bluuebunny/crossref_metadata_2025 huggingface dataset:
Variation and Diagnostic Power of the Internal Transcribed Spacer 2 in Mediterranean and Atlantic Eolid Nudibranchs (Mollusca, Gastropoda)
Authors: Garzia Matteo , Mariottini Paolo , Salvi Daniele , Furfaro Giulia
Published: June 2021

Mediterranean marine biodiversity is still underestimated especially for groups such as nudibranchs. The identification of nudibranchs taxa is challenging because few morphological characters are available and among them chromatic patterns often do not align with species delimitation. Molecular assessments helped unveiling cryptic diversity within nudibranchs and have been mostly based on mitochondrial markers. Fast evolving nuclear markers are much needed to complement phylogenetic and systematic assessments at the species and genus levels. Here, we assess the utility of the nuclear Internal Transcribed Spacer 2 (ITS2) to delimit species in the eolid nudibranchs using both primary and secondary structures. Comparisons between the variation observed at the ITS2 and at the two commonly used mitochondrial markers (COI and 16S) on 14 eolid taxa from 10 genera demonstrate the ability of ITS2 to detect congeneric, closely related, species. While ITS2 has been fruitfully used in several other mollusc taxa, this study represents the first application of this nuclear marker in nudibranchs.
Metabolomics in Prenatal Medicine: A Review
Authors: Monni Giovanni , Atzori Luigi , Corda Valentina , Dessolis Francesca , Iuculano Ambra , Hurt K. Joseph , Murgia Federica
Published: June 2021

Pregnancy is a complicated and insidious state with various aspects to consider, including the well-being of the mother and child. Developing better non-invasive tests that cover a broader range of disorders with lower false-positive rates is a fundamental necessity in the prenatal medicine field, and, in this sense, the application of metabolomics could be extremely useful. Metabolomics measures and analyses the products of cellular biochemistry. As a biomarker discovery tool, the integrated holistic approach of metabolomics can yield new diagnostic or therapeutic approaches. In this review, we identify and summarize prenatal metabolomics studies and identify themes and controversies. We conducted a comprehensive search of PubMed and Google Scholar for all publications through January 2020 using combinations of the following keywords: nuclear magnetic resonance, mass spectrometry, metabolic profiling, prenatal diagnosis, pregnancy, chromosomal or aneuploidy, pre-eclampsia, fetal growth restriction, pre-term labor, and congenital defect. Metabolite detection with high throughput systems aided by advanced bioinformatics and network analysis allowed for the identification of new potential prenatal biomarkers and therapeutic targets. We took into consideration the scientific papers issued between the years 2000–2020, thus observing that the larger number of them were mainly published in the last 10 years. Initial small metabolomics studies in perinatology suggest that previously unidentified biochemical pathways and predictive biomarkers may be clinically useful. Although the scientific community is considering metabolomics with increasing attention for the study of prenatal medicine as well, more in-depth studies would be useful in order to advance toward the clinic world as the obtained results appear to be still preliminary. Employing metabolomics approaches to understand fetal and perinatal pathophysiology requires further research with larger sample sizes and rigorous testing of pilot studies using various omics and traditional hypothesis-driven experimental approaches.
Regulatory Standards in Orphan Medicinal Product Designation in the EU
Authors: Tsigkos Stelios , Mariz Segundo , Sheean Maria Elzbieta , Larsson Kristina , Magrelli Armando , Stoyanova-Beninska Violeta
Published: June 2021

Twenty years of orphan regulation in Europe have now elapsed, with almost 2,400 orphan designated medicinal products and more than 190 orphan products authorised in the EU. Alongside the evolution in understanding of rare diseases, considerable regulatory knowledge has also been accumulated regarding the level of evidence that would support inclusion of products into the framework. This article reviews publications and regulatory documents pertaining to orphan medicinal product designation in the EU and discusses the general expectations in submitted applications as reflected in the current regulatory practise. Important elements to recommend granting a European orphan designation are the key considerations of orphan condition, medical plausibility, seriousness, and prevalence, while significant benefit is also assessed when there are authorised medicinal products for the sought indication. This review attempts to clarify the specific concepts currently used in that regard and discusses how the available data can be used to justify the criteria for designation. Moving away from theoretical expectations or assumptions, it stresses that the applications have to be complemented with nosological and epidemiological justifications pertaining to the proposed condition, as well as relevant data in specific non-clinical in vivo models or in affected patients to support inclusion into the orphan scheme.
Big Data Impacting Dynamic Food Safety Risk Management in the Food Chain
Authors: Donaghy John A. , Danyluk Michelle D. , Ross Tom , Krishna Bobby , Farber Jeff
Published: June 2021

Foodborne pathogens are a major contributor to foodborne illness worldwide. The adaptation of a more quantitative risk-based approach, with metrics such as Food safety Objectives (FSO) and Performance Objectives (PO) necessitates quantitative inputs from all stages of the food value chain. The potential exists for utilization of big data, generated through digital transformational technologies, as inputs to a dynamic risk management concept for food safety microbiology. The industrial revolution in Internet of Things (IoT) will leverage data inputs from precision agriculture, connected factories/logistics, precision healthcare, and precision food safety, to improve the dynamism of microbial risk management. Furthermore, interconnectivity of public health databases, social media, and e-commerce tools as well as technologies such as blockchain will enhance traceability for retrospective and real-time management of foodborne cases. Despite the enormous potential of data volume and velocity, some challenges remain, including data ownership, interoperability, and accessibility. This paper gives insight to the prospective use of big data for dynamic risk management from a microbiological safety perspective in the context of the International Commission on Microbiological Specifications for Foods (ICMSF) conceptual equation, and describes examples of how a dynamic risk management system (DRMS) could be used in real-time to identify hazards and control Shiga toxin-producing Escherichia coli risks related to leafy greens.
Endophytic Bacillus altitudinis Strain Uses Different Novelty Molecular Pathways to Enhance Plant Growth
Authors: Zhang Dening , Xu Hongli , Gao Jingyao , Portieles Roxana , Du Lihua , Gao Xiangyou , Borroto Nordelo Carlos , Borrás-Hidalgo Orlando
Published: June 2021

The identification and use of endophytic bacteria capable of triggering plant growth is an important aim in sustainable agriculture. In nature, plants live in alliance with multiple plant growth-promoting endophytic microorganisms. In the current study, we isolated and identified a new endophytic bacterium from a wild plant species Glyceria chinensis (Keng). The bacterium was designated as a Bacillus altitudinis strain using 16S rDNA sequencing. The endophytic B. altitudinis had a notable influence on plant growth. The results of our assays revealed that the endophytic B. altitudinis raised the growth of different plant species. Remarkably, we found transcriptional changes in plants treated with the bacterium. Genes such as maturase K, tetratricopeptide repeat-like superfamily protein, LOB domain-containing protein, and BTB/POZ/TAZ domain-containing protein were highly expressed. In addition, we identified for the first time an induction in the endophytic bacterium of the major facilitator superfamily transporter and DNA gyrase subunit B genes during interaction with the plant. These new findings show that endophytic B. altitudinis could be used as a favourable candidate source to enhance plant growth in sustainable agriculture.
Characterization of Hypoxia-Related Molecular Subtypes in Clear Cell Renal Cell Carcinoma to Aid Immunotherapy and Targeted Therapy via Multi-Omics Analysis
Authors: Zhong Weimin , Zhong Hongbin , Zhang Fengling , Huang Chaoqun , Lin Yao , Huang Jiyi
Published: June 2021

Objective: Tumor hypoxia is a key factor in resistance to anti-cancer treatment. Herein, this study aimed to characterize hypoxia-related molecular subtypes and assess their correlations with immunotherapy and targeted therapy in clear cell renal cell carcinoma (ccRCC).

Materials: We comprehensively analyzed copy number variation (CNV), somatic mutation, transcriptome expression profile and clinical information for ccRCC from TCGA and ICGC databases. Based on 98 prognosis-related hypoxia genes, samples were clustered using unsupervized non-negative matrix factorization (NMF) analysis. We characterized the differences between subtypes concerning prognosis, CNV, somatic mutations, pathways, immune cell infiltrations, stromal/immune scores, tumor purity, immune checkpoint inhibitors (ICI), response to immunotherapy and targeted therapy and CXC chemokines. Based on differentially expressed genes (DEGs) between subtypes, a prognostic signature was built by LASSO Cox regression analysis, followed by construction of a nomogram incorporating the signature and clinical features.

Results: Two hypoxia-related molecular subtypes (C1 and C2) were constructed for ccRCC. Differential CNV, somatic mutations and pathways were found between subtypes. C2 exhibited poorer prognosis, higher immune/stromal scores, and lower tumor purity than C1. Furthermore, C2 had more sensitivity to immunotherapy and targeted therapy than C1. The levels of CXCL1/2/3/5/6/8 chemokines in C2 were distinctly higher than in C1. Consistently, DEGs between subtypes were significantly enriched in cytokine-cytokine receptor interaction and immune responses. This subtype-specific signature can independently predict patients’ prognosis. Following verification, the nomogram could be utilized for personalized prediction of the survival probability.

Conclusion: Our findings characterized two hypoxia-related molecular subtypes for ccRCC, which can assist in identifying high-risk patients with poor clinical outcomes and patients who can benefit from immunotherapy or targeted therapy.
Reversal of a Spatial Discrimination Task in the Common Octopus (Octopus vulgaris)
Authors: Bublitz Alexander , Dehnhardt Guido , Hanke Frederike D.
Published: June 2021

Reversal learning requires an animal to learn to discriminate between two stimuli but reverse its responses to these stimuli every time it has reached a learning criterion. Thus, different from pure discrimination experiments, reversal learning experiments require the animal to respond to stimuli flexibly, and the reversal learning performance can be taken as an illustration of the animal's cognitive abilities. We herein describe a reversal learning experiment involving a simple spatial discrimination task, choosing the right or left side, with octopus. When trained with positive reinforcement alone, most octopuses did not even learn the original task. The learning behavior changed drastically when incorrect choices were indicated by a visual signal: the octopuses learned the task within a few sessions and completed several reversals thereby decreasing the number of errors needed to complete a reversal successively. A group of octopus trained with the incorrect-choice signal directly acquired the task quickly and reduced their performances over reversals. Our results indicate that octopuses are able to perform successfully in a reversal experiment based on a spatial discrimination showing progressive improvement, however, without reaching the ultimate performance. Thus, depending on the experimental context, octopus can show behavioral flexibility in a reversal learning task, which goes beyond mere discrimination learning.
Impairment of Cardiac Autonomic Nerve Function in Pre-school Children With Intractable Epilepsy
Authors: Yang Zhao , Cheng Tung-Yang , Deng Jin , Wang Zhiyan , Qin Xiaoya , Fang Xi , Yuan Yuan , Hao Hongwei , Jiang Yuwu , Liao Jianxiang , Yin Fei , Chen Yanhui , Zou Liping , Li Baomin , Gao Yuxing , Shu Xiaomei , Huang Shaoping , Gao Feng , Liang Jianmin , Li Luming
Published: June 2021

Objective: Intractable epilepsy and uncontrolled seizures could affect cardiac function and the autonomic nerve system with a negative impact on children's growth. The aim of this study was to investigate the variability and complexity of cardiac autonomic function in pre-school children with pediatric intractable epilepsy (PIE).

Methods: Twenty four-hour Holter electrocardiograms (ECGs) from 93 patients and 46 healthy control subjects aged 3–6 years were analyzed by the methods of traditional heart rate variability (HRV), multiscale entropy (MSE), and Kurths–Wessel symbolization entropy (KWSE). Receiver operating characteristic (ROC) curve analysis was used to estimate the overall discrimination ability. Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) models were also analyzed.

Results: Pre-school children with PIE had significantly lower HRV measurements than healthy controls in time (Mean_RR, SDRR, RMSSD, pNN50) and frequency (VLF, LF, HF, LF/HF, TP) domains. For the MSE analysis, area 1_5 in awake state was lower, and areas 6_15 and 6_20 in sleep state were higher in PIE with a significant statistical difference. KWSE in the PIE group was also inferior to that in healthy controls. In ROC curve analysis, pNN50 had the greatest discriminatory power for PIE. Based on both NRI and IDI models, the combination of MSE indices (wake: area1_5 and sleep: area6_20) and KWSE (m = 2, τ = 1, α = 0.16) with traditional HRV measures had greater discriminatory power than any of the single HRV measures.

Significance: Impaired HRV and complexity were found in pre-school children with PIE. HRV, MSE, and KWSE could discriminate patients with PIE from subjects with normal cardiac complexity. These findings suggested that the MSE and KWSE methods may be helpful for assessing and understanding heart rate dynamics in younger children with epilepsy.
Disease and Patient Characteristics Contributing to Diagnostic Delays in Patients With Guillain-Barré Syndrome
Authors: Pathikonda Chakrapani , Katyal Nakul , Narula Naureen , Govindarajan Raghav
Published: June 2021

Introduction: Diagnosis of Guillain Barre syndrome (GBS) is often made clinically. Certain patient and disease characteristics can cause delays in diagnosis and management.

Methods: Observational retrospective study of forty-four patients diagnosed with GBS either clinically, cerebrospinal fluid analysis, and/or by electro-diagnostic criteria at a teaching hospital (University of Missouri Hospital) in Columbia, Mid-Missouri between 2011 and 2017.

Results: Patients with coexisting neurological conditions had statistically significant delay in diagnosis of GBS [Mean (SD); 13 ± 5 vs. 9.39 ± 4.7; p = 0.03]. Patients presenting with motor + symptoms (sensory and/or autonomic, in addition to motor), compared to those with only motor symptoms had statistically significant delay in diagnosis of GBS [Mean (SD); 11.90 ± 5 vs. 8.58 ± 4; p = 0.04].

Discussion: Presence of co-existing neurological conditions, and motor + symptoms can delay timely diagnosis and management of GBS.
Toward Robust Cognitive 3D Brain-Inspired Cross-Paradigm System
Authors: Ben Abdallah Abderazek , Dang Khanh N.
Published: June 2021

Spiking Neuromorphic systems have been introduced as promising platforms for energy-efficient spiking neural network (SNNs) execution. SNNs incorporate neuronal and synaptic states in addition to the variant time scale into their computational model. Since each neuron in these networks is connected to many others, high bandwidth is required. Moreover, since the spike times are used to encode information in SNN, a precise communication latency is also needed, although SNN is tolerant to the spike delay variation in some limits when it is seen as a whole. The two-dimensional packet-switched network-on-chip was proposed as a solution to provide a scalable interconnect fabric in large-scale spike-based neural networks. The 3D-ICs have also attracted a lot of attention as a potential solution to resolve the interconnect bottleneck. Combining these two emerging technologies provides a new horizon for IC design to satisfy the high requirements of low power and small footprint in emerging AI applications. Moreover, although fault-tolerance is a natural feature of biological systems, integrating many computation and memory units into neuromorphic chips confronts the reliability issue, where a defective part can affect the overall system's performance. This paper presents the design and simulation of R-NASH-a reliable three-dimensional digital neuromorphic system geared explicitly toward the 3D-ICs biological brain's three-dimensional structure, where information in the network is represented by sparse patterns of spike timing and learning is based on the local spike-timing-dependent-plasticity rule. Our platform enables high integration density and small spike delay of spiking networks and features a scalable design. R-NASH is a design based on the Through-Silicon-Via technology, facilitating spiking neural network implementation on clustered neurons based on Network-on-Chip. We provide a memory interface with the host CPU, allowing for online training and inference of spiking neural networks. Moreover, R-NASH supports fault recovery with graceful performance degradation.
Characterization of a Novel Food Grade Emulsion Stabilized by the By- Product Proteins Extracted From the Head of Giant Freshwater Prawn (Macrobrachium rosenbergii)
Authors: Wu Yi , Li Yufeng , Wang Ronghan , Zhao Yong , Liu Haiquan , Wang Jing Jing
Published: June 2021

The aim of this work was to develop a food-grade emulsion that stabilized by the by-product proteins in the head of giant freshwater prawn. The physicochemical properties of protein particles were characterized, and the stability of proteins-stabilized emulsions under different environmental stresses was evaluated. Results showed that the proteins were relatively hydrophilic and preferentially resided in the aqueous phase to form oil/water emulsions. On this basis, the proteins exhibited superior ability to stabilize the emulsions, and remarkably, the emulsions stabilized by 2% proteins and 3:7 oil/water ratio efficiently resisted the freeze-thaw treatment and the change of pH (3–9), salt addition (NaCl, 50–400 mM), and storage temperatures (4–60°C). Furthermore, the emulsions showed a matched long-term stability with the existing biopolymers-stabilized emulsions. Consequently, this is the first finding of the by-product proteins in the head of giant freshwater prawn as an excellent emulsifier to stabilize emulsions, which help to improve the stability of food-grade emulsions and the added value of aquatic products.
Epigenetics in Kawasaki Disease
Authors: Sharma Kaushal , Vignesh Pandiarajan , Srivastava Priyanka , Sharma Jyoti , Chaudhary Himanshi , Mondal Sanjib , Kaur Anupriya , Kaur Harvinder , Singh Surjit
Published: June 2021

Kawasaki disease (KD) is a common febrile multisystemic inflammatory illness in children that preferentially affects coronary arteries. Children with KD who develop coronary artery aneurysms have a life-long risk of premature coronary artery disease. Hypothesis of inherent predisposition to KD is supported by epidemiological evidence that suggests increased risk of development of disease in certain ethnicities and in children with a previous history of KD in siblings or parents. However, occurrence of cases in clusters, seasonal variation, and very low risk of recurrence suggests an acquired trigger (such as infections) for the development of illness. Epigenetic mechanisms that modulate gene expression can plausibly explain the link between genetic and acquired predisposing factors in KD. Analysis of epigenetic factors can also be used to derive biomarkers for diagnosis and prognostication in KD. Moreover, epigenetic mechanisms can also help in pharmacogenomics with the development of targeted therapies. In this review, we analysed the available literature on epigenetic factors such as methylation, micro-RNAs, and long non-coding RNAs in KD and discuss how these mechanisms can help us better understand the disease pathogenesis and advance the development of new biomarkers in KD.
Policies to Encourage the Use of Biosimilars in European Countries and Their Potential Impact on Pharmaceutical Expenditure
Authors: Vogler Sabine , Schneider Peter , Zuba Martin , Busse Reinhard , Panteli Dimitra
Published: June 2021

Introduction: Biosimilar medicines are considered promising alternatives to new biologicals with high price tags. The extent of savings resulting from biosimilar use depends on their price and uptake, which are largely shaped by pricing, reimbursement, and demand-side policies. This article informs about different policy measures employed by European countries to design the biologicals market and explores potential savings from the increased use of biosimilar medicines in Germany.

Methods: Policy measures that target the price and uptake of biosimilar medicines were identified based on a prefilled questionnaire survey with public authorities in 16 European countries, who were the members of the Pharmaceutical Pricing and Reimbursement Information network (July 2020). Potential savings that could have been generated in Germany if different measures identified in the surveyed countries had been implemented were calculated for six publicly funded biological molecules. Price data of the Pharma Price Information service and German consumption data for 2018 were used for the calculation of five scenarios.

Results: Several countries use a price link policy, setting the biosimilar price as a percentage of the price of the reference biological. Also lowering the price of the reference biological upon market entry of a biosimilar is less frequently used. While tendering of biosimilar medicines in the inpatient setting is the norm, it is rarely employed for biosimilars in outpatient use. Reference price systems and INN prescribing of medicines are the commonly used policy measures in the off-patent market, but some countries define exemptions for biologicals. Substituting biosimilars at the pharmacy level is rather an exception. Potential savings in Germany ranged from 5% (simple price link) to 55% (prices at the level of other countries) for the six studied molecules.

Conclusion: Despite some differences, there are discernible tendencies across European countries with regard to their applications of certain policy measures targeting the price and uptake of biosimilar medicines. The potential for savings of some of these policies was clearly demonstrated. Monitoring and evaluation of these rather recent measures is key for obtaining a more comprehensive picture of their impact.
The Use of Oseltamivir as Adjunctive Therapy for the Treatment of Hand-Food-and-Mouth Disease: A Meta-Analysis of Randomized Clinical Trials
Authors: Zhao Yijing , Sun Yangyang , Alolga Raphael N. , Ma Gaoxiang , Wang Fan
Published: June 2021

Background: Hand-foot-and-mouth disease (HFMD) is a common childhood illness caused by enteroviruses. Oseltamivir (OS), a neuraminidase inhibitor, has been frequently used as an adjunctive therapy for the treatment of HFMD. Solid evidence, however, is lacking regarding the efficacy of such adjunctive therapy. This work is to conduct a meta-analysis of randomized clinical trials (RCTs) to assess the efficacy of oseltamivir for HFMD in children.

Methods: Eligible studies from inception to October 10, 2020 were identified by searching six databases (PubMed, Embase, CENTRAL, CNKI, Wanfang, and VIP database). Quality of evidence was assessed using the Cochrane Collaboration tool.

Results: Of a total of 91 entries, 11 RCTs involving 977 HFMD children were included in the final analysis. The results showed that the therapy combined with oseltamivir was more effective, with higher effective rate (RR, 0.84; 95% CI, 0.80 to 0.87; p < 0.01), shorter fever clearance time (days) (SMD, −0.74; 95% CI, −1.12 to −0.35; p < 0.01), shorter rash regression time (days) (MD, −0.89; 95% CI, −1.05 to −0.72; p < 0.01) and shorter clinical cure time (SMD, −1.08; 95% CI, −1.55 to −0.61; p < 0.01). No significant difference was observed in the risk of adverse reactions between the groups with and without oseltamivir.

Conclusion: The use of oseltamivir as adjunctive therapy shows effectiveness and no increased risk of adverse reactions for the treatment of HFMD in children.
Maintenance of Muscle Mass and Cardiorespiratory Fitness to Cancer Patients During COVID-19 Era and After SARS-CoV-2 Vaccine
Authors: Conceição Miguel S. , Derchain Sophie , Vechin Felipe Cassaro , Telles Guilherme , Maginador Guilherme Fiori , Sarian Luís Otávio , Libardi Cleiton Augusto , Ugrinowitsch Carlos
Published: June 2021

There is emerging evidence that decreased muscle mass and cardiorespiratory fitness (CRF) are associated with increased risk of cancer-related mortality. This paper aimed to present recommendations to prescribe effective and safe exercise protocols to minimize losses, maintain or even improve muscle mass, strength, and CRF of the cancer patients who are undergoing or beyond treatment during the COVID-19 era. Overall, we recommend performing exercises with bodyweight, elastic bands, or suspension bands to voluntary interruption (i.e., interrupt the exercise set voluntarily, according to their perception of fatigue, before concentric muscular failure) to maintain or increase muscle strength and mass and CRF during COVID-19 physical distancing. Additionally, rest intervals between sets and exercises (i.e., long or short) should favor maintaining exercise intensities between 50 and 80% of maxHR and/or RPE of 12. In an exercise program with these characteristics, the progression of the stimulus must be carried out by increasing exercise complexity, number of sets, and weekly frequency. With feasible exercises attainable anywhere, modulating only the work-to-rest ratio and using voluntary interruption, it is possible to prescribe exercise for a wide range of patients with cancer as well as training goals. Exercise must be encouraged; however, exercise professionals must be aware of the patient’s health condition even at a physical distance to provide a safe and efficient exercise program. Exercise professionals should adjust the exercise prescription throughout home confinement whenever necessary, keeping in mind that minimal exercise stimuli are beneficial to patients in poor physical condition.
GLUT4 in Mouse Endometrial Epithelium: Roles in Embryonic Development and Implantation
Authors: Long Yun , Wang Yi-cheng , Yuan Dong-zhi , Dai Xin-hua , Liao Lin-chuan , Zhang Xue-qin , Zhang Li-xue , Ma Yong-dan , Lei Yi , Cui Zhi-hui , Zhang Jin-hu , Nie Li , Yue Li-min
Published: June 2021

GLUT4 is involved in rapid glucose uptake among various kinds of cells to contribute to glucose homeostasis. Prior data have reported that aberrant glucose metabolism by GLUT4 dysfunction in the uterus could be responsible for infertility and increased miscarriage. However, the expression and precise functions of GLUT4 in the endometrium under physiological conditions remain unknown or controversial. In this study, we observed that GLUT4 exhibits a spatiotemporal expression in mouse uterus on pregnant days 1–4; its expression especially increased on pregnant day 4 during the window of implantation. We also determined that estrogen, in conjunction with progesterone, promotes the expression of GLUT4 in the endometrial epitheliumin vivoorin vitro. GLUT4 is an important transporter that mediates glucose transport in endometrial epithelial cells (EECs)in vitroorin vivo.In vitro, glucose uptake decreased in mouse EECs when the cells were treated with GLUT4 small interfering RNA (siRNA).In vivo, the injection of GLUT4-siRNA into one side of the mouse uterine horns resulted in an increased glucose concentration in the uterine fluid on pregnant day 4, although it was still lower than in blood, and impaired endometrial receptivity by inhibiting pinopode formation and the expressions of leukemia inhibitory factor (LIF) and integrin ανβ3, finally affecting embryonic development and implantation. Overall, the obtained results indicate that GLUT4 in the endometrial epithelium affects embryo development by altering glucose concentration in the uterine fluid. It can also affect implantation by impairing endometrial receptivity due to dysfunction of GLUT4.
Robotic Technologies for High-Throughput Plant Phenotyping: Contemporary Reviews and Future Perspectives
Authors: Atefi Abbas , Ge Yufeng , Pitla Santosh , Schnable James
Published: June 2021

Phenotyping plants is an essential component of any effort to develop new crop varieties. As plant breeders seek to increase crop productivity and produce more food for the future, the amount of phenotype information they require will also increase. Traditional plant phenotyping relying on manual measurement is laborious, time-consuming, error-prone, and costly. Plant phenotyping robots have emerged as a high-throughput technology to measure morphological, chemical and physiological properties of large number of plants. Several robotic systems have been developed to fulfill different phenotyping missions. In particular, robotic phenotyping has the potential to enable efficient monitoring of changes in plant traits over time in both controlled environments and in the field. The operation of these robots can be challenging as a result of the dynamic nature of plants and the agricultural environments. Here we discuss developments in phenotyping robots, and the challenges which have been overcome and others which remain outstanding. In addition, some perspective applications of the phenotyping robots are also presented. We optimistically anticipate that autonomous and robotic systems will make great leaps forward in the next 10 years to advance the plant phenotyping research into a new era.
The Plant Cuticle: An Ancient Guardian Barrier Set Against Long-Standing Rivals
Authors: Arya Gulab Chand , Sarkar Sutanni , Manasherova Ekaterina , Aharoni Asaph , Cohen Hagai
Published: June 2021

The aerial surfaces of plants are covered by a protective barrier formed by the cutin polyester and waxes, collectively referred to as the cuticle. Plant cuticles prevent the loss of water, regulate transpiration, and facilitate the transport of gases and solutes. As the cuticle covers the outermost epidermal cell layer, it also acts as the first line of defense against environmental cues and biotic stresses triggered by a large array of pathogens and pests, such as fungi, bacteria, and insects. Numerous studies highlight the cuticle interface as the site of complex molecular interactions between plants and pathogens. Here, we outline the multidimensional roles of cuticle-derived components, namely, epicuticular waxes and cutin monomers, during plant interactions with pathogenic fungi. We describe how certain wax components affect various pre-penetration and infection processes of fungi with different lifestyles, and then shift our focus to the roles played by the cutin monomers that are released from the cuticle owing to the activity of fungal cutinases during the early stages of infection. We discuss how cutin monomers can activate fungal cutinases and initiate the formation of infection organs, the significant impacts of cuticle defects on the nature of plant–fungal interactions, along with the possible mechanisms raised thus far in the debate on how host plants perceive cutin monomers and/or cuticle defects to elicit defense responses.
BEL1-like Homeodomain Protein BLH6a Is a Negative Regulator of CAld5H2 in Sinapyl Alcohol Monolignol Biosynthesis in Poplar
Authors: Wang Qiao , Dai Xinren , Pang Hongying , Cheng Yanxia , Huang Xiong , Li Hui , Yan Xiaojing , Lu Fachuang , Wei Hairong , Sederoff Ronald R. , Li Quanzi
Published: June 2021

Lignin is one of the major components of xylem cell walls in tree stems. The lignin in the wood of most flowering plants (dicotyledonous angiosperms) is typically polymerized from three monolignol precursors, coniferyl alcohol, sinapyl alcohol, and p-coumaroyl alcohol, resulting in guaiacyl (G), syringyl (S), and hydroxyphenyl (H) subunits, respectively. In this study, we focus on the transcriptional regulation of a coniferaldehyde 5-hydroxylase (CAld5H2) gene, which encodes a key enzyme for sinapyl alcohol biosynthesis. We carried out a yeast one-hybrid (Y1H) screen to identify candidate upstream transcription factors (TFs) regulating CAld5H2. We obtained 12 upstream TFs as potential regulators of CAld5H2. One of these TF genes, BLH6a, encodes a BEL1-like homeodomain (BLH) protein and negatively regulated the CAld5H2 promoter activity. The direct regulation of CAld5H2 promoter by BLH6a was supported by chromatin immunoprecipitation–quantitative polymerase chain reaction (ChIP–qPCR) and dominant repression of BLH6a in transgenic plants. Luciferase complementation imaging analyses showed extensive protein–protein interactions among these 12 TFs. We propose that BLH6a is a negative regulator of CAld5H2, which acts through combinatorial regulation of multiple TFs for sinapyl alcohol (S monolignol) biosynthesis in poplar.
Humorous Coping With Unrequited Love: Is Perspective Change Important?
Authors: Greve Werner , Hauser Johanna , Rühs Farina
Published: June 2021

A large number of studies suggest that humor is associated with mental well-being and effective as a means of coping. However, it is less well-understood which mechanisms are effective for this particular function of humor. The present study examines whether processes of change of perspective, which are often regarded as constitutive for humor, could be an effective coping-factor when facing unrequited love as a specific psychological burden. In a questionnaire study, N = 148 persons aged 18–65 years (w = 96) with actual or past experiences of unrequited love reported on their subjective burden due to this experience, their self-esteem and satisfaction with life, two scales for humor (Multidimensional Sense of Humor Scale: MSHS, and a self-constructed scale: Humorous Change of Perspective, HCOP) and a coping scale which measure change of perspective in the confrontation with goal blockages (Flexible Goal Adjustment, FGA). Results indicated that the burden of unrequited love [operationalized objectively as actuality of experience (dichotomous) or subjectively as burden experienced] and both indicators of well-being were negatively associated. Multiple regression analyses showed that humor was a significant moderator of this relationship in nearly all combinations of operationalizations of humor and indicators of well-being: Higher levels of humor are associated with better well-being even when the perceived burden was high. In addition, the study examined whether the coping effect of humor can be partly or mainly attributed to the individual's capacity to perspective change as captured by FGA. When including this scale as a covariate in the regression models, the moderation effect for MSHS did not persist; however, for HCOP the moderation effect remained unchanged: the moderator effect of humorous change of perspective proved to be independent of FGA. Taken together the results suggest that perspective-changing skills play a significant role in the coping effect of humor in dealing with psychological burdens. However, depending on which humor facet is measured, the entailed perspective change may or may not appear to go beyond what the individual's FGA can account for. This suggests that the coping effect caused by humorous change of perspective includes aspects that are also discussed for other coping resources as well as its own, humor-specific aspects. Potential avenues for future studies are discussed both with respect to the necessity for replication and extension of the present study and to the determination of other potential alleviativing effects of other facets of humor.
Post-retrieval Distortions of Self-Referential Negative Memory: Valence Consistency Enhances Gist-Directed False, While Non-negative Interference Generates More Intrusive Updates
Authors: Pan Dong-Ni , Li Xuebing
Published: June 2021

According to the theory of reconsolidation, the contents of an original memory can be updated after reactivation with subsequent new learnings. However, there seems to be a lack of an appropriate behavioral paradigm to study the reconsolidation of explicit self-related memory, which is of great significance to further explore its cognitive neural mechanism in the future. In two separate experiments, we adapted a trial-by-trial interfering paradigm with a self-episodic simulation process and investigated (1) whether it is possible to reconsolidate negative memories under the new behavioral paradigm and (2) how the emotional valence of post-retrieval interference material affects the reconsolidation of negative memories. The results showed that the negative memories under trial-by-trial self-simulation can be degraded and updated via post-retrieval interference processes. Individuals whose original memories were reactivated by initial background cues and who were then presented with new interference situations were less able to recall original scenes and showed more memory intrusions on these scenes than those who had experienced new learning without reactivation or only reactivation without interference. Furthermore, the extent and manner of memory change/updating were greatly influenced by the characteristics of interference information. For memories with negative valences, new learning materials with the same valence produced superior interference effects in the form of lower correct recalls and more integrated false; whereas the neutral interference materials can cause more memory intrusion. Post-retrieval memory distortions of negative self-memory may underlie different functional mechanisms.
Differential Associations Between Parents' Versus Children's Perceptions of Parental Socialization Goals and Chinese Adolescent Depressive Symptoms
Authors: Zhou Zexi , Li Mengtong , Wu Jiawen , Li Xiaoru
Published: June 2021

Although prior studies have demonstrated the associations between parental socialization goals and parenting practices, as well as parenting practices and adolescent depressive symptoms, respectively, research examining the comprehensive developmental pathways among these constructs (i. e., the path from parental socialization goals to parenting practices to adolescent depressive symptoms) is scarce, especially in the Chinese context. Grounded in the integrative model of parenting, this study investigated the associations between parental socialization goals and adolescent depressive symptoms by examining the indirect pathways through parents' autonomy support and psychological control as well as the moderating effect of educational stage. In Study 1, 345 Chinese adolescents and their primary caregivers completed a measure on parental socialization goals. Adolescents also reported on their depressive symptoms. Results showed that children who reported more self-development parental goals showed fewer depressive symptoms. However, parents' reports of goals or child-parent perceptual discrepancies were not related to children's depressive symptoms. Drawing on this finding, 424 middle school and 301 high school Chinese adolescents completed measures regarding parental socialization goals, autonomy support, psychological control, and their own depressive symptoms in Study 2. Results showed that parental autonomy support linked the associations of self-development and achievement-oriented parental goals and children's depressive symptoms among middle school students, whereas parental psychological control linked such associations among high school students. Our findings provide a more holistic view on how parents' socialization goals are related to children's depressive symptoms via their parenting practices. We also discussed the practical implications for the clinical work regarding adolescent depressive symptoms.
Gender Differences Related to Spirituality, Coping Skills and Risk Factors of Suicide Attempt: A Cross-Sectional Study of French Adolescent Inpatients
Authors: Mirkovic Bojan , Belloncle Vincent , Pellerin Hugues , Guilé Jean-Marc , Gérardin Priscille
Published: June 2021

Background:Suicide attempts in adolescence represent a major public health concern, since these behaviors are associated with psychosocial burden and an increased risk of suicide. This cross-sectional study aimed to explore possible gender differences related to protective and risk factors in adolescents who have attempted suicide.

Methods:Participants were French adolescents hospitalized for attempt suicide in five French pediatric departments. The participants were evaluated on 12 instruments measuring individual risk and protective factors.

Results:Our sample included 320 adolescents aged 13–17 years (M = 14.43, SD = 1.29), of whom 82% were female and 35% were repeat attempters. Boys had greater difficulties at school and used more lethal means such as strangulation. We failed to find any differences between the two groups as regards the main Axis I psychiatric diagnoses. Boys tend to use more non-productive coping skills such astension reductionorwishful thinkingand girls use more reference to other strategies such asseeking social support. Although spirituality scores were low overall sample, they were significantly higher among girls.

Conclusions:In the end, we find little difference between the two groups in terms of risk factors. However, we have shown gender differences in spirituality and some coping strategies. These results should be taken into consideration when designing suicide prevention programs.
Early-Onset Depression in Stroke Patients: Effects on Unfavorable Outcome 5 Years Post-stroke
Authors: Zeng Ya-Ying , Wu Meng-Xuan , Zhou Sheng-Nan , Geng Dan-Dan , Cheng Lin , Fan Kai-Li , Yu Xin , Tang Wen-Jie , He Jin-Cai
Published: June 2021

Background: Post-stroke depression (PSD) constitutes an essential complication of stroke and is associated with high-risk unfavorable outcome after stroke. The main objective of this prospective study was to determine the relationship between early-onset PSD (1 month after stroke) and functional outcomes 5 years after baseline enrollment.

Methods: Four hundred thirty-six patients who met the criteria were included in this study from October 2013 to February 2015. The follow-up time for each patient was ~5 years, with follow-up every 3 months. Patients received questionnaires including the 17-item Hamilton Depression Scale (HAMD), the Mini-Mental State Examination (MMSE), the National Institutes of Health Stroke Scale (NIHSS), the modified Rankin Scale (mRS), and the Barthel Index (BI).

Results: Of the 436 patients, 154 (35.3%) patients with the prevalence of PSD status at baseline, 26 (7.2%) patients with the prevalence of PSD status, and 73 (20.1%) had an unfavorable outcome 5 years after stroke. The odds ratio (OR) for unfavorable outcome at 5 years in the PSD group was ~2.2 relative to the non-PSD group after adjusting for potential risk factors [OR = 2.217, 95% confidence interval (CI) = 1.179–4.421, P = 0.015]. In the early-onset PSD group, HAMD scores were independently associated with 5-year unfavorable outcome rates (OR = 1.168, 95% CI = 1.015–1.345, P = 0.031).

Conclusions: Our findings indicate that early-onset PSD status in Chinese patients is an independent risk factor for unfavorable outcome 5 years after stroke, and that the severity of PSD is also related to unfavorable outcome.
Feasibility of Repeated Assessment of Cognitive Function in Older Adults Using a Wireless, Mobile, Dry-EEG Headset and Tablet-Based Games
Authors: McWilliams Esther C. , Barbey Florentine M. , Dyer John F. , Islam Md Nurul , McGuinness Bernadette , Murphy Brian , Nolan Hugh , Passmore Peter , Rueda-Delgado Laura M. , Buick Alison R.
Published: June 2021

Access to affordable, objective and scalable biomarkers of brain function is needed to transform the healthcare burden of neuropsychiatric and neurodegenerative disease. Electroencephalography (EEG) recordings, both resting and in combination with targeted cognitive tasks, have demonstrated utility in tracking disease state and therapy response in a range of conditions from schizophrenia to Alzheimer's disease. But conventional methods of recording this data involve burdensome clinic visits, and behavioural tasks that are not effective in frequent repeated use. This paper aims to evaluate the technical and human-factors feasibility of gathering large-scale EEG using novel technology in the home environment with healthy adult users. In a large field study, 89 healthy adults aged 40–79 years volunteered to use the system at home for 12 weeks, 5 times/week, for 30 min/session. A 16-channel, dry-sensor, portable wireless headset recorded EEG while users played gamified cognitive and passive tasks through a tablet application, including tests of decision making, executive function and memory. Data was uploaded to cloud servers and remotely monitored via web-based dashboards. Seventy-eight participants completed the study, and high levels of adherence were maintained throughout across all age groups, with mean compliance over the 12-week period of 82% (4.1 sessions per week). Reported ease of use was also high with mean System Usability Scale scores of 78.7. Behavioural response measures (reaction time and accuracy) and EEG components elicited by gamified stimuli (P300, ERN, Pe and changes in power spectral density) were extracted from the data collected in home, across a wide range of ages, including older adult participants. Findings replicated well-known patterns of age-related change and demonstrated the feasibility of using low-burden, large-scale, longitudinal EEG measurement in community-based cohorts. This technology enables clinically relevant data to be recorded outside the lab/clinic, from which metrics underlying cognitive ageing could be extracted, opening the door to potential new ways of developing digital cognitive biomarkers for disorders affecting the brain.
Comparison of Antipsychotics for the Treatment of Patients With Delirium and QTc Interval Prolongation: A Clinical Decision Analysis
Authors: Kurisu Ken , Yoshiuchi Kazuhiro
Published: June 2021

Background: Antipsychotics are frequently used to treat delirium but often induce corrected QT (QTc) prolongation, which can be lethal by causing torsade de pointes. Nonetheless, the selection of antipsychotics to treat delirium patients with prolonged baseline QTc intervals remains unclear. We aimed to assess the utility of antipsychotics based on their effects on treatment outcomes and QTc intervals.

Methods: A clinical decision analysis was conducted using data on the effects of antipsychotics on treatment outcomes and QTc intervals from published network meta-analyses. We quantified the utility of six antipsychotics (amisulpride, haloperidol, olanzapine, quetiapine, risperidone, and ziprasidone) using a decision tree and the obtained effect sizes. Subsequently, we conducted sensitivity analyses using multiple utility settings and another dataset. We also performed a probabilistic sensitivity analysis using Monte Carlo simulation, in which the effects of antipsychotics were randomly sampled given the plausible range.

Results: Amisulpride showed the highest utility when the baseline QTc interval was 420 ms. Quetiapine showed the highest utility when the baseline QTc interval was ≥450 ms. The sensitivity analyses also showed the superiority of quetiapine when the baseline QTc intervals were prolonged.

Conclusions: Decision analysis suggests that quetiapine is the optimal antipsychotic drug for the treatment of patients with delirium and prolonged baseline QTc intervals.