bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical significance of genetic variation in hypertrophic cardiomyopathy: comparison of computational tools to prioritize missense variants
Authors: Barbosa Pedro , Ribeiro Marta , Carmo-Fonseca Maria , Fonseca Alcides
Published: August 2022

Hypertrophic cardiomyopathy (HCM) is a common heart disease associated with sudden cardiac death. Early diagnosis is critical to identify patients who may benefit from implantable cardioverter defibrillator therapy. Although genetic testing is an integral part of the clinical evaluation and management of patients with HCM and their families, in many cases the genetic analysis fails to identify a disease-causing mutation. This is in part due to difficulties in classifying newly detected rare genetic variants as well as variants-of-unknown-significance (VUS). Multiple computational algorithms have been developed to predict the potential pathogenicity of genetic variants, but their relative performance in HCM has not been comprehensively assessed. Here, we compared the performance of 39 currently available prediction tools in distinguishing between high-confidence HCM-causing missense variants and benign variants, and we developed an easy-to-use-tool to perform variant prediction benchmarks based on annotated VCF files (VETA). Our results show that tool performance increases after HCM-specific calibration of thresholds. After excluding potential biases due to circularity type I issues, we identified ClinPred, MISTIC, FATHMM, MPC and MetaLR as the five best performer tools in discriminating HCM-associated variants. We propose combining these tools in order to prioritize unknown HCM missense variants that should be closely followed-up in the clinic.
Views across the boundary: School-based co-teachers experiences with co-teaching in initial teacher education
Authors: Cooper Rebecca , Marangio Karen
Published: August 2022

School and university partnerships are widely promoted as an effective means to support the preparation of pre-service teachers (PSTs). However, these partnerships are rarely conceived with practicing teachers working in a university context as co-teachers with university teacher educators. School-based co-teachers (SBCTs) (practicing teachers who contribute to Initial Teacher Education (ITE) by teaching alongside university-based teacher educators) contribute to ITE through their support for curriculum and assessment development, providing opportunities for observation and experiences in schools, and teaching with university teacher educators. However, the role of a SBCT requires some careful navigation and negotiation of the educational spaces that a SBCT must cross as they teach in university classrooms and foster a co-teaching relationship. This research articulates the process of boundary crossing that four SBCTs undertook as they supported the development of pre-service science teachers. Boundaries exist between the practices and perspectives of teaching school science students and teaching science PSTs at university. Data were collected from four SBCTs across one academic year, including an initial survey at the beginning of the year, an interview at the end of the year, and documentation from co-teaching meetings across the year. An inductive thematic approach was taken to analyze the data. Five themes were identified that describe the ways SBCTs viewed their role as a co-teacher and their associated learning in this role. Drawing on literature around boundary-crossing dialogical learning mechanisms, the themes are described with illustrative excerpts to represent the range of SBCTs experiences. Our data indicates that SBCTs found many opportunities to share their wealth of knowledge and experience with pre-service science teachers but also identified, and often sought out, opportunities to professionally learn and grow. Findings include the importance of sharing aims and purposes to understand the context and the generation of shared knowledge through peer reflection on teaching. This article offers insights to others who are looking to form and sustain productive relationships with SBCTs to support learning for PSTs in ITE courses.
To use or not to use learning data: A survey study to explain German primary school teachers’ usage of data from digital learning platforms for purposes of individualization
Authors: Hase Alina , Kahnbach Leonie , Kuhl Poldi , Lehr Dirk
Published: August 2022

Digital learning platforms (DLP) provide various types of information about student learning when used for learning and practice. This learning data holds potential for individualized instruction, which has become increasingly necessary for adequately addressing learners’ individual needs. For primary schools in particular, this is important for developing inclusive schools. However, despite the potential of DLP and the learning data that can be obtained from them, they are rarely used by teachers. Furthermore, little is known about factors that lead teachers to use learning data for instruction and individual support. To address this research gap, we conducted an online cross-sectional survey study of N = 272 primary school teachers in Germany. After describing the respondents’ current and previous usage of learning data from DLP, we used structural equation modeling (SEM) to test the influence of predictors on respondents’ intention to use as well as their usage of learning data from DLP. Finally, we discuss the need for increased usage of learning data in teacher education and training, contributing to ongoing debates about the usage of digital learning data in educational research and practice.
Role of estrogen receptors in health and disease
Authors: Chen Peng , Li Bo , Ou-Yang Ling
Published: August 2022

Estrogen receptors (ERs) regulate multiple complex physiological processes in humans. Abnormal ER signaling may result in various disorders, including reproductive system-related disorders (endometriosis, and breast, ovarian, and prostate cancer), bone-related abnormalities, lung cancer, cardiovascular disease, gastrointestinal disease, urogenital tract disease, neurodegenerative disorders, and cutaneous melanoma. ER alpha (ERα), ER beta (ERβ), and novel G-protein-coupled estrogen receptor 1 (GPER1) have been identified as the most prominent ERs. This review provides an overview of ERα, ERβ, and GPER1, as well as their functions in health and disease. Furthermore, the potential clinical applications and challenges are discussed.
The emerging roles and mechanisms of exosomal non-coding RNAs in the mutual regulation between adipose tissue and other related tissues in obesity and metabolic diseases
Authors: Pan Shifeng , Chen Yongfang , Yan Jie , Li Fei , Chen Xinyu , Xu Xingyu , Xing Hua
Published: August 2022

Exosomes (EXs) are the major types of extracellular vesicles (EVs) of 30-100 nm diameter that can be secreted by most cells to the extracellular environment. EXs transport endogenous cargoes (proteins, lipids, RNAs, etc.) to target cells and thereby triggers the release of these bioactive components, which then play important roles in regulating numerous biological processes under both physiological and pathological conditions. Throughout the studies in recent years, growing evidences have shown that EXs-derived non-coding RNAs (EXs-ncRNAs) are emerging as key players in cell-to-cell communication between adipose tissue and other related tissues in obesity and metabolic diseases. In this review, we will summarize the recent findings about EXs-ncRNAs, especially focus on the following aspects: 1) the biogenesis of EXs and emerging roles of EXs-ncRNAs, 2) the role of EXs-ncRNAs (EXs-miRNAs, EXs-lncRNAs, EXs-circRNAs, etc.) that were secreted by adipose-related tissues in promoting the differentiation of preadipocytes into mature and fully functional adipocytes, and 3) the crosstalk between the adipose tissue derived EXs-ncRNAs and the development of insulin resistance, obesity and various cancers. This review aims to reveal the emerging roles and mechanisms of EXs-ncRNAs in the mutual regulation of adipose tissue and its related tissues in obesity and metabolic diseases, so as to provide references for elucidating the etiology of obesity and related metabolic diseases and screening novel therapeutic targets.
Identification of epigenetic dysregulation gene markers and immune landscape in kidney renal clear cell carcinoma by comprehensive genomic analysis
Authors: Xie Linli , Wu Shuang , He Rong , Li Sisi , Lai Xiaodan , Wang Zhe
Published: August 2022

Kidney cancer is one the most lethal cancers of the urinary system, but current treatments are limited and its prognosis is poor. This study focused on kidney renal clear cell carcinoma (KIRC) and analyzed the relationship between epigenetic alterations and KIRC prognosis, and explored the prognostic significance of these findings in KIRC patients. Based on multi-omics data, differentially expressed histone-modified genes were identified using the R package limma package. Gene enhancers were detected from data in the FANTOM5 database. Gene promoters were screened using the R package ChIPseeker, and the Bumphunter in the R package CHAMP was applied to screen differentially methylated regions (DMR). Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and Gene Ontology (GO) functional enrichment analysis of genes was performed using the R package clusterProfiler. We identified 51 dysregulated epigenetic protein coding genes (epi-PCGs) from 872 epi-PCGs, and categorized three molecular subtypes (C1, C2, and C3) of KIRC samples with significantly different prognosis. Notably, among the three molecular subtypes, we found a markedly differential immune features in immune checkpoints, cytokines, immune signatures, and immune cell distribution. C2 subtype had significantly lower enrichment score of IFNγ, cytotoxic score (CYT), and angiogenesis. In addition, an 8-gene signature containing 8 epi-PCGs (ETV4, SH2B3, FATE1, GRK5, MALL, HRH2, SEMA3G, and SLC10A6) was developed for predicting KIRC prognosis. Prognosis of patients with a high 8-gene signature score was significantly worse than those with a low 8-gene signature score, which was also validated by the independent validation data. The 8-gene signature had a better performance compared with previous signatures of KIRC. Overall, this study highlighted the important role of epigenetic regulation in KIRC development, and explored prognostic epi-PCGs, which may provide a guidance for exploiting further pathological mechanisms of KIRC and for developing novel drug targets.
Intrinsic dietary fibers and the gut microbiome: Rediscovering the benefits of the plant cell matrix for human health
Authors: Puhlmann Marie-Luise , de Vos Willem M.
Published: August 2022

Dietary fibers contribute to structure and storage reserves of plant foods and fundamentally impact human health, partly by involving the intestinal microbiota, notably in the colon. Considerable attention has been given to unraveling the interaction between fiber type and gut microbiota utilization, focusing mainly on single, purified fibers. Studying these fibers in isolation might give us insights into specific fiber effects, but neglects how dietary fibers are consumed daily and impact our digestive tract: as intrinsic structures that include the cell matrix and content of plant tissues. Like our ancestors we consume fibers that are entangled in a complex network of plants cell walls that further encapsulate and shield intra-cellular fibers, such as fructans and other components from immediate breakdown. Hence, the physiological behavior and consequent microbial breakdown of these intrinsic fibers differs from that of single, purified fibers, potentially entailing unexplored health effects. In this mini-review we explain the difference between intrinsic and isolated fibers and discuss their differential impact on digestion. Subsequently, we elaborate on how food processing influences intrinsic fiber structure and summarize available human intervention studies that used intrinsic fibers to assess gut microbiota modulation and related health outcomes. Finally, we explore current research gaps and consequences of the intrinsic plant tissue structure for future research. We postulate that instead of further processing our already (extensively) processed foods to create new products, we should minimize this processing and exploit the intrinsic health benefits that are associated with the original cell matrix of plant tissues.
Genome editing for primary immunodeficiencies: A therapeutic perspective on Wiskott-Aldrich syndrome
Authors: Naseem Asma , Steinberg Zohar , Cavazza Alessia
Published: August 2022

Primary immunodeficiency diseases (PIDs) are a group of rare inherited disorders affecting the immune system that can be conventionally treated with allogeneic hematopoietic stem cell transplantation and with experimental autologous gene therapy. With both approaches still facing important challenges, gene editing has recently emerged as a potential valuable alternative for the treatment of genetic disorders and within a relatively short period from its initial development, has already entered some landmark clinical trials aimed at tackling several life-threatening diseases. In this review, we discuss the progress made towards the development of gene editing-based therapeutic strategies for PIDs with a special focus on Wiskott - Aldrich syndrome and outline their main challenges as well as future directions with respect to already established treatments.
CAR-T cell development for Cutaneous T cell Lymphoma: current limitations and potential treatment strategies
Authors: To Van , Evtimov Vera J. , Jenkin Graham , Pupovac Aleta , Trounson Alan O. , Boyd Richard L.
Published: August 2022

Chimeric antigen receptor (CAR)-T therapy has demonstrated remarkable outcomes for B cell malignancies, however, its application for T cell lymphoma, particularly cutaneous T cell lymphoma (CTCL), has been limited. Barriers to effective CAR-T cell therapy in treating CTCL include T cell aplasia in autologous transplants, CAR-T product contamination with leukemic T cells, CAR-T fratricide (when the target antigen is present on normal T cells), and tumor heterogeneity. To address these critical challenges, innovative CAR engineering by targeting multiple antigens to strike a balance between efficacy and safety of the therapy is necessary. In this review, we discuss the current obstacles to CAR-T cell therapy and highlight potential targets in treating CTCL. Looking forward, we propose strategies to develop more powerful dual CARs that are advancing towards the clinic in CTCL therapy.
Research progress on application of single-cell TCR/BCR sequencing technology to the tumor immune microenvironment, autoimmune diseases, and infectious diseases
Authors: He Jinhua , Shen Jian , Luo Wenfeng , Han Zeping , Xie Fangmei , Pang Ting , Liao Liyin , Guo Zhonghui , Li Jianhao , Li Yuguang , Chen Hanwei
Published: August 2022

Single-cell omics is the profiling of individual cells through sequencing and other technologies including high-throughput analysis for single-cell resolution, cell classification, and identification as well as time series analyses. Unlike multicellular studies, single-cell omics overcomes the problem of cellular heterogeneity. It provides new methods and perspectives for in-depth analyses of the behavior and mechanism of individual cells in the cell population and their relationship with the body, and plays an important role in basic research and precision medicine. Single-cell sequencing technologies mainly include single-cell transcriptome sequencing, single-cell assay for transposase accessible chromatin with high-throughput sequencing, single-cell immune profiling (single-cell T-cell receptor [TCR]/B-cell receptor [BCR] sequencing), and single-cell transcriptomics. Single-cell TCR/BCR sequencing can be used to obtain a large amount of single-cell gene expression and immunomics data at one time, and combined with transcriptome sequencing and TCR/BCR diversity data, can resolve immune cell heterogeneity. This paper summarizes the progress in applying single-cell TCR/BCR sequencing technology to the tumor immune microenvironment, autoimmune diseases, infectious diseases, immunotherapy, and chronic inflammatory diseases, and discusses its shortcomings and prospects for future application.
HLA, gut microbiome and hepatic autoimmunity
Authors: Terziroli Beretta-Piccoli Benedetta , Mieli-Vergani Giorgina , Vergani Diego
Published: August 2022

Genetic susceptibility to autoimmune liver diseases is conferred mainly by polymorphisms of genes encoding for the human leukocyte antigens (HLA). The strongest predisposition to autoimmune hepatitis type 1 (AIH-1) is linked to the allele DRB1*03:01, possession of which is associated with earlier disease onset and more severe course. In populations where this allele is very rare, such as in Asia, and in DRB1*03-negative patients, risk of AIH-1 is conferred by DRB1*04, which is associated with later disease onset and milder phenotype. AIH type 2 (AIH-2) is associated with DRB1*07. The pediatric condition referred to as autoimmune sclerosing cholangitis (ASC), is associated with the DRB1*13 in populations of Northern European ancestry. DRB1*1501 is protective from AIH-1, AIH-2 and ASC in Northern European populations. Possession of the DRB1*08 allele is associated with an increased risk of primary biliary cholangitis (PBC) across different populations. DRB1*03:01 and B*08:01 confer susceptibility to primary sclerosing cholangitis (PSC), as well as DRB1*13 and DRB1*15 in Europe. The hepatic blood supply is largely derived from the splanchnic circulation, suggesting a pathophysiological role of the gut microbiome. AIH appears to be associated with dysbiosis, increased gut permeability, and translocation of intestinal microbial products into the circulation; molecular mimicry between microbial and host antigens may trigger an autoaggressive response in genetically-predisposed individuals. In PBC an altered enteric microbiome may affect intestinal motility, immunological function and bile secretion. Patients with PSC have a gut microbial profile different from health as well as from patients with inflammatory bowel disease without PSC.
Utilization of insecticide treated nets among pregnant women in sodo zuria woreda Southern Ethiopia
Authors: Nadew Jemaneh , Obsa Mohammed Suleiman , Alemayehu Akalewold , Haji Yusuf
Published: August 2022

Background

The malaria control strategy has shown an improvement in providing services and allocating resources to enhance malaria elimination. The world malaria report indicated that there was a marked increment of insecticide treated net (ITNs) utilization among pregnant women. However, in Ethiopia, the number of households with possession and utilization of ITNs is still far behind the WHO recommendations. Hence, this study was aimed to measure the magnitude of ITN utilization and to identify factors associated with its utilization among pregnant women from April 4, 2021 to April 15, 2021 in Sodo Zuria Woreda, in Wolaita Zone, Southern Ethiopia.

Methods

A community based cross-sectional study was employed. Data were collected using interviewer administered pretested, structured questionnaires. Simple random sampling method was used to select 459 pregnant women. Data were entered into Epi Info version 7 and then exported to statistical package for the social sciences for further analysis. We used time period for data collection of current study. Binary’s logistic regression was used to determine factors affecting insecticides treated net (ITN) utilization. Adjusted Odd Ratios (OR) with 95% CI was used to measures the strengths of associations.

Results

Of 435 surveyed households with pregnant women, 341(78.39%) with 95% Confidence Interval (CI) (74.5%, 82.3%) possessed at least one insecticide treated net. Among them, 194(56.89%) with 95% CI (51.6%, 61.7%) interviewees had self-reported as they slept under insecticide treated net on the night preceding the data collection day. Utilization of insecticide treated nets by other family members, AOR: 6.615(95% CI: 3.358, 13.032), knowledge that the use of insecticide treated nets can prevent malaria, AOR: 3.221(95% CI: 1.737, 5.974), sleeping under insecticide treated nets, AOR: 3.726(95% CI: 1.974, 7.034), and attending ANC follow up visits, AOR: 1.956(95% CI: 1.097), were found to be significantly associated factors with pregnant women’s insecticide treated net utilization.

Conclusion

The number of households with pregnant women who had possession and utilization of ITNs was much lower than the recommendations set by WHO. Therefore, information dissemination to malaria high risk groups about insecticide treated net utilization and replacement of worn-out insecticide treated nets should be emphasized.
Minimal effects of the 2014-16 marine heatwave on fish assemblages found in eelgrass meadows on the southwestern coast of Vancouver Island, British Columbia, Canada
Authors: Robinson Clifford L.K. , Yakimishyn Jennifer , Evans Rhian
Published: August 2022

The main objective of this study was to ascertain if the 2014 to 2016 spring marine heatwaves, had a significant effect on early summer fish assemblage species composition, abundance and biomass in eelgrass meadows. It was presumed that increased water temperatures above the 90th percentile of the 30y long-term spring temperatures would result in changes to fish growth, survival and ultimately lead to changes in early summer settlement to eelgrass. We assessed this by analyzing the catch per unit effort of 18 common fish species and total fish assemblage biomass in 22 eelgrass meadows from two study areas in the northern California Current during the early summer over an 18 year period from 2004 to 2021. A control chart analysis indicated that eelgrass fish assemblages during heatwave years (2015-16) were significantly higher than the 90th percentile in Bray Curtis dissimilarity of 13 baseline years. Furthermore, analysis of similarity indicated that about one half of the 18 fish species showed variable contributing increases or decreases in catch per unit effort during the heatwave period. In addition, the same fish families from the two study areas only 100km apart did not respond in synchrony to the MHW. We could not however detect any changes in eelgrass fish species composition or assemblage level biomass during the heatwave years. An analysis of the temporal trajectory over the 17y time series in the ordination plots also revealed that changes in fish assemblage dissimilarity during the 2015 and 2016 heatwave returned quickly to levels observed during baseline. Altogether, the results of this study suggest that while the short-term (34-42 d) spring heatwave events resulted in changes fish species abundances, these changes were short-lived. Hence, our results warrant caution about generalizing about the effects of heatwaves on nearshore marine fish.
Advances in lipid-based nanocarriers for breast cancer metastasis treatment
Authors: Joun Ingrid , Nixdorf Sheri , Deng Wei
Published: August 2022

Breast cancer (BC) is the most common cancer affecting women worldwide, with over 2 million women diagnosed every year, and close to 8 million women currently alive following a diagnosis of BC in the last 5-years. The side effects such as chemodrug toxicity to healthy tissues and drug resistance severely affect the quality of life of BC patients. To overcome these limitations, many efforts have been made to develop nanomaterial-based drug delivery systems. Among these nanocarriers, lipid-based delivery platforms represented one of the most successful candidates for cancer therapy, improving the safety profile and therapeutic efficacy of encapsulated drugs. In this review we will mainly discuss and summarize the recent advances in such delivery systems for BC metastasis treatment, with a particular focus on targeting the common metastatic sites in bone, brain and lung. We will also provide our perspectives on lipid-based nanocarrier development for future clinical translation.
Advances in technology and techniques for transcatheter aortic valve replacement with concomitant peripheral arterial disease
Authors: Wong Chun-Ka , Chiu Alston Conrad Ho-On , Chan Kwong-Yue Eric , Sze Shu-Yue , Tam Frankie Chor-Cheung , Un Ka-Chun , Lam Simon Cheung-Chi , Tse Hung-Fat
Published: August 2022

Aortic stenosis (AS) is a prevalent disease affecting 3.7% of the adult population aged 65 or above. In the past, surgical aortic valve replacement (SAVR) was the only definitive therapy available for the treatment of severe AS. Owing to the invasive nature of open-heart surgery, patients with advanced age and frailty could not benefit from SAVR. The advent of transcatheter aortic valve replacement (TAVR) in the past decade has offered an alternative treatment option for patients with severe AS, particularly those who are deemed to have high surgical risks. Nevertheless, a large proportion of patients also have concomitant peripheral arterial disease (PAD), which increases the risk of peri-procedural vascular complication, and precludes the possibility of transfemoral TAVR owing to inadequate luminal size for delivery system deployment. In this review, the prevalence and outcome of TAVR patients with PAD will be discussed. Furthermore, novel technologies and techniques that enable TAVR to be safely performed using transfemoral or alternative access in patients with severe PAD will be reviewed.
Preservation of exopolymeric substances in estuarine sediments
Authors: Duteil Thibault , Bourillot Raphaël , Braissant Olivier , Grégoire Brian , Leloup Maud , Portier Eric , Brigaud Benjamin , Féniès Hugues , Svahn Isabelle , Henry Adrien , Yokoyama Yusuke , Visscher Pieter T.
Published: August 2022

The surface of intertidal estuarine sediments is covered with diatom biofilms excreting exopolymeric substances (EPSs) through photosynthesis. These EPSs are highly reactive and increase sediment cohesiveness notably through organo-mineral interactions. In most sedimentary environments, EPSs are partly to fully degraded by heterotrophic bacteria in the uppermost millimeters of the sediment and so they are thought to be virtually absent deeper in the sedimentary column. Here, we present the first evidence of the preservation of EPSs and EPS-mineral aggregates in a 6-m-long sedimentary core obtained from an estuarine point bar in the Gironde Estuary. EPSs were extracted from 18 depth intervals along the core, and their physicochemical properties were characterized by (i) wet chemical assays to measure the concentrations of polysaccharides and proteins, and EPS deprotonation of functional groups, (ii) acid–base titrations, and (iii) Fourier transform infrared spectroscopy. EPS-sediment complexes were also imaged using cryo-scanning electron microscopy. EPS results were analyzed in the context of sediment properties including facies, grain size, and total organic carbon, and of metabolic and enzymatic activities. Our results showed a predictable decrease in EPS concentrations (proteins and polysaccharides) and reactivity from the surface biofilm to a depth of 0.5 m, possibly linked to heterotrophic degradation. Concentrations remained relatively low down to ca. 4.3 m deep. Surprisingly, at that depth EPSs abundance was comparable to the surface and showed a downward decrease to 6.08 m. cryo-scanning electron microscopy (Cryo-SEM) showed that the EPS complexes with sediment were abundant at all studied depth and potentially protected EPSs from degradation. EPS composition did not change substantially from the surface to the bottom of the core. EPS concentrations and acidity were anti-correlated with metabolic activity, but showed no statistical correlation with grain size, TOC, depth or enzymatic activity. Maximum EPS concentrations were found at the top of tide-dominated sedimentary sequences, and very low concentrations were found in river flood-dominated sedimentary sequences. Based on this observation, we propose a scenario where biofilm development and EPS production are maximal when (i) the point bar and the intertidal areas were the most extensive, i.e., tide-dominated sequences and (ii) the tide-dominated deposit were succeeded by rapid burial beneath sediments, potentially decreasing the probability of encounter between bacterial cells and EPSs.
Characterization of redox and salinity-tolerant alkaline protease from Bacillus halotolerans strain DS5
Authors: Wen Yangxuan , Qiang Jiyu , Zhou Guixu , Zhang Xiaobo , Wang Lei , Shi Yawei
Published: August 2022

Bacillus halotolerans DS5 was isolated and identified as a halophilic microbe according to 16S rRNA analysis and the physical and chemical indices of the strain. A new alkaline protease (designated as prot DS5) from Bacillus halotolerans DS5 was produced, purified, and characterized. After 12 h incubation in the medium with 1% dextrin, 0.5% NaCl, 2% soluble starch, and 1% yeast extract (pH 7.0), it could reach the maximum enzyme activity (279.74 U/ml). The prot DS5 was stable in the pH range of 6.0–12.0 and the temperature range of 40–60°C, with maximal hydrolytic activities at pH 9 and at 50°C. In the presence of Ca2+, Mn2+, Ba2+, Mg2+, and Fe3+, protease activity was enhanced. The prot DS5 was maintained highly stable in NaCl (up to 2.5 mol/L), reducing and oxidizing agents. The prot DS5 also exhibited compatibility in other detergent ingredients, such as non-ionic and anionic surfactants. These properties of prot DS5 make this enzyme suitable for various industrial applications (e.g., detergents and leather).
Integrative analysis of DNA methylation and gene expression data for the diagnosis and underlying mechanism of Parkinson’s disease
Authors: Li Ding , Liang Jiaming , Guo Wenbin , Zhang Yongna , Wu Xuan , Zhang Wenzhou
Published: August 2022

Background

Parkinson’s disease (PD) is the second most common progressive neurodegenerative disorder and the leading cause of disability in the daily activities. In the management of PD, accurate and specific biomarkers in blood for the early diagnosis of PD are urgently needed. DNA methylation is one of the main epigenetic mechanisms and associated with the gene expression and disease initiation of PD. We aimed to construct a methylation signature for the diagnosis of PD patients, and explore the potential value of DNA methylation in therapeutic options.

Materials and methods

Whole blood DNA methylation and gene expression data of PD patients as well as healthy controls were extracted from Gene Expression Omnibus database. Next, differentially expressed genes (DEGs) and differentially methylated genes (DMGs) between PD patients and healthy controls were identified. Least absolute shrinkage and selection operator cox regression analysis was carried out to construct a diagnostic signature based on the overlapped genes. And, the receiver operating characteristic (ROC) curves were drawn and the area under the curve (AUC) was used to assess the diagnostic performance of the signature in both the training and testing datasets. Finally, gene ontology and gene set enrichment analysis were subsequently carried out to explore the underlying mechanisms.

Results

We obtained a total of 9,596 DMGs, 1,058 DEGs, and 237 overlapped genes in the whole blood between PD patients and healthy controls. Eight methylation-driven genes (HIST1H4L, CDC42EP3, KIT, GNLY, SLC22A1, GCM1, INO80B, and ARHGAP26) were identified to construct the gene expression signature. The AUCs in predicting PD patients were 0.84 and 0.76 in training dataset and testing dataset, respectively. Additionally, eight methylation-altered CpGs were also identified to construct the CpGs signature which showed a similarly robust diagnostic capability, with AUCs of 0.8 and 0.73 in training dataset and testing dataset, respectively.

Conclusion

We conducted an integrated analysis of the gene expression and DNA methylation data, and constructed a methylation-driven genes signature and a methylation-altered CpGs signature to distinguish the patients with PD from healthy controls. Both of them had a robust prediction power and provide a new insight into personalized diagnostic and therapeutic strategies for PD.
A narrative sequencing and mentalizing training for adults with autism: A pilot study
Authors: Bylemans Tom , Heleven Elien , Baetens Kris , Deroost Natacha , Baeken Chris , Van Overwalle Frank
Published: August 2022

Adults diagnosed with autism experience difficulties with understanding the mental states of others, or themselves (mentalizing) and with adequately sequencing personal stories (narrative coherence). Given that the posterior cerebellum is implicated in both skills, as well as in the etiology of autism, we developed a narrative sequencing and mentalizing training for autistic adults. Participants with an official autism diagnosis were randomly assigned to a Training group (n = 17) or a waiting-list Control group (n = 15). The Training group took part in six weekly sessions in groups of three participants lasting each about 60 min. During training, participants had to (re)tell stories from the perspective of the original storyteller and answer questions that required mentalizing. We found significant improvements in mentalizing about others’ beliefs and in narrative coherence for the Training group compared to the Control group immediately after the training compared to before the training. Almost all participants from the Training group expressed beneficial effects of the training on their mood and half of the participants reported positive effects on their self-confidence in social situations. All participants recommended the current training to others. Results are discussed in light of cerebellar theories on sequencing of social actions during mentalizing. Further improvements to the program are suggested. Our results highlight the potential clinical utility of adopting a neuroscience-informed approach to developing novel therapeutic interventions for autistic populations.
Profiling mouse cochlear cell maturation using 10× Genomics single-cell transcriptomics
Authors: Xu Zhenhang , Tu Shu , Pass Caroline , Zhang Yan , Liu Huizhan , Diers Jack , Fu Yusi , He David Z. Z. , Zuo Jian
Published: August 2022

Juvenile and mature mouse cochleae contain various low-abundant, vulnerable sensory epithelial cells embedded in the calcified temporal bone, making it challenging to profile the dynamic transcriptome changes of these cells during maturation at the single-cell level. Here we performed the 10x Genomics single-cell RNA sequencing (scRNA-seq) of mouse cochleae at postnatal days 14 (P14) and 28. We attained the transcriptomes of multiple cell types, including hair cells, supporting cells, spiral ganglia, stria fibrocytes, and immune cells. Our hair cell scRNA-seq datasets are consistent with published transcripts from bulk RNA-seq. We also mapped known deafness genes to corresponding cochlear cell types. Importantly, pseudotime trajectory analysis revealed that inner hair cell maturation peaks at P14 while outer hair cells continue development until P28. We further identified and confirmed a long non-coding RNA gene Miat to be expressed during maturation in cochlear hair cells and spiral ganglia neurons, and Pcp4 to be expressed during maturation in cochlear hair cells. Our transcriptomes of juvenile and mature mouse cochlear cells provide the sequel to those previously published at late embryonic and early postnatal ages and will be valuable resources to investigate cochlear maturation at the single-cell resolution.
Prediction model of early biomarkers of massive cerebral infarction caused by anterior circulation occlusion: Establishment and evaluation
Authors: Chen Jingshu , Li Jinze , Xu Zhihua , Zhang Luojin , Qi Shouliang , Yang Benqiang , Chen Zimeng , Wang Xinrui , Duan Yang
Published: August 2022

Objective

The purpose of this study is to establish and evaluate an early biomarker prediction model of massive cerebral infarction caused by anterior circulation occlusion.

Methods

One hundred thirty-four patients with acute cerebral infarction from January 2018 to October 2020 were selected to establish the development cohort for the internal test of the nomogram. Ninety-one patients with acute cerebral infarction hospitalized in our hospital from December 2020 to December 2021 were constituted the validation cohort for the external validation. All patients underwent baseline computed tomography (CT) scans within 12 h of onset and early imaging signs (hyperdense middle cerebral artery sign, obscuration of the lentiform nucleus, insular ribbon sign) of acute cerebral infarction were identified on CT by two neurologists. Based on follow-up CT images, patients were then divided into a massive cerebral infarction group and a non-massive cerebral infarction group. The nomogram model was constructed based on logistic regression analysis with R language. The nomogram was subsequently validated in an independent external validation cohort. Accuracy and discrimination of the prediction model were evaluated by a calibration chart, receiver operating characteristic (ROC) curve, and decision curve.

Results

The indicators, including insular ribbon sign, reperfusion therapy, National Institutes of Health Stroke Scale (NHISS) score, previous cerebral infarction, and atrial fibrillation, were entered into the prediction model through binary logistic regression analysis. The prediction model showed good predictive ability. The area under the ROC curve of the prediction model was 0.848. The specificity, sensitivity, and Youden index were 0.864, 0.733, and 0.597, respectively. This nomogram to the validation cohort also showed good discrimination (AUC = 0.940, 95% CI 0.894–0.985) and calibration.

Conclusion

Demonstrating favorable predictive efficacy and reproducibility, this study successfully established a prediction model of CT imaging signs and clinical data as early biomarkers of massive cerebral infarction caused by anterior circulation occlusion.
Prehospital stroke mimics in the Stockholm Stroke Triage System
Authors: Sjöö Mimmi , Berglund Annika , Sjöstrand Christina , Eriksson Einar E. , Mazya Michael V.
Published: August 2022

Introduction

In 2017, Stockholm implemented a new prehospital stroke triage system (SSTS) directing patients with a likely indication for thrombectomy to the regional comprehensive stroke center (CSC) based on symptom severity and teleconsultation with a physician. In Stockholm, 44% of patients with prehospital code stroke have stroke mimics. Inadvertent triage of stroke mimics to the CSC could lead to inappropriate resource utilization.

Aims

To compare the characteristics between (1) triage-positive stroke mimics and stroke (TP mimics and TP stroke) and (2) triage-negative stroke mimics and stroke (TN mimics and TN stroke) and to (3) compare the distribution of stroke mimic diagnoses between triage-positive and triage-negative cases.

Methods

This prospective observational study collected data from October 2017 to October 2018, including 2,905 patients with suspected stroke who were transported by code-stroke ambulance to a Stockholm regional hospital. Patients directed to the CSC were defined as triage-positive. Those directed to the nearest stroke center were defined as triage-negative.

Results

Compared to individuals with TP stroke (n = 268), those with TP mimics (n = 55, median 64 vs. 75 years, P < 0.001) were younger and had lower NIHSS score (median 7 vs. 15, P < 0.001). Similarly, those with TN mimics (n = 1,221) were younger than those with TN stroke (n = 1,361, median 73 vs. 78 years, P < 0.001) and had lower NIHSS scores (median 2 vs. 4, P < 0.001). Functional paresis was more common in those with TP mimics than in those with TN mimics, 18/55 (32.7%) vs. 82/1,221 (6.7%), P < 0.001. Systemic infection was less common in those with TP mimics than in those with TN mimics, 1/55 (1.8%) vs. 160/1,221 (13.1%), P < 0.011. There was a trend toward “syncope, hypotension, or other cardiovascular diagnosis” being less common in those with TP mimics than in those with TN mimics, 1/55 (1.8%) vs. 118/1,221 (9.7%), P < 0.055.

Conclusions

In the SSTS, those with triage-positive and triage-negative stroke mimics were younger and had less severe symptoms than patients with stroke. All patients with TP mimics who had hemiparesis but overall exhibited less severe symptoms against true stroke but more severe symptoms than those with TN mimics were triaged to the nearest hospital. Over-triage of functional paresis to the CSC was relatively common. Meanwhile, a large majority of cases with minor symptoms caused by stroke mimics was triaged correctly by the SSTS to the nearest stroke center.
Abnormal topological parameters in the default mode network in patients with impaired cognition undergoing maintenance hemodialysis
Authors: Cao Chuanlong , Zhang Die , Liu Wanqing
Published: August 2022

Objective

The role of the default mode network (DMN) in the cognitive impairment experienced by patients with end-stage renal disease (ESRD) undergoing maintenance hemodialysis (MHD) remains unknown. This study tested the hypothesis that the topological architecture of the DMN plays a key role in ESRD-related cognitive impairment.

Methods

For this study, 43 ERSD patients receiving MHD and 41 healthy control (HC) volunteers matched for gender, age and education underwent resting-state functional magnetic resonance imaging examinations. DMN architecture was depicted by 20 selected DMN subregions. Graph theory approaches were applied to investigate multiple topological parameters within the DMN in resting state at the global, local and edge levels.

Results

Globally, the MHD group exhibited topological irregularities as indicated by reduced values for the clustering coeffcient (Cp), normalized Cp (γ), world-index (σ), and local effciency (Eloc) compared with the HC group. Locally, the MHD group showed greater nodal betweenness in the left retrosplenial cortex (RC) compared with the HC group. At the edge level, the MHD group exhibited disconnected resting-state functional connections (RSFCs) in the medial temporal lobe (MTL) subsystem including the ventral medial prefrontal cortex (VMPC)–left posterior inferior parietal lobule, VMPC–right parahippocampal cortex (PC), and right RC–left PC RSFCs. Additionally, the VMPC–right PC RSFC was positively correlated with the Digit Span Test score and Eloc, and the right RC–left PC RSFC was positively correlated with the Montreal Cognitive Assessment score and Eloc in the MHD group.

Conclusions

ESRD patients undergoing MHD showed local inefficiency, abnormal nodal centralities, and hypoconnectivity within the DMN, implying that the functional differentiation and local information transmission efficiency of the DMN are disturbed in ESRD. The disconnected RSFCs in the MTL subsystem likely facilitated topological reconfiguration in the DMN of ESRD patients, leading to impairments of multidomain neurocognition including memory and emotion regulation.
Psychiatric comorbidities and all-cause mortality in epilepsy: A nationwide cohort study
Authors: Puteikis Kristijonas , Kazėnaitė Edita , Mameniškienė Rūta
Published: August 2022

Background

People with epilepsy (PWE) having comorbid psychiatric conditions may be at greater risk of death. We aimed to determine the association between psychiatric disorders and all-cause mortality among PWE after adjustment for somatic comorbidities.

Methods

Based on data from the National Health Insurance Fund, a Cox survival analysis was done within a retrospective open cohort of all PWE (≥12 years) in Lithuania between January 2014 and June 2020. Cox models comparing mortality between PWE with or without psychiatric comorbidities were adjusted for sex, age, hospitalizations, and the epilepsy-specific comorbidity index.

Results

Of 47,964 PWE (age Md = 49, IQR = 34–62 years, 60.3% male, follow-up Md = 4.4, IQR = 2.1–6.1 years), 10,290 (21.5%) died during the study. The diagnosis of any psychiatric disorder (n = 26,137, 54.5%) was associated with increased mortality when adjusted for only sex and age (HR = 1.13, 95% CI = 1.09 to 1.18). After including the epilepsy-specific comorbidity index, the number of hospitalizations and hospital days in the analysis, only self-harm (HR = 1.55, 95% CI = 1.40 to 1.71) and substance use disorders (HR = 1.39 95% CI = 1.32 to 1.47), but not any psychiatric comorbidities (HR = 0.92 95% CI = 0.88 to 0.96) were related to elevated all-cause mortality. Mood, anxiety and behavioral disorders were associated with lower odds of mortality; however, they were rarely documented.

Conclusions

Our results suggest that psychiatric comorbidities increase all-cause mortality among PWE through their association with coexisting somatic conditions as only substance use disorders and self-harm were independently related to elevated all-cause mortality. Future clinical interview-based studies should explore the relationship between mortality in epilepsy and psychiatric comorbidities while adjusting for somatic comorbidities.
Compensatory movement strategies differentially affect attention allocation and gait parameters in persons with Parkinson’s disease
Authors: Yogev-Seligmann Galit , Krasovsky Tal , Kafri Michal
Published: August 2022

Persons with Parkinson’s disease (PwP) are advised to use compensatory strategies such as external cues or cognitive movement strategies to overcome gait disturbances. It is suggested that external cues involve the processing of sensory stimulation, while cognitive-movement strategies use attention allocation. This study aimed to compare over time changes in attention allocation in PwP between prolonged walking with cognitive movement strategy and external cues; to compare the effect of cognitive movement strategies and external cues on gait parameters; and evaluate whether these changes depend on cognitive function. Eleven PwP participated in a single-group pilot study. Participants walked for 10 min under each of three conditions: natural walking, using external cuing, using a cognitive movement strategy. Attention and gait variables were extracted from a single-channel electroencephalogram and accelerometers recordings, respectively. Attention allocation was assessed by the% of Brain Engagement Index (BEI) signals within an attentive engagement range. Cognitive function was assessed using a neuropsychological battery. The walk was divided into 2-min time segments, and the results from each 2-min segment were used to determine the effects of time and condition. Associations between cognitive function and BEI signals were tested. Findings show that in the cognitive movement strategy condition, there was a reduction in the % of BEI signals within the attentive engagement range after the first 2 min of walking. Despite this reduction the BEI did not consistently differ from natural and metronome walking. Spatiotemporal gait variables were better in the cognitive movement strategy condition relative to the other conditions. Global cognitive and information processing scores were significantly associated with the BEI only when the cognitive movement strategy was applied. In conclusion, the study shows that a cognitive movement strategy has positive effects on gait variables but may impose a higher attentional load. Furthermore, when walking using a cognitive movement strategy, persons with higher cognitive function showed elevated attentive engagement. The findings support the idea that cognitive and attentional resources are required for cognitive movement strategies in PwP. Additionally, this study provides support for using single-channel EEG to explore mechanistic aspects of clinical interventions.