bluuebunny/crossref_metadata_2025 huggingface dataset:
Social Science Applications in Sustainable Aviation Biofuels Research: Opportunities, Challenges, and Advancements
Authors: Anderson Brian J. , Mueller Daniel W. , Hoard Season A. , Sanders Christina M. , Rijkhoff Sanne A. M.
Published: January 2022

Social science has an important role in aviation biofuels research, yet social science methods and approaches tend to be underdeveloped and under-utilized in the broader aviation biofuels literature and biofuels overall. Over the last 5 years, social science approaches in aviation biofuels research, particularly site-selection, have made several advances. Where early site-selection models either entirely excluded social science concepts or included only a few measurements using poor proxies, current models more accurately, and more comprehensively capture key social science concepts to better examine and predict project implementation success and long-term sustainability. Despite several studies published within the last 20 years noting the need for more empirical studies of social sustainability and improvement in incorporation of social criteria, progress has remained rather stagnant in several areas. To help move the field forward, we conduct a review of the current state of social science research in aviation biofuels with a focus on sustainability, site-selection, and public acceptance research, identifying key approaches, important developments, and research gaps and weaknesses of current approaches. While several review studies already exist, they tend to focus on a single area of biofuels such as public acceptance. By broadening our review to several areas, we are able to identify several common limitations across these areas that contribute to the continued underutilization of social science approaches in aviation biofuels. This includes the preference for practical and reliable indicators for social criteria that prioritize quantitative methods over other approaches. Based on these limitations, we make several recommendations to improve social science research in aviation biofuels, including ensuring that social scientists are key members of the research team, the adoption of a mixed-methods research designs that combines quantitative and qualitative approaches that better measure some criteria and local-level impacts, and adequate resources for social science research throughout biofuel development projects as these methods are often more time-consuming and costly to implement. We argue that implementing these recommendations in future aviation biofuel development projects will improve social science approaches utilized in aviation biofuels research and address a long-acknowledged gap in the field.
Reassessing the Effect of Low-Carbon City Policy in China: New Evidence From the Nighttime Light Data
Authors: Li Xing , Zhao Chunkai , Huang Mengqi
Published: January 2022

Excessive emissions of carbon dioxide and other greenhouse gases have seriously affected the ecological environment and the normal operation of the social economy, and low-carbon city policy (LCCP) is one of China’s main policies to achieve carbon emission reduction goals. This study focused on the 280 cities in China, and used the difference-in-differences (DID) model and nighttime light data to evaluate the impact and mechanisms of LCCP on carbon emissions from 2003 to 2016. The results show that: 1) The implementation of LCCP can reduce carbon emissions by 16.2%; 2) Mechanism analysis shows that LCCP can achieve carbon reduction through the guidance of government behaviors, improvements of industrial structure and innovation capabilities, reductions of energy consumption, and the optimization of the ecological environment; 3) Heterogeneity analysis shows that the effect of the LCCP in suppressing carbon emissions is more effective in eastern cities with better economic and industrial bases, and large cities with more population. Furthermore, the effect of LCCP shows an inverted U-shaped trend as carbon emissions increase. This study enriches the research on assessing policy effects of China’s low-carbon city construction, and provides some inspiration for the goal of carbon neutrality and other developing countries with high carbon emission.
Surface Evolver Simulation of Droplet Wetting Morphologies on Fiber Without Gravity
Authors: Xu Chengwei , Lu Zhenyan , Li Lirong
Published: January 2022

Droplet wetting phenomenon is encountered in many engineering applications. Three wetting morphologies, namely, barrel, clamshell, and liquid bridge, are investigated by the finite element method, Surface Evolver (SE) simulations. The barrel shape shrinks gradually as contact angle increases. In the shrinkage process, the dimensionless wetting length reduces, and maximum diameter increases. As the increase of the contact angle, the gas–liquid contact line of clamshell droplets bends and contracts inward gradually. The geometry parameters are extracted from the results from simulations. In addition, the critical spacing of liquid bridge rupture is determined. The critical spacing increases rapidly with the expanding of liquid bridge volume. The liquid bridge volume has a significant effect on critical spacing.
MPC with Space Vector Phase-Shift PWM (SV-PSPWM) Technique with Harmonic Mitigation Strategy for Shunt Active Power Filters Based on H-Bridge Multilevel Converter
Authors: Renault Alfredo , Pacher Julio , Comparatore Leonardo , Ayala Magno , Rodas Jorge , Gregor Raul
Published: January 2022

This article presents a model predictive current control of a shunt active power filter based on 7-level cascaded H-bridge converters. By using the spacial vector modulation approach into the model predictive control, a considerable reduction of the computational burden is achieved and makes possible the real-time implementation in a custom experimental setup. Then, the current harmonics on the grid side, caused by non-linear loads connected to the point of common coupling, are compensated. The experimental results confirmed the feasibility and efficacy of the proposed controller.
Removal of Mercury, Cadmium, and Lead Ions by Penicillium sp.
Authors: Sánchez-Castellón Juan , Urango-Cárdenas Iván , Enamorado-Montes Germán , Burgos-Nuñez Saudith , Marrugo-Negrete José , Díez Sergi
Published: January 2022

Discharge of metals into the environment generates significant impact upon human health and biological cycles. Some microorganisms such as fungi are known for their high metal adsorption capacity. The aim of this work was to evaluate the capacity for Penicillium sp. molds in the removal of Pb, Cd, and Hg from aqueous solutions by isolating the fungal strain from an artisanal gold mine soil. The biosorption experiments showed that optimum conditions for metal removal were noted at 150 min, acidic pH (4–5), 60 °C, and 2 g of biomass. The accomplished removal was 92.4% for Pb, 80% for Cd, and 99.6% for Hg, at a concentration of 51.5 mg/L. Kinetic analyses and isotherms best fit the pseudo–second-order and Langmüir models, respectively. Infrared spectra show functional groups (–OH, –NH, C-N, C-H, N-H, and C=O) that play an essential role in the adsorption of Pb, Hg, and Cd on fungal biomass.
Macro- and Microhabitat Predictors of Nest Success and Hatchling Survival in Eastern Box Turtles (Terrapene carolina carolina) and Spotted Turtles (Clemmys guttata) in Oak Savanna Landscapes
Authors: Refsnider Jeanine M. , Carter Sarah E. , Diaz Alexis , Hulbert Austin C. , Kramer Gunnar R. , Madden Paige , Streby Henry M.
Published: January 2022

Differing selection pressures on stationary nest contents compared to mobile offspring mean that the nest-site characteristics resulting in the highest nest success may not be the same characteristics that result in the highest survival of juveniles from those nests. In such cases, maternal nest-site choice may optimize productivity overall by selecting nest sites that balance opposing pressures on nest success and juvenile survival, rather than maximizing survival of either the egg or the juvenile stage. Determining which macro- and microhabitat characteristics best predict overall productivity is critical for ensuring that land management activities increase overall recruitment into a population of interest, rather than benefiting one life stage at the inadvertent expense of another. We characterized nest-site choice at the macro- and microhabitat scale, and then quantified nest success and juvenile survival to overwintering in two declining turtle species, eastern box turtles and spotted turtles, that co-occur in oak savanna landscapes of northwestern Ohio and southern Michigan. Nest success in box turtles was higher in nests farther from macrohabitat edges, constructed later in the year, and at greater total depths. In contrast, survival of juvenile box turtles to overwintering was greater from nests under less shade cover and at shallower total depths. Spotted turtle nest success and juvenile survival were so high that we were unable to detect relationships between nest-site characteristics and the small amount of variation in survival. Our results demonstrate, at least for eastern box turtles, a tradeoff in nest depth between favoring nest success vs. juvenile survival to overwintering. We suggest that heterogeneity in microhabitat structure within nesting areas is important for allowing female turtles to both exercise flexibility in nest-site choice to match nest-site characteristics to prevailing weather conditions, and to place nests in close proximity to habitat that will subsequently be used by hatchlings for overwintering.
Ocean Warming Leads to Increases in Aerobic Demand and Changes to Gene Expression in the Pinfish (Lagodon rhomboides)
Authors: Eaton Katherine M. , Hallaj Adam , Stoeckel James A. , Bernal Moisés A.
Published: January 2022

Anthropogenic climate change is causing increases in the frequency, intensity, and duration of marine heatwaves (MHWs). These short-term warming events can last for days to weeks and can produce severe disruptions in marine ecosystems, as many aquatic species are poikilotherms that depend on the conditions of the environment for physiological processes. It is crucial to investigate the effects of these thermal fluctuations on species that play a disproportionate ecological role in marine ecosystems, such as the pinfish (Lagodon rhomboides) in the Gulf of Mexico and western Atlantic. In this study, we exposed pinfish to a simulated MHW in aquaria and examined the impacts of acute warming on two life stages (juvenile and adult), measuring oxygen consumption and gene expression in two relevant tissue types (liver and muscle). We saw significant increases in routine metabolic rate with increasing temperature in both juveniles (24.58 mgO2/kg/h increase per 1°C of warming) and adults (10.01 mgO2/kg/h increase per 1°C of warming). These results indicate that exposure to increased temperatures was more metabolically costly for juveniles than for adults, on a mass-specific basis. This was also observed in the molecular analyses, where the largest number of differentially expressed genes were observed in the juvenile pinfish. The analyses of gene expression suggest warming produces changes to immune function, cell proliferation, muscle contraction, nervous system function, and oxygen transport. These results indicate that this ecologically relevant species will be significantly impacted by projected increases in frequency and magnitude of MHWs, particularly in the juvenile stage.
Size of Snake Eyes Correlates With Habitat Types and Diel Activity Patterns
Authors: Huang Mason Chen-Wei , Liao Chen-Pan , Chou Chun-Chia , Lin Jhan-Wei , Huang Wen-San
Published: January 2022

Eye size influences visual acuity, sensitivity, and temporal resolution and is a result of vertebrate adaptation to the environment. The habitats of snake species are diverse, ranging from fossorial, terrestrial, arboreal, to aquatic. They also demonstrate a variety of behavioral and physiological characteristics, such as activity time, feeding patterns, and prey detection. In this study, we comparatively investigated how the relative eye size (i.e., eye diameter vs. head width) associated with the ecological (i.e., habitat), behavioral (i.e., diel activity pattern, foraging strategy), and physiological traits (i.e., the presence of pits), respectively, across six snake families from Taiwan. Among the traits we examined, we found that terrestrial and/or diurnal snakes tended to exhibit the larger relative eye size, indicating the evolutionary responses of eye size to changes in habitat types and activity patterns, respectively, while no evidence of how foraging strategies and the presence of pits affected snake eye size was found. Our findings not only shed light on the adaptive significance of the visual system in diversifying the behaviors and the environments exploited in snakes, but also underline the interactive effects of multidimensional evolutionary attributes (e.g., behavior, ecology, physiology and phylogeny) on the evolution of optimal visual performance.
Development of a Sensitive and Specific Novel qPCR Assay for Simultaneous Detection and Differentiation of Mucormycosis and Aspergillosis by Melting Curve Analysis
Authors: Pandey Mragnayani , Xess Immaculata , Sachdev Janya , Yadav Usha , Singh Gagandeep , Pradhan Dibyabhaba , Xess Ashit Bhushan , Rana Bhaskar , Dar Lalit , Bakhshi Sameer , Seth Rachna , Mahapatra Manoranjan , Jyotsna Viveka P. , Jain Arun Kumar , Kumar Rakesh , Agarwal Reshu , Mani Prashant
Published: January 2022

Molecular diagnostic assays can expedite the diagnosis of fungal infections, and subsequently help in early interventions and appropriate management of patients. The aim of this study was to develop a single set of primers for a real-time quantitative polymerase chain reaction (qPCR) assay to detect and identify commonly reported, clinically relevant molds i.e., Aspergillus spp, Mucorales and Fusarium spp., up to genus level by melting curve analysis. This assay was evaluated in whole blood from patients with suspected invasive aspergillosis (IA), and in tissue biopsy, bronchoalveolar lavage (BAL) fluid and other site-specific samples from patients with suspected invasive mucormycosis (IM). The limit of detection (LoD) was determined as 10 copies/μl for all three molds. The mean coefficient of variation (CV) across all sets of intra- and inter-assay data was 0.63% (ranging from 0.42 to 1.56%), showing high reproducibility of the assay. Sensitivity and specificity of the assay were 93.3 and 97.1% respectively for diagnosis of IA, and 99.29 and 83.84% respectively for diagnosis of IM. Fusarium was not detected in any of the clinical samples included and the few laboratory confirmed cases of fusariosis did not meet the inclusion criteria of the study. Hence no ROC curve or cutoff value could be generated for the same. This newly developed qPCR assay therefore appears to be a promising tool in detection of IA and IM.
LncRNA VPS9D1-AS1 Promotes Malignant Progression of Lung Adenocarcinoma by Targeting miRNA-30a-5p/KIF11 Axis
Authors: Liu Jiefeng , Feng Yuhua , Zeng Xinyu , He Miao , Gong Yujing , Liu Yiping
Published: January 2022

Objective: This research probed into the molecular mechanisms of long non-coding RNA (lncRNA) VPS9D1 Antisense RNA 1 (VPS9D1-AS1) in lung adenocarcinoma (LUAD).

Methods: lncRNA expression level was evaluated bioinformatically, and its downstream miRNA/mRNA regulatory axis was predicted by bioinformatics methods as well. qRT-PCR was used to measure VPS9D1-AS1, miRNA-30a-5p, and kinesin family member 11 (KIF11) expression. Western blot was performed to measure KIF11 protein expression. Proliferation, migration, and invasion of LUAD cells were all observed by cell biological function experiments. Dual-luciferase assay detected binding between miRNA-30a-5p and VPS9D1-AS1 or KIF11, respectively. RIP experiment detected interaction between VPS9D1-AS1 and miRNA-30a-5p.

Results: VPS9D1-AS1 and KIF11 were increased in LUAD, whereas miRNA-30a-5p was decreased. VPS9D1-AS1 promoted the malignant progression of LUAD cells and could sponge miRNA-30a-5p. MiRNA-30a-5p could restore the impact of VPS9D1-AS1 on LUAD cells. KIF11 was a target downstream of miRNA-30a-5p. VPS9D1-AS1 could upregulate KIF11 expression through competitively sponging miRNA-30a-5p, and KIF11 could restore the impact of miRNA-30a-5p on LUAD cells.

Conclusion: VPS9D1-AS1 could foster malignant progression of LUAD via regulating miRNA-30a-5p/KIF11 axis, suggesting that VPS9D1-AS1 is key to regulating the malignant progression of LUAD.
Gene Spectrum and Clinical Traits of Nine Patients With Oocyte Maturation Arrest
Authors: Huo Mingzhu , Zhang Yile , Shi Senlin , Shi Hao , Liu Yidong , Zhang Lingyun , Wang Yanchi , Niu Wenbin
Published: January 2022

Background: Oocyte maturation arrest is a disease that produces immature oocytes and cannot be mature after culturing in vitro, which leads to female primary infertility. We aimed to summarize nine representative patients in our center to retrospectively analyze the genetic variants and clinical characteristics of oocyte maturation arrest.

Methods: This study examined and analyzed nine families with oocyte maturation arrest. Whole-exome sequencing (WES) of the probands was performed to detect the pathogenic variants. Sanger sequencing verified the WES findings in patients and available parents. ExAC database was used to search the variant frequency. The variants were assessed by pathogenicity and conservational property prediction analysis and according to the American College of Medical Genetics and Genomics (ACMG). Phenotypes of oocytes were evaluated by a light microscopy, and the phenotype-genotype correlation was also evaluated.

Results: Nine pathogenic variants in five genes were detected in nine patients, of which three were novel variants, including PATL2 [c.1374A > G (p. Ile458Met)] and [1289-1291del TCC (p. Leu430del)] and ZP2 [c.1543C > T (p. Pro515Ser)]. Nine variants were predicted to be pathogenic, resulting in different types of oocyte maturation arrest and clinical phenotypes.

Conclusion: Three novel pathogenic variants were identified, enabling the expansion of the gene variant spectrum. The related pathogenic mutations of the PATL2, TUBB8, and ZP1∼3 genes were highly suggestive of being causative of oocyte maturation arrest.
Solitary Median Maxillary Central Incisor Syndrome: An Exploration of the Pathogenic Mechanism
Authors: Li Jie , Liu Dandan , Liu Yang , Zhang Chenying , Zheng Shuguo
Published: January 2022

This study aimed to identify the genetic cause of one Chinese family with solitary median maxillary central incisor (SMMCI) and explore the relationship between genotype and its phenotype. One Chinese family with clinical diagnosis of SMMCI was collected. Single Nucleotide Polymorphism (SNP) array was performed and identified variation was confirmed by whole-genome sequencing (WGS). The reported chromosomal abnormalities and pathogenic genes in patients with SMMCI in literature were reviewed and summarized. The proband was an 8-year-old boy presenting a typical solitary median maxillary central incisor with a range of other phenotypic anomalies, including ptosis. SNP array revealed a 14.3 Mbp heterozygous deletion at chromosome 18p11.32-p11.21 in the proband but not in the unaffected parents. WGS further confirmed the identified deletion. 194 genes were involved in the chromosome region. Among them, 12 genes had been shown to be associated with diseases, including TGIF1, a reported SMMCI gene. The de novo 18p deletion resulted in SMMCI in the present study. Our results provide new genetic evidence that structural abnormality in chromosome 18p contributes to solitary median maxillary central incisor.
Development and Validation of a Pyroptosis-Related Signature for Predicting Prognosis in Hepatocellular Carcinoma
Authors: Ding Jianfeng , He Xiaobo , Luo Wei , Zhou Weiguo , Chen Rui , Cao Guodong , Chen Bo , Xiong Maoming
Published: January 2022

Hepatocellular carcinoma (HCC) has emerged as a primary health problem and threat to global mortality, especially in China. Since pyroptosis as a new field for HCC prognosis is not well studied, it is important to open a specific prognostic model. In this study, consensus clustering method for 42 pyroptosis-related genes to classify 374 HCC patients in the TCGA database. After cox regression analysis of the differentially expressed genes between the two clusters, LASSO-Cox analysis was then performed to construct a pyroptosis-related prognostic model with 11 genes including MMP1, KPNA2, LPCAT1, NEIL3, CDCA8, SLC2A1, PSRC1, CBX2, HAVCR1, G6PD, MEX3A. The ICGC dataset was served as the validation cohort. Patients in the high-risk group had significantly lower overall survival (OS) rates than those in the low-risk group (p < 0.05). COX regression analysis showed that our model could be used as an independent prognostic factor to predict prognosis of patients and was significantly correlated with clinicopathological characteristics. Nomogram showing the stability of the model predicting the 1, 3, 5 year survival probability of patients. In addition, based on the risk model, ssGSEA analysis revealed significant differences in the level of immune cell infiltration and activation of immune-related functional pathways between high and low-risk groups, and patients with the high-risk score may benefit more from treatment with immune checkpoint inhibitors. Furthermore, patients in the high-risk group were more tend to develop chemoresistance. Overall, we identified a novel pyroptosis-related risk signature for prognosis prediction in HCC patients and revealed the overall immune response intensity of the tumor microenvironment. All these findings make the pyroptosis signature shed light upon a latent therapeutic strategy aimed at the treatment and prevention of cancers.
Case Report: Mutation in AIMP2/P38, the Scaffold for the Multi-Trna Synthetase Complex, and Association With Progressive Neurodevelopmental Disorders
Authors: Mazaheri Mahta , Yavari Mahdie , Zare Marzouni Hadi , Stufano Angela , Lovreglio Piero , D'Amore Simona , Jahantigh Hamid Reza
Published: January 2022

Background: Leukodystrophies constitute a heterogeneous group of inherited disorders primarily affecting the white matter of the central nervous system. Aminoacyl-tRNA synthetases (ARSs) catalyze the attachment of an amino acids to their cognate transfer RNAs (tRNAs). Pathogenic variants in both cytosolic and mitochondrial ARSs have been linked to a broad range of neurological disorders, including hypomyelinating leukodystrophies and pontocerebellar hypoplasias (PCH). Aminoacyl tRNA synthetase-interacting multifunctional protein 2 (AIMP2), one of the three non-catalytic components of multi ARS complex, harbors anti-proliferative activity and functions as a proapoptotic factor thus promoting cell death. We report a case of a 7-month-old infant with a complex clinical presentation, including weight loss, severe anemia, skeletal abnormalities, microcephaly and MR imaging features of leukodystrophy with a novel mutation in AIMP2.

Methods: Whole-exome sequencing (WES) was performed on the proband. Parental samples were analyzed by PCR amplification and Sanger sequencing.

Results: Whole-exome sequencing revealed a novel variant c.A463T in the homozygous state in exon 3 (NM_001,326,607) of AIMP2 [p.(K155X)] in the proband. Parental carrier status was confirmed by target sequencing.

Conclusion: Here, we present an Iranian case with leukodystrophy with a novel AIMP2 mutation. This finding broadens the mutational and phenotypic spectra of AIMP2-related leukodystrophy and offers guidance for proper genetic counselling for pre- and post-natal screenings as well as for disease management.
Causal Relationship Between Gut Microbiota and Autoimmune Diseases: A Two-Sample Mendelian Randomization Study
Authors: Xu Qian , Ni Jing-Jing , Han Bai-Xue , Yan Shan-Shan , Wei Xin-Tong , Feng Gui-Juan , Zhang Hong , Zhang Lei , Li Bin , Pei Yu-Fang
Published: January 2022

Background

Growing evidence has shown that alterations in gut microbiota composition are associated with multiple autoimmune diseases (ADs). However, it is unclear whether these associations reflect a causal relationship.

Objective

To reveal the causal association between gut microbiota and AD, we conducted a two-sample Mendelian randomization (MR) analysis.

Materials and Methods

We assessed genome-wide association study (GWAS) summary statistics for gut microbiota and six common ADs, namely, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, type 1 diabetes (T1D), and celiac disease (CeD), from published GWASs. Two-sample MR analyses were first performed to identify causal bacterial taxa for ADs in discovery samples. Significant bacterial taxa were further replicated in independent replication outcome samples. A series of sensitivity analyses was performed to validate the robustness of the results. Finally, a reverse MR analysis was performed to evaluate the possibility of reverse causation.

Results

Combining the results from the discovery and replication stages, we identified one causal bacterial genus, Bifidobacterium. A higher relative abundance of the Bifidobacterium genus was associated with a higher risk of T1D [odds ratio (OR): 1.605; 95% CI, 1.339–1.922; PFDR = 4.19 × 10−7] and CeD (OR: 1.401; 95% CI, 1.139–1.722; PFDR = 2.03 × 10−3), respectively. Further sensitivity analyses validated the robustness of the above associations. The results of reverse MR analysis showed no evidence of reverse causality from T1D and CeD to the Bifidobacterium genus.

Conclusion

This study implied a causal relationship between the Bifidobacterium genus and T1D and CeD, thus providing novel insights into the gut microbiota-mediated development mechanism of ADs.
Comprehensive Landscape of Immune Infiltration and Aberrant Pathway Activation in Ischemic Stroke
Authors: Liu Rongrong , Song Pingping , Gu Xunhu , Liang Weidong , Sun Wei , Hua Qian , Zhang Yusheng , Qiu Zhengang
Published: January 2022

Ischemic stroke (IS) is a multifactorial disease caused by the interaction of multiple environmental and genetic risk factors, and it is the most common cause of disability. The immune microenvironment and inflammatory response participate in the whole process of IS occurrence and development. Therefore, the rational use of relevant markers or characteristic pathways in the immune microenvironment will become one of the important therapeutic strategies for the treatment of IS. We collected peripheral blood samples from 10 patients diagnosed with IS at the First Affiliated Hospital of Gannan Medical University and First Affiliated Hospital, Jinan" University, and from 10 normal people. The GSE16561 dataset was downloaded from the Gene Expression Omnibus (GEO) database. xCell, gene set enrichment analysis (GSEA), single-sample GSEA (ssGSEA) and immune-related gene analysis were used to evaluate the differences in the immune microenvironment and characteristic pathways between the IS and control groups of the two datasets. xCell analysis showed that the IS-24h group had significantly reduced central memory CD8+ T cell, effector memory CD8+ T cell, B cell and Th1 cell scores and significantly increased M1 macrophage and macrophage scores. GSEA showed that the IS-24h group had significantly increased inflammation-related pathway activity(myeloid leukocyte activation, positive regulation of tumor necrosis factor biosynthetic process, myeloid leukocyte migration and leukocyte chemotaxis), platelet-related pathway activity(platelet activation, signaling and aggregation; protein polymerization; platelet degranulation; cell-cell contact zone) and pathology-related pathway activity (ERBB signaling pathway, positive regulation of ERK1 and ERK2 cascade, vascular endothelial growth factor receptor signaling pathway, and regulation of MAP kinase activity). Immune-related signature analysis showed that the macrophage signature, antigen presentation-related signature, cytotoxicity-related signature, B cell-related signature and inflammation-related signature were significantly lower in the IS-24h group than in the control group. In this study, we found that there were significant differences in the immune microenvironment between the peripheral blood of IS patients and control patients, as shown by the IS group having significantly reduced CD8+ Tcm, CD8+ Tem, B cell and Th1 cell scores and significantly increased macrophage and M1 macrophage scores. Additionally, inflammation-related, pathological, and platelet-related pathway activities were significantly higher in the IS group than in the control group.
Expression Profiles and Prognostic Value of Multiple Inhibitory Checkpoints in Head and Neck Lymphoepithelioma-Like Carcinoma
Authors: Zou Wen-Qing , Luo Wei-Jie , Feng Yan-Fen , Liu Fang , Liang Shao-Bo , Fang Xue-Liang , Liang Ye-Lin , Liu Na , Wang Ya-Qin , Mao Yan-Ping
Published: January 2022

Background

Inhibitory checkpoints are promising antitumor targets and predictive biomarkers in a variety of cancers. We aimed to identify the expression levels and prognostic value of multiple inhibitory checkpoints supported by preclinical and clinical evidence in head and neck lymphoepithelioma-like carcinoma (HNLELC).

Methods

The expression of seven inhibitory checkpoints were evaluated in the tumor nest (TN) and tumor stroma (TS) of 102 HNLELC specimens using immunohistochemistry and digital pathology, and an inhibitory checkpoint-based signature (ICS) was subsequently constructed using the LASSO Cox regression model.

Results

PD-L1, B7H3, and IDO-1 were mostly expressed in the TN, with median H-score of TN vs TS: 63.6 vs 14.6; 8.1 vs 1.0; 61.5 vs 34.7 (all P < 0.001), whereas PD-1, TIM-3, LAG-3, and VISTA were mainly observed in the TS, with median H-score of TN vs TS: 0.2 vs 12.4, 3.4 vs 7.1, 6.2 vs 11.9, 16.4 vs 47.2 (all P < 0.001), respectively. The most common simultaneously expressed combinations consisted of PD-L1 + B7H3 + IDO-1 + TIM-3 + LAG-3 + VISTA and B7H3 + IDO-1 + TIM-3 + LAG-3 in the TN (both occurring in 8.8% of patients) and PD-L1 + B7H3 + IDO-1 in the TS (4.9%). In addition, high-ICS patients had shorter 5-year disease-free (40.6% vs 81.7%; P < 0.001), regional recurrence-free (63.5% vs 88.2%; P = 0.003), and overall survival (73.5% vs 92.9%; P = 0.006) than low-ICS patients. Multivariate analysis revealed that ICS represented an independent predictor, which could significantly complement the predictive performance of TNM stage for 3-year (AUC 0.724 vs 0.619, P = 0.014), 5-year (AUC 0.727 vs 0.640, P = 0.056), and 10-year disease-free survival (AUC 0.815 vs 0.709, P = 0.023).

Conclusions

The expression of inhibitory checkpoints and ICS classifier may increase the prognostic value of the TNM staging system and guide the rational design of personalized inhibitory checkpoint blockade therapy in HNLELC.
Uric Acid and Impairment of Renal Function in Non-diabetic Hypertensive Patients
Authors: Hung Yi-Hsin , Huang Chin-Chou , Lin Liang-Yu , Chen Jaw-Wen
Published: January 2022

Hyperuricemia is a risk factor for renal impairment. However, investigations focusing on patients with hypertension are limited and inconsistent. A single-center prospective cohort study of 411 Han Chinese non-diabetic hypertensive patients was conducted in Taiwan. The mean age of the participants was 62.0 ±14.4 years. The baseline estimated glomerular filtration rate and uric acid level were 86 mL/min/1.73 m2 and 6.2 mg/dL, respectively. All patients underwent serum biochemistry tests for creatinine levels every 3 months. Renal events were defined as >25% and >50% decline in estimated glomerular filtration rate. During an average follow-up period of 4.7 ± 2.9 years (median 4.0 years), a >25 and >50% decline in estimated glomerular filtration rate was noted in 52 and 11 patients, respectively. The multivariate Cox regression analysis revealed that a baseline uric acid level ≥8.0 mg/dL increased the risk of >25% decline (hazard ratio: 3.541; 95% confidence interval: 1.655–7.574, P = 0.001) and >50% decline (hazard ratio: 6.995; 95% confidence interval: 1.309–37.385, P = 0.023) in estimated glomerular filtration rate. Similarly, a baseline uric acid level ≥7.5 mg/dL was independently associated with >25% decline (hazard ratio: 2.789; 95% confidence interval: 1.399–5.560, P = 0.004) and >50% decline (hazard ratio: 6.653; 95% confidence interval: 1.395–31.737, P = 0.017). However, this was not demonstrated at baseline uric acid level ≥7.0 mg/dL. Our study suggests that hyperuricemia is an independent risk factor for the decline in renal function in patients with hypertension. Uric acid level ≥7.5 mg/dL may be considered as the optimal cutoff value for clinical practice in predicting the development of renal impairment.
Establishment and Verification of Neural Network for Rapid and Accurate Cytological Examination of Four Types of Cerebrospinal Fluid Cells
Authors: Jiang Luyue , Niu Gang , Liu Yangyang , Yu Wenjin , Wu Heping , Xie Zhen , Ren Matthew Xinhu , Quan Yi , Jiang Zhuangde , Zhao Gang , Ren Wei
Published: January 2022

Fast and accurate cerebrospinal fluid cytology is the key to the diagnosis of many central nervous system diseases. However, in actual clinical work, cytological counting and classification of cerebrospinal fluid are often time-consuming and prone to human error. In this report, we have developed a deep neural network (DNN) for cell counting and classification of cerebrospinal fluid cytology. The May-Grünwald-Giemsa (MGG) stained image is annotated and input into the DNN network. The main cell types include lymphocytes, monocytes, neutrophils, and red blood cells. In clinical practice, the use of DNN is compared with the results of expert examinations in the professional cerebrospinal fluid room of a First-line 3A Hospital. The results show that the report produced by the DNN network is more accurate, with an accuracy of 95% and a reduction in turnaround time by 86%. This study shows the feasibility of applying DNN to clinical cerebrospinal fluid cytology.
Systematically Displaying the Pathogenesis of Keratoconus via Multi-Level Related Gene Enrichment-Based Review
Authors: Hao Xiao-Dan , Gao Hua , Xu Wen-Hua , Shan Chan , Liu Ying , Zhou Zhi-Xia , Wang Kun , Li Pei-Feng
Published: January 2022

Keratoconus (KC) is an etiologically heterogeneous corneal ectatic disorder. To systematically display the pathogenesis of keratoconus (KC), this study reviewed all the reported genes involved in KC, and performed an enrichment analysis of genes identified at the genome, transcription, and protein levels respectively. Combined analysis of multi-level results revealed their shared genes, gene ontology (GO), and pathway terms, to explore the possible pathogenesis of KC. After an initial search, 80 candidate genes, 2,933 transcriptional differential genes, and 947 differential proteins were collected. The candidate genes were significantly enriched in extracellular matrix (ECM) related terms, Wnt signaling pathway and cytokine activities. The enriched GO/pathway terms of transcription and protein levels highlight the importance of ECM, cell adhesion, and inflammatory once again. Combined analysis of multi-levels identified 13 genes, 43 GOs, and 12 pathways. The pathogenic relationships among these overlapping factors maybe as follows. The gene mutations/variants caused insufficient protein dosage or abnormal function, together with environmental stimulation, leading to the related functions and pathways changes in the corneal cells. These included response to the glucocorticoid and reactive oxygen species; regulation of various signaling (P13K-AKT, MAPK and NF-kappaB), apoptosis and aging; upregulation of cytokines and collagen-related enzymes; and downregulation of collagen and other ECM-related proteins. These undoubtedly lead to a reduction of extracellular components and induction of cell apoptosis, resulting in the loosening and thinning of corneal tissue structure. This study, in addition to providing information about the genes involved, also provides an integrated insight into the gene-based etiology and pathogenesis of KC.
Shionone Attenuates Sepsis-Induced Acute Kidney Injury by Regulating Macrophage Polarization via the ECM1/STAT5 Pathway
Authors: Zhang Biao , Xue Yi , Zhao Jin , Jiang Huojun , Zhu Jiaoli , Yin Hao , Qiu Yizhen , Hu Aihao , Xu Lingqi , Song Yi , Wang Xin
Published: January 2022

Backgrounds

To date, there are no specific drugs approved for the treatment of sepsis associated acute kidney injury (AKI). Shionone is a natural component with anti-inflammatory activity. In this study, we sought to determine the functional role of Shionone in sepsis-induced AKI.

Methods

Animal models of AKI were constructed by cecum ligation and puncture (CLP) surgery. C57BL/6 mice were randomly assigned to the Sham, CLP, 10 mg/kg DXM, 50 mg/kg Shionone and 100 mg/kg Shionone groups. RAW264.7 treated with lipopolysaccharides (LPS) was used as anin vitrosepsis model and cells were divided into control, LPS, 1 μg/mL Shionone and 2 μg/mL Shionone groups. The pathological status was assessed by Hematoxylin-Eosin (HE) staining assay, protein expressions were detected by immunofluorescence staining and Western blot, macrophage typing was detected by flow, and the levels of pro-inflammatory factors (IL-6, IL-12, IL-1β, TNF-α) and anti-inflammatory factors (IL-10 and TGF-β) were measured using the corresponding kits.

Results

ECM1 is highly expressed in tissue-infiltrating macrophages under inflammatory conditions. It has been observed that Shionone inhibits the expression of ECM1 and attenuates sepsis-induced injury in kidney and inflammatory factor levels in serum. In addition, Shionone may reduce inflammatory factor levels through the promotion of M2 macrophages by GM-CSF/STAT5/Arg1 pathway to alleviate sepsis induced inflammationin vitro.

Conclusion

These findings demonstrate that Shionone can alleviate sepsis-induced AKI by promoting M2 macrophage polarization through regulating the ECM1/STAT5 pathway.
Different Types of Hyperfluorescence Observed in Post Anti-VEGF Fluorescein Angiographic Patterns in Retinopathy of Prematurity Patients
Authors: Jin Enzhong , Yin Hong , Liu Kailin , Liang Zhiqiao , Zhao Mingwei
Published: January 2022

Purpose

To demonstrate that the demographic and treatment characteristics of retinopathy of prematurity (ROP) eyes showed different types of hyperfluorescence in fluorescein angiography (FA) initially treated with anti-vascular endothelial growth factor (VEGF) agents.

Methods

A consecutive case series of ROP treated with anti-VEGF agents was retrospectively studied. All the patients underwent FA examinations at least 6 months later after treatment. The demographic and treatment characteristics of eyes with or without hyperfluorescence in FA were analyzed. The different types of hyperfluorescence were divided into three groups, including vascular leakage, fibrous membrane, and vascular abnormality.

Results

Two hundred and forty-two eyes of 123 patients with treatment-required ROP were included. Hyperfluorescence was defined in 51/242 eyes, and 2.08 ± 1.11 injections were performed for them, while the eyes without hyperfluorescence received 1.65 ± 0.80 injections (P = 0.013). Vascular leakage was defined in 26/51 hyperfluorescence eyes. The postmenstrual age (PMA) of first injection for the hyperfluorescence group was 38.56 ± 3.24 weeks, which is earlier than that of infants without hyperfluorescence (P = 0.011). More additional treatments were performed in eyes with hyperfluorescence (23.53 vs. 3.66%, P = 0.000). Among them, the eyes with vascular leakage required more additional treatment than eyes without vascular leakage (42.31 vs. 4.00%, P = 0.004). For the 26 eyes with vascular leakage, 11 eyes of 8 patients received further treatments during further follow-up. No significant difference of refractive errors can be defined between different groups.

Conclusion

Eyes with persistent hyperfluorescencein FA after treatment required more anti-VEGF and additional treatments, including laser and PPV. Not all hyperfluorescences were vascular leakage and required additional treatment.
Association of Novel Androgen Receptor Axis-Targeted Therapies With Diarrhea in Patients With Prostate Cancer: A Bayesian Network Analysis
Authors: Xiong Xingyu , Xu Hang , Wang Sheng , Liao Xinyang , Yi Xianyanling , Jin Kun , Lei Haoran , Bai Shengjiang , Qiu Shi , Yang Lu
Published: January 2022

Objective

To perform a systematic review and network meta-analysis to characterize the effect of novel androgen receptor axis-target (ARAT) agents on diarrhea and constipation.

Methods

We searched the Pubmed, Web of Science, and ClinicalTrials.gov up to September 2021 for phase 3 randomized controlled trials (RCTs) of patients receiving novel ARAT agents for prostate cancer (CaP). A Cochrane risk-of-bias tool was used to assess trial quality. The primary outcomes were risk ratio (RR) of any-grade diarrhea and constipation for patients receiving ARAT treatment. RRs of competing treatments were evaluated by pairwise and Bayesian network meta-analysis.

Results

In this study, 13 trials with 15,117 participants comparing 5 treatments (abiraterone, enzalutamide, apalutamide, darolutamide, and placebo) were identified. Use of novel ARAT agents was associated with a significant increased risk of any-grade diarrhea (RR = 1.30, 95% CI [1.16, 1.44]). As for subgroup analysis, abiraterone, enzalutamide, and apalutamide were all associated with significant increased risk of any-grade diarrhea (abiraterone: RR = 1.40, 95% CI [1.09, 1.81]; enzalutamide: RR = 1.17, 95% CI [1.02, 1.35]; apalutamide: RR = 1.35, 95% CI [1.03, 1.76]). Based on Bayesian modeling, abiraterone and enzalutamide showed the highest and lowest probability to rank first in terms of increasing risk of any-grade diarrhea. There were no significant differences of risk in any-grade constipation, grade 3 or greater diarrhea, and constipation between ARAT and control group.

Conclusion

The present study indicates that the use of novel ARAT agents is associated with a significantly higher risk of diarrhea. Across the four agents, abiraterone may relate to the highest risk of diarrhea among patients with metastatic hormone sensitive prostate cancer (mHSPC) and castration-resistant prostate cancer (CRPC).
Spontaneous Intramuscular Hemorrhage in Anti-MDA5 Positive Dermatomyositis: A Case Series and Literature Review
Authors: Xu Zhangling , Lv Xia , Xu Wenwen , Ye Yan , Wang Xiaodong , Ye Shuang , Ding Huihua , Wu Wanlong
Published: January 2022

Objective

Spontaneous intramuscular hemorrhage (SIH) is a rare but life-threatening complication associated with dermatomyositis (DM). This study reported a case series of SIH associated with DM. In addition, the characteristics and prognostic effects for this complication were analyzed based on literature review.

Methods

We reported seven cases of anti-melanoma differentiation-associated gene five positive dermatomyositis (MDA5+DM) complicated by SIH in our single-center cohort, and a comprehensive literature review was performed. Clinical characteristics, treatment, and outcome data of all eligible reported cases were summarized. Potential prognostic effects were identified by comparisons between the deceased and survivors.

Results

Among cumulatively reported patients with DM patients and SIH, the overall mortality was 60.9% (14/23) (including our cases). Fourteen out of nineteen (73.7%) hemorrhagic events occurred within 6 months of disease onset. Anti-MDA5 antibody predominated in those myositis-specific antibodies available cases (8/10), although patients with positive anti-NXP2 and anti-Mi2 have also been documented. Iliopsoas (52.2%, 12/23) was the most frequently involved bleeding location. Bleeding in deep muscles was identified to be associated with poorer prognosis. The mortality of patients with DM and deep muscular hematoma (non-palpable) (80%, 12/15) was significantly higher than that of patients with only superficial muscular hematoma (palpable) (25%, 2/8) (p =0.023).

Conclusion

Spontaneous hematoma in non-palpable deep muscles probably leads to excess mortality in dermatomyositis, particularly for those with anti-MDA5 antibody, which often occurs within 6 months of disease onset. Clinicians should be vigilant to this rare but potentially fatal complication and carefully balance the risks and benefits of prophylactic anti-thrombotic treatment.
Grape Seed Proanthocyanidins Exert a Radioprotective Effect on the Testes and Intestines Through Antioxidant Effects and Inhibition of MAPK Signal Pathways
Authors: Shen Hui , Han Jun , Liu Chunlei , Cao Fei , Huang Yijuan
Published: January 2022

The testes and intestines are highly sensitive to ionizing radiation. Low-dose radiation can cause infertility and enteritis. However, there is a lack of safe and efficient radioprotective agents. This study aims to investigate the radioprotective effects of grape seed proanthocyanidins (GSPs) on testicular and intestinal damage induced by ionizing radiation. In vitro, GSPs reduced the apoptosis and proliferation inhibition of mouse testicular stromal cells TM3 and human small intestinal crypt epithelial cells HIEC induced by ionizing radiation, and alleviated DNA double-strand breaks. In vivo, GSPs ameliorated the pathological damage of the testes and intestines induced by ionizing radiation, and protected the endocrine function of the testes and the barrier function of the intestines. In addition, we preliminarily proved that the radioprotective effect of GSPs is related to its antioxidant effect and inhibition of MAPK signaling pathways. Our results indicate that GSPs are expected to be a safe and effective radioprotective drug.
A Novel Fibrinolytic Protein From Pheretima vulgaris: Purification, Identification, Antithrombotic Evaluation, and Mechanisms Investigation
Authors: Liu Hai , Yang Jianqiong , Li Yamei , Ma Yunnan , Wang Wenjie , Zhong Wanling , Li Pengyue , Du Shouying
Published: January 2022

Thrombotic diseases have been considered major causes of death around the world. Treatments with thrombolytic drugs, such as recombinant tissue-plasminogen activator, urokinase, and streptokinase, are reported to have a life-threatening bleeding tendency. On the contrary, lumbrokinase, identified from Lumbricus rubellus, is specific to fibrin and does not cause excessive bleeding. It possesses fibrinolytic activity and activation of plasminogen to dissolve fibrin. Hence, the purification of fibrinolytic protein monomer from earthworm and antithrombotic evaluation and investigation of mechanisms are needed. In this study, a novel fibrinolytic protein EPF3, with strong fibrinolytic activity, was purified from Pheretima vulgaris by ion exchange and size exclusion chromatography. SDS PAGE, bottom-up proteomics analysis, de novo sequencing, and circular dichroism (CD) analysis were carried out for identification and characterization of it. EPF3, with a molecular weight of 25136.24 Da, consisted of 241 amino acids and contained various forms of secondary structures, including α-helix (3.9%), β-sheet (42.8%), β-turn (21.2%), and random coil (32.1%). It was a trypsin-like serine protease and stable at pH 7.0 to 11.0 and below 40°C. EPF3 was confirmed to possess an antithrombotic effect by ex vivo clot lysis test and fibrinogen-thrombin time (Fib-TT) assay. The three-dimensional structure of EPF3 was predicted by SWISS-MODEL. Molecular docking analysis predicted that EPF3 could directly interact with antithrombotic target proteins (fibrin, fibrinogen, and plasminogen), which was further confirmed by further studies. The antithrombotic mechanism of EPF3 was clarified to be outstanding direct fibrinolysis, fibrinogenolytic activity, and certain activation of plasminogen. EPF3 possesses the potential to be developed into a promising antithrombotic agent.