bluuebunny/crossref_metadata_2025 huggingface dataset:
Decoding Multiple Sound-Categories in the Auditory Cortex by Neural Networks: An fNIRS Study
Authors: Yoo So-Hyeon , Santosa Hendrik , Kim Chang-Seok , Hong Keum-Shik
Published: April 2021

This study aims to decode the hemodynamic responses (HRs) evoked by multiple sound-categories using functional near-infrared spectroscopy (fNIRS). The six different sounds were given as stimuli (English, non-English, annoying, nature, music, and gunshot). The oxy-hemoglobin (HbO) concentration changes are measured in both hemispheres of the auditory cortex while 18 healthy subjects listen to 10-s blocks of six sound-categories. Long short-term memory (LSTM) networks were used as a classifier. The classification accuracy was 20.38 ± 4.63% with six class classification. Though LSTM networks’ performance was a little higher than chance levels, it is noteworthy that we could classify the data subject-wise without feature selections.
Cell-Type Specific Changes in DNA Methylation of SNCA Intron 1 in Synucleinopathy Brains
Authors: Gu Jeffrey , Barrera Julio , Yun Young , Murphy Susan K. , Beach Thomas G. , Woltjer Randy L. , Serrano Geidy E. , Kantor Boris , Chiba-Falek Ornit
Published: April 2021

Parkinson’s disease (PD) and dementia with Lewy body (DLB) are the most common synucleinopathies. SNCA gene is a major genetic risk factor for these diseases group, and dysregulation of its expression has been implicated in the genetic etiologies of several synucleinopathies. DNA methylation at CpG island (CGI) within SNCA intron 1 has been suggested as a regulatory mechanism of SNCA expression, and changes in methylation levels at this region were associated with PD and DLB. However, the role of DNA methylation in the regulation of SNCA expression in a cell-type specific manner and its contribution to the pathogenesis of PD and DLB remain poorly understood, and the data are conflicting. Here, we employed a bisulfite pyrosequencing technique to profile the DNA methylation across SNCA intron 1 CGI in PD and DLB compared to age- and sex-matched normal control subjects. We analyzed homogenates of bulk post-mortem frozen frontal cortex samples and a subset of neuronal and glia nuclei sorted by the fluorescence-activated nuclei sorting (FANS) method. Bulk brain tissues showed no significant difference in the overall DNA methylation across SNCA intron 1 CGI region between the neuropathological groups. Sorted neuronal nuclei from PD frontal cortex showed significant lower levels of DNA methylation at this region compared to normal controls, but no differences between DLB and control, while sorted glia nuclei exhibited trends of decreased overall DNA methylation in DLB only. In conclusion, our data suggested disease-dependent cell-type specific differential DNA methylation within SNCA intron 1 CGI. These changes may affect SNCA dysregulation that presumably mediates disease-specific risk. Our results can be translated into the development of the SNCA intron 1 CGI region as an attractive therapeutics target for gene therapy in patients who suffer from synucleinopathies due to SNCA dysregulation.
A Graphlet-Based Topological Characterization of the Resting-State Network in Healthy People
Authors: Finotelli Paolo , Piccardi Carlo , Miglio Edie , Dulio Paolo
Published: April 2021

In this paper, we propose a graphlet-based topological algorithm for the investigation of the brain network at resting state (RS). To this aim, we model the brain as a graph, where (labeled) nodes correspond to specific cerebral areas and links are weighted connections determined by the intensity of the functional magnetic resonance imaging (fMRI). Then, we select a number of working graphlets, namely, connected and non-isomorphic induced subgraphs. We compute, for each labeled node, its Graphlet Degree Vector (GDV), which allows us to associate a GDV matrix to each one of the 133 subjects of the considered sample, reporting how many times each node of the atlas “touches” the independent orbits defined by the graphlet set. We focus on the 56 independent columns (i.e., non-redundant orbits) of the GDV matrices. By aggregating their count all over the 133 subjects and then by sorting each column independently, we obtain a sorted node table, whose top-level entries highlight the nodes (i.e., brain regions) most frequently touching each of the 56 independent graphlet orbits. Then, by pairwise comparing the columns of the sorted node table in the top-k entries for various values of k, we identify sets of nodes that are consistently involved with high frequency in the 56 independent graphlet orbits all over the 133 subjects. It turns out that these sets consist of labeled nodes directly belonging to the default mode network (DMN) or strongly interacting with it at the RS, indicating that graphlet analysis provides a viable tool for the topological characterization of such brain regions. We finally provide a validation of the graphlet approach by testing its power in catching network differences. To this aim, we encode in a Graphlet Correlation Matrix (GCM) the network information associated with each subject then construct a subject-to-subject Graphlet Correlation Distance (GCD) matrix based on the Euclidean distances between all possible pairs of GCM. The analysis of the clusters induced by the GCD matrix shows a clear separation of the subjects in two groups, whose relationship with the subject characteristics is investigated.
Plasma Branched-Chain Amino Acids Are Associated With Greater Fasting and Postprandial Insulin Secretion in Non-diabetic Chinese Adults
Authors: Ding Cherlyn , Egli Leonie , Bosco Nabil , Sun Lijuan , Goh Hui Jen , Yeo Khung Keong , Yap Jonathan Jiunn Liang , Actis-Goretta Lucas , Leow Melvin Khee-Shing , Magkos Faidon
Published: April 2021

Background:Plasma branched-chain amino acids (BCAA) are consistently elevated in subjects with obesity and type 2 diabetes (T2DM) and correlate with insulin resistance. The association of BCAA with insulin secretion and clearance rates has not been adequately described.

Objective:To evaluate the relationships between fasting and postprandial plasma BCAA, insulin secretion and insulin clearance.

Design:Ninety-five non-diabetic Chinese subjects (43 females) underwent a mixed-meal tolerance test; blood biomarkers including BCAAs (leucine, isoleucine, valine) were measured for 6 h. Fasting and postprandial insulin secretion rates (ISR) and insulin clearance were determined by oral minimal modeling of glucose and C-peptide.

Results:Fasting and postprandial plasma BCAA correlated strongly with each other (ρ = 0.796,P< 0.001), and both were positively associated with basal ISR (ρ = 0.45/0.36,P< 0.001), total postprandial ISR AUC (ρ = 0.37/0.45,P< 0.001), and negatively with insulin clearance (ρ = −0.29/−0.29,P< 0.01), after adjusting for sex and body mass index. These relationships largely persisted after adjusting further for insulin resistance and postprandial glucose. Compared with subjects in the middle and lowest tertiles for fasting or postprandial plasma BCAA, subjects in the highest tertile had significantly greater postprandial glucose (by 7–10%) and insulin (by 74–98%) concentrations, basal ISRs (by 34–53%), postprandial ISR AUCs (by 41–49%), and lower insulin clearance rates (by 17–22%) (allP< 0.05).

Conclusions:Fasting and postprandial plasma BCAA levels are associated with greater fasting and postprandial insulin secretion and reduced insulin clearance in healthy Chinese subjects. These observations potentially highlight an additional layer of involvement of BCAA in the regulation of glucose homeostasis.
Rheological and Nutritional Characterization of Sweet Corn By-Product (Cob) to Develop a Functional Ingredient Applied in Dressings
Authors: Castillo Sandra , Rodríguez Alexis , Bautista-Villarreal Minerva , García-Solano Nallely , Gallardo-Rivera Claudia , Báez-González Juan G. , Sánchez-García Eduardo , García-Alanis Karla G.
Published: April 2021

In this study, a flour from corn cob (central core of the maize ear, stage R4) was obtained through three treatments. The three flours obtained were characterized by bromatological analysis, yield, and granulometry. Additional dressing-type oil in water (O/W) emulsions were developed, varying the formulation by incorporating distinct amounts of corn cob flour. The formulations' stability was evaluated over a period of 21 days, determining the particle size, creaming index, coalescence rate, consistency coefficient (k), and flow behavior indices (n). Results have shown significant differences in protein, fat, and carbohydrate content in the flour, depending on the cooking treatment. A good percentage of grinding yield was obtained (98%), in addition to several fractions by granulometry (60, 120, 250 MESH), showing differences in their nutritional content. Finally, the particle size of O/W emulsions developed varied among formulations. The combination of 0.6% of xanthan gum (XG) and corn cob flour showed major stability in average droplet size. No significant differences were observed in the coalescence rate values for the three formulations. Still, significant differences in the creaming index were evidenced in those formulations without XG or corn cob flour. The results regarding the consistency coefficient (k) and flow behavior indices (n) suggest a possible synergy between XG and flour of corn cob for enhancing the viscosity and pseudoplasticity of dressings in a concentration-dependent manner.
Hepatic Artery Infusion of Floxuridine in Combination With Systemic Chemotherapy for Pancreatic Cancer Liver Metastasis: A Propensity Score-Matched Analysis in Two Centers
Authors: Peng Changli , Xu Bin , Xiao Juxiong , Zhou Chunhui , Li Xiaodong , Shi Hongbing , Qiang Weiguang , Wang Tianming , Zhao Jiemin , Liu Fei , Li Gang , Li Haiping , Chen Changyong , Shi Liangrong
Published: April 2021

Aim

To evaluate the efficacy of hepatic artery infusion (HAI) of floxuridine (FUDR) in combination with systemic chemotherapy in patients with pancreatic cancer liver metastases (PCLM).

Patients and Methods

We retrospectively collected clinical data of 347 patients with PCLM who underwent first-line chemotherapy at two Chinese centers between 2012 and 2019. Propensity score matching between patients with and without HAI was performed to compensate for differences in baseline characteristics. Objective response rate (ORR) and overall survival (OS) between groups were compared. HAI pump functionality was recorded.

Results

Data of 258 patients (62 patients with HAI and 196 patients without HAI) were used for matching. After 1:1 ratio matching, 62 patients per group were included. The intrahepatic ORR was 66.1% in the HAI group and 22.6% in the non-HAI group (P < 0.001), and the extrahepatic ORR was 25.0 versus 28.9% (P = 0.679). The median OS was significantly longer in HAI group (14.0 versus 10.8 months, P = 0.001). Multivariance COX regression showed HAI led to a decrease in hazard ratio for death by 61.8% (HR = 0.382; 95% CI: 0.252–0.578; P< 0.001). Subgroup analysis revealed that patients without EHM, with higher intrahepatic tumor burden and with synchronous liver metastasis benefited more from HAI. Dysfunction of HAI pump occurred in 5.7% of patients during the period of follow-up.

Conclusions

In patients with PCLM, first-line treatment with HAI FUDR plus SCT resulted in higher intrahepatic response and better OS.
The Protective Role of Maternal Immunization in Early Life
Authors: Cinicola Bianca , Conti Maria Giulia , Terrin Gianluca , Sgrulletti Mayla , Elfeky Reem , Carsetti Rita , Fernandez Salinas Ane , Piano Mortari Eva , Brindisi Giulia , De Curtis Mario , Zicari Anna Maria , Moschese Viviana , Duse Marzia
Published: April 2021

With birth, the newborn is transferred from a quasi-sterile environment to the outside world. At this time, the neonatal immune system is inexperienced and continuously subject to a process of development as it encounters different antigenic stimuli after birth. It is initially characterized by a bias toward T helper 2 phenotype, reduced T helper 1, and cytotoxic responses to microbial stimuli, low levels of memory, and effector T and B cells and a high production of suppressive T regulatory cells. The aim of this setting, during fetal life, is to maintain an anti-inflammatory state and immune-tolerance. Maternal antibodies are transferred during pregnancy through the placenta and, in the first weeks of life of the newborn, they represent a powerful tool for protection. Thus, optimization of vaccination in pregnancy represents an important strategy to reduce the burden of neonatal infections and sepsis. Beneficial effects of maternal immunization are universally recognized, although the optimal timing of vaccination in pregnancy remains to be defined. Interestingly, the dynamic exchange that takes place at the fetal-maternal interface allows the transfer not only of antibodies, but also of maternal antigen presenting cells, probably in order to stimulate the developing fetal immune system in a harmless way. There are still controversial effects related to maternal immunization including the so called “immunology blunting,” i.e., a dampened antibody production following infant's vaccination in those infants who received placentally transferred maternal immunity. However, clinical relevance of this phenomenon is still not clear. This review will provide an overview of the evolution of the immune system in early life and discuss the benefits of maternal vaccination. Current maternal vaccination policies and their rationale will be summarized on the road to promising approaches to enhance immunity in the neonate.
Kawasaki Disease and Systemic Juvenile Idiopathic Arthritis – Two Ends of the Same Spectrum
Authors: Go Ellen , van Veenendaal Mira , Manlhiot Cedric , Schneider Rayfel , McCrindle Brian W. , Yeung Rae S. M.
Published: April 2021

Kawasaki disease (KD) and systemic juvenile idiopathic arthritis (sJIA) are two distinct systemic inflammatory diseases of childhood. Each diagnosis is based on criteria, but numerous clinical features are overlapping. As no specific diagnostic tests are available, differentiation between both disease entities can be challenging. Here, we describe the disease course of patients with co-diagnosis of both KD and sJIA (KD/sJIA). All our KD (n = 1765) and sJIA (n = 112) cases were critically reviewed for co-diagnosis of KD/sJIA. Eight KD/sJIA cases were identified and their clinical presentation, treatment regimens, coronary artery outcome and complications are herein described. Each KD/sJIA patient fulfilled diagnostic criteria for KD and for sJIA. Ongoing fever, rash and arthritis were present in each patient. The KD/sJIA patients had recalcitrant KD requiring multiple doses of intravenous immunoglobulin and steroids. Five patients had coronary artery dilatation at KD diagnosis, which resolved in all by 6 weeks. Pericardial effusion was present in 5 patients. One KD/sJIA patient developed macrophage activation syndrome. In conclusion, a small proportion (0.5%) of our KD patients evolved into sJIA, and 7% of our sJIA population presented initially as KD. KD/sJIA patients were characterized by a recalcitrant KD course and a high prevalence of coronary artery dilatation. Patients with co-diagnoses may provide a clue to potentially shared immunopathology in KD and sJIA, leading us to posit that both entities may be part of the same clinical spectrum.
A Review of the Dose Justification of Phase 3 Trials to Regulatory Authorities for Drugs Intended for the Treatment of Type 2 Diabetes in Europe
Authors: Koomen Jeroen V. , Stevens Jasper , Monster-Simons Margje H. , Heerspink Hiddo J. L. , Mol Peter G. M.
Published: April 2021

Aims: Cardiovascular outcome trials with anti-diabetic drugs suggest that additional cardiovascular benefit can be achieved independent of improving glycaemic control. Nonetheless, dose selection of anti-diabetic drugs is typically based solely on glycaemic effects. We evaluated whether off-target drug effects are currently considered for dose justification to regulatory agencies.

Methods: In the European Union, anti-diabetic drugs are registered by the European Medicines Agency. We extracted available information regarding dose selection from public assessment reports and marketing application dossiers. Descriptive statistics were used to summarise the extracted information.

Results: In total, 14 drugs of three drug classes were included; sodium-glucose co-transporter-2 inhibitors (n = 4), dipeptidyl peptidase-4 inhibitors (n = 4) and glucagon-like peptide-1 receptor agonists (n = 6). For these drugs, 21 dose-finding trials were submitted including results of multiple off-target effects, of which body weight (n = 18) and low-density lipoprotein cholesterol (n = 14) were most frequently reported. Dose-response curves for off-target effects appeared to be different compared to the glycaemic dose-response curve. Glycated hemoglobin (100%) and fasting plasma glucose (42.9%), were used most frequently for the dose justification, but generally off-target effects (<25%) were not.

Conclusions: Dose justification to regulatory authorities was mainly based on glycaemic effects. The dose-response relationship for the off-target effects did not necessarily follow the dose-response relationship of the on-target effects suggesting that selection of the optimal anti-diabetic dose could benefit from including off-target effects in the dose selection process as well.
Deterministic and Stochastic Cellular Mechanisms Contributing to Carbon Monoxide Induced Ventricular Arrhythmias
Authors: Al-Owais Moza M. , Steele Derek S. , Holden Arun V. , Benson Alan P.
Published: April 2021

Chronic exposure to low levels of Carbon Monoxide is associated with an increased risk of cardiac arrhythmia. Microelectrode recordings from rat and guinea pig single isolated ventricular myocytes exposed to CO releasing molecule CORM-2 and excited at 0.2/s show repolarisation changes that develop over hundreds of seconds: action potential prolongation by delayed repolarisation, EADs, multiple EADs and oscillations around the plateau, leading to irreversible repolarisation failure. The measured direct effects of CO on currents in these cells, and ion channels expressed in mammalian systems showed an increase in prolonged late Na+, and a decrease in the maximal T- and L-type Ca++. peak and late Na+, ultra-rapid delayed, delayed rectifier, and the inward rectifier K+ currents. Incorporation of these CO induced changes in maximal currents in ventricular cell models; (Gattoni et al., J. Physiol., 2016, 594, 4193–4224) (rat) and (Luo and Rudy, Circ. Res., 1994, 74, 1071–1096) (guinea-pig) and human endo-, mid-myo- and epi-cardial (O’Hara et al., PLoS Comput. Biol., 2011, 7, e1002061) models, by changes in maximal ionic conductance reproduces these repolarisation abnormalities. Simulations of cell populations with Gaussian distributions of maximal conductance parameters predict a CO induced increase in APD and its variability. Incorporation of these predicted CO induced conductance changes in human ventricular cell electrophysiology into ventricular tissue and wall models give changes in indices for the probability of the initiation of re-entrant arrhythmia.
Alcohol Co-Administration Changes Mephedrone-Induced Alterations of Neuronal Activity
Authors: Grotell Milo , den Hollander Bjørnar , Jalkanen Aaro , Törrönen Essi , Ihalainen Jouni , de Miguel Elena , Dudek Mateusz , Kettunen Mikko I. , Hyytiä Petri , Forsberg Markus M. , Kankuri Esko , Korpi Esa R.
Published: April 2021

Mephedrone (4-MMC), despite its illegal status, is still a widely used psychoactive substance. Its effects closely mimic those of the classical stimulant drug methamphetamine (METH). Recent research suggests that unlike METH, 4-MMC is not neurotoxic on its own. However, the neurotoxic effects of 4-MMC may be precipitated under certain circumstances, such as administration at high ambient temperatures. Common use of 4-MMC in conjunction with alcohol raises the question whether this co-consumption could also precipitate neurotoxicity. A total of six groups of adolescent rats were treated twice daily for four consecutive days with vehicle, METH (5 mg/kg) or 4-MMC (30 mg/kg), with or without ethanol (1.5 g/kg). To investigate persistent delayed effects of the administrations at two weeks after the final treatments, manganese-enhanced magnetic resonance imaging brain scans were performed. Following the scans, brains were collected for Golgi staining and spine analysis. 4-MMC alone had only subtle effects on neuronal activity. When administered with ethanol, it produced a widespread pattern of deactivation, similar to what was seen with METH-treated rats. These effects were most profound in brain regions which are known to have high dopamine and serotonin activities including hippocampus, nucleus accumbens and caudate-putamen. In the regions showing the strongest activation changes, no morphological changes were observed in spine analysis. By itself 4-MMC showed few long-term effects. However, when co-administered with ethanol, the apparent functional adaptations were profound and comparable to those of neurotoxic METH.
Turbulence Upstream and Downstream of Interplanetary Shocks
Authors: Pitňa A. , Šafránková J. , Němeček Z. , Ďurovcová T. , Kis A.
Published: April 2021

The paper reviews the interaction of collisionless interplanetary (IP) shocks with the turbulent solar wind. The coexistence of shocks and turbulence plays an important role in understanding the acceleration of particles via Fermi acceleration mechanisms, the geoeffectiveness of highly disturbed sheaths following IP shocks and, among others, the nature of the fluctuations themselves. Although our knowledge of physics of upstream and downstream shock regions has been greatly improved in recent years, many aspects of the IP-shock/turbulence interaction are still poorly known, for example, the nature of turbulence, its characteristics on spatial and temporal scales, how it decays, its relation to shock passage and others. We discuss properties of fluctuations ahead (upstream) and behind (downstream) of IP shock fronts with the focus on observations. Some of the key characteristics of the upstream/downstream transition are 1) enhancement of the power in the inertial range fluctuations of the velocity, magnetic field and density is roughly one order of magnitude, 2) downstream fluctuations are always more compressible than the upstream fluctuations, and 3) energy in the inertial range fluctuations is kept constant for a significant time after the passage of the shock. In this paper, we emphasize that–for one point measurements–the downstream region should be viewed as an evolutionary record of the IP shock propagation through the plasma. Simultaneous measurements of the recently launched spacecraft probing inner parts of the Solar System will hopefully shed light on some of these questions.
A Prospective Evaluation of the Acute Effects of High Altitude on Cognitive and Physiological Functions in Lowlanders
Authors: Falla Marika , Papagno Costanza , Dal Cappello Tomas , Vögele Anna , Hüfner Katharina , Kim Jenny , Weiss Elisabeth M. , Weber Bernhard , Palma Martin , Mrakic-Sposta Simona , Brugger Hermann , Strapazzon Giacomo
Published: April 2021

Cognitive function impairment due to high altitude exposure has been reported with some contradictory results regarding the possible selective cognitive domain involvement. We prospectively evaluated in 36 lowlanders, exposed for 3 consecutive days to an altitude of 3,269 m, specific cognitive abilities (attention, processing speed, and decision-making) required to safely explore the mountains, as well as to work at altitude. We simultaneously monitored the physiological parameters. Our study provides evidence of a reduced processing speed in lowlanders when exposed to altitude in the first 24 h. There was a fairly quick recovery since this impairment was no more detectable after 36 h of exposure. There were no clinically relevant effects on decision-making, while psychomotor vigilance was unaffected at altitude except for individuals with poor sleep. Significant changes were seen in physiological parameters (increased heart rate and reduced peripheral oxygen saturation). Our results may have practical implications, suggesting that individuals should practice prudence with higher ascent when performing risky activities in the first 24–36 h, even at altitudes below 3,500 m, due to an impairment of the cognitive performance that could worsen and lead to accidents.
Regulation of 2,4-D Isooctyl Ester on Triticum aestivum and Aegilops tauschii Tillering and Endogenous Phytohormonal Responses
Authors: Yu Haiyan , Cui Hailan , Chen Jingchao , Chen Pingping , Ji Meijing , Huang Songtao , Li Xiangju
Published: April 2021

Tillering is an important agronomic trait essential for the yield of Triticum aestivum and the propagation of Aegilops tauschii. However, the effect of phytohormones on T. aestivum and Ae. tauschii tillering and the underlying regulatory mechanisms remain poorly understood. In the study, we found that T. aestivum and Ae. tauschii exhibited different tillering sensitivities to the auxin herbicide 2,4-D isooctyl ester. At 3 days post-application, tiller bud growth was inhibited by 77.50% in T. aestivum, corresponding to 2.0-fold greater inhibition than that in Ae. tauschii (38.71%). Transcriptome analysis showed that differentially expressed genes (DEGs) in the T. aestivum response to 2,4-D isooctyl ester were mainly enriched in plant hormone metabolism and signal transduction pathways, but similar changes were not observed in Ae. tauschii. Among that, the auxin biosynthesis and signaling induced by 2,4-D isooctyl ester was quite different between the two species. A total of nine candidate genes involved in varied tillering responses were selected from the DEGs and validated by quantitative real-time PCR. Endogenous hormone levels were assayed to further verify the RNA-seq results. After 2,4-D isooctyl ester treatment, a significant increase in abscisic acid (ABA) levels was observed in T. aestivum, whereas ABA levels were relatively stable in Ae. tauschii. The herbicide induced more cytokinin (CTK) accumulation in Ae. tauschii than in T. aestivum. External ABA clearly restricted tiller bud growth in both T. aestivum and Ae. tauschii, while 6-benzyl aminopurine had no significant effect. These results indicate that ABA and CTK may be related with 2,4-D isooctyl ester-regulated tillering differences between the two species, which will help to further understand the mechanism of the auxin-mediated regulation of tillering
Comparative Transcriptomics and Proteomics Analyses of Leaves Reveals a Freezing Stress-Responsive Molecular Network in Winter Rapeseed (Brassica rapa L.)
Authors: Wei Jiaping , Zheng Guoqiang , Yu Xingwang , Liu Sushuang , Dong Xiaoyun , Cao Xiaodong , Fang Xinling , Li Hui , Jin Jiaojiao , Mi Wenbo , Liu Zigang
Published: April 2021

Winter rapeseed is susceptible to low temperature during winter in Northwest China, which could lead to a severe reduction of crop production. The freezing temperature could stress the whole plant, especially the leaf, and ultimately harm the survival rate of winter rapeseed. However, the molecular mechanism underlying freezing tolerance is still unclear in winter rapeseed. In this study, a comprehensive investigation of winter rapeseed freezing tolerance was conducted at the levels of transcript, protein, and physiology and biochemistry, using a pair of freezing-sensitive and freezing-resistant cultivars NQF24 and 17NTS57. There were 4,319 unique differentially expressed genes (DEGs) and 137 unique differentially abundant proteins (DAPs) between two cultivars identified in leaf under freezing stress. Function enrichment analysis showed that most of the enriched DEGs and DAPs were involved in plant hormone signal transduction, alpha-linolenic/linoleic acid metabolism, peroxisome, glutathione metabolism, fatty acid degradation, and secondary metabolite biosynthesis pathways. Based on our findings, it was speculated that freezing tolerance formation is caused by increased signal transduction, enhanced biosynthesis of protein, secondary metabolites, and plant hormones, elevated energy supply, greater reactive oxygen species scavenging, and lower lipid peroxidation as well as stronger cell stability in leaf under freezing stress. These results provide a comprehensive profile of leaf response under freezing stress, which have potential to be used as selection indicators of breeding programs to improve freezing tolerance in rapeseed.
Novel Salinity Tolerance Loci in Chickpea Identified in Glasshouse and Field Environments
Authors: Atieno Judith , Colmer Timothy D. , Taylor Julian , Li Yongle , Quealy John , Kotula Lukasz , Nicol Dion , Nguyen Duong T. , Brien Chris , Langridge Peter , Croser Janine , Hayes Julie E. , Sutton Tim
Published: April 2021

A better understanding of the genetics of salinity tolerance in chickpea would enable breeding of salt tolerant varieties, offering potential to expand chickpea production to marginal, salinity-affected areas. A Recombinant Inbred Line population was developed using accelerated-Single Seed Descent of progeny from a cross between two chickpea varieties, Rupali (salt-sensitive) and Genesis836 (salt-tolerant). The population was screened for salinity tolerance using high-throughput image-based phenotyping in the glasshouse, in hydroponics, and across 2 years of field trials at Merredin, Western Australia. A genetic map was constructed from 628 unique in-silico DArT and SNP markers, spanning 963.5 cM. Markers linked to two flowering loci identified on linkage groups CaLG03 and CaLG05 were used as cofactors during genetic analysis to remove the confounding effects of flowering on salinity response. Forty-two QTL were linked to growth rate, yield, and yield component traits under both control and saline conditions, and leaf tissue ion accumulation under salt stress. Residuals from regressions fitting best linear unbiased predictions from saline conditions onto best linear unbiased predictions from control conditions provided a measure of salinity tolerance per se, independent of yield potential. Six QTL on CaLG04, CaLG05, and CaLG06 were associated with tolerance per se. In total, 21 QTL mapped to two distinct regions on CaLG04. The first distinct region controlled the number of filled pods, leaf necrosis, seed number, and seed yield specifically under salinity, and co-located with four QTL linked to salt tolerance per se. The second distinct region controlled 100-seed weight and growth-related traits, independent of salinity treatment. Positional cloning of the salinity tolerance-specific loci on CaLG04, CaLG05, and CaLG06 will improve our understanding of the key determinants of salinity tolerance in chickpea.
Parenting Characteristics among Adults With Social Anxiety and their Influence on Social Anxiety Development in Children: A Brief Integrative Review
Authors: Garcia Katelyn M. , Carlton Corinne N. , Richey John A.
Published: April 2021

The purposes of this brief integrative review are to identify and critically evaluate recent work in the area of parenting processes that are disproportionately observed among parents with social anxiety disorder (SAD) that may ultimately increase risk among offspring, and to further link these processes to specific targets for intervention. Accordingly, we first evaluate the relevance of specific parenting styles as they pertain to increased risk of developing SAD among offspring. Second, we link these parenting processes to observations of certain unfavorable consequences among socially anxious youth, such as low perceived autonomy and poorer social skills. Finally, in light of these consequences we extend our conclusions into potentially modifiable targets among parents with SAD, focusing on the enhancement of autonomy and facilitating offspring's normative period of transition into independence during adolescence. Overall, we conclude that parenting behaviors commonly observed among adults with SAD, such as overcontrol and low parental warmth, likely have a direct impact on the development of social anxiety symptoms among their children. However, these parenting behaviors are plausibly modifiable and therefore repurposing existing interventions for use among parents with SAD in conjunction with interventions with their offspring is likely to provide direct clinical benefit.
Survey on the Progression of Myopia in Children and Adolescents in Chongqing During COVID-19 Pandemic
Authors: Wang Wujiao , Zhu Lu , Zheng Shijie , Ji Yan , Xiang Yongguo , Lv Bingjing , Xiong Liang , Li Zhuoyu , Yi Shenglan , Huang Hongyun , Zhang Li , Liu Fangli , Wan Wenjuan , Hu Ke
Published: April 2021

Background: The Covid-19 pandemic restricts children and adolescents from doing normal daily activities such as playing outdoors and going to school. The incidence and prevalence of myopia have increased during the COVID-19 pandemic. The aim of this study was to investigate and evaluate the impact of the home confinement during the COVID-19 pandemic on the progression of myopia among children and adolescents in Chongqing, China.

Methods: The survey was conducted by using stratified samplings. Samples were randomly selected from the 2019 National Student Physique and Health Survey database, and their visual function and refractive data were compared with those in 2020. Vision-related behavior questionnaire including digital screen exposure was applied to investigate the correlation between eye parameter and eye health-related behavior.

Results: A total of 1,733 and 1,728 students were enrolled in 2020 and 2019, respectively. The percentage of myopia students was 55.02% in 2020, which was higher than that in 2019 (44.62%). The mean uncorrected visual acuity (UCVA, LogMAR, 0.35 ± 0.42) in 2020 was higher than that in 2019 (0.27 ± 0.36, P < 0.001). The mean spherical equivalent (SE) refraction (−1.94 ± 2.13 D) in 2020 was lower than that in 2019 (−1.64 ± 5.49 D, P < 0.001). For students who used digital devices for online courses, the mean SE in the television group (−1.10 ± 1.49 D) was better than that in the computer group (−2.03 ± 2.37 D, P = 0.0017) and in the cell phone group (−2.02 ± 2.09 D, P = 0.0028). The average duration of online classes (r = −0.27, P < 0.0001), the number of online classes per day (r = −0.33, P < 0.0001), as well as digital screen exposure time (r = −0.20, P < 0.0001) were negatively correlated with SE, and the average time of outdoor activity (r = 0.20, P < 0.0001) was positively correlated with SE.

Conclusions: Increased digital screen exposure contributes to myopic progression in children and adolescents of Chongqing during the COVID-19 pandemic. Suitable digital devices should be provided for online classes and outdoor activity should be advocated to prevent myopic pandemic.
Fuzzy Supervisory Passivity-Based High Order-Sliding Mode Control Approach for Tidal Turbine-Based Permanent Magnet Synchronous Generator Conversion System
Authors: Belkhier Youcef , Achour Abdelyazid , Shaw Rabindra Nath , Ullah Nasim , Chowdhury Md. Shahariar , Techato Kuaanan
Published: April 2021

Higher efficiency, predictability, and high-power density are the main advantages of a permanent magnet synchronous generator (PMSG)-based hydro turbine. However, the control of a PMSG is a nontrivial issue, because of its time-varying parameters and nonlinear dynamics. This paper suggests a novel optimal fuzzy supervisor passivity-based high order sliding-mode controller to address problems faced by conventional techniques such as PI controls in the machine side. An inherent advantage of the proposed method is that the nonlinear terms are not canceled but compensated in a damped way. The proposed controller consists of two main parts: the fuzzy gain supervisor-PI controller to design the desired dynamic of the system by controlling the rotor speed, and the fuzzy gain-high order sliding-mode control to compute the controller law. The main objectives are feeding the electrical grid with active power, extracting the maximum tidal power, and regulating the reactive power and DC voltage toward their references, whatever the disturbances caused by the PMSG. The main contribution and novelty of the present work consists in the new robust fuzzy supervisory passivity-based high order sliding-mode controller, which treats the mechanical characteristics of the PMSG as a passive disturbance when designing the controller and compensates it. By doing so, the PMSG tracks the optimal speed, contrary to other controls which only take into account the electrical part. The combined high order sliding-mode controller (HSMC) and passivity-based control (PBC) resulted in a hybrid controller law which attempts to greatly enhance the robustness of the proposed approach regardless of various uncertainties. Moreover, the proposed controller was also validated using a processor in the loop (PIL) experiment using Texas Instruments (TI) Launchpad. The control strategy was tested under parameter variations and its performances were compared to the nonlinear control methods. High robustness and high efficiency were clearly illustrated by the proposed new strategy over compared methods under parameter uncertainties using MATLAB/Simulink and a PIL testing platform.
Melatonin Treatment of Pomegranate Trees Increases Crop Yield and Quality Parameters at Harvest and during Storage
Authors: Medina-Santamarina Jorge , Serrano María , Lorente-Mento Jose M. , García-Pastor María E. , Zapata Pedro J. , Valero Daniel , Guillén Fabián
Published: April 2021

With the aim to study the effect of melatonin treatment of pomegranate trees on crop yield and fruit quality at harvest and during storage, two experiments were carried out in two consecutive years: 2017 and 2018. In the first year, trees were treated with melatonin (at 0.1 and 1 mM) along the developmental growth cycle and fruit quality parameters were evaluated at harvest and during storage at 10 °C for 90 days. Treatments with melatonin led to an increase of crop yield (number of fruits per tree and kg per tree), as well as higher fruit quality attributes, such as fruit size (diameter and weight), color, total soluble solids (TSS), and total acidity (TA), especially with the 0.1 mM dose. Then, in the second year, melatonin at 0.1 mM was selected for repeating the pre-harvest treatments with similar results in terms of crop yield and fruit quality parameters. During storage, pomegranate fruit treated with 0.1 mM melatonin maintained higher quality attributes than controls, such as TSS, TA, and firmness and lower weight losses were observed in fruit from treated trees, in both trials. In addition, the content of the major sugars (glucose and fructose) and organic acids (malic, succinic and ascorbic acid) were higher in melatonin-treated than in non-treated fruit. These results suggest that pre-harvest melatonin treatment could be a useful tool to increase pomegranate crop yield as well as fruit quality parameters at harvest and their maintenance during storage due to an effect of melatonin on reducing the postharvest ripening process.
Cover Cropping: A Malleable Solution for Sustainable Agriculture? Meta-Analysis of Ecosystem Service Frameworks in Perennial Systems
Authors: Crézé Cynthia M. , Horwath William R.
Published: April 2021

Cover crops have been touted for their capacity to enhance multifunctionality and ecosystem services (ESs). Ecosystem services are benefits which people obtain from ecosystems. Despite nearly a century of cover crop research, there has been low adoption of the practice in perennial systems of many parts of the world. Emphasis on the multi-functional dimension of cover crop outcomes may misrepresent the practice as a panacea for sustainable agriculture and distract from the need to tailor the practice to specific contexts and differing value systems. In this study, we explore how cover crop ecosystem service (ES) frameworks reflect the distinct environmental realities of perennial agriculture. We considered that ES value systems are manifested through the non-randomization of research coverage. Therefore, value systems can be elucidated through evidence-based systematic mapping. Our analysis revealed differential systems of ES valuation specific to perennial crop types. While ES frameworks are heavily contextualized, the design of seed mixes is not. We suggest that cover crop adoption could be enhanced by clearly acknowledging the different conceptualizations of agricultural sustainability addressed by various cover crops. Furthermore, explicitly delineating the competing desires of stakeholders is a crucial step in rationally selecting between various cover crop seed mix options.
Confounding Factors in Container-Based Drought Tolerance Assessments in Solanum tuberosum
Authors: Köhl Karin I. , Mulugeta Aneley Gedif , Haas Manuela , Peters Rolf
Published: April 2021

Potato is an important food crop with high water-use-efficiency but low drought tolerance. The bottleneck in drought tolerance breeding is phenotyping in managed field environments. Fundamental research on drought tolerance is predominantly done in container-based test systems in controlled environments. However, the portability of results from these systems to performance under field conditions is debated. Thus, we analyzed the effects of climate conditions, container size, starting material, and substrate on yield and drought tolerance assessment of potato genotypes compared to field trials. A leave one out assessment indicated a minimum of three field trials for stable tolerance prediction. The tolerance ranking was highly reproducible under controlled-conditions, but weakly correlated with field performance. Changing to variable climate conditions, increasing container size, and substituting cuttings by seed tubers did not improve the correlation. Substituting horticultural substrate by sandy soil resulted in yield and tuber size distributions similar to those under field conditions. However, as the effect of the treatment × genotype × substrate interaction on yield was low, drought tolerance indices that depend on relative yields can be assessed on horticultural substrate also. Realistic estimates of tuber yield and tuber size distribution, however, require the use of soil-based substrates.
Classical, Molecular, and Genomic Cytogenetics of the Pig, a Clinical Perspective
Authors: Donaldson Brendan , Villagomez Daniel A. F. , King W. Allan
Published: April 2021

The chromosomes of the domestic pig (Sus scrofa domesticus) are known to be prone to reciprocal chromosome translocations and other balanced chromosome rearrangements with concomitant fertility impairment of carriers. In response to the remarkable prevalence of chromosome rearrangements in swine herds, clinical cytogenetics laboratories have been established in several countries in order to screen young boars for chromosome rearrangements prior to service. At present, clinical cytogenetics laboratories typically apply classical cytogenetics techniques such as giemsa-trypsin (GTG)-banding to produce high-quality karyotypes and reveal large-scale chromosome ectopic exchanges. Further refinements to clinical cytogenetics practices have led to the implementation of molecular cytogenetics techniques such as fluorescent in-situ hybridization (FISH), allowing for rearrangements to be visualized and breakpoints refined using fluorescently labelled painting probes. The next-generation of clinical cytogenetics include the implementation of DNA microarrays, and next-generation sequencing (NGS) technologies such as DNA sequencing to better explore tentative genome architecture changes. The implementation of these cytogenomics techniques allow the genomes of rearrangement carriers to be deciphered at the highest resolution, allowing rearrangements to be detected; breakpoints to be delineated; and, most importantly, potential gene implications of those chromosome rearrangements to be interrogated. Clinical cytogenetics has become an integral tool in the livestock industry, identifying rearrangements and allowing breeders to make informed breeding decisions.
A Low-Cost System for Measuring Wind Speed and Direction Using Thermopile Array and Artificial Neural Network
Authors: Wu Shang-Chen , Tzou Jong-Chyuan , Ding Cheng-Yu
Published: April 2021

Recent developments in wind speed sensors have mainly focused on reducing the size and moving parts to increase reliability and stability. In this study, the development of a low-cost wind speed and direction measurement system is presented. A heat sink mounted on a self-regulating heater is used as means to interact with the wind changes and a thermopile array mounted atop of the heat sink is used to collect temperature data. The temperature data collected from the thermopile array are used to estimate corresponding wind speed and direction data using an artificial neural network. The multilayer artificial neural network is trained using 96 h data and tested on 72 h data collected in an outdoor setting. The performance of the proposed model is compared with linear regression and support vector machine. The test results verify that the proposed system can estimate wind speed and direction measurements with a high accuracy at different sampling intervals, and the artificial neural network can provide significantly a higher coefficient of determination than two other methods.
Celastrol and Triptolide Suppress Stemness in Triple Negative Breast Cancer: Notch as a Therapeutic Target for Stem Cells
Authors: Ramamoorthy Prabhu , Dandawate Prasad , Jensen Roy A. , Anant Shrikant
Published: April 2021

Triple negative breast cancer (TNBC) is observed in ~15% of breast cancers and results in poor survival and increased distant metastases. Within the tumor are present a small portion of cancer stem cells that drive tumorigenesis and metastasis. In this study, we aimed to elucidate whether the two natural compounds, celastrol and triptolide, inhibit stemness in TNBC. MDA-MB-231, BT20, and a patient-derived primary cells (PD-TNBC) were used in the study. Mammosphere assay was performed to assess the stemness. Both celastrol and triptolide treatment suppressed mammosphere formation. Furthermore, the compound suppressed expression of cancer stem cell marker proteins DCLK1, ALDH1, and CD133. Notch signaling plays a critical role in stem cells renewal. Both celastrol or triptolide reduced Notch -1 activation and expression of its downstream target proteins HES-1 and HEY-1. However, when NICD 1 was ectopically overexpressed in the cells, it partially rescued proliferation and mammosphere formation of the cells, supporting the role of notch signaling. Together, these data demonstrate that targeting stem cells and the notch signaling pathway may be an effective strategy for curtailing TNBC progression.
WIN55,212-2, a Dual Modulator of Cannabinoid Receptors and G Protein-Coupled Inward Rectifier Potassium Channels
Authors: An Dongchen , Peigneur Steve , Tytgat Jan
Published: April 2021

The coupling of cannabinoid receptors, CB1 and CB2, to G protein-coupled inward rectifier potassium channels, GIRK1 and GIRK2, modulates neuronal excitability in the human brain. The present study established and validated the functional expression in a Xenopus laevis oocyte expression system of CB1 and CB2 receptors, interacting with heteromeric GIRK1/2 channels and a regulator of G protein signaling, RGS4. This ex vivo system enables the discovery of a wide range of ligands interacting orthosterically or allosterically with CB1 and/or CB2 receptors. WIN55,212-2, a non-selective agonist of CB1 and CB2, was used to explore the CB1- or CB2-GIRK1/2-RGS4 signaling cascade. We show that WIN55,212-2 activates CB1 and CB2 at low concentrations whereas at higher concentrations it exerts a direct block of GIRK1/2. This illustrates a dual modulatory function, a feature not described before, which helps to explain the adverse effects induced by WIN55,212-2 in vivo. When comparing the effects with other typical cannabinoids such as Δ9-THC, CBD, CP55,940, and rimonabant, only WIN55,212-2 can significantly block GIRK1/2. Interestingly, the inward rectifier potassium channel, IRK1, a non-G protein-coupled potassium channel important for setting the resting membrane voltage and highly similar to GIRK1 and GIRK2, is not sensitive to WIN55,212-2, Δ9-THC, CBD, CP55,940, or rimonabant. From this, it is concluded that WIN55,212-2 selectively blocks GIRK1/2.