bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel lysosome-related gene signature coupled with gleason score for prognosis prediction in prostate cancer
Authors: Huang Ying , Yang Fan , Zhang Wenyi , Zhou Yupeng , Duan Dengyi , Liu Shuang , Li Jianmin , Zhao Yang
Published: March 2023

Background: Prostate cancer (PCa) is highly heterogeneous, which makes it difficult to precisely distinguish the clinical stages and histological grades of tumor lesions, thereby leading to large amounts of under- and over-treatment. Thus, we expect the development of novel prediction approaches for the prevention of inadequate therapies. The emerging evidence demonstrates the pivotal role of lysosome-related mechanisms in the prognosis of PCa. In this study, we aimed to identify a lysosome-related prognostic predictor in PCa for future therapies.

Methods: The PCa samples involved in this study were gathered from The Cancer Genome Atlas database (TCGA) (n = 552) and cBioPortal database (n = 82). During screening, we categorized PCa patients into two immune groups based on median ssGSEA scores. Then, the Gleason score and lysosome-related genes were included and screened out by using a univariate Cox regression analysis and the least absolute shrinkage and selection operation (LASSO) analysis. Following further analysis, the probability of progression free interval (PFI) was modeled by using unadjusted Kaplan–Meier estimation curves and a multivariable Cox regression analysis. A receiver operating characteristic (ROC) curve, nomogram and calibration curve were used to examine the predictive value of this model in discriminating progression events from non-events. The model was trained and repeatedly validated by creating a training set (n = 400), an internal validation set (n = 100) and an external validation (n = 82) from the cohort.

Results: Following grouping by ssGSEA score, the Gleason score and two LRGs—neutrophil cytosolic factor 1 (NCF1) and gamma-interferon-inducible lysosomal thiol reductase (IFI30)—were screened out to differentiate patients with or without progression (1-year AUC = 0.787; 3-year AUC = 0.798; 5-year AUC = 0.772; 10-year AUC = 0.832). Patients with a higher risk showed poorer outcomes (p < 0.0001) and a higher cumulative hazard (p < 0.0001). Besides this, our risk model combined LRGs with the Gleason score and presented a more accurate prediction of PCa prognosis than the Gleason score alone. In three validation sets, our model still achieved high prediction rates.

Conclusion: In conclusion, this novel lysosome-related gene signature, coupled with the Gleason score, works well in PCa for prognosis prediction.
Transcriptomic analysis reveals shared gene signatures and molecular mechanisms between obesity and periodontitis
Authors: Cai Yisheng , Zuo Xuemei , Zuo Yuyang , Wu Shuang , Pang Weiwei , Ma Keqiang , Yi Qiaorong , Tan Lijun , Deng Hongwen , Qu Xiaochao , Chen Xiangding
Published: March 2023

Background

Both obesity (OB) and periodontitis (PD) are chronic non-communicable diseases, and numerous epidemiological studies have demonstrated the association between these two diseases. However, the molecular mechanisms that could explain the association between OB and PD are largely unclear. This study aims to investigate the common gene signatures and biological pathways in OB and PD through bioinformatics analysis of publicly available transcriptome datasets.

Methods

The RNA expression profile datasets of OB (GSE104815) and PD (GSE106090) were used as training data, and GSE152991 and GSE16134 as validation data. After screening for differentially expressed genes (DEGs) shared by OB and PD, gene enrichment analysis, protein-protein interaction (PPI) network construction, GeneMANIA analysis, immune infiltration analysis and gene set enrichment analysis (GSEA) were performed. In addition, receiver operating characteristic (ROC) curves were used to assess the predictive accuracy of the hub gene. Finally, we constructed the hub gene-associated TF-miRNA-mRNA regulatory network.

Results

We identified a total of 147 DEGs shared by OB and PD (38 down-regulated and 109 up-regulated). Functional analysis showed that these genes were mainly enriched in immune-related pathways such as B cell receptor signalling, leukocyte migration and cellular defence responses. 14 hub genes (FGR, MNDA, NCF2, FYB1, EVI2B, LY86, IGSF6, CTSS, CXCR4, LCK, FCN1, CXCL2, P2RY13, MMP7) showed high sensitivity and specificity in the ROC curve analysis. The results of immune infiltration analysis showed that immune cells such as macrophages, activated CD4 T cells and immune B cells were present at high infiltration levels in both OB and PD samples.The results of GeneMANIA analysis and GSEA analysis suggested that five key genes (FGR, LCK, FYB1, LY86 and P2RY13) may be strongly associated with macrophages. Finally, we constructed a TF-miRNA-mRNA regulatory network consisting of 233 transcription factors (TFs), 8 miRNAs and 14 mRNAs based on the validated information obtained from the database.

Conclusions

Five key genes (FGR, LCK, FYB1, LY86, P2RY13) may be important biomarkers of OB and PD. These genes may play an important role in the pathogenesis of OB and PD by affecting macrophage activity and participating in immune regulation and inflammatory responses.
Integrated summary of immunogenicity of polatuzumab vedotin in patients with relapsed or refractory B-cell non-Hodgkin’s lymphoma
Authors: Dere Randall C. , Beardsley Richard L. , Lu Dan , Lu Tong , Ku Grace H-W. , Man Gabriel , Nguyen Van , Kaur Surinder
Published: March 2023

Polatuzumab vedotin, marketed under the trade name POLIVY®, is a CD79b-targeted antibody-drug conjugate that preferentially delivers a potent anti-mitotic agent (monomethyl auristatin E) to B cells, resulting in anti-cancer activity against B-cell malignancies. In 2019, polatuzumab vedotin in combination with rituximab and bendamustine was approved by the United States Food and Drug Administration for the treatment of adult patients with diffuse large B-cell lymphoma who have received at least two prior therapies. Recent Health Authority guidance recommendations for submitting an Integrated Summary of Immunogenicity were followed including a comprehensive immunogenicity risk assessment, bioanalytical strategy, and immunogenicity data to support the registration of polatuzumab vedotin. Key components of the polatuzumab vedotin Integrated Summary of Immunogenicity and data are presented. Validated semi-homogeneous bridging enzyme-linked immunosorbent assays were used to detect anti-drug antibodies (ADA) to polatuzumab vedotin and characterize the immune response in patients with non-Hodgkin’s lymphoma. The overall incidence of ADA observed for polatuzumab vedotin was low across seven clinical trials. The low incidence of ADA is likely due to the mechanism of action of polatuzumab vedotin that involves targeting and killing of B cells, thereby limiting the development to plasma cells and ADA secretion. Furthermore, patients are co-medicated with rituximab, which also targets B cells and results in B-cell depletion. Therefore, the immunogenicity risk is considered low and not expected to impact the polatuzumab vedotin benefit/risk profile.
Advances in the study of myeloid-derived suppressor cells in infectious lung diseases
Authors: Zhang Meng-Nan , Yuan Yu-Lai , Ao Su-Hua
Published: March 2023

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous population of immature cells capable of inhibiting T-cell responses. MDSCs have a crucial role in the regulation of the immune response of the body to pathogens, especially in inflammatory response and pathogenesis during anti-infection. Pathogens such as bacteria and viruses use MDSCs as their infectious targets, and even some pathogens may exploit the inhibitory activity of MDSCs to enhance pathogen persistence and chronic infection of the host. Recent researches have revealed the pathogenic significance of MDSCs in pathogens such as bacteria and viruses, despite the fact that the majority of studies on MDSCs have focused on tumor immune evasion. With the increased prevalence of viral respiratory infections, the resurgence of classical tuberculosis, and the advent of medication resistance in common bacterial pneumonia, research on MDSCs in these illnesses is intensifying. The purpose of this work is to provide new avenues for treatment approaches to pulmonary infectious disorders by outlining the mechanism of action of MDSCs as a biomarker and therapeutic target in pulmonary infectious diseases.
The effect of combined knockdowns of Attacins on survival and bacterial load in Tenebrio molitor
Authors: Keshavarz Maryam , Zanchi Caroline , Rolff Jens
Published: March 2023

Introduction

Upon infection, insect hosts simultaneously express a cocktail of antimicrobial peptides (AMPs) which can impede pathogen colonization and increase host fitness. It has been proposed that such a cocktail might be adaptive if the effects of co-expressed AMPs are greater than the sum of individual activities. This could potentially prevent the evolution of bacterial resistance. However, in vivo studies on AMPs in combination are scarce. Attacins are one of the relatively large AMP families, which show anti-Gram-negative activity in vitro.

Material and methods

Here, we used RNA interference (RNAi) to silence three members of the Attacin family genes in the mealworm beetle, Tenebrio molitor: (TmAttacin1a (TmAtt1a), TmAttacin1b (TmAtt1b), and TmAttacin2 (TmAtt2) both individually and in combination. We then infected T. molitor with the Gram negative entomopathogen Pseudomonas entomophila.

Results

We found that survival of the beetles was only affected by the knockdown of TmAttacin1b, TmAttacin2 and the knockdown of all three Attacins together. Triple knockdown, rather than individual or double knockdowns of AMPs, changes the temporal dynamics of their efficiency in controlling the colonization of P. entomophila in the insect body.

Discussion

More precisely, AMP gene expression influences P. entomophila load early in the infection process, resulting in differences in host survival. Our results highlight the importance of studying AMP-interactions in vivo.
Evaluation of preclinical efficacy of human umbilical cord mesenchymal stem cells in ankylosing spondylitis
Authors: Shen Danpeng , Wang Zhiqiang , Wang Hongwei , Zhu Hongyan , Jiang Cuibao , Xie Fan , Zhang Hongpeng , Lv Qian , Liu Qi , Qi Nianmin , Wang Hao
Published: March 2023

Objective

Umbilical cord mesenchymal stem cells (UCMSCs) have significant regenerative, tissue repair, and immunomodulatory properties that can help reduce inflammatory responses in patients with ankylosing spondylitis (AS). In this study, we used a combination of bovine proteoglycan and dimethyldioctadecylammonium (DDA) to establish a mouse model of proteoglycan-induced spondylitis (PGISp). To evaluate the therapeutic effects of UCMSCs, we treated PGISp mice with different doses of hUCMSCs via tail vein injection.

Methods

At week 13, the PGISp mice exhibited thickened, erythematous paws, erythema in the extremities, and lameness. CT scans revealed necrotic lysis of chondrocytes, formation of fissures, visible hemorrhage, connective tissue hyperplasia, and focal infiltration of lymphocytes in the intervertebral discs. At week 14, the PGISp mice were randomly divided into three groups and administered different doses of hUCMSCs (0.25, 0.5, and 1.0×107 cells/kg, iv, QOW×2, n=10). To assess the therapeutic effects of hUCMSCs, we evaluated Th cell subsets in the spleen, spleen and thymus coefficients, peripheral blood inflammatory factors, and pathological and imaging observations of the spines and lumbar spines in the PGISp mice.

Results

The results demonstrated that injection of hUCMSCs shifted the balance axis between Th1 and Th2 cells in the spleen towards Th2 cells. Moreover, the spleen coefficient and levels of inflammatory cytokines (TNF-α and CCL-2) in the serum decreased after hUCMSC injection. CT imaging and pathological analysis indicated that hUCMSC treatment inhibited ectopic osteogenesis and maintained clear small joint gaps, which slowed down the progression of structural lesions in the disc, nucleus pulposus, fibrous ring, and cartilage in PGISp mice.

Conclusion

Administering hUCMSCs at the 14th week after modeling proved to be an effective treatment for PGISp mice. This experiment offers a valuable reference for the pre-clinical use of hUCMSCs in the treatment of AS.
Exosome and virus infection
Authors: Peng Yiqiu , Yang Yuxi , Li Yingying , Shi Tingjuan , Luan Yingyi , Yin Chenghong
Published: March 2023

Exosomes are messengers of intercellular communication in monolayer vesicles derived from cells. It affects the pathophysiological process of the body in various diseases, such as tumors, inflammation, and infection. It has been confirmed that exosomes are similar to viruses in biogenesis, and exosome cargo is widely involved in many viruses’ replication, transmission, and infection. Simultaneously, virus-associated exosomes can promote immune escape and activate the antiviral immune response of the body, which bidirectionally modulates the immune response. This review focuses on the role of exosomes in HIV, HBV, HCV, and SARS-CoV-2 infection and explores the prospects of exosome development. These insights may be translated into therapeutic measures for viral infections and reduce the disease burden.
Alterations in the gut virome in patients with ankylosing spondylitis
Authors: Li Chen , Zhang Yan , Yan Qiulong , Guo Ruochun , Chen Changming , Li Shenghui , Zhang Yue , Meng Jinxin , Ma Jie , You Wei , Wu Zhisong , Sun Wen
Published: March 2023

Introduction

Ankylosing spondylitis (AS), a chronic autoimmune disease, has been linked to the gut bacteriome.

Methods

To investigate the characteristics of the gut virome in AS, we profiled the gut viral community of 193 AS patients and 59 healthy subjects based on a metagenome-wide analysis of fecal metagenomes from two publicly available datasets.

Results

AS patients revealed a significant decrease in gut viral richness and a considerable alteration of the overall viral structure. At the family level, AS patients had an increased abundance of Gratiaviridae and Quimbyviridae and a decreased abundance of Drexlerviridae and Schitoviridae. We identified 1,004 differentially abundant viral operational taxonomic units (vOTUs) between patients and controls, including a higher proportion of AS-enriched Myoviridae viruses and control-enriched Siphoviridae viruses. Moreover, the AS-enriched vOTUs were more likely to infect bacteria such as Flavonifractor, Achromobacter, and Eggerthellaceae, whereas the control-enriched vOTUs were more likely to be Blautia, Ruminococcus, Collinsella, Prevotella, and Faecalibacterium bacteriophages. Additionally, some viral functional orthologs differed significantly in frequency between the AS-enriched and control-enriched vOTUs, suggesting the functional role of these AS-associated viruses. Moreover, we trained classification models based on gut viral signatures to discriminate AS patients from healthy controls, with an optimal area under the receiver operator characteristic curve (AUC) up to 0.936, suggesting the clinical potential of the gut virome for diagnosing AS.

Discussion

This work provides novel insight into the AS gut virome, and the findings may guide future mechanistic and therapeutic studies for other autoimmune diseases.
mRNA melanoma vaccine revolution spurred by the COVID-19 pandemic
Authors: Xu Ziyang , Fisher David E.
Published: March 2023

The advent of mRNA vaccines represents a significant advance in the field of vaccinology. While several vaccine approaches (mRNA, DNA, recombinant protein, and viral-vectored vaccines) had been investigated at the start of the COVID-19 pandemic, mRNA vaccines quickly gained popularity due to superior immunogenicity at a low dose, strong safety/tolerability profiles, and the possibility of rapid vaccine mass manufacturing and deployment to rural regions. In addition to inducing protective neutralizing antibody responses, mRNA vaccines can also elicit high-magnitude cytotoxic T-cell responses comparable to natural viral infections; thereby, drawing significant interest from cancer immunotherapy experts. This mini-review will highlight key developmental milestones and lessons we have learned from mRNA vaccines during the COVID-19 pandemic, with a specific emphasis on clinical trial data gathered so far for mRNA vaccines against melanoma and other forms of cancer.
GRK2 differentially regulates FcεRI and MRGPRB2-mediated responses in mast cells
Authors: Thapaliya Monica , Ali Hydar
Published: March 2023

In addition to high-affinity IgE receptor (FcεRI), a subtype of mouse mast cells (MCs) expresses a G protein-coupled receptor known as Mas-related G protein-coupled receptor (GPCR)-B2 (MRGPRB2; human ortholog MRGPRX2). GPCR kinase 2 (GRK2) is a Serine/Threonine kinase that phosphorylates GPCRs to promote their desensitization and internalization. We previously showed that silencing GRK2 expression in mouse bone marrow-derived MCs (BMMCs) blocks IgE-mediated degranulation. Compound 48/80 (C48/80), substance P (SP) and LL-37 cause degranulation in human and mouse MCs via MRGPRX2 and MRGPRB2, respectively. We also reported that C48/80 and SP cause desensitization and internalization of MRGPRX2, but LL-37 does not. Here, we generated mice with MC-specific deletion of Grk2 (Cpa3Cre+/Grk2fl/fl) to determine its role on IgE-mediated responses and to assess whether it differentially regulates degranulation in response to LL-37, C48/80 and SP. Absence of GRK2 substantially inhibited IgE-mediated tyrosine phosphorylation of STAT5, calcium mobilization, and degranulation in mouse primary lung-derived MCs (PLMCs). By contrast, peritoneal MCs (PMCs) from Cpa3Cre+/Grk2fl/fl mice demonstrated significant enhancement of degranulation in response to C48/80 and SP, but not LL-37. Deletion of Grk2 in MCs attenuated IgE-mediated passive cutaneous anaphylaxis (PCA) and itch but not passive systemic anaphylaxis (PSA). Surprisingly, PSA was significantly reduced in Mrgprb2-/- mice. These findings suggest that GRK2 contributes to PCA and itch but not PSA. By contrast, GRK2 desensitizes MRGPRX2/B2-mediated responses to C48/80 and SP but not LL-37. However, IgE-mediated PSA likely involves the activation of MRGPRB2 by LL-37 or a similar agonist, whose function is resistant to modulation by GRK2.
Fructose potentiates the protective efficiency of live Edwardsiella tarda cell vaccine
Authors: Wang Chao , Peng Xuan-xian , Li Hui
Published: March 2023

Vaccination is an effective measure to prevent infection by pathogens. Live vaccines have higher protective efficacy than inactivated vaccines. However, how live vaccines interact with the host from a metabolic perspective is unknown. The present study aimed to explore whether a live Edwardsiella tarda vaccine regulates host metabolism and whether this regulation is related to the protective efficacy of the vaccine. Therefore, a gas chromatography mass spectrometry (GC-MS)-based metabolomics approach was used to investigate the metabolomic profile of mice serum after vaccination with live E. tarda vaccine. Fructose was identified as a key biomarker that contributes to the immune protection induced by the live vaccine. Moreover, co-administration of exogenous fructose and the live vaccine synergistically promoted survival of mice and fish after bacterial challenge. These results indicate that metabolites, especially fructose, can potentiate the live E. tarda vaccine to increase its protective efficiency.
Development of hybrid SVM-FA, DT-FA and MLR-FA models to predict the flexural strength (FS) of recycled concrete
Authors: Wang Qiang , Zhou Mengmeng
Published: March 2023

Recycled concrete from construction waste used as road material is a current sustainable approach. To provide feasible suggestions for civil engineers to prepare recycled concrete with high flexural strength (FS) for the road pavement, the present study proposed three hybrid machine learning models by combining support vector machine (SVM), decision tree (DT) and multiple linear regression (MLR) with the firefly algorithm (FA) for the computational optimization, named as SVM-FA, DT-FA, and MLR-FA, respectively. Effective water-cement ratio (WC), aggregate-cement ratio (AC), recycled concrete aggregate replacement ratio (RCA), nominal maximum recycled concrete aggregate size (NMR), nominal maximum normal aggregate size (NMN), bulk density of recycled concrete aggregate (BDR), bulk density of normal aggregate (BDN), water absorption of RCA (WAR) and water absorption of NA (WAN) were employed as the input variables. To determine the predicting results of varying hybrid models, root mean square error (RMSE) and correlation coefficient (R) were used as performance indexes. The results showed that the SVM-FA demonstrated the highest R values and the lowest RMSE values, and the fitting effect of the predicted values and the actual values of the FS of recycled concrete is the best. All the above analysis proving that the SVM optimized by FA hyperparameters has the highest prediction accuracy and SVM-FA can provide engineers a more accurate and convenient tool to evaluate the FS of recycled concrete. The results of sensitivity analysis showed that WC has the most significant influence on the FS of recycled concrete, while RCA has the weakest influence on the FS, which should be noticed when engineers apply recycled concrete to road design in the future.
The impact of persistent precarity on patients’ capacity to manage their treatment burden: A comparative qualitative study between urban and rural patients with multimorbidity in South Africa
Authors: van Pinxteren Myrna , Mbokazi Nonzuzo , Murphy Katherine , Mair Frances S. , May Carl , Levitt Naomi
Published: March 2023

Background

People living with multimorbidity in low-and middle-income countries (LMICs) experience a high workload trying to meet the demands of self-management. In an unequal society like South Africa, many people face continuous economic uncertainty, which can impact on their capacity to manage their illnesses and lead to poor health outcomes. Using precariousness – the real and perceived impact of uncertainty – as a lens, this paper aims to identify, characterise, and understand the workload and capacity associated with self-management amongst people with multimorbidity living in precarious circumstances in urban and rural South Africa.

Methods

We conducted qualitative semi-structured interviews with 30 patients with HIV and co-morbidities between February and April 2021. Patients were attending public clinics in Cape Town (Western Cape) and Bulungula (Eastern Cape). Interviews were transcribed and data analysed using qualitative framework analysis. Burden of Treatment Theory (BoTT) and the Cumulative Complexity Model (CuCoM) were used as theoretical lenses through which to conceptualise the data.

Results

People with multimorbidity in rural and urban South Africa experienced multi-faceted precariousness, including financial and housing insecurity, dangerous living circumstances and exposure to violence. Women felt unsafe in their communities and sometimes their homes, whilst men struggled with substance use and a lack of social support. Older patients relied on small income grants often shared with others, whilst younger patients struggled to find stable employment and combine self-management with family responsibilities. Precariousness impacted access to health services and information and peoples’ ability to buy healthy foods and out-of-pocket medication, thus increasing their treatment burden and reducing their capacity.

Conclusion

This study highlights that precariousness reduces the capacity and increases treatment burden for patients with multimorbidity in low-income settings in South Africa. Precariousness is both accumulative and cyclic, as financial insecurity impacts every aspect of peoples’ daily lives. Findings emphasise that current models examining treatment burden need to be adapted to accommodate patients’ experiences in low-income settings and address cumulative precariousness. Understanding treatment burden and capacity for patients in LMICs is a crucial first step to redesign health systems which aim to improve self-management and offer comprehensive person-centred care.
Individualized conservative therapeutic strategies for adenomyosis with the aim of preserving fertility
Authors: Han Lei , Liu Yanni , Lao Kaixue , Jiang Jianxi , Zhang Caiying , Wang Yanlin
Published: March 2023

Adenomyosis is a diffuse or localized organic disease caused by benign invasion of endometrial glands and stroma into the myometrium. It is a common disease that seriously affects reproductive health of women in childbearing age. Due to the unknown etiology and pathophysiological mechanism, and the lack of unified diagnostic criteria and effective treatment methods, total or subtotal hysterectomy has become a radical treatment for adenomyosis, which will lead to the complete loss of fertility. With the continuous exploration of the treatment to adenomyotic patients who have infertility or fertility intentions, new drugs, surgical methods and treating concepts appears. Adopt individualized conservative therapeutic strategies for patients with different conditions, preserve the uterus as much as possible and protect the patient’s fertility, which will play an important role on the follow-up assisted reproductive treatment and long-term management of adenomyosis.
The application of data altruism in clinical research through empirical and legal analysis lenses
Authors: Lalova-Spinks Teodora , Meszaros Janos , Huys Isabelle
Published: March 2023

Background

The legal framework for clinical research in the EU is complex and the lack of harmonization of the relevant legal and ethical rules remains one of the main challenges for stakeholders in the field. The recently adopted Data Governance Act (DGA) and the proposal for a European Health Data Space (EHDS) promise to solve the existing challenges with respect to access to and (re)use of personal data for research, but also risk to further complexify the field. The DGA introduced a novel mechanism – data altruism. Data altruism is understood as the voluntary sharing of personal and non-personal data, based on the consent of data subjects or the permission of natural and legal persons, without seeking a reward and for objectives of general interest. This study aimed to gain insights into the opinion of clinical research stakeholders on data altruism, and to critically discuss key issues pertaining to the application of data altruism from a legal point of view.

Methods

Semi-structured interviews with (1) data protection officers (DPOs) and legal experts working with commercial and academic sponsors of clinical trials, (2) investigators, and (3) members of research ethics committees. Data underwent framework analysis. The legal discussion was comprised of legal doctrinal research with focus on the DGA, EHDS proposal, and the interplay with the EU General Data Protection Regulation (GDPR).

Results

Fourteen experts took part in the interviews, more than half of which were DPOs/legal experts. Interviewees were based in seven EU Member states and the United Kingdom. The majority of participants were critical towards the data altruism mechanism and pointed out challenges and risks associated with its application.

Conclusion

Although data altruism holds the potential to facilitate data sharing, its application in clinical research at the moment is still riddled with uncertainties. The interplay of the DGA rules with the provisions of the GDPR and the EHDS proposal are insufficiently clear and further efforts from the legislator are required to build a working, patient-centered, and research fostering data altruism system.
Targeted plasma metabolomics combined with machine learning for the diagnosis of severe acute respiratory syndrome virus type 2
Authors: Le Anthony T. , Wu Manhong , Khan Afraz , Phillips Nicholas , Rajpurkar Pranav , Garland Megan , Magid Kayla , Sibai Mamdouh , Huang ChunHong , Sahoo Malaya K. , Bowen Raffick , Cowan Tina M. , Pinsky Benjamin A. , Hogan Catherine A.
Published: March 2023

Introduction

The routine clinical diagnosis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is largely restricted to real-time reverse transcription quantitative PCR (RT-qPCR), and tests that detect SARS-CoV-2 nucleocapsid antigen. Given the diagnostic delay and suboptimal sensitivity associated with these respective methods, alternative diagnostic strategies are needed for acute infection.

Methods

We studied the use of a clinically validated liquid chromatography triple quadrupole method (LC/MS–MS) for detection of amino acids from plasma specimens. We applied machine learning models to distinguish between SARS-CoV-2-positive and negative samples and analyzed amino acid feature importance.

Results

A total of 200 samples were tested, including 70 from individuals with COVID-19, and 130 from negative controls. The top performing model overall allowed discrimination between SARS-CoV-2-positive and negative control samples with an area under the receiver operating characteristic curve (AUC) of 0.96 (95%CI 0.91, 1.00), overall sensitivity of 0.99 (95%CI 0.92, 1.00), and specificity of 0.92 (95%CI 0.85, 0.95).

Discussion

This approach holds potential as an alternative to existing methods for the rapid and accurate diagnosis of acute SARS-CoV-2 infection.
Occupational exposure in swine farm defines human skin and nasal microbiota
Authors: Wang Xiran , Chen Dongrui , Du Juan , Cheng Ke , Fang Chang , Liao Xiaoping , Liu Yahong , Sun Jian , Lian Xinlei , Ren Hao
Published: March 2023

Anthropogenic environments take an active part in shaping the human microbiome. Herein, we studied skin and nasal microbiota dynamics in response to the exposure in confined and controlled swine farms to decipher the impact of occupational exposure on microbiome formation. The microbiota of volunteers was longitudinally profiled in a 9-months survey, in which the volunteers underwent occupational exposure during 3-month internships in swine farms. By high-throughput sequencing, we showed that occupational exposure compositionally and functionally reshaped the volunteers’ skin and nasal microbiota. The exposure in farm A reduced the microbial diversity of skin and nasal microbiota, whereas the microbiota of skin and nose increased after exposure in farm B. The exposure in different farms resulted in compositionally different microbial patterns, as the abundance of Actinobacteria sharply increased at expense of Firmicutes after exposure in farm A, yet Proteobacteria became the most predominant in the volunteers in farm B. The remodeled microbiota composition due to exposure in farm A appeared to stall and persist, whereas the microbiota of volunteers in farm B showed better resilience to revert to the pre-exposure state within 9 months after the exposure. Several metabolic pathways, for example, the styrene, aminobenzoate, and N-glycan biosynthesis, were significantly altered through our PICRUSt analysis, and notably, the function of beta-lactam resistance was predicted to enrich after exposure in farm A yet decrease in farm B. We proposed that the differently modified microbiota patterns might be coordinated by microbial and non-microbial factors in different swine farms, which were always environment-specific. This study highlights the active role of occupational exposure in defining the skin and nasal microbiota and sheds light on the dynamics of microbial patterns in response to environmental conversion.
The EJC disassembly factor PYM is an intrinsically disordered protein and forms a fuzzy complex with RNA
Authors: Verma Deepshikha , Hegde Veena , Kirkpatrick John , Carlomagno Teresa
Published: March 2023

The discovery of several functional interactions where one or even both partners remain disordered has demonstrated that specific interactions do not necessarily require well-defined intermolecular interfaces. Here we describe a fuzzy protein–RNA complex formed by the intrinsically unfolded protein PYM and RNA. PYM is a cytosolic protein, which has been reported to bind the exon junction complex (EJC). In the process of oskar mRNA localization in Drosophila melanogaster, removal of the first intron and deposition of the EJC are essential, while PYM is required to recycle the EJC components after localization has been accomplished. Here we demonstrate that the first 160 amino acids of PYM (PYM1–160) are intrinsically disordered. PYM1–160 binds RNA independently of its nucleotide sequence, forming a fuzzy protein–RNA complex that is incompatible with PYM’s function as an EJC recycling factor. We propose that the role of RNA binding consists in down-regulating PYM activity by blocking the EJC interaction surface of PYM until localization has been accomplished. We suggest that the largely unstructured character of PYM may act to enable binding to a variety of diverse interaction partners, such as multiple RNA sequences and the EJC proteins Y14 and Mago.
Creatine in the fetal brain: A regional investigation of acute global hypoxia and creatine supplementation in a translational fetal sheep model
Authors: Tran Nhi T. , Muccini Anna M. , Hale Nadia , Tolcos Mary , Snow Rod J. , Walker David W. , Ellery Stacey J.
Published: March 2023

Background

Creatine supplementation during pregnancy is a promising prophylactic treatment for perinatal hypoxic brain injury. Previously, in near-term sheep we have shown that fetal creatine supplementation reduces cerebral metabolic and oxidative stress induced by acute global hypoxia. This study investigated the effects of acute hypoxia with or without fetal creatine supplementation on neuropathology in multiple brain regions.

Methods

Near-term fetal sheep were administered continuous intravenous infusion of either creatine (6 mg kg–1 h–1) or isovolumetric saline from 122 to 134 days gestational age (dGA; term is approx. 145 dGA). At 131 dGA, global hypoxia was induced by a 10 min umbilical cord occlusion (UCO). Fetuses were then recovered for 72 h at which time (134 dGA) cerebral tissue was collected for either RT-qPCR or immunohistochemistry analyses.

Results

UCO resulted in mild injury to the cortical gray matter, thalamus and hippocampus, with increased cell death and astrogliosis and downregulation of genes involved in regulating injury responses, vasculature development and mitochondrial integrity. Creatine supplementation reduced astrogliosis within the corpus callosum but did not ameliorate any other gene expression or histopathological changes induced by hypoxia. Of importance, effects of creatine supplementation on gene expression irrespective of hypoxia, including increased expression of anti-apoptotic (BCL-2) and pro-inflammatory (e.g., MPO, TNFa, IL-6, IL-1β) genes, particularly in the gray matter, hippocampus, and striatum were identified. Creatine treatment also effected oligodendrocyte maturation and myelination in white matter regions.

Conclusion

While supplementation did not rescue mild neuropathology caused by UCO, creatine did result in gene expression changes that may influence in utero cerebral development.
Prescription trends of antiseizure medications before and during the COVID-19 pandemic
Authors: Lavu Alekhya , Janzen Donica , Aboulatta Laila , Peymani Payam , Haidar Lara , Desrochers Brianne , Alessi-Severini Silvia , Eltonsy Sherif
Published: March 2023

Introduction

Given the lack of evidence on how the COVID-19 pandemic impacted antiseizure medication (ASM) use, we examined the trends of ASMs before and during COVID-19.

Methods

We conducted a population-based study using provincial-level health databases from Manitoba, Canada, between 1 June 2016 and 1 March 2021. We used interrupted time series autoregressive models to examine changes in the prevalence and incidence of ASM prescription rates associated with COVID-19 public health restrictions.

Results

Among prevalent users, the COVID-19 pandemic led to a significant increase in new-generation ASMs with a percentage change of 0.09% (p = 0.03) and a significant decrease in incidence use of all ASMs with a percentage change of −4.35% (p = 0.04). Significant trend changes were observed in the prevalent use of new-generation ASMs (p = 0.04) and incidence use of all (p = 0.04) and new-generation ASMs (p = 0.02). Gabapentin and clonazepam prescriptions contributed 37% of prevalent and 54% of incident use.

Conclusion

With the introduction of public health measures during COVID-19, small but significant changes in the incident and prevalent use of ASM prescriptions were observed. Further studies are needed to examine whether barriers to medication access were associated with potential deterioration in seizure control among patients.

Conference presentation

The results from this study have been presented as an oral presentation at the 38th ICPE, International Society of Pharmacoepidemiology (ISPE) annual conference in Copenhagen.
Comparison efficacy of ultrasound-guided needle release plus corticosteroid injection and mini-open surgery in patients with carpal tunnel syndrome
Authors: Zeng Zeng , Lin Nan , Chen Cong-Xian
Published: March 2023

This retrospective study was to compare clinical outcomes of ultrasound-guided needle release with corticosteroid injection vs. mini-open surgery in patients with carpal tunnel syndrome (CTS). From January 2021 to December 2021, 40 patients (40 wrists) with CTS were analyzed in this study. The diagnosis was based on clinical symptoms, electrophysiological imaging, and ultrasound imaging. A total of 20 wrists were treated with ultrasound-guided needle release plus corticosteroid injection (Group A), and the other 20 wrists were treated with mini-open surgery (Group B). We evaluated the Boston carpal tunnel questionnaire, electrophysiological parameters (distal motor latency, sensory conduction velocity, and sensory nerve action potential of the median nerve), and ultrasound parameters (cross-sectional area, flattening ratio, and the thicknesses of transverse carpal ligament) both before and 3 months after treatment. Total treatment cost, duration of treatment, healing time, and complications were also recorded for the two groups. The Boston carpal tunnel questionnaire and electrophysiological and ultrasound outcomes at preoperatively and 3 months postoperatively had a significant difference for each group (each with P < 0.05). There were no complications such as infection, hemorrhage, vascular, nerve, or tendon injuries in both groups. Ultrasound-guided needle release and mini-open surgery are both effective measures in treating CTS patients. Ultrasound-guided needle release plus corticosteroid injection provides smaller incision, less cost, less time of treatment, and faster recovery compared with mini-open surgery. Ultrasound-guided needle release plus corticosteroid injection is better for clinical application.
Running away from phonological ambiguity, we stumble upon our words: Laboratory induced slips show differences between highly and lowly defensive people
Authors: Thieffry Lola , Olyff Giulia , Pioda Lea , Detandt Sandrine , Bazan Ariane
Published: March 2023

Introduction

Freud proposed that slips of the tongue, including apparently simple ones, always have a sense and constitute « a half-success and a half-failure » compromise resulting from defensive mechanisms.

Material and methods

A total of 55 subjects participated in a French adaptation of theSpoonerisms of Laboratory Induced Predispositionor SLIP-technique including 32 “neutral” and 32 taboo spoonerisms and measures of defensiveness. In accordance with a psychoanalytical and empirically supported distinction, we considered two kinds of defenses: elaborative or primary process and inhibitory or secondary process defenses, which were operationalized with the GeoCat and the Phonological-Nothing (PN) WordList, respectively. The GeoCat is a validated measure of primary process mentation and the PN WordList was shown to measure the defensive avoidance of language ambiguity.

Results

Participants produced 37 slips, with no significant difference in the number of “neutral” and taboo slips. The GeoCat and the N/PN parameters explained 30% of the variance in the production of parapraxes, confirming the defensive logics of slips. When dividing the population into lowly and highly defensive participants (with the Marlowe Crowne Social Desirability scale), primary process mentation appears as a baseline default defense, but only highly defensive participants mobilize an additional inhibitory secondary process type of defense. Taking into account thea prioridifference between taboo and “neutral” parapraxes, highly defensive participants made 2.7 times more taboo parapraxes than lowly defensive participants. However, if “neutral” parapraxes in both subgroups followed the same logic as the total group of parapraxes (significant contribution of primary process mentation in lowly defensives and of primary and secondary process mentation in highly defensives), these measures had no contribution to explain the occurrence of taboo parapraxes.

Conclusion

We propose that Motley et al.’s prearticulatory editor, ensuring the censorship over taboo parapraxes, is an external instance of inhibition, proximal to uttering, equivalent to the censorship between the systems Preconscious and Conscious in Freud’s metapsychology. By contrast, the defenses measured in this research are internal, intimate control systems, probing for the censorship between the systems Unconscious and Preconscious, this is, for repression. This study contributes to support a psychodynamic explanatory model for the production of parapraxes.
Combined transcriptomics and proteomics forecast analysis for potential biomarker in the acute phase of temporal lobe epilepsy
Authors: Huang Cong , You Zhipeng , He Yijie , Li Jiran , Liu Yang , Peng Chunyan , Liu Zhixiong , Liu Xingan , Sun Jiahang
Published: March 2023

Background

Temporal lobe epilepsy (TLE) is a common chronic episodic illness of the nervous system. However, the precise mechanisms of dysfunction and diagnostic biomarkers in the acute phase of TLE are uncertain and hard to diagnose. Thus, we intended to qualify potential biomarkers in the acute phase of TLE for clinical diagnostics and therapeutic purposes.

Methods

An intra-hippocampal injection of kainic acid was used to induce an epileptic model in mice. First, with a TMT/iTRAQ quantitative labeling proteomics approach, we screened for differentially expressed proteins (DEPs) in the acute phase of TLE. Then, differentially expressed genes (DEGs) in the acute phase of TLE were identified by linear modeling on microarray data (limma) and weighted gene co-expression network analysis (WGCNA) using the publicly available microarray dataset GSE88992. Co-expressed genes (proteins) in the acute phase of TLE were identified by overlap analysis of DEPs and DEGs. The least absolute shrinkage and selection operator (LASSO) regression and support vector machine recursive feature elimination (SVM-RFE) algorithms were used to screen Hub genes in the acute phase of TLE, and logistic regression algorithms were applied to develop a novel diagnostic model for the acute phase of TLE, and the sensitivity of the diagnostic model was validated using receiver operating characteristic (ROC) curves.

Results

We screened a total of 10 co-expressed genes (proteins) from TLE-associated DEGs and DEPs utilizing proteomic and transcriptome analysis. LASSO and SVM-RFE algorithms for machine learning were applied to identify three Hub genes: Ctla2a, Hapln2, and Pecam1. A logistic regression algorithm was applied to establish and validate a novel diagnostic model for the acute phase of TLE based on three Hub genes in the publicly accessible datasets GSE88992, GSE49030, and GSE79129.

Conclusion

Our study establishes a reliable model for screening and diagnosing the acute phase of TLE that provides a theoretical basis for adding diagnostic biomarkers for TLE acute phase genes.
Cortico-basal ganglia networks dysfunction associated with disease severity in patients with idiopathic blepharospasm
Authors: Cheng Qinxiu , Xiao Han , Luo Yuhan , Zhong Linchang , Guo Yaomin , Fan Xinxin , Zhang Xiaodong , Liu Ying , Weng Ai , Ou Zilin , Zhang Weixi , Wu Huawang , Hu Qingmao , Peng Kangqiang , Xu Jinping , Liu Gang
Published: March 2023

Background

Structural changes occur in brain regions involved in cortico-basal ganglia networks in idiopathic blepharospasm (iBSP); whether these changes influence the function connectivity patterns of cortico-basal ganglia networks remains largely unknown. Therefore, we aimed to investigate the global integrative state and organization of functional connections of cortico-basal ganglia networks in patients with iBSP.

Methods

Resting-state functional magnetic resonance imaging data and clinical measurements were acquired from 62 patients with iBSP, 62 patients with hemifacial spasm (HFS), and 62 healthy controls (HCs). Topological parameters and functional connections of cortico-basal ganglia networks were evaluated and compared among the three groups. Correlation analyses were performed to explore the relationship between topological parameters and clinical measurements in patients with iBSP.

Results

We found significantly increased global efficiency and decreased shortest path length and clustering coefficient of cortico-basal ganglia networks in patients with iBSP compared with HCs, however, such differences were not observed between patients with HFS and HCs. Further correlation analyses revealed that these parameters were significantly correlated with the severity of iBSP. At the regional level, the functional connectivity between the left orbitofrontal area and left primary somatosensory cortex and between the right anterior part of pallidum and right anterior part of dorsal anterior cingulate cortex was significantly decreased in patients with iBSP and HFS compared with HCs.

Conclusion

Dysfunction of the cortico-basal ganglia networks occurs in patients with iBSP. The altered network metrics of cortico-basal ganglia networks might be served as quantitative markers for evaluation of the severity of iBSP.
Cerebellar control of thalamocortical circuits for cognitive function: A review of pathways and a proposed mechanism
Authors: Heck Detlef H. , Fox Mia B. , Correia Chapman Brittany , McAfee Samuel S. , Liu Yu
Published: March 2023

There is general agreement that cerebrocerebellar interactions via cerebellothalamocortical pathways are essential for a cerebellar cognitive and motor functions. Cerebellothalamic projections were long believed target mainly the ventral lateral (VL) and part of the ventral anterior (VA) nuclei, which project to cortical motor and premotor areas. Here we review new insights from detailed tracing studies, which show that projections from the cerebellum to the thalamus are widespread and reach almost every thalamic subnucleus, including nuclei involved in cognitive functions. These new insights into cerebellothalamic pathways beyond the motor thalamus are consistent with the increasing evidence of cerebellar cognitive function. However, the function of cerebellothalamic pathways and how they are involved in the various motor and cognitive functions of the cerebellum is still unknown. We briefly review literature on the role of the thalamus in coordinating the coherence of neuronal oscillations in the neocortex. The coherence of oscillations, which measures the stability of the phase relationship between two oscillations of the same frequency, is considered an indicator of increased functional connectivity between two structures showing coherent oscillations. Through thalamocortical interactions coherence patterns dynamically create and dissolve functional cerebral cortical networks in a task dependent manner. Finally, we review evidence for an involvement of the cerebellum in coordinating coherence of oscillations between cerebral cortical structures. We conclude that cerebellothalamic pathways provide the necessary anatomical substrate for a proposed role of the cerebellum in coordinating neuronal communication between cerebral cortical areas by coordinating the coherence of oscillations.