bluuebunny/crossref_metadata_2025 huggingface dataset:
Contributions of Regional Transport Versus Local Emissions and Their Retention Effects During PM2.5 Pollution Under Various Stable Weather in Shanghai
Authors: He Baoshan , Yu Guangyuan , Zhang Xin , He Zhiyin , Wang Qian , Liu Qizhen , Mao Jingbo , Zhang Yan
Published: March 2022

Understanding the formation and development processes of air pollution events is key to improving urban air quality. In this study, the air pollution episodes in stable synoptic conditions were selected to analyze the multi-phase evolution processes of heavy air pollution in Shanghai, a coastal city. The observation data and the WRF-CMAQ model were used to diagnose and simulate the pollution characteristics of the heavy pollution episodes. The results showed that the transport and dilution characteristics of PM2.5 were different during autumn and winter in Shanghai as a receptor of pollution transport. The development of PM2.5 pollution events were divided into four stages: accumulation stage, stagnation stage, enhancement stage, and dilution stage. The accumulation stage was before stable weather, and provided the foundations for PM2.5 pollution. The stagnation stage was nighttime during stable weather, in which the low wind speed and temperature inversion weakened regional transport and the dilution of PM2.5, which was defined as “retention effect”. The “retention effect” played a dominant role during the stagnation stage, accounting for 71.2% and 41.2% of total PM2.5 in winter and autumn case, respectively. The enhancement stage followed the stagnation stage, in which the newly regional transport was occurred due to stronger wind speed, accounting for 86.3% and 46.2% in winter and autumn episodes, respectively. The dilution stage was after the whole stable weather, when meteorological conditions were beneficial for PM2.5 dilution. Local emissions were dominant (63.0%) for PM2.5 pollution in the autumn case but regional transport was dominant (81.3%) in the winter case. Therefore, preventing the heavy particulate pollution caused by the diverse stable weather calls for the suitable emission control in a regional scale. Our study also shows that the simulation accuracy during stable weather needs to be improved in future studies.
Are the Agro-Ecosystems Sustainable? Measurement and Evaluation: A Case Study of Sichuan Province, China
Authors: Dai Xiaowen , Chen Yi , Wu Xin , He Yanqiu , Wang Fang
Published: March 2022

In recent years, with the frequent occurrence of global climate problems, China has paid great attention to sustainable development and ecological environment governance. Sichuan Province is a significant grain production and a reserve base in western China, and its sustainable development in agriculture is an important foundation for the healthy development of the regional agricultural economy and food security. In this study, we divided the agricultural production land in Sichuan into cultivated land, water area, grassland, and forest land. We used the ecological footprint method to investigate the ecological footprint and the carrying capacity of agriculture in Sichuan comprehensively. We conclude that 1) generally, the overall agricultural ecosystem in Sichuan has been in a state of ecological surplus for the past 20 y, and the environmental pressure is gradually decreasing. However, the development within the ecosystem is uneven. 2) In terms of subdivision, the cultivated land, forest land, and water area in Sichuan have always been in a state of ecological surplus, but the grassland is in an ecological deficit state. In terms of the trend, the ecological status of cultivated land has declined significantly, while the forest land has gradually improved, and the water area is relatively stable. Yet, the deficit of grassland is still severe. 3) Forest land is considered the most sustainable type and has a high resource utilization rate all the time, followed by water area, cultivated land, and grassland, when measured by ecological indicators. At the same time, in terms of the coordination between economy and ecology, all lands have been improved.
Emerging Contaminants in Soil and Water
Authors: Bayabil Haimanote K. , Teshome Fitsum T. , Li Yuncong C.
Published: March 2022

The global population increase puts tremendous pressure on the already dwindling natural resources such as soil and freshwater. Healthy and productive soils as well as the availability of freshwater resources are critical for agricultural productivity. On the other hand, climate change and variability make the water scarcity problem even worse. Agriculture, being the biggest consumer of fresh water, is expected to be affected significantly. Yet, agriculture is expected to play a significant role in achieving greater food, and fiber needs to meet the growing global population. In addition, soil and water quality are also becoming a bigger threat to soil productivity and freshwater availability. Some portion of nutrients applied to agriculture and urban landscapes end up in runoff and leaching water that feeds streams, rivers, lakes, groundwater, etc. These excess nutrient loadings are causing soil and water quality deterioration, which could have severe impacts on human health, aquatic ecosystems, and environmental sustainability. In addition to nutrient and chemical pollutions, emerging contaminants such as heavy metals are showing an increasing trend in soil and freshwater bodies. These emerging contaminants not only impair soil quality and freshwater sources but could also get into the food chain and affect human and animal health. While growing evidence is becoming available on the increasing threats from emerging contaminants, research and understanding are still limited. This mini-review paper summarizes available research on types of emerging contaminants and their impacts on soil and water quality.
Developmental Plasticity in Primate Coordinated Song: Parallels and Divergences With Duetting Songbirds
Authors: Adret Patrice
Published: March 2022

Homeothermic animals (birds and mammals) are prime model systems for investigating the developmental plasticity and neural mechanisms of vocal duetting, a cooperative acoustic signal that prevails in family-living and pair-bonded species including humans. This review focuses on the nature of this trait and its nurturing during ontogeny and extending into adulthood. I begin by outlining the underpinning concepts of duet codes and pair-specific answering rules as used by birds to develop their learned coordinated song, driven by a complex interaction between self-generated and socially mediated auditory feedback. The more tractable avian model of duetting helps identify research gaps in singing primates that also use duetting as a type of intraspecific vocal interaction. Nevertheless, it has become clear that primate coordinated song—whether overlapping or antiphonal—is subject to some degree of vocal flexibility. This is reflected in the ability of lesser apes, titi monkeys, tarsiers, and lemurs to adjust the structure and timing of their calls through (1) social influence, (2) coordinated duetting both before and after mating, (3) the repair of vocal mistakes, (4) the production of heterosexual song early in life, (5) vocal accommodation in call rhythm, (6) conditioning, and (7) innovation. Furthermore, experimental work on the neural underpinnings of avian and mammalian antiphonal duets point to a hierarchical (cortico-subcortical) control mechanism that regulates, via inhibition, the temporal segregation of rapid vocal exchanges. I discuss some weaknesses in this growing field of research and highlight prospective avenues for future investigation.
The Pivotal Role of Major Chromosomes of Sub-Genomes A and D in Fiber Quality Traits of Cotton
Authors: Razzaq Abdul , Zafar Muhammad Mubashar , Ali Arfan , Hafeez Abdul , Sharif Faiza , Guan Xueing , Deng Xiaoying , Pengtao Li , Shi Yuzhen , Haroon Muhammad , Gong Wankui , Ren Maozhi , Yuan Youlu
Published: March 2022

Lack of precise information about the candidate genes involved in a complex quantitative trait is a major obstacle in the cotton fiber quality improvement, and thus, overall genetic gain in conventional phenotypic selection is low. Recent molecular interventions and advancements in genome sequencing have led to the development of high-throughput molecular markers, quantitative trait locus (QTL) fine mapping, and single nucleotide polymorphisms (SNPs). These advanced tools have resolved the existing bottlenecks in trait-specific breeding. This review demonstrates the significance of chromosomes 3, 7, 9, 11, and 12 of sub-genomes A and D carrying candidate genes for fiber quality. However, chromosome 7 carrying SNPs for stable and potent QTLs related to fiber quality provides great insights for fiber quality-targeted research. This information can be validated by marker-assisted selection (MAS) and transgene in Arabidopsis and subsequently in cotton.
Crucial Roles of microRNA-16-5p and microRNA-27b-3p in Ameloblast Differentiation Through Regulation of Genes Associated With Amelogenesis Imperfecta
Authors: Suzuki Akiko , Yoshioka Hiroki , Liu Teng , Gull Aania , Singh Naina , Le Thanh , Zhao Zhongming , Iwata Junichi
Published: March 2022

Amelogenesis imperfecta is a congenital disorder within a heterogeneous group of conditions characterized by enamel hypoplasia. Patients suffer from early tooth loss, social embarrassment, eating difficulties, and pain due to an abnormally thin, soft, fragile, and discolored enamel with poor aesthetics and functionality. The etiology of amelogenesis imperfecta is complicated by genetic interactions. To identify mouse amelogenesis imperfecta-related genes (mAIGenes) and their respective phenotypes, we conducted a systematic literature review and database search and found and curated 70 mAIGenes across all of the databases. Our pathway enrichment analysis indicated that these genes were enriched in tooth development-associated pathways, forming four distinct groups. To explore how these genes are regulated and affect the phenotype, we predicted microRNA (miRNA)-gene interaction pairs using our bioinformatics pipeline. Our miRNA regulatory network analysis pinpointed that miR-16-5p, miR-27b-3p, and miR-23a/b-3p were hub miRNAs. The function of these hub miRNAs was evaluated through ameloblast differentiation assays with/without the candidate miRNA mimics using cultured mouse ameloblast cells. Our results revealed that overexpression of miR-16-5p and miR-27b-3p, but not miR-23a/b-3p, significantly inhibited ameloblast differentiation through regulation of mAIGenes. Thus, our study shows that miR-16-5p and miR-27b-3p are candidate pathogenic miRNAs for amelogenesis imperfecta.
Chromosome Painting in Gymnotus carapo “Catalão” (Gymnotiformes, Teleostei): Dynamics of Chromosomal Rearrangements in Cryptic Species
Authors: Machado Milla de Andrade , da Silva Maelin , Feldberg Eliana , O’Brien Patricia Caroline Mary , Ferguson-Smith Malcolm Andrew , Pieczarka Julio Cesar , Nagamachi Cleusa Yoshiko
Published: March 2022

The genus Gymnotus is a large monophyletic group of freshwater weakly-electric fishes, with wide distribution in Central and South America. It has 46 valid species divided into six subgenera (Gymnotus, Tijax, Tigre, Lamontianus, Tigrinus and Pantherus) with large chromosome plasticity and diploid numbers (2n) ranging from 34 to 54. Within this rich diversity, there is controversy about whether Gymnotus (Gymnotus) carapo species is a single widespread species or a complex of cryptic species. Cytogenetic studies show different diploid numbers for G. carapo species, ranging from 40 to 54 chromosomes with varied karyotypes found even between populations sharing the same 2n. Whole chromosome painting has been used in studies on fish species and recently has been used for tracking the chromosomal evolution of Gymnotus and assisting in its cytotaxonomy. Comparative genomic mapping using chromosome painting has shown more complex rearrangements in Gymnotus carapo than shown in previous studies by classical cytogenetics. These studies demonstrate that multiple chromosome pairs are involved in its chromosomal reorganization, suggesting the presence of a complex of cryptic species due to a post zygotic barrier. In the present study, metaphase chromosomes of G. carapo occidentalis “catalão” (GCC, 2n = 40, 30m/sm+10st/a) from the Catalão Lake, Amazonas, Brazil, were hybridized with whole chromosome probes derived from the chromosomes of G. carapo (GCA, 2n = 42, 30m/sm+12st/a). The results reveal chromosome rearrangements and a high number of repetitive DNA sites. Of the 12 pairs of G. carapo chromosomes that could be individually identified (GCA 1–3, 6, 7, 9, 14, 16 and 18–21), 8 pairs (GCA 1, 2, 6, 7, 9, 14, 20, 21) had homeology conserved in GCC. Of the GCA pairs that are grouped (GCA [4, 8], [5, 17], [10, 11] and [12, 13, 15]), most kept the number of signals in GCC (GCA [5, 17], [10, 11] and [12, 13, 15]). The remaining chromosomes are rearranged in the GCC karyotype. Analysis of both populations of the G. carapo cytotypes shows extensive karyotype reorganization. Along with previous studies, this suggests that the different cytotypes analyzed here may represent different species and supports the hypothesis that G. carapo is not a single widespread species, but a group of cryptic species.
Population Genetics Reveals That the Western Tianshan Mountains Populations of Agrilus mali (Coleoptera: Buprestidae) May Have Not been Recently Introduced
Authors: Sun Huiquan , Jia Feiran , Zhao Wenxia , Zhou Zhongfu , Li Chengjin , Wang Jianjun , Yao Yanxia
Published: March 2022

Agrilus mali Matsumura is a wood-boring beetle that aggressively attacks species of the genus Malus, that has recently caused serious damage to the wild apple tree M. sieversii (Lebed.) in the western Tianshan Mountains in Xinjiang. It was first detected there in the early 1990s and spread rapidly, being thus considered a regional invasive pest. To explore the possible outbreak mechanism of the local population and characterize the genetic differentiation of A. mali across different regions of China, we used three mitochondrial genes (COI, COII, and CytB) to investigate the genetic diversity and genetic structure of 17 A. mali populations containing 205 individuals collected from five Chinese provinces. Among them, nine populations were from the western Tianshan Mountains. Ultimately, of the 136 pairwise Fst comparisons, 99 showed high genetic differentiation among overall populations, and Tianshan populations exhibited significant differentiation with most of the non-Tianshan populations. Furthermore, A. mali populations represented relatively abundant haplotypes (54 haplotypes). Nine populations from the Tianshan Mountains showed 32 haplotypes (26 of which were unique), displaying relatively high genetic diversity. Additionally, the Mantel test revealed population genetic differentiation among either overall populations or the Tianshan Mountains populations, likely caused by geographical isolation. Phylogenic relationships showed that all populations clustered into three clades, and Tianshan Mountains populations, including CY, occupied one of the three clades. These results suggest that A. mali in the western Tianshan region has possibly been present in the area for a long period, and may not have been introduced recently. Highly frequent gene flows within Tianshan populations are possibly caused by human activities and may enhance the adaptability of A. mali along the western Tianshan Mountains, leading to periodic outbreaks. These findings enhance our understanding of jewel beetle population genetics and provide valuable information for pest management.
Case Report: A Paternal 20q13.2-q13.32 Deletion Patient With Growth Retardation Improved by Growth Hormone
Authors: Liu Yu , Yang Ying , Chu Liming , Ren Shuai , Li Ying , Gao Aimin , Wen Jing , Deng Wanling , Lu Yan , Kong Lingyin , Liang Bo , Shao Xiaoshan
Published: March 2022

Interstitial chromosome 20q deletions, containing GNAS imprinted locus, are rarely reported in the past. Hereby, we presented a Chinese boy with a novel 4.36 Mb deletion at paternal 20q13.2-13.32, showing feeding difficulty, malnutrition, short stature, lower limb asymmetry, sightly abnormal facial appearance and mild intellectual abnormality. With 3 years’ growth hormone treatment, his height was increased from 90 to 113.5 cm. This report is the first time to describe the outcome of clinical treatment on a patient with this rare chromosomal 20 long arm interstitial deletion, containing GNAS locus, which may facilitate the diagnosis and treatment of this type of patient in the future.
Parental Guidance Suggested: Engaging Parents as Partners in Research Studies of Genomic Screening for a Pediatric Population
Authors: Powell Sabrina N. , Byfield Grace , Bennetone Ashley , Frantz Annabelle M. , Harrison Langston K. , James-Crook Erin R. , Osborne Heather , Owens Thomas H. , Shaw Jonathan L. , O’Daniel Julianne , Milko Laura V.
Published: March 2022

Recent advances in genomic sequencing and genomic medicine are reshaping the landscape of clinical care. As a screening modality, genetic sequencing has the potential to dramatically expand the clinical utility of newborn screening (NBS), though significant barriers remain regarding ethical, legal, and social implications (ELSI) and technical and evidentiary challenges. Stakeholder-informed implementation research is poised to grapple with many of these barriers, and parents are crucial stakeholders in this process. We describe the formation and activities of a Community Research Board (CRB) composed of parents with diverse backgrounds assembled to participate in an ongoing research partnership with genomic and public health researchers at the University of North Carolina. The mission of the CRB is to provide insight into parental perspectives regarding the prospect of adding genomic sequencing to NBS and collaboratively develop strategies to ensure its equitable uptake. We describe how these contributions can improve the accessibility of research and recruitment methods and promote trust and inclusivity within diverse communities to maximize the societal benefit of population genomic screening in healthy children.
Cytokinin Oxygenase/Dehydrogenase Inhibitors: An Emerging Tool in Stress Biotechnology Employed for Crop Improvement
Authors: Arora Kavita , Sen Sangeeta
Published: March 2022

In order to meet the global challenges of food security, one of the foremost solutions lies in enhancing the crop productivity. This can be attained by considering key plant hormones such as cytokinins as agrochemicals as cytokinins in particular are known to control the essential processes of the plants. Even though, it has already been established since 1980s that the enzyme, cytokinin oxidase/dehydrogenase (CKO/CKX) deactivates cytokinins; the potential applications of manipulating these enzymes have mostly been speculated to have a high potential in the biotechnology industry and spreads to agriculture, horticulture and agroforestry. The enzyme is critical in maintaining a balanced level of cytokinins in plants. However, it is yet to be fully established that inhibiting this enzyme can be the constant source of improvement in the productivity of plants, even though success has been obtained in some economically important plant species. Furthermore, the impact efficiency of this enzyme may vary from plant to plant, which needs to be evaluated employing tissue culture and other extrinsic applications. This review intends to cover the relevant studies addressing any biological activity of this enzyme in the current context and any associated biotechnological applications specific to enhanced grain yield, abiotic stress tolerance, delayed senescence and in vitro organogenesis among various plants and not only cereals. Moreover, our study will identify the present gaps in research with respect to many important food crops, which will be useful for researchers who are actively involved in providing a foundation for a variety of genetically improved plants achieved through this manner. In addition to this, other ways of engineering the amount of cytokinin levels appropriate for signaling also needs to be analyzed in order to extend the benefits of cytokinin biology to other crops too. The application of these inhibitors can be considered among the best alternates as well as addition to genetically modified plants for overcoming the gaps in crop demand.
A Neurometabolic Pattern of Elevated Myo-Inositol in Children Who Are HIV-Exposed and Uninfected: A South African Birth Cohort Study
Authors: Bertran-Cobo Cesc , Wedderburn Catherine J. , Robertson Frances C. , Subramoney Sivenesi , Narr Katherine L. , Joshi Shantanu H. , Roos Annerine , Rehman Andrea M. , Hoffman Nadia , Zar Heather J. , Stein Dan J. , Donald Kirsten A.
Published: March 2022

Introduction

Exposure to maternal HIV in pregnancy may be a risk factor for impaired child neurodevelopment during the first years of life. Altered neurometabolites have been associated with HIV exposure in older children and may help explain the mechanisms underlying this risk. For the first time, we explored neurometabolic profiles of children who are HIV-exposed and uninfected (CHEU) compared to children who are HIV-unexposed (CHU) at 2-3 years of age.

Methods

The South African Drakenstein Child Health Study enrolled women during pregnancy and is following mother-child pairs through childhood. MRI scans were acquired on a sub-group of children at 2-3 years. We used single voxel magnetic resonance spectroscopy to measure brain metabolite ratios to total creatine in the parietal grey matter, and left and right parietal white matter of 83 children (36 CHEU; 47 CHU). Using factor analysis, we explored brain metabolite patterns in predefined parietal voxels in these groups using logistic regression models. Differences in relative concentrations of individual metabolites (n-acetyl-aspartate, myo-inositol, total choline, and glutamate) to total creatine between CHEU and CHU groups were also examined.

Results

Factor analysis revealed four different metabolite patterns, each one characterized by covarying ratios of a single metabolite in parietal grey and white matter. The cross-regional pattern dominated by myo-inositol, a marker for glial reactivity and inflammation, was associated with HIV exposure status (OR 1.63; 95% CI 1.11–2.50) which held after adjusting for child age, sex, and maternal alcohol use during pregnancy (OR 1.59; 95% CI 1.07 –2.47). Additionally, higher relative concentrations of myo-inositol to total creatine were found in left and right parietal white matter of CHEU compared to CHU (p=0.025 and p=0.001 respectively).

Discussion

Increased ratios of myo-inositol to total creatine in parietal brain regions at age 2-3 years in CHEU are suggestive of early and ongoing neuroinflammatory processes. Altered relative concentrations of neurometabolites were found predominantly in the white matter, which is sensitive to neuroinflammation, and may contribute to developmental risk in this population. Future work on the trajectory of myo-inositol over time in CHEU, alongside markers of neurocognitive development, and the potential for specific neurodevelopmental interventions will be useful.
Antigen Presentation Machinery Signature-Derived CALR Mediates Migration, Polarization of Macrophages in Glioma and Predicts Immunotherapy Response
Authors: Chen Rui , Zhang Hao , Wu Wantao , Li Shuyu , Wang Zeyu , Dai Ziyu , Liu Zaoqu , Zhang Jian , Luo Peng , Xia Zhiwei , Cheng Quan
Published: March 2022

Immunogenicity, influenced by tumor antigenicity and antigen presenting efficiency, critically determines the effectiveness of immune checkpoint inhibitors. The role of immunogenicity has not been fully elucidated in gliomas. In this study, a large-scale bioinformatics analysis was performed to analyze the prognostic value and predictive value of antigen presentation machinery (APM) signature in gliomas. ssGSEA algorithm was used for development of APM signature and LASSO regression analysis was used for construction of APM signature-based risk score. APM signature and risk score showed favorable performance in stratifying survival and predicting tumorigenic factors of glioma patients. APM signature and risk score were also associated with different genomic features in both training cohort TCGA and validating cohort CGGA. Furthermore, APM signature-based risk score was independently validated in three external cohorts and managed to predict immunotherapy response. A prognostic nomogram was constructed based on risk score. Risk score-derived CALR was found to mediate the invasion and polarization of macrophages based on the coculture of HMC3 and U251 cells. CALR could significantly predict immunotherapy response. In conclusion, APM signature and APM signature-based risk score could help promote the clinical management of gliomas.
MicroRNA-Mediated Epigenetic Regulation of Rheumatoid Arthritis Susceptibility and Pathogenesis
Authors: Chang Cen , Xu Lingxia , Zhang Runrun , Jin Yehua , Jiang Ping , Wei Kai , Xu Linshuai , Shi Yiming , Zhao Jianan , Xiong Momiao , Guo Shicheng , He Dongyi
Published: March 2022

MicroRNAs (miRNAs) play crucial roles in regulating the transcriptome and development of rheumatoid arthritis (RA). Currently, a comprehensive map illustrating how miRNAs regulate transcripts, pathways, immune system differentiation, and their interactions with terminal cells such as fibroblast-like synoviocytes (FLS), immune-cells, osteoblasts, and osteoclasts are still laking. In this review, we summarize the roles of miRNAs in the susceptibility, pathogenesis, diagnosis, therapeutic intervention, and prognosis of RA. Numerous miRNAs are abnormally expressed in cells involved in RA and regulate target genes and pathways, including NF-κB, Fas-FasL, JAK-STAT, and mTOR pathways. We outline how functional genetic variants ofmiR-499andmiR-146apartly explain susceptibility to RA. By regulating gene expression, miRNAs affect T cell differentiation into diverse cell types, including Th17 and Treg cells, thus constituting promising gene therapy targets to modulate the immune system in RA. We summarize the diagnostic and prognostic potential of blood-circulating and cell-free miRNAs, highlighting the opportunity to combine these miRNAs with antibodies to cyclic citrullinated peptide (ACCP) to allow accurate diagnosis and prognosis, particularly for seronegative patients. Furthermore, we review the evidence implicating miRNAs as promising biomarkers of efficiency and response of, and resistance to, disease-modifying anti-rheumatic drugs and immunotherapy. Finally, we discuss the autotherapeutic effect of miRNA intervention as a step toward the development of miRNA-based anti-RA drugs. Collectively, the current evidence supports miRNAs as interesting targets to better understand the pathogenetic mechanisms of RA and design more efficient therapeutic interventions.
Assessment of Acute Rejection by Global Longitudinal Strain and Cardiac Biomarkers in Heart-Transplanted Patients
Authors: Clemmensen Tor Skibsted , Firooznia Nilufar , Olawi Fariha Morsal , Løgstrup Brian Bridal , Poulsen Steen Hvitfeldt , Eiskjær Hans
Published: March 2022

Aims

The aim of this study was to evaluate left ventricular global longitudinal strain (LVGLS), N-terminal pro brain natriuretic peptide (Nt-ProBNP), and Troponin T as non-invasive markers for acute cellular rejection (ACR) diagnosis and severity assessment after heart transplantation (HTx).

Methods

We retrospectively included all HTx patients transplanted from 2013 to 2019. At each visit, the patients were subjected to endomyocardial biopsy (EMB), measurement of Nt-ProBNP and Troponin T, and protocoled echocardiography with assessment of LVGLS. Sudden drop in graft function (SDGF) was defined as a drop in LVGLS ≥-2% in combination with either an increase in Troponin T ≥20% or Nt-ProBNP ≥30% compared with levels at the latest visit.

Results

We included 1,436 EMBs from 83 HTx patients. The biopsies were grouped as 0R (n = 857), 1R (n = 538), and ≥2R (n = 41). LVGLS was lower and Troponin T and Nt-ProBNP higher in the 2R group than in the 0R and 1R groups (LVGLS: -12.9 ± 3.8% versus -16.9 ± 3.1% and -16.1 ± 3.3%; Troponin T: 79 [33;230] ng/l versus 27 [13;77] ng/l and 27 [14;68] ng/l; Nt-ProBNP: 4,174 [1,095;9,510] ng/l versus 734 [309;2,210] ng/l and 725 [305;2,082], all p < 0.01). A SDGF was seen at 45 visits of which 19 had ≥2R ACR. EMBs showed ACR in 20 cases without SDGF. Finally, neither was SDGF seen nor did the EMB show rejection in 1,136 cases. Thus, the sensitivity of SDGF for ≥2R ACR detection was 49% (32–65) and specificity 98% (97–99). The positive predictive value (PPV) was 42% (31–55) and the negative predictive value (NPV) 98% (98–99). The diagnostic value improved in a sub-analysis excluding EMBs within 3 months after HTx, clinically interpreted false positive ≥2R ACR cases, and cases with ≥2R ACR who recently (<2 weeks) were treated with intravenous methylprednisolone due to ≥2R ACR (sensitivity 75% (48–93), specificity 97% (96–98), NPV 99% (99–100), and PPV 39% (27–52).

Conclusions

Patients with ≥2R ACR have lower LVGLS and higher Troponin T and Nt-ProBNP than patients without 2R rejection. A non-invasive model combining changes in LVGLS and Troponin T or Nt-ProBNP showed excellent negative predictive value and moderate sensitivity and may be used as a gatekeeper to invasive biopsies after HTx.
Epigenetic Regulation in the Pathogenesis of Rheumatoid Arthritis
Authors: Yang Chao , Li Dan , Teng Dehong , Zhou Yueru , Zhang Lei , Zhong Zhangfeng , Yang Guan-Jun
Published: March 2022

Rheumatoid arthritis (RA) is an autoimmune disease. The etiology of RA remains undetermined and the pathogenesis is complex. There remains a paucity of ideal therapeutic drugs and treatment strategies. The epigenetic modifications affect and regulate the function and characteristics of genes through mechanisms, including DNA methylation, histone modification, chromosome remodeling, and RNAi, thereby exerting a significant impact on the living state of the body. Recently, the phenomenon of epigenetic modification in RA has garnered growing research interest. The application of epigenetically modified methods is the frontier field in the research of RA pathogenesis. This review highlights the research on the pathogenesis of RA based on epigenetic modification in the recent five years, thereby suggesting new methods and strategies for the diagnosis and treatment of RA.
Selection Signatures of Pacific White Shrimp Litopenaeus vannamei Revealed by Whole-Genome Resequencing Analysis
Authors: Wang Hao , Teng Mingxuan , Liu Pingping , Zhao Mingyang , Wang Shi , Hu Jingjie , Bao Zhenmin , Zeng Qifan
Published: March 2022

The Pacific white shrimp Litopenaeus vannamei is among the top aquatic species of commercial importance around the world. Over the last four decades, the breeding works of L. vannamei have been carried out intensively and have generated multiple strains with improved production and performance traits. However, signatures of domestication and artificial selection across the L. vannamei genome remain largely unexplored. In the present study, we conducted whole genomic resequencing of 180 Pacific white shrimps from two artificially selective breeds and four market-leading companies. A total of 37 million single nucleotide polymorphisms (SNPs) were identified with an average density of 22.5 SNPs/Kb across the genome. Ancestry estimation, principal component analysis, and phylogenetic inference have all revealed the obvious stratifications among the six breeds. We evaluated the linkage disequilibrium (LD) decay in each breed and identified the genetic variations driven by selection. Pairwise comparison of the fixation index (Fst) and nucleotide diversity (θπ) has allowed for mining the genomic regions under selective sweep in each breed. The functional enrichment analysis revealed that genes within these regions are mainly involved in the cellular macromolecule metabolic process, proteolysis, structural molecule activity, structure of the constituent ribosome, and responses to stimulus. The genome-wide SNP datasets provide valuable information for germplasm resources assessment and genome-assisted breeding of Pacific white shrimps, and also shed light on the genetic effects and genomic signatures of selective breeding.
Recent Technical Advances in Accelerating the Clinical Translation of Small Animal Brain Imaging: Hybrid Imaging, Deep Learning, and Transcriptomics
Authors: Ren Wuwei , Ji Bin , Guan Yihui , Cao Lei , Ni Ruiqing
Published: March 2022

Small animal models play a fundamental role in brain research by deepening the understanding of the physiological functions and mechanisms underlying brain disorders and are thus essential in the development of therapeutic and diagnostic imaging tracers targeting the central nervous system. Advances in structural, functional, and molecular imaging using MRI, PET, fluorescence imaging, and optoacoustic imaging have enabled the interrogation of the rodent brain across a large temporal and spatial resolution scale in a non-invasively manner. However, there are still several major gaps in translating from preclinical brain imaging to the clinical setting. The hindering factors include the following: (1) intrinsic differences between biological species regarding brain size, cell type, protein expression level, and metabolism level and (2) imaging technical barriers regarding the interpretation of image contrast and limited spatiotemporal resolution. To mitigate these factors, single-cell transcriptomics and measures to identify the cellular source of PET tracers have been developed. Meanwhile, hybrid imaging techniques that provide highly complementary anatomical and molecular information are emerging. Furthermore, deep learning-based image analysis has been developed to enhance the quantification and optimization of the imaging protocol. In this mini-review, we summarize the recent developments in small animal neuroimaging toward improved translational power, with a focus on technical improvement including hybrid imaging, data processing, transcriptomics, awake animal imaging, and on-chip pharmacokinetics. We also discuss outstanding challenges in standardization and considerations toward increasing translational power and propose future outlooks.
Convergence of Biofilm Formation and Antibiotic Resistance in Acinetobacter baumannii Infection
Authors: Roy Subhasree , Chowdhury Goutam , Mukhopadhyay Asish K. , Dutta Shanta , Basu Sulagna
Published: March 2022

Acinetobacter baumannii (A. baumannii) is a leading cause of nosocomial infections as this pathogen has certain attributes that facilitate the subversion of natural defenses of the human body. A. baumannii acquires antibiotic resistance determinants easily and can thrive on both biotic and abiotic surfaces. Different resistance mechanisms or determinants, both transmissible and non-transmissible, have aided in this victory over antibiotics. In addition, the propensity to form biofilms (communities of organism attached to a surface) allows the organism to persist in hospitals on various medical surfaces (cardiac valves, artificial joints, catheters, endotracheal tubes, and ventilators) and also evade antibiotics simply by shielding the bacteria and increasing its ability to acquire foreign genetic material through lateral gene transfer. The biofilm formation rate in A. baumannii is higher than in other species. Recent research has shown how A. baumannii biofilm-forming capacity exerts its effect on resistance phenotypes, development of resistome, and dissemination of resistance genes within biofilms by conjugation or transformation, thereby making biofilm a hotspot for genetic exchange. Various genes control the formation of A. baumannii biofilms and a beneficial relationship between biofilm formation and “antimicrobial resistance” (AMR) exists in the organism. This review discusses these various attributes of the organism that act independently or synergistically to cause hospital infections. Evolution of AMR in A. baumannii, resistance mechanisms including both transmissible (hydrolyzing enzymes) and non-transmissible (efflux pumps and chromosomal mutations) are presented. Intrinsic factors [biofilm-associated protein, outer membrane protein A, chaperon-usher pilus, iron uptake mechanism, poly-β-(1, 6)-N-acetyl glucosamine, BfmS/BfmR two-component system, PER-1, quorum sensing] involved in biofilm production, extrinsic factors (surface property, growth temperature, growth medium) associated with the process, the impact of biofilms on high antimicrobial tolerance and regulation of the process, gene transfer within the biofilm, are elaborated. The infections associated with colonization of A. baumannii on medical devices are discussed. Each important device-related infection is dealt with and both adult and pediatric studies are separately mentioned. Furthermore, the strategies of preventing A. baumannii biofilms with antibiotic combinations, quorum sensing quenchers, natural products, efflux pump inhibitors, antimicrobial peptides, nanoparticles, and phage therapy are enumerated.
Evaluation Effect of Aspiration of 0.2 ml of Cerebrospinal Fluid After Completion of Injection 0.5% Bupivacaine and Reinjection Into Subarachnoid Space on Sensory and Motor Block in Cesarean Section: A Randomized Clinical Trial
Authors: Manouchehrian Nahid , Miri Zahra , Esna-Ashari Farzaneh , Rahimi-Bashar Farshid
Published: March 2022

Background

Spinal anesthesia (SPA) is the most common type of anesthesia administered for cesarean section. The main aim of this study was to evaluate the effect of aspiration of CSF (0.2 mL) immediately after SPA with hyperbaric 0.5% bupivacaine on the extent of sensory and motor block.

Methods

In this clinical trial, 60 women at ≥37 weeks of gestation and aged between 18 and 46 years, candidate for cesarean delivery under spinal anesthesia were randomly allocated into two equal groups (n = 30). Group A (CSF-aspiration group) received the spinal anesthesia with 10 mg of hyperbaric 0.5% bupivacaine with aspiration of 0.2 ml of CSF. Group B (no-CSF-aspiration group) received only 10 mg of 0.5% hyperbaric bupivacaine. Pin-prick analgesia and motor block were tested during the induction.

Results

The mean maximum level of analgesia was T6 in each group. Although the mean time to reach the maximum level of anesthesia (4.43 ± 5.14 vs. 2.76 ± 2.04, P = 0.107) and to reach T10 level (50.56 ± 11.51 vs. 49.10 ± 13.68, P = 0.665) in the CSF-aspiration group is longer than the non-CSF-aspiration group, but this differences were not significant. There were no significant between-group differences regarding sensory and motor block quality (P = 0.389) or failed SPA (four cases in CSF-aspiration group vs. two cases in no-CSF-aspiration group, P = 0.389). The incidence of bradycardia, hypotension, headache, vomiting and nausea were similar in both groups (P > 0.05). In addition, the difference in hemodynamic parameters between the two groups over times was not statistically significant.

Conclusion

Our finding indicated that the aspiration of 0.2 ml of CSF after injection of spinal anesthesia with hyperbaric 0.5% bupivacaine does not seem to affect the extent of sensory and motor block, success rate, or outcome after SPA in cesarean section.

Clinical Trial Registration

[https://www.irct.ir/search/result?query=IRCT20120915010841N25], identifier [IRCT20120915010841N25].
Computed Tomography Radiomics-Based Prediction of Microvascular Invasion in Hepatocellular Carcinoma
Authors: Yao Wenjun , Yang Shuo , Ge Yaqiong , Fan Wenlong , Xiang Li , Wan Yang , Gu Kangchen , Zhao Yan , Zha Rujing , Bu Junjie
Published: March 2022

Background

Due to the high recurrence rate in hepatocellular carcinoma (HCC) after resection, preoperative prognostic prediction of HCC is important for appropriate patient management. Exploring and developing preoperative diagnostic methods has great clinical value in treating patients with HCC. This study sought to develop and evaluate a novel combined clinical predictive model based on standard triphasic computed tomography (CT) to discriminate microvascular invasion (MVI) in hepatocellular carcinoma (HCC).

Methods

The preoperative findings of 82 patients with HCC, including conventional clinical factors, CT imaging findings, and CT texture analysis (TA), were analyzed retrospectively. All included cases were divided into MVI-negative (n = 33; no MVI) and MVI-positive (n = 49; low or high risk of MVI) groups. TA parameters were extracted from non-enhanced, arterial, portal venous, and equilibrium phase images and subsequently calculated using the Artificial Intelligence Kit. After statistical analyses, a clinical model comprising conventional clinical and CT image risk factors, radiomics signature models, and a novel combined model (fused radiomic signature) was constructed. The area under the curve (AUC) of the receiver operating characteristics (ROC) curve was used to assess the performance of the various models in discriminating MVI.

Results

We found that tumor diameter and pathological grade were effective clinical predictors in clinical model and 12 radiomics features were effective for MVI prediction of each CT phase. The AUCs of the clinical, plain, artery, venous, and delay models were 0.77 (95% CI: 0.67–0.88), 0.75 (95% CI: 0.64–0.87), 0.79 (95% CI: 0.69–0.89), 0.73 (95% CI: 0.61–0.85), and 0.80 (95% CI: 0.70–0.91), respectively. The novel combined model exhibited the best performance, with an AUC of 0.83 (95% CI: 0.74–0.93).

Conclusions

Models derived from triphasic CT can preoperatively predict MVI in patients with HCC. Of the models tested here, the novel combined model was most predictive and could become a useful tool to guide subsequent personalized treatment of HCC.
Comfort During Non-invasive Ventilation
Authors: Cammarota Gianmaria , Simonte Rachele , De Robertis Edoardo
Published: March 2022

Non-invasive ventilation (NIV) has been shown to be effective in avoiding intubation and improving survival in patients with acute hypoxemic respiratory failure (ARF) when compared to conventional oxygen therapy. However, NIV is associated with high failure rates due, in most cases, to patient discomfort. Therefore, increasing attention has been paid to all those interventions aimed at enhancing patient's tolerance to NIV. Several practical aspects have been considered to improve patient adaptation. In particular, the choice of the interface and the ventilatory setting adopted for NIV play a key role in the success of respiratory assistance. Among the different NIV interfaces, tolerance is poorest for the nasal and oronasal masks, while helmet appears to be better tolerated, resulting in longer use and lower NIV failure rates. The choice of fixing system also significantly affects patient comfort due to pain and possible pressure ulcers related to the device. The ventilatory setting adopted for NIV is associated with varying degrees of patient comfort: patients are more comfortable with pressure-support ventilation (PSV) than controlled ventilation. Furthermore, the use of electrical activity of the diaphragm (EADi)-driven ventilation has been demonstrated to improve patient comfort when compared to PSV, while reducing neural drive and effort. If non-pharmacological remedies fail, sedation can be employed to improve patient's tolerance to NIV. Sedation facilitates ventilation, reduces anxiety, promotes sleep, and modulates physiological responses to stress. Judicious use of sedation may be an option to increase the chances of success in some patients at risk for intubation because of NIV intolerance consequent to pain, discomfort, claustrophobia, or agitation. During the Coronavirus Disease-19 (COVID-19) pandemic, NIV has been extensively employed to face off the massive request for ventilatory assistance. Prone positioning in non-intubated awake COVID-19 patients may improve oxygenation, reduce work of breathing, and, possibly, prevent intubation. Despite these advantages, maintaining prone position can be particularly challenging because poor comfort has been described as the main cause of prone position discontinuation. In conclusion, comfort is one of the major determinants of NIV success. All the strategies aimed to increase comfort during NIV should be pursued.
Bacterial and Fungal Adaptations in Cecum and Distal Colon of Piglets Fed With Dairy-Based Milk Formula in Comparison With Human Milk
Authors: Elolimy Ahmed , Rosa Fernanda , Tripp Patricia , Zeineldin Mohamed , Bowlin Anne K. , Randolph Christopher , Robeson Michael S. , Yeruva Laxmi
Published: March 2022

Exclusive breastfeeding is recommended to newborns during the first 6 months of life, whereas dairy-based infant formula is an alternative nutrition source offered to infants. Several studies demonstrated that breastfed infants have a different gut bacterial composition relative to formula-fed infants. In addition, animal models have shown that human milk (HM)–fed piglets had a distinct intestinal bacterial composition compared with milk formula (MF)–fed piglets. However, the gut fungal composition and the interactions with the bacterial community in breastfed compared with formula-fed infants remain to be investigated. In an attempt to evaluate such differences, we used an animal model to perform a shotgun metagenomics analysis on the cecal and distal colon contents of neonatal piglets fed with pasteurized HM or a dairy-based infant formula (MF) during the first 21 days of life. At postnatal day 21 (PND 21), a subset of piglets from each diet group (n = 11 per group) was euthanized. The remaining piglets in each group were weaned to a solid diet and euthanized at PND 51 (n = 13 per group). Large intestine contents (i.e., cecum and distal colon) were subjected to shotgun metagenomics analysis. The differential taxonomic composition of bacteria and fungi and the predicted functional gene profiling were evaluated. Bacteroidetes, Firmicutes, Proteobacteria, and Actinobacteria are the most abundant bacterial phyla observed in piglets at PND 21 and PND 51. In the large intestine at PND 21 and PND 51, Proteobacteria phylum was significantly higher in MF-fed group, and species Burkholderiales bacterium of phyla was significantly higher in MF group relative to HM group. In addition, in HM group, several Lactobacillus spp. and Bacteroides spp. were higher relative to MF group in the large intestine at PND 21 and PND 51. Fungal genus Aspergillus was higher in MF, whereas Malassezia was lower relative to HM group. Persistent effects of the neonatal diets were observed at PND 51, where alpha- and beta-diversity differences were detected for bacterial and fungal species in the large intestine. Overall, our findings indicate that neonatal diet affects the large intestinal microbial community during the exclusive milk-feeding period, as well as after the introduction of the complementary food.