bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification and validation of a prognostic model of necroptosis-related lncRNAs in hepatocellular carcinoma
Authors: Chen Min , Wu Guang-Bo , Hua Shan , Zhao Zhi-Feng , Li Hong-Jie , Luo Meng 
Published: September 2022

Background: The study focused on establishing a prognostic survival model with six necroptosis-related lncRNAs to predict overall survival (OS) in patients with hepatocellular carcinoma (HCC).Methods: The data of gene expression and clinical information of HCC patients were obtained from The Cancer Genome Atlas (TCGA). Cox regression with LASSO was used for constructing a necroptosis-related lncRNA survival model, which we further validated with qRT-PCR in vitro. The relative bioinformatics analysis and consensus cluster analysis were performed based on six differentially expressed lncRNAs.Results: The survival prognostic model was constructed by using data from TCGA. Receiver operating characteristic (ROC) curves showed a good survival prediction by this model. GSEA showed that several signaling pathways were related to HCC progression. Immune-related functional analysis showed that aDCs, macrophages, Th2 cells, and Tregs have stronger correlation with the high-risk group. The consensus cluster analysis further validated the 6-lncRNA prognostic model.Conclusion: A novel 6-lncRNA (AL606489.1, NRAV, LINC02870, DUXAP8, “ZFPM2-AS1,” and AL031985.3) prognostic model had an accurately predictive power in HCC prognosis, which might be worthy of clinical application.
Exploring the casual association between coffee intake and bladder cancer risk using Mendelian Randomization
Authors: Deng Yuqing , Wu Tingting , Luo Gang , Chen Lin 
Published: September 2022

Objective: Several observational studies have suggested that coffee consumption is associated with a lower risk of bladder cancer. However, observational studies are susceptible to confounding factors and reverse causality. We used a two-sample Mendelian randomization (MR) method to assess the causal nature of this association.Methods: At the genome-wide significance level (p &lt; 5 × 10−8), 12 single nucleotide polymorphisms (SNPs) strongly associated with coffee consumption were used as instrumental variables (IVs). Summary-level data on genetic variation in bladder cancer were obtained from the United Kingdom biobank (420,838 samples) and FinnGen consortium (175,121 samples). Multiple MR methods were used. Heterogeneity and horizontal pleiotropy were detected using Cochran’s Q test and MR-Egger.Results: Twelve SNPs were included in the primary analysis. After excluding 8 SNPs with potential secondary phenotypes, the remaining 4 SNPs were included in the sensitivity analysis. In all analyses, Cochran’s Q statistic indicated that there was no heterogeneity among SNPs, and the MR-Egger analysis did not reveal the existence of horizontal pleiotropy (p &gt; 0.05). In the United Kingdom Biobank, the odds ratio (OR) for bladder cancer was 1.022 (95% confidence interval (CI), 0.679–1.537) for per 50% increase in coffee consumption. Consistent results were obtained in the FinnGen consortium (OR = 0.890, 95% CI, 0.467–1.697). Sensitivity analysis showed consistent results with primary analysis.Conclusion This study does not support a causal association between habitual coffee consumption and bladder cancer risk.
HTRA1 rs11528744, BCRA1 rs9928736, and B3GLCT rs4381465 are associated with age-related macular degeneration in a Chinese population
Authors: Huang Guo , Li Huan , Lai Shuang , Xiao Jialing , Wang Liang , Xu Huijuan , Lei Chuntao , Zhang Jinglan , Yu Man , Shuai Ping , Liu Yuping , Shi Yi , Wang Kaijie , Gong Bo 
Published: September 2022

Purpose: Age-related macular degeneration (AMD) is a leading cause of vision loss. A Previous study based on the co-localization analysis of the genome-wide association study (GWAS) and eQTL genetic signals have reported that single nucleotide polymorphisms (SNPs), including rs760975, rs11528744, rs3761159, rs7212510, rs6965458, rs7559693, rs56108400, rs28495773, rs9928736, rs11777697, rs4381465 are associated with AMD in Americans. The aim of this study was to investigate the association of these SNPs in a Han Chinese population.Methods: There were 576 patients with wet AMD and 572 healthy controls collected in this study. All SNPs were genotyped by flight mass spectrum. Hardy–Weinberg equilibrium was applied to evaluate allele distributions for both AMD and control groups. The genotype and allele frequencies were evaluated using the χ2 tests. Odds ratio (OR) and 95% confidence intervals (95% CI) were calculated for the risk of genotype and allele.Results: Three of the 11 SNPs (rs11528744 in HTRA1, rs9928736 in BCRA1 and rs4381465 in B3GLCT) were found to be significantly associated with AMD in the allelic model (corrected p = 0.001, OR = 1.391, 95%CI = 1.179–1.640 for rs11528744; corrected p = 0.004, OR = 0.695, 95%CI = 0.544–0.888 for rs9928736; corrected p = 0.002, OR = 0.614, 95%CI = 0.448–0.841 for rs4381465). There were no differences for the remaining eight SNPs between AMD cases and healthy controls.Conclusion: Our results showed that HTRA1 rs11528744, BCRA1 rs9928736, and B3GLCT rs4381465 were associated with wet AMD, suggesting that HTRA1, BCRA1, and B3GLCT genes may be involved in the development of AMD.
A boy with amblyopia and familial exudative vitreoretinopathy harboring a new mutation of LRP5 and OPA1: A case report
Authors: Chen Chunli , Guo Sitong , Zhao Rui , Liu Shoubin , Wu Jingjing , Xiao Yuanyuan , Hou Simeng , Jiang Libin 
Published: September 2022

Background: The study aimed to report a boy with familial exudative vitreoretinopathy and amblyopia harboring a new mutation of the LRP5 and OPA1 gene abnormality.Case presentation: A 9-year-old boy presented with a 2-year history of deteriorating visual acuity in the right eye. His best-corrected visual acuity was −7.00/−1.75 × 100 = 0.3 in the right eye and −2.50/−1.50 × 170 = 0.8 in the left eye. Two autosomal dominant gene mutation sites were identified in the patient: LRP5 (c.2551C &gt; T, p.His851Tyr) from his father and OPA1 (c.565G &gt; A, p.Glu189Lys) from his mother. Interestingly, his fraternal twin brother harbored no abnormal gene mutations, and his eye tests were normal.Conclusion: This case expands the spectrum of LRP5 gene mutations among Chinese patients with familial exudative vitreoretinopathy, and it is the first time to report a patient harboring both LRP5 and OPA1 gene mutations having anisometropic amblyopia and strabismus as the primary manifestations. These four family members exhibited individual heterogeneity of phenotypes and genotypes associated with hereditary ophthalmopathy. A comprehensive analysis of clinical phenotypes and genotypes provides clinical clues for improving the level of clinical and genetic diagnoses and a deeper understanding of the disease.
Determinants of anti-S immune response at 6 months after COVID-19 vaccination in a multicentric European cohort of healthcare workers – ORCHESTRA project
Authors: Collatuzzo Giulia , Visci Giovanni , Violante Francesco S. , Porru Stefano , Spiteri Gianluca , Monaco Maria Grazia Lourdes , Larese Fillon Francesca , Negro Corrado , Janke Christian , Castelletti Noemi , De Palma Giuseppe , Sansone Emanuele , Mates Dana , Teodorescu Silvia , Fabiánová Eleonóra , Bérešová Jana , Vimercati Luigi , Tafuri Silvio , Abedini Mahsa , Ditano Giorgia , Asafo Shuffield S. , Boffetta Paolo ,   Orchestra WP5 Working Group
Published: September 2022

BackgroundThe duration of immune response to COVID-19 vaccination is of major interest. Our aim was to analyze the determinants of anti-SARS-CoV-2 IgG titer at 6 months after 2-dose vaccination in an international cohort of vaccinated healthcare workers (HCWs).MethodsWe analyzed data on levels of anti-SARS-CoV-2 Spike antibodies and sociodemographic and clinical characteristics of 6,327 vaccinated HCWs from 8 centers from Germany, Italy, Romania and Slovakia. Time between 1st dose and serology ranged 150-210 days. Serological levels were log-transformed to account for the skewness of the distribution and normalized by dividing them by center-specific standard errors, obtaining standardized values. We fitted center-specific multivariate regression models to estimate the cohort-specific relative risks (RR) of an increase of 1 standard deviation of log antibody level and corresponding 95% confidence interval (CI), and finally combined them in random-effects meta-analyses.ResultsA 6-month serological response was detected in 99.6% of HCWs. Female sex (RR 1.10, 95%CI 1.00-1.21), past infection (RR 2.26, 95%CI 1.73-2.95) and two vaccine doses (RR 1.50, 95%CI 1.22-1.84) predicted higher IgG titer, contrary to interval since last dose (RR for 10-day increase 0.94, 95%CI 0.91-0.97) and age (RR for 10-year increase 0.87, 95%CI 0.83-0.92). M-RNA-based vaccines (p&lt;0.001) and heterologous vaccination (RR 2.46, 95%CI 1.87-3.24, one cohort) were associated with increased antibody levels.ConclusionsFemale gender, young age, past infection, two vaccine doses, and m-RNA and heterologous vaccination predicted higher antibody level at 6 months. These results corroborate previous findings and offer valuable data for comparison with trends observed with longer follow-ups.
Early immunological responses to the mRNA SARS-CoV-2 vaccine in patients with neuromuscular disorders
Authors: Iwayama Hideyuki , Ishihara Naoko , Kawahara Kohei , Madokoro Yuta , Togawa Yasuko , Muramatsu Kanji , Murakami Ayuka , Kuru Satoshi , Kumagai Toshiyuki , Ohashi Wataru , Nanya Kengo , Hasegawa Shinji , Katsuno Masahisa , Okumura Akihisa 
Published: September 2022

BackgroundsIntramuscular injection of the SARS-CoV-2 vaccine has raised concerns about its use in patients with neuromuscular disorders (NMDs). We evaluated the response of patients with NMDs to the BNT162b2 vaccine.MethodsHealthy subjects, patients with spinal muscular atrophy (SMA), and patients with Duchenne muscular dystrophy (DMD) were included. All participants received two BNT162b2 doses. SARS-CoV-2 antibody titers at baseline and 2 weeks after each vaccination were compared between groups. Residual muscle volume was evaluated in NMDs group. A questionnaire documented adverse reactions.ResultsEleven patients with NMDs (9 with SMA, 2 with DMD; 7 males; aged 32.7 ± 19.3 years) and 346 healthy subjects (60 males, aged 40.0 ± 12.4 years) were included. Antibody titers (U/mL) were similar between groups (baseline: &lt;0.40 vs. &lt;0.40, first vaccination, 145 ± 258 vs. 103 ± 1192, and second vaccination, 1528 ± 1265 vs. 1429 ± 944; p = 1.000, 0.909, and 0.736, respectively). A negative correlation was found between antibody titers and residual muscle volume but was not significant (Mercuri scale, r = −0.429, p = 0.249; fat infiltration rate, r = −0.194, p = 0.618). The adverse reactions were comparable between groups.ConclusionThe BNT162b2 vaccine is safe and effective in patients with NMDs.
Genetic association of leukocyte telomere length with Graves’ disease in Biobank Japan: A two-sample Mendelian randomization study
Authors: Ye Meijie , Wang Yu , Zhan Yiqiang 
Published: September 2022

BackgroundTelomere length (TL) has been recognized to be fundamental to the risk of autoimmune disorders. However, the role of leukocyte TL in Graves’ disease has not yet been fully elucidated. In the study, we exploited the two-sample Mendelian randomization (MR) design to evaluate the causal effect of leukocyte TL on the risk of Graves’ disease.MethodsGenome-wide association study (GWAS) data of leukocyte TL from the Singapore Chinese Health Study (SCHS) cohort and Graves’ disease from Biobank Japan (BBJ, 2176 cases and 210,277 controls) were analyzed. Nine single nucleotide polymorphisms (SNPs) were selected as instrumental variables (IVs) for TL. We used the inverse variance weighted (IVW) approach as the main estimator and MR-Egger regression, weighted median, simple mode, and weighed mode methods as complementary estimators. Horizontal pleiotropy was assessed using the intercept from MR-Egger.ResultsThe analysis demonstrated that genetically predicted longer leukocyte TL was causally associated with a lower risk of Graves’ disease using the IVW method (odds ratio [OR]: 1.64, 95% confidence interval [CI]: 1.23-2.17, P=2.27e-04, and other complementary MR approaches achieved similar results. The intercept from the MR-Egger analysis provided no noticeable evidence of horizontal pleiotropy (β=0.02, P=0.641). MR-PRESSO method reported no outliers (P=0.266).ConclusionsOur results provided evidence to support a genetic predisposition to shorter leukocyte TL with an increased risk of Graves’ disease. Further studies are warranted to explore the mechanism underlying the association.
Peripheral blood marker of residual acute leukemia after hematopoietic cell transplantation using multi-plex digital droplet PCR
Authors: Stanojevic M. , Grant M. , Vesely S. K. , Knoblach S. , Kanakry C. G. , Nazarian J. , Panditharatna E. , Panchapakesan K. , Gress R. E. , Holter-Chakrabarty J. , Williams Kirsten M. 
Published: September 2022

BackgroundRelapse remains the primary cause of death after hematopoietic cell transplantation (HCT) for acute leukemia. The ability to identify minimal/measurable residual disease (MRD) via the blood could identify patients earlier when immunologic interventions may be more successful. We evaluated a new test that could quantify blood tumor mRNA as leukemia MRD surveillance using droplet digital PCR (ddPCR).MethodsThe multiplex ddPCR assay was developed using tumor cell lines positive for the tumor associated antigens (TAA: WT1, PRAME, BIRC5), with homeostatic ABL1. On IRB-approved protocols, RNA was isolated from mononuclear cells from acute leukemia patients after HCT (n = 31 subjects; n = 91 specimens) and healthy donors (n = 20). ddPCR simultaneously quantitated mRNA expression of WT1, PRAME, BIRC5, and ABL1 and the TAA/ABL1 blood ratio was measured in patients with and without active leukemia after HCT.ResultsTumor cell lines confirmed quantitation of TAAs. In patients with active acute leukemia after HCT (MRD+ or relapse; n=19), the blood levels of WT1/ABL1, PRAME/ABL1, and BIRC5/ABL1 exceeded healthy donors (p&lt;0.0001, p=0.0286, and p=0.0064 respectively). Active disease status was associated with TAA positivity (1+ TAA vs 0 TAA) with an odds ratio=10.67, (p=0.0070, 95% confidence interval 1.91 – 59.62). The area under the curve is 0.7544. Changes in ddPCR correlated with disease response captured on standard of care tests, accurately denoting positive or negative disease burden in 15/16 (95%). Of patients with MRD+ or relapsed leukemia after HCT, 84% were positive for at least one TAA/ABL1 in the peripheral blood. In summary, we have developed a new method for blood MRD monitoring of leukemia after HCT and present preliminary data that the TAA/ABL1 ratio may may serve as a novel surrogate biomarker for relapse of acute leukemia after HCT.
Spatial and temporal distribution of phytoplankton community in relation to environmental factors in the southern coastal waters of Korea
Authors: Sun Yanxu , Youn Seok-Hyun , Oh Hyun Joo , Joo Hui-Tae , Kim Yejin , Kang Jae Joong , Lee Dabin , Kim Kwanwoo , Jang Hyo Keun , Jo Naeun , Yun Mi Sun , Sun Linhe , Lee Sang Heon 
Published: September 2022

The spatial and temporal environmental conditions in the southern coastal waters of Korea (SCWK) as a complex area, which is influenced by both ocean currents and anthropogenic nutrient inputs, are highly variable. The impacts of environmental factors on the distribution of phytoplankton community structure in the SCWK remain unclear. Based on high-performance liquid chromatography (HPLC) analysis of a variety of photosynthetic pigments, spatial and temporal variations in phytoplankton community compositions were investigated in the SCWK. Cluster analysis, correlation analysis, and generalized additive models (GAMs) were used to explore the major phytoplankton groups and their response patterns to temperature, salinity, depth, and macronutrients. The results indicated that diatoms were the absolute dominant groups in the SCWK for all seasons, especially in cold seasons. Diatoms mainly concentrated at 1% light depths, while high chlorophyll-a concentrations (&gt;3 µg/L) occurred at 100% and 30% light depths with good light conditions. Both clustering and correlation analyses showed that diatoms had a strong positive correlation with macronutrients such as dissolved inorganic nitrogen (DIN), dissolved inorganic phosphate (DIP), and dissolved silica (DSi). The temperature and salinity discrepancy between surface and bottom layers in summer caused a strong water stratification resulting in blocking nutrient-rich bottom water upwelling and leading cyanobacteria to become the dominant groups at 100% and 30% light depths in summer. Consistently, the cyanobacteria were highly associated with high temperature and low salinity in the correlation analysis and GAM results. Compared with diatom-predominant sites, cryptophytes and diatom-dominated sites are characterized by higher average excess nitrate (ExN). Further research on the responses of small-sized prokaryotic phytoplankton especially cyanobacteria to environmental variations and their primary production contributions would warrant a better understanding of the SCWK ecosystem.
Development of an anisokinetic particle sampling probe for use in a gas turbine engine compressor
Authors: Olshefski Kristopher , Collins Addison , Coulon Thomas , Lowe Todd , Ng Wing 
Published: September 2022

Sand and dust particle ingestion is an inevitability for aircraft operating in arid environments. For conventional takeoff and landing aircraft, significant dust can be ingested into the gas turbine powerplant. Helicopters and vertical takeoff and landing (VTOL) aircraft are at especially high risk due to their tendency to blow significant debris into the air during takeoff and landing operations. The present study highlights the development of an anisokinetic particle sampling probe for use in aircraft engines to obtain real-time measurement of ingested particles often present in these harsh environments. Offtake of particles during engine operation in dusty conditions will provide researchers with an improved understanding of particle breakage tendency and component erosion susceptibility. Three foundational studies were conducted to establish a baseline understanding of probe performance: an aerodynamic study, a particle tracking study, and a particle sampling study. These studies were performed using the Free Jet rig at the Advanced Propulsion and Power Laboratory at Virginia Tech. Particles as large as 1.3 mm were sampled at Mach numbers where M = (0.25, 0.70) and yaw angles ranging from 0° to 45° relative to freestream, conditions not previously investigated. Results indicate that the probe operates sub-isokinetically throughout the full range of test conditions and that probe aerodynamic capture efficiency is inversely proportional to both Mach number and yaw angle. However, this efficiency limitation does not notably influence the sampling probe’s ability to capture the test dust of interest. While the presence of the probe in the flow does result in an airflow velocity reduction of up to 55%, due to their relatively large Stokes numbers the particles of interest only experience a decrease of roughly 5%. These results indicate that this probe is capable of providing researchers with valuable particle size and shape information through effective particle sampling at particle sizes (100 μm ≤ dp ≤ 1,300 μm) and speeds (M ≥ 0.25) not previously investigated.
Cilgavimab/Tixagevimab as alternative therapeutic approach for BA.2 infections
Authors: Dichtl Stefanie , Zaderer Viktoria , Kozubowski Viktoria , Abd El Halim Hussam , Lafon Eliott , Lanser Lukas , Weiss Günter , Lass-Flörl Cornelia , Wilflingseder Doris , Posch Wilfried 
Published: September 2022

ObjectivesThe identification of the SARS-CoV-2 Omicron variants BA.1 and BA.2 immediately raised concerns about the efficacy of currently used monoclonal antibody therapies. Here, we analyzed the activity of Sotrovimab and Regdanvimab, which are used in clinics for treatment of moderate to severe SARS-CoV-2 infections, and Cilgavimab/Tixagevimab, which are approved for prophylactic use, against BA.1 and BA.2 in a 3D model of primary human bronchial epithelial cells.MethodsPrimary human airway epithelia (HAE) cells in a 3D tissue model were infected with clinical isolates of SARS-CoV-2 Delta, BA.1 or BA.2. To mimic the therapeutic use of mAbs, we added Regdanvimab, Sotrovimab or Cilgavimab/Tixagevimab 6 h after infection. In order to mirror the prophylactic use of Cilgavimab/Tixagevimab, we added this compound 6 h prior to infection to the fully differentiated, pseudostratified epithelia cultured in air-liquid interphase (ALI).ResultsWe observed that Sotrovimab, but not Regdanvimab, is active against BA.1; however, both antibodies lose their efficacy against BA.2. In contrast, we found that BA.2 was sensitive to neutralization by the approved prophylactic administration and the therapeutic use, which is not yet permitted, of Cilgavimab/Tixagevimab.ConclusionImportantly, while the use of Tixagevimab/Cilgavimab is effective in controlling BA.2 but not BA.1 infection, monoclonal antibodies (mAbs) with efficacy against BA.1 are ineffective to reduce BA.2 virus replication in a human lung model. Our data may have implications on the variant specific clinical use of monoclonal antibodies.