bluuebunny/crossref_metadata_2025 huggingface dataset:
Urine Proteomics Differentiate Primary Thrombotic Antiphospholipid Syndrome From Obstetric Antiphospholipid Syndrome
Authors: Zhou Zhuochao , You Yijun , Wang Fan , Sun Yue , Teng Jialin , Liu Honglei , Cheng Xiaobing , Su Yutong , Shi Hui , Hu Qiongyi , Chi Huihui , Jia Jinchao , Wan Liyan , Liu Tingting , Wang Mengyan , Shi Ce , Yang Chengde , Ye Junna
Published: August 2021

Antiphospholipid syndrome (APS) is a multisystem disorder characterized by thrombosis and/or recurrent fetal loss. This clinical phenotype heterogeneity may result in differences in response to treatment and prognosis. In this study, we aimed to identify primary thrombotic APS (TAPS) from primary obstetric APS (OAPS) using urine proteomics as a non-invasive method. Only patients with primary APS were enrolled in this study from 2016 to 2018 at a single clinical center in Shanghai. Urine samples from 15 patients with TAPS, 9 patients with OAPS, and 15 healthy controls (HCs) were collected and analyzed using isobaric tags for relative and absolute quantification (iTRAQ) labeling combined with liquid chromatography-tandem mass spectrometry analysis to identify differentially expressed proteins. Cluster analysis of urine proteomics identified differentiated proteins among the TAPS, OAPS, and HC groups. Urinary proteins were enriched in cytokine and cytokine receptor pathways. Representative secreted cytokines screened out (fold change >1.20, or <0.83, p<0.05) in these differentiated proteins were measured by enzyme-linked immunosorbent assay in a validation cohort. The results showed that the levels of C-X-C motif chemokine ligand 12 (CXCL12) were higher in the urine of patients with TAPS than in those with OAPS (p=0.035), while the levels of platelet-derived growth factor subunit B (PDGFB) were lower in patients with TAPS than in those with OAPS (p=0.041). In addition, correlation analysis showed that CXCL12 levels were positively correlated with immunoglobulin G anti-β2-glycoprotein I antibody (r=0.617, p=0.016). Our results demonstrated that urinary CXCL12 and PDGFB might serve as potential non-invasive markers to differentiate primary TAPS from primary OAPS.
A Novel microRNA of Japanese Flounder Regulates Antimicrobial Immunity Involving a Bacteria-Binding CSF3
Authors: Li Wenrui , Guan Xiaolu , Sun Bin , Sun Li
Published: August 2021

MicroRNAs (miRNAs) are small non-coding RNAs that regulate diverse biological processes including immunity. In a previous high-throughput RNA sequencing study, a novel miRNA, pol-miR-novel_642, was identified from Japanese flounder (Paralichthys olivaceus), a farmed fish species with important economic value. In this study, we investigated the regulatory mechanism and the function of pol-miR-novel_642 and its target gene. We found that pol-miR-novel_642 targeted, in a sequence-specific manner, a flounder gene encoding an uncharacterized protein that is a structural homologue of murine granulocyte colony stimulating factor 3 (CSF3). The expression of pol-miR-novel_642 and its target gene (named PoCSF3-1) was regulated, in different manners, by the bacterial pathogen Edwardsiella tarda and the viral pathogen megalocytivirus. Overexpression of pol-miR-novel_642 or interference with PoCSF3-1 expression in flounder cells strongly potentiated E. tarda infection. Consistently, in vivo knockdown of PoCSF3-1 enhanced bacterial dissemination in flounder tissues but blocked viral replication, whereas in vivo overexpression of PoCSF3-1 inhibited bacterial dissemination and facilitated viral infection. Overexpression/knockdown of PoCSF3-1 and pol-miR-novel_642 also affected the activation of autophagy. Recombinant PoCSF3-1 (rPoCSF3-1) interacted with and inhibited the growth of Gram-negative bacteria in a manner relying on a PoCSF3-1-characteristic structural motif that is absent in mouse CSF3. rPoCSF3-1 also regulated the proliferation, inflammatory response, and immune defense of flounder head kidney leukocytes in a structure-dependent fashion. Together, these results reveal the function of a novel miRNA-CSF3 regulatory system of flounder, and add new insights into the role and mechanism of fish miRNA and CSF3 in antimicrobial immunity.
Different Profiles of Antibodies and Cytokines Were Found Between Severe and Moderate COVID-19 Patients
Authors: Guo Yaolin , Li Tianyi , Xia Xinyi , Su Bin , Li Hanping , Feng Yingmei , Han Jingwan , Wang Xiaolin , Jia Lei , Bao Zuoyi , Li Jingyun , Liu Yongjian , Li Lin
Published: August 2021

Objectives

Our objective was to determine the antibody and cytokine profiles in different COVID-19 patients.

Methods

COVID-19 patients with different clinical classifications were enrolled in this study. The level of IgG antibodies, IgA, IgM, IgE, and IgG subclasses targeting N and S proteins were tested using ELISA. Neutralizing antibody titers were determined by using a toxin neutralization assay (TNA) with live SARS-CoV-2. The concentrations of 8 cytokines, including IL-2, IL-4, IL-6, IL-10, CCL2, CXCL10, IFN-γ, and TNF-α, were measured using the Protein Sample Ella-Simple ELISA system. The differences in antibodies and cytokines between severe and moderate patients were compared by t-tests or Mann-Whitney tests.

Results

A total of 79 COVID-19 patients, including 49 moderate patients and 30 severe patients, were enrolled. Compared with those in moderate patients, neutralizing antibody and IgG-S antibody titers in severe patients were significantly higher. The concentration of IgG-N antibody was significantly higher than that of IgG-S antibody in COVID-19 patients. There was a significant difference in the distribution of IgG subclass antibodies between moderate patients and severe patients. The positive ratio of anti-S protein IgG3 is significantly more than anti-N protein IgG3, while the anti-S protein IgG4 positive rate is significantly less than the anti-N protein IgG4 positive rate. IL-2 was lower in COVID-19 patients than in healthy individuals, while IL-4, IL-6, CCL2, IFN-γ, and TNF-α were higher in COVID-19 patients than in healthy individuals. IL-6 was significantly higher in severe patients than in moderate patients. The antibody level of anti-S protein was positively correlated with the titer of neutralizing antibody, but there was no relationship between cytokines and neutralizing antibody.

Conclusions

Our findings show the severe COVID-19 patients’ antibody levels were stronger than those of moderate patients, and a cytokine storm is associated with COVID-19 severity. There was a difference in immunoglobulin type between anti-S protein antibodies and anti-N protein antibodies in COVID-19 patients. And clarified the value of the profile in critical prevention.
Do Ballast Water Management Systems Reduce Phytoplankton Introductions to Canadian Waters?
Authors: Casas-Monroy Oscar , Bailey Sarah A.
Published: August 2021

Global coastal aquatic ecosystems are negatively impacted by the introduction of harmful aquatic species through the discharge of ships’ ballast water. To reduce discharges of harmful aquatic organisms and pathogens, such as toxic phytoplankton species, ships are now transitioning to the use of ballast water management systems (BWMS) instead of ballast water exchange (BWE). This study examines the abundance and diversity of phytoplankton in ballast water managed by BWMS (or a combination of both BWE + BWMS) in comparison to those in ballast water managed by BWE alone (collected from ships arriving to Canada’s Pacific coast in 2017–2018 and 2008, respectively). The abundance and diversity of phytoplankton species were also examined in relation to key variables such as ballast water salinity and ballast water age. Total abundance of phytoplankton was significantly lower in preserved samples managed by either a BWMS or BWE + BWMS compared to BWE alone. Abundances in preserved samples were higher than observed in fresh (unpreserved) samples at the time of collection, with all samples managed by a BWMS meeting international limits for the number of viable organisms ≥10 and <50 μm in minimum dimension (based on six 1-mL live counts). While there was no apparent influence of factors such as treatment type [e.g., ultraviolet (UV) or chlorine], presence of filtration, ballast water salinity, ballast water age, nor location of last ballast water uptake on phytoplankton abundances in preserved samples, power to detect differences may be limited by sample size. Ballast water managed by BWMS also tended to have lower abundances of harmful phytoplankton species, although the difference was not statistically significant – additional research into the community composition of live cells in fresh samples could be valuable to discriminate the risk associated with phytoplankton surviving ballast water treatment.
Low Concentration and High Transparency Keratin Hydrogel Fabricated via Cryoablation
Authors: Wang Xiaoqing , Shi Zhiming , Zhao Le , Shen Xianyi
Published: August 2021

Keratins are highly attractive for medical applications due to their inherent self-assemblies characteristics and biocompatibility. However, nearly all researches have focused on the properties of hybrid hydrogels which was prepared from human hair keratin with other materials, and the preparation methods and properties of pure keratin hydrogels are rarely studied. Thus, we extracted keratins from rabbit hair, and a low concentration and high purity RHK hydrogel was then prepared by a simple freeze–thaw cycle and used to study gelation and the optical properties. The results indicated that RHK keratin hydrogel is a reversible thixotropic system and elastic modulus the storage modulus (G′) substantially improves with freeze–thaw cycles. The systematic assessments including microstructural observation, porosity, and the secondary structure confirmed that the structure and properties of keratin hydrogels can be changed by controlling freeze–thaw cycles. Meanwhile, it is found that RHK hydrogel had high optical transmittance, and still maintained its fluorescent properties, which would be useful to observe the wound healing and locate the drug delivery process.
The Dahl’s Model for the Inelastic Bending Behavior of Textile Composite Preforms. Analysis of its Influence in Draping Simulation
Authors: Ghafour Théo A. , Colmars Julien , Boisse Philippe
Published: August 2021

Most of the numerical simulations of dry textile reinforcements forming are based on a macroscopic approach and continuous material models whose behavior is assumed to be elastic (linear or nonlinear). On the one hand, the experience shows that under loading/unloading stresses, residual inelastic deformations are observed. On the other hand, among the deformations that a woven reinforcement undergoes during forming, in most cases, only bending is subject to loading/unloading stresses. The first objective of this work is to highlight the inelastic bending behavior of textile reinforcements during a forming process and to find the possible origins of inelasticity. The second objective is to find the cases generating bending loading/unloading during forming as well as to study the influence of the bending inelasticity on forming simulation. For this purpose, the inelastic bending behavior was characterized by three-point bending tests. Then, the Dahl friction model was adapted to bending to describe the inelastic behavior. Finally, this model was implemented in a finite element code based on shell elements allowing the study of the influence of taking into account the inelastic behavior in bending on the numerical simulation of forming.
ATENA–A Novel Rapidly Manufactured Medical Invasive Ventilator Designed as a Response to the COVID-19 Pandemic: Testing Protocol, Safety, and Performance Validation
Authors: Rebelo Tiago , Neutel Elizabete , Alves Eurico Castro , Barros Francisco , Oliveira Hélder , Machado Humberto , Mendonça Joana , Araújo João Fortuna , Luís João , Pêgo José M. , Silva José , Oliveira Manuel , Sousa Nuno , Figueiredo Paulo , Barata Pedro , Magalhães Raquel Silva , Magalhães Rui Miguel , Gomes Sara H.
Published: August 2021

Background: The urgent need for mechanical ventilators to support respiratory insufficiency due to SARS-CoV-2 led to a worldwide effort to develop low-cost, easily assembled, and locally manufactured ventilators. The ATENA ventilator project was developed in a community-based approach targeting the development, prototyping, testing, and decentralized manufacturing of a new mechanical ventilator.

Objective: This article aims to demonstrate ATENA's adequate performance and safety for clinical use.

Material: ATENA is a low-cost ventilator that can be rapidly manufactured, easily assembled, and locally produced anywhere in the world. It was developed following the guidelines and requirements provided by European and International Regulatory Authorities (MHRA, ISO 86201) and National Authorities (INFARMED). The device was thoroughly tested using laboratory lung simulators and animal models.

Results: The device meets all the regulatory requirements for pandemic ventilators. Additionally, the pre-clinical experiences demonstrated security and adequate ventilation and oxygenation, in vivo.

Conclusion: The ATENA ventilator had a good performance in required tests in laboratory scenarios and pre-clinical studies. In a pandemic context, ATENA is perfectly suited for safely treating patients in need of mechanical ventilation.
Case Report: Hyperinflammatory Status in an Immunocompromised Child With a Highly Sustained Viral Load of SARS-CoV-2
Authors: Moragas Matias , Gomez Sandra , Fernández María Florencia , Golemba Marcelo Dario , Palladino Marcela , Borgnia Daniela , Ruvinsky Silvina , Fraquelli Lidia , Buchovsky Ana , Bologna Rosa , Mangano Andrea
Published: August 2021

Coronavirus disease 2019 (COVID-19) is spreading throughout the world. Limited data are available for the dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load (VL) in immunocompromised pediatric patients. Here, we report the clinical characteristics and the dynamics of SARS-CoV-2 VL of a pediatric patient with acute myeloid leukemia who developed a hyperinflammatory status mimicked MIS-C. The clinical course was characterized by the late onset of fever, GI symptoms, rash, and respiratory distress, including oxygen requirement with sustained VL of SARS-CoV-2 around 7 log10RNA copies/mL for 6 weeks. It is important to note that the hyperinflammatory status developed early at the third week of hospitalization—in a context of high VL and immunocompromised status. All these characteristics make this clinical case unique. On the other hand, while many reports have characterized the dynamics of SARS-CoV-2 VL in adults and immunocompetent hosts, it remains unreported in pediatrics—even less in immunosuppressed children.
Binding Potassium to Improve Treatment With Renin-Angiotensin-Aldosterone System Inhibitors: Results From Multiple One-Stage Pairwise and Network Meta-Analyses of Clinical Trials
Authors: Lizaraso-Soto Frank , Gutiérrez-Abejón Eduardo , Bustamante-Munguira Juan , Martín-García Débora , Chimeno María Montserrat , Nava-Rebollo Álvaro , Maurtua-Briseño-Meiggs Álvaro , Fernández-Zoppino Darío , Bustamante-Munguira Elena , de Paz Félix Jesús , Grande-Villoria Jesús , Ochoa-Sangrador Carlos , Pascual Manuel , Álvarez F. Javier , Herrera-Gómez Francisco
Published: August 2021

This manuscript presents findings from the first dichotomous data pooling analysis on clinical trials (CT) regarding the effectiveness of binding potassium. The results emanated from pairwise and network meta-analyses aiming evaluation of response to commercial potassium-binding polymers, that is, to achieve and maintain normal serum potassium (n = 1,722), and the association between this response and an optimal dosing of renin-angiotensin-aldosterone system inhibitors (RAASi) needing individuals affected by heart failure (HF) or resistant hypertension, who may be consuming other hyperkalemia-inducing drugs (HKID) (e.g., β-blockers, heparin, etc.), and frequently are affected by chronic kidney disease (CKD) (n = 1,044): According to the surface under the cumulative ranking area (SUCRA), sodium zirconium cyclosilicate (SZC) (SUCRA >0.78), patiromer (SUCRA >0.58) and sodium polystyrene sulfonate (SPS) (SUCRA <0.39) were different concerning their capacity to achieve normokalemia (serum potassium level (sK+) 3.5–5.0 mEq/L) or acceptable kalemia (sK+ ≤ 5.1 mEq/L) in individuals with hyperkalemia (sK+ >5.1 mEq/L), and, when normokalemia is achieved, patiromer 16.8–25.2 g/day (SUCRA = 0.94) and patiromer 8.4–16.8 g/day (SUCRA = 0.41) can allow to increase the dose of spironolactone up to 50 mg/day in subjects affected by heart failure (HF) or with resistant hypertension needing treatment with other RAASi. The potential of zirconium cyclosilicate should be explored further, as no data exists to assess properly its capacity to optimize dosing of RAASi, contrarily as it occurs with patiromer. More research is also necessary to discern between benefits of binding potassium among all type of hyperkalemic patients, for example, patients with DM who may need treatment for proteinuria, patients with early hypertension, etc.

Systematic Review Registration:https://www.crd.york.ac.uk/PROSPERO/, identifier: CRD42020185614, CRD42020185558, CRD42020191430.
Development of an Early Warning Model for Predicting the Death Risk of Coronavirus Disease 2019 Based on Data Immediately Available on Admission
Authors: Wang Hai , Ai Haibo , Fu Yunong , Li Qinglin , Cui Ruixia , Ma Xiaohua , Ma Yan-fen , Wang Zi , Liu Tong , Long Yunxiang , Qu Kai , Liu Chang , Zhang Jingyao
Published: August 2021

Introduction: COVID-19 has overloaded worldwide medical facilities, leaving some potentially high-risk patients trapped in outpatient clinics without sufficient treatment. However, there is still a lack of a simple and effective tool to identify these patients early.

Methods: A retrospective cohort study was conducted to develop an early warning model for predicting the death risk of COVID-19. Seventy-five percent of the cases were used to construct the prediction model, and the remaining 25% were used to verify the prediction model based on data immediately available on admission.

Results: From March 1, 2020, to April 16, 2020, a total of 4,711 COVID-19 patients were included in our study. The average age was 63.37 ± 16.70 years, of which 1,148 (24.37%) died. Finally, age, SpO2, body temperature (T), and mean arterial pressure (MAP) were selected for constructing the model by univariate analysis, multivariate analysis, and a review of the literature. We used five common methods for constructing the model and finally found that the full model had the best specificity and higher accuracy. The area under the ROC curve (AUC), specificity, sensitivity, and accuracy of full model in train cohort were, respectively, 0.798 (0.779, 0.816), 0.804, 0.656, and 0.768, and in the validation cohort were, respectively, 0.783 (0.751, 0.815), 0.800, 0.616, and 0.755. Visualization tools of the prediction model included a nomogram and an online dynamic nomogram (https://wanghai.shinyapps.io/dynnomapp/).

Conclusion: We developed a prediction model that might aid in the early identification of COVID-19 patients with a high probability of mortality on admission. However, further research is required to determine whether this tool can be applied for outpatient or home-based COVID-19 patients.
Metformin in Patients With COVID-19: A Systematic Review and Meta-Analysis
Authors: Li Yin , Yang Xue , Yan Peijing , Sun Tong , Zeng Zhi , Li Sheyu
Published: August 2021

Importance/Background: The coronavirus disease (COVID-19) pandemic is a critical public health issue. Evidence has shown that metformin favorably influences COVID-19 outcomes. This study aimed to assess the benefits and risks of metformin in COVID-19 patients.

Methods: We searched the PubMed, Embase, Cochrane Library, and Chinese Biomedical Literature Database from inception to February 18, 2021. Observational studies assessing the association between metformin use and the outcomes of COVID-19 patients were included. The primary outcome was mortality, and the secondary outcomes included intubation, deterioration, and hospitalization. Random-effects weighted models were used to pool the specific effect sizes. Subgroup analyses were conducted by stratifying the meta-analysis by region, diabetic status, the adoption of multivariate model, age, risk of bias, and timing for adding metformin.

Results: We identified 28 studies with 2,910,462 participants. Meta-analysis of 19 studies showed that metformin is associated with 34% lower COVID-19 mortality [odds ratio (OR), 0.66; 95% confidence interval (CI), 0.56–0.78; I2 = 67.9%] and 27% lower hospitalization rate (pooled OR, 0.73; 95% CI, 0.53–1.00; I2 = 16.8%). However, we did not identify any subgroup effects. The meta-analysis did not identify statistically significant association between metformin and intubation and deterioration of COVID-19 (OR, 0.94; 95% CI, 0.77–1.16; I2 = 0.0% for intubation and OR, 2.04; 95% CI, 0.65–6.34; I2 = 79.4% for deterioration of COVID-19), respectively.

Conclusions: Metformin use among COVID-19 patients was associated with a reduced risk of mortality and hospitalization. Our findings suggest a relative benefit for metformin use in nursing home and hospitalized COVID-19 patients. However, randomized controlled trials are warranted to confirm the association between metformin use and COVID-19 outcomes.

Study Registration: The study was registered on the PROSPERO on Feb 23, 2021 (CRD42021238722).
Joint Modeling of RNAseq and Radiomics Data for Glioma Molecular Characterization and Prediction
Authors: Shboul Zeina A. , Diawara Norou , Vossough Arastoo , Chen James Y. , Iftekharuddin Khan M.
Published: August 2021

RNA sequencing (RNAseq) is a recent technology that profiles gene expression by measuring the relative frequency of the RNAseq reads. RNAseq read counts data is increasingly used in oncologic care and while radiology features (radiomics) have also been gaining utility in radiology practice such as disease diagnosis, monitoring, and treatment planning. However, contemporary literature lacks appropriate RNA-radiomics (henceforth, radiogenomics) joint modeling where RNAseq distribution is adaptive and also preserves the nature of RNAseq read counts data for glioma grading and prediction. The Negative Binomial (NB) distribution may be useful to model RNAseq read counts data that addresses potential shortcomings. In this study, we propose a novel radiogenomics-NB model for glioma grading and prediction. Our radiogenomics-NB model is developed based on differentially expressed RNAseq and selected radiomics/volumetric features which characterize tumor volume and sub-regions. The NB distribution is fitted to RNAseq counts data, and a log-linear regression model is assumed to link between the estimated NB mean and radiomics. Three radiogenomics-NB molecular mutation models (e.g., IDH mutation, 1p/19q codeletion, and ATRX mutation) are investigated. Additionally, we explore gender-specific effects on the radiogenomics-NB models. Finally, we compare the performance of the proposed three mutation prediction radiogenomics-NB models with different well-known methods in the literature: Negative Binomial Linear Discriminant Analysis (NBLDA), differentially expressed RNAseq with Random Forest (RF-genomics), radiomics and differentially expressed RNAseq with Random Forest (RF-radiogenomics), and Voom-based count transformation combined with the nearest shrinkage classifier (VoomNSC). Our analysis shows that the proposed radiogenomics-NB model significantly outperforms (ANOVA test, p < 0.05) for prediction of IDH and ATRX mutations and offers similar performance for prediction of 1p/19q codeletion, when compared to the competing models in the literature, respectively.
Effects of Telemedicine on Obese Patients With Non-alcoholic Fatty Liver Disease: A Systematic Review and Meta-Analysis
Authors: Saokaew Surasak , Kanchanasurakit Sukrit , Kositamongkol Chayanis , Chaiyo Kanyanat , Jirapisut Thirada , Aomsin Narakorn , Leewongsakorn Pit , Chaiyakunapruk Nathorn , Phisalprapa Pochamana
Published: August 2021

Background: Little is known of the efficacy of telemedicine on the clinical outcomes of the high-risk group of non-alcoholic fatty liver disease (NAFLD) patients, such as those with obesity. This study aimed to determine the effects of telemedicine vs. usual care for the management of obese patients with NAFLD.

Methods: Literature searches were performed from inception to 1st June 2021 in the following databases: Cochrane CENTRAL, ScienceDirect, PubMed, and Scopus. Prospective trials assessed the effects of telemedicine on obese patients with NAFLD were included. The outcomes of interest were alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglyceride, high-density lipoprotein cholesterol levels, and body mass index, which were reported as weighted mean difference (WMD) with 95% confidence interval (CI).

Results: Four studies were examined in the systematic review, one was excluded from the meta-analysis due to an inappropriate group-comparison. In all, 285 obese patients with NAFLD were included in the meta-analysis (70% of those received telemedicine intervention). The mean ages of the patients in the telemedicine and usual-care groups were 51.78 ± 5.91 and 47.30 ± 8.14 years, respectively. Telemedicine significantly decreased ALT levels compared with usual care (WMD = −18.93 U/L [95%CI: −25.97, −11.90]; I2 = 53.8%), and it significantly decreased AST levels (WMD = −10.24 U/L [95%CI: −13.43, −7.05]; I2 = 0.0%). However, telemedicine did not show significant benefits for the remaining outcomes.

Conclusion: Compared with usual care, telemedicine significantly reduced the AST and ALT levels of obese patients with NAFLD. Further long-term studies with clinical endpoints are needed to determine the best characteristics of telemedicine and to confirm the benefits.

Systematic Review Registration: PROSPERO [CRD42020207451].
Impact of Soil Disinfestation on Fungal and Bacterial Communities in Soil With Cucumber Cultivation
Authors: Wang Yan , Jin Yujie , Han Ping , Hao Jianjun , Pan Hongyu , Liu Jinliang
Published: August 2021

Soil treatment with disinfectants has been used for controlling soilborne phytopathogens. Besides suppressing specific pathogens, how these disinfectants impact soil health, especially soil microbial communities, is yet to be systemically determined. The objectives of this study were to examine the effects of three representative disinfectants, including the dazomet fumigant, fenaminosulf fungicide, and kasugamycin antibiotic on chemical properties, enzymatic activities, and microbial communities in soil for cucumber cultivation. Results showed that 14 days after soil treatment with these chemicals, residual content of dazomet and kasugamycin quickly declined in soil and were undetectable, while fenaminosulf residues were found at 0.48 ± 0.01 mg/kg. Total nitrogen and total carbon increased in soil after dazomet treatment. Urease and sucrase activities were significantly restrained after disinfectant application. The disinfectants did not significantly change the taxon of predominant bacteria and fungi but altered the relative abundance and diversity of soil microbiome, as well as microbial interspecific relationships. Moreover, cucumber cultivation enhanced the overall soil microbial diversity and enzymatic activities, which diminished the difference of soil microbiome among four treatments. The difference in soil microbial diversity among the four treatments became smaller after planting cucumber. Thus, soil microbial communities were affected by soil disinfectants and gradually recovered by cucumber application.
Laboratory Stock Variants of the Archetype Silver Resistance Plasmid pMG101 Demonstrate Plasmid Fusion, Loss of Transmissibility, and Transposition of Tn7/pco/sil Into the Host Chromosome
Authors: Hooton Steven P.T. , Pritchard Alexander C.W. , Asiani Karishma , Gray-Hammerton Charlotte J. , Stekel Dov J. , Crossman Lisa C. , Millard Andrew D. , Hobman Jon L.
Published: August 2021

Salmonella Typhimurium carrying the multidrug resistance (MDR) plasmid pMG101 was isolated from three burns patients in Boston United States in 1973. pMG101 was transferrable into other Salmonella spp. and Escherichia coli hosts and carried what was a novel and unusual combination of AMR genes and silver resistance. Previously published short-read DNA sequence of pMG101 showed that it was a 183.5Kb IncHI plasmid, where a Tn7-mediated transposition of pco/sil resistance genes into the chromosome of the E. coli K-12 J53 host strain had occurred. We noticed differences in streptomycin resistance and plasmid size between two stocks of E. coli K-12 J53 pMG101 we possessed, which had been obtained from two different laboratories (pMG101-A and pMG101-B). Long-read sequencing (PacBio) of the two strains unexpectedly revealed plasmid and chromosomal rearrangements in both. pMG101-A is a non-transmissible 383Kb closed-circular plasmid consisting of an IncHI2 plasmid sequence fused to an IncFI/FIIA plasmid. pMG101-B is a mobile closed-circular 154 Kb IncFI/FIIA plasmid. Sequence identity of pMG101-B with the fused IncFI/IncFIIA region of pMG101-A was >99%. Assembled host sequence reads of pMG101-B showed Tn7-mediated transposition of pco/sil into the E. coli J53 chromosome between yhiM and yhiN. Long read sequence data in combination with laboratory experiments have demonstrated large scale changes in pMG101. Loss of conjugation function and movement of resistance genes into the chromosome suggest that even under long-term laboratory storage, mobile genetic elements such as transposons and insertion sequences can drive the evolution of plasmids and host. This study emphasises the importance of utilising long read sequencing technologies of plasmids and host strains at the earliest opportunity.
Multi-Task Classification and Segmentation for Explicable Capsule Endoscopy Diagnostics
Authors: Kong Zishang , He Min , Luo Qianjiang , Huang Xiansong , Wei Pengxu , Cheng Yalu , Chen Luyang , Liang Yongsheng , Lu Yanchang , Li Xi , Chen Jie
Published: August 2021

Capsule endoscopy is a leading diagnostic tool for small bowel lesions which faces certain challenges such as time-consuming interpretation and harsh optical environment inside the small intestine. Specialists unavoidably waste lots of time on searching for a high clearness degree image for accurate diagnostics. However, current clearness degree classification methods are based on either traditional attributes or an unexplainable deep neural network. In this paper, we propose a multi-task framework, called the multi-task classification and segmentation network (MTCSN), to achieve joint learning of clearness degree (CD) and tissue semantic segmentation (TSS) for the first time. In the MTCSN, the CD helps to generate better refined TSS, while TSS provides an explicable semantic map to better classify the CD. In addition, we present a new benchmark, named the Capsule-Endoscopy Crohn’s Disease dataset, which introduces the challenges faced in the real world including motion blur, excreta occlusion, reflection, and various complex alimentary scenes that are widely acknowledged in endoscopy examination. Extensive experiments and ablation studies report the significant performance gains of the MTCSN over state-of-the-art methods.
Evaluation of NTRK Gene Fusion by Five Different Platforms in Triple-Negative Breast Carcinoma
Authors: Wu Shafei , Shi Xiaohua , Ren Xinyu , Li Kaimi , Pang Junyi , Liang Zhiyong
Published: August 2021

Triple-negative breast carcinoma (TNBC) is an aggressive disease that has a poor prognosis since it lacks effective treatment methods. Neurotrophic tyrosine receptor kinase (NTRK) fusion genes are excellent candidates for targeted RTK inhibitor therapies and there are available targeted therapy drugs for the treatment of TRK fusion-positive tumors in a tumor agnostic pattern. Our study was designed to investigate the NTRK gene fusion status in TNBC patients and to determine whether RTK-targeted therapies are suitable for TNBC patients. A total of 305 TNBC patients were enrolled in our study. IHC was employed as a prescreening method, and IHC positive cases were further submitted for evaluation by FISH, RT-PCR, and NGS methods. NTRK IHC was evaluated successfully in 287 of the 305 cases, and there were 32 (11.15%) positive cases. FISH was carried out in the 32 IHC positive cases. There were 13 FISH-positive cases if the threshold was set as >15% of the 100 counted tumor cells having a split orange and green signal with more than one signal diameter. There were only 2 FISH-positive cases if the cutoff value was defined as >15% of the counted tumor cells having a split signal with more than two signal diameter widths. One of the FISH-positive cases had a separate NTRK3 FISH signal in 88% of the tumor cells, and its IHC result was strong nuclear staining in all the tumor cells. After evaluation of the morphology, it was re-diagnosed as secretory breast carcinoma, and the NGS result confirmed that it had a NTRK3-ETV6 fusion gene. The other FISH-positive cases were all negative for NTRK gene fusion in the NGS or RT-PCR examination. The NTRK gene fusion rate was low in our TNBC cohort. NTRK gene fusion may be a rare event in TNBC. The high false-positive rate of NTRK gene fusion detected by IHC questions its role as a prescreening method in TNBC. More data may be needed to determine a suitable threshold for NTRK FISH in TNBC in the future. More studies are needed to confirm whether RTK-targeted therapies are appropriate treatments for TNBC patients.
Circulating Cytokines Predict 1H-Proton MRS Cerebral Metabolites in Healthy Older Adults
Authors: Langer Kailey , Cohen Ronald A. , Porges Eric C. , Williamson John B. , Woods Adam J.
Published: August 2021

Background: Changes in both circulating cytokines and neurochemical concentrations have been observed in aging. Patterns of change across these factors are associated with age-related pathologies, including neurodegenerative disease. More evidence to define patterns of change that are characteristic of healthy aging is needed, as is an investigation into how age-related changes in blood cytokines and brain neurochemicals may relate to one another in a healthy older adult population.

Methods: Single voxel 1H-proton magnetic resonance spectroscopy was collected in medial frontal and medial parietal regions. Phosphocholine and glycerophosphocholine (Cho), myo-inositol (MI), N-acetylaspertate and N-acetylasperglutamate (NAA), creatine and phosphocreatine (Cr), and glutamate and glutamine (Glx) were measured in a sample of 83 healthy, cognitively normal adults aged 52–89. Blood data were collected to quantify 12 cytokines: interleukins (IL-) 2, 5, 6, 7, 8, 10, 12, 13, IL-1 β, tumor necrosis factor α (TNF-α), interferon γ (IFN-γ), and IL-17 α. Correlation analyses were performed to assess age relationships between each of these factors. Backward linear regressions were performed. Cytokine data and age were used as predictors of each cerebrospinal fluid (CSF)-corrected metabolite concentration in both voxels.

Results: Associations were identified between a variety of cytokines and concentrations of frontal NAA, Cr, and Glx, and of parietal MI, Cho, NAA, and Cr. In the frontal voxel, NAA was predicted by more IL-1B and less TNF-α, Cr by less TNF-α and more IL-5, and Glx by less TNF-α. In the parietal voxel, MI was predicted by more IL-10 and IL-8 and less IL-2, Cho by more TNF-α and less IL-2, NAA by more IL-1B and TNF-α and less IL-13, IL-2, and IL-7, and Cr by more IL-10 and less IL-2.

Conclusions: Associations were identified between circulating cytokines and neurometabolite concentrations in this sample of older adults. The present results serve as the initial evidence of relationships between circulating cytokines and neurophysiology. Findings invite further investigation to understand the physiological consequences of aging, and how peripheral inflammatory markers may relate to neurochemical concentrations in healthy aging.
L-3,4-Dihydroxyphenylalanine Recovers Circadian Rhythm Disturbances in the Rat Models of Parkinson's Disease by Regulating the D1R-ERK1/2-mTOR Pathway
Authors: Yang Shuyuan , Wan Ying , Wu Na , Song Lu , Liu Zhihua , Zhao Jiahao , Liu Ying , Liu Zhenguo , Gan Jing
Published: August 2021

Objective: Patients with Parkinson's disease (PD) frequently experience disruptions in the 24-h daily profile of both behavioral and biological markers. However, whether L-3,4-dihydroxyphenylalanine (L-dopa) influences these markers associated with circadian rhythm or not is still an open question. This study aims to explore the L-dopa effects on the rhythmic expression of core clock proteins [brain and muscle Arnt-like protein-1 (BMAL1) and circadian locomotor cycle kaput (CLOCK)], in the striatum of the rat model of PD and its underlying molecular mechanisms.

Methods: Unilateral 6-hydroxydopamine (6-OHDA)-lesioned rat models were used in this study. L-dopa administrations were adopted to investigate the changes of circadian rhythm in PD. The behavioral tests and the measurements of the blood pressure (BP) and temperature were evaluated. The striatum was collected at intervals of 4 h. Western blot was used to examine the expressions of clock protein and the molecular protein of the D1R-ERK1/2-mTOR pathway. The rhythmic expressions of symptom parameters and circadian proteins were analyzed using the Cosinor model and/or the coefficient of variability (CV) that was used to describe the variability of the 24-h rhythm.

Results: The circadian rhythms of BP and temperature were disrupted in 6-OHDA-lesioned PD rats compared with the sham group, while this process was reversed mildly by L-dopa treatment. The expressions of BMAL1 and CLOCK protein were rhythmic fluctuated without significant phase alterations when 6-OHDA or L-dopa was applied. Furthermore, the expressions of striatal BMAL1 protein in the 6-OHDA-lesioned group were significantly lower than those in the sham group at 04:00, 08:00, and 12:00, and the CLOCK protein was decreased at 04:00, 08:00, 12:00, 16:00, and 20:00 (all p < 0.05). The CV of the expressions of both BMAL1 and CLOCK was decreased in the 6-OHDA group; this process was reversed by L-dopa. Moreover, the CV of BMAL1 and CLOCK was elevated in the L-dopa rats. The phosphorylation levels of ERK1/2, S6K1, and 4E-BP1 in 6-OHDA-lesioned striatum were increased by L-dopa or D1 receptor agonist SKF38393 (p < 0.05, respectively), not by the combination of L-dopa and D1 receptor antagonist SCH23390, which was similar to the expressions of BMAL1 and CLOCK.

Conclusion: L-dopa recovers the circadian rhythm disturbances in PD rats by regulating the D1R-ERK1/2-mTOR pathway.
The Dual-Task Cost Is Due to Neural Interferences Disrupting the Optimal Spatio-Temporal Dynamics of the Competing Tasks
Authors: Mac-Auliffe Diego , Chatard Benoit , Petton Mathilde , Croizé Anne-Claire , Sipp Florian , Bontemps Benjamin , Gannerie Adrien , Bertrand Olivier , Rheims Sylvain , Kahane Philippe , Lachaux Jean-Philippe
Published: August 2021

Dual-tasking is extremely prominent nowadays, despite ample evidence that it comes with a performance cost: the Dual-Task (DT) cost. Neuroimaging studies have established that tasks are more likely to interfere if they rely on common brain regions, but the precise neural origin of the DT cost has proven elusive so far, mostly because fMRI does not record neural activity directly and cannot reveal the key effect of timing, and how the spatio-temporal neural dynamics of the tasks coincide. Recently, DT electrophysiological studies in monkeys have recorded neural populations shared by the two tasks with millisecond precision to provide a much finer understanding of the origin of the DT cost. We used a similar approach in humans, with intracranial EEG, to assess the neural origin of the DT cost in a particularly challenging naturalistic paradigm which required accurate motor responses to frequent visual stimuli (task T1) and the retrieval of information from long-term memory (task T2), as when answering passengers’ questions while driving. We found that T2 elicited neuroelectric interferences in the gamma-band (>40 Hz), in key regions of the T1 network including the Multiple Demand Network. They reproduced the effect of disruptive electrocortical stimulations to create a situation of dynamical incompatibility, which might explain the DT cost. Yet, participants were able to flexibly adapt their strategy to minimize interference, and most surprisingly, reduce the reliance of T1 on key regions of the executive control network-the anterior insula and the dorsal anterior cingulate cortex-with no performance decrement.
Vocal and Electric Fish: Revisiting a Comparison of Two Teleost Models in the Neuroethology of Social Behavior
Authors: Dunlap Kent D. , Koukos Haley M. , Chagnaud Boris P. , Zakon Harold H. , Bass Andrew H.
Published: August 2021

The communication behaviors of vocal fish and electric fish are among the vertebrate social behaviors best understood at the level of neural circuits. Both forms of signaling rely on midbrain inputs to hindbrain pattern generators that activate peripheral effectors (sonic muscles and electrocytes) to produce pulsatile signals that are modulated by frequency/repetition rate, amplitude and call duration. To generate signals that vary by sex, male phenotype, and social context, these circuits are responsive to a wide range of hormones and neuromodulators acting on different timescales at multiple loci.Bass and Zakon (2005)reviewed the behavioral neuroendocrinology of these two teleost groups, comparing how the regulation of their communication systems have both converged and diverged during their parallel evolution. Here, we revisit this comparison and review the complementary developments over the past 16 years. We (a) summarize recent work that expands our knowledge of the neural circuits underlying these two communication systems, (b) review parallel studies on the action of neuromodulators (e.g., serotonin, AVT, melatonin), brain steroidogenesis (viaaromatase), and social stimuli on the output of these circuits, (c) highlight recent transcriptomic studies that illustrate how contemporary molecular methods have elucidated the genetic regulation of social behavior in these fish, and (d) describe recent studies of mochokid catfish, which use both vocal and electric communication, and that use both vocal and electric communication and consider how these two systems are spliced together in the same species. Finally, we offer avenues for future research to further probe how similarities and differences between these two communication systems emerge over ontogeny and evolution.
Multiple-Factor Analyses of Futile Recanalization in Acute Ischemic Stroke Patients Treated With Mechanical Thrombectomy
Authors: Pan Hui , Lin Changchun , Chen Lina , Qiao Yuan , Huang Peisheng , Liu Bin , Zhu Yueqi , Su Jingjing , Liu Jianren
Published: August 2021

Background and Purpose: Acute ischemic stroke (AIS) is a serious threat to the life and health of middle-aged and elderly people. Mechanical thrombectomy offers the advantages of rapid recanalization, but the response of patients to this treatment varies greatly. This study investigated the risk factors for futile recanalization in AIS patients after thrombectomy through multivariate analyses.

Methods: A retrospective study was conducted in AIS patients with anterior circulation occlusion from a derivation cohort and a validation cohort who underwent thrombectomy and reperfusion defined as a modified Thrombolysis in Cerebral Infarction (mTICI) score of 2b/3. Using the modified Rankin Scale (mRS) at 90 days after the operation, the patients were divided into two groups, the meaningful recanalization group (mRS ≤ 2), and the futile recanalization group (mRS > 2). Multivariate logistic regression analyses were performed, and the receiver operating characteristic (ROC) curve was used to construct a risk prediction model for futile recanalization. The performance of prediction model was evaluated on the validation cohort.

Results: A total of 140 patients in the derivation cohort were enrolled, 46 patients in the meaningful recanalization group and 94 patients in the futile recanalization group. The two groups were significantly different in age, preoperative National Institute of Health Stroke Scale (NIHSS) score, and collateral circulation ASITN/SIR grade (P < 0.05). In multivariate regression analyses, patients' age ≥ 71, NIHSS ≥ 12, and ASITN/SIR ≤ 3 were risk factors for futile recanalization. Hence, an ANA (Age-NIHSS-ASITN/SIR) score scale consisting of age, NIHSS score, and ASITN/SIR grade factors can effectively predict the risk for futile recanalization (area under curve 0.75, 95% CI 0.67–0.83, specificity 67.4%, and sensitivity 73.4%). The proportion of patients with futile recanalization in ANA groups 0, 1, 2, and 3 were 21.05, 56.76, 79.03, and 90.91%, respectively. Furthermore, ANA score scale had also a good performance for predicting futile recanalization on the validation cohort.

Conclusions: Old age, high baseline NIHSS, and poor collateral circulation are risk factors for futile recanalization in AIS patients treated with thrombectomy. An ANA score that considers age, NIHSS, and collateral ASITN/SIR can effectively predict the risk for futile recanalization. Further studies with a larger sample size are needed to validate the prognostic value of this combined score for futile recanalization.
A Pro-social Pill? The Potential of Pharmacological Treatments to Improve Social Outcomes After Pediatric Traumatic Brain Injury
Authors: Semple Bridgette D. , Raghupathi Ramesh
Published: August 2021

Traumatic brain injury (TBI) is a leading cause of injury-induced disability in young children worldwide, and social behavior impairments in this population are a significant challenge for affected patients and their families. The protracted trajectory of secondary injury processes triggered by a TBI during early life—alongside ongoing developmental maturation—offers an extended time window when therapeutic interventions may yield functional benefits. This mini-review explores the scarce but promising pre-clinical literature to date demonstrating that social behavior impairments after early life brain injuries can be modified by drug therapies. Compounds that provide broad neuroprotection, such as those targeting neuroinflammation, oxidative stress, axonal injury and/or myelination, may prevent social behavior impairments by reducing secondary neuropathology. Alternatively, targeted treatments that promote affiliative behaviors, exemplified by the neuropeptide oxytocin, may reduce the impact of social dysfunction after pediatric TBI. Complementary literature from other early life neurodevelopmental conditions such as hypoxic ischemic encephalopathy also provides avenues for future research in neurotrauma. Knowledge gaps in this emerging field are highlighted throughout, toward the goal of accelerating translational research to support optimal social functioning after a TBI during early childhood.