bluuebunny/crossref_metadata_2025_split huggingface dataset:
ACE2 and TMPRSS2 SNPs as Determinants of Susceptibility to, and Severity of, a COVID-19 Infection
Authors: Abdelsattar S. , Kasemy Z. A. , Ewida S. F. , Abo-Elsoud R. A. A. , Zytoon A. A. , Abdelaal G. A. , Abdelgawad A. S. , Khalil F. O. , Kamel H. F. M. 
Published: February 2022

Background: Genetic risk factors may be related to the infectivity and severity of SARS-CoV-2 infection. Angiotensin-converting enzyme 2 (ACE2) and host transmembrane serine protease (TMPRSS2) have key role in viral cell entrance and priming.Methods: This case-control study on 147 healthy controls and 299 COVID-19 patients identified potential determinants and risk factors, including gene polymorphism involved in the severity (mild, moderate, severe) of COVID-19 disease defined by CORAD radiological criteria.Results: The ACE2 s2285666 and TMPRSS2 rs12329760 SNPs were significantly linked with COVID-19 disease severity, as were certain co-morbidities (hypertension, heart disease) and laboratory parameters. Both SNPs were amongst the highest predictors of disease severity: TMPRSS2 rs12329760 CT + TT [odds ratio (95% CI) 17.6 (5.1–61.10), ACE2 rs2285666 CT + TT 9.9 (3.2–30.9), both p &lt; 0.001]. There was an increase in the expression of genotype frequencies of ACE2 rs2285666 and TMPRSS2 rs1232976 (TT), (CT + TT), and (T) allele in severe COVID-19 group compared to control and mild groups. Disease severity was also linked to elevated CRP, ferritin and D-dimer, and lower lymphocytes and platelet count (all p &lt; 0.001).Conclusion: ACE2 rs2285666 and TMPRSS2 rs12329760 SNPs, in addition to lymphocyte count, CRP, D-dimers, ferritin, and hypertension, are predictors of COVID-19 disease severity.
m6A Regulator-Mediated Methylation Modification Patterns and Tumor Microenvironment Cell-Infiltration Characterization in Head and Neck Cancer
Authors: Yang Qinghui , Xu Feng , Jian Aiwen , Yu Hongmei , Ye Tao , Hu Weiqi 
Published: February 2022

Background: Recently, RNA modifications have emerged as essential epigenetic regulators of gene expression. However, the mechanism of how RNA N6-methyladenosine (m6A) modification interacts with tumor microenvironment (TME) infiltration remains obscure.Methods: A total of 876 head and neck cancer samples considering 21 m6A regulators were included and analyzed to determine the m6A modification patterns. These modification patterns were then correlated with TME immune cell-infiltrating characteristics. A scoring system, the m6Ascore, was constructed using principal component analysis algorithms to quantify m6A modification of tumors.Results: Three m6A modification patterns were identified, with TME infiltrating characteristics highly consistent with tumors with three distinct immune phenotypes, including immune-inflamed, immune-exclude, and immune-desert phenotypes. It was demonstrated that the identification of the m6A modification patterns via m6Ascore could predict tumor progression, subtypes, TME stromal activity, variation of relevant genes, and patient prognosis. Low m6Ascore, identified to be an inflamed phenotype, is found to be associated with low stroma activity and tumor mutation burden, high survival probability, increased tumor neoantigen burden, and enhanced response to anti-PD-1/L1 immunotherapy. The therapeutic advantages and clinical benefits of patients with low m6Ascore were further verified in two immunotherapy cohorts.Conclusion: This study identified the significant role that the m6A modification played in the formation of TME characteristics. A more comprehensive understanding of the m6A modification patterns and their correlation with TME infiltration will contribute to the discovery of immunotherapy strategies with better efficacy.
Lipoprotein(a) and Pulmonary Embolism Severity-A Retrospective Data Analysis
Authors: Gressenberger Paul , Posch Florian , Pechtold Moritz , Gütl Katharina , Muster Viktoria , Jud Philipp , Riedl Jakob , Silbernagel Günther , Kolesnik Ewald , Schmid Johannes , Raggam Reinhard B. , Brodmann Marianne , Gary Thomas 
Published: February 2022

AimWe aimed to investigate a correlation between PE severity and Lp(a) levels.MethodsWe performed a retrospective data analysis from our medical records of PE patients admitted to the University Hospital Graz, Austria. Patients with an Lp(a) reading within a 1-year interval before and after PE diagnosis were included. In accordance with the 2019 ESC guidelines for the diagnosis and management of acute PE, severity assessment was carried out classifying patients into four groups: low risk (LR), intermediate low risk (IML), intermediate high risk (IMH) and high risk (HR). The study period of interest was between January 1, 2002 and August 1, 2020.ResultsWe analyzed 811 patients with PE, of whom 323 (40%) had low-risk PE, 343 (42%) had intermediate-low-risk PE, 64 (8%) had intermediate-high-risk PE, and 81 (10%) had high-risk PE, respectively. We did not observe an association between PE severity and Lp(a) concentrations. In detail, median Lp(a) concentrations were 17 mg/dL [25–75th percentile: 10-37] in low-risk PE patients, 16 mg/dL [10–37] in intermediate-low-risk PE patients, 15mg/dL [10–48] in intermediate-high-risk PE patients, and 13mg/dL [10–27] in high-risk PE patients, respectively (Kruskal-Wallis p = 0.658, p for linear trend = 0.358).ConclusionThe current findings suggest no correlation between PE severity and Lp(a) levels.
Middle Eocene Paleoenvironmental Reconstruction in the Gonjo Basin, Eastern Tibetan Plateau: Evidence From Palynological and Evaporite Records
Authors: Wang Licheng , Yuan Qin , Shen Lijian , Ding Lin 
Published: February 2022

The early uplift of the Tibetan Plateau (TP) had a profound influence on the paleoenvironment and paleoclimate. However, we still have little information about the link between the paleoclimatic changes and flora ecosystem caused by the uplift. The Eocene fluvial-lacustrine sequences in the Gonjo Basin, eastern TP, provide excellent archives of the paleoecological and paleoclimatic responses to the surface uplift of the TP. In this study, we investigated a section of the middle Eocene Ranmugou Formation (47.8–&gt;44 Ma) and used the sporomorphs assemblages, sedimentology, and geochemistry of the evaporites to reconstruct the paleoclimate and paleovegetation. The palynological assemblages and coexistence analysis reveal that the middle Eocene ecosystem in the Gonjo Basin was dominated by warm and humid temperate deciduous broad-leaved forests. The 87Sr/86Sr ratios (0.709942–0.710062) of all of the gypsum samples are higher than those of contemporaneous seawater, while the δ34S values (10.3–11.0%) are much lower, indicating a lacustrine environment. Combined with published palynological and paleoelevation data for eastern Tibetan lacustrine basins, we infer that the paleoenvironment changed from warm and humid deciduous broad-leaved forests during 47.8–&gt;44 Ma, to cool and arid temperate forest during 44–40 Ma in the Gonjo Basin, and to arid and cool steppe-desert vegetation in the late Eocene Nangqian Basin. The changes in the paleoclimate and vegetation were primarily driven by the surface uplift of the Central Watershed Mountain, the high topography of which blocked the moisture from the Asian Eocene monsoon.
The Risk Stratification of Papillary Thyroid Cancer With Bethesda Category III (Atypia of Undetermined Significance/Follicular Lesion of Undetermined Significance) by Thyroid Fine‐Needle Aspiration Could Be Assisted by Tumor Size for Precision Treatment
Authors: Zha Xiaojuan , Miao Zhenchun , Huang Xiu , Wang Xingchun , Xie Ruting , Jin Jiaoying , Zou Dajin , Yang Peng , Huang Yueye 
Published: February 2022

PurposeTo investigate the clinical characteristics of papillary thyroid cancer (PTC) classified as Bethesda category III [atypia of undetermined significance (AUS)/follicular lesion of undetermined significance (FLUS)] by fine-needle aspiration (FNA) for precision treatment.MethodsA total of 1,739 patients diagnosed with Bethesda category III (AUS/FLUS) by FNA were investigated, and 290 patients diagnosed with PTC were analyzed.ResultsThe rate of papillary thyroid microcarcinoma (PTMC) was 82.1% (238/290). The rates of lymph node metastases were 44.9% (22/49) and 25.2% (56/222) for PTC and PTMC, respectively (p = 0.006). The rates of extra-thyroid extension were 46.2% (24/52) and 19.8% (47/237) (p &lt; 0.001). Compared with PTMC, PTC had significantly higher odds ratios (ORs) of 3.41 (1.81–6.44, p &lt; 0.001), 2.19 (1.16–4.13, p = 0.016), and 2.51 (1.29–4.88, p = 0.007) for extra-thyroid extension, multifocality, and lymph node metastases, respectively, after adjustment for age and gender. The larger size and BRAF V600E mutation had a robust synergistic effect for invasive features. The rates of lymph node metastases, multifocality, and extra-thyroid extension were significantly increased with larger sizes harboring BRAF V600E mutation. Compared with PTMC harboring wild type (WT)-BRAF, PTC harboring BRAF V600E mutation had adjusted higher ORs of 3.01 (1.26–8.68, p = 0.015), 3.20 (1.22–8.42, p = 0.018), and 5.62 (2.25–14.01, p &lt; 0.001) for lymph node metastases, multifocality, and extra-thyroid extension, respectively.ConclusionsIn this study, risk stratification was recommended for patients with Bethesda category III (AUS/FLUS) nodules with a size under 1 cm harboring WT-BRAF being regarded as low risk and should be recommended for active surveillance. Nodules with a size over 1 cm harboring WT-BRAF or those under 1 cm harboring BRAF V600E mutation could be regarded as moderate risk, and molecular testing should be recommended. However, those with a size over 1 cm harboring BRAF V600E mutation should be regarded as high risk, and a diagnostic surgery should be recommended.
Genetic Influence Underlying Brain Connectivity Phenotype: A Study on Two Age-Specific Cohorts
Authors: Cong Shan , Yao Xiaohui , Xie Linhui , Yan Jingwen , Shen Li ,   and the Alzheimer’s Disease Neuroimaging Initiative
Published: February 2022

Background: Human brain structural connectivity is an important imaging quantitative trait for brain development and aging. Mapping the network connectivity to the phenotypic variation provides fundamental insights in understanding the relationship between detailed brain topological architecture, function, and dysfunction. However, the underlying neurobiological mechanism from gene to brain connectome, and to phenotypic outcomes, and whether this mechanism changes over time, remain unclear.Methods: This study analyzes diffusion-weighted imaging data from two age-specific neuroimaging cohorts, extracts structural connectome topological network measures, performs genome-wide association studies of the measures, and examines the causality of genetic influences on phenotypic outcomes mediated via connectivity measures.Results: Our empirical study has yielded several significant findings: 1) It identified genetic makeup underlying structural connectivity changes in the human brain connectome for both age groups. Specifically, it revealed a novel association between the minor allele (G) of rs7937515 and the decreased network segregation measures of the left middle temporal gyrus across young and elderly adults, indicating a consistent genetic effect on brain connectivity across the lifespan. 2) It revealed rs7937515 as a genetic marker for body mass index in young adults but not in elderly adults. 3) It discovered brain network segregation alterations as a potential neuroimaging biomarker for obesity. 4) It demonstrated the hemispheric asymmetry of structural network organization in genetic association analyses and outcome-relevant studies.Discussion: These imaging genetic findings underlying brain connectome warrant further investigation for exploring their potential influences on brain-related complex diseases, given the significant involvement of altered connectivity in neurological, psychiatric and physical disorders.
Low Intelligence Predicts Higher Risks of Coronary Artery Disease and Myocardial Infarction: Evidence From Mendelian Randomization Study
Authors: Yang Fangkun , Hu Teng , Chen Songzan , Wang Kai , Qu Zihao , Cui Hanbin 
Published: February 2022

Background: Low intelligence has been shown to be associated with a high risk of cardiovascular disease in observational studies. It remains unclear whether the association is causal. This study aimed to explore the causal association of intelligence with coronary artery disease (CAD) and myocardial infarction (MI).Methods: A two-sample Mendelian randomization study was designed to infer the causality. A total of 121 single nucleotide polymorphisms were selected as a genetic instrumental variable for intelligence. Summary data on CAD (n = 184,305) and MI (n = 171,875) were obtained from the Coronary ARtery DIsease Genome-wide Replication and Meta-analysis (CARDIoGRAM) plus The Coronary Artery Disease (C4D) Genetics (CARDIoGRAMplusC4D) consortium and the FinnGen study. Inverse variance weighting method was used to calculate the effect estimates. Sensitivity analyses including other statistical models and leave-one-out analysis were conducted to verify the robustness of results. MR-Egger test was performed to assess the pleiotropy.Results: Genetically predicted higher intelligence was significantly associated with lower risk of CAD (OR, .76; 95%CI, .69–.85; p = 1.5 × 10–7) and MI (OR, .78; 95%CI, .70–.87; p = 7.9 × 10–6). The results remained consistent in the majority of the sensitivity analyses and were repeated in the FinnGen datasets. MR-Egger test suggested no evidence of directional pleiotropy for the association with coronary artery disease (intercept = −.01, p = .19) and myocardial infarction (intercept = −.01, p = .06).Conclusion: This Mendelian randomization analysis provided genetic evidence for the causal association between low intelligence and increased risks of CAD and MI.
Children and Adults With Mild COVID-19: Dynamics of the Memory T Cell Response up to 10 Months
Authors: Kaaijk Patricia , Olivo Pimentel Verónica , Emmelot Maarten E. , Poelen Martien C. M. , Cevirgel Alper , Schepp Rutger M. , den Hartog Gerco , Reukers Daphne F.M. , Beckers Lisa , van Beek Josine , van Els Cécile A. C. M. , Meijer Adam , Rots Nynke Y. , de Wit Jelle 
Published: February 2022

BackgroundSevere acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to considerable morbidity/mortality worldwide, but most infections, especially among children, have a mild course. However, it remains largely unknown whether infected children develop cellular immune memory.MethodsTo determine whether a memory T cell response is being developed, we performed a longitudinal assessment of the SARS-CoV-2-specific T cell response by IFN-γ ELISPOT and activation marker analyses of peripheral blood samples from unvaccinated children and adults with mild-to-moderate COVID-19.ResultsUpon stimulation of PBMCs with heat-inactivated SARS-CoV-2 or overlapping peptides of spike (S-SARS-CoV-2) and nucleocapsid proteins, we found S-SARS-CoV-2-specific IFN-γ T cell responses in infected children (83%) and adults (100%) that were absent in unexposed controls. Frequencies of SARS-CoV-2-specific T cells were higher in infected adults, especially several cases with moderate symptoms, compared to infected children. The S-SARS-CoV-2 IFN-γ T cell response correlated with S1-SARS-CoV-2-specific serum antibody concentrations. Predominantly, effector memory CD4+ T cells of a Th1 phenotype were activated upon exposure to SARS-CoV-2 antigens. Frequencies of SARS-CoV-2-specific T cells were significantly reduced at 10 months after symptom onset, while S1-SARS-CoV-2-specific IgG concentrations were still detectable in 90% of all children and adults.ConclusionsOur data indicate that an antigen-specific T cell and antibody response is developed after mild SARS-CoV-2 infection in children and adults. It remains to be elucidated to what extent this SARS-CoV-2-specific response can contribute to an effective recall response after reinfection.
Broadband Sound Absorption of Subwavelength Porous Meta-Liner
Authors: Xiao Heye , Yuan Tianyue , Song Xiang , Chen Junli , Zhou Jie , Sui Dan , Gu Jintao 
Published: February 2022

This work proposes a subwavelength porous meta-liner with broadband sound absorption from 900 to 1,200 Hz. The meta-liner consists of four subunits, which are made up of porous material and hollow coiling slit embedded in it. Each subunit is designed by adjusting the length of its coiling slit to achieve resonance in the target frequency and examined by the finite element method (FEM). These subunits are arranged in an axial direction uniformly and radial direction periodically to propose a meta-liner duct. Then, the noise reduction of the propeller system with the meta-liner duct is measured by the microphone array. The result shows that the propeller with the meta-liner duct can reduce the noise level of the ducted propeller between 3.6 and 5.5 dB in the design frequency range, which also effectively reduces the noise level in the broadband frequency range. Therefore, the meta-liner shows a good application prospect in the noise reduction of the propeller.
Transcriptome-Based Molecular Networks Uncovered Interplay Between Druggable Genes of CD8+ T Cells and Changes in Immune Cell Landscape in Patients With Pulmonary Tuberculosis
Authors: Alsulaimany Faten Ahmad , Zabermawi Nidal M. Omer , Almukadi Haifa , Parambath Snijesh V. , Shetty Preetha Jayasheela , Vaidyanathan Venkatesh , Elango Ramu , Babanaganapalli Babajan , Shaik Noor Ahmad 
Published: February 2022

BackgroundTuberculosis (TB) is a major infectious disease, where incomplete information about host genetics and immune responses is hindering the development of transformative therapies. This study characterized the immune cell landscape and blood transcriptomic profile of patients with pulmonary TB (PTB) to identify the potential therapeutic biomarkers.MethodsThe blood transcriptome profile of patients with PTB and controls were used for fractionating immune cell populations with the CIBERSORT algorithm and then to identify differentially expressed genes (DEGs) with R/Bioconductor packages. Later, systems biology investigations (such as semantic similarity, gene correlation, and graph theory parameters) were implemented to prioritize druggable genes contributing to the immune cell alterations in patients with TB. Finally, real time-PCR (RT-PCR) was used to confirm gene expression levels.ResultsPatients with PTB had higher levels of four immune subpopulations like CD8+ T cells (P = 1.9 × 10−8), natural killer (NK) cells resting (P = 6.3 × 10−5), monocytes (P = 6.4 × 10−6), and neutrophils (P = 1.6 × 10−7). The functional enrichment of 624 DEGs identified in the blood transcriptome of patients with PTB revealed major dysregulation of T cell-related ontologies and pathways (q ≤ 0.05). Of the 96 DEGs shared between transcriptome and immune cell types, 39 overlapped with TB meta-profiling genetic signatures, and their semantic similarity analysis with the remaining 57 genes, yielded 45 new candidate TB markers. This study identified 9 CD8+ T cell-associated genes (ITK, CD2, CD6, CD247, ZAP70, CD3D, SH2D1A, CD3E, and IL7R) as potential therapeutic targets of PTB by combining computational druggability and co-expression (r2 ≥ |0.7|) approaches.ConclusionThe changes in immune cell proportion and the downregulation of T cell-related genes may provide new insights in developing therapeutic compounds against chronic TB.
Assessment of Eyelid Pressure Using a Novel Pressure Measurement Device in Patients With Moderate-to-Severe Dry Eye Disease
Authors: Wang Jingyi , Bao Jiayu , Song Wenxiu , Li Siyuan , Hao Yiran , Tian Lei , Jie Ying 
Published: February 2022

ObjectiveTo assess a novel eyelid pressure measurement device and study the relationship between eyelid pressure and ocular surface parameters of moderate-to-severe dry eye disease (DED).MethodsThe present study included 70 eyes of 35 moderate-to-severe DED patients. All subjects were subjected to the following examinations for DED assessment: Ocular Surface Disease Index (OSDI) questionnaire, tear meniscus height (TMH), lipid layer thickness (LLT), number of partial blink (PB), total blink (TB) and partial blink rate (PBR), fluorescein tear breakup time (FBUT), corneal fluorescein staining (CFS), lid margin abnormality, meibum expression assessment (meibum score), meibomian gland dropout (MGd) and Schirmer I test. Pressure of the upper eyelid was measured thrice with the novel pressure measurement device. Repeatability of the device was evaluated by intraclass correlation coefficient (ICC). Safety of the device was evaluated by observing ocular adverse reactions of each subject prior to measurement, at day 1 and day 7 following measurement. Correlations between eyelid pressure and ocular surface parameters of moderate-to-severe DED were analyzed by using Pearson correlation coefficient and Kendall's tau-b correlation coefficient.ResultsICC of the measurement results in our study was 0.86. There was no abnormality presenting in all subjects recorded prior to measurement, 1 and 7 days following measurement. The eyelid pressure was significantly correlated with PBR (r = 0.286, P = 0.016), FBUT (r = −0.331, P = 0.005), CFS (r = 0.528, P = 0.000), lid margin abnormality (r = 0.408, P = 0.011) and MGd (r = 0.226, P = 0.016) in moderate-to-severe DED patients, but not significantly correlated with OSDI score (r = 0.016, P = 0.912), TMH (r = −0.002, P = 0.988), meibum score (r = −0.196, P = 0.317), LLT (r = 0.114, P = 0.346), PB (r = 0.116, P = 0.338), TB (r = 0.074, P = 0.544), meibum score (r = −0.196, P = 0.317) and Schirmer I test (r = 0.028, P = 0.821).ConclusionThe novel pressure measurement device exhibited good repeatability and safety in measuring eyelid pressure. Significant correlations were noted between the eyelid pressure and PBR, FBUT, CFS, lid margin abnormality and MGd in moderate-to-severe DED. The measurement of eyelid pressure combined with ocular surface parameters may be valuable for the assessment of DED.
Prior Local or Systemic Treatment: A Predictive Model Could Guide Clinical Decision-Making for Locoregional Recurrent Breast Cancer
Authors: Wu Huai-liang , Lu Yu-jie , Li Jian-wei , Wu Si-yu , Chen Xiao-song , Liu Guang-yu 
Published: February 2022

IntroductionLocoregional recurrent breast cancer indicates poor prognosis. No solid prediction model is available to predict prognosis and guide clinical management. Prior local treatment or systemic treatment remains controversial.MethodsLocoregional recurrent breast cancer patients operated in Fudan University Shanghai Cancer Center were enrolled as a training cohort. An external validation cohort included breast cancer patients after locoregional recurrence from Ruijin Hospital, Shanghai Jiaotong University. A nomogram predicting overall survival after locoregional recurrence was established using multivariable Cox regression analysis while internal and external validation were performed to evaluate its calibration and discrimination.ResultsOverall, 346 and 96 breast cancer patients were included in the training cohort and the validation cohort separately. A nomogram was developed, including age, neoadjuvant chemotherapy, breast surgery, pathology type, tumor size, lymph node status, hormonal receptor and Her-2 status, disease-free interval, and sites of locoregional recurrence. It had modest calibration and discrimination in the training cohort, internal validation and external validation (concordance index: 0.751, 0.734 and 0.722, respectively). The nomogram classified 266 and 80 patients into low and high-risk subgroups with distinctive prognosis. Local treatment after locoregional recurrence was associated with improved overall survival in low-risk group (P = 0.011), while systemic therapies correlated with better outcomes only in high-risk group (P &lt; 0.001).ConclusionA nomogram based on clinicopathological factors can predict prognosis and identify low and high-risk patients. Local treatment is a prior choice for low-risk patients whereas systemic treatment needs to be considered for high-risk patients, warranting further validation and exploration.