bluuebunny/crossref_metadata_2025 huggingface dataset:
LRP5 and LRP6 in Wnt Signaling: Similarity and Divergence
Authors: Ren Qian , Chen Jiongcheng , Liu Youhua
Published: May 2021

The canonical Wnt/β-catenin signaling plays a fundamental role in regulating embryonic development, injury repair and the pathogenesis of human diseases. In vertebrates, low density lipoprotein receptor-related proteins 5 and 6 (LRP5 and LRP6), the single-pass transmembrane proteins, act as coreceptors of Wnt ligands and are indispensable for Wnt signal transduction. LRP5 and LRP6 are highly homologous and widely co-expressed in embryonic and adult tissues, and they share similar function in mediating Wnt signaling. However, they also exhibit distinct characteristics by interacting with different protein partners. As such, each of them possesses its own unique functions. In this review, we systematically discuss the similarity and divergence of LRP5 and LRP6 in mediating Wnt and other signaling in the context of kidney diseases. A better understanding of the precise role of LRP5 and LRP6 may afford us to identify and refine therapeutic targets for the treatment of a variety of human diseases.
Electrochemical Cell Chips Based on Functionalized Nanometals
Authors: El-Said Waleed Ahmed , Yoon Jinho , Lee Sang-Nam , Choi Jeong-Woo
Published: May 2021

The electrochemical technique is one of the most accurate, rapid, and sensitive analytical assays, which becomes promising techniques for biological assays at a single-cell scale. Nanometals have been widely used for modification of the traditional electrodes to develop highly sensitive electrochemical cell chips. The electrochemical cell chips based on the nanostructured surface have been used as label-free, simple, and non-destructive techniques for in vitro monitoring of the effects of different anticancer drugs at the cellular level. Here, we will provide the recent progress in fabrication of nanopatterned surface and cell-based nanoarray, and discuss their applications based on electrochemical techniques such as detection of cellular states and chemicals, and non-destructive monitoring of stem cell differentiation.
Microglia: A Double-Edged Sword in Intracerebral Hemorrhage From Basic Mechanisms to Clinical Research
Authors: Liu Jiachen , Liu Lirong , Wang Xiaoyu , Jiang Rundong , Bai Qinqin , Wang Gaiqing
Published: May 2021

Microglia are the resident immune cells of the central nervous system (CNS). It is well established that microglia are activated and polarized to acquire different inflammatory phenotypes, either pro-inflammatory or anti-inflammatory phenotypes, which act as a critical component in the neuroinflammation following intracerebral hemorrhage (ICH). Microglia produce pro-inflammatory mediators at the early stages after ICH onset, anti-inflammatory microglia with neuroprotective effects appear to be suppressed. Previous research found that driving microglia towards an anti-inflammatory phenotype could restrict inflammation and engulf cellular debris. The principal objective of this review is to analyze the phenotypes and dynamic profiles of microglia as well as their shift in functional response following ICH. The results may further the understanding of the body’s self-regulatory functions involving microglia following ICH. On this basis, suggestions for future clinical development and research are provided.
Skin Responses in Newly Diagnosed Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal Gammopathy, and Skin Changes (POEMS) Syndrome After Therapy With Low-Dose Lenalidomide Plus Dexamethasone
Authors: Gao Yajuan , Zhang Shiyu , Yang Lu , Li Jian , Liu Yuehua , Wang Tao
Published: May 2021

Background

Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome is a rare paraneoplastic disease with a high prevalence of skin symptoms. Few studies have focused on skin responses to systemic treatment of this disease.

Objective

To evaluate skin responses after treatment with low-dose lenalidomide plus dexamethasone and determine their relationship with vascular endothelial growth factor (VEGF) and hematological responses.

Methods

A total of 41 consecutive Chinese patients who were at least 18 years of age with newly diagnosed POEMS syndrome were enrolled. 36 of them completed 12 cycles of treatment. Skin, serum VEGF, hematological and neurological responses were documented at 1, 2, 3, 6, 9, and 12 months during treatment.

Results

Skin manifestations were not associated with serum VEGF levels at baseline. Of the patients with hyperpigmentation, hemangiomas, hypertrichosis, white nails, or acrocyanosis separately, 26/34 (76.5%), 11/30 (36.7%), 14/15 (93.3%), 21/21 (100%), and 4/4 (100%) achieved complete responses at 12 months. Reduction in hyperpigmentation after 12 months reflected a good VEGF response (P = 0.017).

Conclusion

Low-dose lenalidomide plus dexamethasone therapy is effective in reversing skin changes in patients with POEMS syndrome.

Clinical Trial Registration

Clinicaltrials.gov, identifier NCT01816620
Unveiling a Hidden Event in Fluorescence Correlative Microscopy by AFM Nanomechanical Analysis
Authors: Galluzzi Massimiliano , Zhang Bokai , Zhang Han , Wang Lingzhi , Lin Yuan , Yu Xue-Feng , Chu Zhiqin , Li Jiangyu
Published: May 2021

Fluorescent imaging combined with atomic force microscopy (AFM), namely AFM-fluorescence correlative microscopy, is a popular technology in life science. However, the influence of involved fluorophores on obtained mechanical information is normally underestimated, and such subtle changes are still challenging to detect. Herein, we combined AFM with laser light excitation to perform a mechanical quantitative analysis of a model membrane system labeled with a commonly used fluorophore. Mechanical quantification was additionally validated by finite element simulations. Upon staining, we noticed fluorophores forming a diffuse weakly organized overlayer on phospholipid supported membrane, easily detected by AFM mechanics. The laser was found to cause a degradation of mechanical stability of the membrane synergically with presence of fluorophore. In particular, a 30 min laser irradiation, with intensity similar to that in typical confocal scanning microscopy experiment, was found to result in a ∼40% decrease in the breakthrough force of the stained phospholipid bilayer along with a ∼30% reduction in its apparent elastic modulus. The findings highlight the significance of analytical power provided by AFM, which will allow us to “see” the “unseen” in correlative microscopy, as well as the necessity to consider photothermal effects when using fluorescent dyes to investigate, for example, the deformability and permeability of phospholipid membranes.
Cognitive Function Changes in Older People. Results of Second Wave of Cognition of Older People, Education, Recreational Activities, NutritIon, Comorbidities, fUnctional Capacity Studies (COPERNICUS)
Authors: Kujawski Sławomir , Kujawska Agnieszka , Perkowski Radosław , Androsiuk-Perkowska Joanna , Hajec Weronika , Kwiatkowska Małgorzata , Skierkowska Natalia , Husejko Jakub , Bieniek Daria , Newton Julia L. , Morten Karl J. , Zalewski Paweł , Kędziora-Kornatowska Kornelia
Published: May 2021

Background

Cognitive reserve explains why subjects with more years of education, professional achievement, or participation in recreational activities show less cognitive decline with aging. We hypothesize that levels of recreational travel, education, occupation, systemic health, physical performance, and current cognitive activity levels affect the trajectory of cognitive function in older, healthy people in Poland.

Materials and Methods

Healthy, older people (N = 205) were examined and followed-up at 2 years. Participants completed physical and cognitive function assessments: including the Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA) and its two subtests Delayed Recall (DR) and Verbal Fluency (VF), and Trail Making Test Part B (TMT B). Factors associated with cognitive functioning were also examined.

Results

The MMSE result significantly decreased over 2 years. No significant decrease in other cognitive tests was noted. However, the trajectory of cognitive tests results varied between individual participants. Percentage of variance of change was explained by the following predictors: 21 in MMSE, 24 in MoCA, 8 in DR, 25 in VF, and 24 in TMT B. Age and the presence of varicose veins were significantly linked to negative changes in MMSE and MoCA scores, while working in a professional occupational status associated with a higher score. The subgroup with varicose veins did worse on the Delayed Recall subtest of MoCA.

Conclusion

Cognitive reserve could be extended by proxies of reserve that are related to systemic health and travel activity. The latter is a combination of social, physical, and cognitive activity and potentially might serve as an intervention to improve cognitive function in older people. However, due to the limitations of this study, results should be interpreted with caution and needs to be replicated in the further studies.
Beta-Secretase 1 Underlies Reactive Astrocytes and Endothelial Disruption in Neurodegeneration
Authors: Chacón-Quintero María Victoria , Pineda-López Lina Gisela , Villegas-Lanau Carlos Andrés , Posada-Duque Rafael , Cardona-Gómez Gloria Patricia
Published: May 2021

Dysfunction in the neurovascular unit (NVU) is a key component in the progressive deterioration of Alzheimer’s disease (AD) and is critical in vascular dementia. Recent studies have shown that inflammation plays early and perhaps causal roles in the pathogenesis of AD related to NVU damage, possibly in part by overactivating the aspartic acid protease activity of β-site amyloid precursor protein-cleaving enzyme 1 (BACE1), which until now has almost solely been studied in the context of the β-amyloid cascade. In this study, we analyzed the relationship of BACE1 with astrocytes and blood vessels in human brains with sporadic and familial dementia [Autosomal dominant cerebral arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), sporadic Alzheimer’s disease (SAD), and familial Alzheimer’s disease (FAD)] and how BACE1 inhibition affects astrocytes and endothelial cells under conditions of glutamate toxicity. Our results show increased BACE1, PHF (Paired helical filaments)-tau and GFAP (Glial Fibrillary Acid Protein) immunoreactivity (IR) in the CA1 hippocampal regions of FAD and SAD brains. Furthermore, BACE1 immunoprecipitated with GFAP in tissue samples from all study cases, but their immunofluorescence close to (10 μm3) or overlapping blood vessels was only increased in FAD and SAD brains, and PHF-tau was present around the vessels mainly in FAD brains. Interestingly, the increased BACE1 levels were associated with reactive astrocytes, characterized by morphological changes and upregulation of GFAP under pathological and stressful conditions, and endothelial disruption by glutamate excitotoxicity, and these effects were reversed by BACE1 inhibition; further, BACE1-inhibited astrocytes protected endothelial cell integrity by preserving zonula occludens-1 (ZO-1) distribution and decreasing the expression of inflammatory markers. Taken together, these findings suggest that BACE1 dysregulation in astrocytes may have a role in the alterations in NVU integrity implicated in neurodegeneration.
Eculizumab in the Treatment of Aquaporin-4 Seronegative Neuromyelitis Optica Spectrum Disorder: A Case Report
Authors: Digala Lakshmi , Katyal Nakul , Narula Naureen , Govindarajan Raghav
Published: May 2021

Objective: To report the case of a 35-year-old woman with treatment-resistant aquaporin-4 (AQP-4) immunoglobulin G (IgG) seronegative neuromyelitis optica spectrum disorder (NMOSD) successfully treated with eculizumab (a terminal complement inhibitor).

Methods: The investigational procedures and treatment regimens the patient received were documented over 8 years [2012 (first presentation) to 2020].

Results: The patient presented with subacute onset of lower-limb weakness and numbness, gait imbalance, and urinary incontinence. Magnetic resonance imaging (MRI) showed abnormalities in the thoracic spine from T7 to T10, but brain and cervical spine scans, visual evoked potential latencies, and IgG index were normal; cerebrospinal fluid pleocytosis and oligoclonal bands were both present. After treatment with intravenous methylprednisolone 1 g/day for 5 days, the patient was discharged without medication to acute rehabilitation but experienced relapses from 2012 to 2014. She was treated with oral prednisone (initiated at 40 mg/day in 2014; the dose was halved in 2015 due to weight gain) and mycophenolate mofetil (MMF) 1 g twice daily (from June 2015), but between 2014 and 2019 experienced 4–5 relapses/year, requiring treatment with intravenous methylprednisolone, with added maintenance plasma exchange from 2018 onwards. Although the patient tested negative for antibodies to AQP-4 and myelin oligodendrocyte glycoprotein, she was diagnosed with NMOSD in February 2017, based on recurrent episodes of longitudinal extensive transverse myelitis, MRI changes, and area postrema syndrome. By 2018 the patient needed a cane to walk. Prednisone and MMF were discontinued mid-2018, and rituximab was prescribed from July 2018 (maintenance regimen two 1 g doses 2 weeks apart every 6 months) but discontinued in July 2019 owing to lack of significant improvement. From July 2019 eculizumab was prescribed for 6 months (900 mg weekly for the first four doses, then 1200 mg every 2 weeks). The patient had no relapses or adverse events during and after eculizumab treatment (as of August 2020) and was able to walk unaided; her Expanded Disability Status Scale score improved from 4–5 during 2015–2018 to 2 in 2020 following eculizumab treatment.

Conclusion: Eculizumab shows promise as a treatment for AQP-4 IgG-seronegative NMOSD and further studies are warranted.
Stable Meta-Networks, Noise, and Artifacts in the Human Connectome: Low- to High-Dimensional Independent Components Analysis as a Hierarchy of Intrinsic Connectivity Networks
Authors: Wylie Korey P. , Kronberg Eugene , Legget Kristina T. , Sutton Brianne , Tregellas Jason R.
Published: May 2021

Connectivity within the human connectome occurs between multiple neuronal systems—at small to very large spatial scales. Independent component analysis (ICA) is potentially a powerful tool to facilitate multi-scale analyses. However, ICA has yet to be fully evaluated at very low (10 or fewer) and ultra-high dimensionalities (200 or greater). The current investigation used data from the Human Connectome Project (HCP) to determine the following: (1) if larger networks, or meta-networks, are present at low dimensionality, (2) if nuisance sources increase with dimensionality, and (3) if ICA is prone to overfitting. Using bootstrap ICA, results suggested that, at very low dimensionality, ICA spatial maps consisted of Visual/Attention and Default/Control meta-networks. At fewer than 10 components, well-known networks such as the Somatomotor Network were absent from results. At high dimensionality, nuisance sources were present even in denoised high-quality data but were identifiable by correlation with tissue probability maps. Artifactual overfitting occurred to a minor degree at high dimensionalities. Basic summary statistics on spatial maps (maximum cluster size, maximum component weight, and average weight outside of maximum cluster) quickly and easily separated artifacts from gray matter sources. Lastly, by using weighted averages of bootstrap stability, even ultra-high dimensional ICA resulted in highly reproducible spatial maps. These results demonstrate how ICA can be applied in multi-scale analyses, reliably and accurately reproducing the hierarchy of meta-networks, large-scale networks, and subnetworks, thereby characterizing cortical connectivity across multiple spatial scales.
Expression of Oligodendrocyte and Oligoprogenitor Cell Proteins in Frontal Cortical White and Gray Matter: Impact of Adolescent Development and Ethanol Exposure
Authors: Liu Wen , Rohlman Aaron R. , Vetreno Ryan , Crews Fulton T.
Published: May 2021

Adolescent development of prefrontal cortex (PFC) parallels maturation of executive functions as well as increasing white matter and myelination. Studies using MRI and other methods find that PFC white matter increases across adolescence into adulthood in both humans and rodents. Adolescent binge drinking is common and has been found to alter adult behaviors and PFC functions. This study examines development of oligoprogenitor (OPC) and oligodendrocytes (OLs) in Wistar rats from adolescence to adulthood within PFC white matter, corpus callosum forceps minor (fmi), PFC gray matter, and the neurogenic subventricular zone (SVZ) using immunohistochemistry for marker proteins. In addition, the effects of adolescent intermittent ethanol exposure [AIE; 5.0 g/kg/day, intragastric, 2 days on/2 days off on postnatal day (P)25–54], which is a weekend binge drinking model, were determined. OPC markers NG2+, PDGFRα+ and Olig2+IHC were differentially impacted by both age and PFC region. In both fmi and SVZ, NG2+IHC cells declined from adolescence to adulthood with AIE increasing adult NG2+IHC cells and their association with microglial marker Iba1. PFC gray matter decline in NG2+IHC in adulthood was not altered by AIE. Both adult maturation and AIE impacted OL expression of PLP+, MBP+, MAG+, MOG+, CNPase+, Olig1+, and Olig2+IHC in all three PFC regions, but in region- and marker-specific patterns. These findings are consistent with PFC region-specific changes in OPC and OL markers from adolescence to adulthood as well as following AIE that could contribute to lasting changes in PFC function.
Proteasome Inhibition Suppresses KIT-Independent Gastrointestinal Stromal Tumors Via Targeting Hippo/YAP/Cyclin D1 Signaling
Authors: Chen Ting , Ni Nan , Yuan Li , Xu Liangliang , Bahri Nacef , Sun Boshu , Wu Yuehong , Ou Wen-Bin
Published: May 2021

Purpose: Gastrointestinal stromal tumors (GISTs) are the most common malignant tumor of mesenchymal origin of the digestive tract. A yet more challenging resistance mechanism involves transition from oncogenic KIT to a new imatinib-insensitive oncogenic driver, heralded by loss of KIT expression. Our recent studies have shown that inhibition of cyclin D1 and Hippo signaling, which are overexpressed in KIT-independent GIST, is accompanied by anti-proliferative and apoptosis-promoting effects. PRKCQ, JUN, and the Hippo/YAP pathway coordinately regulate GIST cyclin D1 expression. Thus, targeting of these pathways could be effective therapeutically for these now untreatable tumors.

Methods: Targeting cyclin D1 expression of small molecular drugs was screened by a cell monolayer growth and western blotting. The biologic mechanisms of bortezomib to KIT-independent GISTs were assessed by immunoblotting, qRT-PCR, cell viability, colony growth, cell cycle analysis, apoptosis, migration and invasiveness.

Results: In the initial small molecular inhibitor screening in KIT-independent GIST62, we found that bortezomib-mediated inhibition of the ubiquitin-proteasome machinery showed anti-proliferative effects of KIT-independent GIST cells via downregulation of cyclin D1 and induction of p53 and p21. Treatment with proteasome inhibitor, bortezomib, led to downregulation of cyclin D1 and YAP/TAZ and an increase in the cleaved PARP expression in three KIT-independent GIST cell lines (GIST48B, GIST54, and GIST226). Additionally, it induced p53 and p21 expression in GIST48B and GIST54, increased apoptosis, and led to cell cycle G1/G2-phase arrest, decreased cell viability, colony formation, as well as migration and invasiveness in all GIST cell lines.

Conclusion: Although our findings are early proof-of-principle, there are signs of a potential effective treatment for KIT-independent GISTs, the data highlight that targeting of cyclin D1 and Hippo/YAP by bortezomib warrants evaluation as a novel therapeutic strategy in KIT-independent GISTs.
Sharp Changes in Muscle Tone in Humans Under Simulated Microgravity
Authors: Amirova Liubov E. , Plehuna Anastasija , Rukavishnikov Ilya V. , Saveko Alina A. , Peipsi Aleko , Tomilovskaya Elena S.
Published: May 2021

A decrease in muscle tone induced by space flight requires a standardized assessment of changes to control the state of the neuromuscular system. This study is a step toward the development of a unified protocol, aimed at determining the initial effect of the presence or withdrawal of support on muscle tone, the effects of a 2-h supportlessness in Dry Immersion (DI) experiments, and the changes in muscle tone depending on the site of measurement. To perform measurements of changes in muscle tone, we used a MyotonPRO device. The list of muscles that we assessed includes: trunk – mm. deltoideus posterior, trapezius, erector spinae; leg – mm. biceps femoris, rectus femoris, tibialis anterior, soleus, gastrocnemius; foot – m. flexor digitorum brevis, tendo Achillis, aponeurosis plantaris. The study involved 12 healthy volunteers (6 men, 6 women) without musculoskeletal disorders and aged 32.8 ± 1.6 years. At the start of DI, there was a significant decrease in muscle tone of the following muscles: mm. tibialis anterior (−10.9%), soleus (−9.6%), erector spinae (−14.4%), and the tendo Achillis (−15.3%). The decrease continued to intensify over the next 2 h. In contrast, the gastrocnemius muscle demonstrated an increase in muscle tone (+7.5%) 2 h after the start of DI compared to the immediate in-bath baseline. Muscle tone values were found to be site-dependent and varied in different projections of mm. erector spinae and soleus. In previous experiments, we observed a high sensitivity of the myotonometry technique, which was confirmed in this study. To make it possible to compare data from different studies, a standardized protocol for measuring muscle tone for general use in gravitational physiology needs to be developed.
The Effect of COVID-19 Pandemic on Service Sector Sustainability and Growth
Authors: Xiang Shihui , Rasool Saad , Hang Yong , Javid Kamran , Javed Tasawar , Artene Alin Emanuel
Published: May 2021

Coronavirus disease (COVID-19) is having an unprecedented and unpredictable impact on the world's economy. The pandemic has driven the world toward adapting to the current circumstances regardless of the business, sector, or industry. The coronavirus epidemic (COVID19) has affected the global economy and service sector. The purpose of the current study is to assess the effect of COVID-19 on service sector growth and sustainability. Global sectors and industries are trying to anchor themselves amidst the pandemic. The study focuses on the sectors that are badly hit by the outbreak and discussed the strategies and responses different countries are taking to sustain their economies. This study concludes that the vital role of Information Technology and digitization supports the economies in their fight against the pandemic and helps them sustain themselves amid crises. This study also contributes to the body of literature by suggesting IT-based solutions for various industries to elevate effective responsiveness and avoid significant losses.
Mothers as Home DJs: Recorded Music and Young Children’s Well-Being During the COVID-19 Pandemic
Authors: Cho Eun , Ilari Beatriz Senoi
Published: May 2021

As the COVID-19 pandemic continues to disrupt our lives in unimagined ways, families are reinventing daily rituals, and this is likely true for musical rituals. This study explored how parents with young children used recorded music in their everyday lives during the pandemic. Mothers (N = 19) of child(ren) aged 18 months to 5 years living in the United States played the role of home DJ over a period of one week by strategically crafting the sonic home environment, based on resources provided by the authors, in response to their children’s mood and state. Using a newly developed data collection tool, inspired by the Experience Sampling Method, a total of 197 episodes were collected about children’s engagement with recorded music. Findings showed that while mothers utilized music to fulfill various emotional needs, they tended to use it to maintain or reinforce their child’s positive mood rather than to improve a negative mood. Also, mothers’ reports suggested various ways that young children engaged with music, being aligned with the multimodal nature of their musical experiences. Lastly, mothers reported that their strategic approaches to use recorded music seemed to help their children feel less distressed and happier, and this, in turn, aided in the reduction of some of the burdens associated with parenting.
Revisiting False-Positive and Imitated Dissociative Identity Disorder
Authors: Pietkiewicz Igor Jacob , Bańbura-Nowak Anna , Tomalski Radosław , Boon Suzette
Published: May 2021

ICD-10 and DSM-5 do not provide clear diagnosing guidelines for DID, making it difficult to distinguish ‘genuine’ DID from imitated or false-positive cases. This study explores meaning which patients with false-positive or imitated DID attributed to their diagnosis. 85 people who reported elevated levels of dissociative symptoms in SDQ-20 participated in clinical assessment using the Trauma and Dissociation Symptoms Interview, followed by a psychiatric interview. The recordings of six women, whose earlier DID diagnosis was disconfirmed, were transcribed and subjected to interpretative phenomenological analysis. Five main themes were identified: (1) endorsement and identification with the diagnosis. (2) The notion of dissociative parts justifies identity confusion and conflicting ego-states. (3) Gaining knowledge about DID affects the clinical presentation. (4) Fragmented personality becomes an important discussion topic with others. (5) Ruling out DID leads to disappointment or anger. To avoid misdiagnoses, clinicians should receive more systematic training in the assessment of dissociative disorders, enabling them to better understand subtle differences in the quality of symptoms and how dissociative and non-dissociative patients report them. This would lead to a better understanding of how patients with and without a dissociative disorder report core dissociative symptoms. Some guidelines for a differential diagnosis are provided.
Improving Serious Games to Tackle Childhood Obesity
Authors: Belghali Maroua , Statsenko Yauhen , Al-Za’abi Abdulsalam
Published: May 2021

Childhood obesity has become a global public health issue. Today, there are opportunities to promote health through technological devices such as serious games. Despite the major advancement of this field of research, the use of serious games as a validated intervention in clinical practice requires further clarifications on some methodological aspects. In this perspective article, we report the pros and cons of existing serious games. Besides, we attempt to propose a new methodology of design of a serious game that could help to cope with childhood obesity. The proposed idea consists of a serious game in virtual reality based on enjoyment, movement, education, and executive functioning (EF) training. Longitudinal studies and solid research protocol would certainly ensure consistency and aid interpretation.
Przyimek i jego użycie w pracach pisemnych dzieci dyslektycznych
Authors: Boksa Ewa
Published: May 2021

The research presented in this paper is aimed to answer the question whether
dyslexic people who had been diagnosed with delayed speech development before
they started school use prepositions correctly in statements and how their ability
to use prepositional phrases affects their formation of sentence structures. The
material underlying the research on the syntactic functions of prepositions and
prepositional phrases has been extracted from reports on speech development
for six-year-old children and stories created by the same people many years
later, when they were eighth-year students. Analyses of dyslexic students’
essays have confi rmed that one of the key indicators of developmental dyslexia,
which is helpful in diagnosis, could be the preposition acquisition time as well
as understanding and using this part of speech in utterances and statements.
Keywords: preposition – developmental dyslexia – delayed speech development
High Land-Use Intensity Diminishes Stability of Forage Provision of Mountain Pastures under Future Climate Variability
Authors: Berauer Bernd Josef , Wilfahrt Peter Allan , Schuchardt Max Anatol , Schlingmann Marcus , Schucknecht Anne , Jentsch Anke
Published: May 2021

Semi-natural, agriculturally used grasslands provide important ecologic and economic services, such as feed supply. In mountain regions, pastures are the dominant agricultural system and face more severe climate change impacts than lowlands. Climate change threatens ecosystem functions, such as aboveground net primary production [ANPP] and its nutrient content. It is necessary to understand the impacts of climate change and land-management on such ecosystems to develop management practices to sustainably maintain provision of ecosystem services under future climatic conditions. We studied the effect of climate change and different land-use intensities on plant-soil communities by the downslope translocation of plant-soil mesocosms along an elevation gradient in 2016, and the subsequent application of two management types (extensive vs. intensive). Communities’ response to ANPP and leaf carbon (C), nitrogen (N), and phosphorus (P) content was quantified over the subsequent two years after translocation. ANPP increased with warming in 2017 under both management intensities, but this effect was amplified by intensive land-use management. In 2018, ANPP of intensively managed communities decreased, in comparison to 2017, from 35% to 42%, while extensively managed communities maintained their production levels. The changes in ANPP are coupled with an exceptionally dry year in 2018, with up to 100 more days of drought conditions. The C:N of extensively managed communities was higher than those of intensively managed ones, and further increased in 2018, potentially indicating shifts in resource allocation strategies that may explain production stability. Our results revealed a low resistance of intensively managed communities’ ANPP under especially dry conditions. The ability to alter resource allocation likely enables a constant level of production under extensive management, but this ability is lost under intensive management. Thus, future drought events may leave intensive management as a non-sustainable farming practice, and ultimately threaten ecosystem services of montane pastures.
Ploidy Level and Genetic Parameters for Phenotypic Traits in Bermudagrass (Cynodon spp.) Germplasm
Authors: Grossman Adina Y. , Andrade Mario Henrique Murad Leite , Chaves Ana Luisa Arantes , Mendes Ferreira Marco Túlio , Techio Vânia Helena , Lopez Yolanda , Begcy Kevin , Kenworthy Kevin E. , Rios Esteban F.
Published: May 2021

Bermudagrass (Cynodon spp.) is a forage and turf crop commonly used worldwide. The USDA bermudagrass germplasm set is composed of plant introductions (PI’s) collected around the world and contains different Cynodon species, primarily C. dactylon. The collection was screened in a replicated trial in Florida for forage yield, leaf width, nutritive value (NV), and Bermudagrass Stem Maggot (Atherigona reversura) (BSM), which is an invasive pest to the southeastern United States that damages bermudagrass fields. The goal of this research was to determine ploidy level and genome size in this USDA collection, and evaluate the influence of ploidy level in the estimation of genetic parameters for BSM, leaf width, dry matter yield, and NV traits. For chromosome counts using classical cytogenetics techniques, root tips and meristems were collected from a set of PI’s with known ploidy. The PI’s and cultivars with known chromosome counts were used as internal standards to run flow cytometry and estimate genome size of the PI’s with unknown ploidy. Ploidy level was determined for all accessions and were used to estimate genetic parameters of phenotypic traits. By providing information on ploidy levels and genetic parameters, this research will support breeding efforts and future selections for forage bermudagrass.
Pollution by Antibiotics and Antimicrobial Resistance in LiveStock and Poultry Manure in China, and Countermeasures
Authors: Tian Ming , He Xinmiao , Feng Yanzhong , Wang Wentao , Chen Heshu , Gong Ming , Liu Di , Clarke Jihong Liu , van Eerde André
Published: May 2021

The demand for animal protein has increased considerably worldwide, especially in China, where large numbers of livestock and poultry are produced. Antibiotics have been widely applied to promote growth and prevent diseases. However, the overuse of antibiotics in animal feed has caused serious environmental and health risks, especially the wide spread of antimicrobial resistance (AMR), which seriously affects animal and human health, food safety, ecosystems, and the sustainable future development of animal protein production. Unfortunately, AMR has already become a worldwide challenge, so international cooperation is becoming more important for combatting it. China’s efforts and determination to restrict antibiotic usage through law enforcement and effective management are of significance. In this review, we address the pollution problems of antibiotics; in particular, the AMR in water, soil, and plants caused by livestock and poultry manure in China. The negative impact of widespread and intensive use of antibiotics in livestock production is discussed. To reduce and mitigate AMR problems, we emphasize in this review the development of antibiotic substitutes for the era of antibiotic prohibition.
Reconstruction of Ancient Lake after Peat Excavation—A Case Study about Water Quality
Authors: Staniszewski Ryszard , Frankowski Przemysław , Kayzer Dariusz , Zbierska Janina , Achtenberg Krzysztof
Published: May 2021

According to regulations in some European countries, peat is treated as a fossil fuel or soil for mushroom horticulture and its management is subject to the law for mining activities. As a result of the exploitation of peat bogs, the cutaway or pit lakes remain, which when properly prepared can be local water resources. Such post-peat water bodies can be used for recreation and they can be particularly important in areas struggling with water deficiency in the rural landscape. Maintaining good water quality in such reservoirs requires a number of preparatory works, including the removal of the remaining organic matter that would rest at the bottom of the new pit lake, affecting the water quality. Studies of water quality and aquatic plant communities in the studied post-peat lake were carried out during the period 2012–2014 in order to determine the changes in water quality and the usefulness of water for cyprinids. Aquatic plant communities identified in the reservoir showed a simplified species composition, characteristic of initial communities, and they occupied small areas in the water and on the banks. It has been shown that water quality parameters of the studied water body were stable and corresponded to thresholds established for cyprinids.
Short-Term Solar Power Forecasting Using Genetic Algorithms: An Application Using South African Data
Authors: Ratshilengo Mamphaga , Sigauke Caston , Bere Alphonce
Published: May 2021

Renewable energy forecasts are critical to renewable energy grids and backup plans, operational plans, and short-term power purchases. This paper focused on short-term forecasting of high-frequency global horizontal irradiance data from one of South Africa’s radiometric stations. The aim of the study was to compare the predictive performance of the genetic algorithm and recurrent neural network models with the K-nearest neighbour model, which was used as the benchmark model. Empirical results from the study showed that the genetic algorithm model has the best conditional predictive ability compared to the other two models, making this study a useful tool for decision-makers and system operators in power utility companies. To the best of our knowledge this is the first study which compares the genetic algorithm, the K-nearest neighbour method, and recurrent neural networks in short-term forecasting of global horizontal irradiance data from South Africa.
Development of a Novel Omnidirectional Treadmill-Based Locomotion Interface Device with Running Capability
Authors: Pyo Sanghun , Lee Hosu , Yoon Jungwon
Published: May 2021

To achieve an immersive virtual reality (VR) environment, omnidirectional treadmills (ODTs) allow users to perform locomotion in any direction. However, existing ODTs are heavy and complex, and operate at low speeds. This limits fast user motion and prevents natural interactions in real applications such as military training programs and interactive games. In this paper, we introduce a novel locomotion interface device with running capability, which uses an omnidirectional treadmill with a new power transmission mechanism and a locomotion controller that enables the user to make fast movements. As a result of the improved power transmission performance due to the simple and relatively lightweight structure, the proposed two-dimensional treadmill can generate a maximum speed of 3 m/s, with an acceleration of 3 m/s2. Moreover, through a pilot test with the proposed locomotion interface device, we verified that the fast directional changes during walking and running with the designed speed adaptation controller do not exceed the acceleration performance of the proposed system. Due to its wide range of movement speeds and acceleration capabilities, and lack of any motion constraints, the proposed locomotion interface device with a novel ODT can be used as a representative platform in various VR environments to enhance the immersive experience.
Feasibility of Calculating Standardized Precipitation Index with Short-Term Precipitation Data in China
Authors: Zuo Dongdong , Hou Wei , Wu Hao , Yan Pengcheng , Zhang Qiang
Published: May 2021

At present, high-resolution drought indices are scarce, and this problem has restricted the development of refined drought analysis to some extent. This study explored the possibility of calculating the standardized precipitation index (SPI) with short-term precipitation sequences in China, based on data from 2416 precipitation observation stations covering the time period from 1961 to 2019. The result shows that it is feasible for short-sequence stations to calculate SPI index, based on the spatial interpolation of the precipitation distribution parameters of the long-sequence station. Error analysis denoted that the SPI error was small in east China and large in west China, and the SPI was more accurate when the observation stations were denser. The SPI error of short-sequence sites was mostly less than 0.2 in most areas of eastern China and the consistency rate for the drought categories was larger than 80%, which was lower than the error using the 30-year precipitation samples. Further analysis showed that the estimation error of the distribution parameters β and q was the most important cause of SPI error. Two drought monitoring examples show that the SPI of more than 50,000 short-sequence sites can correctly express the spatial distribution of dry and wet and have refined spatial structure characteristics.
Controllability of Fuzzy Solutions for Neutral Impulsive Functional Differential Equations with Nonlocal Conditions
Authors: Acharya Falguni , Kushawaha Vandana , Panchal Jitendra , Chalishajar Dimplekumar
Published: May 2021

In this paper, the controllability of fuzzy solutions for first order nonlocal impulsive neutral functional differential equations is explored using the Banach fixed point theorem. We utilized the concepts of the fuzzy set theory, functional analysis, and the Hausdorff metric. In the conclusion, an illustration is given to bolster the hypothesis.
NOD1-Targeted Immunonutrition Approaches: On the Way from Disease to Health
Authors: Fernández-García Victoria , González-Ramos Silvia , Martín-Sanz Paloma , Laparra José M. , Boscá Lisardo
Published: May 2021

Immunonutrition appears as a field with great potential in modern medicine. Since the immune system can trigger serious pathophysiological disorders, it is essential to study and implement a type of nutrition aimed at improving immune system functioning and reinforcing it individually for each patient. In this sense, the nucleotide-binding oligomerization domain-1 (NOD1), one of the members of the pattern recognition receptors (PRRs) family of innate immunity, has been related to numerous pathologies, such as cancer, diabetes, or cardiovascular diseases. NOD1, which is activated by bacterial-derived peptidoglycans, is known to be present in immune cells and to contribute to inflammation and other important pathways, such as fibrosis, upon recognition of its ligands. Since immunonutrition is a significant developing research area with much to discover, we propose NOD1 as a possible target to consider in this field. It is relevant to understand the cellular and molecular mechanisms that modulate the immune system and involve the activation of NOD1 in the context of immunonutrition and associated pathological conditions. Surgical or pharmacological treatments could clearly benefit from the synergy with specific and personalized nutrition that even considers the health status of each subject.
Methodical Design of Viral Vaccines Based on Avant-Garde Nanocarriers: A Multi-Domain Narrative Review
Authors: Raoufi Ehsan , Bahramimeimandi Bahar , Salehi-Shadkami M. , Chaosri Patcharida , Mozafari M. R.
Published: May 2021

The current health crisis caused by coronavirus 2019 (COVID-19) and associated pathogens emphasize the urgent need for vaccine systems that can generate protective and long-lasting immune responses. Vaccination, employing peptides, nucleic acids, and other molecules, or using pathogen-based strategies, in fact, is one of the most potent approaches in the management of viral diseases. However, the vaccine candidate requires protection from degradation and precise delivery to the target cells. This can be achieved by employing different types of drug and vaccine delivery strategies, among which, nanotechnology-based systems seem to be more promising. This entry aims to provide insight into major aspects of vaccine design and formulation to address different diseases, including the recent outbreak of SARS-CoV-2. Special emphasis of this review is on the technical and practical aspects of vaccine construction and theranostic approaches to precisely target and localize the active compounds.
3D Printed Models—A Useful Tool in Endovascular Treatment of Intracranial Aneurysms
Authors: Marciuc Emilia Adriana , Dobrovat Bogdan Ionut , Popescu Roxana Mihaela , Dobrin Nicolaie , Chiriac Alexandru , Marciuc Daniel , Eva Lucian , Haba Danisia
Published: May 2021

Many developments were made in the area of endovascular treatment of intracranial aneurysms, but this procedure also requires a good assessment of vascular anatomy prior to intervention. Seventy-six cases with brain aneurysms were selected and 1:1 scale 3D printed models were created. We asked three interventional neurosurgeons with different degrees of experience (ten years, four years, and a fourth-year resident) to review the cases using CTA (computed tomography angiogram) with MPR (multiplanar reconstructions) and VRT (volume rendering technique) and make a decision: coil embolization or stent-assisted coil embolization. After we provided them with the 3D printed models, they were asked to review their treatment plan. Statistical analysis was performed and the endovascular approach changed in 11.84% of cases for ten-year experienced neurosurgeons, 13.15% for four years experienced neurosurgeon, and 21.05% for residents. The interobserver agreement was very good between the ten years experienced interventionist and four years experienced interventionist when they analyzed the data set that included the 3D printed model. The agreement was higher between all physicians after they examined the printed model. 3D patient-specific printed models may be useful in choosing between two different endovascular techniques and also help the residents to better understand the vascular anatomy and the overall procedure.
Long-Term Outcome of Neoadjuvant Tyrosine Kinase Inhibitors Followed by Complete Surgery in Locally Advanced Dermatofibrosarcoma Protuberans
Authors: Beaziz Jessica , Battistella Maxime , Delyon Julie , Farges Cécile , Marco Oren , Pages Cécile , Le Maignan Christine , Da Meda Laetitia , Basset-Seguin Nicole , Resche-Rigon Matthieu , Walter Petrich Anouk , Kérob Delphine , Lebbé Céleste , Baroudjian Barouyr
Published: May 2021

In locally advanced dermatofibrosarcoma protuberans (DFSP), imatinib mesylate has been described as an efficient neoadjuvant therapy. This retrospective study included patients with locally advanced DFSP who received neoadjuvant TKI (imatinib or pazopanib) from 2007 to 2017 at Saint Louis Hospital, Paris. The primary endpoint was the evaluation of the long-term status. A total of 27 patients were included, of whom nine had fibrosarcomatous transformation. The median duration of treatment was 7 months. The best response to TKI treatment before surgery, evaluated according to RECIST1.1 on MRI, consisted of complete/partial response (38.5%) or stability (46.2%). DFSP was surgically removed in 24 (89%) patients. A total of 23 patients (85%) were disease-free after 64.8 months of median follow-up (95% confidence interval 47.8; 109.3). One patient developed distant metastases 37 months after surgical tumor resection and finally died. Two patients (7%) did not get surgery because of metastatic progression during TKI treatment, and one patient refused surgery even though the tumor decreased by 30%. Treatment-related adverse events (AE) occurred in 23 patients (85%). Only four patients (imatinib: n = 3, pazopanib: n = 1) had grade ≥3 AE requiring temporary treatment disruption. Neoadjuvant TKI followed by complete surgery with micrographic analysis is an effective strategy for locally advanced and unresectable DFSP, with durable local recurrence disease-free survival.
Clinical Implication of Liquid Biopsy in Colorectal Cancer Patients Treated with Metastasectomy
Authors: Lee Soohyeon , Park Young-Soo , Chang Won-Jin , Choi Jung Yoon , Lim Ahreum , Kim Boyeon , Lee Saet-Byeol , Lee Jong-Won , Kim Seon-Hahn , Kim Jin , Kwak Jung-Myun , Yoon Kyung-Chul , Lee Sung-Ho , Kim Yeul Hong
Published: May 2021

Background & Aims: The application of circulating tumor DNA (ctDNA) has been studied for predicting recurrent disease after surgery and treatment response during systemic treatment. Metastasectomy can be curative for well-selected patients with metastatic colorectal cancer (mCRC). This prospective study investigated the ctDNA level before and after metastasectomy in patients with mCRC to explore its potential as a predictive biomarker. Methods: We collected data on 98 metastasectomies for mCRC performed from March 2017 to February 2020. Somatic mutations in the primary and metastatic tumors were identified and tumor-informed ctDNAs were selected by ultra-deep targeted sequencing. Plasma samples were mandatorily collected before and 3–4 weeks after metastasectomy and serially, if patients agreed. Results: Data on 67 of 98 metastasectomies (58 patients) meeting the criteria were collected. ctDNA was detected in 9 (29%) of 31 cases treated with upfront metastasectomy and in 7 (19.4%) of 36 cases treated with metastasectomy after upfront chemotherapy. The detection rate of ctDNA was higher in liver metastasis (p = 0.0045) and tumors measuring ≥1 cm (p = 0.0183). ctDNA was less likely to be detected if the response to chemotherapy was good. After metastasectomy, ctDNA was found in 4 (6%) cases with rapid progressive disease. Conclusion: The biological factors affecting the ctDNA shedding from the tumor should be considered when applying ctDNA assays in a clinical setting. After metastasectomy for oligometastatic lesions in good responders of chemotherapy, most ctDNA was cleared or existed below the detection level. To assist clinical decision making after metastasectomy for mCRC using ctDNA, further studies for improving specific outcomes are needed.