bluuebunny/crossref_metadata_2025 huggingface dataset:
Deep learning-based gas-phase chemical kinetics kernel emulator: Application in a global air quality simulation case
Authors: Wang Zixi , Li Jie , Wu Lin , Zhu Mingming , Zhang Yujing , Ye Zhilan , Wang Zifa
Published: August 2022

The global atmospheric chemical transport model has become a key technology for air quality forecast and management. However, precise and rapid air quality simulations and forecast are frequently limited by the model’s computational performance. The gas-phase chemistry module is the most time-consuming module in air quality models because its traditional solution method is dynamically stiff. To reduce the solving time of the gas phase chemical module, we built an emulator based on a deep residual neural network emulator (NN) for Carbon Bond Mechanism Z (CBM-Z) mechanism implemented in Global Nested Air Quality Prediction Modeling System. A global high resolution cross-life multi-species dataset was built and trained to evaluate multi-species concentration changes at a single time step of CBM-Z. The results showed that the emulator could accelerate to approximately 300–750 times while maintaining an accuracy similar to that of CBM-Z module (the average correlation coefficient squared was 0.97) at the global scale. This deep learning-based emulator could adequately represent the stiff kinetics of CBM-Z, which involves 47 species and 132 reactions. The emulated ozone (O3), nitrogen oxides (NOx), and hydroxyl radical (OH) were consistent with those of the original CBM-Z module in different global regions, heights, and time. Our results suggest that data-driven emulations have great potential in the construction of hybrid models with process-based air quality models, particularly at larger scales.
Environmental information disclosure and green energy efficiency: A spatial econometric analysis of 113 prefecture-level cities in China
Authors: Du Lei , Wang Fuwei , Tian Minghua
Published: August 2022

As one of the means of informal environmental regulation, environmental information disclosure has an essential impact on improving green energy efficiency. This paper selects the panel data of 113 environmental information disclosure cities in China from 2008 to 2018 and uses the Super-efficiency SBM model with undesirable outputs to measure green energy efficiency. Based on the measurement results, this paper empirically studies the impact of environmental information disclosure on green energy efficiency and its spatial spillover effect using the spatial Durbin model. The main conclusions are as follows: 1) From 2008 to 2018, the average green energy efficiency of 113 environmental information disclosure cities in China was 0.6676, and the regional distribution showed the characteristics of “high in the East and low in the west.” 2) Both environmental information disclosure and green energy efficiency have significant spatial correlation and show the characteristics of “high-high” and “low-low” agglomeration in spatial distribution. 3) Environmental information disclosure can significantly improve green energy efficiency in the region and surrounding areas. After the robustness test and endogenous test, the conclusion is still robust. 4) The impact of environmental information disclosure on green energy efficiency in the eastern region is significantly more significant than in the central and western regions. This paper provides a theoretical reference for the government to formulate corresponding environmental policies to promote green energy efficiency and promote green and sustainable economic development.
A study on land compactness of urban agglomeration-example from Beijing-Tianjin-Hebei
Authors: Wang Huiying , Wang Huimin , Xiong Xuehan
Published: August 2022

Compactness, intensity, efficiency and greenness are becoming the goals of regional governance in China. This study, based on the compact development theory, takes the urban agglomeration of Jingjinji as the research object, uses the composite index to construct a compactness index system based on production-living-ecological space and adopts entropy method to measure and analyze the degree of compactness. The results show that there is an obvious internal differentiation in Jingjinji, and the overall situation is not compact. Composed of production, living and ecological spaces, the compactness of the territorial space differs significantly. Production space is of the highest degree compactness, followed by living space and the lowest is ecological space. By comparing each index, compactness degrees of economic factors and municipal production facilities are better than those of the production land and transportation. Compactness degrees of Social factors of living space are more developed than those of residential land and public services. The overall compactness degree of the ecological space is the lowest, but the degrees of compactness are relatively balanced and there are small differences. The compactness degree of the green land is slightly lower than that of pollution treatment.
The diversity of microfungi associated with grasses in the Sporobolus indicus complex in Queensland, Australia
Authors: Steinrucken Tracey V. , Vitelli Joseph S. , Holdom David G. , Tan Yu Pei
Published: August 2022

There are five closely related Sporobolus species, collectively known as weedy Sporobolus grasses (WSG) or the rat’s tail grasses. They are fast growing, highly competitive, unpalatable weeds of pastures, roadsides and woodlands. An effective biological control agent would be a welcomed alternative to successive herbicide application and manual removal methods. This study describes the initial exploratory phase of isolating and identifying native Australian microfungi associated with WSG, prior to evaluating their efficacy as inundative biological control agents. Accurate species-level identification of plant-pathogenic microfungi associated with WSG is an essential first step in the evaluation and prioritisation of pathogenicity bioassays. Starting with more than 79 unique fungal morphotypes isolated from diseased Sporobolus grasses in Queensland, Australia, we employed multi-locus phylogenetic analyses to classify these isolates into 54 fungal taxa. These taxa belong to 22 Ascomycete families (12 orders), of which the majority fall within the Pleosporales (>24 taxa in 7 families). In the next phase of the study, the putative species identities of these taxa will allow us to prioritise those which are likely to be pathogenic based on existing literature and their known ecological roles. This study represents the first step in a systematic, high-throughput approach to finding potential plant pathogenic biological control agents.
Genetic evaluation of Jatropha backcross hybrid clones (BC4F1) for yield and oil quality
Authors: Jawahar Vishnu M. V. , Parthiban K. T. , Umadevi M. , Sudhagar R. Jude , Fernandaz C. Cinthia , Javed Talha , Kumar Uttam , Alotaibi Saqer S.
Published: August 2022

Jatropha curcas is a tropical species that has been recognized as a promising biodiesel plant. During 2018–2021, researchers at Forest College and Research Institute, Mettupalayam, elicited information on Jatropha’s biochemical characteristics, growth performance, variability, and association studies for biometric variables using five backcross (BC4F1) hybrid clones of Jatropha with a control variety TNMC 7. In terms of seed yield, two hybrid clones, CJH 13 (1,218.60 g) and CJH 12 (1,034.40 g), outperformed the other hybrid clones. The seed oil content was higher in CJH 5 (34.19%). The seed oil content had moderate PCV (16.49%) and GCV (16.39%) values, as well as high heritability (99%) and genetic advance (33.56%) as a percentage of the mean. The number of fruits per bunch (0.845 and 0.850) and the number of bunches per branch (0.771 and 0.788) had significant positive phenotypic and genotypic correlations with seed yield, respectively. The iodine numbers, cetane numbers, and saponification values of all hybrid clones were acceptable and satisfactory and were in good compliance with Indian and international biodiesel standards.
Pooled resequencing of larvae and adults reveals genomic variations associated with Ostreid herpesvirus 1 resistance in the Pacific oyster Crassostrea gigas
Authors: Yao Shanshan , Li Li , Guan Xudong , He Yan , Jouaux Aude , Xu Fei , Guo Ximing , Zhang Guofan , Zhang Linlin
Published: August 2022

The Ostreid herpesvirus 1 (OsHV-1) is a lethal pathogen of the Pacific oyster (Crassostrea gigas), an important aquaculture species. To understand the genetic architecture of the defense against the pathogen, we studied genomic variations associated with herpesvirus-caused mortalities by pooled whole-genome resequencing of before and after-mortality larval samples as well as dead and surviving adults from a viral challenge. Analysis of the resequencing data identified 5,271 SNPs and 1,883 genomic regions covering 3,111 genes in larvae, and 18,692 SNPs and 28,314 regions covering 4,863 genes in adults that were significantly associated with herpesvirus-caused mortalities. Only 1,653 of the implicated genes were shared by larvae and adults, suggesting that the antiviral response or resistance in larvae and adults involves different sets of genes or differentiated members of expanded gene families. Combined analyses with previous transcriptomic data from challenge experiments revealed that transcription of many mortality-associated genes was also significantly upregulated by herpesvirus infection confirming their importance in antiviral response. Key immune response genes especially those encoding antiviral receptors such as TLRs and RLRs displayed strong association between variation in regulatory region and herpesvirus-caused mortality, suggesting they may confer resistance through transcriptional modulation. These results point to previously undescribed genetic mechanisms for disease resistance at different developmental stages and provide candidate polymorphisms and genes that are valuable for understanding antiviral immune responses and breeding for herpesvirus resistance.
Integrative analyses of mRNA and microRNA expression profiles reveal the innate immune mechanism for the resistance to Vibrio parahaemolyticus infection in Epinephelus coioides
Authors: Qiao Xifeng , Lu Yuyou , Xu Jiachang , Deng Niuniu , Lai Wenjie , Wu Ziyi , Lin Haoran , Zhang Yong , Lu Danqi
Published: August 2022

Vibrio parahaemolyticus, as one of the main pathogens of marine vibriosis, has brought huge losses to aquaculture. However, the interaction mechanism between V. parahaemolyticus and Epinephelus coioides remains unclear. Moreover, there is a lack of comprehensive multi-omics analysis of the immune response of grouper spleen to V. parahaemolyticus. Herein, E. coioides was artificially injected with V. parahaemolyticus, and it was found that the mortality was 16.7% in the early stage of infection, and accompanied by obvious histopathological lesions in the spleen. Furthermore, 1586 differentially expressed genes were screened by mRNA-seq. KEGG analysis showed that genes were significantly enriched in immune-related pathways, Acute-phase immune response, Apoptosis, Complement system and Cytokine-cytokine receptor interaction. As for miRNA-seq analysis, a total of 55 significantly different miRNAs were identified. Further functional annotation analysis indicated that the target genes of differentially expressed miRNAs were enriched in three important pathways (Phosphatidylinositol signaling system, Lysosome and Focal adhesions). Through mRNA-miRNA integrated analysis, 1427 significant miRNA–mRNA pairs were obtained and “p53 signaling pathway”, “Intestinal immune network for IgA production” were considered as two crucial pathways. Finally, miR-144-y, miR-497-x, novel-m0459-5p, miR-7133-y, miR-378-y, novel-m0440-5p and novel-m0084-3p may be as key miRNAs to regulate immune signaling pathways via the miRNA-mRNA interaction network. The above results suggest that the mRNA-miRNA integrated analysis not only sheds new light on the molecular mechanisms underlying the interaction between host and V. parahaemolyticus but also provides valuable and new insights into resistance to vibrio infection.
Existence of viable Mycobacterium leprae in natural environment and its genetic profiling in a leprosy endemic region
Authors: Turankar Ravindra P. , Singh Vikram , Lavania Mallika , Singh Itu , Sengupta Utpal , Jadhav Rupendra S.
Published: August 2022

Introduction

Molecular epidemiology of leprosy is very important to study leprosy transmission dynamics and to enhance our understanding of leprosy in endemic areas by utilizing the molecular typing method. Nowadays our understanding of leprosy transmission dynamics has been refined by SNP typing and VNTR marker analysis of M. leprae strains.

Objective

This study was carried out to find out the presence of viable M. leprae in the soil and water samples from residing areas of leprosy patients staying in different blocks of Purulia district of West Bengal, understanding their genotypes and compared with that of M. leprae present in patients.

Material and methods

Slit-skin smear (SSS) samples (n=112) were collected from the active multibacillary leprosy patients from different blocks of leprosy endemic area. Soil samples (n=1060) and water samples (n=620) were collected from residing areas of leprosy patients. SNP subtyping was performed by PCR followed by sequencing. Multiplex PCR was performed using fifteen ML-VNTR loci and results were analysed.

Results

We observed high PCR positivity in soil samples (344 out of 1060; 32%) and water samples (140 out of 620; 23%). These PCR positive samples when further screened for viability, it was observed that 150 soil samples (44%) and 56 water samples (40%) showed presence of 16S rRNA. SNP typing of M. leprae revealed presence of predominantly type 1. SNP subtype 1D (83%) was most prevalent in all the blocks of Purulia followed by subtype 1C (15%) and subtype 1A (2%). SNP subtype 2F was noted in only one sample. SNP and VNTR combination showed presence of similar strain type in certain pockets of Purulia region which was responsible for transmission.

Conclusion

Presence of viable M. leprae in the environment, and presence of SNP Type 1 M. leprae in patients and environment suggests both environment and patients play a role in disease transmission.
Plankton Planet: A frugal, cooperative measure of aquatic life at the planetary scale
Authors: de Vargas Colomban , Le Bescot Noan , Pollina Thibaut , Henry Nicolas , Romac Sarah , Colin Sébastien , Haëntjens Nils , Carmichael Margaux , Berger Calixte , Le Guen David , Decelle Johan , Mahé Frédéric , Poulain Julie , Malpot Emmanuel , Beaumont Carole , Hardy Michel , Guiffant Damien , Probert Ian , Gruber David F. , Allen Andrew E. , Gorsky Gabriel , Follows Michael J. , Pochon Xavier , Troublé Romain , Cael B. B. , Lombard Fabien , Boss Emmanuel , Prakash Manu ,   the Plankton Planet core team
Published: August 2022

In every liter of seawater there are between 10 and 100 billion life forms, mostly invisible, called marine plankton or marine microbiome, which form the largest and most dynamic ecosystem on our planet, at the heart of global ecological and economic processes. While physical and chemical parameters of planktonic ecosystems are fairly well measured and modeled at the planetary scale, biological data are still scarce due to the extreme cost and relative inflexibility of the classical vessels and instruments used to explore marine biodiversity. Here we introduce ‘Plankton Planet’, an initiative whose goal is to engage the curiosity and creativity of researchers, makers, and mariners to (i) co-develop a new generation of cost-effective (frugal) universal scientific instrumentation to measure the genetic and morphological diversity of marine microbiomes in context, (ii) organize their systematic deployment through coastal or open ocean communities of sea-users/farers, to generate uniform plankton data across global and long-term spatio-temporal scales, and (iii) setup tools to flow the data without embargo into public and explorable databases. As proof-of-concept, we show how 20 crews of sailors were able to sample plankton biomass from the world surface ocean in a single year, generating the first seatizen-based, planetary dataset of marine plankton biodiversity based on DNA barcodes. The quality of this dataset is comparable to that generated by Tara Oceans and is not biased by the multiplication of samplers. The data unveil significant genetic novelty and can be used to explore the taxonomic and ecological diversity of plankton at both regional and global scales. This pilot project paves the way for construction of a miniaturized, modular, evolvable, affordable and open-source citizen field-platform that will allow systematic assessment of the eco/morpho/genetic variation of aquatic ecosystems and microbiomes across the dimensions of the Earth system.
The transcriptional regulator CtrA controls gene expression in Alphaproteobacteria phages: Evidence for a lytic deferment pathway
Authors: Mascolo Elia , Adhikari Satish , Caruso Steven M. , deCarvalho Tagide , Folch Salvador Anna , Serra-Sagristà Joan , Young Ry , Erill Ivan , Curtis Patrick D.
Published: August 2022

Pilitropic and flagellotropic phages adsorb to bacterial pili and flagella. These phages have long been used to investigate multiple aspects of bacterial physiology, such as the cell cycle control in the Caulobacterales. Targeting cellular appendages for adsorption effectively constrains the population of infectable hosts, suggesting that phages may have developed strategies to maximize their infective yield. Brevundimonas phage vB_BsubS-Delta is a recently characterized pilitropic phage infecting the Alphaproteobacterium Brevundimonas subvibrioides. Like other Caulobacterales, B. subvibrioides divides asymmetrically and its cell cycle is governed by multiple transcriptional regulators, including the master regulator CtrA. Genomic characterization of phage vB_BsubS-Delta identified the presence of a large intergenic region with an unusually high density of putative CtrA-binding sites. A systematic analysis of the positional distribution of predicted CtrA-binding sites in complete phage genomes reveals that the highly skewed distribution of CtrA-binding sites observed in vB_BsubS-Delta is an unequivocal genomic signature that extends to other pilli- and flagellotropic phages infecting the Alphaproteobacteria. Moreover, putative CtrA-binding sites in these phage genomes localize preferentially to promoter regions and have higher scores than those detected in other phage genomes. Phylogenetic and comparative genomics analyses show that this genomic signature has evolved independently in several phage lineages, suggesting that it provides an adaptive advantage to pili/flagellotropic phages infecting the Alphaproteobacteria. Experimental results demonstrate that CtrA binds to predicted CtrA-binding sites in promoter regions and that it regulates transcription of phage genes in unrelated Alphaproteobacteria-infecting phages. We propose that this focused distribution of CtrA-binding sites reflects a fundamental new aspect of phage infection, which we term lytic deferment. Under this novel paradigm, pili- and flagellotropic phages exploit the CtrA transduction pathway to monitor the host cell cycle state and synchronize lysis with the presence of infectable cells.
Antibacterial effect and mechanism of anthocyanin from Lycium ruthenicum Murr
Authors: Dong Yuhe , Yang Chunmiao , Zhong Wenting , Shu Yan , Zhang Yongze , Yang Dongsheng
Published: August 2022

The inhibitory effects of the anthocyanin obtained from Lycium ruthenicum Murr were tested against several food-borne pathogens were evaluated, such as Staphylococcus aureus (S. aureus), Escherichia coli (E. coli), Aspergillus niger and Penicillium sp. In general, anthocyanin had different antibacterial effect on different bacteria, and the best antibacterial effect on S. aureus, with minimal inhibitory concentration (MIC) of 3.125 mg/mL. Anthocyanin increased the surface hydrophobicity of S. aureus, discharged the intracellular K+, and reduced the total soluble protein, affecting protein synthesis. Fluorescent inverted microscope and flow cytometry (FCM) found a significant increase in fluorescence intensity and lethality relative to the control group, and the dead P3 region to 77.21%. The above suggested a correlation between the antibacterial mechanism of anthocyanin and cell membrane permeability integrity. Biofilm formation was evaluated by the crystal violet assay (CV), silver staining method and methyl thiazolyl tetrazolium (MTT). Scanning electron microscopy (SEM) showed that anthocyanins could change the structure of biofilm.
Plasma metabolomics analyses highlight the multifaceted effects of noise exposure and the diagnostic power of dysregulated metabolites for noise-induced hearing loss in steel workers
Authors: Zhang Xiuzhi , Li Ningning , Cui Yanan , Wu Hui , Jiao Jie , Yu Yue , Gu Guizhen , Chen Guoshun , Zhang Huanling , Yu Shanfa
Published: August 2022

Noise exposure can lead to various kinds of disorders. Noise-induced hearing loss (NIHL) is one of the leading disorders confusing the noise-exposed workers. It is essential to identify NIHL markers for its early diagnosis and new therapeutic targets for its treatment. In this study, a total of 90 plasma samples from 60 noise-exposed steel factory male workers (the noise group) with (NIHL group, n = 30) and without NIHL (non-NIHL group, n = 30) and 30 male controls without noise exposure (control group) were collected. Untargeted human plasma metabolomic profiles were determined with HPLC-MS/MS. The levels of the metabolites in the samples were normalized to total peak intensity, and the processed data were subjected to multivariate data analysis. The Wilcoxon test and orthogonal partial least square-discriminant analysis (OPLS-DA) were performed. With the threshold of p < 0.05 and the variable importance of projection (VIP) value >1, 469 differential plasma metabolites associated with noise exposure (DMs-NE) were identified, and their associated 58 KEGG pathways were indicated. In total, 33 differential metabolites associated with NIHL (DMs-NIHL) and their associated 12 KEGG pathways were identified. There were six common pathways associated with both noise exposure and NIHL. Through multiple comparisons, seven metabolites were shown to be dysregulated in the NIHL group compared with the other two groups. Through LASSO regression analysis, two risk models were constructed for NIHL status predication which could discriminate NIHL from non-NIHL workers with the area under the curve (AUC) values of 0.840 and 0.872, respectively, indicating their efficiency in NIHL diagnosis. To validate the results of the metabolomics, cochlear gene expression comparisons between susceptible and resistant mice in the GSE8342 dataset from Gene Expression Omnibus (GEO) were performed. The immune response and cell death-related processes were highlighted for their close relations with noise exposure, indicating their critical roles in noise-induced disorders. We concluded that there was a significant difference between the metabolite’s profiles between NIHL cases and non-NIHL individuals. Noise exposure could lead to dysregulations of a variety of biological pathways, especially immune response and cell death-related processes. Our results might provide new clues for noise exposure studies and NIHL diagnosis.
Transcriptome changes in DM1 patients’ tissues are governed by the RNA interference pathway
Authors: Braun Maya , Shoshani Shachar , Tabach Yuval
Published: August 2022

Myotonic dystrophy type 1 (DM1) is a multisystemic disease caused by pathogenic expansions of CTG repeats. The expanded repeats are transcribed to long RNA and induce cellular toxicity. Recent studies suggest that the CUG repeats are processed by the RNA interference (RNAi) pathway to generate small interfering repeated RNA (siRNA). However, the effects of the CTG repeat-derived siRNAs remain unclear. We hypothesize that the RNAi machinery in DM1 patients generates distinct gene expression patterns that determine the disease phenotype in the individual patient. The abundance of genes with complementary repeats that are targeted by siRNAs in each tissue determines the way that the tissue is affected in DM1. We integrated and analyzed published transcriptome data from muscle, heart, and brain biopsies of DM1 patients, and revealed shared, characteristic changes that correlated with disease phenotype. These signatures are overrepresented by genes and transcription factors bearing endogenous CTG/CAG repeats and are governed by aberrant activity of the RNAi machinery, miRNAs, and a specific gain-of-function of the CTG repeats. Computational analysis of the DM1 transcriptome enhances our understanding of the complex pathophysiology of the disease and may reveal a path for cure.
Parallel import mechanisms ensure the robust nuclear localization of actin in Drosophila
Authors: Borkúti Péter , Kristó Ildikó , Szabó Anikó , Bajusz Csaba , Kovács Zoltán , Réthi-Nagy Zsuzsánna , Lipinszki Zoltán , Lukácsovich Tamás , Bogdan Sven , Vilmos Péter
Published: August 2022

Actin, as an ancient and fundamental protein, participates in various cytoplasmic as well as nuclear functions in eukaryotic cells. Based on its manifold tasks in the nucleus, it is a reasonable assumption that the nuclear presence of actin is essential for the cell, and consequently, its nuclear localization is ensured by a robust system. However, today only a single nuclear import and a single nuclear export pathway is known which maintain the dynamic balance between cytoplasmic and nuclear actin pools. In our work, we tested the robustness of the nuclear import of actin, and investigated whether the perturbations of nuclear localization affect the viability of the whole organism. For this aim, we generated a genetic system in Drosophila, in which we rescued the lethal phenotype of the null mutation of the Actin5C gene with transgenes that express different derivatives of actin, including a Nuclear Export Signal (NES)-tagged isoform which ensures forced nuclear export of the protein. We also disrupted the SUMOylation site of actin, suggested earlier to be responsible for nuclear retention, and eliminated the activity of the single nuclear import factor dedicated to actin. We found that, individually, none of the above mentioned manipulations led to a notable reduction in nuclear actin levels and thus, fully rescued lethality. However, the NES tagging of actin, together with the knock out of its importin, significantly reduced the amount of nuclear actin and induced lethality, confirming that the presence of actin in the nucleus is essential, and thereby, over-secured. Supporting this, we identified novel nuclear importins specific to actin, which sheds light on the mechanism behind the robustness of nuclear localization of actin, and supports the idea of essentiality of its nuclear functions.
Case Report: Thromboelastography for uremic thrombocytopathy in a patient with COVID-19
Authors: Kannan Lakshmi , Raj Rishi
Published: August 2022

Uremia causes several biochemical and physiological impairments that result in the accumulation of toxins with multiple clinical effects. Bleeding is one of the most common complications of acute and chronic renal failure. The pathogenesis of uremic bleeding is multifactorial, of which uremic thrombocytopathy is the most described clinically. Various tests have been used to evaluate bleeding diathesis in these patients including bleeding time, prothrombin time, activated partial thromboplastin time, and international normalized ratio, but there are only a few studies that use thromboelastography as a point-of-care test to identify platelet dysfunction. In addition, COVID-19 increases hemorrhagic complications due to platelet dysfunction or hemostasis exhaustion. COVID-19 could also potentially cause platelet dysfunction as a secondary consequence of acute kidney injury. There are only a few studies reporting the use of thromboelastography in COVID-19–induced hypercoagulability, but not in diagnosing or managing platelet-related abnormalities. We present a patient with COVID-19 who developed acute kidney injury in the hospital and retroperitoneal hemorrhage from uremic platelet dysfunction. We used point-of-care thromboelastography with platelet mapping to determine uremic platelet dysfunction.
Enlarged perivascular spaces are linked to freezing of gait in Parkinson's disease
Authors: Lin Fangju , Yang Baoling , Chen Ying , Zhao Wei , Li Binghan , Jia Weihua
Published: August 2022

Objective

Freezing of gait (FOG) is one of common and disabling gait impairments of Parkinson's disease (PD). White matter hyperintensity (WMH) and lacunes, as common manifestations of cerebral small vessel diseases (CSVD), have been reported to be associated with gait function in PD patients. However, in the cases with FOG which present with extensive WMH or lacunes, it actually is difficult to distinguish pure PD pathology from vascular origin or combined effects. So far little is known about the correlation between enlarged perivascular space (PVS) and FOG in PD patients. This study aims to explore the role of enlarged PVS in FOG in PD patients.

Methods

A total of 95 patients with PD in the absence of obvious WMH and lacunes were included in our study, which were divided into PD-FOG (+) group and PD-FOG (-) group. Demographic and clinical data were investigated. Enlarged PVS in the centrum semiovale (CSO) and basal ganglia (BG) were assessed. The association between enlarged PVS and FOG in patients with PD was analyzed using the multivariate models and the Spearman's correlation.

Results

There were 36 PD patients grouped into PD-FOG (+) (37.9%), with an older age, a longer PD disease duration, and larger numbers of enlarged PVS in CSO and BG compared with PD-FOG (-) group. The highest-severity degree of enlarged PVS burden in CSO was independently associated with FOG in patients with PD [adjusted odds ratio (OR), 3.869; p = 0.022 in multivariable model]. The percentages of FOG case increased accompanied by the aggravation of enlarged PVS located in CSO. The grade and count of enlarged PVS in CSO and BG both correlated with FOGQ score in PD patients.

Conclusion

Enlarged PVS, particularly in CSO, are associated with FOG in patients with PD, which provides a novel perspective for the mechanisms of FOG in PD.
Development of semicircular canal occlusion
Authors: Fei Su , Guangfei Li , Jie Meng , Yiling Gao , Mingjing Cai , Qingxiang Zhang , Wei Meng , Shuangba He
Published: August 2022

Surgical treatment of vertigo is performed with in-depth study of inner ear diseases. Achieving an effective control of vertigo symptoms while reducing damage to hearing and reducing surgical complications is the principle followed by scholars studying surgical modalities. Semicircular canal occlusion is aimed at treatment of partial peripheral vertigo disease and has attracted the attention of scholars because of the above advantages. This article provides a review of the origins of semicircular canal occlusion, related basic research, clinical applications, and the effects of surgery on vestibular and hearing function.
Pre-harvest and post-harvest farmer experiences and practices in five maize growing regions in Ghana
Authors: Darfour Bernard , Rosentrater Kurt A.
Published: August 2022

Maize is a major staple crop mainly produced by smallholder farmers in developing nations. Grain losses happen in Sub-Saharan Africa, and therefore the objective of this study was to assess the different kinds of pre-harvest and post-harvest losses that maize farmers in Ghana encounter. The storage practices, and farmers' awareness and knowledge of mycotoxin contamination in maize were also assessed. The study area had five regions, and three districts per region. The study sites were selected purposefully because of the prior knowledge of farmers on maize production. A semi-structured questionnaire was used to collect the data, and a purposive sampling technique was used to select 75 maize farmers for the interview. The male maize farmers were many compared to females. Over 70% of farmers were at least 40 years. Over 50% of farmers had basic education except those in the northern region. Grain yields were generally low, and at least 60% of farmers experienced post-harvest loss. The period of grain storage and the storage techniques were the prerogatives of the farmers but largely dependent on farmers' financial status. Farmers basically used synthetic chemicals, and a few of the farmers decided to use plant materials during grain treatment.
The effect of race/ethnicity on cancer-specific mortality after salvage radical prostatectomy
Authors: Wenzel Mike , Würnschimmel Christoph , Nocera Luigi , Colla Ruvolo Claudia , Hoeh Benedikt , Tian Zhe , Shariat Shahrokh F. , Saad Fred , Briganti Alberto , Graefen Markus , Preisser Felix , Becker Andreas , Mandel Philipp , Chun Felix K. H. , Karakiewicz Pierre I.
Published: August 2022

Background

To test the effect of race/ethnicity on cancer-specific mortality (CSM) after salvage radical prostatectomy (SRP).

Material and methods

We relied on the Surveillance, Epidemiology and End Results database (SEER, 2004–2016) to identify SRP patients of all race/ethnicity background. Univariate and multivariate Cox regression models addressed CSM according to race/ethnicity.

Results

Of 426 assessable SRP patients, Caucasians accounted for 299 (69.9%) vs. 68 (15.9%) African-Americans vs. 39 (9.1%) Hispanics vs. 20 (4.7%) Asians. At diagnosis, African-Americans (64 years) were younger than Caucasians (66 years), but not younger than Hispanics (66 years) and Asians (67 years). PSA at diagnosis was significantly higher in African-Americans (13.2 ng/ml), Hispanics (13.0 ng/ml), and Asians (12.2 ng/ml) than in Caucasians (7.8 ng/ml, p = 0.01). Moreover, the distribution of African-Americans (10.3%–36.6%) and Hispanics (0%–15.8%) varied according to SEER region. The 10-year CSM was 46.5% in African-Americans vs. 22.4% in Caucasians vs. 15.4% in Hispanics vs. 15.0% in Asians. After multivariate adjustment (for age, clinical T stage, lymph node dissection status), African-American race/ethnicity was an independent predictor of higher CSM (HR: 2.2, p < 0.01), but not Hispanic or Asian race/ethnicity. The independent effect of African-American race/ethnicity did not persist after further adjustment for PSA.

Conclusion

African-Americans treated with SRP are at higher risk of CSM than other racial/ethnic groups and also exhibited the highest baseline PSA. The independent effect of African-American race/ethnicity on higher CSM no longer applies after PSA adjustment since higher PSA represents a distinguishing feature in African-American patients.
Exploring pathological signatures for predicting the recurrence of early-stage hepatocellular carcinoma based on deep learning
Authors: Qu Wei-Feng , Tian Meng-Xin , Qiu Jing-Tao , Guo Yu-Cheng , Tao Chen-Yang , Liu Wei-Ren , Tang Zheng , Qian Kun , Wang Zhi-Xun , Li Xiao-Yu , Hu Wei-An , Zhou Jian , Fan Jia , Zou Hao , Hou Ying-Yong , Shi Ying-Hong
Published: August 2022

Background

Postoperative recurrence impedes the curability of early-stage hepatocellular carcinoma (E-HCC). We aimed to establish a novel recurrence-related pathological prognosticator with artificial intelligence, and investigate the relationship between pathological features and the local immunological microenvironment.

Methods

A total of 576 whole-slide images (WSIs) were collected from 547 patients with E-HCC in the Zhongshan cohort, which was randomly divided into a training cohort and a validation cohort. The external validation cohort comprised 147 Tumor Node Metastasis (TNM) stage I patients from The Cancer Genome Atlas (TCGA) database. Six types of HCC tissues were identified by a weakly supervised convolutional neural network. A recurrence-related histological score (HS) was constructed and validated. The correlation between immune microenvironment and HS was evaluated through extensive immunohistochemical data.

Results

The overall classification accuracy of HCC tissues was 94.17%. The C-indexes of HS in the training, validation and TCGA cohorts were 0.804, 0.739 and 0.708, respectively. Multivariate analysis showed that the HS (HR= 4.05, 95% CI: 3.40-4.84) was an independent predictor for recurrence-free survival. Patients in HS high-risk group had elevated preoperative alpha-fetoprotein levels, poorer tumor differentiation and a higher proportion of microvascular invasion. The immunohistochemistry data linked the HS to local immune cell infiltration. HS was positively correlated with the expression level of peritumoral CD14+ cells (p= 0.013), and negatively with the intratumoral CD8+ cells (p< 0.001).

Conclusions

The study established a novel histological score that predicted short-term and long-term recurrence for E-HCCs using deep learning, which could facilitate clinical decision making in recurrence prediction and management.
Predicting recurrence and metastasis risk of endometrial carcinoma via prognostic signatures identified from multi-omics data
Authors: Li Ling , Qiu Wenjing , Lin Liang , Liu Jinyang , Shi Xiaoli , Shi Yi
Published: August 2022

Objectives

Endometrial carcinoma (EC) is one of the three major gynecological malignancies, in which 15% - 20% patients will have recurrence and metastasis. Though there are many studies on the prognosis on this cancer, the performances of existing models evaluating the risk of its recurrence and metastasis are yet to be improved. In addition, a comprehensive multi-omics analyses on the prognostic signatures of EC are on demand. In this study, we aimed to construct a relatively stable and reliable model for predicting recurrence and metastasis of EC. This will help determine the risk level of patients and choose appropriate adjuvant therapy, thereby avoiding improper treatment, and improving the prognosis of patients.

Methods

The mRNA, microRNA (miRNA), long non-coding RNA (lncRNA), copy number variation (CNV) data and clinical information of patients with EC were downloaded from The Cancer Genome Atlas (TCGA). Differential expression analyses were performed between the recurrence or metastasis group and the non-recurrence/metastasis group. Then, we screened potential prognostic markers from the four kinds of omics data respectively and established prediction models using three classifiers.

Results

We achieved differential expressed mRNAs, lncRNAs, miRNAs and CNVs between the two groups. According to feature selection scores by the random forest algorithm, 275 CNV features, 50 lncRNA features, 150 miRNA features and 150 mRNA features were selected, respectively. And the prediction model constructed by the features of lncRNA data using random forest method showed the best performance, with an area under the curve of 0.763, and an accuracy of 0.819 under 10-fold cross-validation.

Conclusion

We developed a computational model using omics information, which is able to predicting recurrence and metastasis risk of EC accurately.
Monocytes acquire prostate cancer specific chromatin conformations upon indirect co-culture with prostate cancer cells
Authors: Alshaker Heba , Hunter Ewan , Salter Matthew , Ramadass Aroul , Westra Willem , Winkler Mathias , Green Jayne , Akoulitchev Alexandre , Pchejetski Dmitri
Published: August 2022

Background

Three-dimensional chromosome loop conformations are powerful regulators of gene expression. These chromosome conformations can be detected both in tumour and in circulating cells and have significant disease biomarker potential. We have recently detected specific chromosome conformations in circulating cells of patients with prostate cancer (PCa) which were similar to ones found in their primary tumours, however, the possibility of horizontal transfer of chromosome conformations was not studied previously.

Methods

Human monocytes (U937) were co-cultured in Boyden chambers through 0.4 uM membrane with or without PC-3 human PCa cells or their conditioned media and a custom DNA microarray for 900,000 chromosomal loops covering all coding loci and non-coding RNA genes was performed on each part of the co-culture system.

Results

We have detected 684 PC-3 cell-specific chromosome conformations across the whole genome that were absent in naïve monocytes but appeared in monocytes co-cultured with PC-3 cells or with PC-3-conditioned media. Comparing PC3-specific conformations to the ones we have previously detected in systemic circulation of high-risk PCa patients revealed 9 positive loops present in both settings.

Conclusions

Our results demonstrate for the first time a proof of concept for horizontal transfer of chromosome conformations without direct cell-cell contact. This carries high clinical relevance as we have previously observed chromatin conformations in circulating cells of patients with melanoma and PCa similar to ones in their primary tumours. These changes can be used as highly specific biomarkers for diagnosis and prognosis. Further studies are required to elucidate the specific mechanism of chromosome conformations transfer and its clinical significance in particular diseases.
A correlation between Magnetic Resonance Spectroscopy (1-H MRS) and the neurodevelopment of two-year-olds born preterm in an EPIRMEX cohort study
Authors: Gire Catherine , Berbis Julie , Dequin Marion , Marret Stéphane , Muller Jean-Baptiste , Saliba Elie , Tosello Barthélémy
Published: August 2022

Background

Preterm infants are at risk of neurodevelopmental impairments. At present, proton magnetic resonance spectroscopy (1H-MRS) is currently used to evaluate brain metabolites in asphyxiated term infants. The purpose of this study was to identify in the preterm EPIRMEX cohort any correlations between (1H-MRS) metabolites ratio at term equivalent age (TEA) and neurodevelopmental outcomes at 2 years.

Methods

Our study included EPIRMEX eligible patients who were very preterm infants (gestational age at birth ≤32 weeks) and who underwent a brain MRI at TEA and 1H-MRS using a monovoxel technique. The volumes of interest (VOI) were periventricular white matter posterior area and basal ganglia. The ratio of N Acetyl Aspartate (NAA) to Cho (Choline), NAA to Cr (creatine), Cho to Cr, and Lac (Lactate) to Cr were measured. Neurodevelopment was assessed at 24 months TEA with ASQ (Ages and Stages Questionnaire).

Results

A total of 69 very preterm infants had a 1H-MRS at TEA. In white matter there was a significant correlation between a reduction in the NAA/Cho ratio and a total ASQ and/or abnormal communication score, and an increase in the Lac/Cr ratio and an abnormality of fine motor skills. In the gray nuclei there was a trend correlation between the reduction in the NAA/Cho ratio and sociability disorders; and the increase in the Lac/Cr ratio and an anomaly in problem-solving.

Conclusions

Using NAA as a biomarker, the vulnerability of immature oligodendrocytes in preterm children at TEA was correlated to neurodevelopment at 2 years. Similarly, the presence of lactate at TEA was associated with abnormal neurodevelopment at 2 years in the preterm brain.
Bioactive natural products in COVID-19 therapy
Authors: Wang Zhonglei , Wang Ning , Yang Liyan , Song Xian-qing
Published: August 2022

The devastating COVID-19 pandemic has caused more than six million deaths worldwide during the last 2 years. Effective therapeutic agents are greatly needed, yet promising magic bullets still do not exist. Numerous natural products (cordycepin, gallinamide A, plitidepsin, telocinobufagin, and tylophorine) have been widely studied and play a potential function in treating COVID-19. In this paper, we reviewed published studies (from May 2021 to April 2022) relating closely to bioactive natural products (isolated from medicinal plants, animals products, and marine organisms) in COVID-19 therapyin vitroto provide some essential guidance for anti-SARS-CoV-2 drug research and development.
The evaluation of ADME and pharmacokinetic properties of decoquinate derivatives for the treatment of malaria
Authors: Watson Daniel J. , Laing Lizahn , Beteck Richard M. , Gibhard Liezl , Haynes Richard K. , Wiesner Lubbe
Published: August 2022

The emergence of Plasmodium falciparum (Pf) parasite strains tolerant of the artemisinin component and resistant to the other drug component in artemisinin combination therapies (ACTs) used for treatment now markedly complicates malaria control. Thus, development of new combination therapies are urgently required. For the non-artemisinin component, the quinolone ester decoquinate (DQ) that possesses potent activities against blood stage Pf and acts on a distinct target, namely the Pf cytochrome bc1 complex, was first considered. However, DQ has poor drug properties including high lipophilicity and exceedingly poor aqueous solubility (0.06 μg/ml), rendering it difficult to administer. Thus, DQ was chemically modified to provide the secondary amide derivative RMB005 and the quinoline O-carbamate derivatives RMB059 and RMB060. The last possesses sub-nanomolar activities against multidrug resistant blood stages of Pf, and P. berghei sporozoite liver stages. Here we present the results of ADME analyses in vitro and pharmacokinetic analyses using C57BL/6 mice. The amide RMB005 had a maximum mean whole blood concentration of 0.49 ± 0.02 µM following oral administration; however, the area under the curve (AUC), elimination half-life (t1/2) and bioavailability (BA) were not significantly better than those of DQ. Surprisingly, the quinoline O-carbamates which can be recrystallized without decomposition were rapidly converted into DQ in human plasma and blood samples. The maximum concentrations of DQ reached after oral administration of RMB059 and RMB060 were 0.23 ± 0.05 and 0.11 ± 0.01 µM, the DQ elimination half-lives were 4.79 ± 1.66 and 4.66 ± 1.16 h, and the DQ clearance were 19.40 ± 3.14 and 21.50 ± 3.38 respectively. Under these assay conditions, the BA of DQ could not be calculated Overall although RMB059 and -060 are labile in physiological medium with respect to the DQ parent, the potential to apply these as prodrugs is apparent from the current data coupled with their ease of preparation.
The phytochemical properties, pharmacological effects and traditional uses of Actinidia eriantha Benth.: A review
Authors: Wang Shiyu , Gao Xiaoqi , Sun Qingmei , Zhu Yichun , Qin Luping , Zhu Bo
Published: August 2022

Actinidia eriantha Benth. (Called Maohuamihoutao in China) is a plant that has been utilized as a heat-clearing drug in She ethnic minority group for a long time in China. Specifically, it has been involved in the treatment of stomach cancer, colon cancer, cirrhosis with ascites, chronic hepatitis, leukemia, rectal prolapse, hernia and uterine prolapse. Pharmacological research provides partial evidence for the traditional use of A. eriantha and might have demonstrated the folk utilization of A. eriantha to combat many cancers. Crude extracts and relatively pure components of A. eriantha possess a variety of pharmacological activities, including anti-cancer, immunoregulatory, anti-angiogenic, neuroprotective, anti-inflammatory, and antioxidant activities. In addition, over 104 chemical substances have been determined from A. eriantha, involving terpenoids, alcohols, phenolics, aldehydes, organic acids, flavonoids glycosides, ketones, and glucoside. The existing literature reveals that a large proportion of the therapeutic effects of A. eriantha were rendered by the polysaccharides. However, the mechanisms of action and the structure-function correlations of these compounds, as well as the synergistic and antagonistic effects between them, need to be investigated further. Therefore, we propose that future studies on A. eriantha should focus on comprehensively assessing its medicinal quality, exploring its multi-target nature using network pharmacology approaches, and evaluating its long-term toxicity and efficacy in vivo.