequently, a sub-network including 15 miRNAs as well as 12 lncRNAs was created based on the expanded regulatory modules of 25 key genes. The prognostic analysis results show that CCL5 and lncRNA UCA1 was a significant impact on the prognosis of AML. Besides, we found three potential interactions networks such as lncRNA UCA1/hsa-miR-16-5p/COL4A5, lncRNA UCA1/hsa-miR-16-5p/SPARC, and lncRNA SNORA27/hsa-miR-17-5p/CCL5 may play an important role in AML. Furthermore, the evaluation of the immune infiltration shows that CCL5 is positively correlated with various immune signatures, and lncRNA UCA1 is negatively correlated with the immune signatures. Finally, the result of qRT-PCR showed that CCL5 is down-regulated and lncRNA UCA1 is up-regulated in AML samples separately.Conclusions: In conclusion, we propose that CCL5 and lncRNA UCA1 could be recognized biomarkers for predicting survival prognosis based on constructing competing endogenous RNAs in AML, which will provide us novel insight into developing novel prognostic, diagnostic, and therapeutic for AML.
Chromosome-Level Genome Assembly Reveals Significant Gene Expansion in the Toll and IMD Signaling Pathways of Dendrolimus kikuchii
Authors: Zhou Jielong , Wu Peifu , Xiong Zhongping , Liu Naiyong , Zhao Ning , Ji Mei , Qiu Yu , Yang Bin 
Published: October 2021

A high-quality genome is of significant value when seeking to control forest pests such as Dendrolimus kikuchii, a destructive member of the order Lepidoptera that is widespread in China. Herein, a high quality, chromosome-level reference genome for D. kikuchii based on Nanopore, Pacbio HiFi sequencing and the Hi-C capture system is presented. Overall, a final genome assembly of 705.51 Mb with contig and scaffold N50 values of 20.89 and 24.73 Mb, respectively, was obtained. Of these contigs, 95.89% had unique locations on 29 chromosomes. In silico analysis revealed that the genome contained 15,323 protein-coding genes and 63.44% repetitive sequences. Phylogenetic analyses indicated that D. kikuchii may diverged from the common ancestor of Thaumetopoea. Pityocampa, Thaumetopoea ni, Heliothis virescens, Hyphantria armigera, Spodoptera frugiperda, and Spodoptera litura approximately 122.05 million years ago. Many gene families were expanded in the D. kikuchii genome, particularly those of the Toll and IMD signaling pathway, which included 10 genes in peptidoglycan recognition protein, 19 genes in MODSP, and 11 genes in Toll. The findings from this study will help to elucidate the mechanisms involved in protection of D. kikuchii against foreign substances and pathogens, and may highlight a potential channel to control this pest.
PIV and PILE Score at Baseline Predict Clinical Outcome of Anti-PD-1/PD-L1 Inhibitor Combined With Chemotherapy in Extensive-Stage Small Cell Lung Cancer Patients
Authors: Zeng Ran , Liu Fang , Fang Chen , Yang Jin , Luo Lifeng , Yue Ping , Gao Beili , Dong Yuchao , Xiang Yi 
Published: October 2021

ObjectivesThe objective of this study is to evaluate whether PIV (Pan-Immune-Inflammation Value) and PILE [a score derived from PIV, lactate dehydrogenase (LDH), and Eastern Cooperative Oncology Group Performance Status (ECOG PS)] can predict clinical outcome of anti-PD-1/PD-L1 inhibitor combined with chemotherapy in patients with extensive-stage (ES) small cell lung cancer (SCLC).MethodsA total of 53 patients with ES-SCLC in the control group of clinical trial (NCT03041311) were included in this study. PIV was calculated as follows: (neutrophil count × platelet count × monocyte count)/lymphocyte count. The PILE scores were composited based on PIV, LDH levels, and ECOG PS. The Kaplan–Meier method and Cox hazards regression models were used for survival analyses. Moreover, the predictive ability of PIV and PILE was validated in an independent real-world group consisting of 84 patients.ResultsPatients in the low PIV group (PIV &lt; median) had longer progression-free survival (PFS) and overall survival (OS) than those in the high PIV group (PIV ≥ median), along with the HR, which was 2.157 and 2.359, respectively (PFS HR 95% CI: 1.181–3.940, p = 0.012; OS HR 95% CI: 1.168–4.762, p = 0.020). High PILE score was observed relating to worse treatment efficacy (disease control rate (DCR): 84.21% vs. 100%, p = 0.047; durable clinical benefit (DCB) rate: 10% vs. 48.5%, p = 0.060) and poor clinical outcome (median PFS: 4.75 vs. 5.53 m, p = 0.043; median OS: 7.13 vs. 15.93 m, p = 0.002). Similar results were obtained about the predictive and prognostic abilities of PIV and PILE scores in the validation group.ConclusionsHigh PIV and high PILE were correlated with worse clinical outcomes in ES-SCLC patients treated with anti-PD-1/PD-L1 inhibitor combined with chemotherapy, reflecting that PIV and PILE might be useful to identify patients unlikely to benefit from anti-PD-1/PD-L1 therapy.
Mutations in FIGLA Associated With Premature Ovarian Insufficiency in a Chinese Population
Authors: Mei Libin , Huang Yanru , Wu Xiaoling , He Huang , Ye Ronghui , Ma Jinxiu , He XueMei , Shi Yuhua , Li Ping 
Published: October 2021

Objective: Premature ovarian insufficiency (POI) is one of the most common reproductive endocrinological causes of infertility in women of child-bearing age. The purpose of this study was to identify FIGLA gene mutations in Chinese patients with POI and to investigate the underlying mechanism.Methods: A total of 113 patients with idiopathic POI and 100 healthy controls were recruited for the analysis of FIGLA variants. Based on the identification of common mutations in the FIGLA, wild-type and mutant plasmids were constructed and transfected into HEK293 cells. Luciferase reporter genes were used to determine the effect of wild-type and mutant FIGLA genotypes on the transcriptional activity of its downstream targets, the zona pellucida glycoprotein genes ZP1, ZP2, and ZP3. Chromatin immunoprecipitation was used to determine the level of binding between wild-type and mutant FIGLA with the ZP1, ZP2, and ZP3 promoters.Results: Three different FIGLA mutations were identified in four patients with POI. Two patients carried the mutation c.11C&gt;A (p.A4E), and the other two patients, respectively, carried the mutations c.625G&gt;A (p.V209I) and c.84C&gt;A (p.D28E). The luciferase reporter assay indicated that ZP1, ZP2, and ZP3 transcriptional activities were significantly reduced in individuals with FIGLA mutations. Chromatin immunoprecipitation indicated that the FIGLA mutation significantly decreased binding with the ZP1, ZP2, and ZP3 promoters.Conclusion:FIGLA mutation affects gene transcriptional regulation of its downstream target genes ZP1, ZP2, and ZP3, highlighting a new candidate genetic factor that causes POI. Our study demonstrates that FIGLA has a regulatory effect on reproduction-specific genes, thereby providing a basis for elucidating the specific regulatory mechanism of FIGLA in germ cell growth and development.
Replication of Reduced Pattern Electroretinogram Amplitudes in Depression With Improved Recording Parameters
Authors: Friedel Evelyn B. N. , Tebartz van Elst Ludger , Schmelz Céline , Ebert Dieter , Maier Simon , Endres Dominique , Runge Kimon , Domschke Katharina , Bubl Emanuel , Kornmeier Jürgen , Bach Michael , Heinrich Sven P. , Nickel Kathrin 
Published: October 2021

Background:The retina has gained increasing attention in non-ophthalmological research in recent years. The pattern electroretinogram (PERG), a method to evaluate retinal ganglion cell function, has been used to identify objective correlates of the essentially subjective state of depression. A reduction in the PERG contrast gain was demonstrated in patients with depression compared to healthy controls with normalization after remission. PERG responses are not only modulated by stimulus contrast, but also by check size and stimulation frequency. Therefore, the rationale was to evaluate potentially more feasible procedures for PERG recordings in daily diagnostics in psychiatry.Methods:Twenty-four participants (12 patients with major depression (MDD) and 12 age- and sex-matched healthy controls) were examined in this pilot study. We investigated PERG amplitudes for two steady-state pattern reversal frequencies (12.5/18.75 rps) and four sizes of a checkerboard stimulus (0.8°, 1.6°, 3.2°, and 16°) to optimize the PERG recordings in MDD patients.Results:Smaller PERG amplitudes in MDD patients were observed for all parameters, whereby the extent of the reduction appeared to be stimulus-specific. The most pronounced decline in the PERG of MDD patients was observed at the higher stimulation frequency and the finest pattern, whilst responses for the largest check size were less affected. Following the PERG ratio protocol for early glaucoma, where similar stimulus dependent modulations have been reported, we calculated PERG ratios (0.8°/16°) for all participants. At the higher frequency (18.75 rps), significantly reduced ratios were observed in MDD patients.Conclusion:The “normalization” of the PERG responses—via building a ratio—appears to be a very promising approach with regard to the development of an objective biomarker of the depressive state, facilitating inter-individual assessments of PERG recordings in patients with psychiatric disorders.
Astrocytes Downregulate Inflammation in Lipopolysaccharide-Induced Acute Respiratory Distress Syndrome: Applicability to COVID-19
Authors: Izrael Michal , Molakandov Kfir , Revel Ariel , Slutsky Shalom Guy , Sonnenfeld Tehila , Weiss Julia Miriam , Revel Michel 
Published: October 2021

Background: An acute respiratory distress syndrome (ARDS) is caused by the increased amounts of pro-inflammatory cytokines and neutrophil-mediated tissue injury. To date, there is no effective treatment for the ARDS available, while the need for one is growing due to the most severe complications of the current coronavirus disease-2019 (COVID-19) pandemic. The human astrocytes (AstroRx) have shown immunomodulatory properties in the central nervous system (CNS). This study aimed to evaluate the capacity of astrocytes to decrease lung inflammation and to be applied as a treatment therapy in ARDS.Methods: First, we assessed the ability of clinical-grade AstroRx to suppress T-cell proliferation in a mixed lymphocyte reaction test. Next, we tested the therapeutical potential of AstroRx cells in a lipopolysaccharide (LPS)-based ARDS mouse model by injecting AstroRx intravenously (i.v). We determined the degree of lung injury by using a severity scoring scale of 0–2, based on the American Thoracic Society. The scoring measured the presence of neutrophils, fibrin deposits, and the thickening of alveolar walls. The state of inflammation was further assessed by quantifying the immune-cell infiltration to the bronchoalveolar lavage fluid (BALF) and by the presence of proinflammatory cytokines and chemokines in the BALF and serum.Results: We detected that AstroRx cells were capable to suppress T-cell proliferation in vitro after exposure to the mitogen concanavalin A (ConA). In vivo, AstroRx cells were able to lower the degree of lung injury in LPS-treated animals compared with the sham injected animals (P = 0.039). In this study, 30% of AstroRx treated mice showed no lung lesions (responder mice), these mice presented a steady number of eosinophils, T cells, and neutrophils comparable with the level of naïve control mice. The inflammatory cytokines and chemokines, such as TNFα, IL1b, IL-6, and CXCL1, were also kept in check in responder AstroRx-treated mice and were not upregulated as in the sham-injected mice (P &lt; 0.05). As a result, the LPS-treated ARDS mice had a higher survival rate when they were treated with AstroRx.Conclusions: Our results demonstrate that the immunosuppressive activity of AstroRx cells support the application of AstroRx cells as a cell therapy treatment for ARDS. The immunoregulatory activity may also be a part of the mechanism of action of AstroRx reported in the amyotrophic lateral sclerosis (ALS) neurodegenerative disease.
Longitudinal Associations Between Hand Grip Strength and Non-Alcoholic Fatty Liver Disease in Adults: A Prospective Cohort Study
Authors: Xia Yang , Cao Limin , Liu Yashu , Wang Xuena , Zhang Shunming , Meng Ge , Zhang Qing , Liu Li , Wu Hongmei , Gu Yeqing , Wang Yawen , Zhang Tingjing , Wang Xing , Sun Shaomei , Zhou Ming , Jia Qiyu , Song Kun , Niu Kaijun , Zhao Yuhong 
Published: October 2021

Purpose: This study aimed to determine the longitudinal association between hand grip strength (HGS) and the development of non-alcoholic fatty liver disease (NAFLD) in adults.Design: A cohort study.Methods: This study was conducted in a general Chinese population (n = 14,154) from 2013–2018. NAFLD was diagnosed by liver ultrasonography during evaluating alcohol consumption. The associations between the HGS and NAFLD were assessed using a multivariable Cox proportional hazards regression model.Results: During the study period with a mean follow-up duration of 3.20 years, 2,452 participants developed NAFLD. The risk of NAFLD decreased progressively with increasing HGS in both men and women (P for trend &lt;0.0001). The multivariate-adjusted hazard ratios (95% CI) for NAFLD incidence across the quartiles of HGS were 1 (reference), 0.90 (0.79, 1.02), 0.69 (0.60, 0.79), and 0.44 (0.37, 0.52) for men and 1 (reference), 0.82 (0.69, 0.96), 0.54 (0.45, 0.66), and 0.41 (0.33, 0.52) for women, respectively. The interaction terms for body mass index (BMI)-HGS and waist-HGS were significant in men and women (all P &lt; 0.0001). The participants with normal BMIs and waist circumferences had the lowest hazard ratios on the subgroup analyses. The sensitivity analysis that defined NAFLD using the hepatic steatosis and fatty liver indices revealed results that were similar to the main analyses.Conclusion: The present study indicates that the HGS is inversely associated with the incidence of NAFLD.
Cross-Sectional Characterization of Local Brain Network Connectivity Pre and Post Breast Cancer Treatment and Distinct Association With Subjective Cognitive and Psychological Function
Authors: Kesler Shelli R. , Tang Tien , Henneghan Ashley M. , Wright Michelle , Gaber M. Waleed , Palesh Oxana 
Published: October 2021

Objective: We aimed to characterize local brain network connectivity in long-term breast cancer survivors compared to newly diagnosed patients.Methods: Functional magnetic resonance imaging (fMRI) and subjective cognitive and psychological function data were obtained from a group of 76 newly diagnosed, pre-treatment female patients with breast cancer (mean age 57 ± 7 years) and a separate group of 80, post-treatment, female breast cancer survivors (mean age 58 ± 8; mean time since treatment 44 ± 43 months). The network-based statistic (NBS) was used to compare connectivity of local brain edges between groups. Hubs were defined as nodes with connectivity indices one standard deviation or more above network mean and were further classified as provincial (higher intra-subnetwork connectivity) or connector (higher inter-subnetwork connectivity) using the participation coefficient. We determined the hub status of nodes encompassing significantly different edges and correlated the centralities of edges with behavioral measures.Results: The post-treatment group demonstrated significantly lower subjective cognitive function (W = 3,856, p = 0.004) but there were no group differences in psychological distress (W = 2,866, p = 0.627). NBS indicated significantly altered connectivity (p &lt; 0.042, corrected) in the post-treatment group compared to the pre-treatment group largely in temporal, frontal-temporal and temporal-parietal areas. The majority of the regions projecting these connections (78%) met criteria for hub status and significantly less of these hubs were connectors in the post-treatment group (z = 1.85, p = 0.031). Subjective cognitive function and psychological distress were correlated with largely non-overlapping edges in the post-treatment group (p &lt; 0.05).Conclusion: Widespread functional network alterations are evident in long-term survivors of breast cancer compared to newly diagnosed patients. We also demonstrated that there are both overlapping and unique brain network signatures for subjective cognitive function vs. psychological distress.
Prenatal and Early Childhood Exposure to Lead and Repeated Measures of Metabolic Syndrome Risk Indicators From Childhood to Preadolescence
Authors: Muciño-Sandoval Karla , Ariza Ana Carolina , Ortiz-Panozo Eduardo , Pizano-Zárate María Luisa , Mercado-García Adriana , Wright Robert , Maria Téllez-Rojo Martha , Sanders Alison P. , Tamayo-Ortiz Marcela 
Published: October 2021

Background: Exposure to lead (Pb) during the early life stages has been associated with the development of metabolic syndrome (MetS). Longitudinal studies of Pb exposure in critical developmental windows in children are limited.Methods: Our study included 601 mother–child dyads from the PROGRESS (Programming Research in Obesity, Growth, Environment and Social Stressors) birth cohort. Blood lead levels (BLLs) were assessed during the second and third gestational trimesters, in cord blood at delivery, and at ages 1, 2, and 4 years. Bone lead levels in the patella and tibia were assessed at 1 month postpartum and evaluated in separate models. To account for cumulative exposure (prenatal, postnatal, and cumulative), we dichotomized the BLLs at each stage visit and determined the following: “higher” if a BLL was at least once above the median (HPb) and “lower” if all BLLs were below the median (LPb). We analyzed fasting glucose, HbA1c, triglycerides (TGs), total cholesterol (TC), high-density lipoprotein cholesterol (cHDL), low-density lipoprotein cholesterol (cLDL), body mass index, waist circumference (WC), body fat percentage, and systolic (SBP) and diastolic blood pressure (DBP) at two study visits between 6 and 12 years of age and created cutoff points based on the clinical guidelines for each indicator. Mixed effects models were used to analyze each outcome longitudinally for each BLL score, adjusting for child's sex, size for gestational age, child's age, maternal parity, mother's age, and socioeconomic status.Results: We observed associations for HPb exposure and TC in all stages (OR = 0.53, 95%CI = 0.32–0.86) and postnatally (OR = 0.59, 95%CI = 0.36–0.94) and for prenatal HPb and TGs (OR = 0.65, 95%CI = 0.44–0.95). HPb at all stages was associated with WC (OR = 0.27, 95%CI = 0.08–0.86), BMI (OR = 0.33, 95%CI = 0.11–0.99), SBP (OR = 0.53, 95%CI = 0.32–0.85), and DBP (OR = 0.57, 95%CI = 0.34–0.95). Pb levels in the patella were associated with cHDL (OR = 1.03, 95%CI = 1.00–1.07) and those in the tibia with TGs (OR = 0.95, 95%CI = 0.91–0.99).Conclusion: Early life exposure to Pb may alter early indicators of MetS. A follow-up of these children will allow for more definition on the impact of longer-term exposures.
Confounding Factors Affecting the Emotional Intelligence Amongst Jordanian Nursing and Midwifery Undergraduate Students During the COVID-19 Pandemic's Outbreak: A Cross-Sectional Study Using USMEQ-i
Authors: Alnjadat Rafi , Al-Rawashdeh Ahmad 
Published: October 2021

Objective: This aim of this study was to determine which variables from the demographic data most affect the EI regarding the COVID-19 outbreak and the lockdown amongst the nursing and midwifery students in Jordan.Background: Emotional intelligence (EI) is the ability to recognize, express, comprehend, motivate, influence and regulate emotions proposed the first EI model, which includes three constructs: emotion assessment and expression, emotion consumption and emotion control. During the COVID-19 outbreak and lockdown, face-to-face study methods have been replaced by online teaching, which has caused many psychological effects.Method: A cross-sectional approach was used to measure EI for nursing and midwifery students. The tool was completed online by nursing and midwifery students using Google Forms. All of the findings were received online and then analyzed accordingly. In this study, USMEQ-i was used to gather data from the participants.Results: The general EI score for the student respondents falls into the average score (M = 39.6). Regarding the difference between males and females, the results showed no significant difference. Moreover, the general linear regressions analysis of independent variables on EI score showed four significant factors. Nursing students who study in Years 1 and 4 had significantly higher EI scores than those in Years 2 and 3. EI ability decreased when a student's economic status changed from luxurious to middle income. Moreover, an increase in age significantly decreased the value of EI. This study indicates that all nursing and midwifery students who enrolled in general nursing program tended to have higher EI scores than others (p = 0.006).Conclusion: Year of study, age, average lifestyle and enrollment in a nursing program were found to be the most significant factors associated with EI amongst Jordanian nursing and midwifery students. This issue needs to be researched further, such that appropriate steps can be taken to address it.