bluuebunny/crossref_metadata_2025 huggingface dataset:
Metabolomic and Proteomic Identification of Serum Exosome for Hypoxic Preconditioning Participants
Authors: Fan Fangcheng , Du Yang , Chen Lei , Chen Yuewen , Zhong Zhifeng , Li Peng , Cheng Yong
Published: April 2023

Background. In high-altitude areas, hypoxic stress can elicit a series of physiological responses in humans. Exosomes play important roles in both local and distal cellular communications. Methods. We used ultraperformance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) studies to analyze the differentially expressed metabolomics and proteomics in serum exosome of hypoxic preconditioning participants and control subjects in the hypoxic conditions. Results. Fifty-seven military personnel were divided into hypoxic preconditioning group (

n
=
27

) and control group (

n
=
30

). One hundred thirty-six differentially expressed serum exosomal metabolites were found between the hypoxic preconditioning and control groups in the hypoxic conditions, and these differentially expressed metabolites were enriched in pathways related to lysine degradation, butanoate metabolism, GABAergic synapse, histidine metabolism, and linoleic acid metabolism. In addition, hypoxic preconditioning participants showed 102 excellent differential expressions of proteomics compared to controls, which involved actin cytoskeleton organization, hemostasis, complement and coagulation cascades, vesicle-medicated transport, wound healing, etc. Conclusions. We revealed that the expression of exosomal metabolites and proteomics in hypoxic preconditioning participants was significantly different compared to controls in hypoxic conditions.
Therapeutic Implications of Some Natural Products for Neuroimmune Diseases: A Narrative of Clinical Studies Review
Authors: Wijeweera Gayathri , Wijekoon Nalaka , Gonawala Lakmal , Imran Yoonus , Mohan Chandra , De Silva K. Ranil D.
Published: April 2023

Neuroimmune diseases are a group of disorders that occur due to the dysregulation of both the nervous and immune systems, and these illnesses impact tens of millions of people worldwide. However, patients who suffer from these debilitating conditions have very few FDA‐approved treatment options. Neuroimmune crosstalk is important for controlling the immune system both centrally and peripherally to maintain tissue homeostasis. This review aims to provide readers with information on how natural products modulate neuroimmune crosstalk and the therapeutic implications of natural products, including curcumin, epigallocatechin‐3‐gallate (EGCG), ginkgo special extract, ashwagandha, Centella asiatica, Bacopa monnieri, ginseng, and cannabis to mitigate the progression of neuroimmune diseases, such as Alzheimer’s disease, multiple sclerosis, amyotrophic lateral sclerosis, Parkinson’s disease, depression, and anxiety disorders. The majority of the natural products based clinical studies mentioned in this study have yielded positive results. To achieve the expected results from natural products based clinical studies, researchers should focus on enhancing bioavailability and determining the synergistic mechanisms of herbal compounds and extracts, which will lead to the discovery of more effective phytomedicines while averting the probable negative effects of natural product extracts. Therefore, future studies developing nutraceuticals to mitigate neuroimmune diseases that incorporate phytochemicals to produce synergistic effects must analyse efficacy, bioavailability, gut‐brain axis function safety, chemical modifications, and encapsulation with nanoparticles.
Intelligent Navigation of Indoor Robot Based on Improved DDPG Algorithm
Authors: He Xuemei , Kuang Yin , Song Ning , Liu Fan
Published: April 2023

Targeting the problem of autonomous navigation of indoor robots in large‐scale, complicated, and unknown environments, an autonomous online decision‐making algorithm based on deep reinforcement learning is put forward in this paper. Traditional path planning methods rely on the environment modeling, which can cause more workload of calculating. In this paper, the sensors to detect surrounding obstacles are combined with the DDPG (deep deterministic policy gradient) algorithm to input environmental perception and control the action direct output, which enables robots to complete the tasks of autonomous navigation and distribution without relying on environment modeling. In addition, the algorithm preprocesses the relevant data in the learning sample with Gaussian noise, facilitating the agent to adapt to noisy training environment and improve its robustness. The simulation results show that the optimized DL‐DDPG algorithm is more efficient on online decision‐making for the indoor robot navigation system, which enables the robot to complete autonomous navigation and intelligent control independently.
An Improved Ship Classification Method Based on YOLOv7 Model with Attention Mechanism
Authors: Cen Jian , Feng Hao , Liu Xi , Hu Yongjian , Li Haoliang , Li Haisheng , Huang Weisheng
Published: April 2023

Deep learning (DL) is widely used in ship detection, but there are still some problems in the effective classification, such as inaccurate object feature extraction and inconspicuous feature information in deep layers. To address these problems, we propose a YOLOv7-residual convolutional block attention module (YOLOv7-RCBAM) by combining the convolutional attention mechanism and residual connections to the YOLOv7. First, to accelerate the training speed, the parameters in the backbone network of the pretrained model are frozen by using transfer learning, and the model is fine-tuned for training. Second, to enhance the information relevance of channel dimensional features, an attention mechanism with residual connectivity is adopted. Finally, a feature fusion attention mechanism is introduced to improve the effective feature extraction. The effectiveness of the proposed method is fully validated on the SeaShips dataset. The results show that the YOLOv7-RCBAM model achieves better performance with a 97.59% in

mAP

and effectively extracts object feature in deep layers. Meanwhile, the YOLOv7-RCBAM model can accurately locate ship in complex environments with darkness and noise with the

mAP

reaching 96.13% to achieve effective ship classification detection.
Multislice B1 Mapping Method Using Magnetic Resonance Composite Spin Echo Sequences and Simultaneous Echo Refocusing
Authors: Kumar Suchit , Lee Kyu Chan , Kim Jong-Min , Seo Jeung-Hoon , Lee Chulhyun , Oh Chang-Hyun
Published: April 2023

Radiofrequency (RF) transmit field (B1) mapping is a promising method in mitigating the B1 inhomogeneity in various magnetic resonance imaging (MRI) applications. Although several phase- or magnitude-based B1 mapping methods have been proposed, these methods often require complex modeling, long acquisition time, or specialized MRI sequences. A recently introduced simultaneous echo refocusing (SER) technique can be applied in the B1 mapping method to extend the three-dimensional (3D) spatial coverage only without long data acquisition. Therefore, in this study, a multislice B1 mapping method using composite spin echo sequences and SER techniques is proposed to obtain more accurate B1 mapping with short data acquisition time. To evaluate the performance of the proposed B1 mapping method, computational simulations were performed and compared with Morrell’s method, double angle method, and Yarnykh’s method. These results showed that the angle-to-noise ratio of the proposed B1 mapping method has wider B1 range compared to that of other B1 mapping methods. In addition, the proposed B1 mapping methods were compared to the multislice iterative signal intensity mapping method in both phantom and in vivo human experiments, and there was no remarkable difference between the two methods regarding the flip angle distribution in these experiments. Based on these results, this study demonstrated that the proposed B1 mapping method is suitable for accurately measuring B1 propagation under the condition providing reduced scan time and wider 3D coverage of B1 mapping by applying composite RF pulse and SER techniques into the phase-sensitive method.
[Retracted] Application of Amiodarone and Cedilan in the Treatment of Patients with Arrhythmia after Esophageal and Lung Cancer
Authors: Ge Hongjin
Published: April 2023

Objective. To explore the effect of amiodarone and cedilan in the treatment of patients with arrhythmia after esophageal and lung cancer. Methods. The data of 60 patients with postoperative complications of arrhythmias after esophageal and lung cancer from January 2018 to July 2021 were retrospectively analyzed and divided into an observation group (n = 30) and control group (n = 30) according to the random number grouping principle. The former group was treated with amiodarone, and the latter group received cedilan. Results. The effective rate of treatment was significantly higher in the observation group than the control group (P < 0.05). The observation group had the drug onset time obviously shorter than the control group (P < 0.001). The average ventricular rate after treatment in the observation group was remarkably lower than the control group (P < 0.001). The observation group exhibited obviously better cardiac function after treatment as compared to the control group (P < 0.05). The incidence of adverse reactions in the observation group was notably lower than the control group (P < 0.05). Moreover, the observation group had less stress after treatment than the control group (P < 0.001). The blood pressure level of the observation group after treatment was significantly better than the control group (P < 0.05). Conclusion. Amiodarone can relieve stress in patients with arrhythmia following esophageal and lung cancer surgery, stabilize blood pressure, and mitigate arrhythmia symptoms. Our findings are worthy of promotion and application in clinic.
A Qualitative Study of Professionals’ Experiences and Challenges in the Early Identification of Psychosocial Concerns in Children
Authors: Randell E. , Olsson M. , von Ahlefeld Nisser D. , Ericson J.
Published: April 2023

Aim. Early intervention and detecting early signs are often cited as a goal by professionals working with children, but detecting and describing early signs is not well explored. Thus, the study’s aim was to explore professionals’ experiences and challenges in the early identification of psychosocial concerns in children aged 0–16. Materials and Methods. Data were collected from semistructured interviews with 26 professionals (e.g., nurses, psychologists, social workers, teachers, principals, and managers) working with children. The participants engaged in a pilot cooperation model between preschools, schools, social services, and healthcare to reach out early to children in need of support. The interviews were analyzed using thematic network analysis. Results. Four organizing themes were created as follows: “The idea of promoting and preventing is the key to success,” “Identifying the children who need support and intervention,” “Identifying observable early signs,” and “Occupied with children needing immediate support.” The organizing themes were interpreted into one global theme as follows: “All want an early intervention but putting it into practice is challenging.” Conclusion. The study shows that it is difficult to identify children in need of psychosocial support at an early stage because the early signs are difficult to detect. Thus, our results suggest that both preventive interventions targeting all children and specific interventions for those in need of support are needed to promote health and wellbeing.
Supplementary Table 1 from Significance of RB Loss in Unlocking Phenotypic Plasticity in Advanced Cancers
Authors: Venkadakrishnan Varadha Balaji , Yamada Yasutaka , Weng Kenny , Idahor Osasenaga , Beltran Himisha
Published: April 2023

Loss of RB across cancer types
Supplementary Movie from Discovery of Podofilox as a Potent cGAMP–STING Signaling Enhancer with Antitumor Activity
Authors: Han Jing , Hu Shuiqing , Hu Yawei , Xu Yifang , Hou Yanfei , Yang Yinlong , Su Huili , Zhang Zhengyin , Liu Peng , Sun Xuxu , Zhang Conggang
Published: April 2023

Movie
Data from Driver mutations dictate the immunological landscape and response to checkpoint immunotherapy of glioblastoma
Authors: Yeo Alan T. , Shah Rushil , Aliazis Konstantinos , Pal Rinku , Xu Tuoye , Zhang Piyan , Rawal Shruti , Rose Christopher M. , Varn Frederick S. , Appleman Vicky A. , Yoon Joon , Varma Hemant , Gygi Steven P. , Verhaak Roel G.W. , Boussiotis Vassiliki A. , Charest Al
Published: April 2023

Abstract
The composition of the tumor immune microenvironment (TIME) is considered a key determinant of patients’ response to immunotherapy. The mechanisms underlying TIME formation and development over time are poorly understood. Glioblastoma (GBM) is a lethal primary brain cancer for which there are no curative treatments. GBMs are immunologically heterogeneous and impervious to checkpoint blockade immunotherapies. Utilizing clinically relevant genetic mouse models of GBM, we identified distinct immune landscapes associated with expression of EGFR wild-type and mutant EGFRvIII cancer driver mutations. Over time, accumulation of polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) was more pronounced in EGFRvIII-driven GBMs and was correlated with resistance to PD-1 and CTLA-4 combination checkpoint blockade immunotherapy. We determined that GBM-secreted CXCL1/2/3 and PMN-MDSC–expressed CXCR2 formed an axis regulating output of PMN-MDSCs from the bone marrow leading to systemic increase in these cells in the spleen and GBM tumor-draining lymph nodes (TDLNs). Pharmacologic targeting of this axis induced a systemic decrease in the numbers of PMN-MDSC, facilitated responses to PD-1 and CTLA4 combination checkpoint blocking immunotherapy, and prolonged survival in mice bearing EGFRvIII-driven GBM. Our results uncover a relationship between cancer driver mutations, TIME composition and sensitivity to checkpoint blockade in GBM and support the stratification of patients with GBM for checkpoint blockade therapy based on integrated genotypic and immunological profiles.
Data from Discovery of podofilox as a potent cGAMP–STING signaling enhancer with antitumor activity
Authors: Zhang Conggang , Han Jing , Hu Shuiqing , Hu Yawei , Xu Yifang , Hou Yanfei , Yang Yinlong , Su Huili , Zhang Zhengyin , Liu Peng , Sun Xuxu
Published: April 2023

Abstract
Cyclic GMP–AMP (cGAMP) is a second messenger that activates the stimulator of interferon genes (STING) innate immune pathway to induce the expression of type I interferons (IFNs) and other cytokines. Pharmacological activation of STING is considered a potent therapeutic strategy in cancer. In this study, we employed a cell-based phenotypic screen and identified podophyllotoxin (podofilox), a microtubule destabilizer, as a robust enhancer of the cGAMP–STING signaling pathway. We found that podofilox enhanced the cGAMP-mediated immune response by increasing STING-containing membrane puncta and the extent of STING oligomerization. Furthermore, podofilox changed the trafficking pattern of STING and delayed trafficking-mediated STING degradation. Importantly, the combination of cGAMP and podofilox had profound antitumor effects on mice by activating the immune response through host STING signaling. Together, these data provide insights into the regulation of cGAMP–STING pathway activation and demonstrate what we believe to be a novel approach for modulating this pathway and thereby promoting antitumor immunity.
The Role of Inflammation in the Initiation and Progression of Myeloid Neoplasms
Authors: Balandrán Juan Carlos , Lasry Audrey , Aifantis Iannis
Published: April 2023

Myeloid malignancies are devastating hematologic cancers with limited therapeutic options. Inflammation is emerging as a novel driver of myeloid malignancy, with important implications for tumor composition, immune response, therapeutic options, and patient survival. Here, we discuss the role of inflammation in normal and malignant hematopoiesis, from clonal hematopoiesis to full-blown myeloid leukemia. We discuss how inflammation shapes clonal output from hematopoietic stem cells, how inflammation alters the immune microenvironment in the bone marrow, and novel therapies aimed at targeting inflammation in myeloid disease.

Significance:

Inflammation is emerging as an important factor in myeloid malignancies. Understanding the role of inflammation in myeloid transformation, and the interplay between inflammation and other drivers of leukemogenesis, may yield novel avenues for therapy.
Table S3 from Genome-wide CRISPR screen reveals RAB10 as a synthetic lethal gene in colorectal and pancreatic cancers carrying SMAD4 loss.
Authors: Erasimus Helene , Kolnik Vanessa , Lacroix Frederic , Sidhu Sukhvinder S , D'Agostino Stephane , Lemaitre Olivier , Rohaut Alexandre , Sanchez Isabelle , Thill Gilbert , Didier Michel , Debussche Laurent , Marcireau Christophe
Published: April 2023

sgRNAcounts
Supplementary Figure 8 from Genome-wide CRISPR screen reveals RAB10 as a synthetic lethal gene in colorectal and pancreatic cancers carrying SMAD4 loss.
Authors: Erasimus Helene , Kolnik Vanessa , Lacroix Frederic , Sidhu Sukhvinder S , D'Agostino Stephane , Lemaitre Olivier , Rohaut Alexandre , Sanchez Isabelle , Thill Gilbert , Didier Michel , Debussche Laurent , Marcireau Christophe
Published: April 2023

Determination of RAB10 localization
Supplementary Figure 6 from Genome-wide CRISPR screen reveals RAB10 as a synthetic lethal gene in colorectal and pancreatic cancers carrying SMAD4 loss.
Authors: Erasimus Helene , Kolnik Vanessa , Lacroix Frederic , Sidhu Sukhvinder S , D'Agostino Stephane , Lemaitre Olivier , Rohaut Alexandre , Sanchez Isabelle , Thill Gilbert , Didier Michel , Debussche Laurent , Marcireau Christophe
Published: April 2023

Validation of RAB10 susceptibility in two additional cell lines.
Supplementary Figure 4 from Genome-wide CRISPR screen reveals RAB10 as a synthetic lethal gene in colorectal and pancreatic cancers carrying SMAD4 loss.
Authors: Erasimus Helene , Kolnik Vanessa , Lacroix Frederic , Sidhu Sukhvinder S , D'Agostino Stephane , Lemaitre Olivier , Rohaut Alexandre , Sanchez Isabelle , Thill Gilbert , Didier Michel , Debussche Laurent , Marcireau Christophe
Published: April 2023

RAB10 essentiality in cells having altered SMAD4 is confirmed by the in vitro CRISPR screen database DepMap
Entre antigos e modernos: notas sobre a história em Maquiavel
Authors: Mendes Ricardo Polidoro
Published: April 2023

Em seus Discursos sobre a primeira década de Tito Lívio, Maquiavel discorre sobre as histórias de Roma na busca do sentido da ação, do saber da política entremeado à prática dos antigos. No proêmio ao primeiro livro e no proêmio ao segundo, o florentino tece algumas considerações a respeito das histórias e de como os modernos as apreendem, o que, para ele, se configura como um problema. Com efeito, para Maquiavel, o acesso ao passado não é imediato, seja pela leitura das histórias que busca apenas o deleite, e não o saber delas, seja pelo relato situado dos escritores, que retratam parcialmente as coisas antigas, seja ainda pela nostalgia que os idosos possuem de seus tempos de juventude, os quais eles consideram superiores à velhice, quando já não tem tantas forças. Assim, a relação entre passado e presente se torna problemática, pois os tempos antigos aparecem aos modernos como um passado glorioso, porém inatingível, irremediavelmente perdido e, portanto, em descompasso com o presente corrompido. Nossa proposta, então, é retomar o proêmio ao primeiro livro e o proêmio ao segundo livro dos Discorsi para investigar a relação entre presente e passado, e como Maquiavel elabora essa tensão por meio de uma noção de história que possibilita um saber da política comum a antigos e modernos, logo, uma noção de história que revele o fio de sentido comum que os atravessa no movimento histórico.
Brexit, de Roger Scruton
Authors: Oliveira Vinícius de
Published: April 2023

Trata-se de uma resenha da obra Brexit: Origens e Desafios, de Roger Scruton, cuja tradução foi publicada no Brasil em 2021 pela editora Record. A resenha, além de uma síntese do livro, procura traçar breves considerações sobre o pensamento teórico-político de Scruton, sua concepção de nacionalismo, sua crítica do globalismo econômico e do globalismo político, e, ao final, tece uma crítica sobre a atual crise migratória na Europa.
A mediação da informação no contexto escolar: uma abordagem nas tecnologias digitais de informação e comunicação
Authors: Vicente Alonso Watari Angela , Francisco de Almeida Júnior Oswaldo
Published: April 2023

Na sociedade contemporânea percebe-se que a informação está cada vez mais se caracterizando como um elemento que potencializa o desenvolvimento social e intelectual das pessoas. Com o avanço das tecnologias digitais destaca-se a necessidade de refletir sobre a mediação de informações e conteúdos por meio das tecnologias digitais na construção de conhecimento. Nesse contexto, esse artigo apresenta reflexões que se referem a importância da mediação da informação por meio das tecnologias digitais no qual se faz necessário a interação entre os sujeitos e elementos envolvidos neste processo. O objetivo geral deste artigo é compreender a mediação da informação na construção do conhecimento por meio das Tecnologias Digitais de Informação e Comunicação no contexto escolar. Uma vez que a escola enquanto instituição que lida com conhecimento e a informação precisa acompanhar essas mudanças que acontecem na sociedade, para que consiga atingir a demanda da clientela atual e garantir uma educação de qualidade visando à formação integral dos alunos. A metodologia do estudo é constituída de uma pesquisa bibliográfica mediante análise de estudos de autores diversos que abordam conceitualmente a mediação da informação, mediação pedagógica e as Tecnologias Digitais de Informação e Comunicação.
Assinatura isotópica (Sm-Nd) e faciológica da Formação Barra de Tabatinga: novas considerações sobre o registro de um paleonível marinho pleistocênico no Nordeste brasileiro
Authors: Filgueira José Guilherme , Vital Helenice , Lucena Leandson Roberto F. de
Published: April 2023

Este artigo representa a integração e interpretação de dados pretéritos, atividades de campo — com posterior análise laboratorial —, realizados na região costeira, litoral oriental do Rio Grande do Norte, entre os municípios de Baía Formosa e Natal, acerca do registro estratigráfico de um paleonível marinho pleistocênico. A variação da linha de costa e suas feições morfológicas estão associadas diretamente a interferências tectônicas e paleoclimáticas. Essas variações modelam os sistemas deposicionais localmente atuantes, empilhando unidades litoestatigráficas com assinaturas únicas, no que diz respeito ao litotipo, estruturas sedimentares, diagênese, idades deposicionais e cristalização da rocha fonte. Avaliações sedimentológicas e granulométricas apontam ambientes de baixa energia de deposição, correlatos a sistemas de intermarés. Para tal foram descritos afloramentos, confeccionadas lâminas e realizada análise em granulômetro. Análises isotópicas Sm-Nd, incluindo sedimentos adjacentes a linha de costa, foram realizadas objetivando a caracterização das assinaturas isotópicas e identificação de suas prováveis áreas-fonte. Após o processamento das informações, foi possível caracterizar e inserir, na estratigrafia regional, a Formação Barra de Tabatinga, depositada possivelmente durante o pulso transgressivo pleistocênico, com granulometria de areia média à grossa, e assinatura isotópica concentrada no Paleoproterozoico inferior (Sideriano); diferente das unidades sotoposta e sobreposta, respectivamente, Grupo Barreiras (granulometria bem heterogênea e assinatura isotópica distribuída ao longo de todo Paleoproterozoico) e os Depósitos Eólicos Litorâneos (granulometria de areia fina à média).
A Combination of Distinct Vascular Stem/Progenitor Cells for Neovascularization and Ischemic Rescue
Authors: Zhao Liming , Lee Andrew S. , Sasagawa Koki , Sokol Jan , Wang Yuting , Ransom Ryan C. , Zhao Xin , Ma Chao , Steininger Holly M. , Koepke Lauren S. , Borrelli Mimi R. , Brewer Rachel E. , Lee Lorene L.Y. , Huang Xianxi , Ambrosi Thomas H. , Sinha Rahul , Hoover Malachia Y. , Seita Jun , Weissman Irving L. , Wu Joseph C. , Wan Derrick C. , Xiao Jun , Longaker Michael T. , Nguyen Patricia K. , Chan Charles K.F.
Published: April 2023

Background:

Peripheral vascular disease remains a leading cause of vascular morbidity and mortality worldwide despite advances in medical and surgical therapy. Besides traditional approaches, which can only restore blood flow to native arteries, an alternative approach is to enhance the growth of new vessels, thereby facilitating the physiological response to ischemia.

Methods:

The Actin
CreER
/R26
VT2/GK3
Rainbow reporter mouse was used for unbiased in vivo survey of injury-responsive vasculogenic clonal formation. Prospective isolation and transplantation were used to determine vessel-forming capacity of different populations. Single-cell RNA-sequencing was used to characterize distinct vessel-forming populations and their interactions.

Results:

Two populations of distinct vascular stem/progenitor cells (VSPCs) were identified from adipose-derived mesenchymal stromal cells: VSPC1 is CD45-Ter119-Tie2+PDGFRa-CD31+CD105
high
Sca1
low
, which gives rise to stunted vessels (incomplete tubular structures) in a transplant setting, and VSPC2 which is CD45-Ter119-Tie2+PDGFRa+CD31-CD105
low
Sca1
high
and forms stunted vessels and fat. Interestingly, cotransplantation of VSPC1 and VSPC2 is required to form functional vessels that improve perfusion in the mouse hindlimb ischemia model. Similarly, VSPC1 and VSPC2 populations isolated from human adipose tissue could rescue the ischemic condition in mice.

Conclusions:

These findings suggest that autologous cotransplantation of synergistic VSPCs from nonessential adipose tissue can promote neovascularization and represents a promising treatment for ischemic disease.
AGK Potentiates Arterial Thrombosis by Affecting Talin-1 and αIIbβ3-Mediated Bidirectional Signaling Pathway
Authors: Zhang Peng , Jiang Haojie , Yang Mina , Bi Changlong , Zhang Kandi , Liu Dongsheng , Wei Meng , Jiang Zheyi , Lv Keyu , Fang Chao , Liu Junling , Zhang Tiantian , Xu Yanyan , Zhang Junfeng
Published: April 2023

Background:

AGK (acylglycerol kinase) was first identified as a mitochondrial transmembrane protein that exhibits a lipid kinase function. Recent studies have established that AGK promotes cancer growth and metastasis, enhances glycolytic metabolism and function fitness of CD8
+
T cells, or regulates megakaryocyte differentiation. However, the role of AGK in platelet activation and arterial thrombosis remains to be elaborated.

Methods:

We performed hematologic analysis using automated hematology analyzer and investigated platelets morphology by transmission electron microscope. We explored the role of AGK in platelet activation and arterial thrombosis utilizing transgenic mice, platelet functional experiments in vitro, and thrombosis models in vivo. We revealed the regulation effect of AGK on Talin-1 by coimmunoprecipitation, mass spectrometry, immunofluorescence, and Western blot. We tested the role of AGK on lipid synthesis of phosphatidic acid/lysophosphatidic acid and thrombin generation by specific Elisa kits.

Results:

In this study, we found that AGK depletion or AGK mutation had no effect on the platelet average volumes, the platelet microstructures, or the expression levels of the major platelet membrane receptors. However, AGK deficiency or AGK mutation conspicuously decreased multiple aspects of platelet activation, including agonists-induced platelet aggregation, granules secretion, JON/A binding, spreading on Fg (fibrinogen), and clot retraction. AGK deficiency or AGK mutation also obviously delayed arterial thrombus formation but had no effect on tail bleeding time and platelet procoagulant function. Mechanistic investigation revealed that AGK may promote Talin-1Ser425 phosphorylation and affect the αIIbβ3-mediated bidirectional signaling pathway. However, AGK does not affect lipid synthesis of phosphatidic acid/lysophosphatidic acid in platelets.

Conclusions:

AGK, through its kinase activity, potentiates platelet activation and arterial thrombosis by promoting Talin-1 Ser425 phosphorylation and affecting the αIIbβ3-mediated bidirectional signaling pathway.
The Cardio-Kidney Patient: Epidemiology, Clinical Characteristics and Therapy
Authors: Schuett Katharina , Marx Nikolaus , Lehrke Michael
Published: April 2023

Patients with chronic kidney disease (CKD) are at high risk to develop cardiovascular disease with its manifestations coronary artery disease, heart failure, arrhythmias, and sudden cardiac death. In addition, the presence of CKD has a major impact on the prognosis of patients with cardiovascular disease, leading to an increased morbidity and mortality if both comorbidities are present. Therapeutic options including medical therapy and interventional treatment are often limited in patients with advanced CKD, and in most cardiovascular outcome trials, patients with advanced CKD have been excluded. Thus, in many patients, treatment strategies for cardiovascular disease need to be extrapolated from trials conducted in patients without CKD. The current article summarizes the epidemiology, clinical presentation, and treatment options for the most prevalent manifestations of cardiovascular disease in CKD and discusses the currently available treatment options to reduce morbidity and mortality in this high-risk population.
Fibrosis in Pathology of Heart and Kidney: From Deep RNA-Sequencing to Novel Molecular Targets
Authors: Schreibing Felix , Anslinger Teresa M. , Kramann Rafael
Published: April 2023

Diseases of the heart and the kidney, including heart failure and chronic kidney disease, can dramatically impair life expectancy and the quality of life of patients. The heart and kidney form a functional axis; therefore, functional impairment of 1 organ will inevitably affect the function of the other. Fibrosis represents the common final pathway of diseases of both organs, regardless of the disease entity. Thus, inhibition of fibrosis represents a promising therapeutic approach to treat diseases of both organs and to resolve functional impairment. However, despite the growing knowledge in this field, the exact pathomechanisms that drive fibrosis remain elusive. RNA-sequencing approaches, particularly single-cell RNA-sequencing, have revolutionized the investigation of pathomechanisms at a molecular level and facilitated the discovery of disease-associated cell types and mechanisms. In this review, we give a brief overview over the evolution of RNA-sequencing techniques, summarize most recent insights into the pathogenesis of heart and kidney fibrosis, and discuss how transcriptomic data can be used, to identify new drug targets and to develop novel therapeutic strategies.
NETs-Induced Thrombosis Impacts on Cardiovascular and Chronic Kidney Disease
Authors: Thakur Manovriti , Junho Carolina Victoria Cruz , Bernhard Sarah Maike , Schindewolf Marc , Noels Heidi , Döring Yvonne
Published: April 2023

Arterial and venous thrombosis constitute a major source of morbidity and mortality worldwide. Association between thrombotic complications and cardiovascular and other chronic inflammatory diseases are well described. Inflammation and subsequent initiation of thrombotic events, termed immunothrombosis, also receive growing attention but are still incompletely understood. Nevertheless, the clinical relevance of aberrant immunothrombosis, referred to as thromboinflammation, is evident by an increased risk of thrombosis and cardiovascular events in patients with inflammatory or infectious diseases. Proinflammatory mediators released from platelets, complement activation, and the formation of NETs (neutrophil extracellular traps) initiate and foster immunothrombosis. In this review, we highlight and discuss prominent and emerging interrelationships and functions between NETs and other mediators in immunothrombosis in cardiovascular disease. Also, with patients with chronic kidney disease suffering from increased cardiovascular and thrombotic risk, we summarize current knowledge on neutrophil phenotype, function, and NET formation in chronic kidney disease. In addition, we elaborate on therapeutic targeting of NETs-induced immunothrombosis. A better understanding of the functional relevance of antithrombotic mediators which do not increase bleeding risk may provide opportunities for successful therapeutic interventions to reduce thrombotic risk beyond current treatment options.
Bony Stroke: Ischemic Stroke Caused by Mechanical Stress on Brain Supplying Arteries From Anatomical Bone or Cartilage Anomalies
Authors: Haertl Johanna , Renz Martin , Wunderlich Silke , Hemmer Bernhard , Hofauer Benedikt , Gempt Jens , Kallmayer Michael , Boeckh-Behrens Tobias , Kirschke Jan S. , Ikenberg Benno David
Published: April 2023

Background:

Bone or cartilage anomalies with affection of brain supplying arteries are a potential structural cause for ischemic stroke. In the following, we termed this entity bony stroke. Due to rarity of their description, there is no standardized workup and therapy for bony strokes.

Methods:

Retrospectively, we extracted diagnostic and therapeutic workup of all patients considered to have had a bony stroke between January 2017 to March 2022 at our comprehensive care center.

Results:

In total, 6 patients classified as a bony stroke were identified among 4200 acute patients with ischemic stroke treated during the study period. Each patient had recurrent ischemic strokes in the dependent vascular territory before diagnosis. Diagnosis was achieved by a combination of imaging devices, including sonography, computed tomography, and magnetic resonance imaging. In addition to conventional static imaging, the application of dynamic imaging modalities with the patients’ head in rotation or reclination confirmed a vessel affection following head movements in 3 patients (50%). Treatment options were interdisciplinary assessed and included the following: conservative treatment (n=1), endovascular stenting (n=2) or occlusion (n=2), surgical removal of bone/ cartilage (n=2), and surgical bypass treatment (n=1). In follow-up (mean 11.7 months), no patient experienced further ischemia.

Conclusions:

As a differential diagnosis, bony strokes may be considered in patients with recurrent ischemic stroke of unknown cause in one dependent vascular territory. Interdisciplinary evaluation and treatment may eliminate risk of stroke recurrence.
Spatial Proteomics Analysis of Soft and Stiff Regions in Human Acute Arterial Thrombus
Authors: Mai Hongcheng , Zhang Tianyuan , Zhang Tao , Lu Aijun , Wu Zhengdong , Yang Bing , He Niu , Liu Xiaoyan , Tsang Chi Kwan , Xu Anding , Lu Dan
Published: April 2023

Background:

The soft regions of a thrombus tend to be more susceptible to r-tPA (recombinant tissue-type plasminogen activator)-mediated thrombolysis and are more easily removed by mechanical thrombectomy than the stiff counterpart. This study aimed to understand the molecular pathological differences between the soft and stiff regions of human arterial thrombus.

Methods:

We developed a spatial proteomic workflow combining proteomics with laser-captured microdissection to analyze human arterial thrombi with Masson trichrome staining to identify stiff and soft regions from 2 independent cohorts of patients with acute myocardial or cerebral infarction. Dysregulated proteins in a C57BL6/J male mouse model of arterial thrombosis were identified by pathway enrichment and pairwise analyses from the common gene ontology enrichment and dysregulated proteins between carotid and coronary arterial thrombi, and validated by immunohistochemistry.

Results:

Spatial proteomics of the coronary arterial thrombi collected from 7 patients with myocardial infarct revealed 7 common dysregulated proteins in 2 cohorts of patients, and upregulation of TGF-β1 (transforming growth factor β1) was the most prominent fibrosis-related protein. Inhibition of TGF-β1 resulted in delayed arterial thrombosis and accelerated blood flow restoration in mouse model. We further expanded the spatial proteomic workflow to the carotid artery thrombi collected from 11 patients with cerebral infarction. Pairwise proteomic analysis of stiff and soft regions between carotid and coronary arterial thrombi further revealed 5 common gene ontology clusters including features of platelet activation, and a common dysregulated protein COL1A1 (collagen type 1 alpha 1) that was reported to be influenced by TGF-β1. We also verified the expression in human and mice carotid arterial thrombi.

Conclusions:

This study demonstrates the spatially distinct composition of proteins in the stiff and soft regions of human arterial thrombi, and suggests that TGF-β1 is a key therapeutic target for promoting arterial thrombolysis.
Neurophysiological Measures of Proactive and Reactive Control in Negative Template Use
Authors: Chidharom Matthieu , Carlisle Nancy B.
Published: April 2023

In a visual search task, knowing features of distractors in advance leads to a more efficient visual search. Although previous studies suggested that the benefits of these negative cues rely on attentional control, it is unclear whether proactive or reactive control is involved. In this study, we analyzed the EEG data of participants performing a visual search task (n = 14). Participants searched for a shape-defined target after receiving a positive cue (target color), negative cue (distractor color), or neutral cue (non-informative). To examine proactive control, we measured EEG after the cue onset but before visual search. Our time–frequency analysis revealed a higher power of theta oscillations over frontoparietal regions after the negative cues compared with the positive and neutral cues, as well as higher theta phase synchronization within the prefrontal region, demonstrating negative cues rely more heavily on proactive control compared with other cue types. To examine reactive control, we measured EEG after the search onset. We found a lateralization of posterior alpha power toward the target side in both positive and negative cues conditions, with a later lateralization observed after negative cues. Interestingly, we observed a significant relationship between the increase of proactive theta power after negative cues and the decrease of reactive alpha power after the search. This suggests the coordination of proactive and reactive mechanisms lead to the most efficient search.
The Legal Duty of States to Cooperate in the Fight Against Pandemic Disease under the International Health Regulations
Authors: Yiallourides Constantinos
Published: April 2023

The paper outlines the contemporary legal framework of global health focusing on the legal duty of States to cooperate in the surveillance, prevention, and control of epidemic and pandemic disease. The paper details, in particular, the content and nature of States’ duty to cooperate under the International Health Regulations – the primary international legal instrument governing the global response to such events. It also examines the role of the World Health Organization and other UN bodies in fostering cooperation between States in the fight against epidemics and pandemics.
Unmögliche und unvollständige Gegenstände bei Alexius Meinong
Authors: Lenoci Michele
Published: April 2023

This essay presents a personal remembering of Rudolf Haller and deals with his interpretation and evaluation of Meinong’s theory of impossible and incomplete objects in order to better understand the objects of fiction and imagination.
Rudolf Haller
Authors: Stadler Friedrich
Published: April 2023

Rudolf Haller was one of the pioneers of “Austrian philosophy” and analytic philosophy dealing with Bolzano, Brentano, Meinong, and Mach up to Wittgenstein and the Vienna Circle, especially Schlick and Neurath. As professor at the University of Graz he fostered this field with his teaching and research and promoted it together with a lot of invited renowned foreign scholars. In addition, he created the influential Grazer Forschungs- und Dokumentationsstelle für Österreichische Philosophie which hosts important philosophical archives. Moreover, he co-founded the Austrian Ludwig Wittgenstein Society in Kirchberg/W. in 1976 and supported the Institute Vienna Circle since its establishment in Vienna in 1991. This article is a personal review and remembrance of the author’s pleasing interaction and cooperation with Rudolf Haller, as an appreciation of his extraordinary achievements.
Commenting on Homer
Authors: Schein Seth L.
Published: April 2023

I first reflect generally on the aims, audiences, and pedagogical goals of my recently published commentary on Homer’s Iliad, book 1. Then I discuss several exemplary passages in order to illustrate in detail my methodological concerns and ways of reading Homeric poetry, with a particular focus on its traditional meter, language, and style and on the interpretive significance of the fulfillment or disappointment of listeners’ or readers’ expectations.
Forum: Religion, Security, and Gender: An Unholy Trinity by Maria Alcidi
Authors: Alcidi Maria , Gribaldo Alessandra , Grande Elisabetta , Rosario Carmeliza
Published: April 2023

The paper explores the interplay between religion, security, and gender. By employing a broad analytical security framework ranging from warfare violence against women to violence in the domestic sphere, the paper supports the view that countries with heightened rates of gender inequalities and violence are more insecure and prone to conflict. The paper also questions the role played by religions enforcing hierarchical gender constructs in preserving women’s security and protecting them from gender-based violence. Against this background, the paper maintains that deferring the realisation of women’s security until a comprehensive reform has taken place within the religious precinct must not be an option. Such an approach would signify the capitulation of the egalitarian human rights paradigm. Instead, women’s roles as agents of change within religious institutions should be supported, and the proactive engagement of states to encourage religious institutions to reform and embrace an egalitarian ethos should be promoted. Only in this way will the interplay of religion, security, and gender truly benefit the pursuit of women’s security.
#KeepKidsInnocent: What Twitter Discourse on Drag Queens, Disney, and Dolly Parton Teaches Us about the Intersection of Anti-Queerness with Parenting Politics
Authors: Shenton Jamie E.
Published: April 2023

This essay examines social media discourse related to drag queens, Disney, and Dolly Parton for what it says about how anti-queerness intersects with the present political and cultural obsession with parents’ responsibility to protect their children from “harm.” By analyzing tweets collected from the summer of 2022, I demonstrate the ways in which pedagogy and nostalgia help explain how users evaluate contemporary “threats” to children. Users want to know what children are learning, from whom, and in what context (pedagogy); at the same time, users invoke a reverence for the past (nostalgia) as they try to interpret what they are experiencing in the present. Twitter users’ concerns about children center on “fears” related to gender identity and sexual orientation, for instance, “exposing” children to queerness. This discourse is part of an unsettling trend in which anti-queerness is masquerading as concern for the nation’s children.
Sea Surface Cooling by Rainfall Modulates Earth’s Heat Energy Flow
Authors: Ibrahim Hamed D. , Sun Yunfang
Published: April 2023

Characterizing the physical processes that modulate the continuous partitioning of heat between the ocean and overlying atmosphere is important for monitoring the subsequent flow of the heat accumulating in the ocean because of anthropogenic climate change. Oceanic rainfall sensible heat flux (Qp), whereby rainwater cools the sea surface, is computed and compared to the sea surface heat energy balance in the 60°N–60°S region. Contrary to popular belief, the results show that Qp is large at both short and long time scales, accounting for up to 22.5% of sea surface net heat flux around the 5.8°N line of latitude, 10.1% in the tropical 20°N–20°S region, and 5.7% in the global 60°N–60°S region. In the mixed layer of these same regions, area-average temperature change owing to a 10-yr accumulated Qp is up to −2.6° and −1.4°C, respectively. Further analysis reveals a previously unspecified rainfall–evaporation negative feedback between successive evaporation–rainfall cycles at the sea surface. The Qp depresses sea surface temperature and thus inhibits evaporation (latent heat flux), which in turn inhibits rainfall owing to decrease in water vapor supply to the atmosphere. The decrease in sea surface temperature also inhibits heat conduction from the ocean to the atmosphere (sensible heat flux). To compensate for the weaker latent and sensible heat fluxes, sea surface upward longwave radiation flux strengthens. We conclude that Qp acts like a modulator of Earth’s heat energy flow by controlling the partition of upper-ocean heat energy and the cycle of heat flow in the ocean and between the ocean and the atmosphere.

Significance Statement

Upper-ocean heat energy is partitioned between the ocean and the overlying atmosphere. Characterizing the physical processes that modulate this continuous partitioning is important for monitoring the subsequent flow of the heat energy accumulating in the ocean because of anthropogenic climate change. Here, we identify sea surface cooling by rainwater (oceanic rainfall sensible heat flux) as a modulator of this partition: this cooling depresses sea surface temperature and thus inhibits evaporation (latent heat flux), which in turn inhibits rainfall owing to the decrease in water vapor supply to the atmosphere; depressing sea surface temperature also inhibits heat conduction from the ocean to the atmosphere (sensible heat flux). To compensate for the weaker latent and sensible heat fluxes, sea surface upward longwave radiation flux strengthens.