bluuebunny/crossref_metadata_2025 huggingface dataset:
Virtual care and COVID-19: A survey study of adoption, satisfaction and continuing education preferences of healthcare providers in Newfoundland and Labrador, Canada
Authors: Curran Vernon R. , Hollett Ann , Peddle Emily
Published: January 2023

Introduction

Virtual care has expanded during COVID-19 and enabled continued access to healthcare services. For many healthcare providers, the adoption of virtual care has been a new experience in the provision of healthcare services. The purpose of this survey study was to explore healthcare providers' experiences with virtual care during COVID-19.

Methods

A web-based survey-questionnaire was developed by applying Rogers' theory of diffusion of innovation and distributed to healthcare providers (physicians, nurses and allied health professionals) in Newfoundland and Labrador, Canada to explore virtual care experiences, satisfaction and continuing professional development (CPD) needs. Analyses included descriptive statistics and thematic analysis of survey responses.

Results

Fifty-one percent of respondents (n = 432) indicated they were currently offering virtual care and a majority (68.9%) reported it has improved their work experience. Telephone appointments were preferred over videoconferencing by respondents, with key challenges including the inability to conduct a physical exam, patients' cell phone services being unreliable and patients knowing how to use videoconferencing. Majority of respondents (57.5%) reported quality of care by telephone was lower than in-person, whereas quality of care by videoconferencing was equivalent to in-person. Main benefits of virtual care included increased patient access, ability to work from home, and reduction in no-show appointments. Key supports for adopting virtual care included in-house organizational supports (e.g., technical support staff), local colleague support, and technology training. Important topics for virtual care CPD included complying with regulatory standards/rules, understanding privacy or ethical boundaries, and developing competency and digital professionalism while engaging in virtual care.

Discussion

Beyond the COVID-19 pandemic, virtual care will have a continuing role in enhancing continuity of care through access that is more convenient. Survey findings reveal a number of opportunities for supporting healthcare providers in use of virtual care, including CPD, guidelines and resources to support adaptation to virtual care provision (e.g., virtual examinations/assessments), as well as patient educational support.
Boundary detection capability and influencing factors of electromagnetic resistivity while using drilling tools in a horizontal well
Authors: Tian Yuanshi , Zhu Jun , Die Yong , Liu Limeng , Yue Can , Wang Xuanguang , Zhu Yusha
Published: January 2023

With the increase in the scale of mining in horizontal and highly deviated wells, electromagnetic boundary detection while drilling plays an important role in boundary detection. This paper examines three types of antenna structures commonly used in electromagnetic boundary detection and measurement methods and also performs a numerical simulation of the edge detection capability of the three structures in horizontal wells. The simulation experiment analyzes the influence of formation resistivity contrast, frequency, spacing, and other factors on the capability of edge detection and provides data that supports the design of instrument antenna parameters. The numerical simulation shows that the tilted and orthogonal receiving antennas demonstrate improved performance both in detecting the interface when approaching from high-resistance layers and low-resistance layers. In addition, the capability of boundary detection can be improved by decreasing the frequency and increasing the spacing between the transmitter and receiver.
Integration of differential interferometric synthetic aperture radar and persistent scatterer interferometric approaches to assess deformation in enshi city, hubei, China
Authors: Khan Rehan , Zhong Yanmei , Li Huan , Al-Masnay Yousef A. , Haq Ihtisham ul , Khan Musa , Faheem Haris , Ali Rashid
Published: January 2023

Land surface deformation can severely damage socioeconomic living conditions around the world. This study aimed to identify the Shaziba landslide and further assess deformation activities in Enshi city. For this purpose, the sentinel-1 C-bands data acquired in ascending directions were processed with Sentinel Application Platform and Stanford Method for Persistent Scatterers (StaMPS) software packages. Our results revealed the location of a landslide that occurred on 21 July 2020 in the Shaziba area, Enshi Prefecture. More interesting deformation results were found in Enshi city for the first time with a deformation range from −51.6 to 54.2 mm/year. We conducted a thorough observation of different urban infrastructures such as commercial and residential buildings, roads, bridges, and airports in Enshi city and along the Qingjiang River to evaluate land surface deformation. Observations revealed that there are a number of influencing factors contributing to disturbing the natural environment and resources in Enshi Prefecture. Of these influencing factors, intensive rainfall is a major cause as are the infiltration of rainfall into the subsurface Silurian strata together with the load of infrastructure in the study area. If this issue is not addressed it could lead to devastating geo-hazard disasters in the future. Scientific approaches to determine various causes of frequent geo-hazards in this region are of great significance for developing early warning systems for disasters and ensuring the safety of residents’ lives and property.
Review of the correlation between Chinese medicine and intestinal microbiota on the efficacy of diabetes mellitus
Authors: Su Min , Hu Rao , Tang Ting , Tang Weiwei , Huang Chunxia
Published: January 2023

Diabetes mellitus is a serious metabolic disorder that can lead to a number of life-threatening complications. Studies have shown that intestinal microbiota is closely related to the development of diabetes, making it a potential target for the treatment of diabetes. In recent years, research on the active ingredients of traditional Chinese medicine (TCM), TCM compounds, and prepared Chinese medicines to regulate intestinal microbiota and improve the symptoms of diabetes mellitus is very extensive. We focus on the research progress of TCM active ingredients, herbal compounds, and prepared Chinese medicines in the treatment of diabetes mellitus in this paper. When diabetes occurs, changes in the abundance and function of the intestinal microbiota disrupt the intestinal environment by disrupting the intestinal barrier and fermentation. TCM and its components can increase the abundance of beneficial bacteria while decreasing the abundance of harmful bacteria, regulate the concentration of microbial metabolites, improve insulin sensitivity, regulate lipid metabolism and blood glucose, and reduce inflammation. TCM can be converted into active substances with pharmacological effects by intestinal microbiota, and these active substances can reverse intestinal microecological disorders and improve diabetes symptoms. This can be used as a reference for diabetes prevention and treatment.
Metabolic stress-induced human beta-cell death is mediated by increased intracellular levels of adenosine
Authors: Ngamjariyawat Anongnad , Cen Jing , Said Romain , Incedal Ceren , Idevall-Hagren Olof , Welsh Nils
Published: January 2023

Introduction

High intracellular concentrations of adenosine and 2’-deoxyadenosine have been suggested to be an important mediator of cell death. The aim of the present study was to characterize adenosine-induced death in insulin-producing beta-cells, at control and high glucose + palmitate-induced stress conditions.

Methods

Human insulin-producing EndoC-betaH1 cells were treated with adenosine, 2’-deoxyadenosine, inosine and high glucose + sodium palmitate, and death rates using flow cytometry were studied.

Results

We observed that adenosine and the non-receptor-activating analogue 2-deoxyadenosine, but not the adenosine deamination product inosine, promoted beta-cell apoptosis at concentrations exceeding maximal adenosine-receptor stimulating concentrations. Both adenosine and inosine were efficiently taken up by EndoC-betaH1 cells, and inosine counteracted the cell death promoting effect of adenosine by competing with adenosine for uptake. Both adenosine and 2’-deoxyadenosine promptly reduced insulin-stimulated production of plasma membrane PI(3,4,5)P3, an effect that was reversed upon wash out of adenosine. In line with this, adenosine, but not inosine, rapidly diminished Akt phosphorylation. Both pharmacological Bax inhibition and Akt activation blocked adenosine-induced beta-cell apoptosis, indicating that adenosine/2’-deoxyadenosine inhibits the PI3K/Akt/BAD anti-apoptotic pathway. High glucose + palmitate-induced cell death was paralleled by increased intracellular adenosine and inosine levels. Overexpression of adenosine deaminase-1 (ADA1) in EndoC-betaH1 cells, which increased Akt phosphorylation, prevented both adenosine-induced apoptosis and high glucose + palmitate-induced necrosis. ADA2 overexpression not only failed to protect against adenosine and high glucose + palmitate-activated cell death, but instead potentiated the apoptosis-stimulating effect of adenosine. In line with this, ADA1 overexpression increased inosine production from adenosine-exposed cells, whereas ADA2 did not. Knockdown of ADA1 resulted in increased cell death rates in response to both adenosine and high glucose + palmitate. Inhibition of miR-30e-3p binding to the ADA1 mRNA 3’-UTR promoted the opposite effects on cell death rates and reduced intracellular adenosine contents.

Discussion

It is concluded that intracellular adenosine/2’-deoxyadenosine regulates negatively the PI3K pathway and is therefore an important mediator of beta-cell apoptosis. Adenosine levels are controlled, at least in part, by ADA1, and strategies to upregulate ADA1 activity, during conditions of metabolic stress, could be useful in attempts to preserve beta-cell mass in diabetes.
Continuous glucose monitors and virtual care in high-risk, racial and ethnic minority populations: Toward promoting health equity
Authors: Vrany Elizabeth A. , Hill-Briggs Felicia , Ephraim Patti L. , Myers Alyson K. , Garnica Patricia , Fitzpatrick Stephanie L.
Published: January 2023

Continuous glucose monitors (CGMs) have become an important tool to aid self-management of blood glucose for many patients with diabetes in the U.S., and the benefits of CGM use are well-documented. However, disparities in CGM use exist, with lower use in certain marginalized racial and ethnic groups. CGM may be an important and underutilized tool to help reduce inequities. Evidence supporting the use of CGMs as a part of virtual care is discussed, with an emphasis on designing virtual diabetes care programs to promote health equity. Recommendations for clinical practice and research are presented. In clinical practice, CGM should be an option for all people with diabetes who qualify based on clinical practice guidelines, regardless of race, ethnicity, or other individual characteristics. Future research should characterize the use of, benefit from, and preferences for CGM among individuals from racial and ethnic groups to guide interventions at the health system, clinic, provider, and patient levels to promote equitable, evidence-based, and guideline-directed CGM use in marginalized racial and ethnic groups with diabetes.
Changes in epicardial and visceral adipose tissue depots following bariatric surgery and their effect on cardiac geometry
Authors: Henry J. A. , Abdesselam I. , Deal O. , Lewis A. J. , Rayner J. , Bernard M. , Dutour A. , Gaborit B. , Kober F. , Soghomonian A. , Sgromo B. , Byrne J. , Bege T. , Neubauer S. , Borlaug B. A. , Rider O. J.
Published: January 2023

Introduction

Obesity affects cardiac geometry, causing both eccentric (due to increased cardiac output) and concentric (due to insulin resistance) remodelling. Following bariatric surgery, reversal of both processes should occur. Furthermore, epicardial adipose tissue loss following bariatric surgery may reduce pericardial restraint, allowing further chamber expansion. We investigated these changes in a serial imaging study of adipose depots and cardiac geometry following bariatric surgery.

Methods

62 patients underwent cardiac magnetic resonance (CMR) before and after bariatric surgery, including 36 with short-term (median 212 days), 37 medium-term (median 428 days) and 32 long-term (median 1030 days) follow-up. CMR was used to assess cardiac geometry (left atrial volume (LAV) and left ventricular end-diastolic volume (LVEDV)), LV mass (LVM) and LV eccentricity index (LVei – a marker of pericardial restraint). Abdominal visceral (VAT) and epicardial (EAT) adipose tissue were also measured.

Results

Patients on average had lost 21kg (38.9% excess weight loss, EWL) at 212 days and 36kg (64.7% EWL) at 1030 days following bariatric surgery. Most VAT and EAT loss (43% and 14%, p<0.0001) occurred within the first 212 days, with non-significant reductions thereafter. In the short-term LVM (7.4%), LVEDV (8.6%) and LAV (13%) all decreased (all p<0.0001), with change in cardiac output correlated with LVEDV (r=0.35,p=0.03) and LAV change (r=0.37,p=0.03). Whereas LVM continued to decrease with time (12% decrease relative to baseline at 1030 days, p<0.0001), both LAV and LVEDV had returned to baseline by 1030 days. LV mass:volume ratio (a marker of concentric hypertrophy) reached its nadir at the longest timepoint (p<0.001). At baseline, LVei correlated with baseline EAT (r=0.37,p=0.0040), and decreased significantly from 1.09 at baseline to a low of 1.04 at 428 days (p<0.0001). Furthermore, change in EAT following bariatric surgery correlated with change in LVei (r=0.43,p=0.0007).

Conclusions

Cardiac volumes show a biphasic response to weight loss, initially becoming smaller and then returning to pre-operative sizes by 1030 days. We propose this is due to an initial reversal of eccentric remodelling followed by reversal of concentric remodelling. Furthermore, we provide evidence for a role of EAT contributing to pericardial restraint, with EAT loss improving markers of pericardial restraint.
Chemerin levels in chronic kidney disease: A systematic review and meta-analysis
Authors: Behnoush Amir Hossein , Shobeiri Parnian , Bahiraie Pegah , Amirkhani Nikan , Khalaji Amirmohammad , Peiman Soheil
Published: January 2023

Introduction

Chemerin as an inflammatory biomarker has gained attention in its biomarker capability. Several studies measured its levels in chronic kidney disease (CKD), as one of the common non-communicable causes of mortality and morbidity. Hence, this systematic review and meta-analysis aimed to investigate this association.

Methods

PubMed, Scopus, Embase, and the Web of Science databases were systematically searched for studies investigating chemerin levels in any CKD stage (including end-stage renal disease patients undergoing hemodialysis (HD)) and comparing it with healthy controls. Random effect meta-analysis was performed to calculate the standardized mean difference (SMD) and 95% confidence interval (CI).

Results

A total of eight studies were included, comprised of 875 individuals, with a mean age of 56.92 ± 11.78 years. All studies had high quality based on the New Castle-Ottawa Scale (NOS). Meta-analysis revealed significantly higher levels of chemerin in CKD patients compared to healthy controls (SMD 2.15, 95% CI 0.83-3.48, p-value<0.01). Additionally, HD patients had statistically higher levels of chemerin than controls (SMD 2.10, 95% CI 0.58-3.62, p-value=0.01). In meta-regression, publication year accounted for 23.50% and 24.17% of heterogeneity for these analyses, respectively.

Conclusion

Chemerin can be potentially used as a biomarker in CKD patients, which can suggest the inflammatory pathways for the disease. Further research is warranted for the assessment of its clinical applications and enlightening its role in the pathophysiology of CKD.
Effects of Fe self-ion irradiation on a low carbon MX-ODS steel at 550°C
Authors: Xu Yuwen , Yun Di , Yan Xu , Zhang Ping , Yan Wei , Li Yanfen , Li Chao , Li Jiao , Zhang Tongmin , Li Jun , Zhou Junjun , Kang Long , Lu Chenyang
Published: January 2023

Oxide Dispersion Strengthened (ODS) steels with nano-scale oxides have become one of the candidate materials used in advanced nuclear reactor systems. A novel MX-ODS steel with extremely low carbon content was irradiated with 3 MeV Fe ions at 550°C up to peak damage of 70 dpa. The steel contains uniformly distributed Y2O3 nano-precipitates with an average size of 3.5 nm and a number density of 5 × 1022/m3. A V-rich shell was found surrounding the core of Y, O, and Si at some particles. Two types of large precipitates, Y-Ta-Si oxides, and VN, were observed in the steel instead of carbides. Voids of very small size are present due to irradiation and the calculated void swelling was only 0.004%, suggesting good irradiation tolerance of the MX-ODS steel in this study. Fine and dense oxide nano-precipitates and their shell-core structure remained stable while the shape of large precipitates changed after irradiation.
Effects of precipitation variation and trampling disturbance on seedling emergence of annual plants in a semi-arid grassland
Authors: Liu Xinping , He Yuhui , Cheng Li , Hu Hongjiao , Xu Yuanzhi
Published: January 2023

Precipitation change and grazing are the main factors influencing vegetation structure and dynamics in semi-arid grassland. However, the effects of precipitation variation and livestock trampling on the seedling emergence patterns of plants remain largely unknown. In this study, an experiment with four gradients of trampling (no-trampling, light, moderate, and heavy) and three precipitation treatments (ambient precipitation, +30% precipitation, and −30% precipitation) was conducted to assess the effects of trampling disturbance and precipitation variation on seedling emergence of annual plants. The results showed that an increase in precipitation significantly improved total seedling emergence by 3.5–3.6 times and seedling density of grasses by more than 4.1 times under trampling conditions, while significantly improving total seedling emergence and density of forbs under no-trampling conditions. Moreover, +30% precipitation significantly improved the seedling proportion of grasses under light, moderate, and heavy trampling, while decreasing the seedling proportion of forbs. Seedling emergence of forbs was more sensitive to trampling disturbance, and seedling emergence of grasses was more sensitive to precipitation changes, especially under trampling conditions. Light and moderate trampling with a +30% precipitation increase promoted seedling emergence of grasses, and no trampling with a +30% precipitation increase improved seedling emergence of forbs. Thus, targeted grazing management measures should be implemented for plant communities dominated by either grasses or forbs under changing precipitation conditions.
Addressing climate change and development pressures in an urban estuary through habitat restoration planning
Authors: Beck Marcus W. , Robison Douglas E. , Raulerson Gary E. , Burke Maya C. , Saarinen Justin , Sciarrino Christine , Sherwood Edward T. , Tomasko David A.
Published: January 2023

Native habitats in Florida face dual pressures at the land-sea interface from urban development and sea-level rise. To address these pressures, restoration practitioners require robust tools that identify reasonable goals given historical land use trends, current status of native habitats, and anticipated future impacts from coastal stressors. A restoration framework for native habitats was created for the Tampa Bay watershed that identifies current opportunities and establishes short-term (2030) targets and long-term (2050) goals. The approach was informed through a three-decade habitat change analysis and over 40 years of habitat restoration projects in the region. Although significant gains in subtidal habitats have been observed, expansion of mangroves into salt marshes and loss of native upland habitats to development highlights the need to target these locations for restoration. The long-term loss of potentially restorable lands to both coastal and upland development further underscores the diminishing restoration opportunities in the watershed. The established targets and goals identified habitats to maintain at their present level (e.g., mangroves) and those that require additional progress (e.g., oyster bars) based on past trends and an expected level of effort given the restoration history of the region. The new approach also accounts for the future effects of sea-level rise, climate change, and watershed development by prioritizing native coastal habitats relative to subtidal or upland areas. Maps were created to identify the restoration opportunities where practitioners could focus efforts to achieve the targets and goals, with methods for repeatable analyses also available using an open source workflow.
Molecular genetics and phenotypic assessment of foxtail millet (Setaria italica (L.) P. Beauv.) landraces revealed remarkable variability of morpho-physiological, yield, and yield‐related traits
Authors: Ramesh Palakurthi , Juturu Vijaya Naresh , Yugandhar Poli , Pedersen Sydney , Hemasundar Alavilli , Yolcu Seher , Chandra Obul Reddy Puli , Chandra Mohan Reddy C. V. , Veerabramha Chari P. , Mohan Rajinikanth , Chandra Sekhar Akila
Published: January 2023

Foxtail millet (Setaria italica (L.) P. Beauv.) is highly valued for nutritional traits, stress tolerance and sustainability in resource-poor dryland agriculture. However, the low productivity of this crop in semi-arid regions of Southern India, is further threatened by climate stress. Landraces are valuable genetic resources, regionally adapted in form of novel alleles that are responsible for cope up the adverse conditions used by local farmers. In recent years, there is an erosion of genetic diversity. We have hypothesized that plant genetic resources collected from the semi-arid climatic zone would serve as a source of novel alleles for the development of climate resilience foxtail millet lines with enhanced yield. Keeping in view, there is an urgent need for conservation of genetic resources. To explore the genetic diversity, to identify superior genotypes and novel alleles, we collected a heterogeneous mixture of foxtail millet landraces from farmer fields. In an extensive multi-year study, we developed twenty genetically fixed foxtail millet landraces by single seed descent method. These landraces characterized along with four released cultivars with agro-morphological, physiological, yield and yield-related traits assessed genetic diversity and population structure. The landraces showed significant diversity in all the studied traits. We identified landraces S3G5, Red, Black and S1C1 that showed outstanding grain yield with earlier flowering, and maturity as compared to released cultivars. Diversity analysis using 67 simple sequence repeat microsatellite and other markers detected 127 alleles including 11 rare alleles, averaging 1.89 alleles per locus, expected heterozygosity of 0.26 and an average polymorphism information content of 0.23, collectively indicating a moderate genetic diversity in the landrace populations. Euclidean Ward’s clustering, based on the molecular markers, principal coordinate analysis and structure analysis concordantly distinguished the genotypes into two to three sub-populations. A significant phenotypic and genotypic diversity observed in the landraces indicates a diverse gene pool that can be utilized for sustainable foxtail millet crop improvement.
RNA-seq transcriptome profiling of pigs’ liver in response to diet with different sources of fatty acids
Authors: Fanalli Simara Larissa , Silva Bruna Pereira Martins da , Gomes Julia Dezen , Durval Mariah Castro , Almeida Vivian Vezzoni de , Moreira Gabriel Costa Monteiro , Silva-Vignato Bárbara , Afonso Juliana , Freitas Felipe André Oliveira , Reecy James Mark , Koltes James Eugene , Koltes Dawn , Garrick Dorian , Correia de Almeida Regitano Luciana , Balieiro Júlio Cesar de Carvalho , Mourão Gerson Barreto , Coutinho Luiz Lehmann , Fukumasu Heidge , Alencar Severino Matias de , Luchiari Filho Albino , Cesar Aline Silva Mello
Published: January 2023

Pigs (Sus scrofa) are an animal model for metabolic diseases in humans. Pork is an important source of fatty acids (FAs) in the human diet, as it is one of the most consumed meats worldwide. The effects of dietary inclusion of oils such as canola, fish, and soybean oils on pig gene expression are mostly unknown. Our objective was to evaluate FA composition, identify changes in gene expression in the liver of male pigs fed diets enriched with different FA profiles, and identify impacted metabolic pathways and gene networks to enlighten the biological mechanisms’ variation. Large White male pigs were randomly allocated to one of three diets with 18 pigs in each; all diets comprised a base of corn and soybean meal to which either 3% of soybean oil (SOY), 3% canola oil (CO), or 3% fish oil (FO) was added for a 98-day trial during the growing and finishing phases. RNA sequencing was performed on the liver samples of each animal by Illumina technology for differential gene expression analyses, using the R package DESeq2. The diets modified the FA profile, mainly in relation to polyunsaturated and saturated FAs. Comparing SOY vs. FO, 143 differentially expressed genes (DEGs) were identified as being associated with metabolism, metabolic and neurodegenerative disease pathways, inflammatory processes, and immune response networks. Comparing CO vs. SOY, 148 DEGs were identified, with pathways related to FA oxidation, regulation of lipid metabolism, and metabolic and neurodegenerative diseases. Our results help explain the behavior of genes with differential expression in metabolic pathways resulting from feeding different types of oils in pig diets.
Preliminary investigation of the diagnosis and gene function of deep learning PTPN11 gene mutation syndrome deafness
Authors: Wu Xionghui , Huang Min , Huang Weiqing , Zhao Sijun , Xie Jiang , Liu Guangliang , Chang Shuting
Published: January 2023

Syndromic deafness caused by PTPN11 gene mutation has gradually come into the public’s view. In the past, many people did not understand its application mechanism and role and only focused on non-syndromic deafness, so the research on syndromic deafness is not in-depth and there is a large degree of lack of research in this area. In order to let the public know more about the diagnosis and gene function of deafness caused by PTPN11 gene mutation syndrome, this paper used deep learning technology to study the diagnosis and gene function of deafness caused by syndrome with the concept of intelligent medical treatment, and finally drew a feasible conclusion. This paper provided a theoretical and practical basis for the diagnosis of deafness caused by PTPN11 gene mutation syndrome and the study of gene function. This paper made a retrospective analysis of the clinical data of 85 deaf children who visited Hunan Children’s Hospital,P.R. China from January 2020 to December 2021. The conclusion were as follows: Children aged 1–6 years old had multiple syndrome deafness, while children under 1 year old and children aged 6–12 years old had relatively low probability of complex deafness; girls were not easy to have comprehensive deafness, but there was no specific basis to prove that the occurrence of comprehensive deafness was necessarily related to gender; the hearing loss of patients with Noonan Syndrome was mainly characterized by moderate and severe damage and abnormal inner ear and auditory nerve; most of the mutation genes in children were located in Exon1 and Exon3, with a total probability of 57.65%. In the course of the experiment, it was found that deep learning was effective in the diagnosis of deafness with PTPN11 gene mutation syndrome. This technology could be applied to medical diagnosis to facilitate the diagnosis and treatment of more patients with deafness with syndrome. Intelligent medical treatment was also becoming a hot topic nowadays. By using this concept to analyze and study the pathological characteristics of deafness caused by PTPN11 gene mutation syndrome, it not only promoted patients to find diseases in time, but also helped doctors to diagnose and treat such diseases, which was of great significance to patients and doctors. The study of PTPN11 gene mutation syndrome deafness was also of great significance in genetics. The analysis of its genes not only enriched the gene pool, but also provided reference for future research.
Human N-Alpha-Acetyltransferase 60 Promotes Influenza A Virus Infection by Dampening the Interferon Alpha Signaling
Authors: Ahmed Farjana , Husain Matloob
Published: January 2023

N-alpha-acetyltransferase 60 (NAA60) is the most recently discovered N-terminal acetyltransferase and found only in multicellular eukaryotes. NAA60 localizes to the Golgi complex and is one of the only two N-terminal acetyltransferases known to localize to an organelle. Furthermore, NAA60 possesses a unique ability of catalyzing the acetylation of membrane-anchored proteins at the N-terminus and histones at the lysine side chains. Herein, we demonstrate that NAA60 exhibits proviral properties during influenza A virus (IAV) infection by interfering with the interferon (IFN) α signaling. We found that the depletion and overexpression of NAA60 reduced and enhanced, respectively, the IAV growth in a cell type- and IAV strain-independent manner. Mechanistically, the IAV-induced expression of IFNα was increased and decreased in NAA60-depleted and -overexpressing cells, respectively. Furthermore, the depletion of NAA60 enhanced the level of phosphorylated STAT1 transcription factor as well as the expression of several IFN-stimulated genes (ISGs) such as MX1, CH25H, IFITM3, ISG15 and viperin in infected cells. Whereas the overexpression of NAA60 produced opposite results. Finally, similar results were obtained when the NAA60-depleted cells were treated with purified IFNα. These findings, in conjunction with our recent findings where N-terminal acetylation of many host proteins increased in response to the IAV infection, indicate an important role of N-terminal acetylation during IAV replication.
Identification of autoimmune markers in pulmonary tuberculosis
Authors: Starshinova Anna , Malkova Anna , Zinchenko Yulia , Kudryavtsev Igor , Serebriakova Maria , Akisheva Tatiana , Lapin Sergey , Mazing Aleksandra , Kudlay Dmitry , Glushkova Anzhela , Yablonskiy Piotr , Shoenfeld Yehuda
Published: January 2023

Introduction

Pathogenesis of many autoimmune diseases is mainly promoted by poorly regulated and/or wrong targeted immune response to pathogens including M. tuberculosis. Autoimmunity is one of the processes with are characteristics of tuberculosis (Tbc). The aim was to determine the autoimmune clinical and immunological features in patients with pulmonary Tbc.

Materials and methods

A prospective comparative study was performed in 2017 – 2019 with the inclusion of 46 patients with Tbc. The trigger factors and clinical manifestations, autoantibodies, peripheral blood B cell subsets were stained with fluorochrome-conjugated monoclonal antibodies. 40 healthy volunteers in the control group, were matched for age with no chronic diseases, contacts with TB patients and changes in their laboratory parameters. A statistical analysis was done with GraphPad Prism 6, Statistica 10 (Statsoft) and MedCalc – version 18.2.1 values.

Results

There were no significant ASIA triggers in Tbc patients and control group. 21.1% of Tbc patients had a high level of a rheumatoid factor and in 47.4% complement system factor C3 was high; anti-MCV was detected in 60.7% of Tbc patients. Relative and absolute frequencies of “naïve” Bm1 cells and eBm5 were significantly decreased and activated pre-germinal-center Bm2’ cells were significantly increased in Tbc patients. The CD24++CD38++ B cells were increased in Tbc vs control group (10.25% vs 5.42%), p < 0.001, and 19 cell/1μL (10; 290 vs 11 cell/1μL (6; 20), p = 0.029, respectively). The frequency of CXCR3+CCR4– Tfh1 cells was significantly lower in Tbc vs control one (26.52% vs. 31.00%, p = 0.004), while CXCR3–CCR4+ Tfh2 cells were increased in Tbc (20.31% vs. controls (16.56%, p = 0.030). The absolute numbers of Tfh1 cells were decreased in the Tbc vs. control (24 cell/1μL vs. 37 cell/1μL p = 0.005).

Conclusion

The results of our study showed that the detection of a rheumatoid factor, the components of complement system and anti-MCV in complex with alterations in B cells and follicular Th cell subsets may indicate a presence of autoimmunity in the pathogenesis of tuberculosis, but they are not specific. The indicators of autoimmune-related provide new opportunities in the Tbc treatment.
Emerging role of hypoxia-inducible factor-1α in inflammatory autoimmune diseases: A comprehensive review
Authors: Tang Yang-Yang , Wang Da-Cheng , Wang You-Qiang , Huang An-Fang , Xu Wang-Dong
Published: January 2023

Hypoxia-inducible factor-1α (HIF-1α) is a primary metabolic sensor, and is expressed in different immune cells, such as macrophage, dendritic cell, neutrophil, T cell, and non-immune cells, for instance, synovial fibroblast, and islet β cell. HIF-1α signaling regulates cellular metabolism, triggering the release of inflammatory cytokines and inflammatory cells proliferation. It is known that microenvironment hypoxia, vascular proliferation, and impaired immunological balance are present in autoimmune diseases. To date, HIF-1α is recognized to be overexpressed in several inflammatory autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis, and function of HIF-1α is dysregulated in these diseases. In this review, we narrate the signaling pathway of HIF-1α and the possible immunopathological roles of HIF-1α in autoimmune diseases. The collected information will provide a theoretical basis for the familiarization and development of new clinical trials and treatment based on HIF-1α and inflammatory autoimmune disorders in the future.
Metabolic rearrangements and intratumoral heterogeneity for immune response in hepatocellular carcinoma
Authors: Xu Fei-Qi , Dong Meng-Meng , Wang Zhi-Fei , Cao Li-Dong
Published: January 2023

Liver cancer is one of the most common malignant tumors globally. Not only is it difficult to diagnose, but treatments are scarce and the prognosis is generally poor. Hepatocellular carcinoma (HCC) is the most common type of liver cancer. Aggressive cancer cells, such as those found in HCC, undergo extensive metabolic rewiring as tumorigenesis, the unique feature, ultimately causes adaptation to the neoplastic microenvironment. Intratumoral heterogeneity (ITH) is defined as the presence of distinct genetic features and different phenotypes in the same tumoral region. ITH, a property unique to malignant cancers, results in differences in many different features of tumors, including, but not limited to, tumor growth and resistance to chemotherapy, which in turn is partly responsible for metabolic reprogramming. Moreover, the different metabolic phenotypes might also activate the immune response to varying degrees and help tumor cells escape detection by the immune system. In this review, we summarize the reprogramming of glucose metabolism and tumoral heterogeneity and their associations that occur in HCC, to obtain a better understanding of the mechanisms of HCC oncogenesis.
Progress in the cryoablation and cryoimmunotherapy for tumor
Authors: Chen Zenan , Meng Liangliang , Zhang Jing , Zhang Xiao
Published: January 2023

With the rapid advancement of imaging equipment and minimally invasive technology, cryoablation technology is being used more frequently in minimally invasive treatment of tumors, primarily for patients with early tumors who voluntarily consent to ablation as well as those with advanced tumors that cannot be surgically removed or cannot be tolerated. Cryoablation is more effective and secure for target lesions than other thermal ablation methods like microwave and radiofrequency ablation (RFA). The study also discovered that cryoablation, in addition to causing tumor tissue necrosis and apoptosis, can facilitate the release of tumor-derived autoantigens into the bloodstream and activate the host immune system to elicit beneficial anti-tumor immunological responses against primary. This may result in regression of the primary tumor and distant metastasis. The additional effect called “ Accompanying effects “. It is the basis of combined ablation and immunotherapy for tumor. At present, there is a lot of research on the mechanism of immune response induced by cryoablation. Trying to solve the question: how positively induce immune response. In this review, we focus on: 1. the immune effects induced by cryoablation. 2. the effect and mechanism of tumor immunotherapy combined with cryoablation. 3.The clinical research of this combination therapy in the treatment of tumors.
Identification of tumor antigens and immune landscapes for bladder urothelial carcinoma mRNA vaccine
Authors: Sun Zhuolun , Jing Changying , Zhan Hailun , Guo Xudong , Suo Ning , Kong Feng , Tao Wen , Xiao Chutian , Hu Daoyuan , Wang Hanbo , Jiang Shaobo
Published: January 2023

Background

Bladder urothelial carcinoma (BLCA) is associated with high mortality and recurrence. Although mRNA-based vaccines are promising treatment strategies for combating multiple solid cancers, their efficacy against BLCA remains unclear. We aimed to identify potential effective antigens of BLCA for the development of mRNA-based vaccines and screen for immune clusters to select appropriate candidates for vaccination.

Methods

Gene expression microarray data and clinical information were retrieved from The Cancer Genome Atlas and GSE32894, respectively. The mRNA splicing patterns were obtained from the SpliceSeq portal. The cBioPortal for Cancer Genomics was used to visualize genetic alteration profiles. Furthermore, nonsense-mediated mRNA decay (NMD) analysis, correlation analysis, consensus clustering analysis, immune cell infiltration analysis, and weighted co-expression network analysis were conducted.

Results

Six upregulated and mutated tumor antigens related to NMD, and infiltration of APCs were identified in patients with BLCA, including HP1BP3, OSBPL9, SSH3, ZCCHC8, FANCI, and EIF4A2. The patients were subdivided into two immune clusters (IC1 and IC2) with distinct clinical, cellular and molecular features. Patients in IC1 represented immunologically ‘hot’ phenotypes, whereas those in IC2 represented immunologically ‘cold’ phenotypes. Moreover, the survival rate was better in IC2 than in IC1, and the immune landscape of BLCA indicated significant inter-patient heterogeneity. Finally, CALD1, TGFB3, and ANXA6 were identified as key genes of BLCA through WGCNA analysis, and their mRNA expression levels were measured using qRT-PCR.

Conclusion

HP1BP3, OSBPL9, SSH3, ZCCHC8, FANCI, and EIF4A2 were identified as potential antigens for developing mRNA-based vaccines against BLCA, and patients in IC2 might benefit more from vaccination.
The altering cellular components and function in tumor microenvironment during remissive and relapsed stages of anti-CD19 CAR T-cell treated lymphoma mice
Authors: Zhao Kai , Ren Chunxiao , Tang Donghai , Zhao Li , Chen Xianxian , Wang Ying , Xu Kailin
Published: January 2023

Anti-CD19 chimeric antigen receptor (CAR) T cells represent a highly promising strategy for B-cell malignancies. Despite the inspiring initial achievement, remission in a notable fraction of subjects is short-lived, and relapse remains a major challenge. Tumor microenvironment (TME) was proved to be aroused by CAR T cells; however, little is known about the dynamic characteristics of cellular components in TME especially during the different phases of disease after anti-CD19 CAR T-cell treatment. We took advantage of an immunocompetent model receiving syngeneic A20 lymphoma cells to dissect the changes in TME with or without CAR T-cell injection. We found that anti-CD19 CAR T-cell treatment attenuated the symptoms of lymphoma and significantly prolonged mice survival through eradicating systemic CD19+ cells. Increased myeloid subsets, including CD11c+ DCs and F4/80+ macrophages with higher MHC II and CD80 expression in bone marrow, spleen, and liver, were detected when mice reached remission after anti-CD19 CAR T treatment. Compared to mice without anti-CD19 CAR T administration, intrinsic T cells were triggered to produce more IFN-γ and TNF-α. However, some lymphoma mice relapsed by day 42 after therapy, which coincided with CAR T-cell recession, decreased myeloid cell activation and increased Treg cells. Elevated intrinsic T cells with high PD-1 and TIGIT exhaust signatures and attenuated cytotoxicity in TME were associated with the late-stage relapse of CAR T-cell treatment. In summary, the cellular compositions of TME as allies of CAR T cells may contribute to the anti-tumor efficacy at the initial stage, whereas anti-CD19 CAR T-cell disappearance and host response immunosuppression may work together to cause lymphoma relapse after an initial, near-complete elimination phase.
The association between Parkinson’s disease and autoimmune diseases: A systematic review and meta-analysis
Authors: Li Mingqiang , Wan Juan , Xu Zhenhong , Tang Beisha
Published: January 2023

Parkinson’s disease (PD) is a neurodegenerative disorder that frequently occurs in the older population. Previous epidemiological studies have suggested an association between PD and autoimmune diseases (AIDs). However, some studies have shown conflicting results. This study aimed to summarize existing epidemiological studies on the association between PD with AIDs and to conduct a meta-analysis of combinable results. Four electronic databases (PubMed, Embase, Web of Science Core Collection, and MEDLINE) were searched from each database’s inception date until December 12, 2022. All studies that explored the relationship between PD and AIDs were included for quantitative analysis and qualitative review. The pooled relative risk with 95% confidence intervals (CIs) was calculated using a random or fixed effects model. A total of 46 observational studies involving 873,643 patients and 13,402,821 controls were included; ultimately, 38 studies were included in the meta-analysis. The risk of PD combined with AIDs was significantly higher (odds ratio [OR]=1.55, 95% CI: 1.33–1.81), and subgroup analysis found no significant differences in risk by study type, gender, age, and race. Regarding the AID types, the results showed an increased risk of PD combined with bullous pemphigoid (OR=2.67, 95% CI: 2.15–3.31), inflammatory bowel disease (OR=1.30, 95% CI: 1.18–1.45), Crohn’s disease (OR=1.30, 95% CI: 1.20–1.42), ulcerative colitis (OR=1.31, 95% CI: 1.14–1.50), Sjögren’s syndrome (OR=1.61, 95% CI: 1.24–2.09), and Graves’ disease (OR=1.45, 95% CI: 1.24–1.70) than controls. However, there appeared to be no significant association between PD and systemic lupus erythematosus (OR=0.82, 95% CI: 0.66–1.03), multiple sclerosis (OR=2.02, 95% CI: 0.87–4.70), rheumatoid arthritis (OR=0.79, 95% CI: 0.61–1.03), or celiac disease (OR=1.16, 95% CI: 0.79–1.69). This study supports the existence of a strong link between AIDs and PD. When PD and AIDs are identified, clinicians need to be aware of the possibility of coexistence. However, there are some limitations of this study, such as the apparent heterogeneity of some of the results and the fact that most of the included study types were retrospective. Therefore, future larger prospective cohort studies are needed to further explore the interaction between PD and AIDs.

Systematic review registration

INPLASY, identifier INPLASY202280088.
Research progress of neoantigen-based dendritic cell vaccines in pancreatic cancer
Authors: Zhang Xin , Xu Zheng , Dai Xiangpeng , Zhang Xiaoling , Wang Xueju
Published: January 2023

The mutation of the crucial genes such as tumor suppressors or oncogenes plays an important role in the initiation and development of tumors. The non-synonymous mutations in the tumor cell genome will produce non-autologous proteins (neoantigen) to activate the immune system by activating CD4+ and CD8+ T cells. Neoantigen-based peptide vaccines have exhibited exciting therapeutic effects in treating various cancers alone or in combination with other therapeutic strategies. Furthermore, antigen-loaded DC vaccines are more powerful in inducing stronger immune responses than vaccines generated by antigens and adjuvants. Therefore, neoantigen-based dendritic cell (DC) vaccines could achieve promising effects in combating some malignant tumors. In this review, we summarized and discussed the recent research progresses of the neoantigen, neoantigen-based vaccines, and DC-based vaccine in pancreatic cancers (PCs). The combination of the neoantigen and DC-based vaccine in PC was also highlighted. Therefore, our work will provide more detailed evidence and novel opinions to promote the development of a personalized neoantigen-based DC vaccine for PC.
Microbial derived antimicrobial peptides as potential therapeutics in atopic dermatitis
Authors: Joshi Aaroh Anand , Vocanson Marc , Nicolas Jean-Francois , Wolf Peter , Patra Vijaykumar
Published: January 2023

Atopic dermatitis (AD) is a common chronic inflammatory skin disease that significantly affects the patient’s quality of life. A disrupted skin barrier, type 2 cytokine-dominated inflammation, and microbial dysbiosis with increased Staphylococcus aureus colonization are critical components of AD pathogenesis. Patients with AD exhibit decreased expression of antimicrobial peptides (AMPs) which is linked to increased colonization by Staphylococcus aureus. The skin microbiome itself is a source of several AMPs. These host- and microbiome-derived AMPs define the microbial landscape of the skin based on their differential antimicrobial activity against a range of skin microbes or their quorum sensing inhibitory properties. These are particularly important in preventing and limiting dysbiotic colonization with Staphylococcus aureus. In addition, AMPs are critical for immune homeostasis. In this article, we share our perspectives about the implications of microbial derived AMPs in AD patients and their potential effects on overlapping factors involved in AD. We argue and discuss the potential of bacterial AMPs as therapeutics in AD.