bluuebunny/crossref_metadata_2025 huggingface dataset:
Management of oral anticoagulant therapy after intracranial hemorrhage in patients with atrial fibrillation
Authors: Lucà Fabiana , Colivicchi Furio , Oliva Fabrizio , Abrignani Maurizio , Caretta Giorgio , Di Fusco Stefania Angela , Giubilato Simona , Cornara Stefano , Di Nora Concetta , Pozzi Andrea , Di Matteo Irene , Pilleri Anna , Rao Carmelo Massimiliano , Parlavecchio Antonio , Ceravolo Roberto , Benedetto Francesco Antonio , Rossini Roberta , Calvanese Raimondo , Gelsomino Sandro , Riccio Carmine , Gulizia Michele Massimo
Published: May 2023

Intracranial hemorrhage (ICH) is considered a potentially severe complication of oral anticoagulants (OACs) and antiplatelet therapy (APT). Patients with atrial fibrillation (AF) who survived ICH present both an increased ischemic and bleeding risk. Due to its lethality, initiating or reinitiating OACs in ICH survivors with AF is challenging. Since ICH recurrence may be life-threatening, patients who experience an ICH are often not treated with OACs, and thus remain at a higher risk of thromboembolic events. It is worthy of mention that subjects with a recent ICH and AF have been scarcely enrolled in randomized controlled trials (RCTs) on ischemic stroke risk management in AF. Nevertheless, in observational studies, stroke incidence and mortality of patients with AF who survived ICH had been shown to be significantly reduced among those treated with OACs. However, the risk of hemorrhagic events, including recurrent ICH, was not necessarily increased, especially in patients with post-traumatic ICH. The optimal timing of anticoagulation initiation or restarting after an ICH in AF patients is also largely debated. Finally, the left atrial appendage occlusion option should be evaluated in AF patients with a very high risk of recurrent ICH. Overall, an interdisciplinary unit consisting of cardiologists, neurologists, neuroradiologists, neurosurgeons, patients, and their families should be involved in management decisions. According to available evidence, this review outlines the most appropriate anticoagulation strategies after an ICH that should be adopted to treat this neglected subset of patients.
Severe structural valve deterioration after TAVR with ACURATE Neo: report of two cases
Authors: Schaeffer Thibault , Koechlin Luca , Jeger Raban , Leibundgut Gregor , Reuthebuch Oliver
Published: May 2023

Structural valve deterioration (SVD) of transcatheter implanted aortic valve (TAVR) prostheses leading to prosthesis dysfunction is an uncommon yet increasingly described complication. Literature is scarce on specific mechanisms and clinical presentation of SVD after TAVR, notably on self-expanding valve ACURATE Neo. We report on two cases with severe bioprosthetic failure after ACURATE Neo implantation due to leaflet disruption, and we treated them with surgical aortic valve replacement. Based on the literature, we further discuss the incidence of SVD after TAVR, the durability of ACURATE NEO, and the modes of failure of biological valve prostheses.
Bibliometric analysis of 100 top cited articles of heart failure–associated diseases in combination with machine learning
Authors: Kuang Xuyuan , Zhong Zihao , Liang Wei , Huang Suzhen , Luo Renji , Luo Hui , Li Yongheng
Published: May 2023

Objective

The aim of this paper is to analyze the application of machine learning in heart failure-associated diseases using bibliometric methods and to provide a dynamic and longitudinal bibliometric analysis of heart failure–related machine learning publications.

Materials and methods

Web of Science was screened to gather the articles for the study. Based on bibliometric indicators, a search strategy was developed to screen the title for eligibility. Intuitive data analysis was employed to analyze the top-100 cited articles and VOSViewer was used to analyze the relevance and impact of all articles. The two analysis methods were then compared to get conclusions.

Results

The search identified 3,312 articles. In the end, 2,392 papers were included in the study, which were published between 1985 and 2023. All articles were analyzed using VOSViewer. Key points of the analysis included the co-authorship map of authors, countries and organizations, the citation map of journal and documents and a visualization of keyword co-occurrence analysis. Among these 100 top-cited papers, with a mean of 122.9 citations, the most-cited article had 1,189, and the least cited article had 47. Harvard University and the University of California topped the list among all institutes with 10 papers each. More than one-ninth of the authors of these 100 top-cited papers wrote three or more articles. The 100 articles came from 49 journals. The articles were divided into seven areas according to the type of machine learning approach employed: Support Vector Machines, Convolutional Neural Networks, Logistic Regression, Recurrent Neural Networks, Random Forest, Naive Bayes, and Decision Tree. Support Vector Machines were the most popular method.

Conclusions

This analysis provides a comprehensive overview of the artificial intelligence (AI)-related research conducted in the field of heart failure, which helps healthcare institutions and researchers better understand the prospects of AI in heart failure and formulate more scientific and effective research plans. In addition, our bibliometric evaluation can assist healthcare institutions and researchers in determining the advantages, sustainability, risks, and potential impacts of AI technology in heart failure.
Using concept maps to evaluate preservice biology teachers’ conceptualization of COVID-19 as a complex phenomenon
Authors: Bielik Tom , Jagemann Johannes , Krell Moritz , Krüger Dirk , Ben Zvi Assaraf Orit
Published: May 2023

Introduction

The COVID-19 pandemic showed the critical importance of supporting teachers’ and students’ systems thinking when making sense of complex phenomena. This study sets to explore preservice biology teachers’ (PBTs) mental models of COVID-19 as complex phenomenon using concept maps.

Methods

27 PBTs concept maps of COVID-19 outbreak were collected and taken for analysis. Structural and complexity attributes were identified in participants’ concept maps and the relationships between them were tested, providing statistical analyses using exemplary concept maps.

Results

The results suggest that the appearance of many concepts in a map (structural attribute) does not necessarily indicate high level of complexity, but rather the amount of simple structural relationships (complexity attribute). On the other hand, the results indicate that higher structural sophistication (e.g., high number of connections and junctions) could be associated with the complexity level of the map.

Discussion

This study provides a practical method for evaluating the complexity level of PBTs’ systems thinking, suggests a possible link between structural and complexity attributes in their concept maps, and demonstrates the need to further support PBTs in developing their systems thinking skills in the context of complex biological phenomena.
ZIP9 mediates the effects of DHT on learning, memory and hippocampal synaptic plasticity of male Tfm and APP/PS1 mice
Authors: Song Leigang , Chen Huan , Qiao Dan , Zhang Bohan , Guo Fangzhen , Zhang Yizhou , Wang Chang , Li Sha , Cui Huixian
Published: May 2023

Androgens are closely associated with functions of hippocampal learning, memory, and synaptic plasticity. The zinc transporter ZIP9 (SLC39A9) regulates androgen effects as a binding site distinct from the androgen receptor (AR). However, it is still unclear whether androgens regulate their functions in hippocampus of mice through ZIP9. Compared with wild-type (WT) male mice, we found that AR-deficient male testicular feminization mutation (Tfm) mice with low androgen levels had learning and memory impairment, decreased expression of hippocampal synaptic proteins PSD95, drebrin, SYP, and dendritic spine density. Dihydrotestosterone (DHT) supplementation significantly improved these conditions in Tfm male mice, although the beneficial effects disappeared after hippocampal ZIP9 knockdown. To explore the underlying mechanism, we first detected the phosphorylation of ERK1/2 and eIF4E in the hippocampus and found that it was lower in Tfm male mice than in WT male mice, it upregulated with DHT supplementation, and it downregulated after hippocampal ZIP9 knockdown. Next, we found that the expression of PSD95, p-ERK1/2, and p-eIF4E increased in DHT-treated mouse hippocampal neuron HT22 cells, and ZIP9 knockdown or overexpression inhibited or further enhanced these effects. Using the ERK1/2 specific inhibitor SCH772984 and eIF4E specific inhibitor eFT508, we found that DHT activated ERK1/2 through ZIP9, resulting in eIF4E phosphorylation, thus promoting PSD95 protein expression in HT22 cells. Finally, we found that ZIP9 mediated the effects of DHT on the expression of synaptic proteins PSD95, drebrin, SYP, and dendritic spine density in the hippocampus of APP/PS1 mice through the ERK1/2-eIF4E pathway and affected learning and memory. This study demonstrated that androgen affected learning and memory in mice through ZIP9, providing new experimental evidence for improvement in learning and memory in Alzheimer’s disease with androgen supplementation.
Jinlida granules combined with metformin improved the standard-reaching rate of blood glucose and clinical symptoms of patients with type 2 diabetes: secondary analysis of a randomized controlled trial
Authors: Kang Xiaomin , Sun Yuting , Duan Yingying , Zhang Yuqing , An Xudong , Jin De , Lian Fengmei , Tong Xiaolin
Published: May 2023

Background

Previous studies found that Jinlida granules could significantly reduce blood glucose levels and enhance the low-glucose action of metformin. However, the role of Jinlida in the standard-reaching rate of blood glucose and improving clinical symptoms has yet to be studied. We aimed to elaborate on the efficacy of Jinlida in type 2 diabetes (T2D) patients who experience clinical symptoms based on secondary analysis of a randomized controlled trial.

Methods

Data were analyzed from a 12-week, randomized, placebo-controlled study of Jinlida. The standard-reaching rate of blood glucose, the symptom disappearance rate, the symptom improvement rate, the efficacy of single symptoms, and the total symptom score were evaluated. The correlation between HbA1c and the improvement of clinical symptoms was analyzed.

Results

For 12 weeks straight, 192 T2D patients were randomly assigned to receive either Jinlida or a placebo. The treatment group showed statistically significant differences in the standard-reaching rate of HbA1c < 6.5% (p = 0.046) and 2hPG (< 10 mmol/L, 11.1 mmol/L) (p < 0.001), compared with the control group. The standard-reaching rate of HbA1c < 7% (p = 0.06) and FBG < 7.0 mmol/L (p = 0.079) were not significantly different between the treatment and control groups. Five symptoms exhibited a statistical difference in symptom disappearance rate (p < 0.05). All the symptoms exhibited a significant difference in symptom improvement rate (p < 0.05). The mean change in total symptom score from baseline to week 12 was −5.45 ± 3.98 in the treatment group and −2.38 ± 3.11 in the control group, with statistically significant differences (p < 0.001). No significant correlations were noted between symptom improvement and HbA1c after 12 weeks of continuous intervention with Jinlida granules or placebo.

Conclusion

Jinlida granules can effectively improve the standard-reaching rate of blood glucose and clinical symptoms of T2D patients, including thirst, fatigue, increased eating with rapid hungering, polyuria, dry mouth, spontaneous sweating, night sweat, vexing heat in the chest, palms, and soles, and constipation. Jinlida granules can be used as an effective adjuvant treatment for T2D patients who experience those symptoms.
Association between serum-free thyroxine level and all-cause mortality in critically ill patients: a retrospective study from MIMIC-IV
Authors: Dai Juan-Juan , Du Ding-Fu , Ma Gang , Jiang Ming-Jie
Published: May 2023

Background

Low thyroxine (T4) levels have been observed in critically ill patients; however, controversial results regarding T4 supplemental therapy are reported. The association between serum free T4 (FT4) levels and mortality in critically ill patients has not been fully established and needs to be clarified.

Methods

Data from the Medical Information Mart for Intensive Care (MIMIC)-IV were collected and analyzed. The association between FT4 level and 30-day mortality after ICU admission was analyzed using Kaplan–Meier curves, spline smoothing fitting, martingale residuals of the null Cox model, and restricted cubic spline (RCS). Logistic regression, Cox regression, and receiver operating characteristic curve (ROC) were used to uncover the relationship and predictive value of serum FT4 and 30-day mortality in critically ill patients.

Results

In the final analysis, 888 patients were enrolled, and the serum FT4 levels were divided into four groups. A significant difference in 30-day mortality was observed between the four groups. Kaplan–Meier curves also presented significantly higher 30-day mortality in groups 1 and 2 (p < 0.0001). Further multivariance logistic regression showed that group 1 with FT4 levels lower than 0.7 μg/dl can predict 30-day mortality (odds ratio (OR) = 3.30, 95% confidence interval (CI) = 1.04–11.31). Spline smoothing fitting analysis showed a “V”-shaped line between 30-day mortality and FT4 level within 0–3 μg/dl. Further RCS analysis showed that the risk of death decreased rapidly as FT4 levels increased when serum FT4 levels were lower than 1.2 μg/dl and started to become flat afterward. The area under the ROC of the lower FT4 level to predict 30-day mortality was 0.833 (95% CI = 0.788–0.878). Both multivariant Cox regression and logistic regression showed that FT4 levels lower than 1.2 μg/dl can independently predict 30-day mortality when adjusted for other potential confounders (HR = 0.34, 95% CI = 0.14–0.82; OR = 0.21, 95% CI = 0.06–0.79, respectively), but its predictive power disappeared when adjusted for T3 or total T4.

Conclusion

Serum FT4 levels were significantly negatively associated with 30-day mortality when they were lower than 1.2 μg/dl and could predict the risk of 30-day mortality. A higher FT4 level is potentially related to increased 30-day mortality.
A minimal human physiologically based kinetic model of thyroid hormones and chemical disruption of plasma thyroid hormone binding proteins
Authors: Bagga Anish D. , Johnson Brian P. , Zhang Qiang
Published: May 2023

The thyroid hormones (THs), thyroxine (T4) and triiodothyronine (T3), are under homeostatic control by the hypothalamic-pituitary-thyroid axis and plasma TH binding proteins (THBPs), including thyroxine-binding globulin (TBG), transthyretin (TTR), and albumin (ALB). THBPs buffer free THs against transient perturbations and distribute THs to tissues. TH binding to THBPs can be perturbed by structurally similar endocrine-disrupting chemicals (EDCs), yet their impact on circulating THs and health risks are unclear. In the present study, we constructed a human physiologically based kinetic (PBK) model of THs and explored the potential effects of THBP-binding EDCs. The model describes the production, distribution, and metabolism of T4 and T3 in the Body Blood, Thyroid, Liver, and Rest-of-Body (RB) compartments, with explicit consideration of the reversible binding between plasma THs and THBPs. Rigorously parameterized based on literature data, the model recapitulates key quantitative TH kinetic characteristics, including free, THBP-bound, and total T4 and T3 concentrations, TH productions, distributions, metabolisms, clearance, and half-lives. Moreover, the model produces several novel findings. (1) The blood-tissue TH exchanges are fast and nearly at equilibrium especially for T4, providing intrinsic robustness against local metabolic perturbations. (2) Tissue influx is limiting for transient tissue uptake of THs when THBPs are present. (3) Continuous exposure to THBP-binding EDCs does not alter the steady-state levels of THs, while intermittent daily exposure to rapidly metabolized TBG-binding EDCs can cause much greater disruptions to plasma and tissue THs. In summary, the PBK model provides novel insights into TH kinetics and the homeostatic roles of THBPs against thyroid disrupting chemicals.
Diagnostic value of serum cathepsin S in type 2 diabetic kidney disease
Authors: Ren Xuejing , Wang Wanqing , Cao Huixia , Shao Fengmin
Published: May 2023

Background

Identification of risk factors that have causal effects on the occurrence of diabetic kidney disease (DKD), is of great significance in early screening and intervening for DKD, and in delaying the progression of DKD to end-stage renal disease. Cathepsin S (Cat-S), a novel non-invasive diagnostic marker, mediates vascular endothelial dysfunction. The diagnostic value of Cat-S for DKD has rarely been reported in clinical studies.

Objective

To analyze whether Cat-S is a risk factor for DKD and evaluate the diagnostic value of serum Cat-S for DKD.

Methods

Forty-three healthy subjects and 200 type 2 diabetes mellitus (T2DM) patients were enrolled. T2DM patients were divided into subgroups according to various criteria. Enzyme-linked immunosorbent assay was used to detect serum Cat-S levels among different subgroups. Spearman correlation analysis was used to analyze correlations between serum Cat-S and clinical indicators. Multivariate logistic regression analysis was performed to analyze risk factors for the occurrence of DKD and decreased renal function in T2DM patients.

Results

Spearman analysis showed that serum Cat-S level was positively correlated with urine albumin creatinine ratio (r=0.76, P<0.05) and negatively correlated with estimated glomerular filtration rate (r=−0.54, P<0.01). Logistic regression analysis showed that increased serum Cat-S and cystatin C(CysC) were independent risk factors for DKD and decreased renal function in T2DM patients (P<0.05). The area under the receiver operating characteristic (ROC) curve was 0.900 of serum Cat-S for diagnosing DKD, and when the best cut-off value was 827.42 pg/mL the sensitivity and specificity were 71.6% and 98.8%, respectively. Thus, serum Cat-S was better than CysC for diagnosing DKD (for CysC, the area under the ROC curve was 0.791, and when the cut-off value was 1.16 mg/L the sensitivity and specificity of CysC were 47.4% and 98.8%, respectively).

Conclusion

Increased serum Cat-S were associated with the progression of albuminuria and decreased renal function in T2DM patients. The diagnostic value of serum Cat-S was better than that of CysC for DKD. Monitoring of serum Cat-S levels could be helpful for early screening DKD and assessing the severity of DKD and could provide a new strategy for diagnosing DKD.
Multi-objective optimization of PEMFC performance based on grey correlation analysis and response surface method
Authors: Wu Gang , Luo Na
Published: May 2023

This paper aims to combine grey correlation analysis and response surface method to propose a fast and effective performance optimization method for PEMFC. First, based on orthogonal test data, grey correlation analysis method is used to select four variables that have significant influence on PEMFC’s comprehensive performance from eight common parameters. Secondly, based on grey correlation analysis, the multi-objective optimization problem is transformed into a single objective optimization problem about correlation degree, and applying the response surface method to build the key parameters and the correlation between the second order prediction model. Therefore, the current density, system efficiency and oxygen distribution uniformity on cathode catalyst layer of PEMFC were optimized as a whole. Finally, the optimal parameter combination was obtained by optimizing the prediction model. The simulation results show that the optimized operating conditions are significantly improved in the three performance indexes compared with the basic model, which confirms the feasibility of this method in solving the multi-objective optimization problem, and can provide some reference for the optimal design of hydrogen fuel cells.
Linked mercury methylation and nitrification across oxic subpolar regions
Authors: Despins Marissa C. , Mason Robert P. , Aguilar-Islas Ana M. , Lamborg Carl H. , Hammerschmidt Chad R. , Newell Silvia E.
Published: May 2023

Methylmercury (MeHg) is a neurotoxin that bioaccumulates to potentially harmful concentrations in Arctic and Subarctic marine predators and those that consume them. Monitoring and modeling MeHg bioaccumulation and biogeochemical cycling in the ocean requires an understanding of the mechanisms behind net mercury (Hg) methylation. The key functional gene pair for Hg methylation, hgcAB, is widely distributed throughout ocean basins and spans multiple microbial phyla. While multiple microbially mediated anaerobic pathways for Hg methylation in the ocean are known, the majority of hgcA homologs have been found in oxic subsurface waters, in contrast to other ecosystems. In particular, microaerophilic Nitrospina, a genera of nitrite-oxidizing bacteria containing a hgcA-like sequence, have been proposed as a potentially important Hg methylator in the upper ocean. The objective of this work was therefore to examine the potential of nitrifiers as Hg methylators and quantify total Hg and MeHg across three Arctic and Subarctic seas (the Gulf of Alaska, the Bering Sea and the Chukchi Sea) in regions where Nitrospina are likely present. In Spring 2021, samples for Hg analysis were obtained with a trace metal clean rosette across these seas. Mercury methylation rates were quantified in concert with nitrification rates using onboard incubation experiments with additions of stable isotope-labeled Hg and NH4+. A significant correlation between Hg methylation and nitrification was observed across all sites (R2 = 0.34, p < 0.05), with the strongest correlation in the Chukchi Sea (R2 = 0.99, p < 0.001). Nitrospina-specific hgcA-like genes were detected at all sites. This study, linking Hg methylation and nitrification in oxic seawater, furthers understanding of MeHg cycling in these high latitude waters, and the ocean in general. Furthermore, these studies inform predictions of how climate and human interactions could influence MeHg concentrations across the Arctic in the future.
Health assessment of natural larch forest in arxan guided by forestry remote sensing integrated with canopy feature analysis
Authors: Ri Ana , An Huijun
Published: May 2023

This work aims to propose a more accurate assessment method for forest health in natural larch pine forests of the Arxan by integrating remote sensing technology with tree crown feature analysis. Currently, forest health assessment of natural Larch pine forests relies mainly on ground surveys, and there is a gap in the application of remote sensing technology in this field. This work introduces deep learning technology and proposes a spectral-Gabor space discrimination and classification model to analyze multi-spectral remote sensing image features. Additionally, quantitative indicators, such as tree crown features, are incorporated into the forest health assessment system. The health status of natural Larch pine forests is evaluated using forest resource survey data. The results show that the health levels of natural Larch pine forests in different areas vary and are closely related to factors such as canopy density, community structure, age group, and slope. Both quantitative and qualitative indicators are used in the analysis. The introduction of this innovative method enhances the accuracy and efficiency of forest health assessment, providing significant support for forest protection and management. In addition, the classification accuracy of the health assessment model suggested that the maximum statistical values of average classification accuracy, average classification effectiveness, overall classification accuracy, and Kappa were 74.19%, 61.91%, 63.18%, and 57.63%, respectively. This demonstrates that the model can accurately identify the health status of natural larch forests. This work can effectively assess the health status of the natural larch forest in the Arxan and provide relevant suggestions based on the assessment results to offer a reference for the sustainable development of the forest system.
Monitoring of patients with active inflammatory bowel disease
Authors: Kucharzik T. , Verstockt B. , Maaser C.
Published: May 2023

In the current treat-to-target era, close and tight monitoring of patients with inflammatory bowel disease has become increasingly important. Although the importance of patient reported outcomes (PROMs) cannot be underestimated, its moderate association with biochemical and histo-endoscopic outcomes highlights the need for additional monitoring strategies. Endoscopic and histological remission are linked with improved long-term outcomes, but require more invasive assessments. Hence, non-invasive monitoring modalities are becoming increasingly relevant, with emerging evidence demonstrating the added clinical value of transmural assessment, both in Crohn’s disease and ulcerative colitis. The current review covers the multiple treatment targets present in IBD care, and focusses in particular on the increasing importance of intestinal ultrasound. Finally, we propose a potential algorithm to monitor patients with IBD in daily clinical practice and highlight gaps for future research in monitoring IBD strategies.
Circulating levels of cytokines and risk of cardiovascular disease: a Mendelian randomization study
Authors: Wei Tao , Zhu Zhanfang , Liu Lin , Liu Bo , Wu Min , Zhang Wei , Cui Qianwei , Liu Fuqiang , Zhang Ronghuai
Published: May 2023

Background

Epidemiological studies have linked various circulating cytokines to cardiovascular disease (CVD), which however remains uncertain whether these relationships represent causality or are due to bias. To address this question, we conducted a Mendelian randomization (MR) analysis to systematically investigate the causal effects of circulating cytokine levels on CVD development.

Methods

This study leveraged the summary statistic from respective genome-wide association study (GWAS) of 47 cytokines and four types of CVD. The cis-quantitative trait locus (cis-QTL) definition, derived from a GWAS meta-analysis comprising 31,112 participants of European descent, served as instruments for cytokines. A two-sample MR design was employed, followed by comprehensive sensitivity analyses to validate the robustness of results.

Results

The results of inverse-variance weighted method using cis-protein QTL (cis-pQTL) instruments, showed the causal effects of four cytokines (i.e., IL-1ra, MCSF, SeSelectin, SCF) on the risk of coronary artery disease (CAD). We also identified causal relationships between two cytokines (i.e., IL-2ra, IP-10) and heart failure (HF), as well as two cytokines (i.e., MCP-3, SeSelectin) and atrial fibrillation (AF), after controlling for false discovery rate (FDR). The use of cis-expression QTL (cis-eQTL) revealed additional causal associations between IL-1a, MIF and CAD, between IL-6, MIF, and HF, as well as between FGFBasic and AF. No significant sign was survived for stroke with FDR applied. Results were largely consistent across sensitivity analyses.

Conclusion

The present study provides supportive evidence that genetic predisposition to levels of certain cytokines causally affects the development of specific type of CVD. These findings have important implications for the creation of novel therapeutic strategies targeting these cytokines as a means of preventing and treating CVD.
Defining the pediatric response to SARS-CoV-2 variants
Authors: Ho Reanne M. , Bowen Asha C. , Blyth Christopher C. , Imrie Allison , Kollmann Tobias R. , Stick Stephen M. , Kicic Anthony
Published: May 2023

The global population has been severely affected by the coronavirus disease 2019 (COVID-19) pandemic, however, with older age identified as a risk factor, children have been underprioritized. This article discusses the factors contributing to the less severe response observed in children following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), including, differing viral entry receptor expression and immune responses. It also discusses how emerging and future variants could present a higher risk to children, including those with underlying comorbidities, in developing severe disease. Furthermore, this perspective discusses the differential inflammatory markers between critical and non-critical cases, as well as discussing the types of variants that may be more pathogenic to children. Importantly, this article highlights where more research is urgently required, in order to protect the most vulnerable of our children.
Harnessing type I interferon-mediated immunity to target malignant brain tumors
Authors: Lim Juhee , Kang In , La Jeongwoo , Ku Keun Bon , Kang Byeong Hoon , Kim Yumin , Park Won Hyung , Lee Heung Kyu
Published: May 2023

Type I interferons have long been appreciated as a cytokine family that regulates antiviral immunity. Recently, their role in eliciting antitumor immune responses has gained increasing attention. Within the immunosuppressive tumor microenvironment (TME), interferons stimulate tumor-infiltrating lymphocytes to promote immune clearance and essentially reshape a “cold” TME into an immune-activating “hot” TME. In this review, we focus on gliomas, with an emphasis on malignant glioblastoma, as these brain tumors possess a highly invasive and heterogenous brain TME. We address how type I interferons regulate antitumor immune responses against malignant gliomas and reshape the overall immune landscape of the brain TME. Furthermore, we discuss how these findings can translate into future immunotherapies targeting brain tumors in general.
Identification and characterization of circRNAs from different body color leopard coral grouper (Plectropomus leopardus)
Authors: Hao Ruijuan , Zhu Xiaowen , Tian Changxu , Huang Yang , Li Guangli , Zhu Chunhua
Published: May 2023

Circular RNAs (circRNAs) play key roles in several biological processes in animals and their regulatory mechanism in body color formation or pigmentation in fish remains unclear. Here, circRNAs from black and red individuals of Plectropomus leopardus were identified to clarify the mechanism of circRNAs and the competing endogenous RNA (ceRNA) network (circRNA-microRNA (miRNA)-messenger RNA (mRNA)) in body color formation. We detected a total of 1,424 novel circRNAs. Expression analysis of circRNAs in black vs. red P. leopardus revealed 24 differentially expressed circRNAs (DECs), and 11 and 13 of these DECs were up-regulated and down-regulated in red individuals relative to black individuals, respectively (P<0.05 and |log2 Fold Change (FC)|>1). We identified a total of 19 significant miRNA-circRNA-mRNA ceRNA networks through the analysis of DECs, differentially expressed miRNAs (DEMs) and differentially expressed genes (DEGs). Pathway enrichment analyses of the DEGs involved in the ceRNA network revealed that they were mainly involved in melanin metabolism and immune response. Our findings showed the possibility of the regulatory functions of circRNAs and the corresponding ceRNA network in the body color formation process and will aid the breeding selection process of P. leopardus.
Prime editing strategies to mediate exon skipping in DMD gene
Authors: Happi Mbakam Cedric , Roustant Jeanne , Rousseau Joel , Yameogo Pouire , Lu Yaoyao , Bigot Anne , Mamchaoui Kamel , Mouly Vincent , Lamothe Gabriel , Tremblay Jacques P.
Published: May 2023

Duchenne muscular dystrophy is a rare and lethal hereditary disease responsible for progressive muscle wasting due to mutations in the DMD gene. We used the CRISPR-Cas9 Prime editing technology to develop different strategies to correct frameshift mutations in DMD gene carrying the deletion of exon 52 or exons 45 to 52. With optimized epegRNAs, we were able to induce the specific substitution of the GT nucleotides of the splice donor site of exon 53 in up to 32% of HEK293T cells and 28% of patient myoblasts. We also achieved up to 44% and 29% deletion of the G nucleotide of the GT splice site of exon 53, as well as inserted 17% and 5.5% GGG between the GT splice donor site of exon 51 in HEK293T cells and human myoblasts, respectively. The modification of the splice donor site for exon 51 and exon 53 provoke their skipping and allowed exon 50 to connect to exon 53 and allowed exon 44 to connect to exon 54, respectively. These corrections restored the expression of dystrophin as demonstrated by western blot. Thus, Prime editing was used to induce specific substitutions, insertions and deletions in the splice donor sites for exons 51 and 53 to correct the frameshift mutations in DMD gene carrying deletions of exon 52 and exons 45 to 52, respectively.
Intra-subject variability in oscillometry correlates with acute rejection and CLAD post-lung transplant
Authors: Vasileva Anastasiia , Hanafi Nour , Huszti Ella , Matelski John , Belousova Natalia , Wu Joyce K. Y. , Martinu Tereza , Ghany Rasheed , Keshavjee Shaf , Tikkanen Jussi , Cypel Marcelo , Yeung Jonathan C. , Ryan Clodagh M. , Chow Chung-Wai
Published: May 2023

Background

Chronic lung allograft dysfunction (CLAD) is the major cause of death post-lung transplantation, with acute cellular rejection (ACR) being the biggest contributing risk factor. Although patients are routinely monitored with spirometry, FEV1 is stable or improving in most ACR episodes. In contrast, oscillometry is highly sensitive to respiratory mechanics and shown to track graft injury associated with ACR and its improvement following treatment. We hypothesize that intra-subject variability in oscillometry measurements correlates with ACR and risk of CLAD.

Methods

Of 289 bilateral lung recipients enrolled for oscillometry prior to laboratory-based spirometry between December 2017 and March 2020, 230 had ≥ 3 months and 175 had ≥ 6 months of follow-up. While 37 patients developed CLAD, only 29 had oscillometry at time of CLAD onset and were included for analysis. These 29 CLAD patients were time-matched with 129 CLAD-free recipients. We performed multivariable regression to investigate the associations between variance in spirometry/oscillometry and the A-score, a cumulative index of ACR, as our predictor of primary interest. Conditional logistic regression models were built to investigate associations with CLAD.

Results

Multivariable regression showed that the A-score was positively associated with the variance in oscillometry measurements. Conditional logistic regression models revealed that higher variance in the oscillometry metrics of ventilatory inhomogeneity, X5, AX, and R5-19, was independently associated with increased risk of CLAD (p < 0.05); no association was found for variance in %predicted FEV1.

Conclusion

Oscillometry tracks graft injury and recovery post-transplant. Monitoring with oscillometry could facilitate earlier identification of graft injury, prompting investigation to identify treatable causes and decrease the risk of CLAD.
Return to work after sepsis—a German population-based health claims study
Authors: Fleischmann-Struzek Carolin , Ditscheid Bianka , Rose Norman , Spoden Melissa , Wedekind Lisa , Schlattmann Peter , Günster Christian , Reinhart Konrad , Hartog Christiane S. , Freytag Antje
Published: May 2023

Background

Long-term impairments after sepsis can impede the return to work in survivors. We aimed to describe rates of return to work 6 and 12 months postsepsis.

Methods

This retrospective, population-based cohort study was based on health claims data of the German AOK health insurance of 23.0 million beneficiaries. We included 12-months survivors after hospital-treated sepsis in 2013/2014, who were ≤60 years at the time of the admission and were working in the year presepsis. We assessed the prevalence of return to work (RTW), persistent inability to work and early retirement.

Results

Among 7,370 working age sepsis survivors, 69.2% returned to work at 6 months postsepsis, while 22.8% were on sick leave and 8.0% retired early. At 12 months postsepsis, the RTW rate increased to 76.9%, whereas 9.8% were still on sick leave and 13.3% retired early. Survivors who returned to work had a mean of 70 (SD 93) sick leave days in the 12 months presepsis (median 28 days, IQR 108 days).

Conclusion

One out of four working age sepsis survivors does not resume work in the year postsepsis. Specific rehabilitation and targeted aftercare may be opportunities to reduce barriers to RTW after sepsis.
IncHI1 plasmids are epidemic vectors that mediate transmission of tet(X4) in Escherichia coli isolated from China
Authors: Zhang Yan , Zhang Jie , Cai Ping , Lu Yang , Sun Ruan-Yang , Cao Meng-Tao , Xu Xiao-Li , Webber Mark A. , Jiang Hong-Xia
Published: May 2023

Introduction

This study aimed to investigate the genetic factors promoting widespread Q6 dissemination of tet(X4) between Escherichia coli and to characterize the genetic contexts of tet(X4).

Methods

We isolated E. coli from feces, water, soil and flies collected across a large-scale chicken farm in China in 2020. Antimicrobial susceptibility testing and PFGE typing were used to identify tigecycline resistance and assess clonal relationships among isolates. Plasmids present and genome sequences were analyzed by conjugation, S1 pulsed-field gel electrophoresis (PFGE), plasmid stability testing and whole-genome sequencing.

Results

A total of 204 tigecycline-resistant E. coli were isolated from 662 samples. Of these, we identified 165 tet(X4)-carrying E. coli and these strains exhibited a high degree of multidrug resistance. Based on the geographical location distribution of the sampled areas, number of samples in each area and isolation rate of tigecycline-resistant strains and tet(X4)-carrying isolates, 72 tet(X4)-positive isolates were selected for further investigation. Tigecycline resistance was shown to be mobile in 72 isolates and three types of tet(X4)-carrying plasmids were identified, they were IncHI1 (n = 67), IncX1 (n = 3) and pO111-like/IncFIA(HI1) (n = 2). The pO111-like/IncFIA(HI1) is a novel plasmid capable of transferring tet(X4). The transfer efficiency of IncHI1 plasmids was extremely high in most cases and IncHI1 plasmids were stable when transferred into common recipient strains. The genetic structures flanked by IS1, IS26 and ISCR2 containing tet(X4) were complex and varied in different plasmids.

Discussion

The widespread dissemination of tigecycline-resistant E. coli is a major threat to public health. This data suggests careful use of tetracycline on farms is important to limit spread of resistance to tigecycline. Multiple mobile elements carrying tet(X4) are in circulation with IncHI1 plasmids the dominant vector in this setting.
Contrasting effects of organic materials versus their derived biochars on maize growth, soil properties and bacterial community in two type soils
Authors: Yue Xiaosong , Liu Xing , Wang Fei , Shen Changwei , Zhang Ying
Published: May 2023

The objective of this study was to assess the benefit of applying biochar instead of its feedstock in enhancing soil quality. To accomplish this, we investigated the short-term effects of two organic materials and their derived biochars on maize growth, soil properties, and microbial community in fluvo-aquic and red soil with a pot experiment. Five treatments were applied to each soil, namely, the addition of straw, manure, straw-derived biochar, manure-derived biochar, and the control with no addition of any organic materials and biochar. Our results revealed that straw decreased the shoot biomass of maize in both soils, while straw-derived biochar, manure and manure-derived biochar increased it by 51.50, 35.47 and 74.95% in fluvo-aquic soil and by 36.38, 117.57 and 67.05% in red soil compared with the control, respectively. Regarding soil properties, although all treatments increased soil total organic carbon, straw and manure exhibited more pronounced effects on improving permanganate-oxidizable carbon, basal respiration, and enzyme activity compared with their derived biochars. Manure and its biochar had more significant effects on improving soil available phosphorus, whereas straw and its biochar exhibited more ameliorating effects on available potassium. Straw and manure consistently decreased bacterial alpha diversity (Chao1 and Shannon index) and altered bacterial community composition in the two soils by increasing the relative abundances of Proteobacteria, Firmicutes, and Bacteroidota and decreasing those of Actinobacteriota, Chloroflexi, and Acidobacteriota. More specifically, straw had a greater effect on Proteobacteria, whereas manure affected Firmicutes more. While straw-derived biochar had no effect on bacterial diversity and bacterial community composition in both soils, manure-derived biochar increased bacterial diversity in the fluvo-aquic soil and altered bacterial community composition in the red soil by increasing the relative abundances of Proteobacteria and Bacteroidota and decreasing that of Firmicutes. In summary, owing to the input of active organic carbon, straw and manure exhibited more pronounced short-term effects on soil enzyme activity and bacterial community compared with their derived biochar. Furthermore, straw-derived biochar was found to be a better option than straw in promoting maize growth and nutrient resorption, while the choice of manure and its biochar should be determined by the soil type.
Salmonella antimicrobials inherited and the non-inherited resistance: mechanisms and alternative therapeutic strategies
Authors: Zhou Kaixiang , Sun Lei , Zhang Xuehua , Xu Xiangyue , Mi Kun , Ma Wenjin , Zhang Lan , Huang Lingli
Published: May 2023

Salmonella spp. is one of the most important foodborne pathogens. Typhoid fever and enteritis caused by Salmonella enterica are associated with 16–33 million infections and 500,000 to 600,000 deaths annually worldwide. The eradication of Salmonella is becoming increasingly difficult because of its remarkable capacity to counter antimicrobial agents. In addition to the intrinsic and acquired resistance of Salmonella, increasing studies indicated that its non-inherited resistance, which commonly mentioned as biofilms and persister cells, plays a critical role in refractory infections and resistance evolution. These remind the urgent demand for new therapeutic strategies against Salmonella. This review starts with escape mechanisms of Salmonella against antimicrobial agents, with particular emphasis on the roles of the non-inherited resistance in antibiotic failure and resistance evolution. Then, drug design or therapeutic strategies that show impressive effects in overcoming Salmonella resistance and tolerance are summarized completely, such as overcoming the barrier of outer membrane by targeting MlaABC system, reducing persister cells by limiting hydrogen sulfide, and applying probiotics or predatory bacteria. Meanwhile, according to the clinical practice, the advantages and disadvantages of above strategies are discussed. Finally, we further analyze how to deal with this tricky problems, thus can promote above novel strategies to be applied in the clinic as soon as possible. We believed that this review will be helpful in understanding the relationships between tolerance phenotype and resistance of Salmonella as well as the efficient control of antibiotic resistance.
Lipid A structural diversity among members of the genus Leptospira
Authors: Pětrošová Helena , Mikhael Abanoub , Culos Sophie , Giraud-Gatineau Alexandre , Gomez Alloysius M. , Sherman Matthew E. , Ernst Robert K. , Cameron Caroline E. , Picardeau Mathieu , Goodlett David R.
Published: May 2023

Lipid A is the hydrophobic component of bacterial lipopolysaccharide and an activator of the host immune system. Bacteria modify their lipid A structure to adapt to the surrounding environment and, in some cases, to evade recognition by host immune cells. In this study, lipid A structural diversity within the Leptospira genus was explored. The individual Leptospira species have dramatically different pathogenic potential that ranges from non-infectious to life-threatening disease (leptospirosis). Ten distinct lipid A profiles, denoted L1-L10, were discovered across 31 Leptospira reference species, laying a foundation for lipid A-based molecular typing. Tandem MS analysis revealed structural features of Leptospira membrane lipids that might alter recognition of its lipid A by the host innate immune receptors. Results of this study will aid development of strategies to improve diagnosis and surveillance of leptospirosis, as well as guide functional studies on Leptospira lipid A activity.
Targeting the autophagy-lysosomal pathway in Huntington disease: a pharmacological perspective
Authors: Yang Junsheng , Zhang Chaoyue
Published: May 2023

The autophagy-lysosomal pathway (ALP) is the major biological pathway responsible for clearing intracellular protein aggregates, therefore a promising target for treating diseases featuring the accumulation of aggregation-prone proteins, such as Huntington disease (HD). However, accumulating evidence indicated that targeting ALP to treat HD is pharmacologically challenging due to the complexity of autophagy and the autophagy defects in HD cells. Here in this mini-review, we summarized the current challenges in targeting ALP in HD and discussed a number of latest findings on aggrephagy and targeted protein degradation, which we believe will provide potential new targets and new strategies for treating HD via ALP.
Association between migraine and Alzheimer’s disease: a nationwide cohort study
Authors: Kim Jaeho , Ha Woo Seok , Park Sang Hyun , Han Kyungdo , Baek Min Seok
Published: May 2023

Background and objective

Migraine is a common chronic neurological disease characterized by pulsating headaches, photophobia, phonophobia, nausea, and vomiting. The prevalence of dementia in individuals aged over 65 years in Korea is more than 10%, and Alzheimer’s disease (AD) dementia accounts for most cases. Although these two neurological diseases account for a large portion of the medical burden in Korea, few studies have examined the relationship between the two diseases. Therefore, this study investigated the incidence and risk of AD in patients with migraines.

Methods

We retrospectively collected nationwide data from a national health insurance claims database governed by Korea’s National Health Insurance Service. Among Koreans in the 2009 record, patients with migraine were identified according to the International Classification of Diseases, 10th revision (ICD-10) code G43. First, we screened the database for participants aged over 40 years. Individuals diagnosed with migraine at least twice over more than 3 months in a year were considered to have chronic migraine in this study. Further, all participants with an AD diagnosis (ICD-10 code: Alzheimer’s disease F00, G30) were investigated for AD dementia development. The primary endpoint was AD development.

Results

The overall incidence of AD dementia was higher in individuals with a history of migraine than in those with no migraine history (8.0 per 1,000 person-years vs. 4.1 per 1,000 person-years). The risk of AD dementia was higher in individuals diagnosed with migraine (hazard ratio = 1.37 [95% confidence interval, 1.35–1.39]) than in the control group after adjustments for age and sex. Individuals with chronic migraine had a higher incidence of AD dementia than those with episodic migraine. Younger age (<65 years old) was associated with an increased risk of AD dementia compared to older age (≥65  years old). Higher body mass index (BMI) (≥25 kg/m2) was also associated with an increased risk of AD dementia compared to lower BMI (<25 kg/m2) (p < 0.001).

Conclusion

Our results suggest that individuals with a migraine history are more susceptible to AD than those without a migraine history. Additionally, these associations were more significant in younger and obese individuals with migraine than in individuals without migraine.