bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison between metagenomic next-generation sequencing in bronchoalveolar lavage fluid and blood for the diagnostic performance of respiratory tract infection: a meta-analysis
Authors: Sun Zhou , Liang Guofu , Niu Yulin
Published: August 2024

Objective

Metagenomic next-generation sequencing (mNGS) is emerging to be pivotal in infectious disease diagnosis, particularly in pulmonary infection. However, the utility of bronchoalveolar lavage fluid (BALF) versus blood mNGS remains controversial. Therefore, the current meta-analysis summarized the previous studies regarding BALF or blood mNGS in pulmonary infection, aiming to comprehensively compare the diagnostic efficiency between them.

Methods

Studies reporting paired BALF and blood mNGS data for pulmonary infection diagnosis were searched in the PubMed, Web of Science, Embase, CNKI, and Wanfang from January 2016 to March 2024.

Results

Eleven studies involving 346 assessed patients were eligible and analyzed. The pooled sensitivity, specificity, and area under the curve (AUC) of BALF mNGS were 0.94 [95% confidence interval (CI): 0.90–0.97], 0.27 (95% CI: 0.19–0.36), and 0.86 [standard error (SE): 0.06], respectively. Meanwhile, the pooled sensitivity, specificity, and AUC of blood mNGS were 0.64 (95% CI: 0.56–0.72), 0.69 (95% CI: 0.62–0.76), and 0.81 (SE: 0.05), respectively. By subgroup analyses, the AUCs of BALF mNGS and blood mNGS for viral detection were 0.70 (SE: 0.08) and 0.71 (SE: 0.08), respectively, while the AUCs of BALF mNGS and blood mNGS for nonviral (bacterial or fungal) detection were 0.83 (SE: 0.06) and 0.73 (SE: 0.08), respectively. Moreover, no threshold effect or publication bias existed, and sensitivity analysis revealed that the findings were generally robust.

Conclusion

BALF mNGS surpasses blood mNGS for total pathogen detection in pulmonary infection patients, while they share a similar efficiency for viral detection.

Systematic review registration

https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42024562740.
Multi-omics characterization of type 2 diabetes mellitus-induced gastroenteropathy in the db/db mouse model
Authors: Zhang Yuxin , Zhang Yanjiao , Yin Ruiyang , Fang Xinyi , Miao Runyu , Guan Huifang , Yao Yiqi , Tian Jiaxing
Published: August 2024

Objective

Gastrointestinal dysfunction are often associated with type 2 diabetes mellitus (T2DM), a complicated metabolic illness. Contributing factors have been proposed, including genetic predisposition, gene environmental, and lifestyle interactions, but the pathophysiology remains unknown.

Methods

We aim to explore the possible causes behind gastrointestinal dysfunction caused by type 2 diabetes in this study. A comprehensive analysis of the gastric sinus metabolome, transcriptome, and proteome in db/db mice with gastrointestinal dysfunction was conducted.

Results

The model group of mice had considerably lower small intestine propulsion and gastric emptying rates, higher blood glucose levels, and were significantly obese compared to the control group. We identified 297 genes, 350 proteins, and 1,001 metabolites exhibiting significant differences between db/db and control mice (p < 0.05). Moreover, multi-omics analysis revealed that the genes, proteins, and metabolites in the T2DM-induced gastroenteropathy mice group were involved in arachidonic acid metabolism, glycerophospholipid metabolism and vitamin digestion and absorption. Specifically, Cbr3, Etnppl, and Apob were the major mRNAs associated with T2DM-induced gastrointestinal dysfunction, while Cyp2b10, Cyp2b19, Pgs1, Gpat3, Apoa4, and Tcn2 were the major proteins associated with T2DM-induced gastrointestinal injury, and 16(R)-HET, 5-HETE, LysoPC (22:0), and Pantothenic acid were the major metabolites associated with T2DM-induced gastrointestinal disorders.

Conclusion

The mechanism of action of diabetic gastroenteropathy may be related to vitamin digestion and absorption, glycerophospholipid metabolism, and arachidonic acid metabolism.
Clinical features and outcomes in kidney transplant recipients with COVID-19 pneumonia: a single center retrospective cohort study
Authors: Xu Liang , Chen Xiuxiu , Yang Xuying , Chen Song , Yang Meng , Yuan Zehua , Chen Rentian , Wang Jianli , Jiang Hongtao , Xu Jian , Wang Yi
Published: August 2024

Objective

This retrospective cohort study aimed to assess the clinical features, treatment outcomes, and short-term prognosis in kidney transplant recipients (KTRs) with concurrent coronavirus disease 2019 (COVID-19) pneumonia.

Methods

KTRs with COVID-19 pneumonia who were admitted to our hospital from December 28, 2022, to March 28, 2023 were included in the study. Their clinical symptoms, responses to antiviral medications, and short-term prognosis were analyzed.

Results

A total of 64 KTRs with initial diagnosis of COVID-19 pneumonia were included in this study. The primary symptoms were fever, cough, and myalgia, with an incidence of 79.7%, 89.1%, and 46.9%, respectively. The administration of antiviral drugs (paxlovid or molnupiravir) within 1–5 days and for over 5 days demonstrated a statistically significant reduction in viral shedding time compared to the group without antiviral medication (P=0.002). Both the paxlovid and molnupiravir treatment groups exhibited a significantly shorter duration of viral shedding time in comparison to the group without antiviral drugs (P=0.002). After 6 months of recovery, there was no significantly negative impact on transplant kidney function (P=0.294).

Conclusion

Fever, cough, and myalgia remain common initial symptoms of concurrent COVID-19 pneumonia in KTRs. Early use of antiviral drugs (paxlovid or molnupiravir) is associated with better therapeutic outcomes. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) had a limited impact on the short-term renal function of the KTRs with concurrent moderate or severe COVID-19 pneumonia.
Effect of anti-biofilm peptide CRAMP-34 on the biofilms of Acinetobacter lwoffii derived from dairy cows
Authors: Liu Lin , Li Hui , Ma Chengjun , Liu Jingjing , Zhang Yang , Xu Dengfeng , Xiong Jing , He Yuzhang , Yang Hongzao , Chen Hongwei
Published: August 2024

Dairy mastitis is one of the most common diseases in dairy farming, and the formation of pathogenic bacteria biofilms may be an important reason why traditional antibiotic therapy fails to resolve some cases of dairy mastitis. We isolated and identified three strains of A. lwoffii were with strong biofilm forming ability from dairy cow mastitis samples from Chongqing dairy farms in China. In order to investigate the effect of novel anti-biofilm peptide CRAMP-34 on A.lwoffii biofilms, the anti-biofilm effect was evaluated by crystal violet staining, biofilms viable bacteria counting and confocal laser scanning microscopy (CLSM). In addition, transcriptome sequencing analysis, qRT-PCR and phenotypic verification were used to explore the mechanism of its action. The results showed that CRAMP-34 had a dose-dependent eradicating effect on A. lwoffii biofilms. Transcriptome sequencing analysis showed that 36 differentially expressed genes (11 up-regulated and 25 down-regulated) were detected after the intervention with the sub-inhibitory concentration of CRAMP-34. These differentially expressed genes may be related to enzyme synthesis, fimbriae, iron uptake system, capsular polysaccharide and other virulence factors through the functional analysis of differential genes. The results of subsequent bacterial motility and adhesion tests showed that the motility of A.lwoffii were enhanced after the intervention of CRAMP-34, but there was no significant change in adhesion. It was speculated that CRAMP-34 may promote the dispersion of biofilm bacteria by enhancing the motility of biofilm bacteria, thereby achieving the effect of eradicating biofilms. Therefore, these results, along with our other previous findings, suggest that CRAMP-34 holds promise as a new biofilm eradicator and deserves further research and development.
Analysis of in vitro expression of virulence genes related to antibiotic and disinfectant resistance in Escherichia coli as an emerging periodontal pathogen
Authors: Monroy-Pérez Eric , Hernández-Jaimes Tania , Morales-Espinosa Rosario , Delgado Gabriela , Martínez-Gregorio Héctor , García-Cortés Luis Rey , Herrera-Gabriel Jennefer Paloma , De Lira-Silva Andrea , Vaca-Paniagua Felipe , Paniagua-Contreras Gloria Luz
Published: August 2024

The collective involvement of virulence markers of Escherichia coli as an emerging pathogen associated with periodontitis remains unexplained. This study aimed to implement an in vitro model of infection using a human epithelial cell line to determine the virulome expression related to the antibiotic and disinfectant resistance genotype and pulse field gel electrophoresis (PFGE) type in E. coli strains isolated from patients with periodontal diseases. We studied 100 strains of E. coli isolated from patients with gingivitis (n = 12), moderate periodontitis (n = 59), and chronic periodontitis (n = 29). The identification of E. coli and antibiotic and disinfectant resistance genes was performed through PCR. To promote the expression of virulence genes in the strains, an in vitro infection model was used in the human epithelial cell line A549. RNA was extracted using the QIAcube robotic equipment and reverse transcription to cDNA was performed using the QuantiTect reverse transcription kit (Qiagen). The determination of virulence gene expression was performed through real-time PCR. Overall, the most frequently expressed adhesion genes among the isolated strains of gingivitis, moderate periodontitis, and chronic periodontitis were fimH (48%), iha (37%), and papA (18%); those for toxins were usp (33%); those for iron acquisition were feoB (84%), fyuA (62%), irp-2 (61%), and iroN (35%); those for protectins were traT (50%), KpsMT (35%), and ompT (28%); and those for pathogenicity islands were malX (45%). The most common antibiotic and disinfectant resistance genes among gingivitis, moderate periodontitis, and chronic periodontitis strains were sul-2 (43%), blaSHV (47%), blaTEM (45%), tet(A) (41%), dfrA1 (32%), marR-marO (57%), and qacEA1 (79%). The findings revealed the existence of a wide distribution of virulome expression profiles related to the antibiotic and disinfectant resistance genotype and PFGE type in periodontal strains of E. coli. These findings may contribute toward improving the prevention and treatment measures for periodontal diseases associated with E. coli.
Unraveling the complex interplay: immunopathology and immune evasion strategies of alphaviruses with emphasis on neurological implications
Authors: de Oliveira Souza Raquel , Duarte Júnior José Wandilson Barboza , Della Casa Victória Simões , Santoro Rosa Daniela , Renia Laurent , Claser Carla
Published: August 2024

Arthritogenic alphaviruses pose a significant public health concern due to their ability to cause joint inflammation, with emerging evidence of potential neurological consequences. In this review, we examine the immunopathology and immune evasion strategies employed by these viruses, highlighting their complex mechanisms of pathogenesis and neurological implications. We delve into how these viruses manipulate host immune responses, modulate inflammatory pathways, and potentially establish persistent infections. Further, we explore their ability to breach the blood-brain barrier, triggering neurological complications, and how co-infections exacerbate neurological outcomes. This review synthesizes current research to provide a comprehensive overview of the immunopathological mechanisms driving arthritogenic alphavirus infections and their impact on neurological health. By highlighting knowledge gaps, it underscores the need for research to unravel the complexities of virus-host interactions. This deeper understanding is crucial for developing targeted therapies to address both joint and neurological manifestations of these infections.
Exploring blood transcriptomic signatures in patients with herpes zoster and postherpetic neuralgia
Authors: Wang Chunliang , Zhang Kaiyi , Bao Yuhan , Liu Ye , Zhou You , Ji Yong-Hua , Wang Hongjie , Tan Zhi-Yong
Published: August 2024

Postherpetic neuralgia (PHN) is a common, severe, and hard-to-treat chronic pain condition in clinics. Although PHN is developed from herpes zoster (HZ), the developing mechanism is unknown. A previous study investigated blood metabolomic and proteomic profiling in patients with PHN and HZ. The current study aims to explore the blood transcriptomic signature of PHN compared to HZ patients. Whole blood from eight PHN and 15 HZ patients was used for RNA-Seq analysis. There were 82 and 1,788 genes detected specifically in the PHN and HZ groups, respectively. PHN-specific genes are involved in viral infection, lipid and carbohydrate metabolism, and immune response. For genes coexpressed in PHN and HZ patients, there were 407 differential expression genes (DEGs), including 205 upregulated (UP DEGs) and 202 downregulated (DOWN DEGs) in PHN compared to HZ groups. DEGs are involved in viral infection, type I interferon (IFN), and hemoglobin and oxygen carrier activity. UP DEGs are associated with regulatory T cells (Tregs), activated NK cells, and neutrophils, while DOWN DEGs are associated with Tregs, resting NK cells, and monocytes. The results suggest that the metabolism of lipid, glycan, and nucleotides, type I IFN signaling, and altered neutrophil activation are associated with and might contribute to the development of PHN in HZ. It is also suggested that persistent or altered activation of nonspecific immunity may contribute to the development of PHN from HZ.
In search of a translator: using AI to evaluate what's lost in translation
Authors: Elkins Katherine
Published: August 2024

Machine translation metrics often fall short in capturing the challenges of literary translation in which translators play a creative role. Large Language Models (LLMs) like GPT4o and Mistral offer new approaches to assessing how well a translation mirrors the reading experience from one language to another. Our case study focuses on the first volume of Marcel Proust's “A la recherche du temps perdu,” a work known for its lively translation debates. We use stylometry and emotional arc leveraging the newest multilingual generative AI models to evaluate loss in translation according to different translation theories. AI analysis reveals previously undertheorized aspects of translation. Notably, we uncover changes in authorial style and the evolution of sentiment language over time. Our study demonstrates that AI-driven approaches leveraging advanced LLMs yield new perspectives on literary translation assessment. These methods offer insight into the creative choices made by translators and open up new avenues for understanding the complexities of translating literary works.
Cardiac ultrasound simulation for autonomous ultrasound navigation
Authors: Amadou Abdoul Aziz , Peralta Laura , Dryburgh Paul , Klein Paul , Petkov Kaloian , Housden R. James , Singh Vivek , Liao Rui , Kim Young-Ho , Ghesu Florin C. , Mansi Tommaso , Rajani Ronak , Young Alistair , Rhode Kawal
Published: August 2024

Introduction

Ultrasound is well-established as an imaging modality for diagnostic and interventional purposes. However, the image quality varies with operator skills as acquiring and interpreting ultrasound images requires extensive training due to the imaging artefacts, the range of acquisition parameters and the variability of patient anatomies. Automating the image acquisition task could improve acquisition reproducibility and quality but training such an algorithm requires large amounts of navigation data, not saved in routine examinations.

Methods

We propose a method to generate large amounts of ultrasound images from other modalities and from arbitrary positions, such that this pipeline can later be used by learning algorithms for navigation. We present a novel simulation pipeline which uses segmentations from other modalities, an optimized volumetric data representation and GPU-accelerated Monte Carlo path tracing to generate view-dependent and patient-specific ultrasound images.

Results

We extensively validate the correctness of our pipeline with a phantom experiment, where structures' sizes, contrast and speckle noise properties are assessed. Furthermore, we demonstrate its usability to train neural networks for navigation in an echocardiography view classification experiment by generating synthetic images from more than 1,000 patients. Networks pre-trained with our simulations achieve significantly superior performance in settings where large real datasets are not available, especially for under-represented classes.

Discussion

The proposed approach allows for fast and accurate patient-specific ultrasound image generation, and its usability for training networks for navigation-related tasks is demonstrated.
Case Report: C-reactive protein apheresis in non-ST-elevation ACS—case series from the C-reactive protein apheresis in Acute Myocardial Infarction Registry
Authors: Torzewski J. , Mattecka S. , Esposito F. , Heigl F. , Fiedler J. , Sheriff A.
Published: August 2024

C-reactive protein (CRP) apheresis has been introduced in ST-elevation myocardial infarction and cardiogenic shock. Here, we describe a first-in-man application in non-ST-elevation acute coronary syndrome (NSTE-ACS). Seven NSTE-ACS patients with high CRP levels (range 14.2–154 mg/L) were treated with CRP apheresis. Treatment was well-tolerated. Patients were discharged in good clinical condition.
Multiparameter ranking of carbazoles for anti-trypanosome lead discovery
Authors: Sharma Amrita , Sanz-Rodriguez Carlos E. , Pollastri Michael P. , Purmal Andrei , Mensa-Wilmot Kojo
Published: August 2024

The criteria for the progression of hits in the discovery of leads for human African trypanosomiasis (HAT), a neglected disease caused by the microbial eukaryote Trypanosoma brucei, are not standardized. Hits are advanced upon meeting thresholds for drug-like molecules. Following those principles, pharmacokinetics (Cmax and AUC0–6h) and anti-trypanosome characteristics predicted the arrest of T. brucei proliferation in mice by three curaxins. Unexpectedly, while CBL0137 cured HAT in a mouse model, CBL0174 and CBL0187—structural analogs of CBL0137 with similar drug-like properties—failed to control T. brucei division. We here propose an alternative strategy that integrates physicochemical, metabolic, pharmacokinetic, pharmacodynamic, tissue distribution, and trypanocidality parameters into calculating a score for ranking compounds in hit-to-lead campaigns. Data from our studies of curaxins support the feasibility of this goal. Serum dropped the anti-trypanosome potency of CBL0174 and CBL0187 considerably. Delayed trypanocidal concentrations (DTC25 and DTC90) were used to study modes of curaxin actions in trypanosomes. Efficacy of CBL0137 in mice correlated with (i) a high AUC0–6h:DTC90 ratio, (ii) blocking of transferrin endocytosis, and (iii) the inhibition of protein synthesis. Hydroxylation of the carbazole prevented CBL0137 from inhibiting endocytosis of transferrin. The multiparametric score “Curaxin HAT lead efficacy (CHLE)” score was calculated using pharmacokinetic, physicochemical, metabolic, brain exposure, and pharmacodynamic data; CBL0137 was the highest scoring hit. Complementing these observations and predictive of performance of curaxins in mice, CBL0137, but not CBL0174 or CBL0187, was trypanocidal after the exposure of trypanosomes to AUC0–6h amounts of the hits for 6 hours in vitro. We discuss a role for CHLE scores in ranking curaxins for anti-HAT lead discovery. The principles used to develop CHLE scores may be used to calculate new ones for other scaffolds during the discovery of leads for HAT or other infectious diseases.
Beyond the mirror: an action-based model of knowing through reflection
Authors: Allen Jedediah W. P. , Mirski Robert , Bickhard Mark H.
Published: August 2024

Epistemic reflection involves the creation of qualitatively new knowledge. Different models have been proposed to account for new knowing through reflection that have typically been grounded in an information-processing framework. However, there are in-principle arguments that information-processing approaches preclude the emergence of new representation altogether. Accordingly, any information-processing account of knowing through reflection is plagued by emergence issues. After discussing some of these emergence issues for four prominent models in the cognitive science literature, an alternative action-based model of representation and reflection is presented called interactivism. Interactivism's model of representation, as grounded in action anticipations, serves as the foundational emergence needed to account for subsequent knowing through reflection. After introducing the interactivist models of representation and reflection through knowing levels, some of the implications for consciousness, enculturation, language, and developmental methodology are discussed.
Deep structure of the Wulong goldfield, Liaodong Peninsula, China, revealed by receiver functions: implications for the tectonic and mineralization dynamics
Authors: Zheng Fan , Xu Tao , Ai Yinshuang , Ge Yunping , Zeng Qingdong , Miao Laicheng , Dong Weiyu , Badal José
Published: August 2024

During the Mesozoic, the North China Craton experienced intense tectonic movements that resulted in the formation of numerous gold deposits on the Liaodong and Jiaodong Peninsulas in northeastern China. To investigate the relationship between deep crustal structure and gold mineralization in the Liaodong Peninsula, we deployed 334 dense seismic stations in the Wulong goldfield (WLGF) with the idea of analysing numerous receiver functions at different array stations. The purpose focused on knowing the potential for gold mineralization in the area. The study revealed the following: (1) The WLGF is characterized by a crustal thickness of approximately 32 km and an average Vp/Vs ratio of 1.76. The high value of the Vp/Vs ratio near the Wulong gold deposit suggests that mantle materials have penetrated into the crust and contributed to the mineralization process. (2) A low-velocity layer located at a depth of 10–18 km below the WLGF seems to support the existence of a potentially brittle-ductile transition zone. Also, hydrothermal magma upwelling channels are observed in the upper crust beneath the Wulong gold deposit. (3) The presence of a discontinuous low-velocity layer in the middle crust beneath the Liaodong Peninsula suggests promising prospects for gold ore exploration. The receiver functions method based on a dense seismic array employed in this study can offer valuable references and guidance for the fine exploration and research of ore deposits in other regions globally.
Advancing education-based mental health in low-resource settings during health crises: the mental health initiative of the University of the Philippines during the COVID-19 pandemic
Authors: Gonzalo Richard Philip , Alibudbud Rowalt
Published: August 2024

The COVID-19 pandemic exacerbated students’ mental health challenges worldwide, including in the Philippines. This paper explores the University of the Philippines’ response to this crisis, a crucial endeavor given the country’s limited mental health resources. This paper reviews the relevant documents to the mental health initiative, titled “Sandigan, Sandalan,” which sought to empower university stakeholders to advocate for mental and address mental health needs despite resource constraints and the university’s vastness. The authors also share their experiences and insights in the program. This program is one of the few university mental health programs that were documented in the Philippines after the legislation of the Philippine Mental Health Act and during the COVID-19 pandemic. Key recommendations arising from this experience include enhancing program visibility, fostering stakeholder collaboration toward a clear set of program objectives, leveraging mental health expertise, empowering stakeholders, and designing replicable program models for the different campuses of the university. The initiative underscores the vital role that educational institutions can play and provides valuable insights into supporting students’ mental well-being amid large scale challenges in low-resource settings.
Environmental endocrine disruptor-induced mitochondrial dysfunction: a potential mechanism underlying diabetes and its complications
Authors: He Kunhui , Chen Rumeng , Xu Shuling , Ding Yining , Wu Zhu , Bao Meihua , He Binsheng , Li Sen
Published: August 2024

Diabetes and its complications significantly affect individuals’ quality of life. The etiology of diabetes mellitus and its associated complications is complex and not yet fully understood. There is an increasing emphasis on investigating the effects of endocrine disruptors on diabetes, as these substances can impact cellular processes, energy production, and utilization, ultimately leading to disturbances in energy homeostasis. Mitochondria play a crucial role in cellular energy generation, and any impairment in these organelles can increase susceptibility to diabetes. This review examines the most recent epidemiological and pathogenic evidence concerning the link between endocrine disruptors and diabetes, including its complications. The analysis suggests that endocrine disruptor-induced mitochondrial dysfunction—characterized by disruptions in the mitochondrial electron transport chain, dysregulation of calcium ions (Ca2+), overproduction of reactive oxygen species (ROS), and initiation of signaling pathways related to mitochondrial apoptosis—may be key mechanisms connecting endocrine disruptors to the development of diabetes and its complications.
Understanding requirements, limitations and applicability of QSAR and PTF models for predicting sorption of pollutants on soils: a systematic review
Authors: Neira-Albornoz Angelo , Martínez-Parga-Méndez Madigan , González Mitza , Spitz Andreas
Published: August 2024

Sorption is a key process to understand the environmental fate of pollutants on soils, conduct preliminary risk assessments and fill information gaps. Quantitative Structure-Activity Relationships (QSAR) and Pedotransfer Functions (PTF) are the most common approaches used in the literature to predict sorption. Both models use different outcomes and follow different simplification strategies to represent data. However, the impact of those differences on the interpretation of sorption trends and application of models for regulatory purposes is not well understood. We conducted a systematic review to contextualize the requirements for developing, interpreting, and applying predictive models in different scenarios of environmental concern by using pesticides as a globally relevant organic pollutant model. We found disagreements between predictive model assumptions and empirical information from the literature that affect their reliability and suitability. Additionally, we found that both model procedures are complementary and can improve each other by combining the data treatment and statistical validation applied in PTF and QSAR models, respectively. Our results expose how relevant the methodological and environmental conditions and the sources of variability studied experimentally are to connect the representational value of data with the applicability domain of predictive models for scientific and regulatory decisions. We propose a set of empirical correlations to unify the sorption mechanisms within the dataset with the selection of a proper kind of model, solving apparent incompatibilities between both models, and between model assumptions and empirical knowledge. The application of our proposal should improve the representativity and quality of predictive models by adding explicit conditions and requirements for data treatment, selection of outcomes and predictor variables (molecular descriptors versus soil properties, or both), and an expanded applicability domain for pollutant-soil interactions in specific environmental conditions, helping the decision-making process in regard to both scientific and regulatory concerns (in the following, the scientific and regulatory dimensions).
Addressing the research gap: access to care hinders genetic discovery in systemic lupus erythematosus patients throughout the African diaspora
Authors: Hwang Jihwan , Dzifa Dey Ida , Ayanlowo Olusola , Flower Cindy , King Amanda , Johnson Nicole , Ima-Edomwonyi Uyiekpen , Olasebikan Hakeem , Falasinnu Titilola , Durairaj Pandian Vishnuprabu , Blazer Ashira
Published: August 2024

Systemic lupus erythematosus (SLE) is a complex autoimmune condition that disproportionately impacts non-White ethnic and racial groups, particularly individuals in the African diaspora who experience heightened incidence, prevalence, and adverse outcomes. Genetic and epigenetic factors play significant roles in SLE risk, however these factors neither explain the whole of SLE risk nor the stark racial disparities we observe. Moreover, our understanding of genetic risk factors within African ancestry populations is limited due to social and environmental influences on research participation, disease presentation, and healthcare access. Globally, the African diaspora faces barriers in accessing essential SLE diagnostic tools, therapeutics, healthcare practitioners, and high-quality clinical and translational research studies. Here, we provide insights into the current state of genetic studies within African ancestry populations and highlight the unique challenges encountered in SLE care and research across countries of varying income levels. We also identify opportunities to address these disparities and promote scientific equity for individuals affected by SLE within the global African diaspora.
The demand for welfare institutions in refugee camps
Authors: Bhuiyan Md. Mahmudur Rahman
Published: August 2024

Long-term encampment has become a reality for a large portion of the forcibly displaced population of the contemporary world, given the inadequacies and limitations of the conventional durable solutions to forced displacement. However, encampment is principally a temporary arrangement that prevents long-term programming in camps, making long-term encampment contradictory and an arena of uncertainty, misery, and despair for the camp dwellers. It is rather more rational to admit long-term encampment as a reality and act on it as it involves unjustifiable humanitarian costs. The paper calls for thinking beyond the conventional practices and focusing on the wellbeing of the encamped population from a life-course perspective. It proposes a framework for building welfare institutions in refugee camps.
The causality between use of glucocorticoids and risk of pancreatitis: a Mendelian randomization study
Authors: Lin Wenfeng , Zheng Qiqi , Wang Xiaorong , Lin Xiaolu , Ni Xixi , Pan Jingye , Zippi Maddalena , Fiorino Sirio , Hong Wandong
Published: August 2024

Background and aim

To date, the association between glucocorticoid use and the risk of pancreatitis remains controversial. The aim of this study was the investigation of this possible relationship.

Methods

We carried out a two-sample Mendelian randomization (MR) analysis using GWAS data from European ancestry, East Asian descendants and the FinnGen Biobank Consortium to evaluate this potential causal relationship. Genetic variants associated with glucocorticoid use were selected based on genome-wide significance (p < 5×10-8).

Results

Our MR analysis of European ancestry data revealed no significant causal relationship between glucocorticoid use and AP (IVW: OR=1.084, 95% CI= 0.945-1.242, P=0.249; MR-Egger: OR=1.049, 95% CI= 0.686-1.603, P=0.828; weighted median: OR=1.026, 95% CI= 0.863-1.219, P=0.775) or CP (IVW: OR=1.027, 95% CI= 0.850-1.240, P=0.785; MR-Egger: OR= 1.625, 95% CI= 0.913-2.890, P= 0.111; weighted median: OR= 1.176, 95% CI= 0.909-1.523, P= 0.218). Sensitivity analyses, including MR-Egger and MR-PRESSO, indicated no evidence of pleiotropy or heterogeneity, confirming the robustness of our findings. Multivariable MR analysis adjusted for alcohol consumption, BMI, cholelithiasis and C-reactive protein levels supported these findings. Replicated analysis was performed on datasets from the FinnGen Biobank Consortium and East Asian descendants, and similar results were obtained.

Conclusions

This MR analysis suggests that there is no causal association between glucocorticoid use and the risk of pancreatitis.
Dysregulated gene expression of SUMO machinery components induces the resistance to anti-PD-1 immunotherapy in lung cancer by upregulating the death of peripheral blood lymphocytes
Authors: Wang Ying , Sun Chao , Liu Mengmeng , Xu Panyang , Li Yanyan , Zhang Yongsheng , Huang Jing
Published: August 2024

Background

The majority of patients with lung cancer exhibit drug resistance after anti-PD-1 immunotherapy, leading to shortened patient survival time. Previous studies have suggested an association between epigenetic abnormalities such as methylation and clinical response to anti-PD-1 immunotherapy, while the role of SUMOylation in resistance to anti-PD-1 antibody immunotherapy is still unclear.

Methods

Here, the mRNA expression of 15 SUMO machinery components in PBMC from lung cancer patients receiving anti-PD-1 immunotherapy were analyzed using real-time PCR. Base on the percentage change in mRNA levels, the relationship between the expression of SUMO machinery components and outcomes of anti-PD-1 immunotherapy, and the influencing factors of SUMOylation were evaluated. PBMC was treated with different concentrations of 2-D08 (a specific inhibitor of SUMOylation) in vitro, and analyzed the activation and the death rates of lymphocyte subsets by flow cytometry analysis.

Results

A predictive method, base on the gene expression of three SUMO machinery components (SUMO1, SUMO3 and UBE2I), were developed to distinguish non-responders to PD-1 inhibitors. Furthermore, the number of lymphocytes in peripheral blood significantly reduced in the dysregulated SUMOylation groups (the percentage change >100 or -50 ~ -100 groups). In vitro studies confirmed that lightly low SUMOylation level improved the activation status of T and NK lymphocytes, but extremely low SUMOylation level lead to the increased death rates of lymphocytes.

Conclusion

Our findings implied that dysregulated gene expression of SUMO machinery components could induce the resistance of anti-PD-1 immunotherapy in lung cancer by upregulating the death of peripheral blood lymphocytes. These data might provide effective circulating biomarkers for predicting the efficacy of anti-PD-1 immunotherapy, and uncovered a novel regulatory mechanism of resistance to anti-PD-1 immunotherapy.
A disintegrin and metalloproteinase domain 10 expression inhibition by the small molecules adenosine, cordycepin and N6, N6-dimethyladenosine and immune regulation in malignant cancers
Authors: Zhang Wenqian , Fu Jiewen , Du Jiaman , Liu Xiaoyan , Cheng Jingliang , Wei Chunli , Xu Youhua , Fu Junjiang
Published: August 2024

A disintegrin and metalloproteinase domain 10 (ADAM10), a member of the ADAM family, is a cellular surface protein with potential adhesion and protease/convertase functions. The expression regulations in cancers by natural products [adenosine (AD) and its analogs, cordycepin (CD), and N6, N6-dimethyladenosine (m62A)], and immune regulation are unclear. As results, AD, CD, and m62A inhibited ADAM10 expression in various cancer cell lines, indicating their roles in anti-cancer agents. Further molecular docking with ADAM10 protein found the binding energies of all docking groups were <-7 kcal/mol for all small-molecules (AD, CD and m62A), suggesting very good binding activities. In addition, analysis of the immunomodulatory roles in cancer showed that ADAM10 was negatively correlated with immunomodulatory genes such as CCL27, CCL14, CCL25, CXCR5, HLA-B, HLA-DOB1, LAG3, TNFRSF18, and TNFRSF4 in bladder urothelial carcinoma, thymoma, breast invasive carcinoma, TGCT, kidney renal papillary cell carcinoma, SKCM and thyroid carcinoma, indicating the immune-promoting roles for ADAM10. LAG3 mRNA levels were reduced by both AD and CD in vivo. ADAM10 is also negatively associated with tumor immunosuppression and interrelated with the immune infiltration of tumors. Overall, the present study determined ADAM10 expression by AD, CD and m62A, and in AD or CD/ADAM10/LAG3 signaling in cancers, and suggested a potential method for immunotherapy of cancers by targeting ADAM10 using the small molecules AD, CD and m62A.
Targeting and activation of macrophages in leishmaniasis. A focus on iron oxide nanoparticles
Authors: Palomino-Cano Carmen , Moreno Esther , Irache Juan M. , Espuelas Socorro
Published: August 2024

Macrophages play a pivotal role as host cells for Leishmania parasites, displaying a notable functional adaptability ranging from the proinflammatory, leishmanicidal M1 phenotype to the anti-inflammatory, parasite-permissive M2 phenotype. While macrophages can potentially eradicate amastigotes through appropriate activation, Leishmania employs diverse strategies to thwart this activation and redirect macrophages toward an M2 phenotype, facilitating its survival and replication. Additionally, a competition for iron between the two entities exits, as iron is vital for both and is also implicated in macrophage defensive oxidative mechanisms and modulation of their phenotype. This review explores the intricate interplay between macrophages, Leishmania, and iron. We focus the attention on the potential of iron oxide nanoparticles (IONPs) as a sort of immunotherapy to treat some leishmaniasis forms by reprogramming Leishmania-permissive M2 macrophages into antimicrobial M1 macrophages. Through the specific targeting of iron in macrophages, the use of IONPs emerges as a promising strategy to finely tune the parasite-host interaction, endowing macrophages with an augmented antimicrobial arsenal capable of efficiently eliminating these intrusive microbes.
NK cell based immunotherapy against oral squamous cell carcinoma
Authors: Zhang Ying , Xie Jianming , Wu Haoran , Huang Jinhui , Zheng Danna , Wang Shaotong , Jia Xueqiang , He Zongzhong , Gong Ying , Ju Linling , Sun Qiurong
Published: August 2024

Oral squamous cell carcinoma (OSCC), a major subtype of head and neck cancers, presents significant challenges due to its aggressive feature and limited therapeutic efficacy of conventional treatments. In response to these challenges, Natural Killer (NK) cells, a vital component of the innate immune system, are being explored for their therapeutic potential in OSCC due to their inherent ability to target and eliminate cancer cells without prior sensitization. This review uniquely focuses on the evolving role of NK cells specifically in OSCC, incorporating recent advancements in CAR-NK cell engineering and personalized therapy approaches that have not been comprehensively covered in previous reviews. The mechanisms through which NK cells exert cytotoxic effects on tumor cells include direct killing through the engagement of natural cytotoxic receptors and antibody-dependent cellular cytotoxicity (ADCC), making them promising agents in cancer immunotherapy. Additionally, the article explores recent advancements in engineering NK cells to enhance their antitumor activity, such as the modification with chimeric antigen receptors (CARs) to target specific tumor antigens. Clinical implications of NK cell-based therapies, including the challenges of integrating these treatments with existing protocols and the potential for personalized therapy, are examined. The review highlights the promise of NK cell therapies in improving outcomes for OSCC patients and outlines future directions for research in this dynamic field of oncological immunotherapy.
Anti-inflammatory and antioxidant activity of high concentrations of hydrogen in the lung diseases: a systematic review and meta-analysis
Authors: Xiao Kang , Liu Jianwei , Sun Yuxin , Chen Shangya , Ma Jiazi , Cao Mao , Yang Yong , Pan Zhifeng , Li Peng , Du Zhongjun
Published: August 2024

As a small molecule, hydrogen is colorless, odorless and lightest. Many studies conducted that hydrogen can protect almost every organ, including the brain, heart muscle, liver, small intestine, and lungs. To verify whether high concentrations of hydrogen (HCH) has anti-inflammatory and antioxidant activities on respiratory system, we product a systematic review and meta-analysis. We investigated MEDLINE-PubMed, Cochrane Library, ScienceDirect, Wiley and SpringerLink database and selected in vivo studies related to the anti-inflammatory or antioxidant effects of HCH in the lung diseases which were published until September 2023. We firstly identified 437 studies and only 12 met the inclusion criteria. They all conducted in rodents. The results showed that HCH had a positive effect on the reduction of tumor necrosis factor alpha (TNF-α), interleukin (IL)-1β, IL-4, IL-8, malondialdehyde (MDA), superoxide dismutase (SOD) and reactive oxygen species (ROS); but there is no effect on IL-6, we speculated that may contribute to the test results for different body fluids and at different points in time. This meta-analysis discovered the protective effects on inflammation and oxidative stress, but whether there exists more effects on reduction of inflammatory and oxidant mediators needs to be further elucidated.
High socioeconomic impact on prescription behavior despite unrestricted access to disease-modifying therapies in people with multiple sclerosis
Authors: Samadzadeh S. , Havla J. , Lepka K. , Brinks R. , Meuth S. G. , Klotz L. , Albrecht P.
Published: August 2024

Background

Economic and health care restraints strongly impact on drug prescription for chronic diseases. We aimed to identify potential factors for prescription behavior in chronic disease. Multiple sclerosis was chosen as a model disease due to its chronic character, incidence, and high socioeconomic impact.

Methods

Germany was used as a model country as the health-care system is devoid of economic and drug availability restraints. German statutory health insurance data were analyzed retrospectively. The impact of number of university hospitals and neurologists as well as the gross domestic product (GDP) as potential factors on prescriptions of platform and high-efficacy disease-modifying therapies (DMTs) was analyzed.

Results

Prescription of platform DMTs increased over time in almost all federal states with varying degree of increase. Univariate regression analysis showed that the prescription volume of platform DMTs positively correlated with the number of university hospitals and neurologists, as well as the GDP per federal state. Stepwise forward regression analysis including all potential factors indicated a statistically significant model for platform DMT (R2 = 0.55; 95%-CI [0.28, 0.82]; p=0.001) revealing GDP as the main contributor. This was confirmed in the independent analysis.

Conclusion

This study illustrates that even without overt drug prescription inequity, access to medication is not evenly distributed and depends on economic strength and regional medical care density.
A natural vertical distribution calculation scheme for salinity simulation in free-surface model with quasi-stationary coordinates
Authors: Li Yundong , Han Guijun , Li Wei , Wu Xiaobo , Cao Lige , Zhou Gongfu
Published: August 2024

Introduction

Salinity is a key variable in the dynamic and thermal balance of the entire climate system. To address the complexities of diverse terrains and fluctuating ocean waves, we commonly use free-surface models with quasi-stationary (e.g. height, pressure, or terrain following) coordinates for simulating salinity. In such models, the vertical grid dynamically adjusts with the undulation of seawater. However, this adjustment also occurs when freshwater enters or exits the ocean. Freshwater-induced salinity changes at the ocean’s surface are artificially distributed to each vertical layer within a model time step. This means that the freshwater at the ocean surface instantaneously and directly affects the seafloor. This process is different from physical diffusion processes. The diffusion effects caused by the influx and outflow of freshwater have a very small impact on the seafloor. This error leads to salinity non-conservation and disrupts the vertical distribution structure of salinity. Previous studies have also addressed this issue with solutions such as the vertical Lagrangian-remap method.

Method

This paper proposes a natural vertical distribution calculation scheme (NVDCS) which is different from the approaches of our predecessors. In the discrete formulation of the original ocean equations, freshwater flux is introduced to ensure salinity conservation. In each model time step, by calculating the seawater volume changes due to freshwater inflow or outflow, as well as the vertical grid changes caused by sea surface undulations, the aforementioned artificial error is eliminated from each vertical layer.

Discussion

This scheme ensures that changes in the vertical coordinates of each layer result solely from internal oceanic dynamic processes, avoiding the instantaneous and directly impact of surface freshwater. Ultimately, the influence of freshwater is confined to the ocean surface.

Results

This method is straightforward to implement and user-friendly. Sensitivity experiments indicate that in free-surface models, quasi-stationary coordinates introduce artificial errors. The proposed calculation scheme not only eliminates this error but also achieves a better vertical distribution structure than using virtual salt flux, while ensuring salinity conservation.
Modelling the bottom-up effects of climate change on primary production in the Gulf of St. Lawrence and eastern Scotian Shelf
Authors: Mei Zhi-Ping , Lavoie Diane , Lambert Nicolas , Starr Michel , Chassé Joël , Perrie William , Long Zhenxia
Published: August 2024

The Gulf of St. Lawrence (GSL), along with the St. Lawrence Estuary, is the largest estuarine system in North America. It is a biologically productive sea and an important fishing ground in Canada. The objectives of this study are to determine how climate changes will affect primary production in the GSL and on the eastern Scotian Shelf, and to determine the drivers of the changes. We use a regional ocean model forced with downscaled output of the Max-Planck Institute Earth System Model to study the changes in net primary production under the climate change scenario of Representative Concentration Pathway 8.5 (RCP8.5). Results reveal a projected 13.4% decrease in annual primary production across the GSL system over the next 70 years. This decline primarily stems from reduced nutrient concentrations in the upper layer, despite the increase in nutrients supplied by rivers. Enhanced freshwater influx and ocean surface warming contribute to heightened stratification, that in turn reduce the vertical nutrient fluxes from deeper layers. This mechanism affects the upwelling of nutrient-rich water at the head of the Laurentian Channel in the Lower St. Lawrence Estuary, leading to a 22% reduction in the vertical nitrate flux in the future. Additionally, nutrient concentrations in the water masses entering the GSL at the Strait of Belle Isle and at Cabot Strait are also reduced. Due to declining sea-ice concentration, the phytoplankton bloom is expected to occur between 9 and 23 days earlier under a warmer climate, and last for up to 24 days longer, depending on the GSL subregions, compared to the historical period (2001-2020). Biological productivity at higher trophic levels, and thus fisheries productivity, could be negatively impacted under the RCP8.5 climate change scenario.