bluuebunny/crossref_metadata_2025 huggingface dataset:
Global and Local Manipulation of DNA Repair Mechanisms to Alter Site-Specific Gene Editing Outcomes in Hematopoietic Stem Cells
Authors: Benitez Elizabeth K. , Lomova Kaufman Anastasia , Cervantes Lilibeth , Clark Danielle N. , Ayoub Paul G. , Senadheera Shantha , Osborne Kyle , Sanchez Julie M. , Crisostomo Ralph Valentine , Wang Xiaoyan , Reuven Nina , Shaul Yosef , Hollis Roger P. , Romero Zulema , Kohn Donald B.
Published: December 2020

Monogenic disorders of the blood system have the potential to be treated by autologous stem cell transplantation of ex vivo genetically modified hematopoietic stem and progenitor cells (HSPCs). The sgRNA/Cas9 system allows for precise modification of the genome at single nucleotide resolution. However, the system is reliant on endogenous cellular DNA repair mechanisms to mend a Cas9-induced double stranded break (DSB), either by the non-homologous end joining (NHEJ) pathway or by the cell-cycle regulated homology-directed repair (HDR) pathway. Here, we describe a panel of ectopically expressed DNA repair factors and Cas9 variants assessed for their ability to promote gene correction by HDR or inhibit gene disruption by NHEJ at the HBB locus. Although transient global overexpression of DNA repair factors did not improve the frequency of gene correction in primary HSPCs, localization of factors to the DSB by fusion to the Cas9 protein did alter repair outcomes toward microhomology-mediated end joining (MMEJ) repair, an HDR event. This strategy may be useful when predictable gene editing outcomes are imperative for therapeutic success.
Gene Editing and Genotoxicity: Targeting the Off-Targets
Authors: Blattner Georges , Cavazza Alessia , Thrasher Adrian J. , Turchiano Giandomenico
Published: December 2020

Gene editing technologies show great promise for application to human disease as a result of rapid developments in targeting tools notably based on ZFN, TALEN, and CRISPR-Cas systems. Precise modification of a DNA sequence is now possible in mature human somatic cells including stem and progenitor cells with increasing degrees of efficiency. At the same time new technologies are required to evaluate their safety and genotoxicity before widespread clinical application can be confidently implemented. A number of methodologies have now been developed in an attempt to predict expected and unexpected modifications occurring during gene editing. This review surveys the techniques currently available as state of the art, highlighting benefits and limitations, and discusses approaches that may achieve sufficient accuracy and predictability for application in clinical settings.
A CRISPR-Cas13a Based Strategy That Tracks and Degrades Toxic RNA in Myotonic Dystrophy Type 1
Authors: Zhang Nan , Bewick Brittani , Xia Guangbin , Furling Denis , Ashizawa Tetsuo
Published: December 2020

Cas13a, an effector of type VI CRISPR-Cas systems, is an RNA guided RNase with multiplexing and therapeutic potential. This study employs the Leptotrichia shahii (Lsh) Cas13a and a repeat-based CRISPR RNA (crRNA) to track and eliminate toxic RNA aggregates in myotonic dystrophy type 1 (DM1) – a neuromuscular disease caused by CTG expansion in the DMPK gene. We demonstrate that LshCas13a cleaves CUG repeat RNA in biochemical assays and reduces toxic RNA load in patient-derived myoblasts. As a result, LshCas13a reverses the characteristic adult-to-embryonic missplicing events in several key genes that contribute to DM1 phenotype. The deactivated LshCas13a can further be repurposed to track RNA-rich organelles within cells. Our data highlights the reprogrammability of LshCas13a and the possible use of Cas13a to target expanded repeat sequences in microsatellite expansion diseases.
Olfactory Ecto-Mesenchymal Stem Cell-Derived Exosomes Ameliorate Experimental Colitis via Modulating Th1/Th17 and Treg Cell Responses
Authors: Tian Jie , Zhu Qiugang , Zhang Yidan , Bian Qianying , Hong Yue , Shen Ziwei , Xu Huaxi , Rui Ke , Yin Kai , Wang Shengjun
Published: December 2020

Olfactory ecto-mesenchymal stem cells (OE-MSCs) are a novel population of resident stem cells in the olfactory lamina propria with strong immunosuppressive function. Exosomes released by MSCs are considered to carry various mRNAs, microRNAs and proteins from cells and function as an extension of MSCs. However, it remains unclear whether exosomes derived from OE-MSCs (OE-MSCs-Exos) possess any immunoregulatory functions. In this study, we found that OE-MSCs-Exos possessed strong suppressive function in CD4+T cell proliferation, accompanied by reduced IL-17, IFN-γ and enhanced TGF-β, IL-10 secreted by T cells. In experimental colitis mice, treatment of OE-MSCs-Exos markedly alleviated the severity of disease, and Th1/Th17 subpopulations were remarkably reduced whereas Treg cells were increased after OE-MSCs-Exos treatment. Mechanistically, OE-MSCs-Exos were demonstrated to inhibit the differentiation of Th1 and Th17 cells, but promote the induction of Treg cells in vitro. Taken together, our findings identified a novel function of OE-MSCs-Exos in regulating T-cell responses, indicating that OE-MSCs-Exos may represent a new cell-free therapy for the treatment of IBD and other inflammatory diseases.
Deciphering the Prognostic and Predictive Value of Urinary CXCL10 in Kidney Recipients With BK Virus Reactivation
Authors: Tinel Claire , Vermorel Agathe , Picciotto Daniela , Morin Lise , Devresse Arnaud , Sauvaget Virginia , Lebreton Xavier , Aouni Laïla , Prié Dominique , Brabant Séverine , Avettand-Fenoel Véronique , Scemla Anne , Timsit Marc Olivier , Snanoudj Renaud , Legendre Christophe , Terzi Fabiola , Rabant Marion , Anglicheau Dany
Published: December 2020

BK virus (BKV) replication increases urinary chemokine C-X-C motif ligand 10 (uCXCL10) levels in kidney transplant recipients (KTRs). Here, we investigated uCXCL10 levels across different stages of BKV replication as a prognostic and predictive marker for functional decline in KTRs after BKV-DNAemia. uCXCL10 was assessed in a cross-sectional study (474 paired urine/blood/biopsy samples and a longitudinal study (1,184 samples from 60 KTRs with BKV-DNAemia). uCXCL10 levels gradually increased with urine (P-value < 0.0001) and blood BKV viral load (P < 0.05) but were similar in the viruria and no BKV groups (P > 0.99). In viremic patients, uCXCL10 at biopsy was associated with graft functional decline [HR = 1.65, 95% CI (1.08–2.51), P = 0.02], irrespective of baseline eGFR, blood viral load, or BKVN diagnosis. uCXL10/cr (threshold: 12.86 ng/mmol) discriminated patients with a low risk of graft function decline from high-risk patients (P = 0.01). In the longitudinal study, the uCXCL10 and BKV-DNAemia trajectories were superimposable. Stratification using the same uCXCL10/cr threshold at first viremia predicted the subsequent inflammatory response, assessed by time-adjusted uCXCL10/cr AUC (P < 0.001), and graft functional decline (P = 0.03). In KTRs, uCXCL10 increases in BKV-DNAemia but not in isolated viruria. uCXCL10/cr is a prognostic biomarker of eGFR decrease, and a 12.86 ng/ml threshold predicts higher inflammatory burdens and poor renal outcomes.
Ultrastructural Features of an Abundant and Ubiquitous Marine Ciliate, Uronychia binucleata (Protista, Ciliophora, Euplotida)
Authors: Dong Jingyi , Fan Xinpeng , Zhang Tengyue , Al-Farraj Saleh A. , Stoeck Thorsten , Ma Honggang , Li Lifang
Published: December 2020

The ciliate genusUronychiais a marine group with extremely differentiated cortical and ciliary structures. These structures define its unique evolutionary position in the whole subclass Euplotia. However, to date, few data about the ultrastructure of this genus and related taxa is available. In the present work, a dominant species,Uronychia binucleata, was investigated using scanning electron microscopy and transmission electron microscopy. The findings are as follows: (i) this species lacks the typical alveolar plate in its cortex, whereas the abundant electron-lucent vesicular structures occurred densely; (ii) the subpellicular microtubules form a triad configuration in the dorsal side, while appearing in a single configuration in the ventral side; (iii) the cortical granules are extrusomes, which represent a kind of mucocyst instead of ampules; (iv) two kinetosomes in different rows of one cirrus are linked by the single longitudinal connection; (v) the undulating membrane is highly developed and their insides and outsides are partially covered by the cortical flap; (vi) the single-membrane-bound pharyngeal disks interposed with microtubular sheets, and are distributed in three distinct zones. This first detailed report about the ultrastructural features of the genusUronychiawill be a key to improve the diagnosis and systematics of this widely distributed and ecologically important genus and its family Uronychiidae.
Spatiotemporal Up-Regulation of Mu Opioid Receptor 1 in Striatum of Mouse Model of Huntington’s Disease Differentially Affecting Caudal and Striosomal Regions
Authors: Morigaki Ryoma , Lee Jannifer H. , Yoshida Tomoko , Wüthrich Christian , Hu Dan , Crittenden Jill R. , Friedman Alexander , Kubota Yasuo , Graybiel Ann M.
Published: December 2020

The striatum of humans and other mammals is divided into macroscopic compartments made up of a labyrinthine striosome compartment embedded in a much larger surrounding matrix compartment. Anatomical and snRNA-Seq studies of the Huntington’s disease (HD) postmortem striatum suggest a preferential decline of some striosomal markers, and mRNAs studies of HD model mice concur. Here, by immunohistochemical methods, we examined the distribution of the canonical striosomal marker, mu-opioid receptor 1 (MOR1), in the striatum of the Q175 knock-in mouse model of HD in a postnatal time series extending from 3 to 19 months. We demonstrate that, contrary to the loss of many markers for striosomes, there is a pronounced up-regulation of MOR1 in these Q175 knock-in mice. We show that in heterozygous Q175 knock-in model mice [~192 cytosine-adenine-guanine (CAG) repeats], this MOR1 up-regulation progressed with advancing age and disease progression, and was particularly remarkable at caudal levels of the striatum. Given the known importance of MOR1 in basal ganglia signaling, our findings, though in mice, should offer clues to the pathogenesis of psychiatric features, especially depression, reinforcement sensitivity, and involuntary movements in HD.
Comprehensive Profiling of Gene Expression in the Cerebral Cortex and Striatum of BTBRTF/ArtRbrc Mice Compared to C57BL/6J Mice
Authors: Mizuno Shota , Hirota Jun-na , Ishii Chiaki , Iwasaki Hirohide , Sano Yoshitake , Furuichi Teiichi
Published: December 2020

Mouse line BTBR T+ Iptr3tf/J (hereafter referred as to BTBR/J) is a mouse strain that shows lower sociability compared to the C57BL/6J mouse strain (B6) and thus is often utilized as a model for autism spectrum disorder (ASD). In this study, we utilized another subline, BTBRTF/ArtRbrc (hereafter referred as to BTBR/R), and analyzed the associated brain transcriptome compared to B6 mice using microarray analysis, quantitative RT-PCR analysis, various bioinformatics analyses, and in situ hybridization. We focused on the cerebral cortex and the striatum, both of which are thought to be brain circuits associated with ASD symptoms. The transcriptome profiling identified 1,280 differentially expressed genes (DEGs; 974 downregulated and 306 upregulated genes, including 498 non-coding RNAs [ncRNAs]) in BTBR/R mice compared to B6 mice. Among these DEGs, 53 genes were consistent with ASD-related genes already established. Gene Ontology (GO) enrichment analysis highlighted 78 annotations (GO terms) including DNA/chromatin regulation, transcriptional/translational regulation, intercellular signaling, metabolism, immune signaling, and neurotransmitter/synaptic transmission-related terms. RNA interaction analysis revealed novel RNA–RNA networks, including 227 ASD-related genes. Weighted correlation network analysis highlighted 10 enriched modules including DNA/chromatin regulation, neurotransmitter/synaptic transmission, and transcriptional/translational regulation. Finally, the behavioral analyses showed that, compared to B6 mice, BTBR/R mice have mild but significant deficits in social novelty recognition and repetitive behavior. In addition, the BTBR/R data were comprehensively compared with those reported in the previous studies of human subjects with ASD as well as ASD animal models, including BTBR/J mice. Our results allow us to propose potentially important genes, ncRNAs, and RNA interactions. Analysis of the altered brain transcriptome data of the BTBR/R and BTBR/J sublines can contribute to the understanding of the genetic underpinnings of autism susceptibility.
Synaptic Vesicles Dynamics in Neocortical Epilepsy
Authors: Vannini Eleonora , Restani Laura , Dilillo Marialaura , McDonnell Liam A. , Caleo Matteo , Marra Vincenzo
Published: December 2020

Neuronal hyperexcitability often results from an unbalance between excitatory and inhibitory neurotransmission, but the synaptic alterations leading to enhanced seizure propensity are only partly understood. Taking advantage of a mouse model of neocortical epilepsy, we used a combination of photoconversion and electron microscopy to assess changes in synaptic vesicles pools in vivo. Our analyses reveal that epileptic networks show an early onset lengthening of active zones at inhibitory synapses, together with a delayed spatial reorganization of recycled vesicles at excitatory synapses. Proteomics of synaptic content indicate that specific proteins were increased in epileptic mice. Altogether, our data reveal a complex landscape of nanoscale changes affecting the epileptic synaptic release machinery. In particular, our findings show that an altered positioning of release-competent vesicles represent a novel signature of epileptic networks.
Morphological and Functional Changes of Corneal Nerves and Their Contribution to Peripheral and Central Sensory Abnormalities
Authors: Guerrero-Moreno Adrian , Baudouin Christophe , Melik Parsadaniantz Stéphane , Réaux-Le Goazigo Annabelle
Published: December 2020

The cornea is the most densely innervated and sensitive tissue in the body. The cornea is exclusively innervated by C- and A-delta fibers, including mechano-nociceptors that are triggered by noxious mechanical stimulation, polymodal nociceptors that are excited by mechanical, chemical, and thermal stimuli, and cold thermoreceptors that are activated by cooling. Noxious stimulations activate corneal nociceptors whose cell bodies are located in the trigeminal ganglion (TG) and project central axons to the trigeminal brainstem sensory complex. Ocular pain, in particular, that driven by corneal nerves, is considered to be a core symptom of inflammatory and traumatic disorders of the ocular surface. Ocular surface injury affecting corneal nerves and leading to inflammatory responses can occur under multiple pathological conditions, such as chemical burn, persistent dry eye, and corneal neuropathic pain as well as after some ophthalmological surgical interventions such as photorefractive surgery. This review depicts the morphological and functional changes of corneal nerve terminals following corneal damage and dry eye disease (DED), both ocular surface conditions leading to sensory abnormalities. In addition, the recent fundamental and clinical findings of the importance of peripheral and central neuroimmune interactions in the development of corneal hypersensitivity are discussed. Next, the cellular and molecular changes of corneal neurons in the TG and central structures that are driven by corneal nerve abnormalities are presented. A better understanding of the corneal nerve abnormalities as well as neuroimmune interactions may contribute to the identification of a novel therapeutic targets for alleviating corneal pain.
Accuracy and Workflow Improvements for Responsive Neurostimulation Hippocampal Depth Electrode Placement Using Robotic Stereotaxy
Authors: Karas Patrick J. , Giridharan Nisha , Treiber Jeffrey M. , Prablek Marc A. , Khan A. Basit , Shofty Ben , Krishnan Vaishnav , Chu Jennifer , Van Ness Paul C. , Maheshwari Atul , Haneef Zulfi , Gavvala Jay R. , Sheth Sameer A.
Published: December 2020

Background: Robotic stereotaxy is increasingly common in epilepsy surgery for the implantation of stereo-electroencephalography (sEEG) electrodes for intracranial seizure monitoring. The use of robots is also gaining popularity for permanent stereotactic lead implantation applications such as in deep brain stimulation and responsive neurostimulation (RNS) procedures.

Objective: We describe the evolution of our robotic stereotactic implantation technique for placement of occipital-approach hippocampal RNS depth leads.

Methods: We performed a retrospective review of 10 consecutive patients who underwent robotic RNS hippocampal depth electrode implantation. Accuracy of depth lead implantation was measured by registering intraoperative post-implantation fluoroscopic CT images and post-operative CT scans with the stereotactic plan to measure implantation accuracy. Seizure data were also collected from the RNS devices and analyzed to obtain initial seizure control outcome estimates.

Results: Ten patients underwent occipital-approach hippocampal RNS depth electrode placement for medically refractory epilepsy. A total of 18 depth electrodes were included in the analysis. Six patients (10 electrodes) were implanted in the supine position, with mean target radial error of 1.9 ± 0.9 mm (mean ± SD). Four patients (8 electrodes) were implanted in the prone position, with mean radial error of 0.8 ± 0.3 mm. The radial error was significantly smaller when electrodes were implanted in the prone position compared to the supine position (p = 0.002). Early results (median follow-up time 7.4 months) demonstrate mean seizure frequency reduction of 26% (n = 8), with 37.5% achieving ≥50% reduction in seizure frequency as measured by RNS long episode counts.

Conclusion: Prone positioning for robotic implantation of occipital-approach hippocampal RNS depth electrodes led to lower radial target error compared to supine positioning. The robotic platform offers a number of workflow advantages over traditional frame-based approaches, including parallel rather than serial operation in a bilateral case, decreased concern regarding human error in setting frame coordinates, and surgeon comfort.
A One-Dimensional CNN-LSTM Model for Epileptic Seizure Recognition Using EEG Signal Analysis
Authors: Xu Gaowei , Ren Tianhe , Chen Yu , Che Wenliang
Published: December 2020

Frequent epileptic seizures cause damage to the human brain, resulting in memory impairment, mental decline, and so on. Therefore, it is important to detect epileptic seizures and provide medical treatment in a timely manner. Currently, medical experts recognize epileptic seizure activity through the visual inspection of electroencephalographic (EEG) signal recordings of patients based on their experience, which takes much time and effort. In view of this, this paper proposes a one-dimensional convolutional neural network-long short-term memory (1D CNN-LSTM) model for automatic recognition of epileptic seizures through EEG signal analysis. Firstly, the raw EEG signal data are pre-processed and normalized. Then, a 1D convolutional neural network (CNN) is designed to effectively extract the features of the normalized EEG sequence data. In addition, the extracted features are then processed by the LSTM layers in order to further extract the temporal features. After that, the output features are fed into several fully connected layers for final epileptic seizure recognition. The performance of the proposed 1D CNN-LSTM model is verified on the public UCI epileptic seizure recognition data set. Experiments results show that the proposed method achieves high recognition accuracies of 99.39% and 82.00% on the binary and five-class epileptic seizure recognition tasks, respectively. Comparing results with traditional machine learning methods including k-nearest neighbors, support vector machines, and decision trees, other deep learning methods including standard deep neural network and CNN further verify the superiority of the proposed method.
Decoding Neural Responses to Motion-in-Depth Using EEG
Authors: Himmelberg Marc M. , Segala Federico G. , Maloney Ryan T. , Harris Julie M. , Wade Alex R.
Published: December 2020

Two stereoscopic cues that underlie the perception of motion-in-depth (MID) are changes in retinal disparity over time (CD) and interocular velocity differences (IOVD). These cues have independent spatiotemporal sensitivity profiles, depend upon different low-level stimulus properties, and are potentially processed along separate cortical pathways. Here, we ask whether these MID cues code for different motion directions: do they give rise to discriminable patterns of neural signals, and is there evidence for their convergence onto a single “motion-in-depth” pathway? To answer this, we use a decoding algorithm to test whether, and when, patterns of electroencephalogram (EEG) signals measured from across the full scalp, generated in response to CD- and IOVD-isolating stimuli moving toward or away in depth can be distinguished. We find that both MID cue type and 3D-motion direction can be decoded at different points in the EEG timecourse and that direction decoding cannot be accounted for by static disparity information. Remarkably, we find evidence for late processing convergence: IOVD motion direction can be decoded relatively late in the timecourse based on a decoder trained on CD stimuli, and vice versa. We conclude that early CD and IOVD direction decoding performance is dependent upon fundamentally different low-level stimulus features, but that later stages of decoding performance may be driven by a central, shared pathway that is agnostic to these features. Overall, these data are the first to show that neural responses to CD and IOVD cues that move toward and away in depth can be decoded from EEG signals, and that different aspects of MID-cues contribute to decoding performance at different points along the EEG timecourse.
Eyes Closing and Drowsiness in Human Subjects Decrease Baseline Galvanic Skin Response and Active Palmar Sweating: Relationship Between Galvanic Skin and Palmar Perspiration Responses
Authors: Momose Hideya , Morimitsu Norimasa , Ikeda Eiji , Kanai Shigeki , Sakaguchi Masao , Ohhashi Toshio
Published: December 2020

We previously constructed a perspiration ratemeter for the measurement of palmar sweating in human subjects. Although galvanic skin response (GSR) has been used to evaluate emotional responses in human subjects, little is known about the relationships between the phasic and baseline components in GSR and active palmar sweating. From the aforementioned, we aimed to investigate the relationships in human subjects with handgrip exercise and eyes closing or opening. Fifteen healthy volunteers (mean age: 26.9 ± 8.7 years) participated in the present experiments. We investigated the effects of maximal handgrip exercise, eyes closing or opening, and self-awareness of drowsy on the GSR, active palmar sweating, R-R interval in electrocardiograph (ECG), and percentage of α wave in EEG. The faster phasic component in GSR completely agreed with the starting point of active palmar sweating. Handgrip exercise induced significantly faster spike in GSR, active palmar sweating, and decrease in R-R interval in ECG. Eyes closing produced significant decreases in baseline GSR and active palmar sweating in all human subjects. The percentage of α wave in electroencephalograph (EEG) also increased. In contrast, eyes opening increased significantly the baseline GSR and active palmar sweating. In the equivalent electrical model of human skin, the eyes closing–mediated time-dependent decrease in the baseline GSR completely agreed with the hypothesis that the palmar skin voltage only in the model decreased time dependently to 0.4 of the control during 6 min. The self-awareness of drowsy in mid-night working with computer produced similar decreases in baseline GSR and active palmar sweating to the responses with eyes closing in all human subjects. In conclusion, the faster spike in GSR completely agreed with the starting point of active palmar sweating. Eyes closing and opening or self-awareness of drowsy significantly produced changes in baseline GSR and active palmar sweating, which may become useful tools for evaluating clearness or drowsiness in human subjects.
The Influence of Factors Such as Parenting Stress and Social Support on the State Anxiety in Parents of Special Needs Children During the COVID-19 Epidemic
Authors: Ren Jie , Li Xingkai , Chen Shudan , Chen Suiqing , Nie Yangang
Published: December 2020

Objectives

The study aims to investigate the state anxiety of parents of special needs children during the 2019 coronavirus disease (COVID-19) epidemic and the influence of parental stress, social support, and other related variables on the anxiety of parents.

Methods

Bespoke questionnaires of children’s and parent’s mental and behavioral problems during the epidemic were used in the study. We also used the State Anxiety Inventory (S-AI), the Parenting Stress Index—Short Form-15 (PSI-SF-15), the NEO Five-Factor Inventory (NEO-FFI), and the Multidimensional Scale of Perceived Social Support (MSPSS). The data used in the study were pooled from an online survey of parents of special needs children and analyzed by one-way analysis of variance (ANOVA) and multiple linear regression.

Results

Overall, 1,451 individuals were included, of which 402 were fathers (27.71%) and 1,049 were mothers (72.29%). ANOVA results showed that educational background, family monthly income, and type of their child’s disability made parents’ state anxiety significantly different. The results of multiple linear regression showed that during the epidemic, social support negatively predicted parents’ state anxiety (B = −0.15, p < 0.001), whereas parenting stress (B = 0.07, p = 0.001) and parental mental and behavioral problems (B = 0.37, p < 0.001) positively predicted parents’ state anxiety.

Conclusions

During the outbreak of COVID-19, parents of special needs children suffered mental and behavioral problems, together with parenting stress and social support, which influenced their state anxiety. These findings can be used to develop relevant psychological interventions to improve the mental health of vulnerable groups during a pandemic like COVID-19.
The Effect of Parent Psychological Distress on Child Hyperactivity/Inattention During the COVID-19 Lockdown: Testing the Mediation of Parent Verbal Hostility and Child Emotional Symptoms
Authors: Marchetti Daniela , Fontanesi Lilybeth , Di Giandomenico Serena , Mazza Cristina , Roma Paolo , Verrocchio Maria Cristina
Published: December 2020

The coronavirus disease 2019 (COVID-19) health crisis is strongly affecting the psychological well-being of the general population. According to a very recent literature, the imposed lockdown and social distancing measures have generated a series of negative outcomes, including fear of the future, anxiety, and somatization symptoms. Few studies have investigated the impact of the COVID-19 pandemic on the well-being of parents and children, and still fewer studies have assessed the relationship between the psychological health of parents and children. The present study aimed at understanding the effect of parents’ psychological distress and verbal aggression on behavioral and emotional symptoms of children during the COVID-19 lockdown. Using an online survey administered in the first weeks of the lockdown in Italy, we explored the mediating effects of parent verbal hostility and child emotional symptoms on the relationship between parent distress and child hyperactivity/inattention in a sample of 878 Italian parents (87.4% mothers; meanage = 40.58). Two hypotheses were proposed: (1) parent distress would significantly predict child hyperactivity/inattention, and (2) parent verbal hostility and child emotional symptoms would mediate the association between parent distress and child hyperactivity/inattention. The serial mediated model confirmed both hypotheses, suggesting that higher rates of psychological distress in parents were associated with higher levels of hyperactivity/inattention in children. Parent verbal hostility and child emotional problems were also found to positively mediate this relation. Our results may be used to improve sociopsychological interventions in the general population in the near future. They may also contribute to the clinical definition of therapeutic paths for parents and families.
The Question of Lag: An Exploration of the Relationship Between Conductor Gesture and Sonic Response in Instrumental Ensembles
Authors: Meals Cory D.
Published: December 2020

Group musical performance, especially large instrumental ensembles, present the outward appearance of an asymmetric, temporally immediate stimulus-response relationship between conductor and ensemble. Interestingly, anecdotal reports from both conductors and performers indicate a degree of variability in the timing of orchestral response to the conductor’s gestures. This observation is not present in anecdotal accounts of other instrumental ensemble settings, like wind bands, but commonplace occurrence among orchestral musicians indicates the potential presence of greater complexity in the observed relationship. This study investigates both the quality and quantity of temporal lag between conductor and ensemble in two common instrumental ensemble configurations – wind bands and orchestras – in an effort to describe the interplay present within conducted group performance. The findings indicate that the anecdotally identified lag is present within all ensemble types, and that it presents a flexible, dynamic temporal relationship between conductor and ensemble. Additionally, both the quantity and quality of lag values are significantly different between ensemble types, experience levels, and musical content. Several avenues for future research are identified, and confounds within the sampled ensembles are examined for their potential roles in the observed relationships.
Reduction of Physical Activity Levels During the COVID-19 Pandemic Might Negatively Disturb Sleep Pattern
Authors: Diniz Tiego A. , Christofaro Diego G. D. , Tebar William R. , Cucato Gabriel G. , Botero João Paulo , Correia Marilia Almeida , Ritti-Dias Raphael M. , Lofrano-Prado Mara C. , Prado Wagner L.
Published: December 2020

Background

The outbreak of novel coronavirus disease 2019 (COVID-19) has caused a global panic and public concern due to its mortality ratio and lack of treatments/vaccines. Reduced levels of physical activity have been reported during the outbreak, affecting the normal daily pattern.

Objective

To investigate (i) the relationship of physical activity level with sleep quality and (ii) the effects of reduction physical activity levels on sleep quality.

Methods

A Google form was used to address personal information, COVID-19 personal care, physical activity, and mental health of 1,907 adult volunteers. Binary logistic regression was used to verify the association of physical activity parameters and sleep quality.

Results

Insufficient physical activity levels were a risk factor to have disturbed sleep pattern [OR: 1.28, 95% CI (1.01–1.62)]; however, when the BMI was added to the analysis, there was no more statistical difference [OR: 1.23, 95% CI (0.96–1.57)]. On the other hand, we found that the reduction of physical activity levels was associated with negative changes in sleep quality [OR: 1.73, 95% CI (1.37–2.18)], regardless all the confounders [OR: 1.30, 95% CI (1.01–1.68)], unless when feeling of depression was added in Model 6 [OR: 1.28, 95% CI (0.99–1.66)].

Conclusion

Disruption in daily physical activity routine, rather than physical activity level, negatively influences sleep quality during the COVID-19 quarantine.
Epidemic Spread and Its Management Through Governance and Leadership Response Influencing the Arising Challenges Around COVID-19 in Pakistan—A Lesson Learnt for Low Income Countries With Limited Resource
Authors: Nawaz Ahsan , Su Xing , Barkat Muhammad Qasim , Asghar Sana , Asad Ali , Basit Farwa , Iqbal Shahid , Zahoor Hafiz , Raheel Shah Syyed Adnan
Published: December 2020

The coronavirus disease (COVID-19) was first reported in China (Wuhan) at the end of 2019. It has rapidly spread over 216 countries, including the USA, UK, Europe, Russia, and many Asian countries. It has affected more than 4.5 million people, and around 0.3 million deaths have been reported globally. Many preventive measures have been adopted worldwide to mitigate its spread. The government of Pakistan has also taken many preventive measures to combat the COVID-19 outbreak, such as rapid response by governance, continuous monitoring of the pandemic spread in the affected areas, and integration of resources from multiple sectors, including health, education, defense, and media. According to global statistics, the number of COVID-19 cases in the country remained remarkably lower than the expected number for the first 169 days, as compared to other countries. A total of 286,674 confirmed cases, including 16,475 active, 6,139 deaths, and 264,060 (92%) recoveries were reported. The study finds that strict adherence to national policies, effective governance, and unity at the national level resulted in better outcomes. Hence, the preventive measures, rapid responses, and strategies adopted for combating the challenges could be adopted as a learning tool for other countries having similar work environments and financial constraints. This paper can help and guide governance/public actions in response to the possible rebound of coronavirus this fall/winter.
Potential Effects of the COVID-19 Pandemic on Future Birth Rate
Authors: Ullah Md. Asad , Moin Abu Tayab , Araf Yusha , Bhuiyan Atiqur Rahman , Griffiths Mark D. , Gozal David
Published: December 2020

Here, we examine the potential effect of the COVID-19 pandemic on future birth rates. This highly contagious disease originated in China, and rapidly spread worldwide, leading to extensive lockdown policies being implemented globally with the aim of containing the infection rates and its serious attendant consequences. Based on previous extant literature, this paper overviews the potential demographic consequences of the current progressively widespread epidemic on conception and fertility as driven by the data obtained during similar prior incidents. In general, epidemics manifest a common pattern as far as their impact on population, which is remarkably similar to natural disasters, i.e., a steep decline in birth rates followed by gradual increases and then followed by a baby boom. Additionally, we have also depicted how economic conditions, mental health, fear, and mortality may also influence future birth rates.
Bee Venom—A Potential Complementary Medicine Candidate for SARS-CoV-2 Infections
Authors: Kasozi Keneth Iceland , Niedbała Gniewko , Alqarni Mohammed , Zirintunda Gerald , Ssempijja Fred , Musinguzi Simon Peter , Usman Ibe Michael , Matama Kevin , Hetta Helal F. , Mbiydzenyuy Ngala Elvis , Batiha Gaber El-Saber , Beshbishy Amany Magdy , Welburn Susan Christina
Published: December 2020

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is characterized by severe cytokine storm syndrome following inflammation. SARS-CoV-2 directly interacts with angiotensin-converting enzyme 2 (ACE-2) receptors in the human body. Complementary therapies that impact on expression of IgE and IgG antibodies, including administration of bee venom (BV), have efficacy in the management of arthritis, and Parkinson's disease. A recent epidemiological study in China showed that local beekeepers have a level of immunity against SARS-CoV-2 with and without previous exposure to virus. BV anti-inflammatory properties are associated with melittin and phospholipase A2 (PLA2), both of which show activity against enveloped and non-enveloped viruses, including H1N1 and HIV, with activity mediated through antagonist activity against interleukin-6 (IL-6), IL-8, interferon-γ (IFN-γ), and tumor necrosis factor-α (TNF-α). Melittin is associated with the underexpression of proinflammatory cytokines, including nuclear factor-kappa B (NF-κB), extracellular signal-regulated kinases (ERK1/2), and protein kinase Akt. BV therapy also involves group III secretory phospholipase A2in the management of respiratory and neurological diseases. BV activation of the cellular and humoral immune systems should be explored for the application of complementary medicine for the management of SARS-CoV-2 infections. BV “vaccination” is used to immunize against cytomegalovirus and can suppress metastases through the PLA2 and phosphatidylinositol-(3,4)-bisphosphate pathways. That BV shows efficacy for HIV and H1NI offers opportunity as a candidate for complementary therapy for protection against SARS-CoV-2.
The Impact of Covid-19 Pandemic Lockdown During Spring 2020 on Personal Trainers' Working and Living Conditions
Authors: Bratland-Sanda Solfrid , Mathisen Therese Fostervold , Sundgot-Borgen Christine , Sundgot-Borgen Jorunn , Tangen Jan Ove
Published: December 2020

Purpose:The aim of this study was to map changes in working and living conditions of Norwegian personal trainers (PTs) during the Covid-19 lockdown spring 2020.

Methods:A total of 150 PTs (mean (SD) age 35.5 (8.4) years, with 6.5 (5.3) years of experience as PT, and 61% female) in Norway responded to an online survey.

Results:Number of PT sessions per week was reduced during the lockdown and the majority of the respondents reported loss of clients and negative impact on their working conditions. The official restrictions and guidelines were considered difficult to interpret and somewhat discriminatory compared to restrictions and guidelines for other comparable exercise occupational groups. The lockdown period provided more PTs to offer online and outdoor training. Living conditions were also affected with reported impairments in private economy and reduced vitality (p< 0.05), and with vitality being lower in female compared to male respondents during, but not before, the lockdown period.

Discussion:The reported negative impact of the Covid-19 lockdown period on PTs' working and living conditions are discussed with focus on the reported gender differences and considering the previously reported poor reputation of the fitness industry.
Production of Microsclerotia From Entomopathogenic Fungi and Use in Maize Seed Coating as Delivery for Biocontrol Against Fusarium graminearum
Authors: Rivas-Franco Federico , Hampton John G. , Altier Nora A. , Swaminathan Jayanthi , Rostás Michael , Wessman Per , Saville David J. , Jackson Trevor A. , Jackson Mark A. , Glare Travis R.
Published: December 2020

The commercial use of the entomopathogenic fungiMetarhiziumspp. in biopesticides has gained more interest since the discovery that several species of this genus are able to colonize roots. In general, commercial products withMetarhiziumare formulated based on conidia for insect pest control. The process of mass production, harvesting, and formulation of infective conidia can be detrimental for conidial viability. Entomopathogenic fungi such asMetarhiziumspp. are able to produce high concentrations of resistant structures, known as microsclerotia, when grown in liquid media. Microsclerotia are desiccation tolerant, with excellent storage stability, and are capable of producing high quantities of infective conidia after rehydration. The aim of this study was to evaluate microsclerotia production by different isolates ofMetarhiziumspp. and determine the effect of microsclerotia coated onto maize seeds on plant growth in the presence of soil-borne pathogenFusarium graminearum. On average, ~1 × 105microsclerotia/mL were produced by selected isolates ofM. anisopliae(A1080 and F672) andMetarhizium robertsii(F447). Microsclerotia were formulated as granules with diatomaceous earth and used for seed coating, after which propagules produced around 5 × 106CFU/g of seeds. In the presence of the plant pathogen, maize plants grown from untreated seeds had the lowest growth, while plants treated with theMetarhiziummicrosclerotia had significantly greater growth than the control plants. Hyphae were observed growing on and in root tissues in all theMetarhiziumspp. treatments but not in samples from control plants.Metarhiziumhyphal penetration points' on roots were observed 1 month after sowing, indicating the fungi were colonizing roots as endophytes. The results obtained indicate that microsclerotia can be coated onto seeds, providing plant protection against soil plant pathogens and a method to establishMetarhiziumin the ecto- and endo-rhizosphere of maize roots, allowing the persistence of this biocontrol agent.
Cellular Proliferation of Equine Bone Marrow- and Adipose Tissue-Derived Mesenchymal Stem Cells Decline With Increasing Donor Age
Authors: Bagge Jasmin , MacLeod James N. , Berg Lise C.
Published: December 2020

Background: Bone marrow (BM)- and adipose tissue (AT)-derived mesenchymal stem cells (MSCs) are used increasingly for autologous cell therapy in equine practice to treat musculoskeletal and other injuries. Current recommendations often call for 10–100 million MSCs per treatment, necessitating the expansion of primary cells in culture prior to therapeutic use. Of concern, human and rodent studies have shown a decline of both MSC recovery from sampled tissue and in vitro proliferative capacity with increasing donor age. This may be problematic for applications of autologous cell-based therapies in the important equine demographic of older patients.

Objectives: To investigate the effect of donor age on the cellular proliferation of equine BM- and AT-MSCs.

Study Design:In vitro study.

Methods: BM- and AT-MSCs and dermal fibroblasts (biological control) were harvested from horses in five different age groups (n = 4, N = 60); newborn (0 days), yearling (15–17 months), adult (5–8 years), middle-aged (12–18 years), and geriatric (≥22 years). Proliferation of the cells was tested using an EdU incorporation assay and steady state mRNA levels measured for targeted proliferation, aging, and senescence biomarkers.

Results: The cellular proliferation of equine BM- and AT-MSCs declined significantly in the geriatric cohort relative to the younger age groups. Proliferation levels in the two MSC types were equally affected by donor age. Analysis of steady state mRNA levels showed an up-regulation in tumor suppressors, apoptotic genes, and multiple growth factors in MSCs from old horses, and a down-regulation of some pro-cycling genes with a few differences between cell types.

Main Limitations: Potential age-dependent differences in cell function parameters relevant to cell-therapy application were not investigated.

Conclusions: The cellular proliferation of equine BM- and AT-MSCs declined at advanced donor ages. High levels of in vitro proliferation were observed in both MSC types from horses in the age groups below 18 years of age.
Segment-Based Clustering of Hyperspectral Images Using Tree-Based Data Partitioning Structures
Authors: Ismail Mohamed , Orlandić Milica
Published: December 2020

Hyperspectral image classification has been increasingly used in the field of remote sensing. In this study, a new clustering framework for large-scale hyperspectral image (HSI) classification is proposed. The proposed four-step classification scheme explores how to effectively use the global spectral information and local spatial structure of hyperspectral data for HSI classification. Initially, multidimensional Watershed is used for pre-segmentation. Region-based hierarchical hyperspectral image segmentation is based on the construction of Binary partition trees (BPT). Each segmented region is modeled while using first-order parametric modelling, which is then followed by a region merging stage using HSI regional spectral properties in order to obtain a BPT representation. The tree is then pruned to obtain a more compact representation. In addition, principal component analysis (PCA) is utilized for HSI feature extraction, so that the extracted features are further incorporated into the BPT. Finally, an efficient variant of k-means clustering algorithm, called filtering algorithm, is deployed on the created BPT structure, producing the final cluster map. The proposed method is tested over eight publicly available hyperspectral scenes with ground truth data and it is further compared with other clustering frameworks. The extensive experimental analysis demonstrates the efficacy of the proposed method.
Defoliation Dynamics in Kikuyugrass Pastures Subjected to Intensities of Defoliation
Authors: Medeiros-Neto Cauby , Schmitt Daniel , Martins Clóvis David Medeiros , Diavão Jaciara , Sbrissia André Fischer
Published: December 2020

Some recent papers have recommended moderate intensities of defoliation in order to maximize herbage intake at different time-scales. Most of them, however, did not assess the grazing dynamics of individual tillers during the stocking period. Therefore, the objective of this work was to describe the defoliation dynamics of kikuyugrass (Pennisetum clandestinum Hochst ex. Chiov) pastures subjected to different intensities of defoliation (40, 50, 60, and 70% of the initial height). Twelve 1500 m2 plots were strip-grazed over 24 h, and the frequency and severity of defoliation of individual tillers were assessed in 40 tagged tillers per experimental unit. From these data (n = 1920), we calculated the grazed area in the upper, second, and third horizon, and the total grazed area. We found that the frequency of defoliation by leaf category (expanding, mature, and senescent) increased linearly with the intensity of defoliation, and that reductions in extended tillers could not be used as a proxy to estimate the frequency of defoliation. Moreover, 22% of the second and third horizons were already exploited with intensities of defoliation of 40%, raising the possibility that the exploitation of lower grazing horizons could be more related to stocking density and relatively independent of the grazed area.
Acidified Animal Manure Products Combined with a Nitrification Inhibitor Can Serve as a Starter Fertilizer for Maize
Authors: Regueiro Iria , Siebert Peter , Liu Jingna , Müller-Stöver Dorette , Jensen Lars Stoumann
Published: December 2020

There is an urgent need for better management practices regarding livestock farm nutrient imbalances and for finding alternatives to the actual use of mineral fertilizers. Acidification of animal manure is a mitigation practice used to reduce ammonia emissions to the atmospheric environment during manure storage and land application. Acidification modifies manure physicochemical characteristics, among which soluble N and P significantly increase. The main objective of this study was to investigate if acidification and the addition of a nitrification inhibitor to manure and placement of the treated manure close to the seed can stimulate maize growth by enhancing nutrient availability, specially P and consequently plant P uptake, at early development stages without the use of mineral N and P as a starter fertilizer. Raw dairy slurry and solid fractions from dairy slurry and digestate from a biogas plant were acidified to pH 5.5 and applied with or without a nitrification inhibitor (DMPP, 3,4-dimethyl pyrazole phosphate) to maize in a pot experiment, where biomass productivity, nutrient uptake and soil P availability were examined. Acidification increased the water-extractable P fraction of all slurry and digestate organic residues (by 20–61% of total P) and consequently plant P uptake from solid fractions of both slurry and digestate compared to the untreated products (by 47–49%). However, higher plant biomass from acidification alone was only achieved for the slurry solid fraction, while the combination of acidification and DMPP also increased plant biomass in the digestate solids treatment (by 49%). We therefore conclude that the combination of acidification and a nitrification inhibitor can increase the starter fertilizer value of slurry and digestate products sufficiently to make them suitable as a maize starter fertilizer.