bluuebunny/crossref_metadata_2025 huggingface dataset:
MRGPRX2 and Adverse Drug Reactions
Authors: McNeil Benjamin D.
Published: August 2021

Many adverse reactions to therapeutic drugs appear to be allergic in nature, and are thought to be triggered by patient-specific Immunoglobulin E (IgE) antibodies that recognize the drug molecules and form complexes with them that activate mast cells. However, in recent years another mechanism has been proposed, in which some drugs closely associated with allergic-type events can bypass the antibody-mediated pathway and trigger mast cell degranulation directly by activating a mast cell-specific receptor called Mas-related G protein-coupled receptor X2 (MRGPRX2). This would result in symptoms similar to IgE-mediated events, but would not require immune priming. This review will cover the frequency, severity, and dose-responsiveness of allergic-type events for several drugs shown to have MRGPRX2 agonist activity. Surprisingly, the analysis shows that mild-to-moderate events are far more common than currently appreciated. A comparison with plasma drug levels suggests that MRGPRX2 mediates many of these mild-to-moderate events. For some of these drugs, then, MRGPRX2 activation may be considered a regular and predictable feature after administration of high doses.
Innate Immune System Orchestrates Metabolic Homeostasis and Dysfunction in Visceral Adipose Tissue During Obesity
Authors: Zhen Yu , Shu Wentao , Hou Xintong , Wang Yinan
Published: August 2021

Arising incidence of metabolic disorders and related diseases caused by obesity is a global health concern. Elucidating the role of the immune system in this process will help to understand the related mechanisms and develop treatment strategies. Here, we have focused on innate immune cells in visceral adipose tissue (VAT) and summarized the roles of these cells in maintaining the homeostasis of VAT. Furthermore, this review reveals the importance of quantitative and functional changes of innate immune cells when the metabolic microenvironment changes due to obesity or excess lipids, and confirms that these changes eventually lead to the occurrence of chronic inflammation and metabolic diseases of VAT. Two perspectives are reviewed, which include sequential changes in various innate immune cells in the steady state of VAT and its imbalance during obesity. Cross-sectional interactions between various innate immune cells at the same time point are also reviewed. Through delineation of a comprehensive perspective of VAT homeostasis in obesity-induced chronic inflammation, and ultimately metabolic dysfunction and disease, we expect to clarify the complex interactive networks among distinct cell populations and propose that these interactions should be taken into account in the development of biotherapeutic strategies.
Physiological Synchrony of the Broad Bean Weevil, Bruchus rufimanus Boh., to the Host Plant Phenology, Vicia faba L.
Authors: Hamidi Rachid , Taupin Pierre , Frérot Brigitte
Published: August 2021

The aims of the study were to understand the physiological and phenological relationship between Bruchus rufimanus and Vicia faba in the perspective of IPM strategies. V. faba, an important food resource for humans and livestock is the main host plant of B. rufimanus. Adults feed on the pollen, females lay eggs on pods, and larvae develop into the seeds. Pending the blooming phase, the weevil may feed on the pollen from wild plants. Depending on the sowing date, the phenological time lag should lead the plant parts, most utilized by the weevil, less or more available during the key life stages of the pest. The aims of the study were therefore (1) to assess the impact of the sowing date (i.e., cultivars) on the phenological relationship between B. rufimanus and V. faba, and (2) to identify alternative pollen resources during the vegetative phase. Insects were collected weekly on two cultivars: winter-sown and spring-sown fields. Ovarian development, fecundity, and diet were monitored using dissected adults. Results showed that immature adults colonized the blooming winter-sown field and then 2 weeks later, the blooming spring-sown field. Sexual maturity of the weevils is related with V. faba pollen consumption. The sexual maturity of females increased with the growing density of flowers and the first pods were quickly covered with eggs. In spring-sown field, first pods grew 19 days later, while collected females in winter sown field had already laid most of their eggs. Feeding tests were carried using flowers collected from plants growing close to the fields: wild chervil, oilseed rape and wild Prunus. All this pollen were consumed by the weevils. The study showed a perfect synchrony between the host and the pest. Late sowing date and control of the early blooming wild plants surrounding the crops might reduce the attacks in field beans. More broadly, the study helps to understand the eco-ethology of the insect in cultivated areas.
Cucumaria in Russian Waters of the Barents Sea: Biological Aspects and Aquaculture Potential
Authors: Dvoretsky Alexander G. , Dvoretsky Vladimir G.
Published: August 2021

Sea cucumbers are a popular luxury and delicacy food items in Asian markets. These echinoderms possess a wide range of bioactive substances that can be used to produce pharmaceutical products. Recent depletion of natural populations of sea cucumbers requires involving new objects both in commercial harvesting and aquaculture. The northern sea cucumber Cucumaria frondosa is the most abundant sea cucumber in the Barents Sea. In this paper, we summarized literature data on the biology of this polar species to evaluate its fishery and aquaculture potential in the area. This eurythermic sea cucumber is typically occurs at 20–100 m depth. Cucumaria mainly colonize rocky or pebbly bottoms. Their main food items are detritus, pellets, phytoplankton, and small planktonic crustaceans. Spawning is registered in February–May. The age of commercial specimens (body length 25–30 cm, wet weight 300–350 g) is 10 years. The most abundant stocks of C. frondosa are registered in the central and south-eastern parts of the sea. Due to the low growth rate of Cucumaria the most appropriate cultivation method for these holothurians is a combination of larval culture and sea ranching. Coastal sites of the Barents Sea merit all the criteria for sea ranching of Cucumaria, but the development of their extensive aquaculture requires significant investments with long pay-back periods.
Evaluation of Wave-Ice Parameterization Models in WAVEWATCH III® Along the Coastal Area of the Sea of Okhotsk During Winter
Authors: Iwasaki Shinsuke , Otsuka Junichi
Published: August 2021

Ocean surface waves tend to be attenuated by interaction with sea ice. In this study, six sea ice models in the third-generation wave model WAVEWATCH III® (WW3) were used to estimate wave fields over the Sea of Okhotsk (SO). The significant wave height (Hs) and mean wave period (Tm) derived from the models were evaluated with open ocean and ice-covered conditions, using SO coastal area buoy observations. The models were validated for a period of 3 years, 2008–2010. Additionally, the impact of sea ice on wave fields was demonstrated by model experiments with and without sea ice. In the open ocean condition, the root-mean square error (RMSE) and correlation coefficient for hourly Hs are 0.3 m and 0.92, and for hourly Tm 0.97 s and 0.8. In contrast, for the ice-covered condition, the averaged RMSE and correlation coefficient from all models are 0.44 m (1.6 s) and 0.8 (0.6) for Hs (Tm), respectively. Therefore, except for the bias, the accuracy of model results for the ice-covered condition is lower than for the open water condition. However, there is a significant difference between the six sea ice models. For Hs, the empirical formula whereby attenuation depends on the frequency relatively agrees with the buoy observation. For Tm, the empirical formula that is a function of Hs is better than those of other simulations. In addition, the simulations with sea ice drastically improved the wave field bias in coastal areas compared to the simulations without sea ice. Moreover, sea ice changed the monthly Hs (Tm) by more than 1 m (3 s) in the northwestern part of the SO, which has a high ice concentration.
Identification of Risk Areas for Intestinal Schistosomiasis, Based on Malacological and Environmental Data and on Reported Human Cases
Authors: Coelho Paulo R. S. , Ker Fabrício T. O. , Araújo Amanda D. , Guimarães Ricardo. J. P. S. , Negrão-Corrêa Deborah A. , Caldeira Roberta L. , Geiger Stefan M.
Published: August 2021

The aim of the present study was to use an integrated approach for the identification of risk areas for Schistosoma mansoni transmission in an area of low endemicity in Minas Gerais, Brazil. For that, areas of distribution of Biomphalaria glabrata were identified and were related to environmental variables and communities with reported schistosomiasis cases, in order to determine the risk of infection by spatial analyses with predictive models. The research was carried out in the municipality of Alvorada de Minas, with data obtained between the years 2017 and 2019 inclusive. The Google Earth Engine was used to obtain geo-climatic variables (temperature, precipitation, vegetation index and digital elevation model), R software to determine Pearson's correlation and MaxEnt software to obtain an ecological model. ArcGis Software was used to create maps with data spatialization and risk maps, using buffer models (diameters: 500, 1,000 and 1,500 m) and CoKriging. Throughout the municipality, 46 collection points were evaluated. Of these, 14 presented snails of the genus Biomphalaria. Molecular analyses identified the presence of different species of Biomphalaria, including B. glabrata. None of the snails eliminated S. mansoni cercariae. The distribution of B. glabrata was more abundant in areas of natural vegetation (forest and cerrado) and, for spatial analysis (Buffer), the main risk areas were identified especially in the main urban area and toward the northern and eastern extensions of the municipality. The distribution of snails correlated with temperature and precipitation, with the latter being the main variable for the ecological model. In addition, the integration of data from malacological surveys, environmental characterization, fecal contamination, and data from communities with confirmed human cases, revealed areas of potential risk for infection in the northern and eastern regions of the municipality. In the present study, information was integrated on epidemiological aspects, transmission and risk areas for schistosomiasis in a small, rural municipality with low endemicity. Such integrated methods have been proposed as important tools for the creation of schistosomiasis transmission risk maps, serve as an example for other communities and can be used for control actions by local health authorities, e.g., indicate priority sectors for sanitation measures.
A Combined Digital PCR and Next Generation DNA-Sequencing Based Approach for Tracking Nearshore Pollutant Dynamics Along the Southwest United States/Mexico Border
Authors: Zimmer-Faust Amity G. , Steele Joshua A. , Xiong Xianyi , Staley Christopher , Griffith Madison , Sadowsky Michael J. , Diaz Margarita , Griffith John F.
Published: August 2021

Ocean currents, multiple fecal bacteria input sources, and jurisdictional boundaries can complicate pollution source tracking and associated mitigation and management efforts within the nearshore coastal environment. In this study, multiple microbial source tracking tools were employed to characterize the impact and reach of an ocean wastewater treatment facility discharge in Mexico northward along the coast and across the Southwest United States- Mexico Border. Water samples were evaluated for fecal indicator bacteria (FIB), Enterococcus by culture-based methods, and human-associated genetic marker (HF183) and Enterococcus by droplet digital polymerase chain reaction (ddPCR). In addition, 16S rRNA gene sequence analysis was performed and the SourceTracker algorithm was used to characterize the bacterial community of the wastewater treatment plume and its contribution to beach waters. Sampling dates were chosen based on ocean conditions associated with northern currents. Evidence of a gradient in human fecal pollution that extended north from the wastewater discharge across the United States/Mexico border from the point source was observed using human-associated genetic markers and microbial community analysis. The spatial extent of fecal contamination observed was largely dependent on swell and ocean conditions. These findings demonstrate the utility of a combination of molecular tools for understanding and tracking specific pollutant sources in dynamic coastal water environments.
Application of Engineered Bacteriophage T7 in the Detection of Bacteria in Food Matrices
Authors: Wisuthiphaet Nicharee , Yang Xu , Young Glenn M. , Nitin Nitin
Published: August 2021

Detection of pathogens in a food matrix is challenging due to various constraints including complexity and the cost of sample preparation for microbial analysis from food samples, time period for the detection of pathogens, and high cost and specialized resources required for advanced molecular assays. To address some of these key challenges, this study illustrates a simple and rapid colorimetric detection of target bacteria in distinct food matrices, including fresh produce, without prior isolation of bacteria from a food matrix. This approach combines bacteriophage-induced expression of an exogenous enzyme, alkaline phosphatase, the specific colorimetric substrate that generates insoluble color products, and a simple filtration method to localize the generation of colored signal. Using this approach, this study demonstrates the specific detection of inoculated Escherichia coli in coconut water and baby spinach leaves. Without isolating bacteria from the selected food matrices and using a food sample size that is representative of industrial samples, the inoculated samples were added to the enrichment broth for a short period (5 h) and incubated with an engineered bacteriophage T7 with a phoA gene. The incubation period with the engineered bacteriophage was 30 min for liquid samples and 2 h for fresh produce samples. The samples were then filtered through a 0.2-micron polycarbonate membrane and incubated with a colorimetric substrate, i.e., nitro blue tetrazolium/5-bromo-4-chloro-3-indolyl phosphate (NBT/BCIP). This substrate forms a dark purple precipitate upon interactions with the released enzyme on a filter membrane. This approach successfully detected 10 CFU/ml of E. coli in coconut water and 102 CFU/g of E. coli on baby spinach leaves with 5 h of enrichment. Success of this approach illustrates potential for detecting target bacteria in food systems using a simple visual assay and/or quantitative colorimetric measurements.
Human and Zoonotic Dermatophytoses: Epidemiological Aspects
Authors: Segal Esther , Elad Daniel
Published: August 2021

Introduction

Dermatophytes are a group of molds characterized by the ability to produce keratinases, thereby carving out for themselves specific ecological niches. Their traditional division into three genera, Trichophyton, Microsporum, and Epidermophyton has been expanded to nine and the species in each genus were modified. Dermatophytes are among the most prevalent causes of human and animal mycoses. Their epidemiology is influenced by various factors. These factors may be evolutive such as the predilected environment of the fungus, namely, humans (anthropophilic), animals (zoophilic), or environment (geophilic), is evolutionary and thus may require centuries to develop. Many other factors, however, result from a variety of causes, affecting the epidemiology of dermatophytoses within a shorter time frame.

Objective

This review aims at summarizing the factors that have modified the epidemiology of dermatophytoses during the last decades.

Results

Geographic and climatic conditions, demography such as age and gender, migration, socio-economic conditions, lifestyle, and the environment have had an impact on changes in the epidemiology of dermatophytoses, as have changes in the pattern of human interaction with animals, including pets, farm, and wild animals. A typical example of such changes is the increased prevalence of Trichophyton tonsurans, which spread from Latin America to the United States and subsequently becoming a frequent etiological agent of tinea capitis in Africa, Middle East, and other areas.

Conclusion

The comprehension of the epidemiology of dermatophytoses has a major bearing on their prevention and treatment. Since it is undergoing continuous changes, periodic assessments of the most recent developments of this topic are required. This article aims at providing such an overview.
CUX1 Facilitates the Development of Oncogenic Properties Via Activating Wnt/β-Catenin Signaling Pathway in Glioma
Authors: Feng Fan , Zhao Zongqing , Zhou Yunfei , Cheng Yanhao , Wu Xiujie , Heng Xueyuan
Published: August 2021

Background: Homeobox cut like 1 (CUX1), which often presents aberrated expression in many cancer cells, exerts a crucial role in tumorigenesis. Evidence describing CUX1 in gliomagenesis is scarce, and the effects of CUX1 on the Wnt/β-catenin pathway have not been reported. Our study aimed to explore the biological functions and molecular mechanisms involved in CUX1 activity in glioma.

Methods: Datasets for bioinformatics analysis were obtained from the GEO, TCGA, CGGA, GTEX and CCLE databases. qRT-PCR, western blotting (WB), and immunohistochemistry (IHC) assays were used to investigate the expression patterns of CUX1 among glioma and brain tissues. CUX1 knockdown and overexpression vectors were transfected into glioma cell lines, the CCK-8, clone formation assay, wound healing, Transwell assay, and flow cytometry were performed to detect changes in cell viability, invasiveness, and the cell cycle. WB and immunofluorescence (IF) assays were used to explore changes in cell cycle-related and Wnt/β-catenin signaling protein levels.

Results: Overexpression of CUX1 was identified in glioma tissues, and especially in glioblastoma (GBM), when compared to normal controls and correlated with poor prognosis. In comparison with untreated cells, TJ905 glioma cells overexpressing CUX1 showed higher proliferation and invasion abilities and S phase cell-cycle arrest, while the knockdown of CUX1 suppressed cell invasive ability and induced G1 phase arrest. Active Wnt/β-catenin signaling was enriched and clustered in a CUX1-associated GSEA/GSVA analysis. IF and WB assays indicated that CUX1 regulated the distribution of Axin2/β-catenin in glioma cells and regulated the expression of proteins downstream of the Wnt/β-catenin signaling pathway, suggesting that CUX1 served as an upstream positive regulator of the Wnt/β-catenin pathway. Finally, the knockdown of Axin2 or β-catenin could reverse the tumor-promoting effects caused by CUX1 overexpression, suggesting that CUX1 induced gliomagenesis and malignant phenotype by activating the Wnt/β-catenin signaling pathway.

Conclusion: Our data suggested that the transcription factor CUX1 could be a novel therapeutic target for glioma with gene therapy.
Computational Study on DNA Repair: The Roles of Electrostatic Interactions Between Uracil-DNA Glycosylase (UDG) and DNA
Authors: Xie Yixin , Karki Chitra B. , Chen Jiawei , Liu Dongfang , Li Lin
Published: August 2021

Uracil-DNA glycosylase (UDG) is one of the most important base excision repair (BER) enzymes involved in the repair of uracil-induced DNA lesion by removing uracil from the damaged DNA. Uracil in DNA may occur due to cytosine deamination or deoxy uridine monophosphate (dUMP) residue misincorporation during DNA synthesis. Medical evidences show that an abnormal expression of UDG is related to different types of cancer, including colorectal cancer, lung cancer, and liver cancer. Therefore, the research of UDG is crucial in cancer treatment and prevention as well as other clinical activities. Here we applied multiple computational methods to study UDG in several perspectives: Understanding the stability of the UDG enzyme in different pH conditions; studying the differences in charge distribution between the pocket side and non-pocket side of UDG; analyzing the field line distribution at the interfacial area between UDG and DNA; and performing electrostatic binding force analyses of the special region of UDG (pocket area) and the target DNA base (uracil) as well as investigating the charged residues on the UDG binding pocket and binding interface. Our results show that the whole UDG binding interface, and not the UDG binding pocket area alone, provides the binding attractive force to the damaged DNA at the uracil base.
The Contribution of White Matter Diffusion and Cortical Perfusion Pathology to Vascular Cognitive Impairment: A Multimode Imaging-Based Machine Learning Study
Authors: Wang Yao , Lu Peiwen , Zhan Yafeng , Wu Xiaowei , Qiu Yage , Wang Zheng , Xu Qun , Zhou Yan
Published: August 2021

Widespread impairments in white matter and cerebrovascular integrity have been consistently implicated in the pathophysiology of patients with small vessel disease (SVD). However, the neural circuit mechanisms that underlie the developing progress of clinical cognitive symptoms remain largely elusive. Here, we conducted cross-modal MRI scanning including diffusion tensor imaging and arterial spin labeling in a cohort of 113 patients with SVD, which included 74 patients with vascular mild cognitive impairment (vMCI) and 39 patients without vMCI symptoms, and hence developed multimode imaging-based machine learning models to identify markers that discriminated SVD subtypes. Diffusion and perfusion features, respectively, extracted from individual white matter and gray matter regions were used to train three sets of classifiers in a nested 10-fold fashion: diffusion-based, perfusion-based, and combined diffusion-perfusion-based classifiers. We found that the diffusion-perfusion combined classifier achieved the highest accuracy of 72.57% with leave-one-out cross-validation, with the diffusion features largely spanning the capsular lateral pathway of the cholinergic tracts, and the perfusion features mainly distributed in the frontal-subcortical-limbic areas. Furthermore, diffusion-based features within vMCI group were associated with performance on executive function tests. We demonstrated the superior accuracy of using diffusion-perfusion combined multimode imaging features for classifying vMCI subtype out of a cohort of patients with SVD. Disruption of white matter integrity might play a critical role in the progression of cognitive impairment in patients with SVD, while malregulation of coritcal perfusion needs further study.
Effectiveness and Safety of Acupuncture for Vascular Cognitive Impairment: A Systematic Review and Meta-Analysis
Authors: Su Xin-Tong , Sun Ning , Zhang Na , Wang Li-Qiong , Zou Xuan , Li Jin-Ling , Yang Jing-Wen , Shi Guang-Xia , Liu Cun-Zhi
Published: August 2021

Background: Acupuncture may be a promising complementary therapy for vascular cognitive impairment (VCI) and has been extensively applied in China. However, its potential effects remain uncertain, and the clinical findings are inconsistent. This review aimed to systematically appraise the overall effectiveness and safety of acupuncture in treating VCI.

Methods: To investigate the effects of acupuncture on VCI from inception to February 28, 2021 using randomized clinical trials (RCTs), seven electro-databases [Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, Embase, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Literature Database (CBM), VIP, and Wanfang] were searched. Two independent investigators identified the eligible RCTs and extracted data into predesigned forms. The risk of bias (ROB) within each individual trial was evaluated using the Cochrane Collaboration's tool. Meta-analyses were conducted for calculating comparative effects in the RevMan software (version 5.3). The strength of attained evidence was rated using the online GRADEpro approach.

Results: A total of 48 RCTs involving 3,778 patients with VCI were included. The pooled data demonstrated that acupuncture was more beneficial for a global cognitive function [mean difference (MD) 1.86, 95% CI 1.19–2.54, p < 0.01] and activities of daily living (MD −3.08, 95% CI −4.81 to −1.35, p < 0.01) compared with western medicine (WM). The favorable results were also observed when acupuncture was combined with WM (MD 2.37, 95% CI 1.6–3.14, p < 0.01) or usual care (UC, MD 4.4, 95% CI 1.61–7.19, p = 0.002) in comparison with the corresponding control conditions. Meanwhile, the subgroup analysis did not indicate a statistical effect difference between manual acupuncture (MA) and electroacupuncture (EA) (inter-group I2 < 50% and p > 0.1) when comparing acupuncture with WM. There were no significant differences in the occurrence of adverse events (AEs) between the acupuncture group and the control group (p > 0.05). Owing to the poor methodological quality and considerable heterogeneity among studies, the certainty of the evidence was low or very low.

Conclusions: This review suggests that acupuncture as a monotherapy or an adjuvant therapy may play a positive role in improving the cognition and daily performance of VCI patients associated with few side effects. The difference in styles may not significantly influence its effectiveness. More rigorously designed and preregistered RCTs are highly desirable to verify the therapeutic benefits and determine an optimal acupuncture paradigm. The methodological and reporting quality of future researches should be enhanced by adhering to authoritative standardized statements.

Systematic Review Registration: [PROSPERO], identifier [No. CRD42017071820].
Abnormalities of Brain White Matter in Type 2 Diabetes Mellitus: A Meta-Analysis of Diffusion Tensor Imaging
Authors: Huang Li , Zhang Qingqing , Tang Tong , Yang Minguang , Chen Cong , Tao Jing , Liang Shengxiang
Published: August 2021

Aims: The study aimed to conduct a meta-analysis to determine the abnormalities of white matter in patients with type 2 diabetes mellitus (T2DM) by identifying the consistency of diffusion tensor imaging (DTI).

Method: The literature for DTI comparing patients with T2DM with controls published before October 30, 2020, were reviewed in PubMed, Web of Science, Embase, CNKI, and Wan Fang databases. The meta-analysis was performed using the activation likelihood estimation (ALE) method, including 12 reports and 381 patients with T2DM.

Results: The meta-analysis identified 10 white matter regions that showed a consistent reduction of fractional anisotropy (FA) in patients with T2DM, including genu of the corpus callosum, the body of corpus callosum, bilateral anterior corona radiata, bilateral superior corona radiata, bilateral cingulum, and bilateral superior fronto-occipital fasciculus.

Conclusion: This study revealed the abnormal characteristics of white matter in T2DM, which would be helpful to understand the underlying neuropathological and physiological mechanisms of T2DM and provide evidence for clinical diagnosis and treatment.
Deficiency of TRIM32 Impairs Motor Function and Purkinje Cells in Mid-Aged Mice
Authors: Zhu Jian-Wei , Jia Wei-Qiang , Zhou Hui , Li Yi-Fei , Zou Ming-Ming , Wang Zhao-Tao , Wu Bing-Shan , Xu Ru-Xiang
Published: August 2021

Proper functioning of the cerebellum is crucial to motor balance and coordination in adult mammals. Purkinje cells (PCs), the sole output neurons of the cerebellar cortex, play essential roles in cerebellar motor function. Tripartite motif-containing protein 32 (TRIM32) is an E3 ubiquitin ligase that is involved in balance activities of neurogenesis in the subventricular zone of the mammalian brain and in the development of many nervous system diseases, such as Alzheimer's disease, autism spectrum disorder, attention deficit hyperactivity disorder. However, the role of TRIM32 in cerebellar motor function has never been examined. In this study we found that motor balance and coordination of mid-aged TRIM32 deficient mice were poorer than those of wild-type littermates. Immunohistochemical staining was performed to assess cerebella morphology and TRIM32 expression in PCs. Golgi staining showed that the extent of dendritic arborization and dendritic spine density of PCs were decreased in the absence of TRIM32. The loss of TRIM32 was also associated with a decrease in the number of synapses between parallel fibers and PCs, and in synapses between climbing fibers and PCs. In addition, deficiency of TRIM32 decreased Type I inositol 1,4,5-trisphosphate 5-phosphatase (INPP5A) levels in cerebellum. Overall, this study is the first to elucidate a role of TRIM32 in cerebellar motor function and a possible mechanism, thereby highlighting the importance of TRIM32 in the cerebellum.
The Central Role of Hypothermia and Hyperactivity in Anorexia Nervosa: A Hypothesis
Authors: Smith Lucille Lakier
Published: August 2021

Typically, the development of anorexia nervosa (AN) is attributed to psycho-social causes. Several researchers have recently challenged this view and suggested that hypothermia and hyperactivity (HyAc) are central to AN. The following hypothesis will attempt to clarify their role in AN. Anorexia nervosa patients (ANs) have significantly lower core temperatures (Tcore) compared to healthy controls (HCs). This reduced temperature represents a reset Tcore that needs to be maintained. However, ANs cannot maintain this Tcore due primarily to a reduced basal metabolic rate (BMR); BMR usually supplies heat to sustain Tcore. Therefore, to generate the requisite heat, ANs revert to the behavioral-thermoregulatory strategy of HyAc. The majority of ANs (~89%) are reportedly HyAc. Surprisingly, engagement in HyAc is not motivated by a conscious awareness of low Tcore, but rather by the innocuous sensation of “cold- hands” frequently reported by ANs. That is, local hand-thermoreceptors signal the brain to initiate HyAc, which boosts perfusion of the hands and alters the sensation of “cold-discomfort” to one of “comfort.” This “rewarding” consequence encourages repetition/habit formation. Simultaneously, hyperactivity increases the availability of heat to assist with the preservation of Tcore. Additionally, HyAc induces the synthesis of specific brain neuromodulators that suppress food intake and further promote HyAc; this outcome helps preserve low weight and perpetuates this vicious cycle. Based on this hypothesis and supported by rodent research, external heat availability should reduce the compulsion to be HyAc to thermoregulate. A reduction in HyAc should decrease the production of brain neuromodulators that suppress appetite. If verified, hopefully, this hypothesis will assist with the development of novel treatments to aid in the resolution of this intractable condition.
GABAB Receptor-Mediated Impairment of Intermediate Progenitor Maturation During Postnatal Hippocampal Neurogenesis of Newborn Rats
Authors: Gustorff Charlotte , Scheuer Till , Schmitz Thomas , Bührer Christoph , Endesfelder Stefanie
Published: August 2021

The neurotransmitter GABA and its receptors assume essential functions during fetal and postnatal brain development. The last trimester of a human pregnancy and early postnatal life involves a vulnerable period of brain development. In the second half of gestation, there is a developmental shift from depolarizing to hyperpolarizing in the GABAergic system, which might be disturbed by preterm birth. Alterations of the postnatal GABA shift are associated with several neurodevelopmental disorders. In this in vivo study, we investigated neurogenesis in the dentate gyrus (DG) in response to daily administration of pharmacological GABAA (DMCM) and GABAB (CGP 35348) receptor inhibitors to newborn rats. Six-day-old Wistar rats (P6) were daily injected (i.p.) to postnatal day 11 (P11) with DMCM, CGP 35348, or vehicle to determine the effects of both antagonists on postnatal neurogenesis. Due to GABAB receptor blockade by CGP 35348, immunohistochemistry revealed a decrease in the number of NeuroD1 positive intermediate progenitor cells and a reduction of proliferative Nestin-positive neuronal stem cells at the DG. The impairment of hippocampal neurogenesis at this stage of differentiation is in line with a significantly decreased RNA expression of the transcription factors Pax6, Ascl1, and NeuroD1. Interestingly, the number of NeuN-positive postmitotic neurons was not affected by GABAB receptor blockade, although strictly associated transcription factors for postmitotic neurons, Tbr1, Prox1, and NeuroD2, displayed reduced expression levels, suggesting impairment by GABAB receptor antagonization at this stage of neurogenesis. Antagonization of GABAB receptors decreased the expression of neurotrophins (BDNF, NT-3, and NGF). In contrast to the GABAB receptor blockade, the GABAA receptor antagonization revealed no significant changes in cell counts, but an increased transcriptional expression of Tbr1 and Tbr2. We conclude that GABAergic signaling via the metabotropic GABAB receptor is crucial for hippocampal neurogenesis at the time of rapid brain growth and of the postnatal GABA shift. Differentiation and proliferation of intermediate progenitor cells are dependent on GABA. These insights become more pertinent in preterm infants whose developing brains are prematurely exposed to spostnatal stress and predisposed to poor neurodevelopmental disorders, possibly as sequelae of early disruption in GABAergic signaling.
THERapy–Related InterACTion (THER-I-ACT) in Rehabilitation—Instrument Development and Inter-Rater Reliability
Authors: Platz Thomas , Seidel Jonathan , Müller Andreas , Goldmann Carolin , Pedersen Ann Louise
Published: August 2021

Objective:To develop an instrument for the observation of therapeutic communication interactions during rehabilitation sessions and test its inter-rater reliability.

Methods:The new instrument THER-I-ACT (THERapy–related Inter-ACTion) has been designed to assess both the frequency and timing of therapeutic interactions in the thematic fields information provision, feedback, other motivational interaction, and bonding. For this inter-rater reliability study, a sample of stroke survivors received arm rehabilitation as either arm ability training, arm basis training, or mirror therapy, or neglect training as individually indicated. Therapy sessions were video-recorded (one for each participant) and therapeutic interactions rated by two independent raters using THER-I-ACT.

Results:With regard to the instrument's comprehensiveness to document therapeutic interactions with pre-defined categories the data from 29 sessions suggested almost complete coverage. Inter-rater reliability was very high both for individual categories of therapeutic interaction (frequency and time used for interaction) (intraclass correlation coefficient, ICC 0.91–1.00) and summary scores for the thematic fields of interaction (again for frequency and time used for interaction) (ICC 0.98–1.00).

The inter-rater reliability for rating engagement and being focussed for both the therapist and patient was substantial (ICC 0.71 and 0.86).

Conclusions:The observational study documented that by use of the newly designed THER-I-ACT various types of therapy-related communication interactions performed by therapists can be assessed with a very high inter-rater reliability. In addition, the thematic fields and categories of therapeutic interaction as defined by the instrument comprehensively covered the type of interaction that occurred in the therapeutic sessions observed.
COVID-19 Vaccination Attitudes With Neuromyelitis Optica Spectrum Disorders: Vaccine Hesitancy and Coping Style
Authors: Xu Yafang , Cao Yanpei , Ma Yue , Zhao Yan , Jiang Hong , Lu Jiahong , Zhao Chongbo , Quan Chao
Published: August 2021

Background: Vaccination is an important method by which to stop the spread of coronavirus disease 2019 (COVID-19) in a population. Patients with neuromyelitis optica spectrum disorders (NMOSD) have unstable immune function and receive immunosuppressive therapy frequently, so they are hardly to make a decision to receive vaccination. Our study investigated the vaccine hesitancy and coping styles in patients with NMOSD to analyze the relationship between vaccine hesitancy and coping styles, and elucidate the factors influencing vaccine hesitancy.

Methods: A convenient sampling method was used to recruit participants. The Adult Vaccine Hesitancy Scale and Medical Coping Modes Questionnaire were used to measure the vaccine hesitancy and coping style of the participants. Pearson correlation, multiple stepwise, linear regression, and one-way analysis of variance were used to analyze the data.

Results: A total of 262 NMOSD patients were investigated. The score of vaccine hesitancy in NMOSD patients is lower (21.13 ± 4.355) than 25 points which indicated the patient is not considered to have vaccine hesitancy. The score for vaccine hesitancy was negatively correlated with the confrontation and avoidance coping styles (r = −0.481 and r = 0.423). That adoption of the coping styles of confrontation and avoidance as well as the residence of the patient were predictors of vaccine hesitation in NMOSD patients (R2(adj) = 0.29, P < 0.001). In addition, the vaccine hesitancy scores of NMOSD patients residing in rural areas were significantly higher than those of patients living in urban areas (P < 0.01). Comparing with each level of education, the scores were not statistically significant in vaccine hesitancy and coping styles (P > 0.05).

Conclusions: This study reveals that the NMOSD patients is not considered to have vaccine hesitancy, Patients who tend to adopt confrontation and avoidance coping styles have less vaccine hesitancy. Health authorities and medical specialist teams should strengthen effective vaccination information for patients with NMOSD, such as expert consensus or guidelines through various media to help them with decision-making. The significance of vaccination, the safety and side effects of COVID-19 vaccination and predicting of epidemiological trends of COVID-19 should be emphasized. More attention should be paid to NMOSD patients who living in rural areas.
Sleep Disturbances in Autoimmune Neurologic Diseases: Manifestation and Pathophysiology
Authors: Yin Dou , Chen Sheng , Liu Jun
Published: August 2021

Autoimmune neurologic diseases are a new category of immune-mediated disease demonstrating a widely varied spectrum of clinical manifestations. Recently, sleep disturbances in patients with autoimmune neurologic diseases have been reported to have an immense negative impact on the quality of life. Excessive daytime sleep, rapid eye movement sleep behavior disorder (RBD), and narcolepsy are the most frequent sleep disorders associated with autoimmune neurologic diseases. Sleep disturbances might be the initial symptoms of disease or persist throughout the course of the disease. In this review, we have discussed sleep disturbances in different autoimmune neurologic diseases and their potential pathophysiological mechanisms.
Radiomic Feature-Based Nomogram: A Novel Technique to Predict EGFR-Activating Mutations for EGFR Tyrosin Kinase Inhibitor Therapy
Authors: Weng Qiaoyou , Hui Junguo , Wang Hailin , Lan Chuanqiang , Huang Jiansheng , Zhao Chun , Zheng Liyun , Fang Shiji , Chen Minjiang , Lu Chenying , Bao Yuyan , Pang Peipei , Xu Min , Mao Weibo , Wang Zufei , Tu Jianfei , Huang Yuan , Ji Jiansong
Published: August 2021

Objectives

To develop and validate a radiomic feature-based nomogram for preoperative discriminating the epidermal growth factor receptor (EGFR) activating mutation from wild-type EGFR in non-small cell lung cancer (NSCLC) patients.

Material

A group of 301 NSCLC patients were retrospectively reviewed. The EGFR mutation status was determined by ARMS PCR analysis. All patients underwent nonenhanced CT before surgery. Radiomic features were extracted (GE healthcare). The maximum relevance minimum redundancy (mRMR) and LASSO, were used to select features. We incorporated the independent clinical features into the radiomic feature model and formed a joint model (i.e., the radiomic feature-based nomogram). The performance of the joint model was compared with that of the other two models.

Results

In total, 396 radiomic features were extracted. A radiomic signature model comprising 9 selected features was established for discriminating patients with EGFR-activating mutations from wild-type EGFR. The radiomic score (Radscore) in the two groups was significantly different between patients with wild-type EGFR and EGFR-activating mutations (training cohort: P<0.0001; validation cohort: P=0.0061). Five clinical features were retained and contributed as the clinical feature model. Compared to the radiomic feature model alone, the nomogram incorporating the clinical features and Radscore exhibited improved sensitivity and discrimination for predicting EGFR-activating mutations (sensitivity: training cohort: 0.84, validation cohort: 0.76; AUC: training cohort: 0.81, validation cohort: 0.75). Decision curve analysis demonstrated that the nomogram was clinically useful and surpassed traditional clinical and radiomic features.

Conclusions

The joint model showed favorable performance in the individualized, noninvasive prediction of EGFR-activating mutations in NSCLC patients.
CXCL10 Produced by HPV-Positive Cervical Cancer Cells Stimulates Exosomal PDL1 Expression by Fibroblasts via CXCR3 and JAK-STAT Pathways
Authors: Chen Xiaona , He Hui , Xiao Yue , Hasim Ayshamgul , Yuan Jianlin , Ye Min , Li Xin , Hao Yi , Guo Xia
Published: August 2021

Persistent infection with human papillomavirus (HPV) and immune surveillance failure may be the initiating factors for the carcinogenesis of cervical squamous cell carcinoma (CSCC). HPV infection might affect the innate immune pathway of cervical epithelial cells that constitute the “microenvironment” for tumor cells. Programmed death-ligand 1 (PD-L1) has been reported to be an immunosuppressor that helps cancer cells escape the actions of T cells. In the present study, CXCL10 was substantially upregulated both in cervical tissues of HPV infected patients with cervical intraepithelial neoplasia (CIN) or CSCC, as well as in HPV16 E6/E7 transgenic murine cervix. The HPV-positive (HPV+) cervical cancer cell lines SiHa and Caski secreted increased levels of CXCL10 compared to human foreskin fibroblasts (HFF-1), and its receptor CXCR3 was overexpressed in HFF-1. After co-culture with SiHa or Caski, the JAK-STAT signaling pathway and exosomal PD-L1 expression were both upregulated in HFF-1. Recombinant human CXCL10 induced JAK-STAT and PD-L1, while the CXCL10-CXCR3 and JAK-STAT inhibitors AMG487 or ruxolitinib reduced the expression of PD-L1 in HFF-1 cells. Furthermore, the upregulated expression of PD-L1 was verified in HPV+ but not HPV-negative (HPV-) patients with cervical cancers by analysis of tissue microarray cores in 25 cervical lesion patients (P < 0.05). The results indicate that HPV infection can induce cervical cancer cells to secrete CXCL10, which binds to CXCR3 in the surrounding fibroblast cells,leading to JAK-STAT pathway activation and the subsequent upregulated expression of exosomal PD-L1. These mechanisms may help HPV to escape immune response attack, leading to carcinogenesis.
From CAR-T Cells to CAR-NK Cells: A Developing Immunotherapy Method for Hematological Malignancies
Authors: Lu Hui , Zhao Xiaoyan , Li Ziying , Hu Yu , Wang Huafang
Published: August 2021

The approval of CD19 chimeric antigen receptor (CAR)-engineered T (CAR-T) cell products in B-cell malignancies represents a breakthrough in CAR-T cell immunotherapy. However, the remaining limitations concerning the graft-versus-host disease (GVHD) and other adverse effects (e.g., cytokine release syndromes [CRS] and neurotoxicity) still restrict their wider applications. Natural killer (NK) cells have been identified as promising candidates for CAR-based cellular immunotherapy because of their unique characteristics. No HLA-matching restriction and abundant sources make CAR-engineered NK (CAR-NK) cells potentially available to be off-the-shelf products that could be readily available for immediate clinical use. Therefore, researchers have gradually shifted their focus from CAR-T cells to CAR-NK cells in hematological malignancies. This review discusses the current status and applications of CAR-NK cells in hematological malignancies, as well as the unique advantages of CAR-NK cells compared with CAR-T cells. It also discusses challenges and prospects regarding clinical applications of CAR-NK cells.
Update on the Crosstalk Between Adipose Tissue and Mineral Balance in General Population and Chronic Kidney Disease
Authors: Karava Vasiliki , Christoforidis Athanasios , Kondou Antonia , Dotis John , Printza Nikoleta
Published: August 2021

Adipose tissue is nowadays considered as a major endocrine organ, which apart from controlling lipid metabolism, displays a significant role in energy expenditure, food intake and in the regulation of various systemic physiological processes. Adipose derived pro-inflammatory cytokines and adipokines, particularly leptin and adiponectin, provide inter-communication of adipose tissue with various metabolic pathways, ultimately resulting in a complex network of interconnected organ systems. Recent clinical and experimental research has been focused on exploring the direct interaction between adipokine profile and elements of mineral metabolism, including parathormone (PTH), fibroblast growth factor-23 (FGF23) and calcitriol. The emerging crosstalk between adipose tissue and calcium and phosphorus homeostasis suggests that metabolic disorders from one system may directly affect the other and vice versa. It is current knowledge that fat metabolism disturbance, commonly encountered in obese individuals, influences the expression of calciotriopic hormones in general population, while various clinical trials attempting to successfully achieve body fat loss by modulating mineral profile have been published. In chronic kidney disease (CKD) state, there is an increasing evidence suggesting that mineral disorders, influence adipose tissue and linked endocrine function. On the contrary, the impact of disturbed fat metabolism on CKD related mineral disorders has been also evocated in clinical studies. Recognizing the pathogenetic mechanisms of communication between adipose tissue and mineral balance is critical for understanding the effects of metabolic perturbations from the one system to the other and for identifying possible therapeutic targets in case of disrupted homeostasis in one of the two connected systems. To that end, this review aims to enlighten the recent advances regarding the interplay between mineral metabolism, fat mass and adipokine profile, based on in vitro, in vivo and clinical studies, in general population and in the course of CKD.