bluuebunny/crossref_metadata_2025 huggingface dataset:
Primary human organoids models: Current progress and key milestones
Authors: Calà Giuseppe , Sina Beatrice , De Coppi Paolo , Giobbe Giovanni Giuseppe , Gerli Mattia Francesco Maria
Published: March 2023

During the past 10 years the world has experienced enormous progress in the organoids field. Human organoids have shown huge potential to study organ development, homeostasis and to model diseases in vitro. The organoid technology has been widely and increasingly applied to generate patient-specific in vitro 3D cultures, starting from both primary and reprogrammed stem/progenitor cells. This has consequently fostered the development of innovative disease models and new regenerative therapies. Human primary, or adult stem/progenitor cell-derived, organoids can be derived from both healthy and pathological primary tissue samples spanning from fetal to adult age. The resulting 3D culture can be maintained for several months and even years, while retaining and resembling its original tissue’s properties. As the potential of this technology expands, new approaches are emerging to further improve organoid applications in biology and medicine. This review discusses the main organs and tissues which, as of today, have been modelled in vitro using primary organoid culture systems. Moreover, we also discuss the advantages, limitations, and future perspectives of primary human organoids in the fields of developmental biology, disease modelling, drug testing and regenerative medicine.
Fecal microbiota transplantation in a rodent model of short bowel syndrome: A therapeutic approach?
Authors: Fourati Salma , Dumay Anne , Roy Maryline , Willemetz Alexandra , Ribeiro-Parenti Lara , Mauras Aurélie , Mayeur Camille , Thomas Muriel , Kapel Nathalie , Joly Francisca , Le Gall Maude , Bado André , Le Beyec Johanne
Published: March 2023

Extensive intestinal resection leads to Short Bowel Syndrome (SBS), the main cause of chronic intestinal failure. Colon preservation is crucial for spontaneous adaptation, to improve absorption and reduce parenteral nutrition dependence. Fecal microbiota transplantation (FMT), a promising approach in pathologies with dysbiosis as the one observed in SBS patients, was assessed in SBS rats with jejuno‐colonic anastomosis. The evolution of weight and food intake, the lenght of intestinal villi and crypts and the composition of fecal microbiota of Sham and SBS rats, transplanted or not with high fat diet rat microbiota, were analyzed. All SBS rats lost weight, increased their food intake and exhibited jejunal and colonic hyperplasia. Microbiota composition of SBS rats, transplanted or not, was largely enriched with Lactobacillaceae, and α‐ and β‐diversity were significantly different from Sham. The FMT altered microbiota composition and α‐ and β‐diversity in Sham but not SBS rats. FMT from high fat diet rats was successfully engrafted in Sham, but failed to take hold in SBS rats, probably because of the specific luminal environment in colon of SBS subjects favoring aero‐tolerant over anaerobic bacteria. Finally, the level of food intake in SBS rats was positively correlated with their Lactobacillaceae abundance. Microbiota transfer must be optimized and adapted to this specific SBS environment.
Social cognition and Relevance: How stereotypes impact the processing of definite and indefinite descriptions
Authors: Mari Magali A. , Müller Misha-Laura
Published: March 2023

This paper focuses on the impact of social cognition on thes processing of linguistic information. More specifically, it brings some insights to Relevance theory's construal of MeaningNN, which seeks to account for non-propositional meanings. It shows, through two experiments, how gender and nationality-related stereotypes guide the processing of definite and indefinite descriptions. Experiment 1 consists of a self-paced reading task (with 59 French native speakers), introducing information confirming vs. violating gender stereotypes within a nominal phrase (NP). The NP (e.g., “chirurgien/chirurgienne”, “surgeonmale/female”) was itself introduced either by a definite article (presupposition) or an indefinite article (assertion). Results showed that information violating gender stereotypes was costlier to process than stereotype-congruent information. Moreover, when information violated gender stereotypes, definite descriptions became significantly costlier than indefinite ones, because they required the identification of a salient referent which contradicted stereotypical expectations. Experiment 2 tested the effects of definite vs. indefinite NP on processing nationality-related stereotypes in a self-paced reading task (with 49 French native speakers). Participants read definite vs. indefinite NPs referring to representatives of a country. The NP was subsequently paired with information that confirmed vs. contradicted nationality stereotypes. Results showed that information contradicting nationality stereotypes were significantly costlier to process than information confirming stereotypes. Furthermore, when information contradicted nationality stereotypes, indefinite descriptions (which promote a single occurrence reading) failed to facilitate information processing compared to definite descriptions (which promote a generalized representation of the social category). Overall, the present findings are consistent with research on stereotypes, in that they show that stereotype-incongruent information affect sentence processing. Importantly, while Experiment 1 revealed that stereotypes affected the processing of linguistic markers, Experiment 2 suggested that linguistic markers could not modulate the processing of stereotypes.
Artificial intelligence-enabled electrocardiographic screening for left ventricular systolic dysfunction and mortality risk prediction
Authors: Huang Yu-Chang , Hsu Yu-Chun , Liu Zhi-Yong , Lin Ching-Heng , Tsai Richard , Chen Jung-Sheng , Chang Po-Cheng , Liu Hao-Tien , Lee Wen-Chen , Wo Hung-Ta , Chou Chung-Chuan , Wang Chun-Chieh , Wen Ming-Shien , Kuo Chang-Fu
Published: March 2023

Background

Left ventricular systolic dysfunction (LVSD) characterized by a reduced left ventricular ejection fraction (LVEF) is associated with adverse patient outcomes. We aimed to build a deep neural network (DNN)-based model using standard 12-lead electrocardiogram (ECG) to screen for LVSD and stratify patient prognosis.

Methods

This retrospective chart review study was conducted using data from consecutive adults who underwent ECG examinations at Chang Gung Memorial Hospital in Taiwan between October 2007 and December 2019. DNN models were developed to recognize LVSD, defined as LVEF <40%, using original ECG signals or transformed images from 190,359 patients with paired ECG and echocardiogram within 14 days. The 190,359 patients were divided into a training set of 133,225 and a validation set of 57,134. The accuracy of recognizing LVSD and subsequent mortality predictions were tested using ECGs from 190,316 patients with paired data. Of these 190,316 patients, we further selected 49,564 patients with multiple echocardiographic data to predict LVSD incidence. We additionally used data from 1,194,982 patients who underwent ECG only to assess mortality prognostication. External validation was performed using data of 91,425 patients from Tri-Service General Hospital, Taiwan.

Results

The mean age of patients in the testing dataset was 63.7 ± 16.3 years (46.3% women), and 8,216 patients (4.3%) had LVSD. The median follow-up period was 3.9 years (interquartile range 1.5–7.9 years). The area under the receiver-operating characteristic curve (AUROC), sensitivity, and specificity of the signal-based DNN (DNN-signal) to identify LVSD were 0.95, 0.91, and 0.86, respectively. DNN signal-predicted LVSD was associated with age- and sex-adjusted hazard ratios (HRs) of 2.57 (95% confidence interval [CI], 2.53–2.62) for all-cause mortality and 6.09 (5.83–6.37) for cardiovascular mortality. In patients with multiple echocardiograms, a positive DNN prediction in patients with preserved LVEF was associated with an adjusted HR (95% CI) of 8.33 (7.71 to 9.00) for incident LVSD. Signal- and image-based DNNs performed equally well in the primary and additional datasets.

Conclusion

Using DNNs, ECG becomes a low-cost, clinically feasible tool to screen LVSD and facilitate accurate prognostication.
Pathogenesis of pulmonary hypertension caused by left heart disease
Authors: Xiao Mingzhu , Lai Disheng , Yu Yumin , Wu Qingqing , Zhang Caojin
Published: March 2023

Pulmonary hypertension has high disability and mortality rates. Among them, pulmonary hypertension caused by left heart disease (PH-LHD) is the most common type. According to the 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension, PH-LHD is classified as group 2 pulmonary hypertension. PH-LHD belongs to postcapillary pulmonary hypertension, which is distinguished from other types of pulmonary hypertension because of its elevated pulmonary artery wedge pressure. PH-LHD includes PH due to systolic or diastolic left ventricular dysfunction, mitral or aortic valve disease and congenital left heart disease. The primary strategy in managing PH-LHD is optimizing treatment of the underlying cardiac disease. Recent clinical studies have found that mechanical unloading of left ventricle by an implantable non-pulsatile left ventricular assist device with continuous flow properties can reverse pulmonary hypertension in patients with heart failure. However, the specific therapies for PH in LHD have not yet been identified. Treatments that specifically target PH in LHD could slow its progression and potentially improve disease severity, leading to far better clinical outcomes. Therefore, exploring the current research on the pathogenesis of PH-LHD is important. This paper summarizes and classifies the research articles on the pathogenesis of PH-LHD to provide references for the mechanism research and clinical treatment of PH-LHD, particularly molecular targeted therapy.
Integrated whole-genome gene expression analysis reveals an atlas of dynamic immune landscapes after myocardial infarction
Authors: Wang Yujue , Chen Yu , Zhang Teng
Published: March 2023

Introduction

Myocardial infarction (MI) is a deadly medical condition leading to irreversible damage to the inflicted cardiac tissue. Elevated inflammatory response marks the severity of MI and is associated with the development of heart failure (HF), a long-term adverse outcome of MI. However, the efficacy of anti-inflammatory therapies for MI remains controversial. Deciphering the dynamic transcriptional signatures in peripheral blood mononuclear cells (PBMCs) is a viable and translatable route to better understand post-MI inflammation, which may help guide post-MI anti-inflammatory treatments.

Methods

In this work, integrated whole-genome gene expression analysis was performed to explore dynamic immune landscapes associated with MI.

Results

GSEA and GSVA showed that pathways involved in the inflammatory response and metabolic reprogramming were significantly enriched in PBMCs from MI patients. Based on leukocyte profiles generated by xCell algorithm, the relative abundance of monocytes and neutrophils was significantly increased in PBMCs from MI patients and had positive correlations with typical inflammation-associated transcripts. Mfuzz clustering revealed temporal gene expression profiles of PBMCs during the 6-month post-MI follow-up. Analysis of DEGs and gene sets indicated that PBMCs from HF group were characterized by elevated and lasting expression of genes implicated in inflammation and coagulation. Consensus clustering generated 4 metabolic subtypes of PBMCs with molecular heterogeneity in HF patients.

Discussion

In summary, integrated whole-genome gene expression analysis here outlines a transcriptomic framework that may improve the understanding of dynamic signatures present in PBMCs, as well as the heterogeneity of PBMCs in MI patients with or without long-term clinical outcome of HF. Moreover, the work here uncovers the diversity and heterogeneity of PBMCs from HF patients, providing novel bioinformatic evidence supporting the mechanistic implications of metabolic reprogramming and mitochondrial dysfunction in the post-MI inflammation and HF. Therefore, our work here supports the notion that individualized anti-inflammatory therapies are needed to improve the clinical management of post-MI patients.
Associations of albumin and nutritional index factors with delirium in patients admitted to the cardiac intensive care unit
Authors: Kim Tae Wan , Ko Ryoung Eun , Na Soo Jin , Chung Chi Ryang , Choi Ki Hong , Park Chi-Min , Yang Jeong Hoon
Published: March 2023

Background

Limited data are available on the association of malnutrition with the occurrence of delirium in the cardiac intensive care unit (CICU). Thus, we aimed to analyze whether nutritional indices and their components can predict the development of delirium in CICU.

Methods

We enrolled 2,783 patients admitted to the CICU of Samsung Medical Center for more than 24 h between September 2012 and December 2018. We assessed the nutritional status at admission using three indices, the Prognostic Nutrition Index (PNI), the Geriatric Nutritional Risk Index (GNRI), and the Controlling Nutritional Status (CONUT). Then, we compared predictive performances for the occurrence of delirium among nutritional indices using Delong’s test.

Results

Delirium developed in 678 patients (24.3%) assessed three times daily for 7 days of CICU stay. Nutritional indices had fair predictive performance for development of delirium in critically ill cardiac patients using the area under the receiver-operating characteristic curve (AUROC: 0.729 for the GNRI, 0.728 for PNI, and 0.762 for CONUT). Furthermore, the AUROC of albumin alone (0.77, 95% CI, 0.75–0.79) was significantly greater than that of either GNRI (p < 0.001) or PNI (p < 0.001). In a multivariable analysis including each component of nutritional indices, albumin was a significant predictor for delirium but not absolute lymphocyte count, bodyweight/ideal bodyweight, or total cholesterol level as a component of nutritional indices.

Conclusion

Predictive performances of nutritional indices for the occurrence of delirium were acceptable in patients admitted to CICU. Albumin alone might be a helpful and straightforward indicator for the occurrence of delirium.
Modelling blood flow in patients with heart valve disease using deep learning: A computationally efficient method to expand diagnostic capabilities in clinical routine
Authors: Yevtushenko Pavlo , Goubergrits Leonid , Franke Benedikt , Kuehne Titus , Schafstedde Marie
Published: March 2023

Introduction

The computational modelling of blood flow is known to provide vital hemodynamic parameters for diagnosis and treatment-support for patients with valvular heart disease. However, most diagnosis/treatment-support solutions based on flow modelling proposed utilize time- and resource-intensive computational fluid dynamics (CFD) and are therefore difficult to implement into clinical practice. In contrast, deep learning (DL) algorithms provide results quickly with little need for computational power. Thus, modelling blood flow with DL instead of CFD may substantially enhances the usability of flow modelling-based diagnosis/treatment support in clinical routine. In this study, we propose a DL-based approach to compute pressure and wall-shear-stress (WSS) in the aorta and aortic valve of patients with aortic stenosis (AS).

Methods

A total of 103 individual surface models of the aorta and aortic valve were constructed from computed tomography data of AS patients. Based on these surface models, a total of 267 patient-specific, steady-state CFD simulations of aortic flow under various flow rates were performed. Using this simulation data, an artificial neural network (ANN) was trained to compute spatially resolved pressure and WSS using a centerline-based representation. An unseen test subset of 23 cases was used to compare both methods.

Results

ANN and CFD-based computations agreed well with a median relative difference between both methods of 6.0% for pressure and 4.9% for wall-shear-stress. Demonstrating the ability of DL to compute clinically relevant hemodynamic parameters for AS patients, this work presents a possible solution to facilitate the introduction of modelling-based treatment support into clinical practice.
Feeding-induced hepatokines and crosstalk with multi-organ: A novel therapeutic target for Type 2 diabetes
Authors: Chen Rong-Bin , Wang Qi-Yu , Wang Yuan-Yuan , Wang Ya-Di , Liu Jiang-Hua , Liao Zhe-Zhen , Xiao Xin-Hua
Published: March 2023

Hyperglycemia, which can be caused by either an insulin deficit and/or insulin resistance, is the main symptom of Type 2 diabetes, a significant endocrine metabolic illness. Conventional medications, including insulin and oral antidiabetic medicines, can alleviate the signs of diabetes but cannot restore insulin release in a physiologically normal amount. The liver detects and reacts to shifts in the nutritional condition that occur under a wide variety of metabolic situations, making it an essential organ for maintaining energy homeostasis. It also performs a crucial function in glucolipid metabolism through the secretion of hepatokines. Emerging research shows that feeding induces hepatokines release, which regulates glucose and lipid metabolism. Notably, these feeding-induced hepatokines act on multiple organs to regulate glucolipotoxicity and thus influence the development of T2DM. In this review, we focus on describing how feeding-induced cross-talk between hepatokines, including Adropin, Manf, Leap2 and Pcsk9, and metabolic organs (e.g.brain, heart, pancreas, and adipose tissue) affects metabolic disorders, thus revealing a novel approach for both controlling and managing of Type 2 diabetes as a promising medication.
Highly active MgO catalysts for hydrogenation of levulinic acid to γ-valerolactone using formic acid as the hydrogen source
Authors: Sultana Asima , Lomate Samadhan , Fujitani Tadahiro
Published: March 2023

This study presents an evaluation of catalytic performance of unsupported simple oxide catalysts with varying acid-base properties for the vapor phase hydrogenation of levulinic acid (LA) to γ-valerolactone (GVL) using formic acid (FA) in an aqueous medium. Among the different oxides tested MgO catalyst is found to be highly active. Between the MgO prepared by different methods and commercially obtained, the MgO-UBE showed 100% LA conversion and 100% selectivity to GVL at 270°C. The MgO-UBE catalyst favorably allowed the production of γ-valerolactone in the presence of 50 wt% water relative to the amount of a mixture of levulinic acid and formic acid. Based on the catalytic activity and characterization results, it was concluded that the presence of Mg (OH)2 and a higher number of Lewis acid-base pair sites, Mg2+LCO2−LC are needed to achieve high LA conversion and selectivity to GVL.
Lithium-CO2 batteries and beyond
Authors: Pathak Anil D. , Adhikari Pashupati R. , Choi Wonbong
Published: March 2023

Li-CO2 batteries with a theoretical energy density of 1,876 Wh kg−1 are attractive as a promising energy storage strategy and as an effective way to reduce greenhouse gas emissions by CO2 reduction and the formation of discharge product Li2CO3 and carbon. This article provides critical perspectives on the development of Li-CO2 batteries as well as a description of current issues and challenges associated with cathode catalysts, electrolyte, and anode for Li-CO2 batteries. Furthermore, the development and deployment of materials to overcome these challenges of Li-CO2 batteries are discussed briefly. Finally, a systematic analysis of beyond Li-CO2 batteries (other Metal-CO2 batteries) as a potential research direction in the development of energy storage and CO2 fixation and utilization in practical applications is provided.
The influence of digital development on China’s carbon emission efficiency: In the view of economic and environmental balance
Authors: Ding Yuan , Yang Yalan
Published: March 2023

Introduction: With the worsening global climate problem, carbon peak and carbon neutrality have become crucial objects to realize sustainable development. Regarded as the engine of economic development in the new era, it is worth exploring whether digitalization could contribute to carbon goals. Meanwhile, carbon reduction should not be advocated at the cost of economic recession and contains the risk of reversal when the economy renews in growth.

Material and Methods: This paper evaluates carbon efficiency using the total factor non-radial directional distance function, which reflects the economic performance and environmental performance of 246 China’s prefecture-level cities during 2011–2019. Fixed effect and mediation effect models are used to explore the non-linear relationship and transmission channels between digital development and carbon efficiency.

Results: It is found that: 1) digital development would hinder carbon efficiency first and then promote it after reaching a certain level; 2) digital development could indirectly affect carbon efficiency through industrial agglomeration, industrial structure upgrading, and industrial electricity productivity in non-linear ways. 3) Heterogeneity exists in the relationship between digital development and carbon efficiency due to different regions and development types.

Discussion: Due to digital development itself having high carbon-negative externalities at the initial stage, its impact on carbon efficiency is complex and non-liner even when decomposing through multiple channels. A well-structured development strategy is needed during the digitalization process in order to prompt carbon efficiency.
Steps to operationalize a rewilding decision: Focus on functional types
Authors: du Toit Johan T.
Published: March 2023

If transparent and inclusive stakeholder discussion delivers a consensus for active rewilding, then five steps are recommended for operationalizing that decision, focused initially on the large herbivore assemblage. Consideration of large predators could follow, contingent upon the establishment of prey populations. First, determine the potential biomass density (kg/km2) of large mammalian herbivores in the target landscape. Regression models based on rainfall or primary productivity are helpful if applicable, otherwise comparative studies are needed. Second, use empirical data from reference ecosystems to apportion biomass density among functional types, crudely defined by body size and feeding type (grazer, browser, mixed feeder). Third, identify specific functional traits (coarse grazing, endozoochory, etc.) of particular local importance. Fourth, identify species within each functional type that are already present, estimate their potential biomass densities, and thus identify the shortfall within each cell of the body size x feeding type matrix. A candidate set of native and non-native (surrogate) species is then identified to make up the shortfalls. This is followed by an iterative process of estimating equilibrium population sizes, stakeholder acceptance, and viability of each potential population. Fifth, stakeholders must be inclusively re-engaged to visualize the potential assemblage, its expected functional interactions, the ecosystem services to be delivered, and the long-term costs (including opportunity costs) and benefits. When a plan is supported, local stakeholders should be integrated as active participants in the implementation, monitoring, and championing of their rewilding project.
The lack of genetic variation underlying thermal transcriptomic plasticity suggests limited adaptability of the Northern shrimp, Pandalus borealis
Authors: Leung Christelle , Guscelli Ella , Chabot Denis , Bourret Audrey , Calosi Piero , Parent Geneviève J.
Published: March 2023

Introduction

Genetic variation underlies the populations’ potential to adapt to and persist in a changing environment, while phenotypic plasticity can play a key role in buffering the negative impacts of such change at the individual level.

Methods

We investigated the role of genetic variation in the thermal response of the northern shrimp Pandalus borealis, an ectotherm species distributed in the Arctic and North Atlantic Oceans. More specifically, we estimated the proportion transcriptomic responses explained by genetic variance of female shrimp from three origins after 30 days of exposure to three temperature treatments.

Results

We characterized the P. borealis transcriptome (170,377 transcripts, of which 27.48% were functionally annotated) and then detected a total of 1,607 and 907 differentially expressed transcripts between temperatures and origins, respectively. Shrimp from different origins displayed high but similar level of transcriptomic plasticity in response to elevated temperatures. Differences in transcript expression among origins were not correlated to population genetic differentiation or diversity but to environmental conditions at origin during sampling.

Discussion

The lack of genetic variation explaining thermal plasticity suggests limited adaptability in this species’ response to future environmental changes. These results together with higher mortality observed at the highest temperature indicate that the thermal niche of P. borealis will likely be restricted to higher latitudes in the future. This prediction concurs with current decreases in abundance observed at the southern edge of this species geographical distribution, as it is for other cold-adapted crustaceans.
Hepatic gene expression profiles during fed–fasted–refed state in mice
Authors: Ji Nana , Xiang Liping , Zhou Bing , Lu Yan , Zhang Min
Published: March 2023

Background: Regulation of nutrient status during fasting and refeeding plays an important role in maintaining metabolic homeostasis in the liver. Thus, we investigated the impact of the physiological Fed–Fast–Refed cycle on hepatic gene expression in nutrient-sensitive mice.

Methods: We performed transcriptomic analysis of liver samples in fed, fasted and refed groups of mice. Through mRNA-sequencing (RNA-Seq) and miRNA-Seq, we compared fasted and fed states (fasted versus fed cohort) as well as refed and fasted states (refed versus fasted cohort) to detect dynamic alterations of hepatic mRNA–miRNA expression during the fed–fasted–refed cycle.

Results: We found dozens of dysregulated mRNAs–miRNAs in the transition from fed to fasted and from fasted to refed states. Gene set enrichment analysis showed that gene expression of the two cohorts shared common pathways of regulation, especially for lipid and protein metabolism. We identified eight significant mRNA and three miRNA clusters that were up–downregulated or down–upregulated during the Fed–Fast–Refed cycle. A protein–protein interaction network of dysregulated mRNAs was constructed and clustered into 22 key modules. The regulation between miRNAs and target mRNAs was presented in a network. Up to 42 miRNA–mRNA-pathway pairs were identified to be involved in metabolism. In lipid metabolism, there were significant correlations between mmu-miR-296-5p and Cyp2u1 and between mmu-miR-novel-chr19_16777 and Acsl3.

Conclusion: Collectively, our data provide a valuable resource for the molecular characterization of the physiological Fed–Fast–Refed cycle in the liver.
Characterization of prognostic value and immunological roles of RAB22A in hepatocellular carcinoma
Authors: Wen Fukai , Meng Fanshuai , Li Xuewen , Li Qingyu , Liu Jiaming , Zhang Rui , Zhao Yunzheng , Zhang Yu , Wang Xin , Ju Shuai , Cui Yifeng , Lu Zhaoyang
Published: March 2023

Background

The protein-coding gene RAB22A, a member of the RAS oncogene family, is amplified or overexpressed in certain cancers. However, its action mechanism in hepatocellular carcinoma (HCC) remains unclear. Here, we aimed to examine the connection between RAB22A and survival prognosis in HCC and explore the biological significance of RAB22A.

Methods

A database-based pan-cancer expression analysis of RAB22A was performed. Kaplan–Meier analysis and Cox regression were performed to evaluate the association between RAB22A expression and survival prognosis in HCC. Using Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and Gene Set Enrichment Analysis (GSEA), various potential biological functions and regulatory pathways of RAB22A in HCC were discovered. Tumor immune infiltration was studied using the single sample gene set enrichment analysis (ssGSEA) method. N6-methyladenosine modifications and the regulatory network of competitive endogenous RNA (ceRNA) were verified in the TCGA cohort.

Results

RAB22A was upregulated in HCC samples and cell lines. A high RAB22A expression in HCC was strongly correlated with sex, race, age, weight, TNM stage, pathological stage, tumor status, histologic grade, TP53 mutation status, and alpha fetal protein (AFP) levels. Overexpression of RAB22A indicated a poor prognosis was related to overall survival (OS), disease-specific survival (DSS), and progression-free interval (PFI). GO and KEGG analyses revealed that the differentially expressed genes related to RAB22A might be involved in the proteasomal protein catabolic process, ncRNA processing, ribosome ribosomal subunit, protein serine/threonine kinase activity, protein serine kinase activity, Endocytosis, and non-alcoholic fatty liver disease. GSEA analyses revealed that the differentially expressed genes related to RAB22A might be involved in the T cell receptor, a co-translational protein, that binds to the membrane, axon guidance, ribosome, phagocytosis, and Eukaryotic translation initiation. RAB22A was correlated with N6-methyladenosine expression in HCC and established RAB22A-related ceRNA regulatory networks. Finally,RAB22A expression was positively connected the levels of infiltrating with T helper cells, Tcm cells, and Th2 cells,In contrast, we observed negatively correlations with cytotoxic cells, DCs, and pDCs cells.Moreover,RAB22A expression showed a strong correlation with various immunomarkergroups in HCC.

Conclusions

RAB22A is a potential therapeutic target for improving HCC prognosis and is closely related to immune cell infiltration.
Diversity of immune responses in children highly exposed to SARS-CoV-2
Authors: Úbeda María , Maza María del Carmen , Delgado Pilar , Horndler Lydia , Abia David , García-Bermejo Laura , Serrano-Villar Sergio , Calvo Cristina , Bastolla Ugo , Sainz Talia , Fresno Manuel
Published: March 2023

Background

Children are less susceptible than adults to symptomatic COVID‐19 infection, but very few studies addressed their underlying cause. Moreover, very few studies analyzed why children highly exposed to the virus remain uninfected.

Methods

We analyzed the serum levels of ACE2, angiotensin II, anti-spike and anti-N antibodies, cytokine profiles, and virus neutralization in a cohort of children at high risk of viral exposure, cohabiting with infected close relatives during the lockdown in Spain.

Results

We analyzed 40 children who were highly exposed to the virus since they lived with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-infected relatives during the lockdown for several months without taking preventive measures. Of those, 26 reported mild or very mild symptoms. The induced immune response to the virus was analyzed 3 months after the household infection. Surprisingly, only 15 children had IgG anti-S (IgG+) determined by a sensitive method indicative of a past infection. The rest, negative for IgG anti-N or S in various tests, could be further subdivided, according to IgM antibodies, into those having IgM anti-S and IgM anti-N (IgG−IgMhigh) and those having only IgM anti-N (IgG−IgMlow). Interestingly, those two subgroups of children with IgM antibodies have strikingly different patterns of cytokines. The IgMhigh group had significantly higher IFN-α2 and IFN-γ levels as well as IL-10 and GM-CSF than the IgMlow group. In contrast, the IgMlow group had low levels of ACE2 in the serum. Both groups have a weaker but significant capacity to neutralize the virus in the serum than the IgG+ group. Two children were negative in all immunological antibody tests.

Conclusions

A significant proportion of children highly exposed to SARS-CoV-2 did not develop a classical adaptive immune response, defined by the production of IgG, despite being in close contact with infected relatives. A large proportion of those children show immunological signs compatible with innate immune responses (as secretion of natural antibodies and cytokines), and others displayed very low levels of the viral receptor ACE2 that may have protected them from the virus spreading in the body despite high and constant viral exposure.
Nur77 and PPARγ regulate transcription and polarization in distinct subsets of M2-like reparative macrophages during regenerative inflammation
Authors: Garabuczi Éva , Tarban Nastaran , Fige Éva , Patsalos Andreas , Halász László , Szendi-Szatmári Tímea , Sarang Zsolt , Király Róbert , Szondy Zsuzsa
Published: March 2023

Macrophage polarization is a process whereby macrophages develop a specific phenotype and functional response to different pathophysiological stimuli and tissue environments. In general, two main macrophage phenotypes have been identified: inflammatory (M1) and alternatively activated (M2) macrophages characterized specifically by IL-1β and IL-10 production, respectively. In the cardiotoxin-induced skeletal muscle injury model bone marrow-derived macrophages (BMDMs) play the central role in regulating tissue repair. Bone marrow-derived monocytes arriving at the site of injury differentiate first to M1 BMDMs that clear cell debris and trigger proliferation and differentiation of the muscle stem cells, while during the process of efferocytosis they change their phenotype to M2 to drive resolution of inflammation and tissue repair. The M2 population is formed from at least three distinct subsets: antigen presenting, resolution-related and growth factor producing macrophages, the latest ones expressing the transcription factor PPARγ. Nuclear receptor subfamily 4 group A member 1 (NR4A1; also termed Nur77) transcription factor is expressed as an early response gene, and has been shown to suppress the expression of pro-inflammatory genes during efferocytosis. Here we demonstrate that (1) Nur77 null BMDMs are characterized by elevated expression of PPARγ resulting in enhanced efferocytosis capacity; (2) Nur77 and PPARγ regulate transcription in different subsets of M2 skeletal muscle macrophages during muscle repair; (3) the loss of Nur77 prolongs M1 polarization characterized by increased and prolonged production of IL-1β by the resolution-related macrophages normally expressing Nur77; whereas, in contrast, (4) it promotes M2 polarization detected via the increased number of IL-10 producing CD206+ macrophages generated from the PPARγ-expressing subset.
Mitigating effects on target and by-catch species fished by drifting longlines using circle hooks in the South Adriatic Sea (Central Mediterranean)
Authors: Carbonara Pierluigi , Prato Giulia , Niedermüller Simone , Alfonso Sébastien , Neglia Cosmidano , Donnaloia Marilena , Lembo Giuseppe , Spedicato Maria Teresa
Published: March 2023

Introduction

Longline fishing gear has a higher by-catch rate than any other type of commercial fishing gear. Nowadays, there is an urgent need to find efficient management strategies to mitigate by-catch and the use of new hook types could be one of them. This study investigates the effects of a longline fishery (which targets swordfish, Xiphias gladius, in the South Adriatic Sea) replacing the traditional J-type hook with a circle hook (C-type hook) on target and by-catch species.

Methods

For this purpose, a fishing trip of nine days – with seven fishing sets – was monitored. For both targeted swordfish and by-catch specimens caught (i.e., blue shark, Prionace glauca; pelagic stingray, Pteroplatytrygon violacea; and loggerhead turtle, Caretta caretta), data about the hook type used (J-type vs. C-type), the specimen size, and their capture condition were collected.

Results and discussion

With all species, we observed no significant difference in catch-per-unit-effort (CPUE) or specimen lengths between the two hook types. In addition, the hook type did not significantly affect the capture condition of swordfish, pelagic stingray, or loggerhead turtle specimens; however, it significantly affected the capture condition of blue sharks. The percentage of blue shark specimens found in healthy condition was higher when using a C-type hook (71.5%) than when using a J-type hook (22.6%). Overall, these preliminary results suggest that the use of a C-type hook improves the condition of by-caught blue sharks without affecting the CPUE or size of the target species. In conclusion, the use of a C-type hook could reduce the detrimental effects of by-catch on some species in the Adriatic Sea; however, this finding needs to be confirmed by a study with a larger sample size.
Pulsed turbidite and methane seep records in the north western South China Sea since the last glacial maximum
Authors: Li Jingrui , Miao Xiaoming , Feng Xiuli , Jiang Rui , Zhao Mengwei , Dan Xiaopeng , Xiao Qianwen , Wei Jiangong
Published: March 2023

The small-scale event layers in the continental margin contain abundant dynamic environment information, and pose a challenge to the interpretation of continuous sedimentary records, giving geological significance to their accurate identify and possible genesis. Here, pulsed turbidite layers since the last glacial maximum (LGM) in a gravity core in the northwestern South China Sea (SCS) was analyzed to investigate the precisely identification, possible causes and the role of marine environmental change during the late Quaternary in formation of these small-scale event layers in the SCS. Eight potential pulsed turbidite layers, according to the petrographic characteristics, grain size parameters and element geochemistry, were identified. Meanwhile, indicators including total sulfur (TS)/total organic carbon (TOC) ratio, CaCO3 content, and chromium-reducible sulfur (CRS) revealed these horizons were mostly related to methane seep events. Constrained by foraminifera shells AMS14C results, these events were determined to have occurred from the LGM to early Holocene, Similar records in the northern and southern slopes suggests the universal occurrence of these small-scale layers in the SCS. The comprehensive analysis showed that the development of these event layers over the past 25 ka can be divided into three stages, 25-15.5 ka, 15.5-7 ka and 7 ka to present. Late Quaternary Ocean environment changes, especially sea level and bottom water temperature, controlled the occurrence of regional small-scale event layers in the SCS. The regional scale mechanism is that the pressure and temperature change affect the stability of hydrate and the methane seepage, and thus the strata stability. Corresponding to the lowest, the rapid increase and the highest levels of the sea level and bottom water temperature, the temporal evolution pattern of small-scale event layers in the SCS showed a highest, decreased and lowest frequency, respectively. The linkage between the late Quaternary marine environmental change and turbidite deposition through gas activities in this study can act as a useful reference for further understanding the continental margin sedimentary process.
Impact of diagnostic guidelines on the diagnosis of hypersensitivity pneumonitis
Authors: Huang Yuh Chin , Gu Jessie P.
Published: March 2023

Introduction

Hypersensitivity pneumonitis (HP) is an immune-mediated interstitial lung disease from exposure to environmental antigens. Diagnosing HP could be challenging. The American College of Chest Physicians (CHEST) and American Thoracic Society/Japanese Respiratory Society/and Asociación Latinoamericana del Tórax (ATS/JRS/ALAT) have published diagnostic guidelines in 2021 and 2020 respectively. The CHEST guideline uses four grades of confidence: confident (>90%), provisional high (70–89%), provisional low (51–69%), and unlikely (≤50%). The ATS/JRS/ALAT guideline uses five grades of confidence: definite (>90%), high (80–89%), moderate (70–79%), low (51–69%) and not excluded (≤50%). In this study, we determined how these two guidelines could have affected the diagnosis of HP made before the guidelines.

Methods

Two hundred and fifty-nine adult patients from a previous cohort with HP (ICD-9:495) made between Jan. 1, 2008, and Dec. 31, 2013, at Duke University Medical Center were included. We simplified the diagnostic confidence into three categories so we could compare the guidelines: high (≥90%), intermediate (51–89%), and low (≤50%).

Results

There were 156 female and 103 male. Mean age was 58 (range: 20–90). 68.8% of the patients had restrictive defects (FVC < 80% pred) and 48.6% had lung biopsy. The CHEST guideline classified 33.6% of the patients into high, 59.5% into intermediate and 6.9% into low confidence categories. The ATS/JRS/ALAT guideline classified 29.7% of the patients into high, 21.2% into intermediate and 49.0% into low confidence categories (p < 0.0001 vs. CHEST). Cohen's kappa was 0.331. In patients with identifiable inciting agents (IAs) (N = 168), the CHEST guideline classified 32.1% of the patients into high, 64.3% into intermediate and 3.6% into low confidence categories. The ATS/JRS/ALAT guideline classified 29.2% of the patients into high, 20.8% into intermediate, and 50.0% into low confidence categories. Cohen's kappa was 0.314.

Discussion

In our HP cohort with two-thirds of the patients with restrictive defects, we found the two guidelines had fair agreement in diagnosing HP with or without identifiable IAs. They agreed more when the diagnostic confidence was high. When the diagnostic confidence was lower, however, the ATS/JRS/ALAT guideline was more stringent. Clinicians should be aware of the differences between the two guidelines when evaluating patients suspicious of HP.
sRNA expedites polycistronic mRNA decay in Escherichia coli
Authors: Jeon Heung Jin , Lee Yonho , N Monford Paul Abishek , Kang Changjo , Lim Heon M.
Published: March 2023

In bacteria, most small RNA (sRNA) elicits RNase E-mediated target mRNA degradation by binding near the translation initiation site at the 5′ end of the target mRNA. Spot 42 is an sRNA that binds in the middle of the gal operon near the translation initiation site of galK, the third gene of four, but it is not clear whether this binding causes degradation of gal mRNA. In this study, we measured the decay rate of gal mRNA using Northern blot and found that Spot 42 binding caused degradation of only a specific group of gal mRNA that shares their 3′ end with full-length mRNA. The results showed that in the MG1655Δspf strain in which the Spot 42 gene was removed, the half-life of each gal mRNA in the group increased by about 200% compared to the wild type. Since these mRNA species are intermediate mRNA molecules created by the decay process of the full-length gal mRNA, these results suggest that sRNA accelerates the mRNA decaying processes that normally operate, thus revealing an unprecedented role of sRNA in mRNA biology.
Effect and mechanism of acupuncture on Alzheimer’s disease: A review
Authors: Wu Liu , Dong Yuting , Zhu Chengcheng , Chen Yong
Published: March 2023

With the development trend of an aging society, Alzheimer’s disease (AD) has become an urgent problem in the field of medicine worldwide. Cognitive impairment in AD patients leads to a decline in the ability to perform daily living and abnormalities in behavior and personality, causing abnormal psychiatric symptoms, which seriously affect the daily life of patients. Currently, mainly drug therapy is used for AD patients in the clinic, but a large proportion of patients will experience drug efficacy not working, and even some drugs bring severe sleep disorders. Acupuncture, with its unique concept and treatment method, has been validated through a large number of experiments and proved its reliability of acupuncture in the treatment of AD. Many advances have been made in the study of the neurobiological mechanisms of acupuncture in the treatment of AD, further demonstrating the good efficacy and unique advantages of acupuncture in the treatment of AD. This review first summarizes the pathogenesis of AD and then illustrates the research progress of acupuncture in the treatment of AD, which includes the effect of acupuncture on the changes of biochemical indicators in AD in vivo and the specific mechanism of action to exert the therapeutic effect. Changes in relevant indicators of AD similarly further validate the effectiveness of acupuncture treatment. The clinical and mechanistic studies of acupuncture in the treatment of AD are intensified to fit the need for social development. It is believed that acupuncture will achieve new achievements in the treatment of AD as research progresses.
Daily two-photon neuronal population imaging with targeted single-cell electrophysiology and subcellular imaging in auditory cortex of behaving mice
Authors: Huang Junjie , Liang Susu , Li Longhui , Li Xingyi , Liao Xiang , Hu Qianshuo , Zhang Chunqing , Jia Hongbo , Chen Xiaowei , Wang Meng , Li Ruijie
Published: March 2023

Quantitative and mechanistic understanding of learning and long-term memory at the level of single neurons in living brains require highly demanding techniques. A specific need is to precisely label one cell whose firing output property is pinpointed amidst a functionally characterized large population of neurons through the learning process and then investigate the distribution and properties of dendritic inputs. Here, we disseminate an integrated method of daily two-photon neuronal population Ca2+ imaging through an auditory associative learning course, followed by targeted single-cell loose-patch recording and electroporation of plasmid for enhanced chronic Ca2+ imaging of dendritic spines in the targeted cell. Our method provides a unique solution to the demand, opening a solid path toward the hard-cores of how learning and long-term memory are physiologically carried out at the level of single neurons and synapses.
MRI arterial spin labeling in evaluating hemorrhagic transformation following endovascular recanalization of subacute ischemic stroke
Authors: Wu Liheng , Liu Yanghui , Zhu Liangfu , Li Tianxiao , Wang Li’na , Zhang Yang , Zhou Zhilong , Xing Ying , Wang Meiyun , Gao Bulang
Published: March 2023

Objective

To investigate the value of the MRI arterial spin labeling (ASL) in evaluating the blood-brain barrier permeability of anterior circulation ischemic lesions in subacute ischemic stroke (SIS) and the risk of hemorrhage transformation (HT) after endovascular recanalization.

Materials and methods

Patients with anterior circulation SIS treated with endovascular recanalization were prospectively enrolled. The imaging presentations in the MRI ASL sequences, dynamic contrast-enhanced (DCE) sequence, and Xper CT were studied. The relative cerebral blood flow (rCBF), volume transfer constant (Ktrans), and the weighted Kappa coefficient (rKtrans) were analyzed.

Results

Among 27 eligible patients, HT occurred in 7 patients (25.92%). Patients with HT had significantly higher rCBF value (1.56 ± 0.16 vs. 1.16 ± 0.16), Ktrans, (0.08 ± 0.03 min vs. 0.03 ± 0.01 min) and rKtrans (3.02 ± 0.89 vs. 1.89 ± 0.56). The ASL imaging sequence had a high consistency with the DCE sequence and Xper CT with a high weighted Kappa coefficient of 0.91 for the DCE sequence and 0.70 for the Xper CT imaging. The DCE sequence was also highly consistent with the Xper CT in imaging classification with a high weighted Kappa coefficient of 0.78. The rCBF value in the 21 patients with the subcortical and basal ganglia infarction was significantly lower than that in the other 6 patients with the cortical infarction (1.222 ± 0.221 vs. 1.413 ± 0.259, t = 1.795, P = 0.004).

Conclusion

The MRI ASL sequence has an important role in evaluating the blood-brain barrier permeability and the risk of hemorrhagic transformation of anterior circulation SIS following endovascular recanalization.