bluuebunny/crossref_metadata_2025 huggingface dataset:
Numerical Simulation of Full-Scale Three-Dimensional Fluid Flow in an Oscillating Reactor
Authors: Gong Houjun , Wu Mengqi
Published: June 2021

Marine reactors are subjected to additional motions due to ocean conditions. These additional motions will cause large fluctuation of flow rate and change the coolant flow field, making the system unstable. Therefore, in order to understand the effect of oscillating motion on the flow characteristics, a numerical simulation of fluid flow is carried out based on a full-scale three-dimensional oscillating marine reactor. In this study, the resistance coefficients of the lattice, rod buddle and steam generator are fitted, and the distribution of flow rate, velocity as well as pressure in different regions is investigated through the standard model. After additional oscillation is introduced, the flow field in an oscillating reactor is presented and the effect of oscillating angle and elevation on the flow rate is investigated. Results show that the oscillating motion can greatly change the flow field in the reactor; most of the coolant circulates in the downcommer and lower head with only a small amount of coolant entering the core; the flow fluctuation period is consistent with the oscillating period, and the flow variation patterns under different oscillating conditions are basically the same; since the flow amplitude is related to oscillating speed, the amplitude of flow rate rises when decreasing the maximum oscillating angle; the oscillating elevation has little effect on the flow rate.
Floral Distribution of a Sub-Bituminous Coal Dumpsite in Enugu, Nigeria
Authors: Nsa Imade Y. , Oyebanji Oyetola O. , Igbinigie Eric E. , Odunsi Ayodeji A.
Published: June 2021

The remnant floral diversity of a naturally reclaimed area proximal to an abandoned mine was assessed. The coal mine site, the Incident zone (IZ) and an unsullied site, the Control zone (CZ), were sampled. Using a 5 m2 quadrat, the floristic composition was determined by the occurrence, distribution analysis, and species diversity indices. The study revealed a degraded vegetation type and recorded a total of 60 species, 53 genera and 27 families. Both the IZ and CZ shared 26.67% species similarity, while 36.67% are were unique to each zone. Five species were dominant (Ageratum conyzoides, Panicum maximum, Calopogonium mucunoides, Chromolaena odorata). While the dominant genera vary between IZ (Borreria, Dioscorea, Ipomoea, and Phyllanthus) and CZ (Desmodium, Euphorbia, and Ipomoea), Asteraceae and Poaceae were the dominant families in both zones. Forbs were the most dominant life forms in both zones; Cyclosorus sp. and Adiantum sp. were only found on the IZ, whereas, Kyllinga erecta and Mariscus alternifolius were exclusive to the CZ. Our results reflect that species composition and vegetation paradigm in the study area could be influenced by coal mining, farming, infrastructural installations and climate. Hence, we suggest future studies to investigate how the species adapt to the environment. Although most of the species encountered belonged to lower-risk conservation, the conservation of the species to this area is imperative.
Ferroptosis-Related Gene-Based Prognostic Model and Immune Infiltration in Clear Cell Renal Cell Carcinoma
Authors: Zhao Guo-Jiang , Wu Zonglong , Ge Liyuan , Yang Feilong , Hong Kai , Zhang Shudong , Ma Lulin
Published: June 2021

Clear cell renal cell carcinoma (ccRCC) is one of the most common tumors in the urinary system. Ferroptosis plays a vital role in ccRCC development and progression. We did an update of ferroptosis-related multigene expression signature for individualized prognosis prediction in patients with ccRCC. Differentially expressed ferroptosis-related genes in ccRCC and normal samples were screened using The Cancer Genome Atlas. Univariate and multivariate Cox regression analyses and machine learning methods were employed to identify optimal prognosis-related genes. CARS1, CD44, FANCD2, HMGCR, NCOA4, SLC7A11, and ACACA were selected to establish a prognostic risk score model. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses revealed that these genes were mainly enriched in immune-related pathways; single-sample Gene Set Enrichment Analysis revealed several immune cells potentially related to ferroptosis. Kaplan–Meier survival analysis demonstrated that patients with high-risk scores had significantly poor overall survival (log-rank P = 7.815 × 10–11). The ferroptosis signature was identified as an independent prognostic factor. Finally, a prognostic nomogram, including the ferroptosis signature, age, histological grade, and stage status, was constructed. Analysis of The Cancer Genome Atlas-based calibration plots, C-index, and decision curve indicated the excellent predictive performance of the nomogram. The ferroptosis-related seven-gene risk score model is useful as a prognostic biomarker and suggests therapeutic targets for ccRCC. The prognostic nomogram may assist in individualized survival prediction and improve treatment strategies.
The Role of Type 2 Innate Lymphoid Cells in Allergic Diseases
Authors: Zheng Haocheng , Zhang Yi , Pan Jiachuang , Liu Nannan , Qin Yu , Qiu Linghui , Liu Min , Wang Tieshan
Published: June 2021

Allergic diseases are significant diseases that affect many patients worldwide. In the past few decades, the incidence of allergic diseases has increased significantly due to environmental changes and social development, which has posed a substantial public health burden and even led to premature death. The understanding of the mechanism underlying allergic diseases has been substantially advanced, and the occurrence of allergic diseases and changes in the immune system state are known to be correlated. With the identification and in-depth understanding of innate lymphoid cells, researchers have gradually revealed that type 2 innate lymphoid cells (ILC2s) play important roles in many allergic diseases. However, our current studies of ILC2s are limited, and their status in allergic diseases remains unclear. This article provides an overview of the common phenotypes and activation pathways of ILC2s in different allergic diseases as well as potential research directions to improve the understanding of their roles in different allergic diseases and ultimately find new treatments for these diseases.
Hepatic Macrophage Responses in Inflammation, a Function of Plasticity, Heterogeneity or Both?
Authors: Zwicker Christian , Bujko Anna , Scott Charlotte L.
Published: June 2021

With the increasing availability and accessibility of single cell technologies, much attention has been given to delineating the specific populations of cells present in any given tissue. In recent years, hepatic macrophage heterogeneity has also begun to be examined using these strategies. While previously any macrophage in the liver was considered to be a Kupffer cell (KC), several studies have recently revealed the presence of distinct subsets of hepatic macrophages, including those distinct from KCs both under homeostatic and non-homeostatic conditions. This heterogeneity has brought the concept of macrophage plasticity into question. Are KCs really as plastic as once thought, being capable of responding efficiently and specifically to any given stimuli? Or are the differential responses observed from hepatic macrophages in distinct settings due to the presence of multiple subsets of these cells? With these questions in mind, here we examine what is currently understood regarding hepatic macrophage heterogeneity in mouse and human and examine the role of heterogeneity vs plasticity in regards to hepatic macrophage responses in settings of both pathogen-induced and sterile inflammation.
The Use of Iron Oxide Nanoparticles to Reprogram Macrophage Responses and the Immunological Tumor Microenvironment
Authors: Mulens-Arias Vladimir , Rojas José Manuel , Barber Domingo F.
Published: June 2021

The synthesis and functionalization of iron oxide nanoparticles (IONPs) is versatile, which has enhanced the interest in studying them as theranostic agents over recent years. As IONPs begin to be used for different biomedical applications, it is important to know how they affect the immune system and its different cell types, especially their interaction with the macrophages that are involved in their clearance. How immune cells respond to therapeutic interventions can condition the systemic and local tissue response, and hence, the final therapeutic outcome. Thus, it is fundamental to understand the effects that IONPs have on the immune response, especially in cancer immunotherapy. The biological effects of IONPs may be the result of intrinsic features of their iron oxide core, inducing reactive oxygen species (ROS) and modulating intracellular redox and iron metabolism. Alternatively, their effects are driven by the nanoparticle coating, for example, through cell membrane receptor engagement. Indeed, exploiting these properties of IONPs could lead to the development of innovative therapies. In this review, after a presentation of the elements that make up the tumor immunological microenvironment, we will review and discuss what is currently known about the immunomodulatory mechanisms triggered by IONPs, mainly focusing on macrophage polarization and reprogramming. Consequently, we will discuss the implications of these findings in the context of plausible therapeutic scenarios for cancer immunotherapy.
A New Species of Waginella (Crustacea: Thecostraca: Ascothoracida) Parasitic on a Stalked Crinoid From Tasman Sea, With Notes on Morphology of Related Genera
Authors: Kolbasov Gregory A. , Savchenko Alexandra S. , Newman William A. , Chan Benny K. K.
Published: June 2021

A new ectoparasitic ascothoracidan species has been discovered off northern Tasman Sea at a depth of 520 m. Single female, described herein as Waginella ebonita Kolbasov and Newman sp. nov. in the family Synagogidae Gruvel, 1905, was collected on the column of crinoid Metacrinus sp. This is the first study of a new form of Waginella to be based on the extensive use of both light and scanning electron microscopy to document the fine-scale external morphology. We studied the external morphology of other two species of Waginella, W. cf. axotremata and W. sandersi utilizing SEM and compared fine structures of all congeners. The genus Waginella represents a monophyletic taxon including at least 4 species having similar and unique morphology even on the ultrastructural level. Two species, W. cf. axotremata and W. cf. metacrinicola may represent at least two complexes of species. The morphology of an attachment apparatus in all species of Waginella suggests that they remain attached to the host for a considerable period of time. The lattice organs of Waginella have a unique structure distinguishing from all Thecostraca. Waginella ebonita sp. nov. is the second species of this genus known to harbor hyperparasitic cryptoniscid isopods representing parasitic castrators.
A Comparison of Microplastic in Fish From Australia and Fiji
Authors: Wootton Nina , Ferreira Marta , Reis-Santos Patrick , Gillanders Bronwyn M.
Published: June 2021

Awareness surrounding plastic pollution has increased significantly in the past decade, leading to concerns on potential adverse effects on biota, including the consumption of microplastic by fish. Globally, plastic has been found in many species of fish, but little research has been undertaken in the southern hemisphere. We assessed the abundance and type of plastic in fish captured and sold for human consumption in Australia and Fiji. Fish (goatfish, sea mullet, paddletail, and common coral trout) had their gastrointestinal tracts dissected and microplastic quantified under a microscope. Plastic polymer types were confirmed using μ-FTIR. In Australia, plastic was found in 61.6% of fish gastrointestinal tracts, while in Fiji, 35.3% of fish had plastic. Fish from Australia had almost double the amount of plastic on average than fish caught in Fiji, with 1.58 (± 0.23) pieces per fish in Australia compared to 0.86 (± 0.14) in fish caught in Fiji. The types of plastic differed between countries, with fibers comprising 83.6% of microplastic pieces in fish from Australia whereas 50% of microplastic found in fish from Fiji was film. Polyolefin was the most abundant polymer type in both fibers from Australia and film from Fiji. We hypothesize variations in abundance and plastic type are a reflection of the population density and coastal geomorphology, but may also be a result of legislation and waste management strategies in the two countries. This work adds evidence to the pervasive presence of plastic in fish gastrointestinal tracts, reinforcing the urgent need for efficient plastic waste management, but also a better understanding of the impacts of microplastic on marine biota.
Archaeometrical Characterization of Romanian Late Bronze Age Ceramic Fragments
Authors: Fierascu Irina , Baroi Anda Maria , Brazdis Roxana Ioana , Fistos Toma , Nicolae Cristian Andi , Raditoiu Valentin , Inel Ioan Constantin , Sava Victor , Fierascu Radu Claudiu
Published: June 2021

Knowledge of the past can provide information to protect the future and the potential of the technological development in the analytical sciences can be successfully applied for the study and conservation of cultural objects. In this context, in the present paper we propose an analytical methodology to characterize seven samples of ancient ceramic objects (dating to the Late Bronze Age). The samples were analyzed using optical microscopy, and all the samples presented a strong inhomogeneity on the surface, as suggested by the different colors of the ceramics. X-ray fluorescence (XRF) results reveal a relatively heterogenous composition of the samples, as well as strong differences between the different surfaces of each sample. By comparative analysis of the diffractograms recorded for both sides of the same samples were observed some differences, especially in terms of relative concentration of the component minerals, and, in lesser content, in terms of new phases present in the samples. Corroborated results obtained by XRF and X-ray diffraction (XRD) offered information regarding mineralogical composition of the samples: for some of them illite/muscovite and plagioclase phases are present in higher quantities or a lower quartz content. The presence of these components was confirmed by Fourier-transform infrared spectroscopy (FTIR) analysis. The thermal analysis completes the analytical investigation of the ceramic samples. The thermal behavior of the sample conducted to some explanation regarding the observed differences, due to the raw materials (that the major clay mineral in the samples is represented by illite) or to environmental factors during their burial in the soil.
Combined Loop-Mediated Isothermal Amplification Assays for Rapid Detection and One-Step Differentiation of Campylobacter jejuni and Campylobacter coli in Meat Products
Authors: Kreitlow Antonia , Becker André , Ahmed Marwa F. E. , Kittler Sophie , Schotte Ulrich , Plötz Madeleine , Abdulmawjood Amir
Published: June 2021

A loop-mediated isothermal amplification (LAMP) assay system was established, allowing rplD gene-based simultaneous detection of Campylobacter jejuni and Campylobacter coli in enriched meat products. Additionally, one-step differentiation of target species on agar plates was enabled by cdtC gene- and gyrA gene-based duplex LAMP. Both the rplD and cdtC–gyrA LAMP assays amplified the target sequences in all 62 C. jejuni and 27 C. coli strains used for determining inclusivity and revealed 100% exclusivity toward 85 tested non-target species. Throughout the entire experiments, C. jejuni and C. coli strains were 100% distinguishable by melting curves of cdtC and gyrA LAMP products. After 24-h enrichment, the rplD LAMP assay reliably detected initial inoculation levels of 10–100 CFU/g in artificially contaminated minced meat. Investigation of naturally contaminated meat samples revealed a diagnostic accuracy of 95% toward real-time PCR and 94.1% toward the standard culture method applying the 24-h incubation period. Diagnostic sensitivity and specificity, and positive and negative predictive values were 89.8, 100, 100, and 91.2%, respectively, when measured against real-time PCR, and 89.6, 98.1, 97.7, and 91.2%, respectively, when measured against the standard culture method. After 48-h enrichment, the detection limit of the rplD LAMP assay improved to initial inoculation levels of 1–10 CFU/g in artificially contaminated minced meat. Applying the 48-h incubation period on naturally contaminated meat samples resulted in 100% concordant results between rplD LAMP, real-time PCR, and the standard culture method. The established LAMP assay system was proved to be suitable for rapid meat sample screening. Furthermore, it constitutes a promising tool for investigating other Campylobacter sources and could therefore make a valuable contribution to protect consumers from foodborne illness.
Cocultivation Study of Monascus spp. and Aspergillus niger Inspired From Black-Skin-Red-Koji by a Double-Sided Petri Dish
Authors: Yuan Xi , Chen Fusheng
Published: June 2021

Cocultivation is an emerging and potential way to investigate microbial interaction in the laboratory. Extensive researches has been carried out over the years, but some microorganism cocultivation are not easy to implement in the laboratory, especially the fungus-fungus (FF) cocultivation, owing to the obstacles such as fungal different growth rate, limited growing space, hyphae intertwining, and difficulty of sample separation, etc. In this research, a double-sided petri dish (DSPD) was designed and carried out as a tool to study FF cocultivation in the laboratory. A natural FF cocultivation of Monascus spp. and Aspergillus niger inspired from black-skin-red-koji (BSRK), were studied. By using DSPD, the aforementioned obstacles in the FF cocultivation study were overcome through co-culturing Monascus spp. and A. niger on each side of DSPD. The characteristics of monocultured and co-cultured Monascus spp. and A. niger were compared and analyzed, including colonial and microscopic morphologies, and main secondary metabolites (SMs) of Monascus spp. analyzed by high performance liquid chromatography. And a novel SM was found to be produced by Monascus ruber M7 when co-cultured with A. niger CBS 513.88. Since the above mentioned obstacles, were overcome, we obtained good quality of transcriptome data for further analysis. These results indicate that DSPD might be an efficient tool for investigation of microbial interaction, in particular, for FF interaction.
Effects of Lactobacillus plantarum on the Fermentation Profile and Microbiological Composition of Wheat Fermented Silage Under the Freezing and Thawing Low Temperatures
Authors: Zhang Miao , Wang Lei , Wu Guofang , Wang Xing , Lv Haoxin , Chen Jun , Liu Yuan , Pang Huili , Tan Zhongfang
Published: June 2021

The corruption and/or poor quality of silages caused by low temperature and freeze-thaw conditions makes it imperative to identify effective starters and low temperature silage fermentation technology that can assist the animal feed industry and improve livestock productivity. The effect of L. plantarum QZ227 on the wheat silage quality was evaluated under conditions at constant low temperatures followed by repeated freezing and thawing at low temperatures. QZ227 became the predominant strain in 10 days and underwent a more intensive lactic acid bacteria fermentation than CK. QZ227 accumulated more lactic acid, but lower pH and ammonia nitrogen in the fermentation. During the repeated freezing and thawing process, the accumulated lactic acid in the silage fermented by QZ227 remained relatively stable. Relative to CK, QZ227 reduced the abundance of fungal pathogens in silage at a constant 5°C, including Aspergillus, Sporidiobolaceae, Hypocreaceae, Pleosporales, Cutaneotrichosporon, Alternaria, and Cystobasidiomycetes. Under varying low temperature conditions from days 40 to days 60, QZ227 reduced the pathogenic abundance of fungi such as Pichia, Aspergillus, Agaricales, and Plectosphaerella. QZ227 also reduced the pathogenic abundance of Mucoromycota after the silage had been exposed to oxygen. In conclusion, QZ227 can be used as a silage additive in the fermentation process at both constant and variable low temperatures to ensure fast and vigorous fermentation because it promotes the rapid accumulation of lactic acid, and reduces pH values and aerobic corruption compared to the CK.
The Macleaya cordata Symbiont: Revealing the Effects of Plant Niches and Alkaloids on the Bacterial Community
Authors: Lei Fangying , Liu Xueduan , Huang Haonan , Fu Shaodong , Zou Kai , Zhang Shuangfei , Zhou Li , Zeng Jianguo , Liu Hongwei , Jiang Luhua , Miao Bo , Liang Yili
Published: June 2021

Endophytes are highly associated with plant growth and health. Exploring the variation of bacterial communities in different plant niches is essential for understanding microbe-plant interactions. In this study, high-throughput gene sequencing was used to analyze the composition and abundance of bacteria from the rhizospheric soil and different parts of the Macleaya cordata. The results indicated that the bacterial community structure varied widely among compartments. Bacterial diversity was observed to be the highest in the rhizospheric soil and the lowest in fruits. Proteobacteria, Actinobacteria, and Bacteroidetes were found as the dominant phyla. The genera Sphingomonas (∼47.77%) and Methylobacterium (∼45.25%) dominated in fruits and leaves, respectively. High-performance liquid chromatography (HPLC) was employed to measure the alkaloid content of different plant parts. Significant correlations were observed between endophytic bacteria and alkaloids. Especially, Sphingomonas showed a significant positive correlation with sanguinarine and chelerythrine. All four alkaloids were negatively correlated with the microbiota of stems. The predicted result of PICRUST2 revealed that the synthesis of plant alkaloids might lead to a higher abundance of endophytic microorganisms with genes related to alkaloid synthesis, further demonstrated the correlation between bacterial communities and alkaloids. This study provided the first insight into the bacterial community composition in different parts of Macleaya cordata and the correlation between the endophytic bacteria and alkaloids.
Neurofeedback and the Aging Brain: A Systematic Review of Training Protocols for Dementia and Mild Cognitive Impairment
Authors: Trambaiolli Lucas R. , Cassani Raymundo , Mehler David M. A. , Falk Tiago H.
Published: June 2021

Dementia describes a set of symptoms that occur in neurodegenerative disorders and that is characterized by gradual loss of cognitive and behavioral functions. Recently, non-invasive neurofeedback training has been explored as a potential complementary treatment for patients suffering from dementia or mild cognitive impairment. Here we systematically reviewed studies that explored neurofeedback training protocols based on electroencephalography or functional magnetic resonance imaging for these groups of patients. From a total of 1,912 screened studies, 10 were included in our final sample (N= 208 independent participants in experimental andN= 81 in the control groups completing the primary endpoint). We compared the clinical efficacy across studies, and evaluated their experimental designs and reporting quality. In most studies, patients showed improved scores in different cognitive tests. However, data from randomized controlled trials remains scarce, and clinical evidence based on standardized metrics is still inconclusive. In light of recent meta-research developments in the neurofeedback field and beyond, quality and reporting practices of individual studies are reviewed. We conclude with recommendations on best practices for future studies that investigate the effects of neurofeedback training in dementia and cognitive impairment.
RNA Interference and Nanotechnology: A Promising Alliance for Next Generation Cancer Therapeutics
Authors: Swaminathan Guruprasadh , Shigna Aisha , Kumar Aviral , Byroju Vishnu Vardhan , Durgempudi Varsha Reddy , Dinesh Kumar Lekha
Published: June 2021

Cancer is a significant health hazard of the 21st century, and GLOBOCAN predicts increasing cancer incidence in the coming decades. Though several conventional treatment modalities exist, most of them end up causing off-target and debilitating effects, and drug resistance acquisition. Advances in our understanding of tumor molecular biology offer alternative strategies for precise, robust, and potentially less toxic treatment paradigms for circumventing the disease at the cellular and molecular level. Several deregulated molecules associated with tumorigenesis have been developed as targets in RNA interference (RNAi) based cancer therapeutics. RNAi, a post-transcriptional gene regulation mechanism, has significantly gained attention because of its precise multi-targeted gene silencing. Although the RNAi approach is favorable, the direct administration of small oligonucleotides has not been fruitful because of their inherent lower half-lives and instability in the biological systems. Moreover, the lack of an appropriate delivery system to the primary site of the tumor that helps determine the potency of the drug and its reach, has limited the effective medical utilization of these bio-drugs. Nanotechnology, with its unique characteristics of enhanced permeation and better tumor-targeting efficiency, offers promising solutions owing to the various possibilities and amenability for modifications of the nanoparticles to augment cancer therapeutics. Nanoparticles could be made multimodal, by designing and synthesizing multiple desired functionalities, often resulting in unique and potentially applicable biological structures. A small number of Phase I clinical trials with systemically administered siRNA molecules conjugated with nanoparticles have been completed and the results are promising, indicating that, these new combinatorial therapies can successfully and safely be used to inhibit target genes in cancer patients to alleviate some of the disease burden. In this review, we highlight different types of nano-based delivery strategies for engineering Nano-RNAi-based bio drugs. Furthermore, we have highlighted the insights gained from current research that are entering the preclinical evaluation and information about initial clinical developments, shaping the future for next generation cancer therapeutics.
A Dynamical Generative Model of Social Interactions
Authors: Salatiello Alessandro , Hovaidi-Ardestani Mohammad , Giese Martin A.
Published: June 2021

The ability to make accurate social inferences makes humans able to navigate and act in their social environment effortlessly. Converging evidence shows that motion is one of the most informative cues in shaping the perception of social interactions. However, the scarcity of parameterized generative models for the generation of highly-controlled stimuli has slowed down both the identification of the most critical motion features and the understanding of the computational mechanisms underlying their extraction and processing from rich visual inputs. In this work, we introduce a novel generative model for the automatic generation of an arbitrarily large number of videos of socially interacting agents for comprehensive studies of social perception. The proposed framework, validated with three psychophysical experiments, allows generating as many as 15 distinct interaction classes. The model builds on classical dynamical system models of biological navigation and is able to generate visual stimuli that are parametrically controlled and representative of a heterogeneous set of social interaction classes. The proposed method represents thus an important tool for experiments aimed at unveiling the computational mechanisms mediating the perception of social interactions. The ability to generate highly-controlled stimuli makes the model valuable not only to conduct behavioral and neuroimaging studies, but also to develop and validate neural models of social inference, and machine vision systems for the automatic recognition of social interactions. In fact, contrasting human and model responses to a heterogeneous set of highly-controlled stimuli can help to identify critical computational steps in the processing of social interaction stimuli.
Leber's Hereditary Optic Neuropathy: A Report on Novel mtDNA Pathogenic Variants
Authors: Peverelli Lorenzo , Catania Alessia , Marchet Silvia , Ciasca Paola , Cammarata Gabriella , Melzi Lisa , Bellino Antonella , Fancellu Roberto , Lamantea Eleonora , Capristo Mariantonietta , Caporali Leonardo , La Morgia Chiara , Carelli Valerio , Ghezzi Daniele , Bianchi Marzoli Stefania , Lamperti Costanza
Published: June 2021

Leber's hereditary optic neuropathy (LHON) is due to missense point mutations affecting mitochondrial DNA (mtDNA); 90% of cases harbor the m.3460G>A, m.11778G>A, and m.14484T>C primary mutations. Here, we report and discuss five families with patients affected by symptomatic LHON, in which we found five novel mtDNA variants. Remarkably, these mtDNA variants are located in complex I genes, though without strong deleterious effect on respiration in cellular models: this finding is likely linked to the tissue specificity of LHON. This study observes that in the case of a strong clinical suspicion of LHON, it is recommended to analyze the whole mtDNA sequence, since new rare mtDNA pathogenic variants causing LHON are increasingly identified.
Post-Surgical Outcome and Its Determining Factors in Patients Operated on With Focal Cortical Dysplasia Type II—A Retrospective Monocenter Study
Authors: Rácz Attila , Becker Albert J. , Quesada Carlos M. , Borger Valeri , Vatter Hartmut , Surges Rainer , Elger Christian E.
Published: June 2021

Purpose: Focal cortical dysplasias (FCDs) are a frequent cause of drug-resistant focal epilepsies. These lesions are in many cases amenable to epilepsy surgery. We examined 12-month and long-term post-surgical outcomes and its predictors including positive family history of epilepsy.

Methods: Twelve-month and long-term outcomes regarding seizure control after epilepsy surgery in patients operated on with FCD type II between 2002 and 2019 in the Epilepsy Center of Bonn were evaluated based on patient records and telephone interviews.

Results: Overall, 102 patients fulfilled the inclusion criteria. Seventy-one percent of patients at 12 months of follow-up (FU) and 54% of patients at the last available FU (63 ± 5.00 months, median 46.5 months) achieved complete seizure freedom (Engel class IA), and 84 and 69% of patients, respectively, displayed Engel class I outcome. From the examined variables [histopathology: FCD IIA vs. IIB, lobar lesion location: frontal vs. non-frontal, family history for epilepsy, focal to bilateral tonic–clonic seizures (FTBTCS) in case history, completeness of resection, age at epilepsy onset, age at surgery, duration of epilepsy], outcomes at 12 months were determined by interactions of age at onset, duration of epilepsy, age at surgery, extent of resection, and lesion location. Long-term post-surgical outcome was primarily influenced by the extent of resection and history of FTBTCS. Positive family history for epilepsy had a marginal influence on long-term outcomes only.

Conclusion: Resective epilepsy surgery in patients with FCD II yields very good outcomes both at 12-month and long-term follow-ups. Complete lesion resection and the absence of FTBTCS prior to surgery are associated with a better outcome.
Genetic Polymorphisms in Enzymes Involved in One-Carbon Metabolism and Anti-epileptic Drug Monotherapy on Homocysteine Metabolism in Patients With Epilepsy
Authors: Zhu Shaofang , Ni Guanzhong , Sui Lisen , Zhao Yiran , Zhang Xiaoxu , Dai Qilin , Chen Aohan , Lin Wanrong , Li Yinchao , Huang Min , Zhou Liemin
Published: June 2021

Aims: To investigate the effects of single nucleotide polymorphisms (SNPs) in genes of one-carbon metabolism (OCM) related enzymes and anti-epileptic drug (AED) monotherapy on homocysteine (Hcy) metabolism in patients with epilepsy, and to further explore specific SNPs that may increase patients' susceptibility to the effects of AEDs on the Hcy imbalance.

Method: This case-control study analyzed 279 patients with epilepsy, including patients receiving monotherapy with valproate (VPA) (n = 53), oxcarbazepine (OXC) (n = 71), lamotrigine (LTG) (n = 55), or levetiracetam (LEV) (n = 35) and patients who had not taken any AEDs (controls, n = 65) for at least 6 months. Serum levels of vitamin B12 (vit B12), folate (FA) and Hcy were measured, and 23 SNPs in 13 genes of OCM-related enzymes were genotyped in all patients.

Results: Methylenetetrahydrofolate reductase (MTHFR) rs1801133 was associated with elevated serum Hcy levels in patients with epilepsy (P < 0.001), and patients presenting the TT genotype exhibited higher serum Hcy levels than patients with the CC (P < 0.001) or CT (P < 0.001) genotype. A subsequent multiple linear regression analysis showed that AED monotherapy with VPA (vs. control: P = 0.023) or OXC (vs. control: P = 0.041), and genotypes of MTHFR rs1801133 TT (vs. CC: P < 0.001; vs. CT: P < 0.001), transcobalamin 2 (TCN2) rs1801198 CC (vs. GC: P = 0.039) and folate receptor 1 (FOLR1) rs2071010 AA (vs. GA: P = 0.031) were independent risk factors for higher Hcy levels. In the subgroup analysis of patients taking OXC, we found that patients with genotypes of MTHFR rs1801133 TT (vs. CC: P = 0.001; vs. CT: P < 0.001) and TCN2 rs1801198 CC (vs. GC: P = 0.021; vs. GG: P = 0.018) exhibited higher serum Hcy levels.

Conclusions: VPA, OXC, and genotypes of MTHFR rs1801133 TT, TCN2 rs1801198 CC, and FOLR1 rs2071010 AA are all independent risk factors for elevated Hcy levels in patients with epilepsy. Moreover, genotypes of MTHFR rs1801133 TT and TCN2 rs1801198 CC may increase patients' susceptibility to the effect of OXC on disrupting Hcy homeostasis.
Bilateral Amygdala Radio-Frequency Ablation for Refractory Aggressive Behavior Alters Local Cortical Thickness to a Pattern Found in Non-refractory Patients
Authors: Gouveia Flavia Venetucci , Germann Jürgen , Devenyi Gabriel A. , Fonoff Erich T. , Morais Rosa M. C. B. , Brentani Helena , Chakravarty M. Mallar , Martinez Raquel C. R.
Published: June 2021

Aggressive behaviors comprise verbal and/or physical aggression directed toward oneself, others, or objects and are highly prevalent among psychiatric patients, especially patients diagnosed with autism spectrum disorder and severe intellectual disabilities. Some of these patients are considered refractory to treatment, and functional neurosurgery targeting the amygdala can result in widespread plastic brain changes that might reflect ceasing of some abnormal brain function, offering symptom alleviation. This study investigated cortical thickness changes in refractory aggressive behavior patients that were treated with bilateral amygdala ablation and compared to control patients presenting non-refractory aggressive behavior [three refractory and seven non-refractory patients, all males diagnosed with autism spectrum disorder (ASD) and intellectual disabilities]. The Overt Aggression Scale (OAS) was used to quantify behavior and magnetic resonance imaging was performed to investigate cortical thickness. Before surgery, both groups presented similar total OAS score, however refractory patients presented higher physical aggression against others. After surgery the refractory group showed 88% average reduction of aggressive behavior. Imaging analysis showed that while refractory patients present an overall reduction in cortical thickness compared to non-refractory patients across both timepoints, the local pattern of thickness difference found in areas of the neurocircuitry of aggressive behavior present before surgery is diminished and no longer detected after surgery. These results corroborate the hypotheses on induction of widespread neuronal plasticity following functional neurosurgical procedures resulting in modifications in brain morphology and improvement in behavior. Further studies are necessary to determine the underlying cause of these morphological changes and to better understand and improve treatment options.
Neural Entrainment Meets Behavior: The Stability Index as a Neural Outcome Measure of Auditory-Motor Coupling
Authors: Rosso Mattia , Leman Marc , Moumdjian Lousin
Published: June 2021

Understanding rhythmic behavior in the context of coupled auditory and motor systems has been of interest to neurological rehabilitation, in particular, to facilitate walking. Recent work based on behavioral measures revealed an entrainment effect of auditory rhythms on motor rhythms. In this study, we propose a method to compute the neural component of such a process from an electroencephalographic (EEG) signal. A simple auditory-motor synchronization paradigm was used, where 28 healthy participants were instructed to synchronize their finger-tapping with a metronome. The computation of the neural outcome measure was carried out in two blocks. In the first block, we used Generalized Eigendecomposition (GED) to reduce the data dimensionality to the component which maximally entrained to the metronome frequency. The scalp topography pointed at brain activity over contralateral sensorimotor regions. In the second block, we computed instantaneous frequency from the analytic signal of the extracted component. This returned a time-varying measure of frequency fluctuations, whose standard deviation provided our “stability index” as a neural outcome measure of auditory-motor coupling. Finally, the proposed neural measure was validated by conducting a correlation analysis with a set of behavioral outcomes from the synchronization task: resultant vector length, relative phase angle, mean asynchrony, and tempo matching. Significant moderate negative correlations were found with the first three measures, suggesting that the stability index provided a quantifiable neural outcome measure of entrainment, with selectivity towards phase-correction mechanisms. We address further adoption of the proposed approach, especially with populations where sensorimotor abilities are compromised by an underlying pathological condition. The impact of using stability index can potentially be used as an outcome measure to assess rehabilitation protocols, and possibly provide further insight into neuropathological models of auditory-motor coupling.
Proteomic Approaches to Study Cysteine Oxidation: Applications in Neurodegenerative Diseases
Authors: Pham Trong Khoa , Buczek Weronika A. , Mead Richard J. , Shaw Pamela J. , Collins Mark O.
Published: June 2021

Oxidative stress appears to be a key feature of many neurodegenerative diseases either as a cause or consequence of disease. A range of molecules are subject to oxidation, but in particular, proteins are an important target and measure of oxidative stress. Proteins are subject to a range of oxidative modifications at reactive cysteine residues, and depending on the level of oxidative stress, these modifications may be reversible or irreversible. A range of experimental approaches has been developed to characterize cysteine oxidation of proteins. In particular, mass spectrometry-based proteomic methods have emerged as a powerful means to identify and quantify cysteine oxidation sites on a proteome scale; however, their application to study neurodegenerative diseases is limited to date. Here we provide a guide to these approaches and highlight the under-exploited utility of these methods to measure oxidative stress in neurodegenerative diseases for biomarker discovery, target engagement and to understand disease mechanisms.
Factors Determining Consumer Acceptance of Biofortified Food: Case of Zinc-Fortified Wheat in Pakistan's Punjab Province
Authors: Rizwan Muhammad , Zhu Yueji , Qing Ping , Zhang Debin , Ahmed Umar I. , Xu Hui , Iqbal Muhammad A. , Saboor Abdul , Malik Arshad M. , Nazir Adnan , Wu Xuelian , He Puming , Tariq Azam
Published: June 2021

Zinc (Zn) is a fundamental micronutrient required by all living organisms. Zn deficiency among children under 5 years, pregnant, and child-bearing women has been identified in developing countries such as Pakistan. Biofortified crops can increase micronutrient levels and decrease deficiencies. Meanwhile, consumer acceptance is essential, given that genetic alterations can occur during biofortification, resulting in changes in sensory traits and the quality of grains. Therefore, the present study focuses on the determining factors for consumer acceptance of Zn-biofortified wheat., an experimental survey was conducted to achieve the study's objectives. Qualitative and quantitative data were collected and analyzed from 203 respondents in the Punjab province. The results regarding sensory perceptions revealed that people attached great importance to the appearance of the chapati prepared with Zn-biofortified wheat. Therefore, they were willing to purchase Zn-biofortified wheat when asked to choose between the conventional wheat and the Zn-biofortified wheat. Moreover, the probit model illustrates that the level of education in the family and having young children aged under 5 years in the household positively impacted the acceptance of Zn-biofortified wheat among the participants. The findings suggest that there is significant scope for promoting Zn-biofortified wheat in the country. It is also imperative to ensure its availability across various regions so that households with weak purchasing power can buy and address their Zn deficiency. Furthermore, policymakers could introduce reforms targeting business communities for food management, keeping Zn-biofortified wheat in the priority stream.
Pre- and Post-harvest Melatonin Application Boosted Phenolic Compounds Accumulation and Altered Respiratory Characters in Sweet Cherry Fruit
Authors: Michailidis Michail , Tanou Georgia , Sarrou Eirini , Karagiannis Evangelos , Ganopoulos Ioannis , Martens Stefan , Molassiotis Athanassios
Published: June 2021

The aim of the present study was to investigate the impact of exogenous melatonin (0. 5 mM) application through pre-harvest foliar spray and postharvest immersion, alone or in combination, on ripening parameters of sweet cherry (cv. Ferrovia) fruit and their relationship with bioactive compounds and gene expression at harvest as well after cold storage (0°C) for 12 days and subsequent room temperature (20°C) exposure for 8 h. Although several ripening traits were not influenced by melatonin, the combining pre- and post-harvest treatments delayed fruit softening at post-cold period. Preharvest spray with melatonin depressed fruit respiration at time of harvest while all applied treatments induced respiratory activity following cold, indicating that this anti-ripening action of melatonin is reversed by cold. Several genes related to the tricarboxylic acid cycle, such as PaFUM, PaOGDH, PaIDH, and PaPDHA1 were upregulated in fruit exposed to melatonin, particularly following combined pre- and post-harvest application. The accumulation of phenolic compounds, such as neochlorogenic acid, chlorogenic acid, epicatechin, procyanidin B1, procyanidin B2+B4, cyanidin-3-O-galactoside, and cyanidin-3-O-rutinoside along with the expression of several genes involved in phenols biosynthesis, such as PaSK, PaPAL, Pa4CL, PaC4H, and PaFNR were at higher levels in melatonin-treated cherries at harvest and after cold exposure, the highest effects being observed in fruits subjected to both pre- and post-harvest treatments. This study provides a comprehensive understanding of melatonin-responsive ripening framework at different melatonin application conditions and sweet cherry stages, thereby helps to understand the action of this molecule in fruit physiology.
Scaling Up the Family Integrated Care Model in a Level IIIC Neonatal Intensive Care Unit: A Systematic Approach to the Methods and Effort Taken for Implementation
Authors: Moreno-Sanz Bárbara , Montes María Teresa , Antón Marta , Serrada María Teresa , Cabrera Marta , Pellicer Adelina
Published: June 2021

Background: Family Integrated Care (FICare) integrates parents in the direct care of their child while the healthcare personnel act as teachers and guides. To this date, most reports on the feasibility of this model refer to stable preterm infants admitted to Neonatal Intensive Care Units (NICUs).

Objectives: To scale up and adapt FICare to make it suitable in level IIIC NICUs, which care for extreme prematurity and other complex medical or surgical neonatal conditions.

Materials and Methods: Step 1 was the creation of the FICare implementation team (FICare-IT) and baseline analysis of current procedures for critical care to identify needs, wishes, and requirements; we aimed for protocol elaboration tailored to our cultural, architectural, and clinical context (March 2017 to April 2018). Step 2 as a dissemination strategy by FICare-IT acting as primary trainers and mentors to ensure the education of 90% of nursing staff (May 2018 to July 2018). Step 3 involved piloting and evaluation with the aim to refine the procedure (July 2018 to December 2020).

Results: A rigorous but flexible protocol was edited. The FICare educational manual included two curricula: for healthcare professionals/staff (Training the trainers) and for families (Education of caregivers), the latter being categorized in two intervention levels (basic and advanced), depending on the infant care needs and parent's decision. In total, 76 families and 91 infants (74.7% preterm; 18.7% complex surgery; 6.6% others) were enrolled in the pilot. No differences in acceptance rate (overall 86.4%) or in the number of infant-family dyads in the program per month were observed when considering the pre- and post-Covid-19 pandemic periods. All families, except for one who dropped out of the program, completed the agreed individualized training. Mothers spent more time in NICU than fathers (p < 0.05); uninterrupted time spent by mothers in NICU was longer during the pre-pandemic period (p < 0.01). Observed time to reach proficiency by task was within the expected time in 70% of the program contents. The parents revealed educational manuals, workshops, and cot-side teaching sessions as essential for their training, and 100% said they would accept entry into the FICare program again.

Conclusions: The principles of the FICare model are suitable for all levels of care in NICUs. Leadership and continuous evaluation/refinement of implementation procedures are essential components to achieve the objectives.