bluuebunny/crossref_metadata_2025 huggingface dataset:
Modern Pollen Assemblages in Typical Agro-Pastoral Ecotone in the Eastern Tibetan Plateau and Its Implications for Anthropogenic Activities
Authors: Duan Ronglei , Wei Haicheng , Hou Guangliang , Gao Jingyi , Du Yongsheng , Qin Zhanjie
Published: July 2021

Long-term evolution of human-environment interaction in the Qinghai-Tibetan Plateau (QTP) has been discussed intensively in recent years. The identification of human-related pollen types may help explore the coupled process of climate change, ecological response and anthropogenic activities on the QTP. The aim of this study is to evaluate the impact of anthropogenic activities on surface pollen assemblages and identify pollen indicators associated with grazing and cultivation in typical agro-pastoral ecotone of the eastern QTP. Totally 84 surface samples were analyzed from five vegetational communities in the eastern QTP, which are identifiable based on surface pollen assemblages. Principal component analysis of 29 pollen types and two supplementary variables of human influences were used to assess the impact of anthropogenic activities on surface pollen assemblages in eastern QTP. Severe grazing led to increase of Rosaceae, Ranunculaceae, Fabaceae, Taraxacum-Type, Aster-type and Saussurea-Type in pollen assemblages. Highland agricultural cultivation can be identified by the content and morphological characteristic of Brassicaceae and Cerealia Poaceae pollen. The aerial dispersed distances of Brassicaceae and Cerealia Poaceae pollen are very short, and domesticated herbivores are important factors, which disperse the Cerealia Poaceae pollen into pastures in agro-pastoral ecotone of the QTP. Modern pollen indicators of cultivation and grazing activity will provide precise references for fossil pollen study of prehistoric human activities in the QTP.
Life in the Canopy: Using Camera-Traps to Inventory Arboreal Rainforest Mammals in Borneo
Authors: Haysom Jessica Karen , Deere Nicolas J. , Wearn Oliver R. , Mahyudin Azniza , Jami Jamiluddin bin , Reynolds Glen , Struebig Matthew J.
Published: July 2021

Arboreal mammals form a diverse group providing ecologically important functions such as predation, pollination and seed dispersal. However, their cryptic and elusive nature, and the heights at which they live, makes studying these species challenging. Consequently, our knowledge of rainforest mammals is heavily biased towards terrestrial species, limiting our understanding of overall community structure and the possible impacts of human-induced disturbance. We undertook the first in-depth appraisal of an arboreal mammal community in Southeast Asia, using camera-traps set in unlogged and logged tropical rainforest in Sabah, Borneo. Using paired canopy and terrestrial camera-traps at 50 locations (25 in unlogged forest, 25 in logged), we assessed the effectiveness of camera-trapping at characterising the arboreal versus terrestrial community, and tested the influence of strata and forest type on community structure and composition. The paired design detected 55 mammal species across 15,817 camera-trap nights (CTNs), and additional canopy sampling in a subset of trees added a further two arboreal species to the inventory. In total, thirty species were detected exclusively by terrestrial camera-traps, eighteen exclusively by canopy camera-traps, and nine by units set at both heights, demonstrating significant differences between arboreal and terrestrial communities. This pattern was strongest in unlogged forest, reflecting greater structural diversity of this habitat, but held in logged forest as well. Species accumulation curves revealed that canopy camera-trapping significantly boosted species inventories compared to terrestrial-only sampling, and was particularly effective at detecting gliding mammals, rodents and primates. Canopy inventories took longer to reach an asymptote, suggesting that a greater sampling effort is required when deploying canopy camera-traps compared to those set on the ground. We demonstrate that arboreal mammals in Borneo’s rainforest form a diverse and distinct community, and can be sampled effectively using canopy camera-traps. However, the additional costs incurred by sampling in the canopy can be substantial. We provide recommendations to maximise sampling effectiveness, while bringing down costs, to help encourage further study into one of the last frontiers of tropical forest research.
Why and How to Switch to Genomic Selection: Lessons From Plant and Animal Breeding Experience
Authors:   R2D2 Consortium, Fugeray-Scarbel Aline , Bastien Catherine , Dupont-Nivet Mathilde , Lemarié Stéphane
Published: July 2021

The present study is a transversal analysis of the interest in genomic selection for plant and animal species. It focuses on the arguments that may convince breeders to switch to genomic selection. The arguments are classified into three different “bricks.” The first brick considers the addition of genotyping to improve the accuracy of the prediction of breeding values. The second consists of saving costs and/or shortening the breeding cycle by replacing all or a portion of the phenotyping effort with genotyping. The third concerns population management to improve the choice of parents to either optimize crossbreeding or maintain genetic diversity. We analyse the relevance of these different bricks for a wide range of animal and plant species and sought to explain the differences between species according to their biological specificities and the organization of breeding programs.
Case Report: Diagnosis of Human Alveolar Echinococcosis via Next-Generation Sequencing Analysis
Authors: Li Ke , Ma Yubao , Ban Rui , Shi Qiang
Published: July 2021

Introduction: Alveolar echinococcosis (AE) is a rare parasitic disease caused by the infection of Echinococcus multilocularis. AE may mimic malignancy both in clinical presentation and radiological imaging, which is often misdiagnosed as metastatic tumor. Recently, next-generation sequencing (NGS) technologies are increasingly being used to address a diverse range of biological questions. Here, we describe a rare case of alveolar echinococcosis diagnosed by pan-pathogen screening, using next-generation sequencing. To the best of our knowledge, this is the first reported case of AE which was definitely diagnosed relying NGS of cerebrospinal fluid (CSF).

Case Presentation: A 33-year-old man presented with repeat seizure and progressive headache for six months. Head magnetic resonance imaging (MRI) showed multiple masses with edema. Lung and abdominal computer tomography (CT) revealed multiple masses in bilateral lung, liver and the right adrenal gland. Bacterial, tuberculosis and fungal infection were excluded by CSF examination. Repeated target biopsy on the masses in the lung and liver showed as fibrous connective tissue without positive findings. NGS of CSF was performed and detected nucleic acid sequences of E. multilocularis. Consequently, the patient has accepted 1-year albendazole therapy. His case was followed up through imaging procedures.

Conclusion: The next-generation sequencing of CSF is a reliable and sensitive diagnostic method for the detection of pathogenic microorganisms, and may allow the accurate diagnosis of alveolar echinococcosis. In view of this case, we recommend NGS as a potential tool for diagnosis of cerebral AE, especially if repeated biopsies are negative.
Circulating miRNAs in Serum as Biomarkers for Early Diagnosis of Non-small Cell Lung Cancer
Authors: Duan Xiaotong , Qiao Simiao , Li Dianhe , Li Shangbiao , Zheng Zhihao , Wang Qin , Zhu Xiaoxia
Published: July 2021

Background

Non-small cell lung cancer (NSCLC) accounts for about 85% of lung cancers. This study aimed to discover the potential miRNA biomarkers for early detection of NSCLC.

Methods

Total circulating miRNAs were extracted from six patients and six volunteers and run on the miRNA chip. The differentially expressed miRNAs acquired by data mining were intersected with chip results, and qRT-PCR were carried out. Then the differentially miRNAs were validated by using a validation cohort (120 participants). ROC curves were established to evaluate the diagnostic efficacy of the differentially circulating miRNAs. The target genes of the differential miRNAs were identified using the miRTarBase database, and follow-up GO and KEGG enrichment analysis were conducted.

Results

We identified 577 miRNA which screened according to the criteria (fold change > 2 and p value < 0.05). Among them, seven circulating miRNAs passed additional filtering based on data mining. These miRNAs were further validated in the training and validation cohort. miR-492, miR-590-3p, and miR-631 were differentially expressed in the patients’ serum, and the area under the ROC curve (AUC) values of these miRNAs were 0.789, 0.792, and 0.711, respectively. When using them as a combination to discriminate healthy volunteers from patients, the AUC reached 0.828 (95% CI, 0.750–0.905, p = 0.000) with a sensitivity of 86.7% and specificity of 71.7%. The follow-up enrichment analysis showed that target genes of three miRNA were associated with tumorigenesis and progression, such as cell cycle and P53 signaling pathway.

Conclusions

The combination of miR-492, miR-590-3p, and miR-631 can be utilized to distinguish healthy individuals and early-stage NSCLC patients.

Impact

The combination of miR-492, miR-590-3p, and miR-631 might be a promising serum biomarker in patients for the early diagnosis of NSCLC.
PTX3 Deficiency Promotes Enhanced Accumulation and Function of CD11c+CD11b+ DCs in a Murine Model of Allergic Inflammation
Authors: Balhara Jyoti , Koussih Latifa , Mohammed Ashfaque , Shan Lianyu , Lamkhioued Bouchaib , Gounni Abdelilah S.
Published: July 2021

PTX3 is a unique member of the long pentraxins family and plays an indispensable role in regulating the immune system. We previously showed that PTX3 deletion aggravates allergic inflammation via a Th17 -dominant phenotype and enhanced CD4 T cell survival using a murine model of ovalbumin (OVA) induced allergic inflammation. In this study, we identified that upon OVA exposure, increased infiltration of CD11c+CD11b+ dendritic cells (DCs) was observed in the lungs of PTX3-/- mice compared to wild type littermate. Further analysis showed that a short-term OVA exposure led to an increased number of bone marrow common myeloid progenitors (CMP) population concomitantly with increased Ly6Chigh CCR2high monocytes and CD11c+CD11b+ DCs in the lungs. Also, pulmonary CD11c+CD11b+ DCs from OVA-exposed PTX3-/- mice exhibited enhanced expression of maturation markers, chemokines receptors CCR2, and increased OVA uptake and processing compared to wild type controls. Taken together, our data suggest that PTX3 deficiency heightened lung CD11c+CD11b+DC numbers and function, hence exacerbating airway inflammatory response.
Global Transcriptomics Uncovers Distinct Contributions From Splicing Regulatory Proteins to the Macrophage Innate Immune Response
Authors: Wagner Allison R. , Scott Haley M. , West Kelsi O. , Vail Krystal J. , Fitzsimons Timothy C. , Coleman Aja K. , Carter Kaitlyn E. , Watson Robert O. , Patrick Kristin L.
Published: July 2021

Pathogen sensing via pattern recognition receptors triggers massive reprogramming of macrophage gene expression. While the signaling cascades and transcription factors that activate these responses are well-known, the role of post-transcriptional RNA processing in modulating innate immune gene expression remains understudied. Given their crucial role in regulating pre-mRNA splicing and other RNA processing steps, we hypothesized that members of the SR/hnRNP protein families regulate innate immune gene expression in distinct ways. We analyzed steady state gene expression and alternatively spliced isoform production in ten SR/hnRNP knockdown RAW 264.7 macrophage-like cell lines following infection with the bacterial pathogen Salmonella enterica serovar Typhimurium (Salmonella). We identified thousands of transcripts whose abundance is increased or decreased by SR/hnRNP knockdown in macrophages. Notably, we observed that SR and hnRNP proteins influence expression of different genes in uninfected versus Salmonella-infected macrophages, suggesting functionalization of these proteins upon pathogen sensing. Likewise, we found that knockdown of SR/hnRNPs promoted differential isoform usage (DIU) for thousands of macrophage transcripts and that these alternative splicing changes were distinct in uninfected and Salmonella-infected macrophages. Finally, having observed a surprising degree of similarity between the differentially expressed genes (DEGs) and DIUs in hnRNP K and U knockdown macrophages, we found that hnRNP K and U knockdown macrophages are both more restrictive to Vesicular Stomatitis Virus (VSV), while hnRNP K knockdown macrophages are more permissive to Salmonella Typhimurium. Based on these findings, we conclude that many innate immune genes evolved to rely on one or more SR/hnRNPs to ensure the proper magnitude of their induction, supporting a model wherein pre-mRNA splicing is critical for regulating innate immune gene expression and controlling infection outcomes in macrophages ex vivo.
Hematopoietic Stem Cells in Type 1 Diabetes
Authors: Pastore Ida , Assi Emma , Ben Nasr Moufida , Bolla Andrea Mario , Maestroni Anna , Usuelli Vera , Loretelli Cristian , Seelam Andy Joe , Abdelsalam Ahmed , Zuccotti Gian Vincenzo , D’Addio Francesca , Fiorina Paolo
Published: July 2021

Despite the increasing knowledge of pathophysiological mechanisms underlying the onset of type 1 diabetes (T1D), the quest for therapeutic options capable of delaying/reverting the diseases is still ongoing. Among all strategies currently tested in T1D, the use of hematopoietic stem cell (HSC)-based approaches and of teplizumab, showed the most encouraging results. Few clinical trials have already demonstrated the beneficial effects of HSCs in T1D, while the durability of the effect is yet to be established. Investigators are also trying to understand whether the use of selected and better-characterized HSCs subsets may provide more benefits with less risks. Interestingly, ex vivo manipulated HSCs showed promising results in murine models and the recent introduction of the humanized mouse models accelerated the translational potentials of such studies and their final road to clinic. Indeed, immunomodulatory as well as trafficking abilities can be enhanced in genetically modulated HSCs and genetically engineered HSCs may be viewed as a novel “biologic” therapy, to be further tested and explored in T1D and in other autoimmune/immune-related disorders.
Argo Float Reveals Biogeochemical Characteristics Along the Freshwater Gradient Off Western Patagonia
Authors: Galán Alexander , Saldías Gonzalo S. , Corredor-Acosta Andrea , Muñoz Richard , Lara Carlos , Iriarte José Luis
Published: July 2021

The coastal region off Chilean Patagonia has been poorly studied due to the lack of available observations. Here we analyzed, by the very first time, biogeochemical (BGC) data to elucidate the role that biological and physical processes play on nitrate, oxygen, pH and hydrographic variables, along a salinity gradient off central Patagonia. Argo float profiles covering the upper ocean from December 2015 to July 2019 reveal that offshore waters are characterized by low temperatures and high salinities related to high oxygen and medium-high values of pH and nitrate. As the Argo float drifted onshore, freshwater influences the upper 50–100 m with low salinity and high temperature. Waters under the influence of the continental runoff were characterized by medium-to-high oxygen and pH levels, and the lowest nitrate concentrations. Interestingly, oxygen-deficient waters located beneath the freshwater-modified layer showed the lowest pH and highest nitrate. A comprehensive analysis of the temporal and vertical variability of the oxygen:nitrate ratio, in conjunction with biological-related and physical parameters, indicates that the BGC variability seems to be the result of a synergistic interaction between physical and biological processes, where the stratification sets up the environment and promotes the biological response that, in turn, is auto-regulated by modifying the chemical composition in the freshwater-influenced zone. The arrival of future floats with additional sensors (Chlorophyll/Fluorescence, Photosynthetically Active Radiation, Backscatter, etc.) will add new BGC properties that improve our understanding of the coastal marine response to the increasing freshwater input off western Patagonia in the context of climate change.
Applying Limnological Feature-Based Machine Learning Techniques to Chemical State Classification in Marine Transitional Systems
Authors: Concepcion Ronnie , Dadios Elmer , Bandala Argel , Caçador Isabel , Fonseca Vanessa F. , Duarte Bernardo
Published: July 2021

On a global scale, marine transitional waters have been severely impacted by anthropogenic activities. Historically, developing human civilizations have often settled in coastal areas with about 2/3 of the human population inhabiting areas within 20-km range from coastal areas. Environmental management worldwide strives for sustainable development while minimizing impacts to ecosystem integrity and has resulted in several framework directives, management programs, and legislation compelling governments to monitor their coastal systems and improve environmental quality. Among the most significant anthropogenic impacts to these ecosystems are land reclamation, dredging, pollution (sediment discharges, hazardous substances, litter, oil spills, and eutrophication), unsustainable exploitation of marine resources (sand extraction, oil and gas exploitation, and fishing), unmanaged tourism activities, the introduction of non-indigenous species, and climate change. The multitude of stressors is not independent, and as such, the chemical status of marine systems has serious implications on its ecological status and needs to be addressed efficiently. Public monitoring databases provide a large amount of physico-chemical (nutrient, dissolved oxygen, and chlorophyll a concentration) and contaminant (trace metals and polycyclic aromatic hydrocarbons) data for all Portuguese transitional systems (estuaries and coastal lagoons). These data are used to classify the chemical status (eutrophication and contamination level) of these ecosystems considering pre-defined classification thresholds, which facilitates communication to government authorities and management entities. Artificial intelligence and machine learning techniques provide an automated and efficient opportunity to improve simulation accuracy and further advance our understanding of environmental problems in estuarine and coastal waters when dealing with large environmental datasets. In the present work, we applied machine learning models, namely, linear discriminant analysis, classification tree, naive Bayesian, and support vector machine, to nutrient, dissolved oxygen, chlorophyll a, trace metals, and polycyclic aromatic hydrocarbon concentrations to produce a chemical status classification of the Portuguese marine transition systems. This approach allowed us to efficiently classify in an automated way the transitional water’s chemical status within the pre-defined classification thresholds, producing numerical index values that can easily be communicated to the general public and managers alike.
Changes in the Movement and Calling Behavior of Minke Whales (Balaenoptera acutorostrata) in Response to Navy Training
Authors: Durbach Ian N. , Harris Catriona M. , Martin Cameron , Helble Tyler A. , Henderson E. Elizabeth , Ierley Glenn , Thomas Len , Martin Stephen W.
Published: July 2021

Many marine mammals rely on sound for foraging, maintaining group cohesion, navigation, finding mates, and avoiding predators. These behaviors are potentially disrupted by anthropogenic noise. Behavioral responses to sonar have been observed in a number of baleen whale species but relatively little is known about the responses of minke whales (Balaenoptera acutorostrata). Previous analyses demonstrated a spatial redistribution of localizations derived from passive acoustic detections in response to sonar activity, but the lack of a mechanism for associating localizations prevented discriminating between movement and cessation of calling as possible explanations for this redistribution. Here we extend previous analyses by including an association mechanism, allowing us to differentiate between movement responses and calling responses, and to provide direct evidence of horizontal avoidance responses by individual minke whales to sonar during U.S. Navy training activities. We fitted hidden Markov models to 627 tracks that were reconstructed from 3 years of minke whale (B. acutorostrata) vocalizations recorded before, during, and after naval training events at the U.S. Navy’s Pacific Missile Range Facility, Kauai, Hawaii. The fitted models were used to identify different movement behaviors and to investigate the effect of sonar activity on these behaviors. Movement was faster and more directed during sonar exposure than in baseline phases. The mean direction of movement differed during sonar exposure, and was consistent with movement away from sonar-producing ships. Animals were also more likely to cease calling during sonar. There was substantial individual variation in response. Our findings add large-sample support to previous demonstrations of horizontal avoidance responses by individual minke whales to sonar in controlled exposure experiments, and demonstrate the complex nature of behavioral responses to sonar activity: some, but not all, whales exhibited behavioral changes, which took the form of horizontal avoidance or ceasing to call.
Effects of Light Intensity and Wavelength on the Phototaxis of the Crassostrea gigas (♂) and Crassostrea sikamea (♀) Hybrid Larvae
Authors: Zhang Xuekai , Fan Chao , Zhang Xingzhi , Li Qiongzhen , Li Yangchun , Wang Zhaoping
Published: July 2021

Light sensitivity is important for marine benthic invertebrates, and it plays a vital role in the oysters settling. Generally, the emerging of eyespot is a signal of oyster larvae settling, while like most of the other coastal species, the oysters are threatened by artificial light pollution. Crassostrea gigas and Crassostrea sikamea are two oyster species naturally distributed in China, and their hybrids are potential material for oyster cross-breeding. Therefore, we investigated the phototaxis of hybrid eyespot larvae and eyeless larvae under different light intensities and wavelengths to uncover how light affects their behaviors. The results indicated that hybrid oyster larvae had positive phototaxis to specific light intensity and wavelength. We further concluded that 5 lx was the positive phototaxis light intensity for the eyeless hybrid larvae, and that the acceptable light intensity range of the eyespot hybrid larvae expanded to 5–10 lx, but no higher than 15 lx; besides, the hybrid larvae behaved negatively to the light over 25 lx. The present study also suggested the positive effects of green light on larvae gathering and the induction of red light on eyespot larvae settling. In conclusion, our study may contribute to the understanding of phototaxis of hybrid oyster larvae, as well as the further perspective of light pollution on benthic communities and coastal system restoration.
Association Between Lower Extremity Venous Insufficiency and Intrapartum Fetal Compromise: A Nationwide Cross-Sectional Study
Authors: Asúnsolo Ángel , Chaowen Chen , Ortega Miguel A. , Coca Santiago , Borrell Luisa N. , De León-Luis Juan , García-Honduvilla Natalio , Álvarez-Mon Melchor , Buján Julia
Published: July 2021

Introduction: Chronic venous disorder (CVeD) has a high prevalence, being commonly diagnosed by the presence of varicose veins. In fact, the development of varicose veins in lower extremities and/or pelvic venous insufficiency (LEPVI) is frequent. However, its potential impact on fetal health has not been investigated. This study aimed to examine whether the presence of varicose veins in women's LEPVI is related to an intrapartum fetal compromise event.

Materials: A cross-sectional, national study was conducted using medical administrative records (CMBD) of all vaginal births (n = 256,531) recorded in 2015 in Spain. The independent variable was defined as the presence of varicose veins in the legs, vulva, and perineum or hemorrhoids. A logistic regression model was used to assess the association of interest.

Results: Among women with vaginal deliveries, those with varicose veins in their LEPVI have a significantly greater odds of intrapartum fetal compromise (OR = 1.30, 99.55%CI = 1.08–1.54) than their counterparts without varicose veins. After adjustment, this association remained significant (OR = 1.25, 99.5%CI = 1.05–1.50).

Conclusions: Our findings of an association between varicose veins in women's lower extremities and/or pelvis and intrapartum fetal compromise suggest that varicose veins may be a novel and important clinical risk factor for fetal well-being and health.
Body Mass Index and Disease Activity Are Associated With Moderate to Severe Disability in Crohn's Disease: A Cross-Sectional Study in Shanghai
Authors: Bian DongSheng , Jiang Yongmei , Gu Yubei , He Zirui , Chen Qi , Tang Yonghua , Zhong Jie , Shi Yongmei
Published: July 2021

Background: The inflammatory bowel disease disability index (IBD-DI) was used to access body functional consequences and disease burden. However, Chinese population data are considerably limited.

Objective: We aimed to screen for disability in patients with Crohn's disease (CD) and to assess potential associations with clinical parameters as well as indices related to sarcopenia.

Methods: This cross-sectional study includes 146 CD patients from Ruijin Hospital in Shanghai, China. All patients were screened for disability and sarcopenia on the basis of the IBD-DI scale, and the criteria for Asian Working Group for Sarcopenia, respectively. Clinical and demographic variables were collected.

Results: Approximately 52.05% of the subjects suffered from moderate or severe disabilities. The prevalence of sarcopenia (48.68 vs. 31.43%, P = 0.043), Patient-Generated Subjective Global Assessment score or PG-SGA≥4 (39.47 vs. 17.14%, P = 0.003), and high-level C- reactive protein (27.63 vs. 11.43%, P = 0.021) were higher in patients with moderate to severe disability than in those without to minimal disability. By multivariate regression modeling, the following were identified as independent factors related to moderate to severe disability: disease activity (OR:10.47, 95% CI: 2.09–52.42) and body mass index (BMI) (OR:4.11, 95% CI: 1.80–9.38).

Conclusions: Disability is common in CD patients. Our study showed that moderate to severe disability is not directly associated with muscle mass or muscle quantity but is mostly correlated with disease activity as well as BMI. Thus, close monitoring and follow-up should be conducted on patients who are at high risk of disability, and effective measures should be taken, which may be the best way to prevent disability.
An Overview of Ontologies in Virtual Reality-Based Training for Healthcare Domain
Authors: Mohamad Ummul Hanan , Ahmad Mohammad Nazir , Benferdia Youcef , Shapi'i Azrulhizam , Bajuri Mohd Yazid
Published: July 2021

Virtual reality (VR) is one of the state-of-the-art technological applications in the healthcare domain. One major aspect of VR applications in this domain includes virtual reality-based training (VRT), which simplifies the complicated visualization process of diagnosis, treatment, disease analysis, and prevention. However, not much is known on how well the domain knowledge is shared and considered in the development of VRT applications. A pertinent mechanism, known as ontology, has acted as an enabler toward making the domain knowledge more explicit. Hence, this paper presents an overview to reveal the basic concepts and explores the extent to which ontologies are used in VRT development for medical education and training in the healthcare domain. From this overview, a base of knowledge for VRT development is proposed to initiate a comprehensive strategy in creating an effective ontology design for VRT applications in the healthcare domain.
The Prognostic Accuracy of National Early Warning Score 2 on Predicting Clinical Deterioration for Patients With COVID-19: A Systematic Review and Meta-Analysis
Authors: Zhang Kai , Zhang Xing , Ding Wenyun , Xuan Nanxia , Tian Baoping , Huang Tiancha , Zhang Zhaocai , Cui Wei , Huang Huaqiong , Zhang Gensheng
Published: July 2021

Background: During the coronavirus disease 2019 (COVID-19) pandemic, the National Early Warning Score 2 (NEWS2) is recommended for the risk stratification of COVID-19 patients, but little is known about its ability to detect severe cases. Therefore, our purpose is to assess the prognostic accuracy of NEWS2 on predicting clinical deterioration for patients with COVID-19.

Methods: We searched PubMed, Embase, Scopus, and the Cochrane Library from December 2019 to March 2021. Clinical deterioration was defined as the need for intensive respiratory support, admission to the intensive care unit, or in-hospital death. Sensitivity, specificity, and likelihood ratios were pooled by using the bivariate random-effects model. Overall prognostic performance was summarized by using the area under the curve (AUC). We performed subgroup analyses to assess the prognostic accuracy of NEWS2 in different conditions.

Results: Eighteen studies with 6,922 participants were included. The NEWS2 of five or more was commonly used for predicting clinical deterioration. The pooled sensitivity, specificity, and AUC were 0.82, 0.67, and 0.82, respectively. Benefitting from adding a new SpO2 scoring scale for patients with hypercapnic respiratory failure, the NEWS2 showed better sensitivity (0.82 vs. 0.75) and discrimination (0.82 vs. 0.76) than the original NEWS. In addition, the NEWS2 was a sensitive method (sensitivity: 0.88) for predicting short-term deterioration within 72 h.

Conclusions: The NEWS2 had moderate sensitivity and specificity in predicting the deterioration of patients with COVID-19. Our results support the use of NEWS2 monitoring as a sensitive method to initially assess COVID-19 patients at hospital admission, although it has a relatively high false-trigger rate. Our findings indicated that the development of enhanced or modified NEWS may be necessary.
Additive Value of Dynamic FDOPA PET/CT for Glioma Grading
Authors: Girard Antoine , Le Reste Pierre-Jean , Metais Alice , Chaboub Nibras , Devillers Anne , Saint-Jalmes Hervé , Jeune Florence Le , Palard-Novello Xavier
Published: July 2021

Purpose: The aim of this study was to assess the value of the FDOPA PET kinetic parameters extracted using full kinetic analysis for tumor grading with neuronavigation-guided biopsies as reference in patients with newly-diagnosed gliomas.

Methods: Fourteen patients with untreated gliomas were investigated. Twenty minutes of dynamic positron-emission tomography (PET) imaging and a 20-min static image 10 min after injection were reconstructed from a 40-min list-mode acquisition immediately after FDOPA injection. Tumors volume-of-interest (VOI) were generated based on the MRI-guided brain biopsies. Static parameters (TBRmax and TBRmean) and kinetic parameters [K1 and k2 using full kinetic analysis with the reversible single-tissue compartment model with blood volume parameter and the time-to-peak (TTP)] were extracted. Performances of each parameter for differentiating low-grade gliomas (LGG) from high-grade gliomas (HGG) were evaluated by receiver-operating characteristic analyses (area under the curve; AUC).

Results: Thirty-two tumoral VOI were analyzed. K1, k2, and TTP were significantly higher for HGG than for LGG (median K1-value = 0.124 vs. 0.074 ml/ccm/min, p = 0.025, median k2-value = 0.093 vs. 0.063 min−1, p = 0.025, and median TTP-value = 10.0 vs. 15.0 min, p = 0.025). No significant difference was observed for the static parameters. The AUC for the kinetic parameters was higher than the AUC for the static parameters (respectively, AUCK1 = 0.787, AUCk2 = 0.785, AUCTTP = 0.775, AUCTBRmax = 0.551, AUCTBRmean = 0.575), significantly compared to TBRmax (respectively, p = 0.001 for K1, p = 0.031 for k2, and p = 0.029 for TTP).

Conclusion: The present study suggests an additive value of FDOPA PET/CT kinetic parameters for newly-diagnosed gliomas grading.
Application of Double-Strand RNAs Targeting Chitin Synthase, Glucan Synthase, and Protein Kinase Reduces Fusarium graminearum Spreading in Wheat
Authors: Yang Peng , Yi Shu-Yuan , Nian Jun-Na , Yuan Qing-Song , He Wei-Jie , Zhang Jing-Bo , Liao Yu-Cai
Published: July 2021

Controlling the devastating fungal pathogen Fusarium graminearum (Fg) is a challenge due to inadequate resistance in nature. Here, we report on the identification of RNAi molecules and their applications for controlling Fg in wheat through silencing chitin synthase 7 (Chs7), glucan synthase (Gls) and protein kinase C (Pkc). From transgenic Fg strains four RNAi constructs from Chs7 (Chs7RNAi−1, −2, −3, and −4), three RNAi constructs from Gls (GlsRNAi−2, −3, and −6), and one RNAi construct from Pkc (PkcRNAi−5) were identified that displayed effective silencing effects on mycelium growth in medium and pathogenicity in wheat spikes. Transcript levels of Chs7, Gls and Pkc were markedly reduced in those strains. Double-strand RNAs (dsRNAs) of three selected RNAi constructs (Chs7RNAi-4, GlsRNAi-6 and PkcRNA-5) strongly inhibited mycelium growth in vitro. Spray of those dsRNAs on detached wheat leaves significantly reduced lesion sizes; the independent dsRNAs showed comparable effects on lesions with combination of two or three dsRNAs. Expression of three targets Chs7, Gls, and Pkc was substantially down-regulated in Fg-infected wheat leaves. Further application of dsRNAs on wheat spikes in greenhouse significantly reduced infected spikelets. The identified RNAi constructs may be directly used for spray-induced gene silencing and stable expression in plants to control Fusarium pathogens in agriculture.
Prediction of Minocycline Activity in the Gut From a Pig Preclinical Model Using a Pharmacokinetic -Pharmacodynamic Approach
Authors: Vallé Quentin , Roques Béatrice B. , Bousquet-Mélou Alain , Dahlhaus David , Ramon-Portugal Felipe , Dupouy Véronique , Bibbal Delphine , Ferran Aude A.
Published: July 2021

The increase of multidrug-resistant (MDR) bacteria has renewed interest in old antibiotics, such as minocycline, that can be active against various MDR Gram-negative pathogens. The elimination of minocycline by both kidneys and liver makes it suitable for impaired renal function patients. However, the drawback is the possible elimination of a high amount of drug in the intestines, with potential impact on the digestive microbiota during treatment. This study aimed to predict the potential activity of minocycline against Enterobacterales in the gut after parenteral administration, by combining in vivo and in vitro studies. Total minocycline concentrations were determined by UPLC-UV in the plasma and intestinal content of piglets following intravenous administration. In parallel, the in vitro activity of minocycline was assessed against two Escherichia coli strains in sterilized intestinal contents, and compared to activity in a standard broth. We found that minocycline concentrations were 6–39 times higher in intestinal contents than plasma. Furthermore, minocycline was 5- to 245-fold less active in large intestine content than in a standard broth. Using this PK-PD approach, we propose a preclinical pig model describing the link between systemic and gut exposure to minocycline, and exploring its activity against intestinal Enterobacterales by taking into account the impact of intestinal contents.
Phenotypic and Genetic Characterization of Temperature-Induced Mutagenesis and Mortality in Cupriavidus metallidurans
Authors: Van Houdt Rob , Vandecraen Joachim , Heylen Wietse , Leys Natalie , Monsieurs Pieter , Provoost Ann , Aertsen Abram
Published: July 2021

Cupriavidus metallidurans strains display a decreased viability when incubated in rich medium at a temperature of 37°C compared to their normal growth temperature of 30°C, a phenomenon coined “temperature-induced mortality and mutagenesis” (TIMM). To scrutinize this aberrant phenotype further, the contributions of specific inducers and protective agents were determined. Different growth media, including lysogeny broth (LB) and Schatz, and components, including casamino acids, in particular amino acids (proline, cysteine, glycine, glutamine, leucine, histidine and phenylalanine) and ammonium, were found to induce TIMM at 37°C. Sorbitol was found to counteract TIMM. Furthermore, although TIMM is well conserved within the C. metallidurans species, multiple and strain-specific TIMM inducers exist. Twenty-nine percent of the TIMM survivors inherited resistance to TIMM. Whole-genome sequencing of two resistant derivatives revealed an important role of an uncharacterized oxidoreductase, indicating putative metabolic poisoning when grown in high-concentration nitrogen-containing media at 37°C.
Protein Surface Interactions—Theoretical and Experimental Studies
Authors: Almeida Fabio C. L. , Sanches Karoline , Pinheiro-Aguiar Ramon , Almeida Vitor S. , Caruso Icaro P.
Published: July 2021

In this review, we briefly describe a theoretical discussion of protein folding, presenting the relative contribution of the hydrophobic effect versus the stabilization of proteins via direct surface forces that sometimes may be overlooked. We present NMR-based studies showing the stability of proteins lacking a hydrophobic core which in turn present hydrophobic surface clusters, such as plant defensins. Protein dynamics measurements by NMR are the key feature to understand these dynamic surface clusters. We contextualize the measurement of protein dynamics by nuclear relaxation and the information available at protein surfaces and water cavities. We also discuss the presence of hydrophobic surface clusters in multidomain proteins and their participation in transient interactions which may regulate the function of these proteins. In the end, we discuss how surface interaction regulates the reactivity of certain protein post-translational modifications, such as S-nitrosation.
The Distributional Characteristics of Multiple Sclerosis Lesions on Quantitative Susceptibility Mapping and Their Correlation With Clinical Severity
Authors: Guo Zhuoxin , Long Liu , Qiu Wei , Lu Tingting , Zhang Lina , Shu Yaqing , Zhang Ke , Fang Ling , Chen Shaoqiong
Published: July 2021

Background: Multiple sclerosis (MS) patients have a wide spectrum of severity and responses to therapy; the personalization of treatment relies on sensitive and specific biomarkers. Previous studies have suggested that susceptibility contrast in demyelinated plaques is associated with iron-related pathology in multiple sclerosis which may indicate clinical severity. The aims of this study were to characterize the spatial distribution of MS lesions with different iron patterns by using quantitative susceptibility mapping and to explore neuroradiological findings that correlate with poor clinical outcome.

Methods: Twenty-six patients with relapsing–remitting MS [14 men, 12 women; mean age, 29 ± 8 (standard deviation) years; age range, 21–52 years] were included in this study. Differences in lesion number, T2 volume, and susceptibility were compared among lesions subcategorized by location and by the presence or absence of a hyperintense rim on quantitative susceptibility mapping. Associations between these imaging features and clinical outcomes including Expanded Disability Status Scale scores and annual relapse rates were investigated.

Results: A total of 811 unifocal MS lesions were included, and their QSM patterns were nodular hyperintensity with no rim (rim–, 540, 67%) or with a hyperintense rim on the edge (rim+, 172, 21%) and nodular isointensity (99, 12%). Rim+ lesions had significantly larger volume (115 ± 142 vs. 166 ± 185 mm3, p < 0.001) and lower susceptibility (4 ± 15 vs. 8 ± 16 ppb, p < 0.05) than rim– lesions. More rim+ lesions were found in periventricular areas [median, 45%; interquartile range (IQR), 36%], whereas a larger proportion of rim– lesions were distributed in juxtacortical (median, 32%; IQR, 21%) and deep white matter (median, 38%; IQR, 22%) areas. The annual relapse rate was positively correlated with the proportion of periventricular rim+ lesions (p < 0.001, r = 0.65) and the proportion of subtentorial rim+ lesions (p < 0.05, r = 0.40). Additionally, a significant association was found between the burden of periventricular rim+ lesions (β = 0.64, p < 0.001) and the burden of subtentorial rim– lesions (β = 0.36, p < 0.05).

Conclusions: A high number or lesion burden of periventricular rim+ lesions or subtentorial lesions is associated with frequent clinical relapses.
Rate of Force Development as an Indicator of Neuromuscular Fatigue: A Scoping Review
Authors: D’Emanuele Samuel , Maffiuletti Nicola A. , Tarperi Cantor , Rainoldi Alberto , Schena Federico , Boccia Gennaro
Published: July 2021

Because rate of force development (RFD) is an emerging outcome measure for the assessment of neuromuscular function in unfatigued conditions, and it represents a valid alternative/complement to the classical evaluation of pure maximal strength, this scoping review aimed to map the available evidence regarding RFD as an indicator of neuromuscular fatigue. Thus, following a general overview of the main studies published on this topic, we arbitrarily compared the amount of neuromuscular fatigue between the “gold standard” measure (maximal voluntary force, MVF) and peak, early (≤100 ms) and late (>100 ms) RFD. Seventy full-text articles were included in the review. The most-common fatiguing exercises were resistance exercises (37% of the studies), endurance exercises/locomotor activities (23%), isokinetic contractions (17%), and simulated/real sport situations (13%). The most widely tested tasks were knee extension (60%) and plantar flexion (10%). The reason (i.e., rationale) for evaluating RFD was lacking in 36% of the studies. On average, the amount of fatigue for MVF (−19%) was comparable to late RFD (−19%) but lower compared to both peak RFD (−25%) and early RFD (−23%). Even if the rationale for evaluating RFD in the fatigued state was often lacking and the specificity between test task and fatiguing exercise characteristics was not always respected in the included studies, RFD seems to be a valid indicator of neuromuscular fatigue. Based on our arbitrary analyses, peak RFD and early phase RFD appear even to be more sensitive to quantify neuromuscular fatigue than MVF and late phase RFD.
The Role of Interhemispheric Interactions in Cortical Plasticity
Authors: Jablonka Jan Antoni , Binkowski Robert , Kazmierczak Marcin , Sadowska Maria , Sredniawa Władysław , Szlachcic Aleksandra , Urban Paulina
Published: July 2021

Despite the fact that there is a growing awareness to the callosal connections between hemispheres the two hemispheres of the brain are commonly treated as independent structures when peripheral or cortical manipulations are applied to one of them. The contralateral hemisphere is often used as a within-animal control of plastic changes induced onto the other side of the brain. This ensures uniform conditions for producing experimental and control data, but it may overlook possible interhemispheric interactions. In this paper we provide, for the first time, direct proof that cortical, experience-dependent plasticity is not a unilateral, independent process. We mapped metabolic brain activity in rats with 2-[14C] deoxyglucose (2DG) following experience-dependent plasticity induction after a month of unilateral (left), partial whiskers deprivation (only row B was left). This resulted in ∼45% widening of the cortical sensory representation of the spared whiskers in the right, contralateral barrel field (BF). We show that the width of 2DG visualized representation is less than 20% when only contralateral stimulation of the spared row of whiskers is applied in immobilized animals. This means that cortical map remodeling, which is induced by experience-dependent plasticity mechanisms, depends partially on the contralateral hemisphere. The response, which is observed by 2DG brain mapping in the partially deprived BF after standard synchronous bilateral whiskers stimulation, is therefore the outcome of at least two separately activated plasticity mechanisms. A focus on the integrated nature of cortical plasticity, which is the outcome of the emergent interactions between deprived and non-deprived areas in both hemispheres may have important implications for learning and rehabilitation. There is also a clear implication that there is nothing like “control hemisphere” since any plastic changes in one hemisphere have to have influence on functioning of the opposite one.
Behavioral Differences Across Theta Burst Stimulation Protocols. A Study on the Sense of Agency in Healthy Humans
Authors: Zito Giuseppe A. , Worbe Yulia , Lamy Jean-Charles , Kälin Joel , Bühler Janine , Weber Samantha , Müri René M. , Aybek Selma
Published: July 2021

Background

Theta burst stimulation (TBS) is a non-invasive brain stimulation method. Various stimulation protocols have been proposed, for instance, stimulation at 50 Hz with pattern at 5 Hz, or at 30 Hz with pattern at 6 Hz. To identify better stimulation parameters for behavioral applications, we investigated the effects of 50-Hz continuous TBS (cTBS) on the sense of agency (SoA), and compared them with a previously published study with 30-Hz cTBS.

Methods

Based on power analysis from a previous sample using two applications of 30-Hz cTBS, we recruited 20 healthy subjects in a single-blind, Vertex-controlled, randomized, crossover trial. Participants were stimulated with one application of 50-Hz cTBS over the right posterior parietal cortex (rPPC), a key area for agency processing, and the vertex, in a random order. A behavioral task targeting the SoA was done before and after stimulation. After controlling for baseline differences across samples, we studied the effect of stimulation in the two protocols separately.

Results

Compared to the previously published 30-Hz protocol, 50-Hz cTBS over the rPPC did not reveal significant changes in the SoA, similar to sham Vertex stimulation.

Conclusion

One application of 50-Hz cTBS was not sufficient to elicit behavioral effects, compared to two applications of 30-Hz cTBS, as previously described. This may be due to a mechanism of synaptic plasticity, consolidated through consecutive stimulation cycles. Our results are relevant for future studies aiming at modulating activity of the rPPC in cognitive domains other than agency, and in patients affected by abnormal agency, who could benefit from treatment options based on TBS.