bluuebunny/crossref_metadata_2025 huggingface dataset:
Maize (Zea mays L.) Seedlings Rhizosphere Microbial Community as Responded to Acidic Biochar Amendment Under Saline Conditions
Authors: Soothar Mukesh Kumar , Hamani Abdoul Kader Mounkaila , Sardar Muhammad Fahad , Sootahar Mahendar Kumar , Fu Yuanyuan , Rahim Riffat , Soothar Jay Kumar , Bhatti Saleem Maseeh , Abubakar Sunusi Amin , Gao Yang , Sun Jingsheng
Published: December 2021

Biochar has extensively been used for multiple purposes in agriculture, including improving soil microbial biomass. The current study aimed to investigate the effect of acidic biochar on maize seedlings’ rhizosphere bacterial abundance under salinity. There were seven treatments and three replicates in a controlled greenhouse coded as B0S1, B1S1, and B2S1 and B0S2, B1S2, and B2S2. CK is control (free of biochar and salt); B0, B1, and B2 are 0, 15, and 30 g biochar (kg soil)–1; and S1 and S2 are 2.5 and 5 g salt pot–1 that were amended, respectively. After harvesting the maize seedlings, the soil samples were collected and analyzed for soil microbial biomass, bacterial abundance, and diversity. The results revealed that relative abundance of Proteobacteria, Actinobacteria, and Chloroflexi increased on phylum level, whereas Actinomarinales, Alphaproteobacteria, and Streptomyces enhanced on genus level, respectively, in B2S1 and B2S2, when compared with CK and non-biochar amended soil under saline conditions. The relative abundance of Actinomarinales was positively correlated with total potassium (TK) and Gematimonadetes negatively correlated with total phosphorus (TP). Biochar addition slightly altered the Ace1, Chao1, and alpha diversity. Principal component analysis corresponded to the changes in soil bacterial community that were closely associated with biochar when compared with CK and salt-treated soils. In conclusion, acidic biochar showed an improved soil microbial community under salinity.
DNA Damage Protection for Enhanced Bacterial Survival Under Simulated Low Earth Orbit Environmental Conditions in Escherichia coli
Authors: Puig Jaume , Knödlseder Nastassia , Quera Jaume , Algara Manuel , Güell Marc
Published: December 2021

Some organisms have shown the ability to naturally survive in extreme environments, even outer space. Some of these have natural mechanisms to resist severe DNA damage from conditions such as ionizing and non-ionizing radiation, extreme temperatures, and low pressures or vacuum. A good example can be found in Deinococcus radiodurans, which was exposed to severe conditions such as those listed in the Exposure Facility of the International Space Station (ISS) for up to three years. Another example are tardigrades (Ramazzottius varieornatus) which are some of the most resilient animals known. In this study, the survival under simulated Low earth Orbit (LEO) environmental conditions was tested in Escherichia coli. The radiation resistance of this bacteria was enhanced using the Dsup gene from R. varieornatus, and two more genes from D. radiodurans involved in DNA damage repair, RecA and uvrD. The enhanced survival to wide ranges of temperatures and low pressures was then tested in the new strains. This research constitutes a first step in the creation of new bacterial strains engineered to survive severe conditions and adapting existing species for their survival in remote environments, including extra-terrestrial habitats. These strains could be key for the development of environments hospitable to life and could be of use for ecological restoration and space exploration. In addition, studying the efficacy and the functioning of the DNA repair mechanisms used in this study could be beneficial for medical and life sciences engineering.
Significantly Low Levels of IgG Antibodies Against Oncogenic Merkel Cell Polyomavirus in Sera From Females Affected by Spontaneous Abortion
Authors: Mazziotta Chiara , Pellielo Giulia , Tognon Mauro , Martini Fernanda , Rotondo John Charles
Published: December 2021

Merkel cell polyomavirus (MCPyV) is a small DNA tumor virus ubiquitous in humans. MCPyV establishes a clinically asymptomatic lifelong infection in healthy immunocompetent individuals. Viral infections are considered to be risk factors for spontaneous abortion (SA), which is the most common adverse complication of pregnancy. The role of MCPyV in SA remains undetermined. Herein, the impact of MCPyV infection in females affected by SA was investigated. Specifically, an indirect enzyme-linked immunosorbent assay (ELISA) method with two linear synthetic peptides/mimotopes mimicking MCPyV antigens was used to investigate immunoglobulin G (IgG) antibodies against MCPyV in sera from 94 females affected by SA [mean ± standard deviation (SD) age 35 ± (6) years] and from 96 healthy females undergoing voluntary pregnancy interruption [VI, mean (±SD) age 32 ± (7) years]. MCPyV seroprevalence and serological profiles were analyzed. The overall prevalence of serum IgG antibodies against MCPyV was 35.1% (33/94) and 37.5% (36/96) in SA and VI females, respectively (p > 0.05). Notably, serological profile analyses indicated lower optical densities (ODs) in females with SA compared to those undergoing VI (p < 0.05), thus indicating a reduced IgG antibody response in SA females. Circulating IgGs were identified in sera from SA and VI females. Our immunological findings indicate that a relatively reduced fraction of pregnant females carry serum anti-MCPyV IgG antibodies, while SA females presented a more pronounced decrease in IgG antibody response to MCPyV. Although yet to be determined, this immunological decrease might prompt an increase in MCPyV multiplication events in females experiencing abortive events. The role of MCPyV in SA, if present, remains to be determined.
Lateral Transmission of Yeast Symbionts Among Lucanid Beetle Taxa
Authors: Ueki Gaku , Zhang Sheng-Nan , Zhu Xue-Jiao , Wen Xiu-Jun , Tojo Koji , Kubota Kôhei
Published: December 2021

To deepen understanding the evolutionary process of lucanid–yeast association, the lateral transmission process of yeast symbionts among stag beetle genera Platycerus and Prismognathus around the border between Japan and South Korea was estimated based on molecular analyses and species distribution modelings. Phylogenetic analyses were based on yeast ITS and IGS sequences and beetle COI sequences using Prismognathus dauricus from the Tsushima Islands and Pr. angularis from Kyushu, Japan, as well as other sequence data from our previous studies. The range overlap based on the species distribution model (SDM) and differentiation in ecological space were analyzed. Based on the IGS sequences, Clade II yeast symbionts were shared by Platycerus hongwonpyoi and Pr. dauricus in South Korea and the Tsushima Islands, and Platycerus viridicuprus in Japan. Clade III yeasts were shared by Pr. dauricus from the Tsushima Islands and Pr. angularis in Japan. During the Last Interglacial period when the land bridge between Japan and the Korean Peninsula existed, range overlap was predicted to occur between Pl. viridicuprus and Pr. dauricus in Kyushu and between Pr. dauricus and Pr. angularis in Kyushu and the Tsushima Islands. The ecological space of Pl. hongwonpyoi was differentiated from that of Pl. viridicuprus and Pr. angularis. We demonstrated the paleogeographical lateral transmission process of Scheffersomyces yeast symbionts among lucanid genera and species: putative transmission of yeasts from Pr. dauricus to Pl. viridicuprus in Kyushu and from Pr. angularis to Pr. dauricus in Kyushu or the Tsushima Islands. We also found that the yeast symbionts are likely being replaced in Pr. dauricus on the Tsushima Islands. We present novel estimates of the lateral transmission process of microbial symbionts based on phylogenetic, SDM and environmental analyses among lucanid beetles.
The HBV Core Protein and Core Particle Both Bind to the PPiase Par14 and Par17 to Enhance Their Stabilities and HBV Replication
Authors: Saeed Umar , Piracha Zahra Zahid , Kwon Hyeonjoong , Kim Jumi , Kalsoom Fadia , Chwae Yong-Joon , Park Sun , Shin Ho-Joon , Lee Hyun Woong , Lim Jin Hong , Kim Kyongmin
Published: December 2021

We recently reported that the PPIase Par14 and Par17 encoded by PIN4 upregulate HBV replication in an HBx-dependent manner by binding to conserved arginine–proline (RP) motifs of HBx. HBV core protein (HBc) has a conserved 133RP134 motif; therefore, we investigated whether Par14/Par17 bind to HBc and/or core particles. Native agarose gel electrophoresis (NAGE) and immunoblotting and co-immunoprecipitation were used. Chromatin immunoprecipitation from HBV-infected HepG2-hNTCP-C9 cells was performed. NAGE and immunoblotting revealed that Par14/Par17 bound to core particles and co-immunoprecipitation revealed that Par14/Par17 interacted with core particle assembly-defective, and dimer-positive HBc-Y132A. Thus, core particles and HBc interact with Par14/Par17. Par14/Par17 interacted with the HBc 133RP134 motif possibly via substrate-binding E46/D74 and E71/D99 motifs. Although Par14/Par17 dissociated from core particles upon heat treatment, they were detected in 0.2 N NaOH-treated opened-up core particles, demonstrating that Par14/Par17 bind outside and inside core particles. Furthermore, these interactions enhanced the stabilities of HBc and core particles. Like HBc-Y132A, HBc-R133D and HBc-R133E were core particle assembly-defective and dimer-positive, demonstrating that a negatively charged residue at position 133 cannot be tolerated for particle assembly. Although positively charged R133 is solely important for Par14/17 interactions, the 133RP134 motif is important for efficient HBV replication. Chromatin immunoprecipitation from HBV-infected cells revealed that the S19 and E46/D74 residues of Par14 and S44 and E71/D99 residues of Par17 were involved in recruitment of 133RP134 motif-containing HBc into cccDNA. Our results demonstrate that interactions of HBc, Par14/Par17, and cccDNA in the nucleus and core particle–Par14/Par17 interactions in the cytoplasm are important for HBV replication.
Evasion of I Interferon-Mediated Innate Immunity by Pseudorabies Virus
Authors: Zhang Rui , Tang Jun
Published: December 2021

Type I interferon (IFN-I) mediated innate immunity serves as the first line of host defense against viral infection, ranging from IFN-I production upon viral detection, IFN-I triggered signaling pathway that induces antiviral gene transcription the antiviral effects of IFN-I induced gene products. During coevolution, herpesviruses have developed multiple countermeasures to inhibit the various steps involved to evade the IFN response. This mini-review focuses on the strategies used by the alphaherpesvirus Pseudorabies virus (PRV) to antagonize IFN-I mediated innate immunity, with a particular emphasis on the mechanisms inhibiting IFN-I induced gene transcription through the JAK-STAT pathway. The knowledge obtained from PRV enriches the current understanding of the alphaherpesviral immune evasion mechanisms and provides insight into the vaccine development for PRV control.
Unveiling the Gating Mechanism of CRAC Channel: A Computational Study
Authors: Guardiani Carlo , Sun Delia , Giacomello Alberto
Published: December 2021

CRAC channel is ubiquitous and its importance in the regulation of the immune system is testified by the severe immunodeficiencies caused by its mutations. In this work we took advantage of the availability of open and closed structures of this channel to run for the first time simulations of the whole gating process reaching the relevant time-scale with an enhanced sampling technique, Targeted Molecular Dynamics. Our simulations highlighted a complex allosteric propagation of the conformational change from peripheral helices, where the activator STIM1 binds, to the central pore helices. In agreement with mutagenesis data, our simulations revealed the key role of residue H206 whose displacement creates an empty space behind the hydrophobic region of the pore, thus releasing a steric brake and allowing the opening of the channel. Conversely, the process of pore closing culminates with the formation of a bubble that occludes the pore even in the absence of steric block. This mechanism, known as “hydrophobic gating”, has been observed in an increasing number of biological ion channels and also in artificial nanopores. Our study therefore shows promise not only to better understand the molecular origin of diseases caused by disrupted calcium signaling, but also to clarify the mode of action of hydrophobically gated ion channels, possibly even suggesting strategies for the biomimetic design of synthetic nanopores.
The Stereological Analysis and Spatial Distribution of Neurons in the Human Subthalamic Nucleus
Authors: Bokulić Ema , Medenica Tila , Knezović Vinka , Štajduhar Andrija , Almahariq Fadi , Baković Marija , Judaš Miloš , Sedmak Goran
Published: December 2021

The subthalamic nucleus (STN) is a small, ovoid structure, and an important site of deep brain stimulation (DBS) for the treatment of Parkinson’s disease. Although the STN is a clinically important structure, there are many unresolved issues with regard to it. These issues are especially related to the anatomical subdivision, neuronal phenotype, neuronal composition, and spatial distribution. In this study, we have examined the expression pattern of 8 neuronal markers [nNOS, NeuN, parvalbumin (PV), calbindin (CB), calretinin (CR), FOXP2, NKX2.1, and PAX6] in the adult human STN. All of the examined markers, except CB, were present in the STN. To determine the neuronal density, we have performed stereological analysis on Nissl-stained and immunohistochemical slides of positive markers. The stereology data were also used to develop a three-dimensional map of the spatial distribution of neurons within the STN. The nNOS population exhibited the largest neuronal density. The estimated total number of nNOS STN neurons is 281,308 ± 38,967 (± 13.85%). The STN neuronal subpopulations can be divided into two groups: one with a neuronal density of approximately 3,300 neurons/mm3 and the other with a neuronal density of approximately 2,200 neurons/mm3. The largest density of STN neurons was observed along the ventromedial border of the STN and the density gradually decreased toward the dorsolateral border. In this study, we have demonstrated the presence of 7 neuronal markers in the STN, three of which were not previously described in the human STN. The human STN is a collection of diverse, intermixed neuronal subpopulations, and our data, as far as the cytoarchitectonics is concerned, did not support the tripartite STN subdivision.
Assessment of a Robotic Walker in Older Adults With Parkinson's Disease in Daily Living Activities
Authors: Sierra M. Sergio D. , Garcia A. Daniel E. , Otálora Sophia , Arias-Castro María Camila , Gómez-Rodas Alejandro , Múnera Marcela , Cifuentes Carlos A.
Published: December 2021

The constant growth of the population with mobility impairments, such as older adults and people suffering from neurological pathologies like Parkinson's disease (PD), has encouraged the development of multiple devices for gait assistance. Robotic walkers have emerged, improving physical stability and balance and providing cognitive aid in rehabilitation scenarios. Different studies evaluated human gait behavior with passive and active walkers to understand such rehabilitation processes. However, there is no evidence in the literature of studies with robotic walkers in daily living scenarios with older adults with Parkinson's disease. This study presents the assessment of the AGoRA Smart Walker using Ramps Tests and Timed Up and Go Test (TUGT). Ten older adults participated in the study, four had PD, and the remaining six had underlying conditions and fractures. Each of them underwent a physical assessment (i.e., Senior Fitness, hip, and knee strength tests) and then interacted with the AGoRA SW. Kinematic and physical interaction data were collected through the AGoRA walker's sensory interface. It was found that for lower limb strength tests, older adults with PD had increases of at least 15% in all parameters assessed. For the Sit to Stand Test, the Parkinson's group evidenced an increase of 23%, while for the Chair Sit and Reach Test (CSRT), this same group was only 0.04 m away from reaching the target. For the Ramp Up Test (RUT), the subjects had to make a greater effort, and significant differences (p-value = 0.04) were evidenced in the force they applied to the device. For the Ramp Down Test (RDT), the Parkinson's group exhibited a decrease in torque, and there were statistically significant differences (p-value = 0.01) due to the increase in the complexity of the task. In the Timed Up and Go Test (TUGT), the subjects presented significant differences in torque (p-value of 0.05) but not in force (p-value of 0.22) due to the effect of the admittance controller implemented in the study. Finally, the results suggested that the walker, represents a valuable tool for assisting people with gait motor deficits in tasks that demanded more physical effort adapting its behavior to the specific needs of each user.
Emotions as Abstract Evaluation Criteria in Biological and Artificial Intelligences
Authors: Gros Claudius
Published: December 2021

Biological as well as advanced artificial intelligences (AIs) need to decide which goals to pursue. We review nature's solution to the time allocation problem, which is based on a continuously readjusted categorical weighting mechanism we experience introspectively as emotions. One observes phylogenetically that the available number of emotional states increases hand in hand with the cognitive capabilities of animals and that raising levels of intelligence entail ever larger sets of behavioral options. Our ability to experience a multitude of potentially conflicting feelings is in this view not a leftover of a more primitive heritage, but a generic mechanism for attributing values to behavioral options that can not be specified at birth. In this view, emotions are essential for understanding the mind. For concreteness, we propose and discuss a framework which mimics emotions on a functional level. Based on time allocation via emotional stationarity (TAES), emotions are implemented as abstract criteria, such as satisfaction, challenge and boredom, which serve to evaluate activities that have been carried out. The resulting timeline of experienced emotions is compared with the “character” of the agent, which is defined in terms of a preferred distribution of emotional states. The long-term goal of the agent, to align experience with character, is achieved by optimizing the frequency for selecting individual tasks. Upon optimization, the statistics of emotion experience becomes stationary.
Circulating Soluble CD163: A Potential Predictor for the Functional Outcome of Acute Ischemic Stroke
Authors: Sun Houchao , Zhang Xiaogang , Ma Jingxi , Liu Zhao , Qi Yunwen , Fang Li , Zheng Yongling , Cai Zhiyou
Published: December 2021

Background: CD163 is a transmembrane glycoprotein receptor expressed on innate immune cells that sheds from the cell membrane and circulates as a soluble form (sCD163). This study aimed to investigate the circulating levels and clinical relevance of soluble CD163 (sCD163) in acute ischemic stroke (AIS).

Methods: This study recruited 300 patients with AIS and 78 healthy controls. The patients were followed up for 1 month to observe the functional outcomes. The neurological functions of the patients were assessed using the NIH Stroke Scale (NIHSS) and the modified Rankin Scale (mRS). The plasma concentrations of sCD163 at the baseline (patient admission) were determined by ELISA.

Results: We found that patients with AIS had significantly higher plasma sCD163 concentrations than the healthy control. Patients with high sCD163 concentrations had better functional outcomes than patients with low sCD163 concentrations. The plasma sCD163 concentrations were positively associated with the NIHSS scores and infarction volume at the baseline. The plasma sCD163 was positively associated with the improvement of the NIHSS scores but was negatively associated with the risk of poor functional outcomes during follow-up.

Conclusions: These findings indicate that circulating sCD163 is a potential biomarker that is associated with disease severity and the functional outcome of AIS.
Real-World Cost-Effectiveness of Late Time Window Thrombectomy for Patients With Ischemic Stroke
Authors: Gao Lan , Bivard Andrew , Parsons Mark , Spratt Neil J. , Levi Christopher , Butcher Kenneth , Kleinig Timothy , Yan Bernard , Dong Qiang , Cheng Xin , Lou Min , Yin Congguo , Chen Chushuang , Wang Peng , Lin Longting , Choi Philip , Miteff Ferdinand , Moodie Marj
Published: December 2021

Background: To compare the cost-effectiveness of providing endovascular thrombectomy (EVT) for patients with ischemic stroke in the >4.5 h time window between patient groups who met and did not meet the perfusion imaging trial criteria.

Methods: A discrete event simulation (DES) model was developed to simulate the long-term outcome post EVT in patients meeting or not meeting the extended time window clinical trial perfusion imaging criteria at presentation, vs. medical treatment alone (including intravenous thrombolysis). The effectiveness of thrombectomy in patients meeting the landmark trial criteria (DEFUSE 3 and DAWN) was derived from a prospective cohort study of Australian patients who received EVT for ischemic stroke, between 2015 and 2019, in the extended time window (>4.5 h).

Results: Endovascular thrombectomy was shown to be a cost-effective treatment for patients satisfying the clinical trial criteria in our prospective cohort [incremental cost-effectiveness ratio (ICER) of $11,608/quality-adjusted life year (QALY) for DEFUSE 3-postive or $34,416/QALY for DAWN-positive]. However, offering EVT to patients outside of clinical trial criteria was associated with reduced benefit (−1.02 QALY for DEFUSE 3; −1.43 QALY for DAWN) and higher long-term patient costs ($8,955 for DEFUSE 3; $9,271 for DAWN), thereby making it unlikely to be cost-effective in Australia.

Conclusions: Treating patients not meeting the DAWN or DEFUSE 3 clinical trial criteria in the extended time window for EVT was associated with less gain in QALYs and higher cost. Caution should be exercised when considering this procedure for patients not satisfying the trial perfusion imaging criteria for EVT.
Neurodegeneration and Vascular Burden on Cognition After Midlife: A Plasma and Neuroimaging Biomarker Study
Authors: Huang Kuo-Lun , Hsiao Ing-Tsung , Chang Ting-Yu , Yang Shieh-Yueh , Chang Yeu-Jhy , Wu Hsiu-Chuan , Liu Chi-Hung , Wu Yi-Ming , Lin Kun-Ju , Ho Meng-Yang , Lee Tsong-Hai
Published: December 2021

Background and Objectives: Neurodegeneration and vascular burden are the two most common causes of post-stroke cognitive impairment. However, the interrelationship between the plasma beta-amyloid (Aβ) and tau protein, cortical atrophy and brain amyloid accumulation on PET imaging in stroke patients is undetermined. We aimed to explore: (1) the relationships of cortical thickness and amyloid burden on PET with plasma Aβ40, Aβ42, tau protein and their composite scores in stroke patients; and (2) the associations of post-stroke cognitive presentations with these plasma and neuroimaging biomarkers.

Methods: The prospective project recruited first-ever ischemic stroke patients around 3 months after stroke onset. The plasma Aβ40, Aβ42, and total tau protein were measured with the immunomagnetic reduction method. Cortical thickness was evaluated on MRI, and cortical amyloid plaque deposition was evaluated by 18F-florbetapir PET. Cognition was evaluated with Mini-Mental State Examination (MMSE), Geriatric Depression Scale (GDS), Dementia Rating Scale-2 (DRS-2).

Results: The study recruited 24 stroke patients and 13 normal controls. The plasma tau and tau*Aβ42 levels were correlated with mean cortical thickness after age adjustment. The Aβ42/Aβ40 ratio was correlated with global cortical 18F-florbetapir uptake value. The DRS-2 and GDS scores were associated with mean cortical thickness and plasma biomarkers, including Aβ42/Aβ40, tau, tau*Aβ42, tau/Aβ42, and tau/Aβ40 levels, in stroke patients.

Conclusion: Plasma Aβ, tau, and their composite scores were associated with cognitive performance 3 months after stroke, and these plasma biomarkers were correlated with corresponding imaging biomarkers of neurodegeneration. Further longitudinal studies with a larger sample size are warranted to replicate the study results.
Recognition of Electroencephalography-Related Features of Neuronal Network Organization in Patients With Schizophrenia Using the Generalized Choquet Integrals
Authors: Plechawska-Wójcik Małgorzata , Karczmarek Paweł , Krukow Paweł , Kaczorowska Monika , Tokovarov Mikhail , Jonak Kamil
Published: December 2021

In this study, we focused on the verification of suitable aggregation operators enabling accurate differentiation of selected neurophysiological features extracted from resting-state electroencephalographic recordings of patients who were diagnosed with schizophrenia (SZ) or healthy controls (HC). We built the Choquet integral-based operators using traditional classification results as an input to the procedure of establishing the fuzzy measure densities. The dataset applied in the study was a collection of variables characterizing the organization of the neural networks computed using the minimum spanning tree (MST) algorithms obtained from signal-spaced functional connectivity indicators and calculated separately for predefined frequency bands using classical linear Granger causality (GC) measure. In the series of numerical experiments, we reported the results of classification obtained using numerous generalizations of the Choquet integral and other aggregation functions, which were tested to find the most appropriate ones. The obtained results demonstrate that the classification accuracy can be increased by 1.81% using the extended versions of the Choquet integral called in the literature, namely, generalized Choquet integral or pre-aggregation operators.
Impact of Canal-Otolith Integration on Postural Control
Authors: Wagner Andrew R. , Kobel Megan J. , Merfeld Daniel M.
Published: December 2021

Roll tilt vestibular perceptual thresholds, an assay of vestibular noise, have recently been shown to be associated with suboptimal balance performance in healthy older adults. However, despite the strength of this correlation, the use of a categorical (i.e., pass/fail) balance assessment limits insight into the impacts of vestibular noise on postural sway. As a result, an explanation for this correlation has yet to be determined. We hypothesized that the correlation between roll tilt vestibular thresholds and postural control reflects a shared influence of sensory noise. To address this hypothesis, we measured roll tilt perceptual thresholds at multiple frequencies (0.2 Hz, 0.5 Hz, 1 Hz) and compared each threshold to quantitative measures of quiet stance postural control in 33 healthy young adults (mean = 24.9 years, SD = 3.67). Our data showed a significant linear association between 0.5 Hz roll tilt thresholds and the root mean square distance (RMSD) of the center of pressure in the mediolateral (ML; β = 5.31, p = 0.002, 95% CI = 2.1–8.5) but not anteroposterior (AP; β = 5.13, p = 0.016, 95% CI = 1.03–9.23) direction (Bonferroni corrected α of 0.006). In contrast, vestibular thresholds measured at 0.2 Hz and 1 Hz did not show a significant correlation with ML or AP RMSD. In a multivariable regression model, controlling for both 0.2 Hz and 1 Hz thresholds, the significant effect of 0.5 Hz roll tilt thresholds persisted (β = 5.44, p = 0.029, CI = 0.60–10.28), suggesting that the effect cannot be explained by elements shared by vestibular thresholds measured at the three frequencies. These data suggest that vestibular noise is significantly associated with the temporospatial control of quiet stance in the mediolateral plane when visual and proprioceptive cues are degraded (i.e., eyes closed, standing on foam). Furthermore, the selective association of quiet-stance sway with 0.5 Hz roll tilt thresholds, but not thresholds measured at lower (0.2 Hz) or higher (1.0 Hz) frequencies, may reflect the influence of noise that results from the temporal integration of noisy canal and otolith cues.
Kampo Formulae for the Treatment of Neuropathic Pain ∼ Especially the Mechanism of Action of Yokukansan ∼
Authors: Sunagawa Masataka , Takayama Yasunori , Kato Mami , Tanaka Midori , Fukuoka Seiya , Okumo Takayuki , Tsukada Mana , Yamaguchi Kojiro
Published: December 2021

Kampo medicine has been practiced as traditional medicine (TM) in Japan. Kampo medicine uses Kampo formulae that are composed of multiple crude drugs to make Kampo formulae. In Japan, Kampo formulae are commonly used instead of or combined with Western medicines. If drug therapy that follows the guidelines for neuropathic pain does not work or cannot be taken due to side effects, various Kampo formulae are considered as the next line of treatment. Since Kampo formulae are composed of two or more kinds of natural crude drugs, and their extracts contain many ingredients with pharmacological effects, one Kampo formula usually has multiple effects. Therefore, when selecting a formula, we consider symptoms other than pain. This review outlines the Kampo formulae that are frequently used for pain treatment and their crude drugs and the basic usage of each component. In recent years, Yokukansan (YKS) has become one of the most used Kampo formulae for pain treatment with an increasing body of baseline research available. We outline the known and possible mechanisms by which YKS exerts its pharmacologic benefits as an example of Kampo formulae’s potency and holistic healing properties.
Cell-Type-Specific Adaptions in Striatal Medium-Sized Spiny Neurons and Their Roles in Behavioral Responses to Drugs of Abuse
Authors: Allichon Marie-Charlotte , Ortiz Vanesa , Pousinha Paula , Andrianarivelo Andry , Petitbon Anna , Heck Nicolas , Trifilieff Pierre , Barik Jacques , Vanhoutte Peter
Published: December 2021

Drug addiction is defined as a compulsive pattern of drug-seeking- and taking- behavior, with recurrent episodes of abstinence and relapse, and a loss of control despite negative consequences. Addictive drugs promote reinforcement by increasing dopamine in the mesocorticolimbic system, which alters excitatory glutamate transmission within the reward circuitry, thereby hijacking reward processing. Within the reward circuitry, the striatum is a key target structure of drugs of abuse since it is at the crossroad of converging glutamate inputs from limbic, thalamic and cortical regions, encoding components of drug-associated stimuli and environment, and dopamine that mediates reward prediction error and incentive values. These signals are integrated by medium-sized spiny neurons (MSN), which receive glutamate and dopamine axons converging onto their dendritic spines. MSN primarily form two mostly distinct populations based on the expression of either DA-D1 (D1R) or DA-D2 (D2R) receptors. While a classical view is that the two MSN populations act in parallel, playing antagonistic functional roles, the picture seems much more complex. Herein, we review recent studies, based on the use of cell-type-specific manipulations, demonstrating that dopamine differentially modulates dendritic spine density and synapse formation, as well as glutamate transmission, at specific inputs projecting onto D1R-MSN and D2R-MSN to shape persistent pathological behavioral in response to drugs of abuse. We also discuss the identification of distinct molecular events underlying the detrimental interplay between dopamine and glutamate signaling in D1R-MSN and D2R-MSN and highlight the relevance of such cell-type-specific molecular studies for the development of innovative strategies with potential therapeutic value for addiction. Because drug addiction is highly prevalent in patients with other psychiatric disorders when compared to the general population, we last discuss the hypothesis that shared cellular and molecular adaptations within common circuits could explain the co-occurrence of addiction and depression. We will therefore conclude this review by examining how the nucleus accumbens (NAc) could constitute a key interface between addiction and depression.
Case Report: Pleuropulmonary Blastoma in a 2.5-Year-Old Boy: 18F-FDG PET/CT Findings
Authors: Ruan Dan , Sun Long
Published: December 2021

Pleuropulmonary blastoma (PPB) is a rare invasive primary malignancy in the thoracic cavity that occurs mainly in infants and children. It is often misdiagnosed and not treated correctly and promptly due to the lack of specificity of clinical symptoms and conventional imaging presentations. We report a 2.5-year-old boy who underwent X-ray chest radiography, chest CT, and 18F-FDG PET/CT. PET/CT images demonstrated a sizeable cystic-solid mass with heterogeneous increased glucose metabolism in the left thoracic cavity. The diagnosis of PPB (type II) was finally confirmed by a CT-guided puncture biopsy of the active tumor tissue. This case highlights the critical role of 18F-FDG PET/CT in the diagnosis of PPB in children.
Hepatocyte Growth Factor Overexpression Slows the Progression of 4NQO-Induced Oral Tumorigenesis
Authors: He Xiaoxi , Chen Si , Tang Yinghua , Zhao Xiaomin , Yan Liting , Wu Lihong , Wu Zhicong , Liu Weijia , Chen Xinming , Wang Xinhong
Published: December 2021

Objectives

To investigate the role of hepatocyte growth factor (HGF)/c-Met signaling in oral malignant transformation.

Methods

We used immunohistochemistry to investigate HGF and c-Met expression in 53 oral squamous cell carcinoma (OSCC) specimens and 21 adjacent nontumor specimens and evaluated the associations between HGF and c-Met expression and clinicopathological parameters. Additionally, HGF-overexpression transgenic (HGF-Tg) and wild-type (Wt) mice were treated with 4-nitroquinoline-1-oxide (4NQO) to induce oral carcinogenesis for 16 weeks. At 16, 20, and 24 weeks, tongue lesions were collected for clinical observation; estimation of HGF, c-Met, and PCNA expression; apoptosis (TUNEL) assays; and RNA sequencing (RNA-seq).

Results

HGF and c-Met were positively expressed in 92.5% and 64% of OSCC samples, respectively. High HGF expression was significantly associated with smaller tumor size (p = 0.006) and inferior TNM stage (p = 0.032). No correlation between HGF and c-Met levels and other clinical parameters or prognosis was noted. In addition, HGF and c-Met expression was elevated in 4NQO-induced lesions of Wt mice. Compared with Wt mice, HGF-Tg mice have lower tumor incidence, number, volume, and lesion grade. In addition, the percentage of PCNA-positive cells in Wt mice was significantly higher than that in HGF-Tg mice at different time points. At 16 weeks, HGF-Tg mice exhibited less apoptotic cells compared with Wt mice (p < 0.000), and these levels gradually increased until the levels were greater than that of Wt mice at 24 weeks (p < 0.000). RNA-seq data revealed that 140 genes were upregulated and 137 genes were downregulated in HGF-Tg mice. KEGG enrichment analysis showed that upregulated differentially expressed genes (DEGs) are highly correlated with oxidative and metabolic signaling and that downregulated DEGs are related to MAPK and PI3K-AKT signaling.

Conclusions

HGF and c-Met expression is upregulated in OSCC tissues and is associated with the occurrence and development of OSCC. HGF overexpression in normal oral epithelial tissue can inhibit 4NQO-induced tumorigenesis potentially through inhibiting proliferation and accelerating apoptosis via MAPK and PI3K-AKT signaling.
NK4 Regulates Laryngeal Squamous Cell Carcinoma Cell Properties and Inhibits Tumorigenicity by Modulating the DKK1/Wnt/β-Catenin Axis
Authors: Zhang Shoukai , Wei Hulai , Ha Xiaoqin , Zhang Yueyu , Guo Yufen
Published: December 2021

Objective

To investigate the effects of NK4 gene on the properties and tumorigenicity in laryngeal squamous cell carcinoma cell.

Methods

Here, we used the attenuated Salmonella carrying the NK4 gene to transfect the AMC-HN-8 cells and detected the expression of NK4 by the real-time quantitative polymerase chain reaction (q RT-PCR). The properties of NK4 gene was determined by MTT method, cell scratch test, and flow cytometry. A nude mouse tumorigenesis model was used to evaluate the effect of NK4 gene on the growth of AMC-HN-8 cells in vivo. While a western blot assay was used to assess the expression of DKK1, Wnt1 and β-Catenin in nude mouse tumors.

Results

qRT-PCR showed that the expression of NK4 in the transfection group was significantly higher than that in the control group (P<0.01), and the expression increased with the time of transfection. MTT results showed NK4 overexpression inhibited the proliferation of AMC-HN-8 cells, and the inhibitory activity no longer increased with increasing dose when 30% expression supernatant was added (P<0.01). Scratch experiment showed that NK4 overexpression decreased the cell migration ability (P<0.01). Annexin V/PI double staining experiment showed that NK4 gene induced AMC-HN-8 cell apoptosis (P<0.01), and cell cycle arrest in S phase (P<0.01). NK4 overexpression inhibited tumor formation ability of AMC-HN-8 cells in vivo (P <0.05). WB detection showed that the expression of DKK1 increased, Wnt1 and β-Catenin protein decreased after the high expression of NK4.

Conclusions

NK4 gene inhibit cell proliferation and migration, while promote cell apoptosis, and induce cell cycle arrest in S phase of laryngeal carcinoma AMC-HN-8 cells. NK4 overexpression inhibit the tumorigenesis ability of AMC-HN-8 cells, which may be related to the regulation of DKK1/Wnt1/β-Catenin signal axis.
In Pursuit of Distinctiveness: Transmembrane Nucleoporins and Their Disease Associations
Authors: Bindra Divya , Mishra Ram Kumar
Published: December 2021

The bi-directional nucleocytoplasmic shuttling of macromolecules like molecular signals, transcription factors, regulatory proteins, and RNAs occurs exclusively through Nuclear Pore Complex (NPC) residing in the nuclear membrane. This magnanimous complex is essentially a congregation of ~32 conserved proteins termed Nucleoporins (Nups) present in multiple copies and mostly arranged as subcomplexes to constitute a functional NPC. Nups participate in ancillary functions such as chromatin organization, transcription regulation, DNA damage repair, genome stabilization, and cell cycle control, apart from their central role as nucleocytoplasmic conduits. Thus, Nups exert a role in the maintenance of cellular homeostasis. In mammals, precisely three nucleoporins traverse the nuclear membrane, are called transmembrane Nups (TM-Nups), and are involved in multiple cellular functions. Owing to their vital roles in cellular processes and homeostasis, dysregulation of nucleoporin function is implicated in various diseases. The deregulated functioning of TM-Nups can thus act as an opportune window for the development of diseases. Indeed, mounting evidence exhibits a strong association of TM-Nups in cancer and numerous other physiological disorders. These findings have provided much-needed insights into the novel mechanisms of disease progression. While nucleoporin’s functions have often been summarized in the disease context, a focus on TM-Nups has always lacked. This review emphasizes the elucidation of distinct canonical and non-canonical functions of mammalian TM-Nups and the underlying mechanisms of their disease association.
Maternal and Fetal Outcomes of Acute Leukemia in Pregnancy: A Retrospective Study of 52 Patients
Authors: Wang Peng , Yang Zhen , Shan Meng , Lu Shenqi , Zhang Luwei , Li Shijia , Hu Shuhong , Tian Hong , Xu Yang , Wu Depei
Published: December 2021

Acute leukemia during pregnancy (P-AL) is a rare disease with limited data regarding the management and outcomes of mothers and fetuses. We retrospectively analyzed the characteristics, pregnancy outcomes and maternal and neonatal prognoses of 52 patients with P-AL collected from January 2013 to December 2020 in our center. Seventeen (32.7%) patients received chemotherapy during pregnancy (exposed cohort), while 35 (67.3%) received chemotherapy after abortion/delivery (nonexposed cohort). Twenty-six (50.0%) pregnancies ended with abortion, and 26 (50.0%) babies were born through spontaneous delivery or cesarean section. Seven infants (26.9%) were born in the exposed cohort, while 19 infants (73.1%) were born in the nonexposed cohort. Fetuses in the exposed cohort had lower gestational ages (P=0.030) and birth weights (P=0.049). Considering the safety of the fetus, seven patients in the exposed cohort received low-dose chemotherapy, one patient received all-trans retinoic acid (ATRA) and one patient only received corticosteroids as induction therapy. Patients received low-dose chemotherapy as induction therapy had a lower complete remission (CR) rate (P=0.041), and more patients in this group received HSCT (P=0.010) than patients received intensive chemotherapy. Patients who delayed chemotherapy in the nonexposed cohort experienced a trend toward a higher mortality rate than patients who received timely chemotherapy (P=0.191). The CR (P = 0.488), OS (P=0.655), and DFS (P=0.453) were similar between the exposed and nonexposed cohorts. Overall, the 4-year overall survival (OS) and disease-free survival (DFS) rates were estimated at 49.1% and 57.8%, respectively. All newborns were living, without deformities, or developmental and intellectual disabilities. Our study indicated that P-AL patients in the first trimester might tend to receive chemotherapy after abortion. Both the status of disease and patients’ willingness should be taken into consideration when clinicians were planning treatment strategies in the second or third trimester. Low-dose or delayed chemotherapy might decrease the efficacy of induction therapy and survival rate of patients, but HSCT could improve the prognosis.
Plasma EBV DNA: A Promising Diagnostic Marker for Endemic Burkitt Lymphoma
Authors: Xian Rena R. , Kinyera Tobias , Otim Isaac , Sampson Joshua N. , Nabalende Hadijah , Legason Ismail D. , Stone Jennifer , Ogwang Martin D. , Reynolds Steven J. , Kerchan Patrick , Bhatia Kishor , Goedert James J. , Mbulaiteye Sam M. , Ambinder Richard F.
Published: December 2021

Endemic Burkitt lymphoma (eBL) is the most common childhood cancer in regions of equatorial Africa where P. falciparum malaria is holoendemic. The tumor is consistently associated with Epstein-Barr virus (EBV). Screening for EBV DNA in plasma in a high-risk population in Hong Kong has been shown to be useful in facilitating the early diagnosis of nasopharyngeal carcinoma, another EBV-associated tumor. Here, we investigate plasma EBV as a diagnostic marker for eBL in children in Uganda. We studied plasma specimens from 25 children with eBL and 25 controls matched for age (<3-16 years), gender and geography, including many with asymptomatic P. falciparum infection. These specimens were previously collected under the auspices of the EMBLEM (Epidemiology of Burkitt lymphoma in East African children and minors) study. After cell-free DNA isolation, plasma EBV DNA was measured using a quantitative PCR assay that amplifies the large internal repeats of the EBV genome. All children with eBL had measurable plasma EBV, as compared to 84% of control children. The median plasma EBV DNA level was 5.23 log10 copies/mL (interquartile range 3.54-6.08 log10 copies/mL) in children with eBL. In contrast, the median plasma EBV DNA level was 0.37 log10 copies/mL (interquartile range 0.18-1.05 log10 copies/mL) in children without lymphoma. An EBV threshold of 2.52 log10 copies/mL yielded a sensitivity of.88 and a specificity of 1. The estimated AUC was 0.936 (95% CI: 0.8496 – 1.00) for the corresponding ROC curve. Plasma EBV copy number did not depend on age, gender, or malaria screening status. However, two control children with asymptomatic P. falciparum infection and parasitemia also had high plasma EBV copy number. Our analysis suggests that measurements of EBV copy number in plasma may be useful in identifying children with eBL versus control children. A promising area for future research is the differentiation of high copy number associated with tumor versus high copy number associated with asymptomatic parasitemia.
Ilexsaponin A1 Ameliorates Diet-Induced Nonalcoholic Fatty Liver Disease by Regulating Bile Acid Metabolism in Mice
Authors: Zhao Wen-wen , Xiao Meng , Wu Xia , Li Xiu-wei , Li Xiao-xi , Zhao Ting , Yu Lan , Chen Xiao-qing
Published: December 2021

Bile acid (BA) metabolism is an attractive therapeutic target in nonalcoholic fatty liver disease (NAFLD). We aimed to investigate the effect of ilexsaponin A1 (IsA), a major bioactive ingredient of Ilex, on high-fat diet (HFD)-induced NAFLD in mice with a focus on BA homeostasis. Male C57BL/6J mice were fed an HFD to induce NAFLD and were treated with IsA (120 mg/kg) for 8 weeks. The results showed that administration of IsA significantly decreased serum total cholesterol (TC), attenuated liver steatosis, and decreased total hepatic BA levels in HFD-induced NAFLD mice. IsA-treated mice showed increased BA synthesis in the alternative pathway by upregulating the gene expression levels of sterol 27-hydroxylase (CYP27A1) and cholesterol 7b-hydroxylase (CYP7B1). IsA treatment accelerated efflux and decreased uptake of BA in liver by increasing hepatic farnesoid X receptor (FXR) and bile salt export pump (BSEP) expression, and reducing Na+-taurocholic acid cotransporting polypeptide (NTCP) expression. Alterations in the gut microbiota and increased bile salt hydrolase (BSH) activity might be related to enhanced fecal BA excretion in IsA-treated mice. This study demonstrates that consumption of IsA may prevent HFD-induced NAFLD and exert cholesterol-lowering effects, possibly by regulating the gut microbiota and BA metabolism.
Proton Pump Inhibitors Were Associated With Reduced Pseudocysts in Acute Pancreatitis: A Multicenter Cohort Study
Authors: Zhang Shengyu , Han Ziying , Zhang Yuelun , Gao Xiaomao , Zheng Shicheng , Wang Ruifeng , Wu Dong
Published: December 2021

Background: Acute pancreatitis (AP) is a systemic inflammatory disorder with a wide spectrum of clinical symptoms that can range from mild to severe. Previous preclinical study results suggest that proton pump inhibitors (PPIs) can inhibit exocrine pancreatic secretion and exert anti-inflammatory properties, which might in turn improve the outcome of AP.

Aim: We conducted this multicenter, retrospective cohort study to investigate the potential effects of PPIs on the mortality, and total duration of hospital stay and local complication occurrence of patients with AP.

Methods: A total of 858 patients with AP were included. All patients presented to the hospital within 48 h of symptom onset and were divided into the following two groups: patients who were treated with PPIs (n = 684) and those not treated with PPIs (n = 174). We used propensity score matching (PSM) analysis to reduce confounding bias before comparing the outcomes between the two groups.

Results: Before PSM analysis, there were significant differences in a number of parameters between the two groups, including age, sex, hematocrit, blood urea nitrogen, peritonitis signs, Ranson’s score, and Acute Physiology Chronic Health Evaluation II score and organ failure occurrence. Before PSM, the PPIs group had a higher rate of mortality than the control group [RR = 1.065; 95% confidence ratio (CI) 1.045–1.086; p = 0.001]. After PSM, there was no significant difference in mortality (RR = 1.009; 95% CI, 0.999–1.019; p = 0.554) or total hospital stay (p = 0.856), although the PPIs group had a lower occurrence of pancreatic pseudocyst (RR = 0.416; 95% CI 0.221–0.780; p = 0.005).

Conclusion: This study showed that PPIs therapy was not associated with reduced mortality or total hospital stay, but was associated with a reduction in the occurrence of pseudocysts in patients with acute pancreatitis.