bluuebunny/crossref_metadata_2025 huggingface dataset:
Confidence and motivation to teach primary physical education: A survey of specialist primary physical education pre-service teachers in Australia
Authors: Spittle Sharna , Spittle Michael , Encel Kim , Itoh Sho
Published: November 2022

Introduction

This study explored confidence and motivation to teach physical education of pre-service teachers specialising in primary school physical education.

Methods

Participants were 277 pre-service teachers with a mean age of 21.37 years (SD = 3.09) enrolled in a Bachelor of Education (P-12) who were specialising in primary physical education (P-6). Pre-service teachers completed the Confidence and Motivation to Teach Primary Physical Education Questionnaire (CMTPPEQ), which measures confidence (management and planning and implementation) and intrinsic, extrinsic, and amotivated types of motivation (knowledge, performance, practice, professional expectations, student outcomes, and disengagement) toward teaching primary school physical education.

Results

Pre-service teachers reported higher confidence in implementation and higher motivation in practice and performance, with very low disengagement. Pre-service teachers in first-year were significantly less confident in both management and planning and implementation than other year levels (p < 0.05). Pre-service teachers with less training and experience (completed no units in physical education or who had taught less than one hour of physical education on teaching rounds) were significantly less confident in both management and planning and implementation (p < 0.05). Pre-service teachers reported higher intrinsic motivation for practice and extrinsic motivation for performance, with males reporting significantly higher extrinsic motivation in professional expectations than females (p < 0.05).

Discussion

The study has highlighted the confidence of pre-service primary physical education specialist teachers in implementing physical education, but lower confidence in management and planning. A practical implication from the findings is the importance of training and experience in developing confidence and motivation, even for those specialising in physical education.
Bariatric endoscopic-surgical therapies for NAFLD. Should they be considered viable options among current treatments?
Authors: Juárez-Hernández Eva , Velázquez-Alemán Alain P. , Castro-Narro Graciela , Uribe Misael , López-Méndez Iván
Published: November 2022

Nowadays, non-alcoholic fatty liver disease is one of the first causes of liver transplant worldwide; many efforts have been done to find the perfect drug for this multifactorial disease. Presently we just have a few drugs that could be used in specific and limited clinical scenarios. Current evidence suggests that bariatric endoscopic and surgical therapies could be strategies with optimal outcomes, with high impact in quality of life, decrease of cardiovascular risk, and improvement in metabolic profile, despite being considered expensive procedures. This review proposes to consider these therapies early together with liver fibrosis evaluation, with long term cost-effectiveness benefits in the absence of response to lifestyle modifications and pharmacological treatments.
Polycystic ovary syndrome: Identification of novel and hub biomarkers in the autophagy-associated mRNA-miRNA-lncRNA network
Authors: Huang Jiayu , Huang Baoyi , Kong Yanxiang , Yang Yazhu , Tian Chengzi , Chen Lin , Liao Yan , Ma Lin
Published: November 2022

Introduction

Polycystic ovary syndrome (PCOS) is a common metabolic and endocrine disorder prevalent among women of reproductive age. Recent studies show that autophagy participated in the pathogenesis of PCOS, including anovulation, hyperandrogenism, and metabolic disturbances. This study was designed to screen autophagy-related genes (ATGs) that may play a pivotal role in PCOS, providing potential biomarkers and identifying new molecular subgroups for therapeutic intervention.

Methods

Gene expression profiles of the PCOS and control samples were obtained from the publicly available Gene Expression Omnibus database. The gene lists of ATGs from databases were integrated. Then, the weighted gene co-expression network analysis was conducted to obtain functional modules and construct a multifactorial co-expression network. Gene Ontology and KEGG pathway enrichment analyses were performed for further exploration of ATG's function in the key modules. Differentially expressed ATGs were identified and validated in external datasets with the Limma R package. To provide guidance on PCOS phenotyping, the dysfunction module consists of a co-expression network mapped to PCOS patients. A PCOS-Autophagy-related co-expression network was established using Cytoscape, followed by identifying molecular subgroups using the Limma R package. ps. RNA-sequencing analysis was used to confirm the differential expression of hub ATGs, and the diagnostic value of hub ATGs was assessed by receiver operating characteristic curve analysis.

Results

Three modules (Brown, Turquoise, and Green) in GSE8157, three modules (Blue, Red, and Green) in GSE43264, and four modules (Blue, Green, Black, and Yellow) in GSE106724 were identified to be PCOS-related by WGCNA analysis. 29 ATGs were found to be the hub genes that strongly correlated with PCOS. These hub ATGs were mainly enriched in autophagy-related functions and pathways such as autophagy, endocytosis, apoptosis, and mTOR signaling pathways. The mRNA-miRNA-lncRNA multifactorial network was successfully constructed. And three new molecular subgroups were identified via the K-means algorithm.

Discussion

We provide a novel insight into the mechanisms behind autophagy in PCOS. BRCA1, LDLR, MAP1B, hsa-miR-92b-3p, hsa-miR-20b-5p, and NEAT1 might play a considerably important role in PCOS dysfunction. As a result, new potential biomarkers can be evaluated for use in PCOS diagnosis and treatment in the future.
Cyp17a2 is involved in testicular development and fertility in male Nile tilapia, Oreochromis niloticus
Authors: Yang Lanying , Wu You , Su Yun , Zhang Xuefeng , Chakraborty Tapas , Wang Deshou , Zhou Linyan
Published: November 2022

Background

Steroid hormones play an essential role in many reproductive processes of vertebrates. Previous studies revealed that teleost-specific Cyp17a2 (cytochrome P450 family 17 subfamily a 2) might be required for the production of cortisol in the head-kidney and 17α,20β-dihydroxy-4-pregnen-3-one (DHP) in ovary during oocyte maturation. However, the role of Cyp17a2 in male reproduction remains to be largely unknown. The aim of this study was to explore the essentiality of cyp17a2 gene in male steroidogenesis, spermatogenesis, and male fertility.

Methods

A homozygous mutation line of cyp17a2 gene was constructed in tilapia by CRISPR/Cas9 gene editing technology. The expression level of germ cell and meiosis-related genes and steroidogenic enzymes were detected by qRT-PCR, IHC, and Western blotting. EIA and LC-MS/MS assays were used to measure the steroid production levels. And sperm quality was examined by Sperm Quality Analyzer software.

Results

In this study, cyp17a2 gene mutation resulted in the significant decline of serum DHP and cortisol levels. On the contrary, significant increases in intermediate products of cortisol and DHP were found in cyp17a2-/- male fish. The deficiency of cyp17a2 led to the arrest of meiotic initiation in male fish revealing as the reduction of the expression of germ cell-related genes (vasa, piwil, oct4) and meiosis-related genes (spo11 and sycp3) by 90 dah. Afterwards, spermatogenesis was gradually recovered with the development of testis in cyp17a2-/- males, but it showed a lower sperm motility and reduced fertility compared to cyp17a2+/+ XY fish. Deletion of cyp17a2 led to the abnormal upregulation of steroidogenic enzymes for cortisol production in the head-kidney. Moreover, unaltered serum androgens and estrogens, as well as unchanged related steroidogenic enzymes were found in the testis of cyp17a2-/- male fish.

Conclusion

This study proved that, for the fist time, Cyp17a2 is indispensable for cortisol and DHP production, and cyp17a2 deficiency associated curtailed meiotic initiation and subfertility suggesting the essentiality of DHP and cortisol in the male fertility of fish.
Complex (multispecies) livestock keeping: Highland agricultural strategy in the northern Horn of Africa during the Pre-Aksumite (1600 BCE–400 BCE) and Aksumite (400 BCE–CE 800) periods
Authors: Woldekiros Helina S. , D’Andrea A. Catherine
Published: November 2022

The earliest settlements and states in the Horn of Africa were founded in mid to high-elevation areas by farmers and herders who were pioneers in agriculture and herding. Even today, places between mid- and high-elevation remain densely populated. The ancient Pre-Aksumites and Aksumites (1600 cal BCE–800 cal CE) of the north Ethiopian and Eritrean highlands established one of the most powerful states in the Horn of Africa in these high elevation areas through control of long-distance trade and intensive and extensive agriculture. However, despite the fact that agriculture was a significant source of wealth and subsistence for these ancient polities, there has been little research into the agricultural strategies of Pre-Aksumite and Aksumite societies. Using archaeological and faunal data collected from the site of Mezber dating from 1600 cal BCE to 400 cal CE, as well as prevsiously published data, this article provides zooarchaeological evidence for the earliest farming practices in the Horn of Africa. The research demonstrates a resilient highland agricultural strategy based on multispecies animal and plant resources, similar to most tropical agricultural systems today. A second important strategy of Pre-Aksumite farmers was the incorporation of both indigenous and exogenous plants and animals into their subsistance strategies. The Mezber site also offers one of the most thoroughly collected data to support multispecies farming practice in the north Ethiopian and Eritrean highlands.
A heterozygous mutation in NOTCH3 in a Chinese family with CADASIL
Authors: Li Juyi , Luo Tao , Wang Xiufang , Wang Mengjie , Zheng Tao , Dang Xiao , Deng Aiping , Zhang Youzhi , Ding Sheng , Jing Ping , Zhu Lin
Published: November 2022

Introduction: Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an autosomal-dominant systemic vascular disease that primarily involves small arteries. Patients with CADASIL experience migraines, recurrent ischemic strokes, cognitive decline, and dementia. The NOTCH3 gene, which is located on chromosome 19p13.12, is one of the disease-causing genes in CADASIL. Herein, we investigate the genetic and phenotypic features in a Chinese CADASIL family with heterozygous NOTCH3 mutation.

Methods and Results: In the family, the proband suffered from dizziness, stroke, and cognitive deficits. Brain magnetic resonance imaging (MRI) demonstrated symmetrical white matter lesions in the temporal lobe, outer capsule, lateral ventricle, and deep brain. Whole-exome sequencing identified a known missense mutation in the proband, c.397C>T (p.Arg133Cys), which was identified in his son and granddaughter using Sanger sequencing. The proband’s younger brother and younger sister also have a history of cognitive impairment or cerebral infarction, but do not have this genetic mutation, which may highlight the impact of lifestyle on this neurological disease.

Conclusion: We identified a known CADASIL-causing mutation NOTCH3 (c.397C>T, p.Arg133Cys) in a Chinese family. The clinical manifestations of mutation carriers in this family are highly heterogeneous, which is likely a common feature for the etiology of different mutations in CADASIL. Molecular genetic analyses are critical for accurate diagnosis, as well as the provision of genetic counselling for CADASIL.
More than meets the eye: The role of microglia in healthy and diseased retina
Authors: Murenu Elisa , Gerhardt Maximilian-Joachim , Biel Martin , Michalakis Stylianos
Published: November 2022

Microglia are the main resident immune cells of the nervous system and as such they are involved in multiple roles ranging from tissue homeostasis to response to insults and circuit refinement. While most knowledge about microglia comes from brain studies, some mechanisms have been confirmed for microglia cells in the retina, the light-sensing compartment of the eye responsible for initial processing of visual information. However, several key pieces of this puzzle are still unaccounted for, as the characterization of retinal microglia has long been hindered by the reduced population size within the retina as well as the previous lack of technologies enabling single-cell analyses. Accumulating evidence indicates that the same cell type may harbor a high degree of transcriptional, morphological and functional differences depending on its location within the central nervous system. Thus, studying the roles and signatures adopted specifically by microglia in the retina has become increasingly important. Here, we review the current understanding of retinal microglia cells in physiology and in disease, with particular emphasis on newly discovered mechanisms and future research directions.
Vesicle-mediated transport-related genes are prognostic predictors and are associated with tumor immunity in lung adenocarcinoma
Authors: Qian Changrui , Jiang Zewei , Zhou Tong , Wu Tao , Zhang Yi , Huang Ju , Ouyang Jinglin , Dong Zhixiong , Wu Guang , Cao Jiawei
Published: November 2022

Background

Globally, lung adenocarcinoma (LUAD) is the leading cause of cancer-related deaths. It is a progressive disorder that arises from multiple genetic and environmental factors. Dysregulated expression of vesicle-mediated transport-related genes (VMTRGs) have been reported in several cancers. However, the prognostic significance of VMTRGs in LUAD has yet to be established.

Methods

The VMTRG profiling data for 482 LUAD patients and 59 normal controls were downloaded from The Cancer Genome Altas (TCGA). Univariate Cox regression and Least Absolute Shrinkage and Selection Operator (LASSO) regression analyses were performed to construct and optimize the risk model. Several GEO datasets were used to validate the risk model. The roles of these genes were investigated via the Kyoto Encyclopedia of Genes and Genomes (KEGG) and gene ontology (GO) enrichment analyses. Differences in immune cell infiltrations between risk groups were evaluated using five algorithms. “pRRophetic” was used to investigate anti-cancer drug sensitivities in two groups. Expression of these five genes in LUAD samples and adjacent normal tissues were evaluated by qRT-PCR. Colony formation and wound healing assays were performed to assess the significance of CNIH1 and AP3S1 in LUAD cells.

Results

We identified 85 prognosis-associated VMTRGs that could be constructed a risk model for LUAD patients, indicating their potential importance in LUAD development. The risk model including the five VMTRGs (CNIH1, KIF20A, GALNT2, GRIA1, and AP3S1) was associated with clinical outcomes. Tumor stage and risk score were found to be independent prognostic factors for LUAD patients. The five VMTRGs were also correlated with activation of the Notch and p53 signaling pathways. The risk model was significantly associated with immune responses and with high-level expression of immune checkpoints. High-risk group patients were more sensitive to several chemotherapeutic drugs and Lapatinib. Furthermore, CNIH1 and AP3S1 promoted LUAD cell growth and migration in vitro.

Conclusion

We constructed a VMTRG-based risk model for effective prediction of prognostic outcomes for LUAD patients. The risk model was associated with immune infiltration levels. These five hub genes are potential targets for immune therapy combined with chemotherapy in LUAD.
Case report: Dynamic antibody monitoring in a case of anti-recombinant human erythropoietin-mediated pure red cell aplasia with prolonged course after kidney transplantation
Authors: Chen Xiao-Mei , Li Hui , Wu Yu , Wang Lan-Lan , Bai Yang-Juan , Shi Yun-Ying
Published: November 2022

Anti-erythropoietin (anti-EPO) antibody-mediated pure red cell aplasia (PRCA) is a rarely seen disease. Anti-EPO antibodies were mostly found in patients with chronic kidney disease who received recombinant human erythropoietin (rHuEPO) injections subcutaneously. The treatment against anti-EPO antibody-mediated PRCA included discontinuation of rHuEPO, immunosuppressive agents, intravenous immunoglobulin, plasmapheresis, or kidney transplantation. We reported a case of kidney transplant recipient with anti-EPO antibody-mediated PRCA, who had no trend of recovery after stopping rHuEPO, receiving regular induction and maintenance immunosuppressive regimens. He was further given 6 consecutive plasmapheresis sessions, cyclophosphamide, and adjusted maintenance immunosuppressive regimen into cyclosporine, sirolimus and prednisone. We monitored his anti-EPO antibody levels with a self-created simple mixing test. At 10 months post kidney transplant, his anti-EPO antibody finally turned negative, and his reticulocyte count dramatically increased. Cyclosporine, sirolimus and prednisone combined with roxadustat eventually alleviated the patient’s anti-EPO antibody-mediated PRCA. Our self-created simple mixing test for anti-EPO antibody titer was very helpful in disease monitoring and therapeutic guidance.
Analyzing the immunogenicity of bivalent booster vaccinations in healthcare workers: The SWITCH ON trial protocol
Authors: Tan Ngoc H. , Sablerolles Roos S. G. , Rietdijk Wim J. R. , Goorhuis Abraham , Postma Douwe F. , Visser Leo G. , Bogers Susanne , Geers Daryl , Zaeck Luca M. , Koopmans Marion P. G. , Dalm Virgil A. S. H. , Kootstra Neeltje A. , Huckriede Anke L. W. , van Baarle Debbie , Lafeber Melvin , GeurtsvanKessel Corine H. , de Vries Rory D. , van der Kuy Paul-Hugo Marie
Published: November 2022

Vaccination against coronavirus disease 2019 (COVID-19) has contributed greatly to providing protection against severe disease, thereby reducing hospital admissions and deaths. Several studies have reported reduction in vaccine effectiveness over time against the Omicron sub-lineages. However, the willingness to receive regular booster doses in the general population is declining. To determine the need for repeated booster vaccinations in healthy individuals and to aid policymakers in future public health interventions for COVID-19, we aim to gain insight into the immunogenicity of the additional bivalent booster vaccination in a representative sample of the healthy Dutch population. The SWITCH ON study was initiated to investigate three main topics: i) immunogenicity of bivalent vaccines after priming with adenovirus- or mRNA-based vaccines, ii) immunological recall responses and reactivity with relevant variants after booster vaccination, and iii) the necessity of booster vaccinations for the healthy population in the future.

Clinical trial registration

https://clinicaltrials.gov/, identifier NCT05471440.
The prognostic value of the systemic immune-inflammation index for patients with bladder cancer after radical cystectomy
Authors: Zhang Shiyu , Du Jiajia , Zhong Xin , Tan Ping , Xu Hang , Zhang Jiapeng , Jin Di , Li Yifan , Le Weizhen , Xiong Xingyu , Lin Tianhai , Wei Qiang
Published: November 2022

Background

Biomarkers acquired from blood samples are easy to obtain and cost-effective, have attracted considerable interest, and have been widely investigated. Inflammation plays a crucial role in cancer cell initiation, proliferation, and metastasis. We aimed to evaluate the association of the preoperative systemic immune-inflammation index (SII) with the clinical outcomes of patients diagnosed with bladder cancer and who underwent radical cystectomy (RC).

Materials and methods

Data from patients diagnosed with bladder cancer and who underwent RC from December 2010 to May 2020 in West China Hospital were retrospectively collected according to the inclusion and exclusion criteria. Patients were divided into a low-SII group and a high-SII group according to the SII level. Survival outcomes were obtained during follow-up. The primary endpoints were overall survival (OS) and recurrence-free survival (RFS). Cox proportional hazard models were performed to estimate the effect of SII on OS and RFS and control for potential confoundings. Subgroup analyses were conducted, and the log likelihood ratio test was used to inspect the interaction.

Results

A total of 725 patients who underwent RC were ultimately involved in this study. Of these patients, 621 (85.66%) were men and 104 (14.34%) were women. The median age was 65 years. The median follow-up was 36 months for OS and 33.6 months for RFS. The optimal cutoff value was identified as 554.23 × 109/l. A total of 467 (64.41%) patients were divided into the low-SII group (SII <554 × 109/l), and 258 (35.59%) patients were divided into the high-SII group (SII ≥554 × 109/l) accordingly. Multivariable Cox proportional hazard regression demonstrated that a high SII was an independent prognostic factor for worse OS (HR: 1.69 95% CI: 1.02–2.81, P = 0.0436) and RFS (HR: 1.88, 95% CI: 1.09–3.24, P = 0.0229) in NMIBC patients. A high SII was found to be an independent prognostic factor for worse RFS in patients with HBP (HR: 2.11, 95% CI: 1.34–3.30, P = 0.0012), with DM (HR: 3.76, 95% CI: 1.73–8.15, P = 0.0008), and without PNI (HR: 1.32, 95% CI: 1.04–1.69, P = 0.0238).

Conclusions

The SII was a potential prognostic predictor for bladder cancer patients who underwent RC. Further prospective multicenter investigations are warranted.
C2GAP2 is a common regulator of Ras signaling for chemotaxis, phagocytosis, and macropinocytosis
Authors: Xu Xuehua , Pots Henderikus , Gilsbach Bernd K. , Parsons Dustin , Veltman Douwe M. , Ramachandra Sharmila G. , Li Haoran , Kortholt Arjan , Jin Tian
Published: November 2022

Phagocytosis, macropinocytosis, and G protein coupled receptor-mediated chemotaxis are Ras-regulated and actin-driven processes. The common regulator for Ras activity in these three processes remains unknown. Here, we show that C2GAP2, a Ras GTPase activating protein, highly expressed in the vegetative growth state in model organism Dictyostelium. C2GAP2 localizes at the leading edge of chemotaxing cells, phagosomes during phagocytosis, and macropinosomes during micropinocytosis. c2gapB− cells lacking C2GAP2 displayed increased Ras activation upon folic acid stimulation and subsequent impaired chemotaxis in the folic acid gradient. In addition, c2gaB- cells have elevated phagocytosis and macropinocytosis, which subsequently results in faster cell growth. C2GAP2 binds multiple phospholipids on the plasma membrane and the membrane recruitment of C2GAP2 requires calcium. Taken together, we show a shared negative regulator of Ras signaling that mediates Ras signaling for chemotaxis, phagocytosis, and macropinocytosis.
Bioinformatics identification and validation of biomarkers and infiltrating immune cells in endometriosis
Authors: Jiang Hong , Zhang Xia , Wu Yalan , Zhang Baozhu , Wei Juanbing , Li Jianhua , Huang Yuxiu , Chen Lihong , He Xinqin
Published: November 2022

Background

Endometriosis (EM) is a common gynecological disorder that often leads to irregular menstruation and infertility. The pathogenesis of EM remains unclear and delays in diagnosis are common. Thus, it is urgent to explore potential biomarkers and underlying molecular mechanisms for EM diagnosis and therapies.

Methods

Three EM-related datasets (GSE11691, GSE25628, and GSE86534) were downloaded from the Gene Expression Omnibus (GEO) which were integrated into a combined dataset after removing batch effect. Differentially expressed immune cell-related genes were obtained by CIBERSORT, WGCNA, and the identification of differentially expressed genes. Random forest model (RF), support vector machine model (SVM), and generalized linear model (GLM) were then constructed and the biomarkers for EM were determined. A nomogram evaluating the risk of disease was constructed and the validity was assessed by the calibration curve, DCA curve, and clinical impact curve. Single-gene Gene Set Enrichment Analysis (GSEA)was performed to explore the molecular mechanisms of biomarkers. The ceRNA regulatory network of biomarkers was created by Cytoscape and potential target drugs were obtained in the DGIdb database (Drug-Gene Interaction database).The expression levels of biomarkers from clinical samples was quantified by RT-qPCR.

Results

The ratio of eight immune cells was significantly different between the eutopic and ectopic endometrium samples. A total of eight differentially expressed immune cell-related genes were investigated. The SVM model was a relatively suitable model for the prediction of EM and five genes (CXCL12, PDGFRL, AGTR1, PTGER3, and S1PR1) were selected from the model as biomarkers. The calibration curve, DCA curve, and clinical impact curve indicated that the nomogram based on the five biomarkers had a robust ability to predict disease. Single gene GSEA result suggested that all five biomarkers were involved in labyrinthine layer morphogenesis and transmembrane transport-related biological processes in EM. A ceRNA regulatory network containing 184 nodes and 251 edges was constructed. Seven drugs targeting CXCL12, 49 drugs targeting AGTR1, 16 drugs targeting PTGER3, and 21 drugs targeting S1PR1 were extracted as potential drugs for EM therapy. Finally, the expression of PDGFRL and S1PR1 in clinical samples was validated by RT-qPCR, which was consistent with the result of public database.

Conclusions

In summary, we identified five biomarkers (CXCL12, PDGFRL, AGTR1, PTGER3, and S1PR1) and constructed diagnostic model, furthermore predicted the potential therapeutic drugs for EM. Collectively, these findings provide new insights into EM diagnosis and treatment.
The description of a new brackish water ciliate species from China, Trachelostyla aestuarina n. sp., with a species key and biogeographic investigation for Trachelostyla (Ciliophora, Sporadotrichida)
Authors: Zhang Zihui , Hines Hunter N. , Pan Hongbo , Jiang Jiamei
Published: November 2022

The ciliated protists are a diverse group of microbial eukaryotes that play an important role in the functioning of microbial food webs. The genus Trachelostyla Borror, 1972, comprised a few species with a non-twisted distinctly cephalized shape. The overall taxonomy has been challenging for this group, and the understanding of their diversity and distribution is therefore relatively limited. To further investigate this group, we report here on two species from the East China Sea, Trachelostyla aestuarina n. sp. and Trachelostyla caudata Borror, 1972, including their in vivo morphology, infraciliature, and phylogenetic relationships based on 18S rRNA gene sequences. The physiological reorganization stages of the latter were also investigated. T. aestuarina is characterized by a combination of features including a bipartite cell shape, a size of 150–220 × 15–35 μm, scattered cortical granules, and multiple macronuclear nodules (37–55). T. caudata has only 10 cirri in the frontal region, fewer than its congeners; thus, we improved the definition of the genus. The global distribution of Trachelostyla was summarized based on the available literature and a key to the valid species provided. This work improves the overall knowledge of hypotrich biodiversity and provides underpinning for future researchers in global regions for environmental monitoring and resource investigations.
Multimodal measurement of glycocalyx degradation during coronary artery bypass grafting
Authors: Bol Martine E. , Huckriede J. B. , van de Pas K. G. H. , Delhaas T. , Lorusso R. , Nicolaes G. A. F. , Sels J. E. M. , van de Poll M. C. G.
Published: November 2022

Background

Glycocalyx shedding and subsequent endothelial dysfunction occur in many conditions, such as in sepsis, in critical illness, and during major surgery such as in coronary artery bypass grafting (CABG) where it has been shown to associate with organ dysfunction. Hitherto, there is no consensus about the golden standard in measuring glycocalyx properties in humans. The objective of this study was to compare different indices of glycocalyx shedding and dysfunction. To this end, we studied patients undergoing elective CABG surgery, which is a known cause of glycocalyx shedding.

Materials and methods

Sublingual glycocalyx thickness was measured in 23 patients by: 1) determining the perfused boundary region (PBR)—an inverse measure of glycocalyx thickness—by means of sidestream dark field imaging technique. This is stated double, 2) measuring plasma levels of the glycocalyx shedding products syndecan-1, hyaluronan, and heparan sulfate and 3) measuring plasma markers of impaired glycocalyx function and endothelial activation (Ang-2, Tie-2, E-selectin, and thrombomodulin). Measurements were performed directly after induction, directly after onset of cardiopulmonary bypass (CPB), and directly after cessation of CPB. We assessed changes over time as well as correlations between the various markers.

Results

The PBR increased from 1.81 ± 0.21 μm after induction of anesthesia to 2.27 ± 0.25 μm (p < 0.0001) directly after CPB was initiated and did not change further during CPB. A similar pattern was seen for syndecan-1, hyaluronan, heparan sulfate, Ang-2, Tie-2, and thrombomodulin. E-selectin levels also increased between induction and the start of CPB and increased further during CPB. The PBR correlated moderately with heparan sulfate, E-selectin, and thrombomodulin and weakly with Syndecan-1, hyaluronan, and Tie-2. Shedding markers syndecan-1 and hyaluronan correlated with all functional markers. Shedding marker heparan sulfate only correlated with Tie-2, thrombomodulin, and E-selectin. Thrombomodulin correlated with all shedding markers.

Conclusion

Our results show that glycocalyx thinning, illustrated by increased sublingual PBR and increased levels of shedding markers, is paralleled with impaired glycocalyx function and increased endothelial activation in CABG surgery with CPB. As correlations between different markers were limited, no single marker could be identified to represent the glycocalyx in its full complexity.
Novel oxazolidinones harbor potent in vitro activity against the clinical isolates of multidrug-resistant Mycobacterium tuberculosis in China
Authors: Wang Chenqian , Wang Guirong , Huo Fengmin , Xue Yi , Jia Junnan , Dong Lingling , Zhao Liping , Wang Fen , Huang Hairong , Duan Hongfei
Published: November 2022

Objective

To investigate the in vitro activities of five oxazolidinones in parallel against the reference strains of different mycobacterial species and clinical isolates of Mycobacterium tuberculosis (Mtb), and shed light on the differences in the efficacy of these homolog drugs.

Materials and methods

The minimum inhibitory concentrations (MICs) of linezolid, tedizolid, sutezolid, delpazolid, and contezolid against 16 mycobacterial reference strains and 69 M. tuberculosis clinical isolates, including 17 drug-susceptible isolates and 52 multidrug-resistant (MDR) isolates, were determined by microplate alamarBlue assay (MABA). The intracellular killing activities of contezolid and linezolid against Mtb H37Rv were compared. In addition, mutations in the linezolid resistance-related genes (rplC, rplD, and 23S rRNA) of the Mtb clinical isolates were also analyzed.

Results

Tedizolid exhibited the strongest inhibitory activities against the reference strains of both rapidly growing mycobacteria (RGM) and slowly growing mycobacteria (SGM), among the tested oxazolidinones. In contrast, sutezolid only manifested potent activity against reference strains of SGM. Linezolid, delpazolid, and contezolid were less active against the non-tuberculous mycobacterial references. For the Mtb clinical isolates, the antimicrobial action was ranked as: sutezolid > tedizolid > contezolid and linezolid > delpazolid, whereas no difference between drug-sensitive and multiple drug-resistant isolates was observed. Notably, contezolid demonstrated obviously superior intracellular antimicrobial activity than linezolid. Few strains harbored mutations in rrl gene or rplD genes, although these strains had drug susceptible profiles to linezolid.

Conclusion

Different oxazolidinones can have discrepant antimicrobial activity against different mycobacterial species, or have different manifestations out of cell or in cell. Understanding these differences would be helpful in choosing the appropriate drug in clinical practice.
Nutrient niche specificity for glycosaminoglycans is reflected in polysaccharide utilization locus architecture of gut Bacteroides species
Authors: Overbeeke Annelieke , Hausmann Bela , Nikolov Georgi , Pereira Fatima C. , Herbold Craig W. , Berry David
Published: November 2022

Introduction

Glycosaminoglycans (GAGs) present in the mucosal layer can be used as nutrients by certain intestinal bacteria, particularly members of the Bacteroides. GAG abundances are altered in some diseases such as inflammatory bowel diseases, which may affect microbial composition and activity, and it is therefore important to understand GAG utilization by members of the gut microbiota.

Methods

We used growth assays, transcriptomics, and comparative genomics to evaluate chondroitin sulfate (CS) and hyaluronan (HA) degradation ability by multiple gut Bacteroides species.

Results and discussion

We found that not all Bacteroides species able to degrade CS could also degrade HA, despite having lyases which act on both compounds. We propose that in the model organism Bacteroides thetaiotaomicron, the lyase BT_3328 in combination with surface binding proteins BT_3329 and BT_3330 and potentially BT_4411 are involved in HA breakdown. Furthermore, degradation of both compounds provides public goods for other Bacteroides, including non-degraders, suggesting that cooperative degradation as well as cross-feeding may be widespread in the mucosal glycan utilization clade.
Catchment characteristics and seasonality control the composition of microbial assemblages exported from three outlet glaciers of the Greenland Ice Sheet
Authors: Vrbická Kristýna , Kohler Tyler J. , Falteisek Lukáš , Hawkings Jon R. , Vinšová Petra , Bulínová Marie , Lamarche-Gagnon Guillaume , Hofer Stefan , Kellerman Anne M. , Holt Amy D. , Cameron Karen A. , Schön Martina , Wadham Jemma L. , Stibal Marek
Published: November 2022

Glacial meltwater drains into proglacial rivers where it interacts with the surrounding landscape, collecting microbial cells as it travels downstream. Characterizing the composition of the resulting microbial assemblages in transport can inform us about intra-annual changes in meltwater flowpaths beneath the glacier as well as hydrological connectivity with proglacial areas. Here, we investigated how the structure of suspended microbial assemblages evolves over the course of a melt season for three proglacial catchments of the Greenland Ice Sheet (GrIS), reasoning that differences in glacier size and the proportion of glacierized versus non-glacierized catchment areas will influence both the identity and relative abundance of microbial taxa in transport. Streamwater samples were taken at the same time each day over a period of 3 weeks (summer 2018) to identify temporal patterns in microbial assemblages for three outlet glaciers of the GrIS, which differed in glacier size (smallest to largest; Russell, Leverett, and Isunnguata Sermia [IS]) and their glacierized: proglacial catchment area ratio (Leverett, 76; Isunnguata Sermia, 25; Russell, 2). DNA was extracted from samples, and 16S rRNA gene amplicons sequenced to characterize the structure of assemblages. We found that microbial diversity was significantly greater in Isunnguata Sermia and Russell Glacier rivers compared to Leverett Glacier, the latter of which having the smallest relative proglacial catchment area. Furthermore, the microbial diversity of the former two catchments continued to increase over monitored period, presumably due to increasing hydrologic connectivity with proglacial habitats. Meanwhile, diversity decreased over the monitored period in Leverett, which may have resulted from the evolution of an efficient subglacial drainage system. Linear discriminant analysis further revealed that bacteria characteristic to soils were disproportionately represented in the Isunnguata Sermia river, while putative methylotrophs were disproportionately abundant in Russell Glacier. Meanwhile, taxa typical for glacierized habitats (i.e., Rhodoferax and Polaromonas) dominated in the Leverett Glacier river. Our findings suggest that the proportion of deglaciated catchment area is more influential to suspended microbial assemblage structure than absolute glacier size, and improve our understanding of hydrological flowpaths, particulate entrainment, and transport.
Seed endophytic ammonia oxidizing bacteria in Elymus nutans transmit to offspring plants and contribute to nitrification in the root zone
Authors: Liang Danni , Bowatte Saman
Published: November 2022

Background

Ammonia oxidizing bacteria (AOB) in soil are of great biological importance as they regulate the cycling of N in agroecosystems. Plants are known to harbor AOB but how they occupy the plant is an unresolved question.

Methods

Metabarcoding studies were carried out using Illumina MiSeq sequencing to test the potential of seed vectored AOB exchange between plants and soil.

Results and discussion

We found 27 sequences associated with AOB strains belonging to the genera Nitrosospira, Nitrosovibrio, and Nitrosomonas inhabiting Elymus nutans seeds collected from four geographically distanced alpine meadows. Nitrosospira multiformis was the most dominant across the four locations. The AOB community in E. nutans seeds was compared with that of the leaves, roots and soil in one location. Soil and seeds harbored a rich but dissimilar AOB community, and Nitrosospira sp. PJA1, Nitrosospira sp. Nsp17 and Nitrosovibrio sp. RY3C were present in all plant parts and soils. When E. nutans seeds were germinated in sterilized growth medium under greenhouse conditions, the AOB in seeds later appeared in leaves, roots and growth medium, and contributed to nitrification. Testing the AOB community of the second-generation seeds confirmed vertical transmission, but low richness was observed.

Conclusion

These results suggest seed vectored AOB may play a critical role in N cycle.
Screening of β -damascenone-producing strains in light-flavor Baijiu and its production optimization via response surface methodology
Authors: Tang Jie , Lin Bin , Jiang Wei , Li Qun , Zhu Liping , Zhang Gang , Chen Qianjin , Yang Qiang , Yang Shengzhi , Chen Shenxi
Published: November 2022

As a C13-norisoprenoid aroma substance, β-damascenone is a highly important aromatic compound and an active constituent. The purpose of this study was to investigate the change law of β-damascenone during the light-flavor Baijiu brewing process, and screen the indigenous microbial strains that produce this compound and optimize fermentation parameters for improving β-damascenone production using a statistical approach. In this project, Wickerhamomyces anomalus YWB-1 exhibited the highest producing activity of β-damascenone. Fermentation conditions were optimized for β-damascenone production using a one-factor-at-a-time (OFAT) approach. A Plackett-Burman design was subsequently adopted to assess the effects of initial pH, incubation temperature, inoculum size, fermentation period, and original Brix degree. Analysis of variance (ANOVA) showed that the correlation coefficient (R2) of the executive model was 0.9795, and this value was significant (p < 0.05). Three significant variables were optimized at three different coded levels using a Box-Behnken design (BBD) of response surface methodology (RSM). Here, 7.25 μg/L β-damascenone was obtained under the following optimum conditions: initial pH of 3.31, original Brix degree of 10.53%, and fermentation period of 52.13 h. The yield was increased 3.02-fold compared with that obtained under unoptimized conditions. This information is conducive to the control of flavor production by regulating variable parameters in Baijiu fermentation.
Predicting AT(N) pathologies in Alzheimer’s disease from blood-based proteomic data using neural networks
Authors: Zhang Yuting , Ghose Upamanyu , Buckley Noel J. , Engelborghs Sebastiaan , Sleegers Kristel , Frisoni Giovanni B. , Wallin Anders , Lleó Alberto , Popp Julius , Martinez-Lage Pablo , Legido-Quigley Cristina , Barkhof Frederik , Zetterberg Henrik , Visser Pieter Jelle , Bertram Lars , Lovestone Simon , Nevado-Holgado Alejo J. , Shi Liu
Published: November 2022

Background and objective

Blood-based biomarkers represent a promising approach to help identify early Alzheimer’s disease (AD). Previous research has applied traditional machine learning (ML) to analyze plasma omics data and search for potential biomarkers, but the most modern ML methods based on deep learning has however been scarcely explored. In the current study, we aim to harness the power of state-of-the-art deep learning neural networks (NNs) to identify plasma proteins that predict amyloid, tau, and neurodegeneration (AT[N]) pathologies in AD.

Methods

We measured 3,635 proteins using SOMAscan in 881 participants from the European Medical Information Framework for AD Multimodal Biomarker Discovery study (EMIF-AD MBD). Participants underwent measurements of brain amyloid β (Aβ) burden, phosphorylated tau (p-tau) burden, and total tau (t-tau) burden to determine their AT(N) statuses. We ranked proteins by their association with Aβ, p-tau, t-tau, and AT(N), and fed the top 100 proteins along with age and apolipoprotein E (APOE) status into NN classifiers as input features to predict these four outcomes relevant to AD. We compared NN performance of using proteins, age, and APOE genotype with performance of using age and APOE status alone to identify protein panels that optimally improved the prediction over these main risk factors. Proteins that improved the prediction for each outcome were aggregated and nominated for pathway enrichment and protein–protein interaction enrichment analysis.

Results

Age and APOE alone predicted Aβ, p-tau, t-tau, and AT(N) burden with area under the curve (AUC) scores of 0.748, 0.662, 0.710, and 0.795. The addition of proteins significantly improved AUCs to 0.782, 0.674, 0.734, and 0.831, respectively. The identified proteins were enriched in five clusters of AD-associated pathways including human immunodeficiency virus 1 infection, p53 signaling pathway, and phosphoinositide-3-kinase–protein kinase B/Akt signaling pathway.

Conclusion

Combined with age and APOE genotype, the proteins identified have the potential to serve as blood-based biomarkers for AD and await validation in future studies. While the NNs did not achieve better scores than the support vector machine model used in our previous study, their performances were likely limited by small sample size.
Identification of the prognostic and immunological roles of aquaporin 4: A potential target for survival and immunotherapy in glioma patients
Authors: Lan Yu-Long , Nie Tian , Zou Shuang
Published: November 2022

Recent studies have revealed the critical role of AQP4 in the occurrence and development of gliomas. However, the role of AQP4 in immune regulation has not yet been reported. Many recent reports have identified the lymphatic system’s occurrence within the central nervous system (CNS) and the vital role of immune regulation in treating brain tumors. Therefore, the present study aimed to explore the role of AQP4 in the immune regulation of glioma. We used bioinformatics analysis to investigate the immunoregulatory function of AQP4, including its correlation with immunity, anti-tumor immune processes, immunotherapy, immune infiltration, tumor mutational burden (TMB), stemness, mutation, and pan-cancer. The results revealed that AQP4 was significantly associated with the expression of multiple immune checkpoints, immune cells, as well as multiple immune cell effector genes, and antigen presentation and processing abilities. Although no significant correlation was found between the AQP4 gene and IDH mutation and MGMT, AQP4 demonstrated substantial expression differences in different immunophenotypes and molecular types. Using the TTD database, we discovered that EGFR, ABAT, and PDGFRA are strongly associated with AQP4 expression in the glioblastoma (GBM) classification, and these factors could be the potential AQP4-related immunotherapy targets. Afterward, we screened the differential genes in the high and low AQP4 gene expression group, the high and low immune score group, and the high and low matrix score group and took the intersection as the candidate factor. Finally, univariate Cox analysis was used to find eight prognostic variables with significant differences across the candidate genes. After lasso dimensionality reduction, three genes built the model (RARRES1, SOCS3, and TTYH1). The scoring model generated by the three genes was eventually obtained after the multi-factor screening of the three genes. Finally, combined with clinical information and cox regression analysis, it was further confirmed that the model score could be used as an independent prognostic factor.
Restoration of spinal cord injury: From endogenous repairing process to cellular therapy
Authors: Wu Yaqi , Tang Zhijian , Zhang Jun , Wang Yu , Liu Shengwen
Published: November 2022

Spinal cord injury (SCI) disrupts neurological pathways and impacts sensory, motor, and autonomic nerve function. There is no effective treatment for SCI currently. Numerous endogenous cells, including astrocytes, macrophages/microglia, and oligodendrocyte, are involved in the histological healing process following SCI. By interfering with cells during the SCI repair process, some advancements in the therapy of SCI have been realized. Nevertheless, the endogenous cell types engaged in SCI repair and the current difficulties these cells confront in the therapy of SCI are poorly defined, and the mechanisms underlying them are little understood. In order to better understand SCI and create new therapeutic strategies and enhance the clinical translation of SCI repair, we have comprehensively listed the endogenous cells involved in SCI repair and summarized the six most common mechanisms involved in SCI repair, including limiting the inflammatory response, protecting the spared spinal cord, enhancing myelination, facilitating neovascularization, producing neurotrophic factors, and differentiating into neural/colloidal cell lines.
Disrupted visual input unveils the computational details of artificial neural networks for face perception
Authors: Li Yi-Fan , Ying Haojiang
Published: November 2022

Background

Convolutional Neural Network (DCNN), with its great performance, has attracted attention of researchers from many disciplines. The studies of the DCNN and that of biological neural systems have inspired each other reciprocally. The brain-inspired neural networks not only achieve great performance but also serve as a computational model of biological neural systems.

Methods

Here in this study, we trained and tested several typical DCNNs (AlexNet, VGG11, VGG13, VGG16, DenseNet, MobileNet, and EfficientNet) with a face ethnicity categorization task for experiment 1, and an emotion categorization task for experiment 2. We measured the performance of DCNNs by testing them with original and lossy visual inputs (various kinds of image occlusion) and compared their performance with human participants. Moreover, the class activation map (CAM) method allowed us to visualize the foci of the “attention” of these DCNNs.

Results

The results suggested that the VGG13 performed the best: Its performance closely resembled human participants in terms of psychophysics measurements, it utilized similar areas of visual inputs as humans, and it had the most consistent performance with inputs having various kinds of impairments.

Discussion

In general, we examined the processing mechanism of DCNNs using a new paradigm and found that VGG13 might be the most human-like DCNN in this task. This study also highlighted a possible paradigm to study and develop DCNNs using human perception as a benchmark.