bluuebunny/crossref_metadata_2025 huggingface dataset:
Prediction and Analysis in silico of Genomic Islands in Aeromonas hydrophila
Authors: da Silva Filho Antonio Camilo , Marchaukoski Jeroniza Nunes , Raittz Roberto Tadeu , De Pierri Camilla Reginatto , de Jesus Soares Machado Diogo , Fadel-Picheth Cyntia Maria Telles , Picheth Geraldo
Published: December 2021

Aeromonas are Gram-negative rods widely distributed in the environment. They can cause severe infections in fish related to financial losses in the fish industry, and are considered opportunistic pathogens of humans causing infections ranging from diarrhea to septicemia. The objective of this study was to determinein silicothe contribution of genomic islands toA. hydrophila. The complete genomes of 17A. hydrophilaisolates, which were separated into two phylogenetic groups, were analyzed using a genomic island (GI) predictor. The number of predicted GIs and their characteristics varied among strains. Strains from group 1, which contains mainly fish pathogens, generally have a higher number of predicted GIs, and with larger size, than strains from group 2 constituted by strains recovered from distinct sources. Only a few predicted GIs were shared among them and contained mostly genes from the core genome. Features related to virulence, metabolism, and resistance were found in the predicted GIs, but strains varied in relation to their gene content. In strains from group 1, O Ag biosynthesis clusters OX1 and OX6 were identified, while strains from group 2 each had unique clusters. Metabolic pathways for myo-inositol, L-fucose, sialic acid, and a cluster encoding QueDEC, tgtA5, and proteins related to DNA metabolism were identified in strains of group 1, which share a high number of predicted GIs. No distinctive features of group 2 strains were identified in their predicted GIs, which are more diverse and possibly better represent GIs in this species. However, some strains have several resistance attributes encoded by their predicted GIs. Several predicted GIs encode hypothetical proteins and phage proteins whose functions have not been identified but may contribute toAeromonasfitness. In summary, features with functions identified on predicted GIs may confer advantages to host colonization and competitiveness in the environment.
Biochemical and Physiological Responses of Harmful Karenia mikimotoi to Algicidal Bacterium Paracoccus homiensis O-4
Authors: Ding Ning , Wang Yanbing , Chen Junfeng , Man Siyu , Lan Feng , Wang Chao , Hu Lijun , Gao Peike , Wang Renjun
Published: December 2021

Harmful algal blooms caused by Karenia mikimotoi frequently occur worldwide and severely threaten the marine environment. In this study, the biochemical and physiological responses of K. mikimotoi to the algicidal bacterium Paracoccus homiensis O-4 were investigated, and the effects on the levels of reactive oxygen species (ROS), malondialdehyde content, multiple antioxidant systems and metabolites, photosynthetic pigments, and photosynthetic index were examined. The cell-free supernatant in strain O-4 significantly inhibited K. mikimotoi cell growth. The bacterium caused the K. mikimotoi cells to activate their antioxidant defenses to mitigate ROS, and this effect was accompanied by the upregulation of intracellular antioxidant enzymes and non-enzyme systems. However, the overproduction of ROS induced lipid peroxidation and oxidative damage within K. mikimotoi cells, ultimately leading to algal death. In addition, the photosynthetic efficiency of the algal cells was significantly inhibited by O-4 and was accompanied by a reduction in photosynthetic pigments. This study indicates that O-4 inhibits K. mikimotoi through excessive oxidative stress and impaired photosynthesis. This research into the biochemical and physiological responses of K. mikimotoi to algicidal bacteria provides insights into the prophylaxis and control of harmful algal blooms via interactions between harmful algae and algicidal bacteria.
The Storage Period Discrimination of Bolete Mushrooms Based on Deep Learning Methods Combined With Two-Dimensional Correlation Spectroscopy and Integrative Two-Dimensional Correlation Spectroscopy
Authors: Dong Jian-E , Zhang Ji , Li Tao , Wang Yuan-Zhong
Published: December 2021

Boletes are favored by consumers because of their delicious taste and high nutritional value. However, as the storage period increases, their fruiting bodies will grow microorganisms and produce substances harmful to the human body. Therefore, we need to identify the storage period of boletes to ensure their quality. In this article, two-dimensional correlation spectroscopy (2DCOS) images are directly used for deep learning modeling, and the complex spectral data analysis process is transformed into a simple digital image processing problem. We collected 2,018 samples of boletes. After laboratory cleaning, drying, grinding, and tablet compression, their Fourier transform mid-infrared (FT-MIR) spectroscopy data were obtained. Then, we acquired 18,162 spectral images belonging to nine datasets which are synchronous 2DCOS, asynchronous 2DCOS, and integrative 2DCOS (i2DCOS) spectra of 1,750–400, 1,450–1,000, and 1,150–1,000 cm–1 bands. For these data sets, we established nine deep residual convolutional neural network (ResNet) models to identify the storage period of boletes. The result shows that the accuracy with the train set, test set, and external validation set of the synchronous 2DCOS model on the 1,750–400-cm–1 band is 100%, and the loss value is close to zero, so this model is the best. The synchronous 2DCOS model on the 1,150–1,000-cm–1 band comes next, and these two models have high accuracy and generalization ability which can be used to identify the storage period of boletes. The results have certain practical application value and provide a scientific basis for the quality control and market management of bolete mushrooms. In conclusion, our method is novel and extends the application of deep learning in the food field. At the same time, it can be applied to other fields such as agriculture and herbal medicine.
Postdiagenetic Bacterial Transformation of Nickel and Vanadyl Sedimentary Porphyrins of Organic-Rich Shale Rock (Fore-Sudetic Monocline, Poland)
Authors: Stasiuk Robert , Matlakowska Renata
Published: December 2021

Nickel and vanadyl porphyrins belong to the so-called fossil geo- or sedimentary porphyrins. They occur in different types of organic matter-rich sediments but mostly occur in crude oils and their source rocks, oil shales, coals, and oil sands. In this study, we aimed to understand the process of bacterial transformation of geoporphyrins occurring in the subsurface shale rock (Fore-Sudetic Monocline, SW Poland). We studied these transformations in rock samples directly obtained from the field; in rock samples treated with bacterial strain isolated from shale rock (strain LM27) in the laboratory; and using synthetic nickel and vanadyl porphyrins treated with LM27. Our results demonstrate the following: (i) cleavage and/or degradation of aliphatic and aromatic substituents of porphyrins; (ii) degradation of porphyrin (tetrapyrrole) ring; (iii) formation of organic compounds containing 1, 2, or 3 pyrrole rings; (iv) formation of nickel- or vanadium-containing organic compounds; and (v) mobilization of nickel and vanadium. Our results also showed that the described bacterial processes change the composition and content of geoporphyrins, composition of extractable organic matter, as well as nickel and vanadium content in shale rock.
A DedA Family Membrane Protein in Indium Extrusion in Rhodanobacter sp. B2A1Ga4
Authors: Caldeira Joana B. , Chung Ana Paula , Piedade Ana Paula , Morais Paula V. , Branco Rita
Published: December 2021

Indium (In) is a critical metal widely used in electronic equipment, and the supply of this precious metal is a major challenge for sustainable development. The use of microorganisms for the recovery of this critical high-tech element has been considered an excellent eco-friendly strategy. TheRhodanobactersp. B2A1Ga4 strain, highly resistant to In, was studied in order to disclose the bacterial mechanisms closely linked to the ability to cope with this metal. The mutation of the gene encoding for a DedA protein homolog, YqaA, affected drastically the In resistance and the cellular metabolic activity of strainRhodanobactersp. B2A1Ga4 in presence of this metal. This indicates that this protein plays an important role in its In resistance phenotype. The negative impact of In might be related to the high accumulation of the metal into the mutant cells showing In concentration up to approximately 4-fold higher than the native strain. In addition, the expression of theyqaAgene in this mutant reverted the bacterial phenotype with a significant decrease of In accumulation levels into the cells and an increase of In resistance. Membrane potential measurements showed similar values for native and mutant cells, suggesting that there was no loss of proton-motive force in the mutant cells. The results from this study suggest a potential role of this DedA family protein as a membrane transporter involved in the In efflux process. The mutant strain also has the potential to be used as a biotool in bioaccumulation strategies, for the recovery of In in biomining activities.
Redescription, Morphogenesis, and Molecular Phylogeny of Pseudosincirra longicirrata nov. comb., With Establishment of a New Genus Pseudosincirra nov. gen. (Ciliophora, Hypotrichia)
Authors: Gao Qi , Shao Chen , Tang Qiuyue , Li Jingbao
Published: December 2021

The morphology and morphogenesis of Pseudosincirra longicirrata nov. gen. and nov. comb., isolated from southern China, were investigated with living observation and protargol staining. Our population is similar to the original population in living characteristics and ciliary patterns. The main determinable morphogenetic features of P. longicirrata nov. comb. are the presence of five frontoventral-transverse cirral anlagen (FVT-anlagen) and a dorsomarginal kinety anlage. According to the origin of FVT-anlagen IV and V in proter, it can be determined that P. longicirrata nov. comb. possesses two frontoventral rows and one right marginal row. Hence, a new genus, Pseudosincirra nov. gen., is proposed, and the diagnosis of P. longicirrata nov. comb. is improved. The new genus is diagnosed as follows: adoral zone of membranelles and undulating membranes is in a Gonostomum pattern; there are three enlarged frontal cirri, one buccal cirrus, and one parabuccal cirrus; postperistomial cirrus and transverse cirri are lacking; there are two more or less long frontoventral rows and one right and two or more left marginal rows; cirri within all rows very widely spaced; dorsal kinety pattern is of Urosomoida type, that is, three dorsal kineties and one dorsomarginal kinety; and caudal cirri are present. Phylogenetic analyses based on the small subunit ribosomal (SSU rDNA) sequence data indicate that P. longicirrata nov. comb. clusters with Deviata and Perisincirra. It is considered that Pseudosincirra nov. gen. and Perisincirra paucicirrata should be assigned to the family Deviatidae; fine cirri, and cirri within all rows being relatively widely spaced, should be considered as plesiomorphies of Deviatidae; and Deviatidae is closely related to Dorsomarginalia or Strongylidium–Hemiamphisiella–Pseudouroleptus.
Reducing Phenanthrene Contamination in Trifolium repens L. With Root-Associated Phenanthrene-Degrading Bacterium Diaphorobacter sp. Phe15
Authors: Zhao Hui , Gu Yujun , Liu Xiangyu , Liu Juan , Waigi Michael Gatheru
Published: December 2021

Some root-associated bacteria could degrade polycyclic aromatic hydrocarbons (PAHs) in contaminated soil; however, their dynamic distribution and performance on root surface and in inner plant tissues are still unclear. In this study, greenhouse container experiments were conducted by inoculating the phenanthrene-degrading bacterium Diaphorobacter sp. Phe15, which was isolated from root surfaces of healthy plants contaminated with PAHs, with the white clover (Trifolium repens L.) via root irrigation or seed soaking. The dynamic colonization, distribution, and performance of Phe15 in white clover were investigated. Strain Phe15 could efficiently degrade phenanthrene in shaking flasks and produce IAA and siderophore. After cultivation for 30, 40, and 50 days, it could colonize the root surface of white clover by forming aggregates and enter its inner tissues via root irrigation or seed soaking. The number of strain Phe15 colonized on the white clover root surfaces was the highest, reaching 6.03 Log CFU⋅g–1 FW, followed by that in the roots and the least in the shoots. Colonization of Phe15 significantly reduced the contents of phenanthrene in white clover; the contents of phenanthrene in Phe15-inoculated plants roots and shoots were reduced by 29.92–43.16 and 41.36–51.29%, respectively, compared with the Phe15-free treatment. The Phe15 colonization also significantly enhanced the phenanthrene removal from rhizosphere soil. The colonization and performance of strain Phe15 in white clove inoculated via root inoculation were better than seed soaking. This study provides the technical support and the resource of strains for reducing the plant PAH pollution in PAH-contaminated areas.
A Novel Diagnostic Biomarker, PZP, for Detecting Colorectal Cancer in Type 2 Diabetes Mellitus Patients Identified by Serum-Based Mass Spectrometry
Authors: Yang Jiayue , Fang Weigang , Wu Wenjun , Tian Zhen , Gao Rong , Yu Lu , Chen Dayang , Weng Xiaohua , Zhu Shengwei , Yang Cheng
Published: December 2021

Background: Growing evidence has confirmed that populations with type 2 diabetes mellitus (T2DM) have an increasing risk of developing colorectal cancer (CRC). Thus, convenient and effective screening strategies for CRC should be developed for the T2DM population to increase the detection rate of CRC.

Methods: Twenty serum samples extracted from five healthy participants, five T2DM patients, five CRC patients and five T2DM patients with CRC (T2DM + CRC) were submitted to data-independent acquisition mass spectrometry (DIA-MS) analysis to discover unique differentially altered proteins (DAPs) for CRC in patients with T2DM. Then, the diagnostic value of pregnancy zone protein (PZP) was validated by ELISA analysis in the validated cohort.

Results: Based on DIA-MS analysis, we found eight unique proteins specific to T2DM patients with CRC. Among these proteins, four proteins showed different expression between the T2DM + CRC and T2DM groups, and PZP exhibited the largest difference. Next, the diagnostic value of serum PZP was validated by ELISA analysis with an AUC of 0.713. Moreover, the combination of PZP, CA199 and CEA exhibited encouraging diagnostic value, and the AUC reached 0.916.

Conclusion: Overall, our current research implied that PZP could be regarded as a newfound serum biomarker for CRC medical diagnosis in T2DM patients.
Simultaneous Assignment and Structure Determination of Proteins From Sparsely Labeled NMR Datasets
Authors: Mondal Arup , Perez Alberto
Published: December 2021

Sparsely labeled NMR samples provide opportunities to study larger biomolecular assemblies than is traditionally done by NMR. This requires new computational tools that can handle the sparsity and ambiguity in the NMR datasets. The MELD (modeling employing limited data) Bayesian approach was assessed to be the best performing in predicting structures from sparsely labeled NMR data in the 13th edition of the Critical Assessment of Structure Prediction (CASP) event—and limitations of the methodology were also noted. In this report, we evaluate the nature and difficulty in modeling unassigned sparsely labeled NMR datasets and report on an improved methodological pipeline leading to higher-accuracy predictions. We benchmark our methodology against the NMR datasets provided by CASP 13.
LigD: A Structural Guide to the Multi-Tool of Bacterial Non-Homologous End Joining
Authors: Amare Benhur , Mo Anthea , Khan Noorisah , Sowa Dana J. , Warner Monica M. , Tetenych Andriana , Andres Sara N.
Published: December 2021

DNA double-strand breaks are the most lethal form of damage for living organisms. The non-homologous end joining (NHEJ) pathway can repair these breaks without the use of a DNA template, making it a critical repair mechanism when DNA is not replicating, but also a threat to genome integrity. NHEJ requires proteins to anchor the DNA double-strand break, recruit additional repair proteins, and then depending on the damage at the DNA ends, fill in nucleotide gaps or add or remove phosphate groups before final ligation. In eukaryotes, NHEJ uses a multitude of proteins to carry out processing and ligation of the DNA double-strand break. Bacterial NHEJ, though, accomplishes repair primarily with only two proteins–Ku and LigD. While Ku binds the initial break and recruits LigD, it is LigD that is the primary DNA end processing machinery. Up to three enzymatic domains reside within LigD, dependent on the bacterial species. These domains are a polymerase domain, to fill in nucleotide gaps with a preference for ribonucleotide addition; a phosphoesterase domain, to generate a 3′-hydroxyl DNA end; and the ligase domain, to seal the phosphodiester backbone. To date, there are no experimental structures of wild-type LigD, but there are x-ray and nuclear magnetic resonance structures of the individual enzymatic domains from different bacteria and archaea, along with structural predictions of wild-type LigD via AlphaFold. In this review, we will examine the structures of the independent domains of LigD from different bacterial species and the contributions these structures have made to understanding the NHEJ repair mechanism. We will then examine how the experimental structures of the individual LigD enzymatic domains combine with structural predictions of LigD from different bacterial species and postulate how LigD coordinates multiple enzymatic activities to carry out DNA double-strand break repair in bacteria.
Effect of Fear of Falling on Mobility Measured During Lab and Daily Activity Assessments in Parkinson’s Disease
Authors: Atrsaei Arash , Hansen Clint , Elshehabi Morad , Solbrig Susanne , Berg Daniela , Liepelt-Scarfone Inga , Maetzler Walter , Aminian Kamiar
Published: December 2021

In chronic disorders such as Parkinson’s disease (PD), fear of falling (FOF) is associated with falls and reduced quality of life. With inertial measurement units (IMUs) and dedicated algorithms, different aspects of mobility can be obtained during supervised tests in the lab and also during daily activities. To our best knowledge, the effect of FOF on mobility has not been investigated in both of these settings simultaneously. Our goal was to evaluate the effect of FOF on the mobility of 26 patients with PD during clinical assessments and 14 days of daily activity monitoring. Parameters related to gait, sit-to-stand transitions, and turns were extracted from IMU signals on the lower back. Fear of falling was assessed using the Falls Efficacy Scale-International (FES-I) and the patients were grouped as with (PD-FOF+) and without FOF (PD-FOF−). Mobility parameters between groups were compared using logistic regression as well as the effect size values obtained using the Wilcoxon rank-sum test. The peak angular velocity of the turn-to-sit transition of the timed-up-and-go (TUG) test had the highest discriminative power between PD-FOF+ and PD-FOF− (r-value of effect size = 0.61). Moreover, PD-FOF+ had a tendency toward lower gait speed at home and a lower amount of walking bouts, especially for shorter walking bouts. The combination of lab and daily activity parameters reached a higher discriminative power [area under the curve (AUC) = 0.75] than each setting alone (AUC = 0.68 in the lab, AUC = 0.54 at home). Comparing the gait speed between the two assessments, the PD-FOF+ showed higher gait speeds in the capacity area compared with their TUG test in the lab. The mobility parameters extracted from both lab and home-based assessments contribute to the detection of FOF in PD. This study adds further evidence to the usefulness of mobility assessments that include different environments and assessment strategies. Although this study was limited in the sample size, it still provides a helpful method to consider the daily activity measurement of the patients with PD into clinical evaluation. The obtained results can help the clinicians with a more accurate prevention and treatment strategy.
The Effects of a Novel Non-catechol Dopamine Partial Agonist on Working Memory in the Aged Rhesus Monkey
Authors: Moore Tara L. , Young Damon A. , Killiany Ronald J. , Fonseca Kari R. , Volfson Dmitri , Gray David L. , Balice-Gordon Rita , Kozak Rouba
Published: December 2021

Aged-related declines in cognition, especially working memory and executive function, begin in middle-age and these abilities are known to be mediated by the prefrontal cortex (PFC) and more specifically the dopamine (DA) system within the PFC. In both humans and monkeys, there is significant evidence that the PFC is the first cortical region to change with age and the PFC appears to be particularly vulnerable to age-related loss of dopamine (DA). Therefore, the DA system is a strong candidate for therapeutic intervention to slow or reverse age related declines in cognition. In the present study, we administered a novel selective, potent, non-catechol DA D1 R agonist PF-6294 (Pfizer, Inc.) to aged female rhesus monkeys and assessed their performance on two benchmark tasks of working memory – the Delayed Non-match to Sample Task (DNMS) and Delayed Recognition Span Task (DRST). The DNMS task was administered first with the standard 10 s delay and then with 5 min delays, with and without distractors. The DRST was administered each day with four trials with unique sequences and one trial of a repeated sequence to assess evidence learning and retention. Overall, there was no significant effect of drug on performance on any aspect of the DNMS task. In contrast, we demonstrated that a middle range dose of PF-6294 significantly increased memory span on the DRST on the first and last days of testing and by the last day of testing the increased memory span was driven by the performance on the repeated trials.
Deficits in N-Methyl-D-Aspartate Receptor Function and Synaptic Plasticity in Hippocampal CA1 in APP/PS1 Mouse Model of Alzheimer’s Disease
Authors: Xu Le , Zhou Yiying , Hu Linbo , Jiang Hongde , Dong Yibei , Shen Haowei , Lou Zhongze , Yang Siyu , Ji Yunxin , Ruan Liemin , Zhang Xiaoqin
Published: December 2021

The N-methyl-D-aspartate receptor is a critical molecule for synaptic plasticity and cognitive function. Impaired synaptic plasticity is thought to contribute to the cognitive impairment associated with Alzheimer’s disease (AD). However, the neuropathophysiological alterations of N-methyl-D-aspartate receptor (NMDAR) function and synaptic plasticity in hippocampal CA1 in transgenic rodent models of AD are still unclear. In the present study, APP/PS1 mice were utilized as a transgenic model of AD, which exhibited progressive cognitive impairment including defective working memory, recognition memory, and spatial memory starting at 6 months of age and more severe by 8 months of age. We found an impaired long-term potentiation (LTP) and reduced NMDAR-mediated spontaneous excitatory postsynaptic currents (sEPSCs) in the hippocampal CA1 of APP/PS1 mice with 8 months of age. Golgi staining revealed that dendrites of pyramidal neurons had shorter length, fewer intersections, and lower spine density in APP/PS1 mice compared to control mice. Further, the reduced expression levels of NMDAR subunits, PSD95 and SNAP25 were observed in the hippocampus of APP/PS1 mice. These results suggest that NMDAR dysfunction, impaired synaptic plasticity, and disrupted neuronal morphology constitute an important part of the neuropathophysiological alterations associated with cognitive impairment in APP/PS1 mice.
Impaired Cognitive Function and Hippocampal Changes Following Chronic Diazepam Treatment in Middle-Aged Mice
Authors: Furukawa Tomonori , Nikaido Yoshikazu , Shimoyama Shuji , Masuyama Nozomu , Notoya Ayaka , Ueno Shinya
Published: December 2021

Background: Gamma-aminobutyric acid (GABA) type A receptors are positively allosterically modulated by benzodiazepine binding, leading to a potentiated response to GABA. Diazepam (DZP, a benzodiazepine) is widely prescribed for anxiety, epileptic discharge, and insomnia, and is also used as a muscle relaxant and anti-convulsant. However, some adverse effects – such as tolerance, dependence, withdrawal effects, and impairments in cognition and learning – are elicited by the long-term use of DZP. Clinical studies have reported that chronic DZP treatment increases the risk of dementia in older adults. Furthermore, several studies have reported that chronic DZP administration may affect neuronal activity in the hippocampus, dendritic spine structure, and cognitive performance. However, the effects of chronic DZP administration on cognitive function in aged mice is not yet completely understood.

Methods: A behavioral test, immunohistochemical analysis of neurogenic and apoptotic markers, dendritic spine density analysis, and long-term potentiation (LTP) assay of the hippocampal CA1 and CA3 were performed in both young (8 weeks old) and middle-aged (12 months old) mice to investigate the effects of chronic DZP administration on cognitive function. The chronic intraperitoneal administration of DZP was performed by implanting an osmotic minipump. To assess spatial learning and memory ability, the Morris water maze test was performed. Dendritic spines were visualized using Lucifer yellow injection into the soma of hippocampal neurons, and spine density was analyzed. Moreover, the effects of exercise on DZP-induced changes in spine density and LTP in the hippocampus were assessed.

Results: Learning performance was impaired by chronic DZP administration in middle-aged mice but not in young mice. LTP was attenuated by DZP administration in the CA1 of young mice and the CA3 of middle-aged mice. The spine density of hippocampal neurons was decreased by chronic DZP administration in the CA1 of both young and middle-aged mice as well as in the CA3 of middle-aged mice. Neither neurogenesis nor apoptosis in the hippocampus was affected by chronic DZP administration.

Conclusion: The results of this study suggest that the effects of chronic DZP are different between young and middle-aged mice. The chronic DZP-induced memory retrieval performance impairment in middle-aged mice can likely be attributed to decreased LTP and dendritic spine density in hippocampal neurons in the CA3. Notably, prophylactic exercise suppressed the adverse effects of chronic DZP on LTP and spine maintenance in middle-aged mice.
Low-Temperature Chemical Vapor Deposition Growth of MoS2 Nanodots and Their Raman and Photoluminescence Profiles
Authors: Mawlong Larionette P. L. , Biroju Ravi K. , Giri P. K.
Published: December 2021

We report on the growth of an ordered array of MoS2 nanodots (lateral sizes in the range of ∼100–250 nm) by a thermal chemical vapor deposition (CVD) method directly onto SiO2 substrates at a relatively low substrate temperature (510–560°C). The temperature-dependent growth and evolution of MoS2 nanodots and the local environment of sulfur-induced structural defects and impurities were systematically investigated by field emission scanning electron microscopy, micro-Raman spectroscopy, and X-ray photoelectron spectroscopy (XPS) techniques. At the substrate temperature of 560°C, we observed mostly few-layer MoS2, and at 510°C, multilayer MoS2 growth, as confirmed from the Raman line shape analysis. With reduced substrate temperature, the density of MoS2 nanodots decreases, and layer thickness increases. Raman studies show characteristic Raman modes of the crystalline MoS2 layer, along with two new Raman modes centered at ∼346 and ∼361 cm−1, which are associated with MoO2 and MoO3 phases, respectively. Room temperature photoluminescence (PL) studies revealed strong visible PL from MoS2 layers, which is strongly blue-shifted from the bulk MoS2 flakes. The strong visible emission centered at ∼ 658 nm signifies a free excitonic transition in the direct gap of single-layer MoS2. Position-dependent PL profiles show excellent uniformity of the MoS2 layers for samples grown at 540 and 560°C. These results are significant for the low-temperature CVD growth of a few-layer MoS2 dots with direct bandgap photoluminescence on a flexible substrate.
A Novel Balance Control Strategy Based on Enhanced Stability Pyramid Index and Dynamic Movement Primitives for a Lower Limb Human-Exoskeleton System
Authors: Xu Fashu , Qiu Jing , Yuan Wenbo , Cheng Hong
Published: December 2021

The lower limb exoskeleton is playing an increasing role in enabling individuals with spinal cord injury (SCI) to stand upright, walk, turn, and so on. Hence, it is essential to maintain the balance of the human-exoskeleton system during movements. However, the balance of the human-exoskeleton system is challenging to maintain. There are no effective balance control strategies because most of them can only be used in a specific movement like walking or standing. Hence, the primary aim of the current study is to propose a balance control strategy to improve the balance of the human-exoskeleton system in dynamic movements. This study proposes a new safety index named Enhanced Stability Pyramid Index (ESPI), and a new balance control strategy is based on the ESPI and the Dynamic Movement Primitives (DMPs). To incorporate dynamic information of the system, the ESPI employs eXtrapolated Center of Mass (XCoM) instead of the center of mass (CoM). Meanwhile, Time-to-Contact (TTC), the urgency of safety, is used as an automatic weight assignment factor of ESPI instead of the traditional manual one. Then, the balance control strategy utilizing DMPs to generate the gait trajectory according to the scalar and vector values of the ESPI is proposed. Finally, the walking simulation in Gazebo and the experiments of the human-exoskeleton system verify the effectiveness of the index and balance control strategy.
Closing the Critical Period Is Required for the Maturation of Binocular Integration in Mouse Primary Visual Cortex
Authors: Chan Jiangping , Hao Xiangwen , Liu Qiong , Cang Jianhua , Gu Yu
Published: December 2021

Binocular matching of orientation preference between the two eyes is a common form of binocular integration that is regarded as the basis for stereopsis. How critical period plasticity enables binocular matching under the guidance of normal visual experience has not been fully demonstrated. To investigate how critical period closure affects the binocular matching, a critical period prolonged mouse model was constructed through the administration of bumetanide, an NKCC1 transporter antagonist. Using acute in vivo extracellular recording and molecular assay, we revealed that binocular matching was transiently disrupted due to heightened plasticity after the normal critical period, together with an increase in the density of spines and synapses, and the upregulation of GluA1 expression. Diazepam (DZ)/[(R, S)-3-(2-carboxypiperazin-4-yl) propyl-1-phosphonic acid (CPP)] could reclose the extended critical period, and rescue the deficits in binocular matching. Furthermore, the extended critical period, alone, with normal visual experience is sufficient for the completion of binocular matching in amblyopic mice. Similarly, prolonging the critical period into adulthood by knocking out Nogo-66 receptor can prevent the normal maturation of binocular matching and depth perception. These results suggest that maintaining an optimal plasticity level during adolescence is most beneficial for the systemic maturation. Extending the critical period provides new clues for the maturation of binocular vision and may have critical implications for the treatment of amblyopia.
Characterizing the Neuroimaging and Histopathological Correlates of Cerebral Small Vessel Disease in Spontaneously Hypertensive Stroke-Prone Rats
Authors: Hannawi Yousef , Caceres Eder , Ewees Mohamed G. , Powell Kimerly A. , Bratasz Anna , Schwab Jan M. , Rink Cameron L. , Zweier Jay L.
Published: December 2021

Introduction: Spontaneously hypertensive stroke-prone rats (SHRSP) are used to model clinically relevant aspects of human cerebral small vessel disease (CSVD). To decipher and understand the underlying disease dynamics, assessment of the temporal progression of CSVD histopathological and neuroimaging correlates is essential.

Materials and Methods: Eighty age-matched male SHRSP and control Wistar Kyoto rats (WKY) were randomly divided into four groups that were aged until 7, 16, 24 and 32 weeks. Sensorimotor testing was performed weekly. Brain MRI was acquired at each study time point followed by histological analyses of the brain.

Results: Compared to WKY controls, the SHRSP showed significantly higher prevalence of small subcortical hyperintensities on T2w imaging that progressed in size and frequency with aging. Volumetric analysis revealed smaller intracranial and white matter volumes on brain MRI in SHRSP compared to age-matched WKY. Diffusion tensor imaging (DTI) showed significantly higher mean diffusivity in the corpus callosum and external capsule in WKY compared to SHRSP. The SHRSP displayed signs of motor restlessness compared to WKY represented by hyperactivity in sensorimotor testing at the beginning of the experiment which decreased with age. Distinct pathological hallmarks of CSVD, such as enlarged perivascular spaces, microbleeds/red blood cell extravasation, hemosiderin deposits, and lipohyalinosis/vascular wall thickening progressively accumulated with age in SHRSP.

Conclusions: Four stages of CSVD severity in SHRSP are described at the study time points. In addition, we find that quantitative analyses of brain MRI enable identification of in vivo markers of CSVD that can serve as endpoints for interventional testing in therapeutic studies.
Five-Years Angiographic Follow-Up of Wide-Neck Intracranial Aneurysms Treated With LEO Plus Stent
Authors: Pumar José M. , Sucasas Paula , Mosqueira Antonio , Vega Pedro , Murias Eduardo
Published: December 2021

Background: This study aimed to evaluate the angiographic and clinical outcome, with an emphasis on long-term follow-up, of the LEO Plus stent for wide-neck intracranial aneurysms treated in a single center.

Methods: We retrospectively examined a prospectively maintained database of patients treated with LEO Plus devices between January 2004 and December 2016. Data regarding patient demographics, aneurysm characteristics, and technical procedures were analyzed. Angiographic and clinical findings were recorded during the procedure and followed up over a period of at least 5 years.

Results: We identified 101 patients with 116 aneurysms. In 16 patients, the stent could not safely be placed. Thus, a total of 97 LEO Plus devices were implanted in 97 aneurysms of 85 patients. Adverse events (acute and delayed) were observed in 21.6% of cases (17/85), and most were resolved (70.6%; 12/17). Moreover, 5 years after the procedure, total morbidity and mortality were 2.3% (2/85) and 3.5% (3/85), respectively. Long-term imaging follow-up showed complete occlusions, neck remnants, and residual aneurysms in 73.1% (57/78), 14.1% (11/78), and 12.8% (10/78) of cases, respectively.

Conclusions: Long-term results of treatment of brain aneurysms with LEO stent show high rates of adequate and stable occlusion over time, with acceptable morbidity and mortality.
A National Representative, Cross-Sectional Study by the Hellenic Academy of NeuroImmunology (HEL.A.NI.) on COVID-19 and Multiple Sclerosis: Overall Impact and Willingness Toward Vaccination
Authors: Boziki Marina , Styliadis Charis , Bakirtzis Christos , Grigoriadou Eleni , Sintila Aggeliki-Styliani , Nikolaidis Ioannis , Vrienniou Aliki , Geys Lotte , Pelidou Sygkliti-Henrietta , Probert Lesley , Papazisis Georgios , Bamidis Panagiotis , Grigoriadis Nikolaos
Published: December 2021

Background: In the context of the coronavirus disease 2019 (COVID-19) pandemic, the constant needs of people with multiple sclerosis (PwMS) and their caregivers were urgently highlighted.

Aim: The present study aims to capture the effects of the COVID-19 pandemic in several aspects of the quality of life of PwMS, in perception and behavior to COVID-19 and multiple sclerosis (MS), as well as concerning healthcare, working conditions, and the willingness toward COVID-19 vaccination.

Methods: This study is an initiative of the Hellenic Academy of Neuroimmunology (HEL.A.NI.) and it has been included in the MS Data Alliance (MSDA) Catalog, which can be accessed after creating an account on https://msda.emif-catalogue.eu/login. Two online questionnaires were administered: (i) impact of the COVID-19 pandemic on the quality of life, behavior, and healthcare of PwMS (Questionnaire A) and (ii) vaccination against COVID-19 (Questionnaire B). People with MS were invited to participate by the Hellenic Federation of Persons with Multiple Sclerosis (HFoPwMS).

Results: Three-hundred-ninety PwMS responded to Questionnaire A, whereas 176 PwMS provided answers for Questionnaire B. Older age, longer disease duration, and higher MS-related disability were associated with the increased perceived sensitivity toward severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, as well as the increased perceived severity of COVID-19 upon potential infection. A significant proportion of PwMS experienced restricted access to MS-related health professionals, disease-modifying therapy (DMT) prescription, and/or to MS-related laboratory examination due to the pandemic. Subgroups of PwMS reported exacerbated symptoms (i.e., chronic MS-related symptoms, fatigue and/or worsening of pre-existing fatigue, and sexual dysfunction and or/worsening of pre-existing sexual dysfunction). Overall, the majority of the participants reported either a strong willingness to get vaccinated against COVID-19 or a likeliness to undergo vaccination. Being aware of the HEL.A.NI. recommendations regarding COVID-19 vaccination for PwMS were reported to increase the willingness of the participants to receive the vaccine.

Conclusions: Our results highlight the necessity of scientific and patient organizations in taking joint action to increase awareness on health-related issues during the pandemic and to provide accurate and up-to-date guidance for PwMS. Online information and communications technology (ICT) tools for polling public belief and behavior may prove valuable as means of retaining active routes of communication between stakeholders.
Frailty in Glioblastoma Is Independent From Chronological Age
Authors: Krenzlin Harald , Jankovic Dragan , Alberter Christoph , Kalasauskas Darius , Westphalen Christiane , Ringel Florian , Keric Naureen
Published: December 2021

Objective: Treatment of glioblastoma in elderly patients is particularly challenging due to their general condition and comorbidities. Treatment decisions are often based on chronological age. Frailty screening tests promise an assessment tool to stratify geriatric patients and identify those at risk for an unfavorable outcome. This study aims to evaluate the impact of age and frailty on the surgical outcome and overall survival in geriatric patients with glioblastoma.

Methods: Data acquisition was conducted as a single-center retrospective analysis. From January 1st 2015, and December 31st 2019, 104 glioblastoma patients over 70 years of age were included in our study. Demographic data, tumor size, Karnofsky Performance Score (KPS), and Eastern Cooperative Oncology Group Performance Status (ECOG), as well as treatment modalities, were assessed. The Geriatric 8 health status screening tool (G8) and Groningen Frailty Index (GFI) were compiled pre-and postoperatively.

Results: The mean patient age was 76.86 ± 4.11 years. Forty-nine (47%) patients were female, 55 (53%) male. Sixty-seven patients underwent microsurgical tumor resection, 37 received tumor biopsy alone. Mean G8 on admission was 12.4 ± 2.0, mean GFI 5.0 ± 2.5. In our cohort, frailty was independent of patient age, tumor size, or localization. Frailty, defined by G8 and GFI, is associated with shorter overall survival (G8: p = 0.0035; GFI: p = 0.0136) and higher numbers of surgical complications (G8: p = 0.0326; GFI: p = 0.0388). Frailer patients are more likely to receive best supportive care (p = 0.004). Nevertheless, frailty did not affect adjuvant treatment decision-making toward either single-use of chemo- or radiation therapy, stratified treatment, or concomitant therapy. The surgical decision on the extent of resection was not based on pre-operative frailty.

Conclusion: In our study, frailty is a predictor of poorer surgical outcomes, post-operative complications, and impaired overall survival independent of chronological age. Frailty screening tests offer an additional assessment tool to stratify geriatric patients with glioblastoma and identify those at risk for a detrimental outcome and thus should be implemented in therapeutic decision making.
The Safety and Efficacy of Pregabalin Add-on Therapy in Restless Legs Syndrome Patients
Authors: Bae Hyoeun , Cho Yong Won , Kim Keun Tae , Allen Richard P. , Earley Christopher J.
Published: December 2021

Pregabalin is increasingly being used as a first-line treatment for symptomatic control of restless legs syndrome (RLS). This study aimed to evaluate the efficacy and safety of pregabalin as add-on therapy in RLS patients already taking dopamine agonists (DA) but still in need of further management. Patients with idiopathic RLS were enrolled, and all had already been prescribed DA for at least 3 months but still had either persistent symptoms, side effects, or comorbid insomnia. An initial dose of 75 mg pregabalin was begun, adjusted as needed, and maintained at a stable dose for 4 weeks, followed by observation for a total of 8 weeks. RLS symptoms and insomnia scores were evaluated before and after add-on pregabalin treatment. Patients were monitored for side effects that could be attributed to pregabalin. A total of 32 RLS patients were enrolled, and 20 subjects remained until the endpoint. After the pregabalin add-on, the mean IRLS score showed significant improvement compared to the baseline (p < 0.001). The insomnia severity index score also improved (p = 0.036), and no serious adverse effects were observed. Our preliminary data suggests the potential for pregabalin as an add-on therapy to DA with regards to both efficacy and safety in patients who have inadequate RLS improvement.
Repeated Clinical Assessment Using Sensory Modality Assessment and Rehabilitation Technique for Diagnosis in Prolonged Disorders of Consciousness
Authors: da Conceição Teixeira Liliana , Blacker Danielle , Campos Carlos , Garrett Carolina , Duport Sophie , Rocha Nuno Barbosa
Published: December 2021

Purpose: The recommended way to assess consciousness in prolonged disorders of consciousness is to observe the patient’s responses to sensory stimulation. Multiple assessment sessions have to be completed in order to reach a correct diagnosis. There is, however, a lack of data on how many sessions are sufficient for validity and reliability. The aim of this study was to identify the number of Sensory Modality Assessment and Rehabilitation Technique (SMART) assessment sessions needed to reach a reliable diagnosis. A secondary objective was to identify which sensory stimulation modalities are more useful to reach a diagnosis.

Materials and Methods: A retrospective analysis of all the adult patients (who received a SMART assessment) admitted to a specialist brain injury unit over the course of 4 years was conducted (n = 35). An independent rater analyzed the SMART levels for each modality and session and provided a suggestive diagnosis based on the highest SMART level per session.

Results: For the vast majority of patients between 5 and 6 sessions was sufficient to reach the final clinical diagnosis. The visual, auditory, tactile, and motor function modalities were found to be more associated with the final diagnosis than the olfactory and gustatory modalities.

Conclusion: These findings provide for the first time a rationale for optimizing the time spent on assessing patients using SMART.
Electrophysiological Biomarkers of Epileptogenicity in Alzheimer’s Disease
Authors: Yu Tingting , Liu Xiao , Wu Jianping , Wang Qun
Published: December 2021

Cortical network hyperexcitability is an inextricable feature of Alzheimer’s disease (AD) that also might accelerate its progression. Seizures are reported in 10–22% of patients with AD, and subclinical epileptiform abnormalities have been identified in 21–42% of patients with AD without seizures. Accurate identification of hyperexcitability and appropriate intervention to slow the compromise of cognitive functions of AD might open up a new approach to treatment. Based on the results of several studies, epileptiform discharges, especially those with specific features (including high frequency, robust morphology, right temporal location, and occurrence during awake or rapid eye movement states), frequent small sharp spikes (SSSs), temporal intermittent rhythmic delta activities (TIRDAs), and paroxysmal slow wave events (PSWEs) recorded in long-term scalp electroencephalogram (EEG) provide sufficient sensitivity and specificity in detecting cortical network hyperexcitability and epileptogenicity of AD. In addition, magnetoencephalogram (MEG), foramen ovale (FO) electrodes, and computational approaches help to find subclinical seizures that are invisible on scalp EEGs. We performed a comprehensive analysis of the aforementioned electrophysiological biomarkers of AD-related seizures.