bluuebunny/crossref_metadata_2025 huggingface dataset:
Artificial Intelligence Assisted Topographic Mapping System for Endoscopic Submucosal Dissection Specimens
Authors: Xiao Yu , Song Zhigang , Zou Shuangmei , You Yan , Cui Jie , Wang Shuhao , Ku Calvin , Wu Xi , Xue Xiaowei , Han Wenqi , Zhou Weixun
Published: June 2022

Background

Endoscopic submucosal dissection (ESD), a minimally invasive surgery used to treat early gastrointestinal malignancies, has been widely embraced around the world. The gross reconstruction of ESD specimens can facilitate a more precise pathological diagnosis and allow endoscopists to explore lesions thoroughly. The traditional method of mapping is time-consuming and inaccurate. We aim to design a topographic mapping system via artificial intelligence to perform the job automatically.

Methods

The topographic mapping system was built using computer vision techniques. We enrolled 23 ESD cases at the Peking Union Medical College Hospital from September to November 2019. The reconstruction maps were created for each case using both the traditional approach and the system.

Results

Using the system, the time saved per case ranges from 34 to 3,336 s. Two approaches revealed no significant variations in the shape, size, or tumor area.

Conclusion

We developed an AI-assisted system that would help pathologists complete the ESD topographic mapping process rapidly and accurately.
Effects of Early Bedside Cycle Exercise on Gastrointestinal Function in Intensive Care Unit Patients Receiving Mechanical Ventilation
Authors: Yu Tingting , Cai Fuliang , Jiang Rong
Published: June 2022

Background

A prolonged stay in the intensive care unit (ICU) is associated with gastrointestinal failure, which may have a destructive effect on functional status within 1 year after hospital discharge. The aim was to investigate the effects of a daily exercise session, using a bedside cycle ergometer, on gastrointestinal functions, such as diarrhea, gastric retention, and vomiting, in patients with severe pneumonia who received mechanical ventilation (MV).

Methods

The study was a randomized controlled trial, and its setting was the ICU of a tertiary hospital in Eastern China. A total of 102 critically ill patients who received MV were recruited only when their cardiorespiratory function was deemed stable to perform a bedside cycling exercise. Those patients were expected to spend a minimum of 7 days in the ICU. All subjects received respiratory physiotherapy and performed a daily standardized passive or active motion session of their limbs. The patients were randomized into two groups, namely, the treatment group, which were administered passive or active leg exercise intervention for 20 min/day using a bedside ergometer, and the control group, which did not. Gastrointestinal (GI) functions and the nutritional status of both groups were evaluated on the first, fourth, and seventh days of training and at discharge.

Results

During the 7 days of the study, the number of patients with diarrhea in the treatment group was significantly lower than that in the control group. In contrast, there were significantly more patients in the treatment group with increased bowel sounds (P < 0.05). However, there was no significant difference in the number of patients with vomiting and gastric retention between these two groups. Moreover, when the patients were discharged from the hospital, the albumin level and lymphocyte count were significantly higher in the treatment group (P < 0.05). In addition, the number of invasive ventilation days in the treatment group was less than that in the control group (P < 0.05). While the ICU length of stay and the total hospitalization time were not significantly different between the two groups.

Conclusion

Early exercise training in critical ICU survivors who received MV enhanced the recovery of gastrointestinal functions and improved the patient’s nutrition status at hospital discharge.
Severe Thrombocytopenia Caused by Vancomycin in the Intensive Care Unit: A Case Report
Authors: Li Xiao-xiao , Wang Guan-ru , Li Chao , He Na , Yao Peng , Cheng Yin-chu , Wang Chu-hui , Ge Qing-gang , Yi Min , Wang Zong-yu , Shi Lu-wen , Zhao Rong-sheng
Published: June 2022

Thrombocytopenia can cause substantial morbidity and mortality in critically ill patients. There are multiple etiology factors and various mechanisms associated with thrombocytopenia, of which drug-induced thrombocytopenia (DITP) deserves attention. Herein, we describe a case of severe thrombocytopenia during intensive care unit (ICU) hospitalization that was likely to be associated with vancomycin. By revealing the process of identifying this case of DITP and reviewing relevant clinical studies, a risk alert of vancomycin-related severe hematotoxicity should be considered.
COVID-Net CXR-2: An Enhanced Deep Convolutional Neural Network Design for Detection of COVID-19 Cases From Chest X-ray Images
Authors: Pavlova Maya , Terhljan Naomi , Chung Audrey G. , Zhao Andy , Surana Siddharth , Aboutalebi Hossein , Gunraj Hayden , Sabri Ali , Alaref Amer , Wong Alexander
Published: June 2022

As the COVID-19 pandemic devastates globally, the use of chest X-ray (CXR) imaging as a complimentary screening strategy to RT-PCR testing continues to grow given its routine clinical use for respiratory complaint. As part of the COVID-Net open source initiative, we introduce COVID-Net CXR-2, an enhanced deep convolutional neural network design for COVID-19 detection from CXR images built using a greater quantity and diversity of patients than the original COVID-Net. We also introduce a new benchmark dataset composed of 19,203 CXR images from a multinational cohort of 16,656 patients from at least 51 countries, making it the largest, most diverse COVID-19 CXR dataset in open access form. The COVID-Net CXR-2 network achieves sensitivity and positive predictive value of 95.5 and 97.0%, respectively, and was audited in a transparent and responsible manner. Explainability-driven performance validation was used during auditing to gain deeper insights in its decision-making behavior and to ensure clinically relevant factors are leveraged for improving trust in its usage. Radiologist validation was also conducted, where select cases were reviewed and reported on by two board-certified radiologists with over 10 and 19 years of experience, respectively, and showed that the critical factors leveraged by COVID-Net CXR-2 are consistent with radiologist interpretations.
A Novel Phenotype of the Factor 5 Gene Mutation (Homozygote Met1736Val and Heterozygote Asp68His) Is Associated With Moderate Factor V Deficiency
Authors: Chang Yueh-Shih , Lan Yi-Cheng , Chen Ya-Jyun , Huang Jen-Seng , Yang Chia-Ning , Huang Chi-Ying F. , Yeh Kun-Yun
Published: June 2022

Background

Factor V (FV) deficiency is a rare disease, with a low incidence rate in Asia. Therefore, the F5 mutation in the Taiwanese population is poorly understood.

Methods

A Chinese family with FV deficiency was included, and the patient and his family members underwent mutation analysis. Then, patients from Keelung City (Taiwan) were screened for F5 polymorphism; the Chang Gung Human Database was used to determine single-nucleotide variants in the non-FV-deficient patient population.

Results

Eight mutation sites on the F5 gene locus, including exon 16 homozygote Met1736Val and seven heterozygous mutations, including Asp68His, were found. Moreover, Met1736Val was found to be the dominant mutation in people living in the Taiwan community, and this result was compared with the records of the Chang Gung Human Database. The above-mentioned polymorphisms may result in a variable incidence of FV deficiency in Keelung City, thereby facilitating carrier diagnosis and prenatal diagnosis in most FV-deficient families.

Conclusion

The homozygote Met1736Val and the co-inheritance of the Asp68His F5 gene are unique and worthy of screening in FV-deficient patients.
Compartmentalization of Intrarenal Programmed Cell Death Protein 1-Ligand 1 and Its Receptor in Kidney Injury Related to Immune Checkpoint Inhibitor Nephrotoxicity
Authors: Tampe Désirée , Kopp Sarah Birgit , Baier Eva , Hakroush Samy , Tampe Björn
Published: June 2022

Background

Due to advances in cancer therapy, immune checkpoint inhibitors (ICIs) are new classes of drugs targeting programmed cell death protein 1-ligand 1 (PD-L1) or its receptor (PD-1) used in many cancer therapies. Acute interstitial nephritis (AIN) is a potential and deleterious immune-related adverse events (irAE) and the most common biopsy-proven diagnosis in ICI-related nephrotoxicity. AIN in patients receiving ICIs is was only seen in cases with tubular PD-L1 positivity, while PD-1 expression is limited to inflammatory cells and also observed in injured kidneys independent of ICI therapy. We have previously described that PD-L1 positivity can also be detected in glomerular and endothelial compartments. We here aimed to describe compartmentalization of renal PD-L1 expression specifically in injured kidneys with confirmed nephrotoxicity related to ICIs, its association with presence of PD-1, and clinical findings.

Methods

We included human kidney samples with AIN related to ICI therapy to describe PD-L1 and PD-1 expression localized to different renal compartments in association with clinical and laboratory parameters.

Results

We herein report compartmentalization of PD-L1 with tubular positivity in all cases, partially overlapping with glomerular and endothelial PD-L1 positivity. Furthermore, we provide evidence that tubular PD-L1 in ICI-related nephrotoxicity correlates with levels of C-reactive protein (CRP), while glomerular and endothelial PD-L1 positivity with lower serum levels of complement component C4. Interestingly, glomerular PD-L1 correlated with kidney function, while interstitial cell PD-1 positivity specifically with severity of kidney injury. Finally, we provide evidence for signaling pathways associated with intrarenal PD-L1/PD-1 expression.

Conclusion

Our findings implicate that that AIN related to ICI therapy requires presence of interstitial cells positive for PD-1, and that blocking PD-L1/PD-1 signaling may contribute to nephrotoxicity specifically related to these agents.
Recovery of High Quality Metagenome-Assembled Genomes From Full-Scale Activated Sludge Microbial Communities in a Tropical Climate Using Longitudinal Metagenome Sampling
Authors: Haryono Mindia A. S. , Law Ying Yu , Arumugam Krithika , Liew Larry C. -W. , Nguyen Thi Quynh Ngoc , Drautz-Moses Daniela I. , Schuster Stephan C. , Wuertz Stefan , Williams Rohan B. H.
Published: June 2022

The analysis of metagenome data based on the recovery of draft genomes (so called metagenome-assembled genomes, or MAG) has assumed an increasingly central role in microbiome research in recent years. Microbial communities underpinning the operation of wastewater treatment plants are particularly challenging targets for MAG analysis due to their high ecological complexity, and remain important, albeit understudied, microbial communities that play ssa key role in mediating interactions between human and natural ecosystems. Here we consider strategies for recovery of MAG sequence from time series metagenome surveys of full-scale activated sludge microbial communities. We generate MAG catalogs from this set of data using several different strategies, including the use of multiple individual sample assemblies, two variations on multi-sample co-assembly and a recently published MAG recovery workflow using deep learning. We obtain a total of just under 9,100 draft genomes, which collapse to around 3,100 non-redundant genomic clusters. We examine the strengths and weaknesses of these approaches in relation to MAG yield and quality, showing that co-assembly may offer advantages over single-sample assembly in the case of metagenome data obtained from closely sampled longitudinal study designs. Around 1,000 MAGs were candidates for being considered high quality, based on single-copy marker gene occurrence statistics, however only 58 MAG formally meet the MIMAG criteria for being high quality draft genomes. These findings carry broader broader implications for performing genome-resolved metagenomics on highly complex communities, the design and implementation of genome recoverability strategies, MAG decontamination and the search for better binning methodology.
Improving the Diagnostic Potential of Extracellular miRNAs Coupled to Multiomics Data by Exploiting the Power of Artificial Intelligence
Authors: Paolini Alessandro , Baldassarre Antonella , Bruno Stefania Paola , Felli Cristina , Muzi Chantal , Ahmadi Badi Sara , Siadat Seyed Davar , Sarshar Meysam , Masotti Andrea
Published: June 2022

In recent years, the clinical use of extracellular miRNAs as potential biomarkers of disease has increasingly emerged as a new and powerful tool. Serum, urine, saliva and stool contain miRNAs that can exert regulatory effects not only in surrounding epithelial cells but can also modulate bacterial gene expression, thus acting as a “master regulator” of many biological processes. We think that in order to have a holistic picture of the health status of an individual, we have to consider comprehensively many “omics” data, such as miRNAs profiling form different parts of the body and their interactions with cells and bacteria. Moreover, Artificial Intelligence (AI) and Machine Learning (ML) algorithms coupled to other multiomics data (i.e., big data) could help researchers to classify better the patient’s molecular characteristics and drive clinicians to identify personalized therapeutic strategies. Here, we highlight how the integration of “multiomic” data (i.e., miRNAs profiling and microbiota signature) with other omics (i.e., metabolomics, exposomics) analyzed by AI algorithms could improve the diagnostic and prognostic potential of specific biomarkers of disease.
Understanding the Variation of Bacteria in Response to Summertime Oxygen Depletion in Water Column of Bohai Sea
Authors: Wang Jing , Guo Xiaoxiao , Li Yanying , Song Guisheng , Zhao Liang
Published: June 2022

Aiming to reveal the variation in bacteria community under oxygen depletion formed every summer in water column of central Bohai Sea, a time-scenario sampling from June to August in 2018 at a 20-day interval along one inshore–offshore transect was settled. Water samples were collected at the surface, middle, and bottom layer and then analyzed by high-throughput sequencing targeting both 16S rRNA and nosZ genes. Compared to the surface and middle water, oxygen depletion occurred at bottom layer in August. In top two layers, Cyanobacteria dominated the bacterial community, whereas heterotrophic bacteria became dominant in bottom water of Bohai Sea. Based on the time scenario, distinct community separation was observed before (June and July) and after (August) oxygen depletion (p = 0.003). Vertically, strict stratification of nosZ gene was stably formed along 3 sampling layers. As a response to oxygen depletion, the diversity indices of both total bacteria (16S rRNA) and nosZ gene-encoded denitrification bacteria all increased, which indicated the intense potential of nitrogen lose when oxygen depleted. Dissolved oxygen (DO) was the key impacting factor on the community composition of total bacteria in June, whereas nutrients together with DO play the important roles in August for both total and denitrifying bacteria. The biotic impact was revealed further by strong correlations which showed between Cyanobacteria and heterotrophic bacteria in June from co-occurrence network analysis, which became weak in August when DO was depleted. This study discovered the variation in bacteria community in oxygen-depleted water with further effort to understand the potential role of denitrifying bacteria under oxygen depletion in Bohai Sea for the first time, which provided insights into the microbial response to the world-wide expanding oxygen depletion and their contributions in the ocean nitrogen cycling.
Coinfection of Two Mycoviruses Confers Hypovirulence and Reduces the Production of Mycotoxin Alternariol in Alternaria alternata f. sp. mali
Authors: Li Bo , Cao Yuhan , Ji Zixuan , Zhang Jingyi , Meng Xianglong , Dai Pengbo , Hu Tongle , Wang Shutong , Cao Keqiang , Wang Yanan
Published: June 2022

Alternaria leaf blotch caused by Alternaria alternata apple pathotype (Alternaria mali) is an important fungal disease that affects the production of apples worldwide. Mycoviruses harbored in plant pathogenic fungi can confer hypovirulence in their hosts and have attracted widespread attention as potential biocontrol tools. In this study, the coinfection of two mycoviruses, named A. alternata chrysovirus 1 strain QY2 (AaCV1-QY2) and A. alternata magoulivirus 1 (AaMV1), respectively, were isolated from A. alternata f. sp. mali strain QY21. Sequence analyses revealed that AaCV1-QY2 virus belonged to the genus Betachrysovirus and AaMV1 virus belonged to the genus Magoulvirus. These two mycoviruses were found to be associated with hypovirulence in A. alternata, among which AaCV1-QY2 might play a relatively leading role. Because the elimination of AaMV1 from the strain QY21 does not affect the hypovirulence trait, which indicates that the virus AaCV1-QY2 can independently induce slow growth and reduce host virulence. Moreover, the presence of viruses decreased the accumulation of the mycotoxin alternariol (AOH) in A. alternata strains. Intriguingly, AaCV1-QY2/AaMV1 mycoviruses can be horizontally transmitted to other A. alternata strains, and this coinfection can promote the interspecific transmission efficiency of AaCV1-QY2. To our knowledge, this study reports the first description of the member of Chrysovirus is related to hypovirulence in Alternaria spp. that facilitates the development of biocontrol measures of A. mali Roberts.
Bacteriophage-Resistant Mutant of Enterococcus faecalis Is Impaired in Biofilm Formation
Authors: Liu Jiazhen , Zhu Yanpeng , Li Yang , Lu Yuwen , Xiong Kun , Zhong Qiu , Wang Jing
Published: June 2022

Enterococcus faecalis is a common gram-positive non-spore-forming bacterium in nature and is found in the upper respiratory tract, intestine, and mouth of healthy people. E. faecalis is also one of the common pathogens causing nosocomial infections and is resistant to several antibiotics commonly used in practice. Thus, treating drug-resistant E. faecalis with antibiotics is challenging, and new approaches are needed. In this study, we isolated a bacteriophage named EFap02 that targets E. faecalis strain EFa02 from sewage at Southwest Hospital. Phage EFap02 belongs to the Siphoviridae family with a long tail of approximately 210 nm, and EFap02 can tolerate a strong acid and alkali environment and high temperature. Its receptor was identified as the capsular polysaccharide. Phage-resistant mutants had loss-of-function mutations in glycosyltransferase (gtr2), which is responsible for capsular polysaccharide biosynthesis, and this caused the loss of capsular polysaccharide and interruption of phage adsorption. Although phage-resistant mutants against EFap02 can be selected, such mutants are impaired in biofilm formation due to the loss of capsular polysaccharide, which compromises its virulence. Therefore, this study provided a detailed description of the E. faecalis EFap02 phage with the potential for treating E. faecalis infection.
Co-existence of Multiple Anaplasma Species and Variants in Ticks Feeding on Hedgehogs or Cattle Poses Potential Threats of Anaplasmosis to Humans and Livestock in Eastern China
Authors: Qi Yong , Ai Lele , Zhu Changqiang , Lu Yongfeng , Lv Ruichen , Mao Yingqing , Lu Nianhong , Tan Weilong
Published: June 2022

Background

Anaplasma spp., causative agents of anaplasmosis, pose significant a threat to public health and economic losses in livestock farming. Co-infections/co-existence of various Anaplasma spp. may facilitate pathogen interactions and the emergence of novel variants, represent potential dangers to public health and economic losses from livestock farming, and raise challenges of detection and diagnosis. The information regarding co-infection/co-existence of Anaplasma in their vector ticks and wild animals is limited and needs urgent investigation.

Methods

Wild hedgehogs and ticks from hedgehogs and cattle were collected from Jiangsu province, Eastern China, and DNA was extracted from hedgehog organs and tick homogenates. Various genera of species-specific polymerase chain reaction (PCR) or nested PCR amplifications targeting 16S ribosomal RNA (rrs), msp4, or groEL gene coupled with sequencing were conducted to identify Anaplasma spp.

Results

Anaplasma phagocytophilum (1, 0.6%), A. marginale (2, 1.2%), A. platys variants xyn10pt-1 (13, 7.7%), xyn21pt-2 (3, 1.8%), and xyn3pt-3 (3, 1.8%), A. bovis variant cwp72bo-1 (12, 7.1%), and a novel Candidatus Cryptoplasma sp. (1, 0.6%) were identified in 168 Haemaphysalis longicornis ticks from cattle. A. platys variant xyn10pt-1 (20, 11.4%) and A. bovis variants cwp72bo-1 (12, 6.9%) and cwp55-36bo-2 (1, 0.6%) were detected in 173 H. flava ticks from hedgehogs. However, only A. bovis variant cwp72bo-1 (15, 46.7%) was identified in 32 Erinaceus amurensis hedgehogs. Various co-existence combinations were found only in ticks.

Conclusion

The co-existence of various Anaplasma spp. and variants in H. flava and H. longicornis was detected for the first time in the world. The high infection rate of A. bovis in hedgehogs and its moderate infection rate in their parasitic ticks suggest that Er. amurensis hedgehog could be an important reservoir of A. bovis, rather than A. platys. Horizontal transmission of Anaplasma spp. may exist among different tick species via their shared hosts in the investigated area. This study provided epidemiological data that could be crucial for strategy development for early warning, prevention, and control of potential Anaplasma infections.
Architectural Features and Resistance to Food-Grade Disinfectants in Listeria monocytogenes-Pseudomonas spp. Dual-Species Biofilms
Authors: Rodríguez-López Pedro , Rodríguez-Herrera Juan José , López Cabo Marta
Published: June 2022

Listeria monocytogenes is considered a foodborne pathogen of serious concern capable of forming multispecies biofilms with other bacterial species, such as Pseudomonas spp., adhered onto stainless steel (SS) surfaces. In an attempt to link the biofilms’ morphology and resistance to biocides, dual-species biofilms of L. monocytogenes, in co-culture with either Pseudomonas aeruginosa, Pseudomonas fluorescens, or Pseudomonas putida, were assayed to ascertain their morphological characteristics and resistance toward benzalkonium chloride (BAC) and neutral electrolyzed water (NEW). Epifluorescence microscopy analysis revealed that each dual-species biofilm was distributed differently over the SS surface and that these differences were attributable to the presence of Pseudomonas spp. Confocal laser scanning microscopy (CLSM) assays demonstrated that despite these differences in distribution, all biofilms had similar maximum thicknesses. Along with this, colocalization analyses showed a strong trend of L. monocytogenes to share location within the biofilm with all Pseudomonas assayed whilst the latter distributed throughout the surface independently of the presence of L. monocytogenes, a fact that was especially evident in those biofilms in which cell clusters were present. Finally, a modified Gompertz equation was used to fit biofilms’ BAC and NEW dose-response data. Outcomes demonstrated that L. monocytogenes was less susceptible to BAC when co-cultured with P. aeruginosa or P. fluorescens, whereas susceptibility to NEW was reduced in all three dual-species biofilms, which can be attributable to both the mechanism of action of the biocide and the architectural features of each biofilm. Therefore, the results herein provided can be used to optimize already existing and develop novel target-specific sanitation treatments based on the mechanism of action of the biocide and the biofilms’ species composition and structure.
Does Shift in Vegetation Abundance After Nitrogen and Phosphorus Additions Play a Key Role in Regulating Fungal Community Structure in a Northern Peatland?
Authors: Cao Chenhao , Huang Jingjing , Ge Leming , Li Tong , Bu Zhao-Jun , Wang Shengzhong , Wang Zucheng , Liu Ziping , Liu Shasha , Wang Meng
Published: June 2022

Soil fungal communities are key players in biogeochemical processes of peatlands, which are important carbon stocks globally. Although it has been elucidated that fungi are susceptible to environmental changes, little is known about the intricate and interactive effect of long-term nitrogen (N) and phosphorus (P) enrichment on fungal community structure in northern peatlands. In this study, we compared a short- (2 years) with a long-term (10 years) fertilization experiment in a peatland complex in northeastern China to assess how N and/or P additions influence fungal community structure. The results showed that fungal community composition and diversity were altered by N addition, without a significant interactive effect with P addition. Not only the long-term but also the short-term nutrient addition could change the abundance of different plant functional types. However, there were no strong cascading effects on the fungal community in any of the fertilization experiments. Long-term nutrient addition showed a stronger effect on the relative abundance of different fungal functional guilds; an increase in the relative abundance of saprotrophs after fertilization did not jeopardize mycorrhizal fungi. Moreover, the decline in Sphagnum cover after long-term N addition did not parallel changes in the relative abundance of Sphagnum-associated fungi (Clavaria sphagnicola, Galerina tibiicystis, G. sphagnicola, and G. paludosa). Given that short- and long-term fertilization showed strongly contrasting effects on fungal community structure, our study highlights the necessity of assessing the long-term effects of nutrient enrichment on the association between vegetation and fungal community in peatland ecosystems. Future research priorities should emphasize the connection between the community structure of fungal functional guilds and their functionality, which is of paramount importance to better understand their influences on C storage in the face of uncertain N and P deposition regimes.
Multifunctional Roles of MicroRNAs in Schistosomiasis
Authors: Zhong Haoran , Jin Yamei
Published: June 2022

Schistosomiasis is a parasitic disease that is caused by helminths of the genus Schistosoma. The dioecious schistosomes mate and lay eggs after undergoing a complex life cycle. Schistosome eggs are mostly responsible for the transmission of schistosomiasis and chronic fibrotic disease induced by egg antigens is the main cause of the high mortality rate. Currently, chemotherapy with praziquantel (PZQ) is the only effective treatment against schistosomiasis, although the potential of drug resistance remains a concern. Hence, there is an urgent demand for new and effective strategies to combat schistosomiasis, which is the second most prevalent parasitic disease after malaria. MicroRNAs (miRNAs) are small non-coding RNAs that play pivotal regulatory roles in many organisms, including the development and sexual maturation of schistosomes. Thus, miRNAs are potential targets for treatment of schistosomiasis. Moreover, miRNAs can serve as multifunctional “nano-tools” for cross-species delivery in order to regulate host-parasite interactions. In this review, the multifunctional roles of miRNAs in the growth and development of schistosomes are discussed. The various regulatory functions of host-derived and worm-derived miRNAs on the progression of schistosomiasis are also thoroughly addressed, especially the promotional and inhibitory effects on schistosome-induced liver fibrosis. Additionally, the potential of miRNAs as biomarkers for the diagnosis and treatment of schistosomiasis is considered.
Comparison of Intestinal Microbes in Noninfectious Anterior Scleritis Patients With and Without Rheumatoid Arthritis
Authors: Li Mengyao , Yang Li , Zhao Liangliang , Bai Feng , Liu Xiaoli
Published: June 2022

We compared intestinal microbes in anterior noninfectious scleritis patients with and without rheumatoid arthritis. Active noninfectious anterior scleritis patients without other immune diseases (G group, 16 patients) or with active rheumatoid arthritis (GY group, seven patients) were included in this study. Eight age- and sex-matched healthy subjects served as controls (N group). DNA was extracted from fecal samples. The V3-V4 16S rDNA region was amplified and sequenced by high-throughput 16S rDNA analysis, and microbial contents were determined. A significant decrease in species richness in the GY group was revealed by α- and β-diversity analyses (p = 0.02 and p = 0.004, respectively). At the genus level, 14 enriched and 10 decreased microbes in the G group and 13 enriched and 18 decreased microbes in the GY group were identified. Among them, four microbes were enriched in both the G and GY groups, including Turicibacter, Romboutsia, Atopobium, and Coprobacillus. Although two microbes (Lachnospiraceae_ND3007_group and Eggerthella) exhibited similar tendencies in the G and GY groups, changes in these microbes were more significant in the GY group (p < 0.05). Interaction analysis showed that Intestinibacter, Romboutsia, and Turicibacter, which were enriched in both the G and GY groups, correlated positively with each other. In addition, nine microbes were decreased in the GY group, which demonstrates a potential protective role for these microbes in the pathogenesis of scleritis via interactions with each other.
Limited Impacts of Cover Cropping on Soil N-Cycling Microbial Communities of Long-Term Corn Monocultures
Authors: Kim Nakian , Riggins Chance W. , Zabaloy María C. , Rodriguez-Zas Sandra L. , Villamil María B.
Published: June 2022

Cover cropping (CC) is a promising in-field practice to mitigate soil health degradation and nitrogen (N) losses from excessive N fertilization. Soil N-cycling microbial communities are the fundamental drivers of these processes, but how they respond to CC under field conditions is poorly documented for typical agricultural systems. Our objective was to investigate this relationship for a long-term (36 years) corn [Zea mays L.] monocultures under three N fertilizer rates (N0, N202, and N269; kg N/ha), where a mixture of cereal rye [Secale cereale L.] and hairy vetch [Vicia villosa Roth.] was introduced for two consecutive years, using winter fallows as controls (BF). A 3 × 2 split-plot arrangement of N rates and CC treatments in a randomized complete block design with three replications was deployed. Soil chemical and physical properties and potential nitrification (PNR) and denitrification (PDR) rates were measured along with functional genes, including nifH, archaeal and bacterial amoA, nirK, nirS, and nosZ-I, sequenced in Illumina MiSeq system and quantified in high-throughput quantitative polymerase chain reaction (qPCR). The abundances of nifH, archaeal amoA, and nirS decreased with N fertilization (by 7.9, 4.8, and 38.9 times, respectively), and correlated positively with soil pH. Bacterial amoA increased by 2.4 times with CC within N269 and correlated positively with soil nitrate. CC increased the abundance of nirK by 1.5 times when fertilized. For both bacterial amoA and nirK, N202 and N269 did not differ from N0 within BF. Treatments had no significant effects on nosZ-I. The reported changes did not translate into differences in functionality as PNR and PDR did not respond to treatments. These results suggested that N fertilization disrupts the soil N-cycling communities of this system primarily through soil acidification and high nutrient availability. Two years of CC may not be enough to change the N-cycling communities that adapted to decades of disruption from N fertilization in corn monoculture. This is valuable primary information to understand the potentials and limitations of CC when introduced into long-term agricultural systems.
A Novel and Secure Pseudovirus Reporter System Based Assay for Neutralizing and Enhancing Antibody Assay Against Marburg Virus
Authors: Bi Jinhao , Wang Haojie , Pei Hongyan , Han Qiuxue , Feng Na , Wang Qi , Wang Xinyue , Wang Zhenshan , Wei Shimeng , Ge Liangpeng , Wu Meng , Liang Hao , Yang Songtao , Yan Feihu , Zhao Yongkun , Xia Xianzhu
Published: June 2022

Marburg virus (MARV) is one of the principal members of the filovirus family, which can cause fatal hemorrhagic fever in humans. There are currently no prophylactic and therapeutic drugs on the market, and the high pathogenicity and infectivity of MARV make its research highly dependent on biosafety level 4 conditions, severely hindering the development of vaccines and therapies. Therefore, the development of medicines, such as MARV serological diagnosis, vaccines, and therapeutic antibody drugs, urgently needs a safe, convenient, and biosafety level 2 detection method to measure the neutralizing activity of MARV antibodies. To this end, we report a neutralization assay relying on a Rabies virus (RABV) reverse genetic operating system. We constructed infectious clones carrying the eGFP reporter gene and the full length of the original unmodified MARV GP gene. Based on the critical parameters of phylogenetic analysis, recombinant viruses targeting representative strains in the two major MARV lineages were successfully rescued. These pseudoviruses are safe in mice, and their inability to infect cells after being neutralized by antibodies can be visualized under a fluorescence microscope. We tested the system using the neutralizing antibody MR191. MR191 can significantly block the infection of BSR cells with pseudovirus. We compared it with the traditional lentivirus-type pseudovirus system to verify the system’s credibility and obtained the same results as reported in the literature. In general, we have established a safe and visualized method for evaluating the neutralizing activity of MARV antibodies. Compared with traditional methods, it has the advantages of convenient operation, short cycle, and low cost. It is a candidate method that can replace actual viruses for a neutralization assay.
Xanthomonas oryzae Pv. oryzicola Response Regulator VemR Is Co-opted by the Sensor Kinase CheA for Phosphorylation of Multiple Pathogenicity-Related Targets
Authors: Cai Lulu , Ma Wenxiu , Zou Lifang , Xu Xiameng , Xu Zhengyin , Deng Chaoying , Qian Wei , Chen Xiaobin , Chen Gongyou
Published: June 2022

Two-component systems (TCSs) (cognate sensor histidine kinase/response regulator pair, HK/RR) play a crucial role in bacterial adaptation, survival, and productive colonization. An atypical orphan single-domain RR VemR was characterized by the non-vascular pathogen Xanthomonas oryzae pv. oryzicola (Xoc) is known to cause bacterial leaf streak (BLS) disease in rice. Xoc growth and pathogenicity in rice, motility, biosynthesis of extracellular polysaccharide (EPS), and the ability to trigger HR in non-host tobacco were severely compromised in the deletion mutant strain RΔvemR as compared to the wild-type strain RS105. Site-directed mutagenesis and phosphotransfer experiments revealed that the conserved aspartate (D56) residue within the stand-alone phosphoacceptor receiver (REC) domain is essential for phosphorelay and the regulatory activity of Xoc VemR. Yeast two-hybrid (Y2H) and co-immunoprecipitation (co-IP) data identified CheA as the HK co-opting the RR VemR for phosphorylation. Affinity proteomics identified several downstream VemR-interacting proteins, such as 2-oxoglutarate dehydrogenase (OGDH), DNA-binding RR SirA, flagellar basal body P-ring formation protein FlgA, Type 4a pilus retraction ATPase PilT, stress-inducible sensor HK BaeS, septum site-determining protein MinD, cytoskeletal protein CcmA, and Type III and VI secretion system proteins HrpG and Hcp, respectively. Y2H and deletion mutant analyses corroborated that VemR interacted with OGDH, SirA, FlgA, and HrpG; thus, implicating multi-layered control of diverse cellular processes including carbon metabolism, motility, and pathogenicity in the rice. Physical interaction between VemR and HrpG suggested cross-talk interaction between CheA/VemR- and HpaS/HrpG-mediated signal transduction events orchestrating the hrp gene expression.
Influences of Biochar on Bioremediation/Phytoremediation Potential of Metal-Contaminated Soils
Authors: Narayanan Mathiyazhagan , Ma Ying
Published: June 2022

A number of anthropogenic and weathering activities accumulate heavy metals in soils, causing adverse effects on soil characteristics, microbial activity (diversity), agricultural practices, and underground aquifers. Controlling soil heavy metal pollution is difficult due to its persistence in soils, resulting in the deposition and transmission into the food web via agricultural food products, ultimately affecting human health. This review critically explores the potential for remediation of metal-contaminated soils using a biochar-based responsible approach. Plant-based biochar is an auspicious bio-based residue substance that can be used for metal-polluted soil remediation and soil improvement as a sustainable approach. Plants with rapid growth and increased biomass can meet the requirements for phytoremediation in large quantities. Recent research indicates significant progress in understanding the mechanisms of metal accumulation and contaminant movement in plants used for phytoremediation of metal-contaminated soil. Excessive contamination reduces plant biomass and growth, which has substantial hyperaccumulating possibilities and is detrimental to the phytoremediation process. Biochar derived from various plant sources can promote the growth and phytoremediation competence of native or wild plants grown in metal-polluted soil. Carbon-enriched biochar encourages native microbial growth by neutralizing pH and providing nutritional support. Thus, this review critically discusses the influence of plant and agricultural waste-based biochar on plant phytoremediation potential in metal-contaminated soils.
Establishment and Validation of a Two-Step LAMP Assay for Detection of Bacillus cereus-Group Isolates in Food and Their Possibility of Non-haemolytic Enterotoxin Production
Authors: Busch Annemarie , Schotte Ulrich , Jeßberger Nadja , Frentzel Hendrik , Plötz Madeleine , Abdulmawjood Amir
Published: June 2022

The closely related members of the Bacillus cereus-group can mainly only be differentiated by whole genome sequencing. Among them, there are potentially toxin-producing bacteria. When consumed with food, these can cause vomiting or diarrhea and abdominal cramps. To date, although no EU-wide threshold exists, a bacterial count of 105 CFU/g can be regarded as critical. Specific and rapid detection of the bacteria is difficult due to their close relationship, and no loop-mediated isothermal amplification (LAMP) assay has been developed so far to detect potentially toxin-producing members of the B. cereus-group. Aim of this study was to develop a LAMP method to detect critical cell counts specifically and rapidly of potentially non-haemolytic enterotoxin (NHE)-producing cells of this group. A two-step LAMP assay was developed. First, the target sequence groEL was used to determine the representatives of the B. cereus-group. Second, since bacteria in which nheB is present are basically capable of producing enterotoxins, this gene was chosen for detection. The specificity of the developed assay was 100% for B. cereus-group isolates and 93.7% for the detection of nheB. The analytical sensitivity was 0.1 pg DNA/μl. Using simplified DNA extraction by boiling, cell-based sensitivity was determined. Targeting groEL and nheB, 11.35–27.05 CFU/reaction and 11.35–270.5 CFU/reaction were detectable, respectively. Artificially contaminated samples were investigated to prove the application in foods. Direct detection of the critical value of B. cereus-group cells was possible in 83.3% of samples and detecting the toxin-gene 50% thereof. After a 6-h incubation period, the detection rate increased to 100 and 91.7%, respectively. Additionally, 100 natively contaminated food samples were tested, also quantitatively and culturally. Samples with relevant contamination levels were reliably detected using groEL-LAMP. After a 6-h incubation period, isolates bearing the toxin gene nheB could also be reliably detected. In addition, colony material was boiled and used as a LAMP template for simple detection. Specificity for the B. cereus-group was 100 and 93.22% detecting nheB. The study demonstrated that screening of food samples with the groEL/nheB-LAMP assay can be performed within 1 day, making it possible to detect critical levels of potentially NHE-toxin-producing cells of the B. cereus-group.
Worse Sleep Quality Aggravates the Motor and Non-Motor Symptoms in Parkinson's Disease
Authors: Yi Qu , Yu-Peng Chen , Jiang-Ting Li , Jing-Yi Li , Qi-Xiong Qin , Dan-Lei Wang , Jing-Wei Zhao , Zhi-Juan Mao , Yong-Jie Xiong , Zhe Min , Zheng Xue
Published: June 2022

Backgrounds

Sleep disorders are the most common and disabling symptoms in patients with Parkinson's disease (PD). Understanding the associations between sleep characteristics and motor and non-motor symptoms (NMSs) in PD can provide evidence to guide therapeutic interventions and nursing strategies. We aimed to investigate the association between sleep characteristics and motor function and NMSs in PD using multiple approaches.

Methods

A total of 328 participants were included, and all participants underwent Pittsburgh Sleep Quality Index (PSQI) evaluation and clinical assessments of PD symptoms. We conducted Spearman's correlation to evaluate the associations between sleep and PD symptoms, nonlinear regression to assess the relationships between sleep habits and PD, and mediated analyses to test the effects of NMSs on global PSQI and PD severity, quality of life, and motor symptoms.

Results

Poor sleep was associated with more severe PD symptoms. In addition, the reflection point for bedtime was around 21:52, associated with motor symptoms, and insufficient and excessive total time spent in bed and nocturnal sleep duration were correlated with higher NMS burdens. The optimal points were 8–9.2 and 6.2–6.9 h, respectively. It was also discovered that NMSs played the mediating roles in global sleep with the quality of life, PD stages, and motor symptoms to a varying range of 6.8–95.4%.

Conclusions

Sleep disorders have a significant effect on the burden of PD symptoms. The current findings provide new insights into the monitoring and management of sleep and PD and need to be further explored in the future studies.
Coenzyme A-Dependent Tricarboxylic Acid Cycle Enzymes Are Decreased in Alzheimer’s Disease Consistent With Cerebral Pantothenate Deficiency
Authors: Sang Crystal , Philbert Sasha A. , Hartland Danielle , Unwin Richard. D , Dowsey Andrew W. , Xu Jingshu , Cooper Garth J. S.
Published: June 2022

Sporadic Alzheimer’s disease (sAD) is the commonest cause of age-related neurodegeneration and dementia globally, and a leading cause of premature disability and death. To date, the quest for a disease-modifying therapy for sAD has failed, probably reflecting our incomplete understanding of aetiology and pathogenesis. Drugs that target aggregated Aβ/tau are ineffective, and metabolic defects are now considered to play substantive roles in sAD pathobiology. We tested the hypothesis that the recently identified, pervasive cerebral deficiency of pantothenate (vitamin B5) in sAD, might undermine brain energy metabolism by impairing levels of tricarboxylic acid (TCA)-cycle enzymes and enzyme complexes, some of which require the pantothenate-derived cofactor, coenzyme A (CoA) for their normal functioning. We applied proteomics to measure levels of the multi-subunit TCA-cycle enzymes and their cytoplasmic homologues. We analysed six functionally distinct brain regions from nine sAD cases and nine controls, measuring 33 cerebral proteins that comprise the nine enzymes of the mitochondrial-TCA cycle. Remarkably, we found widespread perturbations affecting only two multi-subunit enzymes and two enzyme complexes, whose function is modulated, directly or indirectly by CoA: pyruvate dehydrogenase complex, isocitrate dehydrogenase, 2-oxoglutarate dehydrogenase complex, and succinyl-CoA synthetase. The sAD cases we studied here displayed widespread deficiency of pantothenate, the obligatory precursor of CoA. Therefore, deficient cerebral pantothenate can damage brain-energy metabolism in sAD, at least in part through impairing levels of these four mitochondrial-TCA-cycle enzymes.
C9orf72-Related Neurodegenerative Diseases: From Clinical Diagnosis to Therapeutic Strategies
Authors: Zampatti Stefania , Peconi Cristina , Campopiano Rosa , Gambardella Stefano , Caltagirone Carlo , Giardina Emiliano
Published: June 2022

Hexanucleotide expansion in C9orf72 has been related to several phenotypes to date, complicating the clinical recognition of these neurodegenerative disorders. An early diagnosis can improve the management of patients, promoting early administration of therapeutic supportive strategies. Here, we report known clinical presentations of C9orf72-related neurodegenerative disorders, pointing out suggestive phenotypes that can benefit the genetic characterization of patients. Considering the high variability of C9orf72-related disorder, frequent and rare manifestations are described, with detailed clinical, instrumental evaluation, and supportive therapeutical approaches. Furthermore, to improve the understanding of molecular pathways of the disease and potential therapeutical targets, a detailed description of the cellular mechanisms related to the pathological effect of C9orf72 is reported. New promising therapeutical strategies and ongoing studies are reported highlighting their molecular role in cellular pathological pathways of C9orf72. These therapeutic approaches are particularly promising because they seem to stop the disease before neuronal damage. The knowledge of clinical and molecular features of C9orf72-related neurodegenerative disorders improves the therapeutical application of known strategies and will lay the basis for the development of new potential therapies.
Deconvoluting the Complexity of Reactive Oxygen Species (ROS) in Neurodegenerative Diseases
Authors: Zhou Yuxin , Zhen Yongqi , Wang Guan , Liu Bo
Published: June 2022

Neurodegenerative diseases (NDs) are becoming a serious public health concern as the world’s population continues to age, demanding the discovery of more effective therapies. Excessive formation of reactive oxygen species (ROS) can result in oxidative stress (OS), which can be regarded as one of the common causes of neurodegenerative diseases (NDs). Thus, in this review, we focus on summarizing the consequences of ROS NDs, while taking the four prevalent NDs as examples, including Alzheimer’s disease (AD), Parkinson’s disease (PD), Amyotrophic lateral sclerosis (ALS), and Huntington’s disease (HD), to illustrate the key signaling pathways and relevant drugs. Together, these findings may shed new light on a field in which ROS-related pathways play a key role; thereby setting the groundwork for the future therapeutic development of neurodegenerative diseases.