bluuebunny/crossref_metadata_2025 huggingface dataset:
Identifying Imaging Genetics Biomarkers of Alzheimer’s Disease by Multi-Task Sparse Canonical Correlation Analysis and Regression
Authors: Ke Fengchun , Kong Wei , Wang Shuaiqun
Published: August 2021

Imaging genetics combines neuroimaging and genetics to assess the relationships between genetic variants and changes in brain structure and metabolism. Sparse canonical correlation analysis (SCCA) models are well-known tools for identifying meaningful biomarkers in imaging genetics. However, most SCCA models incorporate only diagnostic status information, which poses challenges for finding disease-specific biomarkers. In this study, we proposed a multi-task sparse canonical correlation analysis and regression (MT-SCCAR) model to reveal disease-specific associations between single nucleotide polymorphisms and quantitative traits derived from multi-modal neuroimaging data in the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort. MT-SCCAR uses complementary information carried by multiple-perspective cognitive scores and encourages group sparsity on genetic variants. In contrast with two other multi-modal SCCA models, MT-SCCAR embedded more accurate neuropsychological assessment information through linear regression and enhanced the correlation coefficients, leading to increased identification of high-risk brain regions. Furthermore, MT-SCCAR identified primary genetic risk factors for Alzheimer’s disease (AD), including rs429358, and found some association patterns between genetic variants and brain regions. Thus, MT-SCCAR contributes to deciphering genetic risk factors of brain structural and metabolic changes by identifying potential risk biomarkers.
Re-Evaluating the Effects of Obesity on Cancer Immunotherapy Outcomes in Renal Cancer: What Do We Really Know?
Authors: Farag Kristine I. , Makkouk Amani , Norian Lyse A.
Published: August 2021

Obesity has reached global epidemic proportions and its effects on interactions between the immune system and malignancies, particularly as related to cancer immunotherapy outcomes, have come under increasing scrutiny. Although the vast majority of pre-clinical murine studies suggest that host obesity should have detrimental effects on anti-tumor immunity and cancer immunotherapy outcomes, the opposite has been found in multiple retrospective human studies. As a result, acceptance of the “obesity paradox” paradigm, wherein obesity increases cancer risk but then improves patient outcomes, has become widespread. However, results to the contrary do exist and the biological mechanisms that promote beneficial obesity-associated outcomes remain unclear. Here, we highlight discrepancies in the literature regarding the obesity paradox for cancer immunotherapy outcomes, with a particular focus on renal cancer. We also discuss multiple factors that may impact research findings and warrant renewed research attention in future studies. We propose that specific cancer patient populations may be affected in fundamentally different ways by host obesity, leading to divergent effects on anti-tumor immunity and/or immunotherapy outcomes. Continued, thoughtful analysis of this critical issue is therefore needed to permit a more nuanced understanding of the complex effects of host obesity on cancer immunotherapy outcomes in patients with renal cancer or other malignancies.
Overexpression of miR-223 Promotes Tolerogenic Properties of Dendritic Cells Involved in Heart Transplantation Tolerance by Targeting Irak1
Authors: Yuan Shun , Chen Yuanyang , Zhang Min , Wang Zhiwei , Hu Zhipeng , Ruan Yongle , Ren Zongli , Shi Feng
Published: August 2021

Dendritic cells (DCs) are key mediators of transplant rejection. Numerous factors have been identified that regulate transplant immunopathology by modulating the function of DCs. Among these, microRNAs (miRNAs), small non-coding RNA molecules, have received much attention. The miRNA miR-223 is very highly expressed and tightly regulated in hematopoietic cells. It plays an important role in modulating the immune response by regulating neutrophils and macrophages, and its dysregulation contributes to multiple types of immune diseases. However, the role of miR-223 in immune rejection is unclear. Here, we observed expression of miR-223 in patients and mice who had undergone heart transplantation and found that it increased in the serum of both, and also in DCs from the spleens of recipient mice, although it was unchanged in splenic T cells. We also found that miR-223 expression decreased in lipopolysaccharide-stimulated DCs. Increasing the level of miR-223 in DCs promoted polarization of DCs toward a tolerogenic phenotype, which indicates that miR-223 can attenuate activation and maturation of DCs. MiR-223 effectively induced regulatory T cells (Tregs) by inhibiting the function of antigen-presenting DCs. In addition, we identified Irak1 as a miR-223 target gene and an essential regulator of DC maturation. In mouse allogeneic heterotopic heart transplantation models, grafts survived longer and suffered less immune cell infiltration in mice with miR-223-overexpressing immature (im)DCs. In the miR-223-overexpressing imDC recipients, T cells from spleen differentiated into Tregs, and the level of IL-10 in heart grafts was markedly higher than that in the control group. In conclusion, miR-223 regulates the function of DCs via Irak1, differentiation of T cells into Tregs, and secretion of IL-10, thereby suppressing allogeneic heart graft rejection.
Optimizing T Cell-Based Therapy for Glioblastoma
Authors: Karachi Aida , Dastmalchi Farhad , Nazarian Saina , Huang Jianping , Sayour Elias J. , Jin Linchun , Yang Changlin , Mitchell Duane A. , Rahman Maryam
Published: August 2021

Evading T cell surveillance is a hallmark of cancer. Patients with solid tissue malignancy, such as glioblastoma (GBM), have multiple forms of immune dysfunction, including defective T cell function. T cell dysfunction is exacerbated by standard treatment strategies such as steroids, chemotherapy, and radiation. Reinvigoration of T cell responses can be achieved by utilizing adoptively transferred T cells, including CAR T cells. However, these cells are at risk for depletion and dysfunction as well. This review will discuss adoptive T cell transfer strategies and methods to avoid T cell dysfunction for the treatment of brain cancer.
An Improved Tat/Rev Induced Limiting Dilution Assay With Enhanced Sensitivity and Breadth of Detection
Authors: Mehta Kavita , Gohil Yuvrajsinh , Mishra Swarnima , D’silva Anish , Amanullah Afzal , Selvam Deepak , Pargain Neelam , Nala Narendra , Sanjeeva G. N. , Ranga Udaykumar
Published: August 2021

Tat/Rev Induced Limiting Dilution Assay (TILDA) is instrumental in estimating the size of latent reservoirs of HIV-1. Here, we report an optimized TILDA containing a broader detection range compared to the reported methods and high sensitivity. Giving priority to sequence conservation, we positioned the two forward primers and the probe in exon-1 of HIV-1. The reverse primers are positioned in highly conserved regions of exon-7. The optimized TILDA detected eight molecular clones belonging to five major genetic subtypes of HIV-1 with a comparable detection sensitivity. Using the optimized assay, we show that only a minor proportion of CD4+ T cells of primary clinical samples can spontaneously generate multiply spliced viral transcripts. A significantly larger proportion of the cells produced viral transcripts following activation. The optimized TILDA is suitable to characterize HIV-1 latent reservoirs and the therapeutic strategies intended to target the reservoir size.
Key Gene and Functional Pathways Identified in Unexplained Recurrent Spontaneous Abortion Using Targeted RNA Sequencing and Clinical Analysis
Authors: Gu Heng , Li Longyu , Du Mengxuan , Xu Hang , Gao Mengge , Liu Xiaohua , Wei Xiangcai , Zhong Xingming
Published: August 2021

Identifying the mechanisms underlying unexplained recurrent spontaneous abortion (URSA) can help develop effective treatments. This study provides novel insights into the biological characteristics and related pathways of differentially expressed genes (DEGs) in URSA. Nineteen patients with URSA and three healthy fertile women with regular menstruation (control group) were recruited. RNA was extracted from the two groups to determine the differential expression of immunoregulatory gene sequences. Gene ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) enrichment analyses were used to identify the biological functions and pathways of the identified DEGs. A protein-protein interaction (PPI) network was constructed using the STRING database. Furthermore, qRT-PCR and ELISA were performed to validate the differential expression of the hub genes. We also explored the regulatory mechanism of Th1/Th2 imbalance. A total of 99 DEGs were identified, comprising 94 upregulated and five downregulated genes. Through GO analysis, nine immune cell function-related clusters were selected, and genes with significant differential expression were primarily enriched in eight immune regulatory functions related to the KEGG signalling pathway. Subsequently, five hub genes (TLR2, CXCL8, IFNG, IL2RA,andITGAX) were identified using Cytoscape software; qRT-PCR confirmed the differential expression among the hub genes, whereas ELISA revealed a significant difference in extracellular IFN-γ and IL-8 levels. The levels of Th1 (IFN-γ) and the Th1/Th2 ratio were higher in the peripheral blood of URSA patients than in control group patients. These findings suggest that the occurrence of URSA may be associated with the abnormal expression of some specific immunoregulatory genes involved in T-cell activation and differentiation. Among the identified DEGs,IFNGmay play a key role in regulating maternal immune response. Although further validation is required, our data provide an important theoretical basis for elucidating the pathogenesis of recurrent spontaneous abortion.
Acoustic Telemetry Around Western Australia’s Oil and Gas Infrastructure Helps Detect the Presence of an Elusive and Endangered Migratory Giant
Authors: Thomson Paul G. , Pillans Richard , Jaine Fabrice R. A. , Harcourt Robert G. , Taylor Michael D. , Pattiaratchi Charitha B. , McLean Dianne L.
Published: August 2021

Subsea infrastructure of the oil and gas industry attracts commercial fish species as well as megafauna including sea lions, turtles, sharks and whales. Potential impacts of this attraction, whether positive or negative, are unknown. As part of a pilot study, we deployed acoustic telemetry equipment around offshore infrastructure to assess its effectiveness in detecting tagged marine animals and to gain insights into patterns of megafauna occurrence around these structures. Acoustic receivers were placed around four oil and gas platforms and on two remotely operated vehicles (ROVs) on Australia’s North West Shelf. Two whale sharks (Rhincodon typus) tagged in the World Heritage Ningaloo Reef Marine Park were detected at two platforms, North Rankin A and Pluto, located up to 340 km to the northeast. The shark at North Rankin A was detected infrequently and only 15 times over ∼6 weeks. The shark at Pluto was detected each day of the 24-day deployment, in total 4,894 times. Detections at Pluto platform were highest during the day, with peaks at dusk and dawn. Our study indicates that acoustic telemetry around platforms may be an effective method for understanding how marine megafauna utilise these structures. We recommend collaborating with industry to undertake receiver detection range testing to understand the effectiveness of the method. Furthermore, future studies should co-occur with tagging programs at sites like Ningaloo Reef and around the structures themselves to maximise the probability of detecting animals at these sites, thereby improving our understanding of how marine megafauna interact with these structures.
Distance-Based Sampling Methods for Assessing the Ecological Effects of Offshore Wind Farms: Synthesis and Application to Fisheries Resource Studies
Authors: Methratta Elizabeth T.
Published: August 2021

Renewable energy, sustainable seafood, and a healthy marine ecosystem are integral elements of a sustainable blue economy. The rapid global advancement of offshore wind coupled with its potential to affect marine life compels an urgent need for robust methodologies to assess the impacts of this industry on fisheries resource species. Basic Before-After-Control-Impact (BACI) and Control-Impact (CI) designs are the most common experimental designs used to study the effects of offshore wind development on fisheries resources. These designs do not account for spatial heterogeneity which presents a challenge because empirical evidence shows that impact gradients occur at wind farms, with larger effect sizes close to turbine foundations that attenuate with increasing distance. Combining the before-after sampling design with distance-based methods could provide a powerful approach for characterizing both the spatial and temporal variance associated with wind development. Toward enhancing future monitoring designs for fisheries resource species at offshore wind farms, this paper aims to: (1) examine distance-based sampling methods that have been or could potentially be used to study impacts on fisheries resources at offshore wind farms including distance-stratified BACI, distance-stratified CI, Before-After-Gradient (BAG), and After-Gradient (AG) methods; (2) synthesize the methods and findings of studies conducted to date that have used distance-based methods to examine ecological impacts of offshore wind development for benthic macroinvertebrates, finfish, birds, and small mammals; (3) examine some of the central methodological elements and issues to consider in developing distance-based impact studies; and (4) offer recommendations for how to incorporate distance-based sampling methods into monitoring plans at offshore wind farms.
Microbial Ecology of Qatar, the Arabian Gulf: Possible Roles of Microorganisms
Authors: Al-Thani Roda F. , Yasseen Bassam T.
Published: August 2021

The Arabian Gulf ranks among the world’s most arid and warm regions; the land has high salinity levels with many Sabkhas and receives little precipitation. This region holds about one-third of the world’s oil supply. Qatar is the leading gas producer worldwide, which raises many concerns about the pollution of the sea, groundwater, and soil. Thus, the Arabian Gulf area has paid particular attention to environmental studies since the environmental status of this region imposed unique biological diversity, and microbial ecology has gained special importance following the identification of promising roles of microorganisms. This review article discusses the microbial ecology at the main habitats of the State of Qatar. We discuss important principles for successful ecological restoration and future perspectives of using biological approaches to solve many problems related to health, the economy, and agriculture. There are at least five microbial communities that have been recognized at the Qatari habitats: marine environment, salt marshes and mangrove forests, the arid lands (including dune communities), wetlands (including pond communities), and Rawdahs (including the Ghaf tree communities). Although, the environmental conditions of this region are almost the same, these habitats are compared with those at other countries of the Arabian Gulf whenever necessary, as each habitat has its own peculiar characteristics. Some case studies are presented to describe the biochemical characterizations of bacterial isolates from soils and leaf surface of native plants, including halophytes and xerophytes at these habitats. These studies rarely went beyond the general identification at species levels. There is a discussion about the possible roles of microorganisms at the rhizosphere, non-rhizosphere, and phyllosphere, and using plant exudates to control microbial activity. However, modern approach (culture-independent methods) addressing these topics has opened the door for deeper investigations, and to explore the roles played by microorganisms at these habitats. These methods have already begun during the last decade as serious step to solve many environmental issues. In the future, it is very likely that microorganisms will be used to tackle many pollution issues, as well as health, agricultural, and economic problems.
Unsupervised Phonocardiogram Analysis With Distribution Density Based Variational Auto-Encoders
Authors: Li Shengchen , Tian Ke
Published: August 2021

This paper proposes an unsupervised way for Phonocardiogram (PCG) analysis, which uses a revised auto encoder based on distribution density estimation in the latent space. Auto encoders especially Variational Auto-Encoders (VAEs) and its variant β−VAE are considered as one of the state-of-the-art methodologies for PCG analysis. VAE based models for PCG analysis assume that normal PCG signals can be represented by latent vectors that obey a normal Gaussian Model, which may not be necessary true in PCG analysis. This paper proposes two methods DBVAE and DBAE that are based on estimating the density of latent vectors in latent space to improve the performance of VAE based PCG analysis systems. Examining the system performance with PCG data from the a single domain and multiple domains, the proposed systems outperform the VAE based methods. The representation of normal PCG signals in the latent space is also investigated by calculating the kurtosis and skewness where DBAE introduces normal PCG representation following Gaussian-like models but DBVAE does not introduce normal PCG representation following Gaussian-like models.
Predictive Value of Serum Cytokeratin 19 Level for the Feasibility of Conserving Ovaries in Endometrial Cancer
Authors: Xu Jie , Chen Can , Xiong Jing , Wang Hui , Linghu Hua
Published: August 2021

Objective: To determine the predictive value of cytokeratin 19 (CK19) for evaluating the safety of ovarian preservation in patients with endometrial cancer (EC).

Methods: Five hundred and seventeen EC patients hospitalized from November 2010 to June 2016 were reviewed retrospectively. Pre-operative tumor biomarkers including CA125, HE4, CK19, and CA19-9 were obtained. Predictive biomarkers associated with ovarian metastasis were selected using univariate and multivariate Logistic regression. The cut-off values were determined by receiver operating characteristic (ROC) curves. Kaplan-Meier method and Cox multivariate regression model was used to perform survival analysis.

Results: Among clinical parameters and biomarkers included, age > 65, type II EC, CA125 ≥ 35 u/ml, CK19 > 3.3 ng/ml, and myometrial invasion ≥ 50% depth appeared as significant predictors of the risk of ovarian involvement in univariable logistic analysis. In multivariable analysis, CK19 > 3.3 ng/ml (OR = 11.541, 95%CI: 1.968–67.668, P = 0.007) and Type II EC (OR = 8.336, 95%CI: 1.456–47.722, P = 0.017) were independent risk predictors of ovarian metastasis in pre-menopausal women. In pre-menopausal women with Type I EC (n = 142), CK19 level could satisfactorily predict the risk of ovarian metastasis (AUC = 0.860, 95%CI: 0.792–0.912, P < 0.001), and when the cut-off point was set as 2.45 ng/ml, the negative predictive value and negative likelihood ratio were 99% and 0.19, with the maximum Youden index of 0.598.

Conclusions: The present study advocates the necessity of incorporating serum CK19 measurement into the pre-operative evaluation of EC, especially as extension of current standard approach with ovarian preservation counseling.
Gender Differences in Idiopathic Pulmonary Fibrosis: Are Men and Women Equal?
Authors: Sesé Lucile , Nunes Hilario , Cottin Vincent , Israel-Biet Dominique , Crestani Bruno , Guillot-Dudoret Stephanie , Cadranel Jacques , Wallaert Benoit , Tazi Abdellatif , Maître Bernard , Prévot Gregoire , Marchand-Adam Sylvain , Hirschi Sandrine , Dury Sandra , Giraud Violaine , Gondouin Anne , Bonniaud Philippe , Traclet Julie , Juvin Karine , Borie Raphael , Carton Zohra , Freynet Olivia , Gille Thomas , Planès Carole , Valeyre Dominique , Uzunhan Yurdagül
Published: August 2021

Background: Idiopathic pulmonary fibrosis (IPF) is characterized by a male predominance. The aim of the study was to explore gender differences in a well-designed French multicentre prospective IPF cohort (COhorte FIbrose, COFI) with a 5-year follow-up.

Methods: Between 2007 and 2010, 236 patients with incident IPF were included in COFI. Gender characteristics were compared using a t-test, Chi-squared test and ANOVA, as appropriate. Survival analyses were performed.

Results: Fifty-one (22%) females and 185 (78%) males with an average age at diagnosis of 70.1 ± 9.20 and 67.4 ± 10.9 years, respectively, were included in the cohort. Women were significantly less exposed to tobacco smoke [never n = 32 (62.7%) vs. n = 39 (21.1%), p < 0.001] and to occupational exposure [n = 7 (13.7%) vs. n = 63 (34.1%), p = 0.012]. Baseline forced vital capacity, % of predicted (FVC%) was significantly better in women compare to men (83.0% ± 25.0 v. 75.4% ± 18.7 p = 0.046). At presentation honeycombing and emphysema on CT scan were less common in women [n = 40 (78.4%) vs. n = 167 (90.3%) p = 0.041] and [n = 6 (11.8%) vs. n = 48 (25.9%) p = 0.029], respectively. During follow-up fewer women were transplanted compared to men [n = 1 (1.96%) vs. n = 20 (10.8%) p = 0.039]. Medians of survival were comparable by gender [31 months (CI 95%: 28–40) vs. 40 months (CI 95%: 33–72) p = 0.2]. After adjusting for age and FVC at inclusion, being a woman was not associated to a better survival.

Conclusions: Women appear to have less advanced disease at diagnosis, maybe due to less exposure history compare to men. Disease progression and overall survival remains comparable regardless gender, but women have less access to lung transplantation.
Lauric Acid Is a Potent Biological Control Agent That Damages the Cell Membrane of Phytophthora sojae
Authors: Liang Changhui , Gao Wenteng , Ge Ting , Tan Xinwei , Wang Jiayu , Liu Huaxin , Wang Yong , Han Chao , Xu Qian , Wang Qunqing
Published: August 2021

Sustainable management of plant pathogens is becoming more challenging, and novel solutions are needed. Plant biologically active secondary metabolites are important sources of novel crop protection chemistry. Effective individual compounds of these natural products have the potential to be successful new agrochemicals. In this study, we identified lauric acid (LA) from soybean defense leaf volatiles. LA inhibited the growth of Phytophthora sojae, the causal agent of soybean root rot. It influenced mycelial development, sporangium formation, and zoospore generation and germination by damaging the P. sojae cell membrane. Additionally, we showed that LA and several of its derivatives, such as glycerol monolaurate (GML), had similar biological activities. Both LA and GML were safe to soybean plants when used at less than 0.3 g a.i./plant and could promote soybean growth, implying their potential as eco-friendly biological control agents.
Chitosan Oligosaccharide Production Potential of Mitsuaria sp. C4 and Its Whole-Genome Sequencing
Authors: Chen Duo , Chen Congcong , Zheng Xuehai , Chen Jiannan , He Wenjin , Lin Chentao , Chen Huibin , Chen Youqiang , Xue Ting
Published: August 2021

Chitooligosaccharide is a kind of functional food, which is the degradation product of chitosan (COS) catalyzed by the endo-chitosanase (COSE) enzyme. A COSE with a molecular weight of 34 kDa was purified and characterized from a newly isolated Mitsuaria sp. C4 (C4), and a 38.46% recovery rate and 4.79-fold purification were achieved. The purified C4 COSE exhibited optimum activity at 40°C and pH 7.2 and was significantly inhibited in the presence of Cu2+ and Fe3+. The Km and Vmin of the COSE toward COS were 2.449 g/L and 0.042 g/min/L, respectively. The highest COSE activity reached 8.344 U/ml after optimizing, which represented a 1.34-fold of increase. Additionally, chitooligosaccharide obtained by COSE hydrolysis of COS was verified by using thin-layer chromatography and high-performance liquid chromatography analysis. Whole-genome sequencing demonstrated that the C4 strain contains 211 carbohydrate enzymes, our purified COSE belonging to GHs-46 involved in carbohydrate degradation. Phylogenetic analysis showed that the novel COSE obtained from the C4 strain was clustered into the degree of polymerization = two to three groups, which can perform catalysis in a similar manner to produce (GlcN)2 and (GlcN)3. This work indicates that the C4 strain could be a good resource for enhancing carbohydrate degradation and might represent a useful tool for chitooligosaccharide production in the functional food industry.
Dynamic Expressions of TIGIT on Splenic T Cells and TIGIT-Mediated Splenic T Cell Dysfunction of Mice With Chronic Toxoplasma gondii Infection
Authors: Li Haoran , Zhang Jing , Su Changwei , Tian Xiaowei , Mei Xuefang , Zhang Zhenchao , Wang Mingyong , Li Xiangrui , Wang Shuai
Published: August 2021

As an immunosuppressive receptor, T-cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) play a critical part in cellular immune regulation mediated by pathogen infection. Whereas, TIGIT expression on splenic T cells in hosts infected with Toxoplasma gondii cysts has not been studied. In this study, we detected TIGIT expression and the changes of immune function in the spleen by flow cytometry and real-time PCR (RT-PCR). We found that TIGIT expression on splenic T cells increased significantly post infection. At the same time, splenic TIGIT+TCM cells were activated and transformed into TIGIT+TEM cells during the infection, and the cytotoxicity of TIGIT+ T cells was reduced in the later stage of infection. This study shows that chronic T. gondii infection can upregulate TIGIT expression on the surface of T cells and affect immune cell function.
New Perkinsea Parasitoids of Dinoflagellates Distantly Related to Parviluciferaceae Members
Authors: Reñé Albert , Alacid Elisabet , Gallisai Rachele , Chambouvet Aurélie , Fernández-Valero Alan D. , Garcés Esther
Published: August 2021

Perkinsea is a phylogenetic group of protists that includes parasites of distantly related hosts. However, its diversity is still mainly composed of environmental sequences, mostly obtained from freshwater environments. Efforts to isolate and culture parasitoids of dinoflagellates have led to the description of several phylogenetically closely related species constituting the Parviluciferaceae family. In this study, two new parasitoid species infecting dinoflagellates during recurrent coastal blooms are reported. Using the ribosomal RNA (rRNA) gene phylogenies, we show that both cluster within Perkinsea, one of them at the base of Parviluciferaceae and the other in a distinct branch unrelated to other described species. The establishment of host-parasite lab cultures of the latter allowed its morphological characterization, resulting in the formal description ofMaranthos nigrumgen. nov., sp. nov. The life-cycle development of the two parasitoids is generally the same as that of other members of the Parviluciferaceae family but they differ in the features of the trophont and sporont stages, including the arrangement of zoospores during the mature sporangium stage and the lack of specialized structures that release the zoospores into the environment. Laboratory cross-infection experiments showed that the parasitoid host range is restricted to dinoflagellates, although it extends across several different genera. The maximum prevalence reached in the tested host populations was lower than in other Parviluciferaceae members. The findings from this study suggest that Perkinsea representatives infecting dinoflagellates are more widespread than previously thought.
Decreased Expression of PACSIN1 in Brain Glioma Samples Predicts Poor Prognosis
Authors: Zimu Zhou , Jia Zhang , Xian Fu , Rui Ma , Yuting Ren , Yuan Wei , Tianhong Wen , Mian Ma , Yinlong Liu , Enfang Shan
Published: August 2021

Gliomas are the most severe brain tumours with a poor prognosis. Although surgery, postoperative radiotherapy and chemotherapy can improve the survival rate of glioma patients, the prognosis of most glioma patients is still poor. In recent years, the influence of gene-targeted therapy on gliomas has been gradually discovered, and intervening the occurrence and development of brain gliomas from the perspective of the gene will significantly improve treatment prognosis. Protein Kinase C and Casein Kinase Substrate in Neurons 1 (PACSIN1) is a member of the conserved peripheral membrane protein family in eukaryotes. Improper expression of PACSIN1 can lead to neurological diseases such as Huntington’s disease and schizophrenia. However, its relationship with tumours or even gliomas has not been explored. The study aims to explore PACSIN1 as a prognostic factor that can predict overall survival (OS) for gliomas. We collected the data from CGGA, TCGA, GEO databases and the pathological glioma tissue specimens from 15 clinical glioma patients surgically resected. The differential expression of PACSIN1 in various clinical indicators, the genes related to PACSIN1 expression, the prognostic value of PACSIN1 and the functional annotations and pathway analysis of differently expressed genes (DEGs) were analysed. The results revealed that PACSIN1 had low expression levels in grade IV, IDH1 wild-type and 1p/19q non-codel group gliomas, and PACSIN1 was considered a mesenchymal molecular subtype marker. PACSIN1 expression is positively correlated with OS in all gliomas and it was found that PACSIN1 influenced the occurrence and development of gliomas through synaptic transmission. The PACSIN1 expression is negatively correlated with the malignant degree of gliomas and positively associated with the OS, indicating that PACSIN1 would play an essential role in the occurrence and development of gliomas and might be a potential new biomarker and targeted therapy site for gliomas.
A Rhesus Monkey Model of Non-suicidal Self-Injury
Authors: Novak Melinda A. , Meyer Jerrold S.
Published: August 2021

Non-suicidal self-injury (NSSI) is a type of behavioral pathology seen not only in a variety of clinical conditions but also among non-clinical populations, particularly adolescents and young adults. With the exception of rare genetic conditions that give rise to self-harming behaviors, the etiology of NSSI and the events that trigger specific episodes of this behavior remain poorly understood. This review presents the features of an important, extensively studied animal model of NSSI, namely spontaneously occurring self-injurious behavior (SIB) in rhesus macaque monkeys. We compare and contrast rhesus monkey SIB with NSSI with respect to form, prevalence rates, environmental and biological risk factors, behavioral correlates, proposed functions, and treatment modalities. Many parallels between rhesus monkey SIB and NSSI are demonstrated, which supports the validity of this animal model across several domains. Determining the etiology of spontaneously occurring SIB in monkeys, its underlying biological mechanisms, and which pharmacological agents are most effective for treating the disorder may aid in identifying potential risk factors for the occurrence of NSSI in humans and developing medications for severe cases that are resistant to conventional psychotherapeutic approaches.
Drugs of Abuse Differentially Alter the Neuronal Excitability of Prefrontal Layer V Pyramidal Cell Subtypes
Authors: Leyrer-Jackson Jonna M. , Hood Lauren E. , Olive M. Foster
Published: August 2021

The medial prefrontal cortex (mPFC) plays an important role in regulating executive functions including reward seeking, task flexibility, and compulsivity. Studies in humans have demonstrated that drugs of abuse, including heroin, cocaine, methamphetamine, and alcohol, alter prefrontal function resulting in the consequential loss of inhibitory control and increased compulsive behaviors, including drug seeking. Within the mPFC, layer V pyramidal cells, which are delineated into two major subtypes (type I and type II, which project to subcortical or commissurally to other cortical regions, respectively), serve as the major output cells which integrate information from other cortical and subcortical regions and mediate executive control. Preclinical studies examining changes in cellular physiology in the mPFC in response to drugs of abuse, especially in regard to layer V pyramidal subtypes, are relatively sparse. In the present study, we aimed to explore how heroin, cocaine, methamphetamine, ethanol, and 3,4-methylenedioxypyrovalerone (MDPV) alter the baseline cellular physiology and excitability properties of layer V pyramidal cell subtypes. Specifically, animals were exposed to experimenter delivered [intraperitoneal (i.p.)] heroin, cocaine, the cocaine-like synthetic cathinone MDPV, methamphetamine, ethanol, or saline as a control once daily for five consecutive days. On the fifth day, whole-cell physiology recordings were conducted from type I and type II layer V pyramidal cells in the mPFC. Changes in cellular excitability, including rheobase (i.e., the amount of injected current required to elicit action potentials), changes in input/output curves, as well as spiking characteristics induced by each substance, were assessed. We found that heroin, cocaine, methamphetamine, and MDPV decreased the excitability of type II cells, whereas ethanol increased the excitability of type I pyramidal cells. Together, these results suggest that heroin, cocaine, MDPV, and methamphetamine reduce mPFC commissural output by reducing type II excitability, while ethanol increases the excitability of type I cells targeting subcortical structures. Thus, separate classes of abused drugs differentially affect layer V pyramidal subtypes in the mPFC, which may ultimately give rise to compulsivity and inappropriate synaptic plasticity underlying substance use disorders.
Effects of Combined Endurance and Resistance Training in Women With Multiple Sclerosis: A Randomized Controlled Study
Authors: Correale Luca , Buzzachera Cosme Franklim , Liberali Giulia , Codrons Erwan , Mallucci Giulia , Vandoni Matteo , Montomoli Cristina , Bergamaschi Roberto
Published: August 2021

Purpose: To test the hypothesis that combined resistance and endurance training would improve muscle strength, fatigue, depression, and quality of life in persons with MS.

Methods: Twenty-seven women with MS were randomly assigned to either control (CON, n = 13) or the experimental (EXP, n = 14) group. The participants in the EXP group trained twice a week for 12 weeks, followed by 12 weeks of detraining. Both CON and EXP groups were tested before and after 12 weeks of the intervention period, as well as 12 weeks after training cessation (follow-up), where measures of muscle strength, fatigue, depression, and quality of life were evaluated.

Results: There were significant changes in maximal voluntary isometric contraction (MVIC), 1RM leg extension, and 1RM chest press following the intervention period in the EXP group (P < 0.05), but not in the CON group (P > 0.05). These changes persisted after 12 weeks of detraining. Similar findings were found for fatigue, depression, and physical and mental composites of quality of life.

Conclusion: These results suggest that combined exercise training, at a minimum, prevents the disease-related deterioration of muscular performance and quality of life and well-being in persons with MS.
On-Reading (Chinese-Style Pronunciation) Predominance Over Kun-Reading (Native Japanese Pronunciation) in Japanese Semantic Dementia
Authors: Sakurai Yasuhisa , Uchiyama Yumiko , Takeda Akitoshi , Terao Yasuo
Published: August 2021

Japanese kanji (morphograms) have two ways of reading: on-reading (Chinese-style pronunciation) and kun-reading (native Japanese pronunciation). It is known that some Japanese patients with semantic dementia read kanji with on-reading but not with kun-reading. To characterize further reading impairments of patients with semantic dementia, we analyzed data from a total of 9 patients who underwent reading and writing tests of kanji and kana (Japanese phonetic writing) and on-kun reading tests containing two-character kanji words with on-on reading, kun-kun reading, and specific (so-called Jukujikun or irregular kun) reading. The results showed that on-reading preceding (pronouncing first with on-reading) and kun-reading deletion (inability to recall kun-reading) were observed in nearly all patients. In the on-kun reading test, on-reading (57.6% correct), kun-reading (46.6% correct), and specific-reading (30.0% correct) were more preserved in this decreasing order (phonology-to-semantics gradient), although on-reading and kun-reading did not significantly differ in performance, according to a more rigorous analysis after adjusting for word frequency (and familiarity). Furthermore, on-substitution (changing to on-reading) errors in kun-reading words (27.0%) were more frequent than kun-substitution (changing to kun-reading) errors in on-reading words (4.0%). These results suggest that kun-reading is more predominantly disturbed than on-reading, probably because kun-reading and specific-reading are closely associated with the meaning of words.
Dissociable Neural Representations of Adversarially Perturbed Images in Convolutional Neural Networks and the Human Brain
Authors: Zhang Chi , Duan Xiao-Han , Wang Lin-Yuan , Li Yong-Li , Yan Bin , Hu Guo-En , Zhang Ru-Yuan , Tong Li
Published: August 2021

Despite the remarkable similarities between convolutional neural networks (CNN) and the human brain, CNNs still fall behind humans in many visual tasks, indicating that there still exist considerable differences between the two systems. Here, we leverage adversarial noise (AN) and adversarial interference (AI) images to quantify the consistency between neural representations and perceptual outcomes in the two systems. Humans can successfully recognize AI images as the same categories as their corresponding regular images but perceive AN images as meaningless noise. In contrast, CNNs can recognize AN images similar as corresponding regular images but classify AI images into wrong categories with surprisingly high confidence. We use functional magnetic resonance imaging to measure brain activity evoked by regular and adversarial images in the human brain, and compare it to the activity of artificial neurons in a prototypical CNN—AlexNet. In the human brain, we find that the representational similarity between regular and adversarial images largely echoes their perceptual similarity in all early visual areas. In AlexNet, however, the neural representations of adversarial images are inconsistent with network outputs in all intermediate processing layers, providing no neural foundations for the similarities at the perceptual level. Furthermore, we show that voxel-encoding models trained on regular images can successfully generalize to the neural responses to AI images but not AN images. These remarkable differences between the human brain and AlexNet in representation-perception association suggest that future CNNs should emulate both behavior and the internal neural presentations of the human brain.
Revealing the Dynamic Nature of Amplitude Modulated Neural Entrainment With Holo-Hilbert Spectral Analysis
Authors: Juan Chi-Hung , Nguyen Kien Trong , Liang Wei-Kuang , Quinn Andrew J. , Chen Yen-Hsun , Muggleton Neil G. , Yeh Jia-Rong , Woolrich Mark W. , Nobre Anna C. , Huang Norden E.
Published: August 2021

Patterns in external sensory stimuli can rapidly entrain neuronally generated oscillations observed in electrophysiological data. Here, we manipulated the temporal dynamics of visual stimuli with cross-frequency coupling (CFC) characteristics to generate steady-state visual evoked potentials (SSVEPs). Although CFC plays a pivotal role in neural communication, some cases reporting CFC may be false positives due to non-sinusoidal oscillations that can generate artificially inflated coupling values. Additionally, temporal characteristics of dynamic and non-linear neural oscillations cannot be fully derived with conventional Fourier-based analyses mainly due to trade off of temporal resolution for frequency precision. In an attempt to resolve these limitations of linear analytical methods, Holo-Hilbert Spectral Analysis (HHSA) was investigated as a potential approach for examination of non-linear and non-stationary CFC dynamics in this study. Results from both simulation and SSVEPs demonstrated that temporal dynamic and non-linear CFC features can be revealed with HHSA. Specifically, the results of simulation showed that the HHSA is less affected by the non-sinusoidal oscillation and showed possible cross frequency interactions embedded in the simulation without any a priori assumptions. In the SSVEPs, we found that the time-varying cross-frequency interaction and the bidirectional coupling between delta and alpha/beta bands can be observed using HHSA, confirming dynamic physiological signatures of neural entrainment related to cross-frequency coupling. These findings not only validate the efficacy of the HHSA in revealing the natural characteristics of signals, but also shed new light on further applications in analysis of brain electrophysiological data with the aim of understanding the functional roles of neuronal oscillation in various cognitive functions.
Effect of Dietary Supplementation With Mixed Organic Acids on Immune Function, Antioxidative Characteristics, Digestive Enzymes Activity, and Intestinal Health in Broiler Chickens
Authors: Ma Jiayu , Mahfuz Shad , Wang Jian , Piao Xiangshu
Published: August 2021

The purpose of this study was to explore the effect of dietary supplementation with mixed organic acids on intestinal health, enzyme activity, and antioxidative characteristics in broilers. A total of 192 1-day-old chicks were evenly allocated to three experimental groups with eight replicates, a basal diet with 0 (Control), 3,000 mg/kg (LMOA), 6,000 mg/kg (HMOA) mixed organic acid. The tissue and serum samples were gathered on 21 and 42 d of the experiment. An increased (P < 0.05) concentration of IgA, D-lactate (D-LA), and interleukin-10 (IL-10) in the serum of broilers diets with HMOA was observed. The levels of total antioxidant capacity (T-AOC) and catalase activity (CAT) in serum were enhanced (P < 0.05) with dietary and mixed organic acid, respectively, and increased (P < 0.05) content of superoxide dismutase (SOD) and CAT in the duodenum of broilers diets with LMOA was noticed. Also, LMOA decreased (P < 0.05) the pH value of the duodenum and enhanced (P < 0.05) the amylase activity of the pancreas, the tight junction protein (mainly Claudin-1, Claudin-2, and ZO-1) in the duodenum of broilers fed with mixed organic acid were promoted (P < 0.05), and the LMOA group performed better in the small intestine. In cecum microbiota, LMOA and HMOA modulated the structure of microbiota and mainly reduced the relative abundance of Escherichia coli. In brief, dietary supplemented mixed organic acid improved the health status of broilers by promoting the immune function, enhancing the antioxidative characteristics and tight junction proteins expression as well as cecum microbiota. However, LMOA groups may be a better fit considering the comprehensive effects of experiments and economic costs.
Impact of Ramadan Fasting on Dietary Intakes Among Healthy Adults: A Year-Round Comparative Study
Authors: Shatila Hibeh , Baroudi Mariam , El Sayed Ahmad Raeda , Chehab Rana , Forman Michele R. , Abbas Nada , Faris MoezAlIslam , Naja Farah
Published: August 2021

Religious rituals are considered among the principle factors that impact dietary behaviors and food selections. The main objective of this study is to characterize food intake among Lebanese adults observant of the fasting month of Ramadan and compare it to their intake of the rest of the year. During a year-round study, including the month of Ramadan, Lebanese adults (n= 62), completed multiple (9 to 13) 24-h dietary recalls. Information about sociodemographic and lifestyle characteristics was also obtained. Dietary intake was examined using food groups as well as energy, macro, and micronutrient consumption. Significant differences in dietary intakes were observed for 12 of the 19 food groups (expressed as a percent of total energy) during Ramadan as compared to the rest of the year. More specifically, the intakes of cereals, cereal-based products, pasta, eggs, nuts and seeds, milk and dairy, and fats and oils were lower, while vegetables, dried fruit, Arabic sweets, cakes and pastries, and sugar-sweetened-beverages intakes were higher during Ramadan as compared to the remainder of the year (p< 0.05). Such differences in food groups' intakes were reflected in nutrients intakes, including carbohydrates, cholesterol, calcium, beta-carotene, vitamin C, folate, and magnesium. The findings of this study highlighted major differences in dietary intakes between the fasting month as compared to the rest of the year. With the large number of adults who observe fasting during Ramadan, the particularities of dietary intake during Ramadan ought to be considered in the development of context and culture-specific dietary recommendations.
Elucidation of Novel Molecular Targets for Therapeutic Strategies in Urothelial Carcinoma: A Literature Review
Authors: Nelson Blessie Elizabeth , Hong Angelina , Jana Bagi
Published: August 2021

Urothelial carcinoma therapy is a rapidly evolving and expanding field. Traditional cytotoxic chemotherapy regimens have not produced optimal long-term outcomes, and many urothelial cancer patients have comorbidities that disqualify them as chemotherapy candidates. In recent years, a plethora of novel therapeutic agents that target diverse molecular pathways has emerged as alternative treatment modalities for not only metastatic urothelial carcinoma, but also for muscle-invasive bladder cancer and non-muscle invasive bladder cancer in adjuvant and definitive settings. This review paper aims to discuss the various categories of therapeutic agents for these different types of urothelial cancer, discussing immunotherapy, antibody-drug conjugates, kinase inhibitors, CAR-T cell therapy, peptide vaccination, and other drugs targeting pathways such as angiogenesis, DNA synthesis, mTOR/PI3K/AKT, and EGFR/HER-2.