bluuebunny/crossref_metadata_2025 huggingface dataset:
Hilbert mathematics versus Gödel mathematics III. Hilbert mathematics by itself, and Gödel mathematics versus the physical world within it: both as its particular cases
Authors: Penchev Vasil
Published: April 2023

The paper discusses Hilbert mathematics, a kind of Pythagorean mathematics, to which the physical world is a particular case. The parameter of the “distance between finiteness and infinity” is crucial. Any nonzero finite value of it features the particular case in the frameworks of Hilbert mathematics where the physical world appears “ex nihilo” by virtue of an only mathematical necessity or quantum information conservation physically. One does not need the mythical Big Bang which serves to concentrate all the violations of energy conservation in a “safe”, maximally remote point in the alleged “beginning of the universe”. On the contrary, an omnipresent and omnitemporal medium obeying quantum information conservation rather than energy conservation permanently generates action and thus the physical world. The utilization of that creation “ex nihilo” is accessible to humankind, at least theoretically, as long as one observes the physical laws, which admit it in their new generalization
Membangun Rantai Pasok Anti Rapuh: Perspektif Pelaku UMKM
Authors: Diah Ayu Septi Fauji  , Sudarmiatin  , Agus Hermawan
Published: April 2023

This study aims to find ways to build an anti-fragile supply chain based on the perspective of SMEs in Kediri Regency. This research conducts observations on phenomena intensively and is practice-oriented using case study qualitative methods. The findings of the theme show that the character of MSME actors who master the fields, language, art of communication, can establish closeness with customers through interaction, reduce dependence on suppliers and the willingness to grow in uncertainty and/or disruption are the keys for MSMEs to be able to build and manage anti-corruption supply chains fragile.

 

Abstrak

Penelitian ini bertujuan untuk menemukan cara membangun rantai pasok anti rapuh berdasarkan perspektif UMKM yang ada di Kabupaten Kediri. Penelitian ini melakukan pengamatan pada fenomena secara intensif dan berorientasi pada praktik (practice oriented research) menggunakan metode kualitatif studi kasus. Adapun hasil temuan tema menunjukkan bahwa karakter pelaku UMKM yang menguasai bidang, bahasa, seni berkomunikasi, dapat menjalin kedekatan dengan pelanggan melalui interaksi, mengurangi ketergantungan dengan pemasok serta kemauan untuk bertumbakuh dalam ketidakpastian dan/ gangguan menjadi kunci UMKM dapat membangun dan mengelola rantai pasok yang anti rapuh.
Projeto político pedagógico (PPP): a necessária gestão democrática em sua elaboração e/ou reformulação
Authors: Santana Junior Neto , Mataruco Sonia Maria Crivelli
Published: April 2023

O objetivo do presente estudo consiste em analisar o quanto importante é a gestão democrática na elaboração e/ou reformulação do Projeto Político Pedagógico (PPP), considerando ser um grande subsídio para qualidade do ensino. Partimos do princípio que tratar desse assunto apresenta ser relevante, pois infelizmente na maioria dos estabelecimentos de ensino, o tratado com o PPP acaba ficando a cargo do(a) pedagogo(a), secundarizando assim a necessidade de dar voz e vez aos demais envolvidos no processo educacional. Sobretudo, a discussão pode promover inquietações nos leitores, que por sua vez, poderão realizar outros estudos a respeito e assim subsidiar a superação da problemática já citada. Para tanto, o mesmo consiste em uma pesquisa qualitativa e exploratória, correspondente a uma revisão bibliográfica, no qual, nos amparamos em Araújo (2000), Libâneo (2004), Veiga (2009), entre outros autores que discutem o tema. Ademais, também inclui uma análise documental, haja visto, as bases legais do PPP preconizadas nas políticas educacionais, como a Lei de Diretrizes e Bases da Educação (LDB). Elaborar e/ou reformular o PPP mediante o trabalho coletivo e participativo, implica de fato subsidiar uma educação de qualitativa e por via compreendida por todos da comunidade escolar.
O lúdico como instrumento significativo na qualidade de ensino de crianças da educação infantil com transtorno de déficit de atenção e hiperatividade
Authors: Vitoriano Matilde
Published: April 2023

O presente trabalho busca demonstrar que o lúdico na aprendizagem das crianças, da educação infantil, com Transtorno de Déficit de Atenção e Hiperatividade pode ser de suma importância para a aprendizagem, bem como servir de estímulo para desenvolver o gosto pela aprendizagem. Tendo o professor o conhecimento da criança, pode perceber as suas limitações e criar estratégias que ajudem a amenizar essas dificuldades. Assim cabe a escola promover um ensino de qualidade, independentemente de suas dificuldades, procurando juntamente com os educadores instituir estratégias que auxiliem na compreensão dos conteúdos. O lúdico na aprendizagem desenvolve o lado emocional, cognitivo e psicomotor por meio da magia, do que diz respeito a brincadeira, com aqueles que reconhecem sua importância e contribuição para um melhor futuro.
The role of hearing professionals for over-the-counter hearing aids
Authors: Perez-Heydrich Carlos A. , Zenczak Colleen , Roque Lindsey , Ryan Colleen , Agrawal Yuri , Sayyid Zahra N.
Published: April 2023

Adults with all levels of hearing loss have faced financial and accessibility constraints in obtaining prescription hearing aids. To increase access to hearing aids, the Food and Drug Administration (FDA) has created a new designation of over-the-counter (OTC) hearing aids for adults with perceived mild to moderate hearing loss. The goal of this article is to describe the incorporation of OTC hearing aid users into established audiology services. A proposed workflow was created by otolaryngologists and audiologists at Johns Hopkins University School of Medicine and is being implemented at outpatient audiology offices. We used published criteria for appropriate OTC hearing aid usage and disqualifying criteria hearing specialists should be aware of. The proposed workflow describes the multiple entry points for OTC hearing aid users seeking access to care and appropriate objectives for these visits. The new FDA ruling has increased the accessibility of hearing assistance devices; however, the varying degrees of retailer support systems could lead to improper fitting and other technical problems for some patients trialing new hearing aids. Our proposed workflow aims to describe the incorporation of established hearing assistance services with the new OTC hearing aid market.
Human induced pluripotent stem cells (hiPSC), enveloped in elastin-like recombinamers for cell therapy of type 1 diabetes mellitus (T1D): preliminary data
Authors: Montanucci Pia , Pescara Teresa , Greco Alessia , Basta Giuseppe , Calafiore Riccardo
Published: April 2023

Introduction: Therapeutic application and study of type 1 diabetes disease could benefit from the use of functional β islet-like cells derived from human induced pluripotent stem cells (hiPSCs). Considerable efforts have been made to develop increasingly effective hiPSC differentiation protocols, although critical issues related to cost, the percentage of differentiated cells that are obtained, and reproducibility remain open. In addition, transplantation of hiPSC would require immunoprotection within encapsulation devices, to make the construct invisible to the host’s immune system and consequently avoid the recipient’s general pharmacologic immunosuppression.

Methods: For this work, a microencapsulation system based on the use of “human elastin-like recombinamers” (ELRs) was tested to envelop hiPSC. Special attention was devoted to in vitro and in vivo characterization of the hiPSCs upon coating with ERLs.

Results and Discussion: We observed that ELRs coating did not interfere with viability and function and other biological properties of differentiated hiPSCs, while in vivo, ELRs seemed to afford immunoprotection to the cell grafts in preliminary in vivo study. The construct ability to correct hyperglycemia in vivo is in actual progress.
Electrochemical degradation of surfactants in domestic wastewater using a DiaClean® cell equipped with a boron-doped diamond electrode
Authors: Cisneros-León Dayana G. , Espinoza-Montero Patricio J. , Bolaños-Mendez Diego , Alvarez-Paguay Jocelyne , Fernández Lenys , Saavedra-Alulema Pablo F. , Lopez Kelly , Astorga Diana , Piñeiros José Luis
Published: April 2023

Treating domestic wastewater has become more and more complicated due to the high content of different types of detergents. In this context, advanced electro-oxidation (AEO) has become a powerful tool for complex wastewater remediation. The electrochemical degradation of surfactants present in domestic wastewater was carried out using a DiaClean® cell in a recirculation system equipped with boron-doped diamond (BDD) as the anode and stainless steel as the cathode. The effect of recirculation flow (1.5, 4.0 and 7.0 L min−1) and the applied current density (j = 7, 14, 20, 30, 40, and 50 mA cm−2) was studied. The degradation was followed by the concentration of surfactants, chemical oxygen demand (COD), and turbidity. pH value, conductivity, temperature, sulfates, nitrates, phosphates, and chlorides were also evaluated. Toxicity assays were studied through evaluating Chlorella sp. performance at 0, 3, and 7 h of treatment. Finally, the mineralization was followed by total organic carbon (TOC) under optimal operating conditions. The results showed that applying j = 14 mA cm−2 and a flow rate of 1.5 L min−1 during 7 h of electrolysis were the best conditions for the efficient mineralization of wastewater, achieving the removal of 64.7% of surfactants, 48.7% of COD, 24.9% of turbidity, and 44.9% of mineralization analyzed by the removal of TOC. The toxicity assays showed that Chlorella microalgae were unable to grow in AEO-treated wastewater (cellular density: 0 × 104 cells ml−1 after 3- and 7-h treatments). Finally, the energy consumption was analyzed, and the operating cost of 1.40 USD m−3 was calculated. Therefore, this technology allows for the degradation of complex and stable molecules such as surfactants in real and complex wastewater, if toxicity is not taken into account.
Different regulatory mechanisms of the capsule in hypervirulent Klebsiella pneumonia: “direct” wcaJ variation vs. “indirect” rmpA regulation
Authors: Wang Weiwen , Tian Dongxing , Hu Dakang , Chen Wenjie , Zhou Ying , Jiang Xiaofei
Published: April 2023

Introduction

Hypervirulent Klebsiella pneumoniae produce an increased amount of capsular substance and are associated with a hypermucoviscous phenotype. Capsule production is regulated by capsular regulatory genes and capsular gene cluster variations. In the present study, we focus on the effect of rmpA and wcaJon capsule biosynthesis.

Methods

Phylogenetic trees were constructed to analyze wcaJ and rmpA sequence diversity in different serotypes hypervirulent strains. Then mutant strains (K2044ΔwcaJ, K2044K1wcaJ, K2044K2wcaJand K2044K64wcaJ) were used to verify the effects of wcaJ and its diversity on capsule synthesis and strain virulence. Furthmore, the role of rmpA in capsular synthesis and its mechanisms were detected in K2044ΔrmpA strain.

Results

RmpA sequences are conversed in different serotypes. And rmpA promoted the production of hypercapsules by simultaneously acting on three promoters in cps cluster. Whereas wcaJ, its sequences are different in different serotypes, and its loss result in the termination of capsular synthesis. Moreover, the results verified that K2 wcaJ could form hypercapsule in K2044 strains (K1 serotype), but K64 wcaJ could not.

Discussion

The interaction of multiple factors is involved in capsule synthesis, including wcaJ and rmpA. RmpA, an known conserved capsular regulator gene, acts on cps cluster promoters to promote the production of the hypercapsule. WcaJ as initiating enzyme of CPS biosynthesis, its presence determines the synthesis of capsule. Besides, different from rmpA, wcaJ sequence consistency is limited to the same serotype, which cause wcaJ functioning in different serotype strains with sequence recognition specificity.
Epithelial immune activation and intracellular invasion by non-typeable Haemophilus influenzae
Authors: Brown Mary A. , Morgan Sophie B. , Donachie Gillian E. , Horton Katie L. , Pavord Ian D. , Arancibia-Cárcamo Carolina V. , Hinks Timothy S. C.
Published: April 2023

Type-2 low asthma affects 30-50% of people with severe asthma and includes a phenotype characterized by sputum neutrophilia and resistance to corticosteroids. Airways inflammation in type-2 low asthma or COPD is potentially driven by persistent bacterial colonization of the lower airways by bacteria such as non-encapsulated Haemophilus influenzae (NTHi). Although pathogenic in the lower airways, NTHi is a commensal of the upper airways. It is not known to what extent these strains can invade airway epithelial cells, persist intracellularly and activate epithelial cell production of proinflammatory cytokines, and how this differs between the upper and lower airways. We studied NTHi infection of primary human bronchial epithelial cells (PBECs), primary nasal epithelial cells (NECs) and epithelial cell lines from upper and lower airways. NTHi strains differed in propensity for intracellular and paracellular invasion. We found NTHi was internalized within PBECs at 6 h, but live intracellular infection did not persist at 24 h. Confocal microscopy and flow cytometry showed NTHi infected secretory, ciliated and basal PBECs. Infection of PBECs led to induction of CXCL8, interleukin (IL)-1β, IL-6 and TNF. The magnitude of cytokine induction was independent of the degree of intracellular invasion, either by differing strains or by cytochalasin D inhibition of endocytosis, with the exception of the inflammasome-induced mediator IL-1β. NTHi-induced activation of TLR2/4, NOD1/2 and NLR inflammasome pathways was significantly stronger in NECs than in PBECs. These data suggest that NTHi is internalized transiently by airway epithelial cells and has capacity to drive inflammation in airway epithelial cells.
Gut microbiota and cardiac arrhythmia
Authors: Fan Hongxuan , Liu Xuchang , Ren Zhaoyu , Fei Xiaoning , Luo Jing , Yang Xinyu , Xue Yaya , Zhang Fenfang , Liang Bin
Published: April 2023

One of the most prevalent cardiac diseases is cardiac arrhythmia, however the underlying causes are not entirely understood. There is a lot of proof that gut microbiota (GM) and its metabolites have a significant impact on cardiovascular health. In recent decades, intricate impacts of GM on cardiac arrythmia have been identified as prospective approaches for its prevention, development, treatment, and prognosis. In this review, we discuss about how GM and its metabolites might impact cardiac arrhythmia through a variety of mechanisms. We proposed to explore the relationship between the metabolites produced by GM dysbiosis including short-chain fatty acids(SCFA), Indoxyl sulfate(IS), trimethylamine N-oxide(TMAO), lipopolysaccharides(LPS), phenylacetylglutamine(PAGln), bile acids(BA), and the currently recognized mechanisms of cardiac arrhythmias including structural remodeling, electrophysiological remodeling, abnormal nervous system regulation and other disease associated with cardiac arrythmia, detailing the processes involving immune regulation, inflammation, and different types of programmed cell death etc., which presents a key aspect of the microbial-host cross-talk. In addition, how GM and its metabolites differ and change in atrial arrhythmias and ventricular arrhythmias populations compared with healthy people are also summarized. Then we introduced potential therapeutic strategies including probiotics and prebiotics, fecal microbiota transplantation (FMT) and immunomodulator etc. In conclusion, the GM has a significant impact on cardiac arrhythmia through a variety of mechanisms, offering a wide range of possible treatment options. The discovery of therapeutic interventions that reduce the risk of cardiac arrhythmia by altering GM and metabolites is a real challenge that lies ahead.
3D histopathology of stenotic aortic valve cusps using ex vivo microfocus computed tomography
Authors: Pestiaux Camille , Pyka Grzegorz , Quirynen Louise , De Azevedo David , Vanoverschelde Jean-Louis , Lengelé Benoît , Vancraeynest David , Beauloye Christophe , Kerckhofs Greet
Published: April 2023

Background

Calcific aortic stenosis (AS) is the most prevalent heart valve disease in developed countries. The aortic valve cusps progressively thicken and the valve does not open fully due to the presence of calcifications. In vivo imaging, usually used for diagnosis, does not allow the visualization of the microstructural changes associated with AS.

Methods

Ex vivo high-resolution microfocus computed tomography (microCT) was used to quantitatively describe the microstructure of calcified aortic valve cusps in full 3D. As case study in our work, this quantitative analysis was applied to normal-flow low-gradient severe AS (NF-LG-SAS), for which the medical prognostic is still highly debated in the current literature, and high-gradient severe AS (HG-SAS).

Results

The volume proportion of calcification, the size and number of calcified particles and their density composition was quantified. A new size-based classification considering small-sized particles that are not detected with in vivo imaging was defined for macro-, meso- and microscale calcifications. Volume and thickness of aortic valve cusps, including the complete thickness distribution, were also determined. Moreover, changes in the cusp soft tissues were also visualized with microCT and confirmed by scanning electron microscopy images of the same sample. NF-LG-SAS cusps contained lower relative amount of calcifications than HG-SAS. Moreover, the number and size of calcified objects and the volume and thickness of the cusps were also lower in NF-LG-SAS cusps than in HG-SAS.

Conclusions

The application of high-resolution ex vivo microCT to stenotic aortic valve cusps provided a quantitative description of the general structure of the cusps and of the calcifications present in the cusp soft tissues. This detailed description could help in the future to better understand the mechanisms of AS.
Relationship between weight-adjusted-waist index and erectile dysfunction in the United State: results from NHANES 2001-2004
Authors: Cao Shangqi , Hu Xu , Shao Yanxiang , Wang Yaohui , Tang Yaxiong , Ren Shangqing , Li Xiang
Published: April 2023

Objective

The purpose of this study is to examine the association between a novel adiposity parameter, the weight-adjusted-waist index (WWI), and erectile dysfunction (ED).

Methods

According to National Health and Nutrition Examination Survey (NHANES) 2001-2004, a total of 3884 participants were categorized as ED and non-ED individuals. WWI was calculated as waist circumference (WC, cm) divided by the square root of weight (kg). Weighted univariable and multivariable logistic regression models were conducted to assess the correlation between WWI and ED. Smooth curve fitting was utilized to examine the linear association. The receiver operating characteristic (ROC) curve and DeLong et al.’s test were applied to compare the area under curve (AUC) value and predictive power among WWI, body mass index (BMI), and WC for ED.

Results

WWI was positively related to ED with the full adjustment [odds ratio (OR)=1.75, 95% confidence interval (95% CI): 1.32-2.32, p=0.002]. After converting WWI to a categorical variable by quartiles (Q1-Q4), compared to Q1 the highest WWI quartile was linked to an obviously increased likelihood of ED (OR=2.78, 95% CI: 1.39-5.59. p=0.010). Subgroup analysis revealed the stability of the independent positive relationship between WWI and ED. It was shown that WWI had a stronger prediction for ED (AUC=0.745) than BMI (AUC=0.528) and WC (AUC=0.609). Sensitivity analysis was performed to verify the significantly positive connection between WWI and stricter ED (OR=2.00, 95% CI: 1.36-2.94, p=0.003).

Conclusion

An elevated WWI was related to higher risks of ED in the United State adults, and a stronger predictive power of WWI for ED was observed than BMI and WC.
Intraperitoneal metastasis of ovarian cancer: new insights on resident macrophages in the peritoneal cavity
Authors: Miyamoto Taito , Murphy Brennah , Zhang Nan
Published: April 2023

Ovarian cancer metastasis occurs primarily in the peritoneal cavity. Orchestration of cancer cells with various cell types, particularly macrophages, in the peritoneal cavity creates a metastasis-favorable environment. In the past decade, macrophage heterogeneities in different organs as well as their diverse roles in tumor settings have been an emerging field. This review highlights the unique microenvironment of the peritoneal cavity, consisting of the peritoneal fluid, peritoneum, and omentum, as well as their own resident macrophage populations. Contributions of resident macrophages in ovarian cancer metastasis are summarized; potential therapeutic strategies by targeting such cells are discussed. A better understanding of the immunological microenvironment in the peritoneal cavity will provide a stepping-stone to new strategies for developing macrophage-based therapies and is a key step toward the unattainable eradication of intraperitoneal metastasis of ovarian cancer.
Microbiome analysis of Brazilian women cervix reveals specific bacterial abundance correlation to RIG-like receptor gene expression
Authors: Britto Alan Messala A. , Siqueira Juliana D. , Curty Gislaine , Goes Livia R. , Policarpo Cintia , Meyrelles Angela R. , Furtado Yara , Almeida Gutemberg , Giannini Ana Lucia M. , Machado Elizabeth S. , Soares Marcelo A.
Published: April 2023

The relationship among microbiome, immunity and cervical cancer has been targeted by several studies, yet many questions remain unanswered. We characterized herein the virome and bacteriome from cervical samples and correlated these findings with innate immunity gene expression in a Brazilian convenience sample of HPV-infected (HPV+) and uninfected (HPV-) women. For this purpose, innate immune gene expression data were correlated to metagenomic information. Correlation analysis showed that interferon (IFN) is able to differentially modulate pattern recognition receptors (PRRs) expression based on HPV status. Virome analysis indicated that HPV infection correlates to the presence of Anellovirus (AV) and seven complete HPV genomes were assembled. Bacteriome results unveiled that vaginal community state types (CST) distribution was independent of HPV or AV status, although bacterial phyla distribution differed between groups. Furthermore, TLR3 and IFNαR2 levels were higher in the Lactobacillus no iners-dominated mucosa and we detected correlations among RIG-like receptors (RLR) associated genes and abundance of specific anaerobic bacteria. Collectively, our data show an intriguing connection between HPV and AV infections that could foster cervical cancer development. Besides that, TLR3 and IFNαR2 seem to create a protective milieu in healthy cervical mucosa (L. no iners-dominated), and RLRs, known to recognize viral RNA, were correlated to anaerobic bacteria suggesting that they might be related to dysbiosis.
CD73 mediated host purinergic metabolism in intestine contributes to the therapeutic efficacy of a novel mesenchymal-like endometrial regenerative cells against experimental colitis
Authors: Shao Bo , Ren Shao-hua , Wang Zhao-bo , Wang Hong-da , Zhang Jing-yi , Qin Hong , Zhu Yang-lin , Sun Cheng-lu , Xu Yi-ni , Li Xiang , Wang Hao
Published: April 2023

Background

The disruption of intestinal barrier functions and the dysregulation of mucosal immune responses, mediated by aberrant purinergic metabolism, are involved in the pathogenesis of inflammatory bowel diseases (IBD). A novel mesenchymal-like endometrial regenerative cells (ERCs) has demonstrated a significant therapeutic effect on colitis. As a phenotypic marker of ERCs, CD73 has been largely neglected for its immunosuppressive function in regulating purinergic metabolism. Here, we have investigated whether CD73 expression on ERCs is a potential molecular exerting its therapeutic effect against colitis.

Methods

ERCs either unmodified or with CD73 knockout (CD73-/-ERCs), were intraperitoneally administered to dextran sulfate sodium (DSS)-induced colitis mice. Histopathological analysis, colon barrier function, the proportion of T cells, and maturation of dendritic cells (DCs) were investigated. The immunomodulatory effect of CD73-expressing ERCs was evaluated by co-culture with bone marrow-derived DCs under LPS stimulation. FACS determined DCs maturation. The function of DCs was detected by ELISA and CD4+ cell proliferation assays. Furthermore, the role of the STAT3 pathway in CD73-expressing ERCs-induced DC inhibition was also elucidated.

Results

Compared with untreated and CD73-/-ERCs-treated groups, CD73-expressing ERCs effectively attenuated body weight loss, bloody stool, shortening of colon length, and pathological damage characterized by epithelial hyperplasia, goblet cell depletion, the focal loss of crypts and ulceration, and the infiltration of inflammatory cells. Knockout of CD73 impaired ERCs-mediated colon protection. Surprisingly, CD73-expressing ERCs significantly decreased the populations of Th1 and Th17 cells but increased the proportions of Tregs in mouse mesenteric lymph nodes. Furthermore, CD73-expressing ERCs markedly reduced the levels of pro-inflammatory cytokines (IL-6, IL-1β, TNF-α) and increased anti-inflammatory factors (IL-10) levels in the colon. CD73-expressing ERCs inhibited the antigen presentation and stimulatory function of DCs associated with the STAT-3 pathway, which exerted a potent therapeutic effect against colitis.

Conclusions

The knockout of CD73 dramatically abrogates the therapeutic ability of ERCs for intestinal barrier dysfunctions and the dysregulation of mucosal immune responses. This study highlights the significance of CD73 mediates purinergic metabolism contributing to the therapeutic effects of human ERCs against colitis in mice.
PM10 promotes an inflammatory cytokine response that may impact SARS-CoV-2 replication in vitro
Authors: Marín-Palma Damariz , Tabares-Guevara Jorge H. , Zapata-Cardona María I. , Zapata-Builes Wildeman , Taborda Natalia , Rugeles Maria T. , Hernandez Juan C.
Published: April 2023

Introduction

In the last decades, a decrease in air quality has been observed, mainly associated with anthropogenic activities. Air pollutants, including particulate matter (PM), have been associated with adverse effects on human health, such as exacerbation of respiratory diseases and infections. High levels of PM in the air have recently been associated with increased morbidity and mortality of COVID-19 in some regions of the world.

Objective

To evaluate the effect of coarse particulate matter (PM10) on the inflammatory response and viral replication triggered by SARS-CoV-2 using in vitro models.

Methods

Peripheral blood mononuclear cells (PBMC) from healthy donors were treated with PM10 and subsequently exposed to SARS-CoV-2 (D614G strain, MOI 0.1). The production of pro-inflammatory cytokines and antiviral factors was quantified by qPCR and ELISA. In addition, using the A549 cell line, previously exposed to PM, the viral replication was evaluated by qPCR and plaque assay.

Results

SARS-CoV-2 stimulation increased the production of pro-inflammatory cytokines in PBMC, such as IL-1β, IL-6 and IL-8, but not antiviral factors. Likewise, PM10 induced significant production of IL-6 in PBMCs stimulated with SARS-CoV-2 and decreased the expression of OAS and PKR. Additionally, PM10 induces the release of IL-1β in PBMC exposed to SARS-CoV-2 as well as in a co-culture of epithelial cells and PBMCs. Finally, increased viral replication of SARS-CoV-2 was shown in response to PM10.

Conclusion

Exposure to coarse particulate matter increases the production of pro-inflammatory cytokines, such as IL-1β and IL-6, and may alter the expression of antiviral factors, which are relevant for the immune response to SARS-CoV-2. These results suggest that pre-exposure to air particulate matter could have a modest role in the higher production of cytokines and viral replication during COVID-19, which eventually could contribute to severe clinical outcomes.
Functional lung imaging using novel and emerging MRI techniques
Authors: Foo Chuan T. , Langton David , Thompson Bruce R. , Thien Francis
Published: April 2023

Respiratory diseases are leading causes of death and disability in the world. While early diagnosis is key, this has proven difficult due to the lack of sensitive and non-invasive tools. Computed tomography is regarded as the gold standard for structural lung imaging but lacks functional information and involves significant radiation exposure. Lung magnetic resonance imaging (MRI) has historically been challenging due to its short T2 and low proton density. Hyperpolarised gas MRI is an emerging technique that is able to overcome these difficulties, permitting the functional and microstructural evaluation of the lung. Other novel imaging techniques such as fluorinated gas MRI, oxygen-enhanced MRI, Fourier decomposition MRI and phase-resolved functional lung imaging can also be used to interrogate lung function though they are currently at varying stages of development. This article provides a clinically focused review of these contrast and non-contrast MR imaging techniques and their current applications in lung disease.
Assessment of aggregate index of systemic inflammation and systemic inflammatory response index in dry age-related macular degeneration: a retrospective study
Authors: Sannan Naif S.
Published: April 2023

Introduction

Inflammation is known to contribute to the development of age-related macular degeneration (AMD). Several inflammatory indices derived from routine complete blood counts have been proposed as biomarkers in multiple disorders.

Methods

In this study, clinical and laboratory data were retrospectively collected from medical records to assess the aggregate index of systemic inflammation (AISI) and the systemic inflammatory response index (SIRI) as potential biomarkers of systemic inflammation in patients with early diagnosis of dry AMD.

Results

The study included 90 patients with dry AMD and 270 age/sex-matched patients with cataracts as a control group. There were no significant differences in the AISI and SIRI results between the cases and controls (p = 0.16 and 0.19, respectively).

Conclusion

This suggests that AISI and SIRI may be inadequate metrics for AMD or lack sensitivity in detecting inflammatory changes. Exploring other routine blood markers may help to identify and prevent the early stages of AMD.
Gastric juice microbiota in pediatric chronic gastritis that clinically tested positive and negative for Helicobacter pylori
Authors: Chen Ying , Xia Shou-Yue , Ru Fu-Xia , Feng Jun-Jie , Tao Ji , Wei Zhi-Yuan , Li Xiu , Qian Chengjia , Lin Qiong , Chen Jian-Huan
Published: April 2023

Purpose

Helicobacter pylori (HP) infection is an identified risk factor for pediatric chronic gastritis (PCG), but its impact on gastric juice microbiota (GJM) remains to be further elucidated in PCG. This study aimed to analyze and compare the microbial communities and microbial interactive networks of GJM in PCG that clinically tested positive and negative for HP (HP+ and HP−, respectively).

Methods

A total of 45 PCG patients aged from 6 to 16 years were recruited, including 20 HP+ and 25 HP− patients tested by culture and rapid urease test. Gastric juice samples were collected from these PCG patients and subjected to high-throughput amplicon sequencing and subsequent analysis of 16S rRNA genes.

Results

While no significant change in alpha diversity, significant differences in beta diversity were observed between HP+ and HP− PCG. At the genus level, Streptococcus, Helicobacter, and Granulicatella were significantly enriched in HP+ PCG, whereas Campylobacter and Absconditabacteriales (SR1) were significantly enriched in HP− PCG. Network analysis showed that Streptococcus was the only genus positively correlated with Helicobacter (r = 0.497) in the GJM network of overall PCG. Moreover, compared to HP− PCG, HP+ PCG showed a reduction in microbial network connectivity in GJM. Netshift analysis identified driver microbes including Streptococcus and other four genera, which substantially contributed to the GJM network transition from HP− PCG to HP+ PCG. Furthermore, Predicted GJM function analysis indicated up-regulated pathways related to the metabolism of nucleotides, carbohydrates, and L-Lysine, the urea cycle, as well as endotoxin peptidoglycan biosynthesis and maturation in HP+ PCG.

Conclusion

GJM in HP+ PCG exhibited dramatically altered beta diversity, taxonomic structure, and function, with reduced microbial network connectivity, which could be involved in the disease etiology.
Assessing Acanthamoeba cytotoxicity: comparison of common cell viability assays
Authors: Loufouma Mbouaka Alvie , Lesiak-Markowicz Iwona , Heredero-Bermejo Irene , Mazumdar Rounik , Walochnik Julia , Martín-Pérez Tania
Published: April 2023

Background

In vitro models for studying interactions between Acanthamoeba and host cells are crucial for understanding the pathomechanism of Acanthamoeba and assessing differences between strains and cell types. The virulence of Acanthamoeba strains is usually assessed and monitored by using cell cytotoxicity assays. The aim of the present study was to evaluate and compare the most widely used cytotoxicity assays for their suitability to assess Acanthamoeba cytopathogenicity.

Methods

The viability of human corneal epithelial cells (HCECs) after co-culture with Acanthamoeba was evaluated in phase contrast microscopy.

Results

It was shown that Acanthamoeba is unable to considerably reduce the tetrazolium salt and the NanoLuc® Luciferase prosubstrate to formazan and the luciferase substrate, respectively. This incapacity helped to generate a cell density-dependent signal allowing to accurately quantify Acanthamoeba cytotoxicity. The lactate dehydrogenase (LDH) assay led to an underestimation of the cytotoxic effect of Acanthamoeba on HCECs since their co-incubation negatively affected the lactate dehydrogenase activity.

Discussion

Our findings demonstrate that cell-based assays using the aqueous soluble tetrazolium-formazan, and the NanoLuc® Luciferase prosubstrate products, in contrast to LDH, are excellent markers to monitor the interaction of Acanthamoeba with human cell lines and to determine and quantify effectively the cytotoxic effect induced by the amoebae. Furthermore, our data indicate that protease activity may have an impact on the outcome and thus the reliability of these tests.
Surface EMG analysis of weakness distribution in upper limb muscles post-stroke
Authors: Lv Wenwen , Liu Kai , Zhou Ping , Huang Fei , Lu Zhiyuan
Published: April 2023

Weakness is a common symptom after a stroke. This study aims to depict weakness distribution among forearm muscles given that joints in the upper limb are usually driven by a group of muscles. Multi-channel electromyography (EMG) was applied to assess the muscle group, and an EMG-based index was proposed to quantify the weakness of individual muscles. By using this method, four weakness distribution patterns were observed in extensor muscles from five out of eight subjects after stroke. Complex weakness distribution patterns were observed in flexor muscles from seven out of the eight subjects when they performed grasp, tripod pinch, and hook grip. The findings can help determine the weak muscles in a clinic and facilitate the development of appropriate interventions in stroke rehabilitation targeting specific muscle weakness.
Altered amide proton transfer weighted and diffusion signals in patients with multiple sclerosis: correlation with neurofilament light chain and disease duration
Authors: Huang Jing , Liang Yan , Shan Yi , Zhao Cheng , Li Qiongge , Shen Zhiwei , Dong Huiqing , Qi Zhigang , Lu Jie
Published: April 2023

Objectives

To compare the signal alterations of amide proton transfer (APT), apparent diffusion coefficient (ADC), and fractional anisotropy (FA) in white matter (WM) lesions in multiple sclerosis (MS), compared with healthy controls (HCs), and to investigate the relationships between these changes and clinical measurements such as serum neurofilament light chain (sNfL).

Materials and methods

Twenty-nine patients with relapsing-remitting MS (21 females and 8 males) and 30 HCs (23 females and 7 males) were recruited. APT-weighted (APTw) and diffusion tensor imaging (DTI) data were acquired using a 3.0-T magnetic resonance system. APTw and DTI images were registered to FLAIR-SPIR images and assessed by two neuroradiologists. MTRasym (3.5 ppm), ADC, FA values for MS and HC are calculated using mean values from all regions of interest (ROI). The ROI criteria were: (1) for MS patients, ROI were defined as MS lesions, and each lesion was identified. (2) The WM around each HC’s lateral ventricle (frontal lobe, parietal lobe, and centrum semiovale) was assessed bilaterally. The diagnostic efficacy of MTRasym (3.5 ppm), ADC, and FA in the lesions of MS patients was compared using receiver operating characteristic (ROC) curve analysis. The associations between MTRasym (3.5 ppm), ADC, and FA values and the clinical measurements were investigated further.

Results

The MTRasym (3.5 ppm) and ADC values of brain lesions were increased, while FA values were decreased in patients with MS. The diagnostic area under curve (AUC) of MTRasym (3.5 ppm), ADC, and FA value was 0.891 (95% CI: 0.813, 0.970), 0.761 (95% CI: 0.647, 0.875) and 0.970 (95% CI: 0.924, 1.0), respectively. sNfL was considerably positively correlated with MTRasym (3.5 ppm) (P = 0.043, R = 0.38) and disease durations were significantly negatively correlated with FA (P = 0.046, R = −0.37).

Conclusion

Amide proton transfer-weighted (APTw) and DTI are potential imaging methods for assessing brain lesions in patients with MS at the molecular and microscopic levels, respectively. The association between APTw, DTI parameters and clinical factors implies that they may play a role in disease damage monitoring.
Breast cancer: a randomized controlled trial assessing the effect of a decision aid on mammography screening uptake: study protocol
Authors: Hild Sandrine , Teigné Delphine , Ferrat Emilie , Banaszuk Anne-Sophie , Berquet Karine , Lebon Aline , Bataille Emmanuelle , Nanin France , Gaultier Aurélie , Rat Cédric
Published: April 2023

Introduction

Breast cancer (BC) is the primary cancer among women. The World Health Organization recommends a bilateral screening mammogram every 2 years for women aged 50 to 74 years. However, it has been shown that there is an absence of information about the benefits and risks of screening. Shared medical decision-making is important to ensure patients are involved in the decision process. Decision aids can facilitative this decision-making process. This article presents a protocol to evaluate the effect of a decision aid on participation rates in the French organized BC screening program.

Methods and analysis

Design and setting. The design is a 2 arm randomized controlled study, performed in the Pays de la Loire region (French West Coast). Randomization will be based on general medicine practices (Primary Care).

Participants

Women aged between 50 and 74 years, eligible for BC screening. In this region, there are 75000 women, and 2800 general practitioners eligible for recruitment.

Intervention

In the « Decision aid for organized cancer screening » arm, the intervention will distribute invitation letters to eligible women combined with the provision of decision aid to these women and their general practitioners and an incentive to implement shared medical decision-making. In the « Standard organized cancer screening » arm, only the screening invitation will be sent to eligible women.

Primary endpoint

BC screening participation rates will be assessed after an 18-month follow-up period.

Statistical analysis

In this non-inferiority trial, the percentage of women who are up-to-date with their screening at 18 months after the intervention will be compared across arms using a generalized mixed linear model.

Discussion

The research team expect to demonstrate that providing a better explanation of the benefits and risks of BC screening is not at odds with screening participation. The study results should help policy makers thinking about implementing shared medical decision-making within the framework of organized BC screening programs in the future.

Ethics and dissemination

On 6 December 2021, the protocol received a favorable opinion from the French Committee for the Protection of Persons (2021-A01583-38). This study is registered with ClinicalTrials.gov, number NCT05607849. (Version 1, November 7, 2022; https://www.clinicaltrials.gov/ct2/show/NCT05607849). The study findings will be used for publication in peer-reviewed scientific journals and presentations in scientific meetings.
The m6A methyltransferase METTL16 inhibits the proliferation of pancreatic adenocarcinoma cancer cells via the p21 signaling pathway
Authors: Xie Fuming , Zheng Yao , Fu Wen , Chi Bojing , Wang Xianxing , Zhang Junfeng , Gu Jianyou , Yin Jingyang , Zhou Qiang , Guo Shixiang , Cai Lei , Yang Jiali , Liu Songsong , Wang Huaizhi
Published: April 2023

Background

Many studies have reported that N6-methyladenosine (m6A) modification plays a critical role in the epigenetic regulation of organisms and especially in the pathogenesis of malignant diseases. However, m6A research has mainly focused on methyltransferase activity mediated by METTL3, and few studies have focused on METTL16. The aim of this study was to investigate the mechanism of METTL16, which mediates m6A modification, and its role in pancreatic adenocarcinoma (PDAC) cell proliferation.

Methods

Clinicopathologic and survival data were retrospectively collected from 175 PDAC patients from multiple clinical centers to detect the expression of METTL16. CCK-8, cell cycle, EdU and xenograft mouse model experiments were used to evaluate the proliferation effect of METTL16. Potential downstream pathways and mechanisms were explored via RNA sequencing, m6A sequencing, and bioinformatic analyses. Regulatory mechanisms were studied through methyltransferase inhibition, RIP, MeRIP‒qPCR assays.

Results

We found that METTL16 expression was markedly downregulated in PDAC, and multivariate Cox regression analyses revealed that METTL16 was a protective factor for PDAC patients. We also demonstrated that METTL16 overexpression inhibited PDAC cell proliferation. Furthermore, we identified a METTL16-p21 signaling axis, with downregulation of METTL16 resulting in inhibition of CDKN1A (p21). Additionally, METTL16 silencing and overexpression experiments highlighted m6A modification alterations in PDAC.

Conclusions

METTL16 plays a tumor-suppressive role and suppresses PDAC cell proliferation through the p21 pathway by mediating m6A modification. METTL16 may be a novel marker of PDAC carcinogenesis and target for the treatment of PDAC.
EB-OCT: a potential strategy on early diagnosis and treatment for lung cancer
Authors: Long Hang , Ji Jiaqi , Chen Lijuan , Feng Jiayue , Liao Jie , Yang Yang
Published: April 2023

Lung cancer is the leading cause of cancer-related death in China and the world, mainly attributed to delayed diagnosis, given that currently available early screening strategies exhibit limited value. Endobronchial optical coherence tomography (EB-OCT) has the characteristics of non-invasiveness, accuracy, and repeatability. Importantly, the combination of EB-OCT with existing technologies represents a potential approach for early screening and diagnosis. In this review, we introduce the structure and strengths of EB-OCT. Furthermore, we provide a comprehensive overview of the application of EB-OCT on early screening and diagnosis of lung cancer from in vivo experiments to clinical studies, including differential diagnosis of airway lesions, early screening for lung cancer, lung nodules, lymph node biopsy and localization and palliative treatment of lung cancer. Moreover, the bottlenecks and difficulties in developing and popularizing EB-OCT for diagnosis and treatment during clinical practice are analyzed. The characteristics of OCT images of normal and cancerous lung tissues were in good agreement with the results of pathology, which could be used to judge the nature of lung lesions in real time. In addition, EB-OCT can be used as an assistant to biopsy of pulmonary nodules and improve the success rate of biopsy. EB-OCT also plays an auxiliary role in the treatment of lung cancer. In conclusion, EB-OCT is non-invasive, safe and accurate in real-time. It is of great significance in the diagnosis of lung cancer and suitable for clinical application and is expected to become an important diagnostic method for lung cancer in the future.
Integrative analysis of metabolite and transcriptome reveals biosynthetic pathway and candidate genes for eupatilin and jaceosidin biosynthesis in Artemisia argyi
Authors: Lee Suhyeon , Won Hyo Jun , Ban Seunghyun , Park Yun Ji , Kim Sang Min , Kim Hyoung Seok , Choi Jaeyoung , Kim Ho-Youn , Lee Jae Hoon , Jung Je Hyeong
Published: April 2023

Artemisia argyi (A. argyi) is a medicinal plant belonging to the Asteraceae family and Artemisia genus. Flavonoids abundant in A. argyi are associated with anti-inflammatory, anticancer, and antioxidative effects. Eupatilin and jaceosidin are representative polymethoxy flavonoids with medicinal properties significant enough to warrant the development of drugs using their components. However, the biosynthetic pathways and related genes of these compounds have not been fully explored in A. argyi. This study comprehensively analyzed the transcriptome data and flavonoids contents from four different tissues of A. argyi (young leaves, old leaves, trichomes collected from stems, and stems without trichomes) for the first time. We obtained 41,398 unigenes through the de-novo assembly of transcriptome data and mined promising candidate genes involved in the biosynthesis of eupatilin and jaceosidin using differentially expressed genes, hierarchical clustering, phylogenetic tree, and weighted gene co-expression analysis. Our analysis led to the identification of a total of 7,265 DEGs, among which 153 genes were annotated as flavonoid-related genes. In particular, we were able to identify eight putative flavone-6-hydroxylase (F6H) genes, which were responsible for providing a methyl group acceptor into flavone basic skeleton. Furthermore, five O-methyltransferases (OMTs) gene were identified, which were required for the site-specific O-methylation during the biosynthesis of eupatilin and jaceosidin. Although further validation would be necessary, our findings pave the way for the modification and mass-production of pharmacologically important polymethoxy flavonoids through genetic engineering and synthetic biological approaches.