bluuebunny/crossref_metadata_2025 huggingface dataset:
Behavioral and Developmental Changes in Brown Trout After Exposure to the Antidepressant Venlafaxine
Authors: Ziegler Michael , Banet Michel , Bauer Rebecca , Köhler Heinz-R. , Stepinski Sabine , Tisler Selina , Huhn Carolin , Zwiener Christian , Triebskorn Rita
Published: January 2021

During the last decades, depression has been diagnosed in increasing numbers, accompanied by rising prescription rates of antidepressants. Concomitantly, these pharmaceuticals are frequently detected in surface waters. Serotonin and noradrenalin reuptake inhibitors such as venlafaxine form the second largest group of antidepressants worldwide, and venlafaxine is the second most prescribed antidepressant in Germany. As drug targets are evolutionary highly conserved, venlafaxine can potentially change not only behavior and related physiological processes in humans but also in non-target species, especially aquatic organisms. In order to test this hypothesis for fish, we exposed brown trout larvae and juveniles to venlafaxine at concentrations ranging from 1 to 1,000 μg/L. Larvae were exposed for 5 months from the eyed ova stage until 8 weeks post yolk-sac consumption at 7 and 11 °C. Juveniles were exposed for 4 weeks at 7 °C. Mortality, weight, length, behavior during exposure and behavior in a stressful environment were recorded in both experiments. For larvae, additionally, hatching rate and heart rate were analyzed. In juvenile fish, tissue cortisol levels were determined. Our results clearly showed, that brown trout, irrespective of their life stage, change their behavior when being exposed to venlafaxine: During exposure, venlafaxine at 7 °C caused larvae to sojourn in the upper part of the aquaria for a longer time, with a lowest observed effect concentration of 100 μg/L. In a stressful environment with limited space, fish exposed to ≥10 μg/L venlafaxine were less active than controls. Furthermore, venlafaxine reduced the growth of larvae (length at ≥10 μg/L, weight at 1 mg/L) and their survival after 5 months (at 1 mg/L). Hatching rate and heart rate of larvae as well as tissue cortisol concentration of juveniles were not affected by venlafaxine treatment.
Strengthening the Network of High Conservation Value Forests in Boreal Landscapes
Authors: Mikusiński Grzegorz , Orlikowska Ewa H. , Bubnicki Jakub W. , Jonsson Bengt Gunnar , Svensson Johan
Published: January 2021

The natural and old-growth forests and their associated biodiversity continues to fade worldwide due to anthropogenic impact in various forms. The boreal forests in Fennoscandia have been subject to intensive clearfelling forestry since the middle of twentieth century. As a result, only a fraction of forests with long temporal continuity remains at the landscape level. In Sweden, some of these primary forests have been formally protected, whereas other forests with known high conservation values are not. Collectively, both protected and not protected known valuable primary forests are included in a nationally delineated network of high conservation value forests (HCVF). In addition to HCVF, older forests that have not been clearfelled since the mid-1900s, i.e., “proxy continuity forests,” have recently been mapped across the entire boreal biome in Sweden. In this paper, we analyze how these proxy continuity forests may strengthen the HCVF network from a green infrastructure perspective. First, we evaluate the spatial overlap between proxy continuity forests and HCVF. Second, we perform a large-scale connectivity analysis, in which we show that adding proxy continuity forests located outside HCVF strongly increases the structural connectivity of the network of protected forests. Finally, by assessing habitat suitability for virtual species specialized in pine, spruce, and broadleaf forests, we find large regional differences in the ability to secure habitat and thereby functional green infrastructure by considering currently unprotected primary forest. We show that, by adding those forests to the network, the area of habitat for low-demanding species dependent on spruce or pine forests can be largely increased. For high-demanding species, additional habitat restoration in the landscape matrix is needed. By contrast, even counting all valuable broadleaf forests available is not enough to provide a suitable habitat for their associated species, which indicates a large need for landscape-scale habitat restoration initiatives, in particular, for broadleaf forests.
Comparative mRNA and LncRNA Analysis of the Molecular Mechanisms Associated With Low Silk Production in Bombyx mori
Authors: Ruan Jinghua , Wu Meiyu , Ye Xiaogang , Zhao Shuo , Liang Jianshe , Ye Lupeng , You Zhengying , Zhong Boxiong
Published: January 2021

Naked pupa sericin and Naked pupa are two mutant strains of Bombyx mori with extremely low or no fibroin production compared to the Qiufeng and Baiyu strains, both of which exhibit very high silk fibroin production. However, the molecular mechanisms by which long non-coding RNAs regulate fibroin synthesis need further study. In this study, we performed high-throughput RNA-seq to investigate lncRNA and mRNA expression profiles in the posterior silk gland of Qiufeng, Baiyu, Nd-sD, and Nd silkworms at the third day of the 5th instar. Our efforts yielded 26,767 novel lncRNAs and 6,009 novel mRNAs, the expression levels of silk protein genes and silk gland transcription factors were decreased in Qiufeng vs. Nd-sD and Qiufeng vs. Nd, while those of many genes related to autophagy, apoptosis, RNA degradation, ubiquitin-mediated proteolysis and heat shock proteins were increased. Moreover, the expression of a large number of genes responsible for protein synthesis and secretion was significantly decreased in Nd. GO and KEGG analysis results showed that nucleotide excision repair, mRNA surveillance pathways, amino acid degradation, protein digestion and absorption, ER-associated degradation and proteasome pathways were significantly enriched for the Qiufeng vs. Nd-sD and Qiufeng vs. Nd comparisons. In conclusion, our findings contribute to the lncRNA and mRNA database of Bombyx mori, and the identified differentially expressed mRNAs and lncRNAs help to reveal the molecular mechanisms of low silk production in Nd-sD and Nd, providing new insights for improvement of silk yield and elucidation of silk mechanical properties.
Genomic Prediction Based on SNP Functional Annotation Using Imputed Whole-Genome Sequence Data in Korean Hanwoo Cattle
Authors: Lopez Bryan Irvine M. , An Narae , Srikanth Krishnamoorthy , Lee Seunghwan , Oh Jae-Don , Shin Dong-Hyun , Park Woncheoul , Chai Han-Ha , Park Jong-Eun , Lim Dajeong
Published: January 2021

Whole-genome sequence (WGS) data are increasingly being applied into genomic predictions, offering a higher predictive ability by including causal mutations or single-nucleotide polymorphisms (SNPs) putatively in strong linkage disequilibrium with causal mutations affecting the trait. This study aimed to improve the predictive performance of the customized Hanwoo 50 k SNP panel for four carcass traits in commercial Hanwoo population by adding highly predictive variants from sequence data. A total of 16,892 Hanwoo cattle with phenotypes (i.e., backfat thickness, carcass weight, longissimus muscle area, and marbling score), 50 k genotypes, and WGS imputed genotypes were used. We partitioned imputed WGS data according to functional annotation [intergenic (IGR), intron (ITR), regulatory (REG), synonymous (SYN), and non-synonymous (NSY)] to characterize the genomic regions that will deliver higher predictive power for the traits investigated. Animals were assigned into two groups, the discovery set (7324 animals) used for predictive variant detection and the cross-validation set for genomic prediction. Genome-wide association studies were performed by trait to every genomic region and entire WGS data for the pre-selection of variants. Each set of pre-selected SNPs with different density (1000, 3000, 5000, or 10,000) were added to the 50 k genotypes separately and the predictive performance of each set of genotypes was assessed using the genomic best linear unbiased prediction (GBLUP). Results showed that the predictive performance of the customized Hanwoo 50 k SNP panel can be improved by the addition of pre-selected variants from the WGS data, particularly 3000 variants from each trait, which is then sufficient to improve the prediction accuracy for all traits. When 12,000 pre-selected variants (3000 variants from each trait) were added to the 50 k genotypes, the prediction accuracies increased by 9.9, 9.2, 6.4, and 4.7% for backfat thickness, carcass weight, longissimus muscle area, and marbling score compared to the regular 50 k SNP panel, respectively. In terms of prediction bias, regression coefficients for all sets of genotypes in all traits were close to 1, indicating an unbiased prediction. The strategy used to select variants based on functional annotation did not show a clear advantage compared to using whole-genome. Nonetheless, such pre-selected SNPs from the IGR region gave the highest improvement in prediction accuracy among genomic regions and the values were close to those obtained using the WGS data for all traits. We concluded that additional gain in prediction accuracy when using pre-selected variants appears to be trait-dependent, and using WGS data remained more accurate compared to using a specific genomic region.
MeCP2: The Genetic Driver of Rett Syndrome Epigenetics
Authors: Good Katrina V. , Vincent John B. , Ausió Juan
Published: January 2021

Mutations in methyl CpG binding protein 2 (MeCP2) are the major cause of Rett syndrome (RTT), a rare neurodevelopmental disorder with a notable period of developmental regression following apparently normal initial development. Such MeCP2 alterations often result in changes to DNA binding and chromatin clustering ability, and in the stability of this protein. Among other functions, MeCP2 binds to methylated genomic DNA, which represents an important epigenetic mark with broad physiological implications, including neuronal development. In this review, we will summarize the genetic foundations behind RTT, and the variable degrees of protein stability exhibited by MeCP2 and its mutated versions. Also, past and emerging relationships that MeCP2 has with mRNA splicing, miRNA processing, and other non-coding RNAs (ncRNA) will be explored, and we suggest that these molecules could be missing links in understanding the epigenetic consequences incurred from genetic ablation of this important chromatin modifier. Importantly, although MeCP2 is highly expressed in the brain, where it has been most extensively studied, the role of this protein and its alterations in other tissues cannot be ignored and will also be discussed. Finally, the additional complexity to RTT pathology introduced by structural and functional implications of the two MeCP2 isoforms (MeCP2-E1 and MeCP2-E2) will be described. Epigenetic therapeutics are gaining clinical popularity, yet treatment for Rett syndrome is more complicated than would be anticipated for a purely epigenetic disorder, which should be taken into account in future clinical contexts.
Development of a Chimeric Vaccine Against Pseudomonas aeruginosa Based on the Th17-Stimulating Epitopes of PcrV and AmpC
Authors: Wang Ying , Cheng Xin , Wan Chuang , Wei Jinning , Gao Chen , Zhang Yi , Zeng Hao , Peng Liusheng , Luo Ping , Lu Dongshui , Zou Quanming , Gu Jiang
Published: January 2021

Pulmonary infection caused by Pseudomonas aeruginosa (PA) has created an urgent need for an efficient vaccine, but the protection induced by current candidates is limited, partially because of the high variability of the PA genome. Antigens targeting pulmonary Th17 responses are able to provide antibody-independent and broad-spectrum protection; however, little information about Th17-stimulating antigens in PA is available. Herein, we identified two novel PA antigens that effectively induce Th17-dependent protection, namely, PcrV (PA1706) and AmpC (PA4110). Compared to intramuscular immunization, intranasal immunization enhanced the protection of rePcrV due to activation of a Th17 response. The Th17-stimulating epitopes of PcrV and AmpC were identified, and the recombinant protein PVAC was designed and generated by combining these Th17-stimulating epitopes. PVAC was successfully produced in soluble form and elicited broad protective immunity against PA. Our results provide an alternative strategy for the development of Th17-based vaccines against PA and other pathogens.
The Role of Tenascin-C in Tissue Injury and Repair After Stroke
Authors: Okada Takeshi , Suzuki Hidenori
Published: January 2021

Stroke is still one of the most common causes for mortality and morbidity worldwide. Following acute stroke onset, biochemical and cellular changes induce further brain injury such as neuroinflammation, cell death, and blood-brain barrier disruption. Matricellular proteins are non-structural proteins induced by many stimuli and tissue damage including stroke induction, while its levels are generally low in a normal physiological condition in adult tissues. Currently, a matricellular protein tenascin-C (TNC) is considered to be an important inducer to promote neuroinflammatory cascades and the resultant pathology in stroke. TNC is upregulated in cerebral arteries and brain tissues including astrocytes, neurons, and brain capillary endothelial cells following subarachnoid hemorrhage (SAH). TNC may be involved in blood-brain barrier disruption, neuronal apoptosis, and cerebral vasospasm via the activation of mitogen-activated protein kinases and nuclear factor-kappa B following SAH. In addition, post-SAH TNC levels in cerebrospinal fluid predicted the development of delayed cerebral ischemia and angiographic vasospasm in clinical settings. On the other hand, TNC is reported to promote fibrosis and exert repair effects for an experimental aneurysm via macrophages-induced migration and proliferation of smooth muscle cells. The authors review TNC-induced inflammatory signal cascades and the relationships with other matricellular proteins in stroke-related pathology.
Hunting by the Stroke: How Foraging Drives Diving Behavior and Locomotion of East-Greenland Narwhals (Monodon monoceros)
Authors: Tervo Outi M. , Ditlevsen Susanne , Ngô Manh C. , Nielsen Nynne H. , Blackwell Susanna B. , Williams Terrie M. , Heide-Jørgensen Mads Peter
Published: January 2021

Deep diving air-breathing species by necessity must balance submergence time and level of exercise during breath-holding: a low activity level preserves oxygen stores and allows longer duration submergence whereas high activity levels consume oxygen quickly and shorten submergence time. In this study, we combined high-resolution multi sensor animal-borne tag data to investigate diving behavior and locomotion styles of the narwhal (Monodon monoceros) (n= 13, mean record length 91 h)–a deep diving Arctic species. Narwhals in this study dove down to >800 m but despite the deep diving abilities, one-third of the dives (33%) were shallow (>100 m) and short in duration (<5 min). Narwhals utilized energy saving measures such as prolonged gliding during descent with increasing target depth but stroked actively throughout the ascent indicating excess oxygen storages. Foraging behavior, as detected by the presence of buzzes, was a key factor influencing dive depth and spinning behavior—the rolling movement of the animal along its longitudinal axes. Narwhals in East Greenland utilized two foraging strategies, while transiting and while stationary, with different target depths and buzzing rates. The first targeted deep-dwelling, possibly solitary prey items and the latter, more schooling prey closer to the surface. The buzzing rate during stationary foraging was on average twice as high as during transiting foraging. Spinning was an integrated part of narwhal swimming behavior but the amount of spinning was correlated with foraging behavior. The odds for spinning during all dive phases were 2–3 times higher during foraging than non-foraging. Due to the spinning behavior, stroking rate might be better suited for estimating energy consumption in narwhals than ODBA (overall dynamic body acceleration). The narwhal is considered as one of the most sensitive species to climate change–the results from this study can act as a baseline essential for evaluating changes in the behavior and energy usage of narwhals caused by stressors evolving in the Arctic.
Tourist Preferences for Seamount Conservation in the Galapagos Marine Reserve
Authors: Ison Sierra , Ison Theo , Marti-Puig Patricia , Needham Katherine , Tanner Michael K. , Roberts J. Murray
Published: January 2021

Seamounts provide oases of hard substrate in the deep sea that are frequently associated with locally enhanced biological productivity and diversity. There is now increasing recognition of their ecological and socio-economic importance. However, management strategies for these habitats are constrained not only by limited ecological understanding but by the general public’s understanding of the pressures facing these ecosystems. This study adds to the growing literature on willingness to pay for conservation of deep-sea ecosystems and species by undertaking a stated preference survey to assess tourist’s awareness of seamounts and their preferences for protection within the Galapagos Marine Reserve. Visitors’ perceptions of seamount biodiversity must be studied because tourists are key drivers of the Galapagos economy and account for 41% of the Marine Reserve budget. Our survey captured the attitudes, perceptions and willingness to pay of tourists for an increase in the entrance fee to the Galapagos Marine Reserve. Results showed tourists were willing to pay on average US$48.93 in addition to existing entrance fees. The results of this study support the willingness to develop a multiuse management plan for the Galapagos Marine Reserve, balancing conservation, local communities livelihoods and sustainable tourism. Our results evidence a willingness to support and fund conservation, which is of critical importance to both the Galapagos National Park and local non-governmental organizations heavily reliant for their work on entrance fees and donations respectively. Overall, the conclusion from this study is that, despite limited knowledge, visitors of the Galapagos Islands attach positive and significant values to the conservation of seamount biodiversity.
Iron Speciation in Fram Strait and Over the Northeast Greenland Shelf: An Inter-Comparison Study of Voltammetric Methods
Authors: Ardiningsih Indah , Zhu Kechen , Lodeiro Pablo , Gledhill Martha , Reichart Gert-Jan , Achterberg Eric P. , Middag Rob , Gerringa Loes J. A.
Published: January 2021

Competitive ligand exchange – adsorptive cathodic stripping voltammetry (CLE-AdCSV) is a widely used technique to determine dissolved iron (Fe) speciation in seawater, and involves competition for Fe of a known added ligand (AL) with natural organic ligands. Three different ALs were used, 2-(2-thiazolylazo)-p-cresol (TAC), salicylaldoxime (SA) and 1-nitroso-2-napthol (NN). The total ligand concentrations ([Lt]) and conditional stability constants (log K′Fe’L) obtained using the different ALs are compared. The comparison was done on seawater samples from Fram Strait and northeast Greenland shelf region, including the Norske Trough, Nioghalvfjerdsfjorden (79N) Glacier front and Westwind Trough. Data interpretation using a one-ligand model resulted in [Lt]SA (2.72 ± 0.99 nM eq Fe) > [Lt]TAC (1.77 ± 0.57 nM eq Fe) > [Lt]NN (1.57 ± 0.58 nM eq Fe); with the mean of log K′Fe’L being the highest for TAC (log ′KFe’L(TAC) = 12.8 ± 0.5), followed by SA (log K′Fe’L(SA) = 10.9 ± 0.4) and NN (log K′Fe’L(NN) = 10.1 ± 0.6). These differences are only partly explained by the detection windows employed, and are probably due to uncertainties propagated from the calibration and the heterogeneity of the natural organic ligands. An almost constant ratio of [Lt]TAC/[Lt]SA = 0.5 – 0.6 was obtained in samples over the shelf, potentially related to contributions of humic acid-type ligands. In contrast, in Fram Strait [Lt]TAC/[Lt]SA varied considerably from 0.6 to 1, indicating the influence of other ligand types, which seemed to be detected to a different extent by the TAC and SA methods. Our results show that even though the SA, TAC and NN methods have different detection windows, the results of the one ligand model captured a similar trend in [Lt], increasing from Fram Strait to the Norske Trough to the Westwind Trough. Application of a two-ligand model confirms a previous suggestion that in Polar Surface Water and in water masses over the shelf, two ligand groups existed, a relatively strong and relatively weak ligand group. The relatively weak ligand group contributed less to the total complexation capacity, hence it could only keep part of Fe released from the 79N Glacier in the dissolved phase.
Molecular Design of Amphiphilic Plasma Membrane-Targeted Azobenzenes for Nongenetic Optical Stimulation
Authors: Vurro Vito , Bondelli Gaia , Sesti Valentina , Lodola Francesco , Paternò Giuseppe Maria , Lanzani Guglielmo , Bertarelli Chiara
Published: January 2021

We present a series of cationic membrane-targeted azobenzene molecules, with the aim to understand how variations in molecular architecture influence the relative optical and biological properties. 1,4-Amino-substituted azobenzene was chosen as the switching unit while the number of linked alkyl chains and their cationic end-group were systematically varied. Their photophysics, membrane partitioning, and electrophysiological efficacy were studied. We found that the polar end group is a key-factor determining the interaction with the phospholipid heads in the plasma membrane bilayer and consequently the ability to dimerize. The monosubstituted photoswitch with a pyridinium-terminated alkyl chain was found to be the best candidate for photostimulation. This study provides a structure-property investigation that can guide the chemical engineering of a new generation of molecular photo-actuators.
RNA-Binding Protein MSI2 Binds to miR-301a-3p and Facilitates Its Distribution in Mitochondria of Endothelial Cells
Authors: Guo Qian Qian , Gao Jing , Wang Xiao Wei , Yin Xian Lun , Zhang Shu Cui , Li Xue , Chi Lian Li , Zhou Xiao Ming , Wang Zhe , Zhang Qun Ye
Published: January 2021

Numerous miRNAs have been detected in mitochondria, which play important roles in many physiological and pathophysiological processes. However, the dynamic changes of miRNA distribution in mitochondria and their mechanisms in reactive oxygen species (ROS)-induced endothelial injury remain unclear. Therefore, miRNA levels in whole cells and mitochondria of H2O2-treated endothelial cells were analyzed by small RNA sequencing in the present study. The results showed that H2O2 significantly reduced the relative mitochondrial distribution of dozens of miRNAs in human umbilical vein endothelial cells (HUVECs). Among the high-abundance miRNAs, miR-301a-3p has the most significant changes in the redistribution between cytosol and mitochondria confirmed by absolute quantitative polymerase chain reaction (qPCR). To unravel the mechanism of miR-301a-3p distribution in mitochondria, RNA pull-down followed by label-free quantitative proteomic analysis was performed, and RNA-binding protein Musashi RNA binding protein 2 (MSI2) was found to specifically bind to miR-301a-3p. Western blotting and immunofluorescence colocalization assay showed that MSI2 was located in mitochondria of various cell types. H2O2 significantly downregulated MSI2 expression in whole endothelial cells, promoted the distribution of MSI2 in cytosol and decreased its distribution in the mitochondria. Moreover, overexpression of MSI2 increased the mitochondrial distribution of miR-301a-3p, whereas inhibition of MSI2 decreased its distribution in mitochondria. Thus, MSI2 might be responsible for the distribution of miR-301a-3p between cytosol and mitochondria in endothelial cells. Our findings revealed for the first time that MSI2 was involved in the regulation of miRNA distribution in mitochondria and provided valuable insight into the mechanism of mitochondrial distribution of miRNAs.
Attenuation of Native Hyperpolarization-Activated, Cyclic Nucleotide-Gated Channel Function by the Volatile Anesthetic Sevoflurane in Mouse Thalamocortical Relay Neurons
Authors: Schwerin Stefan , Kopp Claudia , Pircher Elisabeth , Schneider Gerhard , Kreuzer Matthias , Haseneder Rainer , Kratzer Stephan
Published: January 2021

As thalamocortical relay neurons are ascribed a crucial role in signal propagation and information processing, they have attracted considerable attention as potential targets for anesthetic modulation. In this study, we analyzed the effects of different concentrations of sevoflurane on the excitability of thalamocortical relay neurons and hyperpolarization-activated, cyclic-nucleotide gated (HCN) channels, which play a decisive role in regulating membrane properties and rhythmic oscillatory activity. The effects of sevoflurane on single-cell excitability and native HCN channels were investigated in acutely prepared brain slices from adult wild-type mice with the whole-cell patch-clamp technique, using voltage-clamp and current-clamp protocols. Sevoflurane dose-dependently depressed membrane biophysics and HCN-mediated parameters of neuronal excitability. Respective half-maximal inhibitory and effective concentrations ranged between 0.30 (95% CI, 0.18–0.50) mM and 0.88 (95% CI, 0.40–2.20) mM. We witnessed a pronounced reduction of HCN dependent Ih current amplitude starting at a concentration of 0.45 mM [relative change at −133 mV; 0.45 mM sevoflurane: 0.85 (interquartile range, 0.79–0.92), n = 12, p = 0.011; 1.47 mM sevoflurane: 0.37 (interquartile range, 0.34–0.62), n = 5, p < 0.001] with a half-maximal inhibitory concentration of 0.88 (95% CI, 0.40–2.20) mM. In contrast, effects on voltage-dependent channel gating were modest with significant changes only occurring at 1.47 mM [absolute change of half-maximal activation potential; 1.47 mM: −7.2 (interquartile range, −10.3 to −5.8) mV, n = 5, p = 0.020]. In this study, we demonstrate that sevoflurane inhibits the excitability of thalamocortical relay neurons in a concentration-dependent manner within a clinically relevant range. Especially concerning its effects on native HCN channel function, our findings indicate substance-specific differences in comparison to other anesthetic agents. Considering the importance of HCN channels, the observed effects might mechanistically contribute to the hypnotic properties of sevoflurane.
Assessment of Potential Risk Factors for the Development of Persistent Postural-Perceptual Dizziness: A Case-Control Pilot Study
Authors: Trinidade Aaron , Harman Paula , Stone Jon , Staab Jeffrey P. , Goebel Joel A.
Published: January 2021

Objectives: (1) To assess whether neuroticism, state anxiety, and body vigilance are higher in patients with persistent postural-perceptual dizziness (PPPD) compared to a recovered vestibular patient group and a non-dizzy patient group; (2) To gather pilot data on illness perceptions of patients with PPPD.

Materials and Methods: 15 cases with PPPD and two control groups: (1) recovered vestibular patients (n = 12) and (2) non-dizzy patients (no previous vestibular insult, n = 12). Main outcome measures: Scores from the Big Five Inventory (BFI) of personality traits, Generalized Anxiety Disorder - 7 (GAD-7) scale, Body Vigilance Scale (BVS), Dizziness Handicap Inventory (DHI), modified Vertigo Symptom Scale (VSS) and Brief Illness Perception Questionnaire (BIPQ).

Results: Compared to non-dizzy patients, PPPD cases had higher neuroticism (p = 0.02), higher introversion (p = 0.008), lower conscientiousness (p = 0.03) and higher anxiety (p = 0.02). There were no differences between PPPD cases and recovered vestibular patients in BFI and GAD-7. PPPD cases had higher body vigilance to dizziness than both control groups and their illness perceptions indicated higher levels of threat than recovered vestibular patients.

Conclusion: PPPD patients showed statistically significant differences to non-dizzy patients, but not recovered vestibular controls in areas such as neuroticism and anxiety. Body vigilance was increased in PPPD patients when compared with both recovered vestibular and non-dizzy patient groups. PPPD patients also exhibited elements of negative illness perception suggesting that this may be the key element driving the development of PPPD. Large scale studies focusing on this area in the early stages following vestibular insult are needed.
Changes in Gray Matter Asymmetries of the Fusiform and Parahippocampal Gyruses in Patients With Subcortical Ischemic Vascular Disease
Authors: Cheng Runtian , Chen Li , Liu Xiaoshuang , Luo Tianyou , Gong Junwei , Jiang Peiling
Published: January 2021

Objective: Changes in the normal asymmetry of the human brain often mean pathology. Current studies on the correlation between asymmetry and cognitive impairment have focused on Alzheimer's disease (AD) and AD-related mild cognitive impairment (MCI). The purpose of this study was to investigate changes in gray matter asymmetry and their relationship with cognitive impairment in patients with subcortical ischemic vascular disease (SIVD) by using voxel-based morphological measurements.

Methods: Fifty-nine SIVD patients with (subcortical vascular cognitive impairment, SVCI, N = 30) and without (pre-SVCI, N = 29) cognitive impairment and 30 normal controls (NC, N = 30) underwent high-resolution structural MRI and neuropsychological examinations. The differences in gray matter asymmetry among the three groups were estimated by using one-way ANOVA. Moreover, partial correlation analysis was performed to explore the relationships between the asymmetry index (AI) values and cognitive assessments controlled for age, sex, and education.

Results: The gray matter asymmetries in the fusiform and parahippocampal gyruses of the SVCI group were significantly different from those of the NC group and the pre-SVCI group, while no differences were found between the NC group and the pre-SVCI group in the same areas. More specifically, in the fusiform and parahippocampal gyruses, the SVCI group displayed a dramatic rightward asymmetry, whereas the NC group and pre-SVCI group exhibited a marked leftward asymmetry. The results of the correlation analysis showed that the “mean AI” in significant cluster was strongly correlated with the changes in cognitive outcomes.

Conclusion: This study demonstrated different lateralization in the fusiform and parahippocampal gyruses of SIVD patients with cognitive impairment compared to healthy subjects and SIVD patients without cognitive decline. Our findings may contribute to better understanding the possible mechanism of cognitive impairment in patients with SIVD, and they suggest the possibility of using gray matter asymmetry as a biomarker for disease progression.
The Relation Between Consumers' Frontal Alpha Asymmetry, Attitude, and Investment Decision
Authors: Di Gruttola Francesco , Malizia Andrea P. , D'Arcangelo Sonia , Lattanzi Nicola , Ricciardi Emiliano , Orfei Maria Donata
Published: January 2021

The frontal alpha asymmetry (FAA) is a neurophysiological measure of motivation and preference. Despite the FAA is associated to commercial pleasantness, conflicting evidence emerged in the literature regarding its relationship with behavior. To study the association between FAA and consumers' decision, we manipulated a commercial script to elicit diverse consumers' attitudes and decisions and to evaluate whether the FAA score is associated to their final investment. A little informative script (S1) was used to polarize consumers' attitudes and investments toward unfavorable scores, while a more personalized message (S2) to elicit in customers a favorable attitude and higher investments. Twenty-one participants listened to the scripts, and their FAA, attitude, and monetary investment were measured. In S1, the FAA did not correlate with neither attitude nor the investment decision, while a robust negative correlation between these variables was found in S2. No other peripheral body and neural measures associated with attitude or final decision. Our data suggest that the FAA correlates with attitude and decision, when a commercial script is customized and provides an adequate information, likely leading the consumer to a more reasoned and planned decision-making process. When facilitating a favorable attitude toward an offer, the negative correlation of FAA and behavior may reflect the involvement of a control system, whose role is to monitor and govern possible conflicts between approach and avoidance motivations. This observation provides additional indication on the value of FAA as a marker of consumer behaviors, and how it could be affected by experimental and contextual bias.
Alterations of Iron Level in the Bilateral Basal Ganglia Region in Patients With Middle Cerebral Artery Occlusion
Authors: Du Lei , Zhao Zifang , Liu Xiuxiu , Chen Yue , Gao Wenwen , Wang Yige , Liu Jian , Liu Bing , Ma Guolin
Published: January 2021

Background and Purpose:The purpose of this study was to explore the changes of iron level using quantitative susceptibility mapping (QSM) in the bilateral basal ganglia region in middle cerebral artery occlusion (MCAO) patients with long-term ischemia.

Methods:Twenty-seven healthy controls and nine patients with MCAO were recruited, and their QSM images were obtained. The bilateral caudate nucleus (Cd), putamen (Pt), and globus pallidus (Gp) were selected as the regions of interest (ROIs). Susceptibility values of bilateral ROIs were calculated and compared between the affected side and unaffected side in patients with MCAO and between patients with MCAO and healthy controls. In addition, receiver operating characteristic (ROC) curves were performed to evaluate the diagnostic capability of susceptibility values in differentiating healthy controls and patients with MCAO by the area under the curve (AUC).

Results:The susceptibility values of bilateral Cd were asymmetric in healthy controls; however, this asymmetry disappeared in patients with MCAO. In addition, compared with healthy controls, the average susceptibility values of the bilateral Pt in patients with MCAO were increased (P< 0.05), and the average susceptibility value of the bilateral Gp was decreased(P< 0.05). ROC curves showed that the susceptibility values of the Pt and Gp had a larger AUC (AUC = 0.700 and 0.889, respectively).

Conclusion:As measured by QSM, the iron levels of the bilateral basal ganglia region were significantly changed in patients with MCAO. Iron dyshomeostasis in the basal ganglia region might be involved in the pathophysiological process of middle cerebral artery stenosis and occlusion. These findings may provide a novel insight to profoundly address the pathophysiological mechanisms of MCAO.
Nogo-C Inhibits Peripheral Nerve Regeneration by Regulating Schwann Cell Apoptosis and Dedifferentiation
Authors: Jia Bo , Huang Wei , Wang Yu , Zhang Peng , Wang Zhiwei , Zheng Ming , Wang Tianbing
Published: January 2021

While Nogo protein demonstrably inhibits nerve regeneration in the central nervous system (CNS), its effect on Schwann cells in peripheral nerve repair and regeneration following sciatic nerve injury remains unknown. In this research, We assessed the post-injury expression of Nogo-C in an experimental mouse model of sciatic nerve-crush injury. Nogo-C knockout (Nogo-C–/–) mouse was generated to observe the effect of Nogo-C on sciatic nerve regeneration, Schwann cell apoptosis, and myelin disintegration after nerve injury, and the effects of Nogo-C on apoptosis and dedifferentiation of Schwann cells were observed in vitro. We found that the expression of Nogo-C protein at the distal end of the injured sciatic nerve increased in wild type (WT) mice. Compared with the injured WT mice, the proportion of neuronal apoptosis was significantly diminished and the myelin clearance rate was significantly elevated in injured Nogo-C–/– mice; the number of nerve fibers regenerated and the degree of myelination were significantly elevated in Nogo-C–/– mice on Day 14 after injury. In addition, the recovery of motor function was significantly accelerated in the injured Nogo-C–/– mice. The overexpression of Nogo-C in primary Schwann cells using adenovirus-mediated gene transfer promoted Schwann cells apoptosis. Nogo-C significantly reduced the ratio of c-Jun/krox-20 expression, indicating its inhibition of Schwann cell dedifferentiation. Above all, we hold the view that the expression of Nogo-C increases following peripheral nerve injury to promote Schwann cell apoptosis and inhibit Schwann cell dedifferentiation, thereby inhibiting peripheral nerve regeneration.
The Effect of Spinal Cord Stimulation Frequency on the Neural Response and Perceived Sensation in Patients With Chronic Pain
Authors: Gmel Gerrit Eduard , Santos Escapa Rosana , Parker John L. , Mugan Dave , Al-Kaisy Adnan , Palmisani Stefano
Published: January 2021

Background

The effect of spinal cord stimulation (SCS) amplitude on the activation of dorsal column fibres has been widely studied through the recording of Evoked Compound Action Potentials (ECAPs), the sum of all action potentials elicited by an electrical stimulus applied to the fibres. ECAP amplitude grows linearly with stimulus current after a threshold, and a larger ECAP results in a stronger stimulus sensation for patients. This study investigates the effect of stimulus frequency on both the ECAP amplitude as well as the perceived stimulus sensation in patients undergoing SCS therapy for chronic back and/or leg pain.

Methods

Patients suffering with chronic neuropathic lower-back and/or lower-limb pain undergoing an epidural SCS trial were recruited. Patients were implanted according to standard practice, having two 8-contact leads (8 mm inter-electrode spacing) which overlapped 2–4 contacts around the T9/T10 interspace. Both lead together thus spanning about three vertebral levels. Neurophysiological recordings were taken during the patient’s trial phase at two routine follow-ups using a custom external stimulator capable of recording ECAPs in real-time from all non-stimulating contacts. Stimulation was performed at various vertebral levels, varying the frequency (ranging from 2 to 455 Hz) while all other stimulating variables were kept constant. During the experiments subjects were asked to rate the stimulation-induced sensation (paraesthesia) on a scale from 0 to 10.

Results

Frequency response curves showed an inverse relationship between stimulation sensation strength and ECAP amplitude, with higher frequencies generating smaller ECAPs but stronger stimulation-induced paraesthesia (at constant stimulation amplitude). Both relationships followed logarithmic trends against stimulus frequency meaning that the effects on ECAP amplitude and sensation are larger for smaller frequencies.

Conclusion

This work supports the hypothesis that SCS-induced paraesthesia is conveyed through both frequency coding and population coding, fitting known psychophysics of tactile sensory information processing. The inverse relationship between ECAP amplitude and sensation for increasing frequencies at fixed stimulus amplitude questions common assumptions of monotonic relationships between ECAP amplitude and sensation strength.
Mutational Landscape for Indian Hereditary Breast and Ovarian Cancer Cohort Suggests Need for Identifying Population Specific Genes and Biomarkers for Screening
Authors: Kadri Mohammed Shaad N. , Patel Komal M. , Bhargava Poonam A. , Shah Franky D. , Badgujar Nutan V. , Tarapara Bhoomi V. , Patel Prabhudas S. , Shaikh Mohammed Inayatullah , Shah Krati , Patel Apurva , Pandya Shashank , Vora Hemangini , Joshi Chaitanya G. , Joshi Madhvi N.
Published: January 2021

Background

Breast and ovarian cancers are the most prevalent cancers and one of the leading causes of death in Indian women. The healthcare burden of breast and ovarian cancers and the rise in mortality rate are worrying and stress the need for early detection and treatment.

Methods

We performed amplicon sequencing of 144 cases who had breast/ovarian cancer disease (total 137 cases are patients and seven are tested for BRCA1/2 carrier) Using our custom designed gene panel consisting of 14 genes, that are associated with high to moderate risk of breast and ovarian cancers. Variants were called using Torrent Variant Caller and were annotated using ThermoFisher’s Ion Reporter software. Classification of variants and their clinical significance were identified by searching the variants against ClinVar database.

Results

From a total of 144 cases, we were able to detect 42 pathogenic mutations in [40/144] cases. Majority of pathogenic mutations (30/41) were detected in BRCA1 gene, while (7/41) pathogenic mutations were detected in BRCA2 gene, whereas, (2/41) pathogenic mutations were detected in TP53 gene and BRIP1, PALB2, and ATM genes respectively. So, BRCA genes contributed 88.09% of pathogenic mutations, whereas non-BRCA genes contributed 11.91% of pathogenic mutations. We were also able to detect 25 VUS which were predicted to be damaging by in silico prediction tools.

Conclusion

Early detection of cancers in the Indian population can be done by genetic screening using customized multi-gene panels. Indications of our findings show that in the Indian population, apart from the common BRCA genes, there are other genes that are also responsible for the disease. High frequency mutations detected in the study and variants of uncertain significance predicted to be damaging by in silico pathogenicity prediction tools can be potential biomarkers of hereditary breast and ovarian cancer in Indian HBOC patients.
Temporal Lobe Necrosis Following Radiotherapy in Nasopharyngeal Carcinoma: New Insight Into the Management
Authors: Zhou Xin , Liu Peiyao , Wang Xiaoshen
Published: January 2021

Cerebral radiation necrosis (CRN) is one of the most prominent sequelae following radiation therapy for nasopharyngeal carcinoma (NPC), which might have devastating effects on patients’ quality of life (QOL). Advances in histopathology and neuro-radiology have shed light on the management of CRN more comprehensively, yet effective therapeutic interventions are still lacking. CRN was once regarded as progressive and irreversible, however, in the past 20 years, with the application of intensity-modulated radiation therapy (IMRT), both the incidence and severity of CRN have declined. In addition, newly developed medical agents including bevacizumab-a humanized monoclonal antibody against vascular endothelial growth factor (VEGF), nerve growth factor (NGF), monosialotetrahexosylganglioside (GM1), etc., have shown great potency in successfully reversing radiation-induced CRN. As temporal lobes are most frequently compromised in NPC patients, this review will summarize the state-of-the-art progress regarding the incidence, pathophysiology, prevention, treatment, and prognosis of temporal lobe necrosis (TLN) after IMRT in NPC.
Laparoscopic Proximal Gastrectomy Versus Laparoscopic Total Gastrectomy for Proximal Gastric Cancer: A Systematic Review and Meta−Analysis
Authors: Tian Peirong , Liu Yang , Bian Shibo , Li Mengyi , Zhang Meng , Liu Jia , Jin Lan , Zhang Peng , Zhang Zhongtao
Published: January 2021

Background

To compare laparoscopic proximal gastrectomy (LPG) and laparoscopic total gastrectomy (LTG) with regard to outcomes, including efficacy and safety, in patients with proximal gastric cancer.

Methods

Original English-language articles comparing LPG and LTG for proximal gastric cancer up to November 2019 were systematically searched in the Embase, PubMed, Cochrane Library, Web of Knowledge, and ClinicalTrials.gov databases by two independent reviewers. Our main endpoints were surgery-related features (operation time, blood loss, harvested lymph nodes, and postoperative hospital stay), postoperative complications (anastomotic leakage, anastomotic bleeding, anastomotic stenosis, and reflux esophagitis), and oncologic outcomes (5-year overall survival and recurrent cancer).

Results

Fourteen studies including a total of 1,282 cases (510 LPG and 772 LTG) were enrolled. Fewer lymph nodes were harvested (WMD = −13.33, 95% CI: −15.66 to −11.00, P < 0.00001) and more postoperative anastomotic stenosis (OR = 2.03, 95% CI: 1.21 to 3.39, P = 0.007) observed in LPG than LTG. There were no significant differences in other explored parameters between the two methods. However, based on a subgroup analysis of digestive tract reconstruction, LPG with esophagogastrostomy (LPG-EG) had shorter operative time (WMD = −42.51, 95% CI: −58.99 to −26.03, P < 0.00001), less intraoperative blood loss (WMD = −79.52, 95% CI: −116.63 to −42.41, P < 0.0001), and more reflux esophagitis (OR = 3.92, 95% CI: 1.56 to 9.83, P = 0.004) than was observed for LTG. There was no difference between LPG performed with the double tract anastomosis/double-flap technique (DT/DFT) and LTG.

Conclusion

LPG can be performed as an alternative to LTG for proximal gastric cancer, especially LPG-DT/DFT, with comparable safety and efficacy.
Survival and Complications in Pediatric Patients With Cancer and COVID-19: A Meta-Analysis
Authors: Dorantes-Acosta Elisa , Ávila-Montiel Diana , Klünder-Klünder Miguel , Juárez-Villegas Luis , Márquez-González Horacio
Published: January 2021

Background

The pandemic caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected all age groups, including the pediatric population, in 3–5% of all cases. We performed a meta-analysis to understand the survival and associated complications in pediatric cancer patients as well as their hospitalization, intensive care, and ventilation care (supplemental oxygen/endotracheal intubation) needs.

Methods

A systematic search was performed using MEDLINE, TRIP Database, International Clinical Trials Registry Platform (WHO), The Cochrane Library, Wiley, LILACS, and Google Scholar. Additionally, a search using the snowball method was performed in Nature, New England Journal of Medicine, Science, JAMA, ELSEVIER editorial, Oxford University Press, The Lancet, and MedRxiv. Searches were conducted until July 18, 2020. A total of 191 cancer patients with coronavirus disease 2019 (COVID-19) were integrated from 15 eligible studies. In a sub-analysis, patients were stratified into two groups: hematological cancer and solid tumors. Outcome measures were overall survival, risk of hospitalized or needing intensive care, and need for ventilatory support in any modality. The random effects statistical analysis was performed with Cochran’s chi square test. The odds ratio (OR) and heterogeneity were calculated using the I2 test.

Results

The overall survival was 99.4%. There were no statistically significant differences in the risk of hospitalization between hematological malignancies and solid tumors (95% confidence interval [CI] 0.48–18.3; OR = 2.94). The risk of being admitted to the intensive care unit was also not different between hematological malignancies and other tumors (95% CI 0.35–5.81; OR = 1.42). No differences were found for the need of ventilatory support (95% CI 0.14–3.35; OR = 0.68). Although all the studies were cross-sectional, the mortality of these patients was 0.6% at the time of analysis.

Conclusions

In the analyzed literature, survival in the studied group of patients with COVID-19 was very high. Suffering from hematological neoplasia or other solid tumors and COVID-19 was not a risk factor in children with cancer for the analyzed outcomes.