bluuebunny/crossref_metadata_2025 huggingface dataset:
An Assessment of the Impact of Natural Resource Price and Global Economic Policy Uncertainty on Financial Asset Performance: Evidence From Bitcoin
Authors: Dai Maoyu , Qamruzzaman Md. , Hamadelneel Adow Anass
Published: June 2022

The aim of this study is to gauge the impact of global economic policy uncertainty and natural resource prices, that is, oil prices and gold prices, on Bitcoin returns by using monthly data spanning from May 2013 to December 2021. The study applies ARDL and nonlinear ARDL for evaluating the symmetric and asymmetric effects of Global Economic Uncertainty (GU), oil price (O), and natural gas price on Bitcoin volatility investigated by using the ARCH-GARCH-ERAGCH and non-granger causality test. ARDL model estimation establishes a long-run cointegration between GU, O, G, and Bitcoin. Moreover, GU and oil price exhibits a negative association with Bitcoin and positive influences running from gold price shock to Bitcoin in the long run. NARDL results ascertain the long-run asymmetric relations between GU, oil price, gold price (G), and Bitcoin return. Furthermore, GU’s asymmetric effect and positive shock in gold price negatively linked to Bitcoin return in the long run, whereas asymmetric shock in oil price and negative shocks in gold price established a positive linkage with Bitcoin. The results of ARCH effects disclose the volatility persistence in the variables. The causality test reveals that the feedback hypothesis explains the causal effects between GU and Bitcoin and unidirectional causality running from Bitcoin to gold price and oil price to Bitcoin.
The Antibiotic Resistance Genes Contamination of Strawberries With the Long-Term Use of Raw, Aerobic Composting, and Anaerobic Composting Livestock Manure: A Comparative Study
Authors: Zhang Wei-Guo , Zhang Ming-Sha , Li Wen
Published: June 2022

Strawberry fruits are easily contaminated with antibiotic resistance genes (ARGs) in the soil fertilized with livestock manure, which is widely used by farmers in order to increased yield and fruit quality. Composting can reduce the ARGs contamination in livestock manure. However, there is a knowledge gap in understanding and comparing the ARGs contamination of strawberries with the long-term use of raw, aerobic composting, and anaerobic composting livestock manure. In this study, our results suggested that compared with the long-term use of raw livestock manure, both aerobic and anaerobic composting livestock manure reduced the ARGs diversity and abundance of strawberries. Mobile genetic elements (MGEs) closely determined the ARGs dissemination. The correlation analysis between ARGs and MGEs revealed the ARGs dissemination from fruits to human was attenuated when strawberries were fertilized with long-term use of composting livestock manure. In addition, this study illustrated the correlations between the antibiotic resistome and microbiome via network co-occurrence analysis, finding that the phylum Proteobacteria, Firmicutes, and Myxococcota were identified as the potential ARGs hosts which exerted the vital role in the environmental behavior of ARGs. The most important highlight was that the contamination of ARGs of strawberries was alleviated by the long-term use of composting livestock manure, especially the anaerobiotic composting manure.
Convergent Variation in the Leaf Traits of Desert Plants in the Ebinur Lake Basin
Authors: Nurbolat Saltanat , Guanghui Lv , Lamei Jiang , Lei Zhang
Published: June 2022

Elucidating the relationship between the variation of plant leaf functional traits and the environment is necessary for understanding the adaptation mechanism of plants and predicting changes in ecosystem structure. In this study, the leaf traits of desert plants in Ebinur Lake National Wetland Nature Reserve in Xinjiang, China were studied from the aspects of plant life forms (annuals, perennials and shrubs), phylogenetic signals, and relation to soil properties, using the principal component analysis, variance decomposition, and one-way analysis of variance. The results showed that: (1) There were significant differences in leaf carbon concentration (annuals>shrubs>perennials), leaf nitrogen concentration (shrubs ≥ perennials ≥ annuals), and leaf moisture content (perennials ≥ annuals ≥ shrubs) among the life forms, but there was no significant difference in leaf phosphorus concentration. Besides, soil nitrogen and phosphorus were significantly positively correlated with leaf carbon concentration and leaf nitrogen concentration. (2) There were significant differences in leaf carbon concentration, leaf nitrogen concentration, specific leaf area, and leaf moisture content between C3 and C4 plants, while the differences in P and leaf dry matter content were not significant. Besides, there were significant differences in leaf carbon concentration, leaf nitrogen concentration, specific leaf area, and leaf moisture content between leguminous and non-leguminous plants. Leguminous plants had higher leaf carbon concentration, leaf nitrogen concentration, and specific leaf area than non-leguminous plants, while non-leguminous plants had higher leaf moisture content than leguminous plants. (3) One way ANOVA analysis showed that taxonomy had a more significant effects on leaf carbon concentration, leaf nitrogen concentration, specific leaf area, and leaf moisture content than soil properties, and the coefficient of variation of leaf carbon concentration was greater than 50%. The phylogenetically independent contrasts analysis showed that the phylogenetic signal of all leaf traits was detected in all species and low (K value < 1, p > 0.05), indicating that the functional traits were weakly affected by phylogenetics. Therefore, desert plants in the Ebinur Lake Basin evolved to adapt to arid environments, and leaf traits showed convergent variation.
N7-Methylguanosine Genes Related Prognostic Biomarker in Hepatocellular Carcinoma
Authors: Regmi Parbatraj , He Zhi-Qiang , Lia Thongher , Paudyal Aliza , Li Fu-Yu
Published: June 2022

Background: About 90% of liver cancer-related deaths are caused by hepatocellular carcinoma (HCC). N7-methylguanosine (m7G) modification is associated with the biological process and regulation of various diseases. To the best of our knowledge, its role in the pathogenesis and prognosis of HCC has not been thoroughly investigated.

Aim: To identify N7-methylguanosine (m7G) related prognostic biomarkers in HCC. Furthermore, we also studied the association of m7G–related prognostic gene signature with immune infiltration in HCC.

Methods: The TCGA datasets were used as a training and GEO dataset “GSE76427” for validation of the results. Statistical analyses were performed using the R statistical software version 4.1.2.

Results: Functional enrichment analysis identified some pathogenesis related to HCC. We identified 3 m7G-related genes (CDK1, ANO1, and PDGFRA) as prognostic biomarkers for HCC. A risk score was calculated from these 3 prognostic m7G-related genes which showed the high-risk group had a significantly poorer prognosis than the low-risk group in both training and validation datasets. The 3- and 5-years overall survival was predicted better with the risk score than the ideal model in the entire cohort in the predictive nomogram. Furthermore, immune checkpoint genes like CTLA4, HAVCR2, LAG3, and TIGT were expressed significantly higher in the high-risk group and the chemotherapy sensitivity analysis showed that the high-risk groups were responsive to sorafenib treatment.

Conclusion: These 3 m7G genes related signature model can be used as prognostic biomarkers in HCC and a guide for immunotherapy and chemotherapy response. Future clinical study on this biomarker model is required to verify its clinical implications.
Differentials in Contraceptive Use Among Selected Minority Ethnic Groups in Nigeria
Authors: Ayinmoro Aboluwaji Daniel , Fayehun Olufunke A.
Published: June 2022

Ethnicity is one of the critical factors that shape contraceptive use in Nigeria. While there are growing disparities in contraceptive uptake among women of reproductive age in the three major ethnic groups (Hausa, Igbo and Yoruba), not much is known about differentials in contraceptive use among the minority ethnic groups. This study examined differentials in contraceptive use among a sample of 1,072 respondents comprising the Ebira (352), Igala (358) and Okun (361) ethnic groups in Nigeria. Questionnaire was administered to respondents proportionately in the selected minority ethnic groups with six key informant interviews and 12 focus group discussions to generate quantitative and qualitative data among ever-married women. Quantitative data were analyzed at bivariable and multivariable levels. The qualitative data were content-analyzed. Differentials in contraception are shaped by ethnic affiliations and socio-demographic characteristics of couples. The use of modern contraceptives was low among the Ebira (25.7%) and Igala (24.1%) ethnic groups, but high among Okun (67%) women of reproductive age. The odd of using a modern contraceptive is significantly higher among the Okun women (UOR = 5.618, 95% CI 4.068–7.759) than the Ebira and Igala. There is no significant difference between the Ebira and Igala minority ethnic groups on modern contraceptive use. Ethnicity as a factor is not a stand-alone predictor of the use of modern contraception among the study groups, other socio-economic variables such as residence, religion, income and marital status were significant predictors of modern contraceptive use among minority ethnic groups. We suggest introducing reproductive health intervention programmes targeted at sensitizing the minority ethnic groups on effective modern contraceptive use while addressing their specific modern contraceptive need in Nigeria.
Innate Immune Responses and P. falciparum CS Repeat-Specific Neutralizing Antibodies Following Vaccination by Skin Scarification
Authors: Mitchell Robert A. , Altszuler Rita , Gonzalez Sandra , Johnson Roshawn , Frevert Ute , Nardin Elizabeth
Published: June 2022

The skin is the site of host invasion by the mosquito-bornePlasmodiumparasite, which caused an estimated 229 million infections and 409,000 deaths in 2019 according to WHO World Malaria report 2020. In our previous studies, we have shown that skin scarification (SS) with aP. falciparumcircumsporozoite (CS) peptide in the oil-in-water adjuvant AddaVax containing a combination of TLR 7/8 and TLR 9 agonists can elicit sporozoite neutralizing antibodies. SS with AddaVax + TLR agonists, but not AddaVax alone, elicited CD4+ Th1 cells and IgG2a/c anti-repeat antibody. To explore the innate immune responses that may contribute to development of adaptive immunity following SS, we examined the skin at 4h and 24h post priming with CS peptide in AddaVax with or without TLR agonists. H&E stained and IHC-labeled dorsal skin sections obtained 24h post SS demonstrated a marked difference in the pattern of infiltration with F4/80+, CD11b+ and Ly6G+ cells at the immunization site, with the lowest intensity noted following SS with AddaVax + TLR agonists. Serum collected at 4h post SS, had reproducible increases in IL-6, MIP-3α, IL-22 and IP-10 (CXCL10) following SS with AddaVax + TLR agonists, but not with AddaVax alone. To begin to decipher the complex roles of these pro-inflammatory cytokines/chemokines, we utilized IP-10 deficient (IP-10 -/-) mice to examine the role of this chemokine in the development of anti-repeat antibody response following SS. In the absence of IP-10, the levels of Th1-type IgG2a/c antibody and kinetics of the primary anti-repeat antibody response were reduced following prime and boost. The IP-10 chemokine, present as early as 4h post prime, may provide an early serological marker for rapid screening of adjuvant formulations and delivery platforms to optimize SS-induced humoral immunity to CS repeats as well as other pathogens.
A Recombinant Acetylcholine Receptor α1 Subunit Extracellular Domain Is a Promising New Drug Candidate for Treatment Of Myasthenia Gravis
Authors: Lazaridis Konstantinos , Fernandez-Santoscoy Maria , Baltatzidou Vasiliki , Andersson Jan-Olof , Christison Richard , Grünberg John , Tzartos Socrates , Löwenadler Björn , Fribert Charlotte
Published: June 2022

Background and Aims

Myasthenia gravis (MG) is a T-cell dependent antibody-mediated autoimmune disease in which the nicotinic acetylcholine receptor (AChR) is the major autoantigen, comprising several T and B cell auto-epitopes. We hypothesized that an efficacious drug candidate for antigen-specific therapy in MG should comprise a broad range of these auto-epitopes and be administered in a noninflammatory and tolerogenic context.

Methods

We used a soluble mutated form of the extracellular domain of the α1 chain of the AChR (α1-ECDm), which represents the major portion of auto-epitopes involved in MG, and investigated, in a well-characterized rat model of experimental autoimmune myasthenia gravis (EAMG) whether its intravenous administration could safely and efficiently treat the autoimmune disease.

Results

We demonstrated that intravenous administration of α1-ECDm abrogates established EAMG, in a dose and time dependent manner, as assessed by clinical symptoms, body weight, and compound muscle action potential (CMAP) decrement. Importantly, the effect was more pronounced compared to drugs representing current standard of care for MG. The protein had a short plasma half-life, most of what could be recovered was sequestered in the liver, kidneys and spleen. Further, we did not observe any signs of toxicity or intolerability in animals treated with α1-ECDm.

Conclusion

We conclude that intravenous treatment with α1-ECDm is safe and effective in suppressing EAMG. α1-ECDm is in preclinical development as a promising new drug candidate for MG.
Differentially Expressed miRNAs in Ulcerative Colitis and Crohn’s Disease
Authors: Yarani Reza , Shojaeian Ali , Palasca Oana , Doncheva Nadezhda T. , Jensen Lars Juhl , Gorodkin Jan , Pociot Flemming
Published: June 2022

Differential microRNA (miRNA or miR) regulation is linked to the development and progress of many diseases, including inflammatory bowel disease (IBD). It is well-established that miRNAs are involved in the differentiation, maturation, and functional control of immune cells. miRNAs modulate inflammatory cascades and affect the extracellular matrix, tight junctions, cellular hemostasis, and microbiota. This review summarizes current knowledge of differentially expressed miRNAs in mucosal tissues and peripheral blood of patients with ulcerative colitis and Crohn’s disease. We combined comprehensive literature curation with computational meta-analysis of publicly available high-throughput datasets to obtain a consensus set of miRNAs consistently differentially expressed in mucosal tissues. We further describe the role of the most relevant differentially expressed miRNAs in IBD, extract their potential targets involved in IBD, and highlight their diagnostic and therapeutic potential for future investigations.
Antibody Response to COVID-19 Booster Vaccination in Healthcare Workers
Authors: Pani Arianna , Romandini Alessandra , Schianchi Alice , Senatore Michele , Gagliardi Oscar M. , Gazzaniga Gianluca , Agliardi Stefano , Conti Tommaso , Schenardi Paolo A. , Maggi Matteo , D’Onghia Stefano , Panetta Valentina , Renica Silvia , Molteni Silvia Nerini , Vismara Chiara , Campisi Daniela , Bertuzzi Michaela , Giroldi Simona , Zoppini Laura , Moreno Mauro , Merli Marco , Bosio Marco , Puoti Massimo , Scaglione Francesco
Published: June 2022

Objective

To evaluate the mean increase of anti-S IgG antibody titer between the basal, pre-booster level to the titer assessed 14 days after the booster dose of BNT162b2.

Patients and Methods

The RENAISSANCE study is an observational, longitudinal, prospective, population-based study, conducted on healthcare workers of Niguarda Hospital in Milan, Italy who received a BNT162b2 booster dose at least 180 days after their second dose or after positivity for SARS-CoV-2 and accepted to take part in the study. The RENAISSANCE study was conducted from January 1, 2021 through December 28, 2021.

Findings

1,738 subjects were enrolled among healthcare workers registered for the booster administration at our hospital. Overall, 0.4% of subjects were seronegative at the pre-booster evaluation, and 1 subject had a titer equal to 50 AU/ml: none of the evaluated subjects was seronegative after the booster dose. Thus, the efficacy of the booster in our population was universal. Mean increase of pre- to post-booster titer was more significant in subjects who never had SARS-CoV-2 (44 times CI 95% 42-46) compared to those who had it, before (33 times, CI 95% 13-70) or after the first vaccination cycle (12 times, CI 95% 11-14). Differently from sex, age and pre-booster titers affected the post-booster antibody response. Nevertheless, the post-booster titer was very similar in all subgroups, and independent of a prior exposure to SARS-CoV-2, pre-booster titer, sex or age.

Conclusion

Our study shows a potent universal antibody response of the booster dose of BNT162b2, regardless of pre-booster vaccine seronegativity.
Identification of Ligand-Receptor Pairs Associated With Tumour Characteristics in Clear Cell Renal Cell Carcinoma
Authors: Liu Fahui , Wang Ping , Sun Wenjuan , Jiang Yan , Gong Qiming
Published: June 2022

The tumour microenvironment (TME) of clear cell renal cell carcinoma (ccRCC) comprises multiple cell types, which promote tumour progression and modulate drug resistance and immune cell infiltrations via ligand-receptor (LR) interactions. However, the interactions, expression patterns, and clinical relevance of LR in the TME in ccRCC are insufficiently characterised. This study characterises the complex composition of the TME in ccRCC by analysing the single-cell sequencing (scRNA-seq) data of patients with ccRCC from the Gene expression omnibus database. On analysing the scRNA-seq data combined with the cancer genome atlas kidney renal clear cell carcinoma (TCGA-KIRC) dataset, 46 LR-pairs were identified that were significantly correlated and had prognostic values. Furthermore, a new molecular subtyping model was proposed based on these 46 LR-pairs. Molecular subtyping was performed in two ccRCC cohorts, revealing significant differences in prognosis between the subtypes of the two ccRCC cohorts. Different molecular subtypes exhibited different clinicopathological features, mutational, pathway, and immune signatures. Finally, the LR.score model that was constructed using ten essential LR-pairs that were identified based on LASSO Cox regression analysis revealed that the model could accurately predict the prognosis of patients with ccRCC. In addition, the differential expression of ten LR-pairs in tumour and normal cell lines was identified. Further functional experiments showed that CX3CL1 can exert anti-tumorigenic role in ccRCC cell line. Altogether, the effects of immunotherapy were connected to LR.scores, indicating that potential medications targeting these LR-pairs could contribute to the clinical benefit of immunotherapy. Therefore, this study identifies LR-pairs that could be effective biomarkers and predictors for molecular subtyping and immunotherapy effects in ccRCC. Targeting LR-pairs provides a new direction for immunotherapy regimens and prognostic evaluations in ccRCC.
Identification of SCRG1 as a Potential Therapeutic Target for Human Synovial Inflammation
Authors: Liu Guoqiang , He Guisong , Zhang Jie , Zhang Zhongmin , Wang Liang
Published: June 2022

Synovial inflammation of joint tissue is the most important cause of tissue damage, joint destruction, and disability and is associated with higher morbidity or mortality. Therefore, this study aims to identify key genes in osteoarthritis synovitis tissue to increase our understanding of the underlying mechanisms of osteoarthritis and identify new therapeutic targets. Five GEO datasets with a total of 41 normal synovial membrane tissues and 45 osteoarthritis synovial membrane samples were used for analysis, and seven common differential genes were identified. The classification model constructed by LASSO analysis showed that six genes including CDKN1A, FOSB, STMN2, SLC2A3, TAC, and SCRG1 can be used as biomarkers of osteoarthritis, and the SCRG1 gene shows importance in osteoarthritis. Furthermore, drug database enrichment found that these six DEGs may be the drug targets of synovitis in osteoarthritis, and Valproic Acid CTD 00006977 may be a potential targeted therapeutic drug of SCRG1. Spearman correlation analysis was performed on the SCRG1 gene, and 27 genes with consistent expression were obtained. Functional analysis showed that 27 genes were mainly involved in metabolism, complement, antigen presentation, apoptosis, and regulation of immune pathways. The co-regulatory network of TFs-miRNA suggested that the SCRG1 gene may be regulated by hsa-miR-363-3p miRNA. In conclusion, SCRG1, as a diagnostic marker of osteoarthritis, co-regulates immune-related pathways through the interaction of related proteins, playing an important role in the occurrence and development of osteoarthritis, which may be a novel drug target.
Exploring the Use of Seabirds as a Dynamic Ocean Management Tool to Mitigate Anthropogenic Risk to Large Whales
Authors: Silva Tammy L. , Powers Kevin D. , Robbins Jooke , Asmutis-Silvia Regina , Cole Timothy V. N. , Hill Alex N. , Howes Laura J. , Mayo Charles A. , Schulte Dianna , Thompson Michael A. , Welch Linda J. , Zerbini Alexandre N. , Wiley David N.
Published: June 2022

Vessel strike and entanglement in fishing gear are global threats to large whales. United States management actions to reduce human-induced serious injury and mortality to large whales have been inadequate, partially due to static, spatial protection schemes that fail to adjust to distribution shifts of highly mobile animals. Whale conservation would benefit from dynamic ocean management, but few tools exist to inform dynamic approaches. Seabirds are often found in association with whales and can be tagged at lower cost and in higher numbers than whales. We explored the use of satellite-tagged seabirds (great shearwaters) as dynamic ocean management tools for near real-time identification of habitats where humpback and North Atlantic right whales aggregate, potentially increasing anthropogenic risk. We identified shearwater habitat use areas in the Gulf of Maine with 50% kernel density utilization distributions at yearly, monthly, and weekly scales using satellite-telemetry data from 2013-2018. We quantified overlap using whale sightings and whale satellite telemetry data at two spatial scales: Stellwagen Bank National Marine Sanctuary and the Gulf of Maine. Within the sanctuary, shearwaters overlapped with >50% of humpback sightings in 4 of 6 (67%) years, 15 of 23 (65%) months, and 50 of 89 (56%) of weeks. At the Gulf of Maine scale, shearwater use areas overlapped >50% of humpback sightings in 5 of 6 years (83%) and 16 of 22 (73%) months, and encompassed humpback 50% utilization distributions (based on satellite telemetry) in 2 of 3 (66%) years and 7/12 (58%) months analyzed. Overlap between shearwaters and right whales was much lower, with >50% overlap in only 1 of 6 (17%) years and 3 of 23 (13%) months. These initial results demonstrate that satellite-tagged shearwaters can be indicators of humpback whale habitat use in both space and time. With further study, tagged shearwaters may provide near-real time information necessary to operationalize dynamic management to mitigate human impacts on humpback whales.
Fabrication of Fibrous Materials Based on Cyclodextrin and Egg Shell Waste as an Affordable Composite for Dental Applications
Authors: Amini Amirhesam , Kazemzadeh Parya , Jafari Mojtaba , Moghaddam-Manesh Mohammadreza , Chauhan Narendra Pal Singh , Fazelian Nafiseh , Sargazi Ghasem
Published: June 2022

In this study, the fibrous nanostructures based on cyclodextrin from egg shell waste were fabricated using electrospinning technique under optimal conditions. Scanning electron microscopy (SEM), thermal stability analysis and abrasion testing were used to characterise the final products. The cyclodextrin nanofibrous products were used as new nanostructures in the field of dental coatings due to the obtained properties such as uniform shape, small particle size distribution, high thermal stability and optimal abrasion resistance. The DFT calculations confirmed the chemical stability of the final products. The MTT test results confirmed that the fibrous nanocoatings of the egg shell have no significant side effects on healthy cells. These fibrous nanostructures could be a promising candidate for use as a dental nanocoating material.
The Impact of Alcohol Consumption on Cognitive Impairment in Patients With Diabetes, Hypertension, or Chronic Kidney Disease
Authors: Yen Fu-Shun , Wang Shiow-Ing , Lin Shih-Yi , Chao Yung-Hsiang , Wei James Cheng-Chung
Published: June 2022

To investigate the impact of alcohol use on the risk of cognitive impairment in older adults with chronic illness, we used the Digit Symbol Substitution Test (DSST) to evaluate cognitive function in older adults (≥ 60 years) in the National Health and Nutrition Examination Survey. Participants were categorized as light drinkers, moderate and heavy drinkers. Logistic regression analyses were used to explore associations between cognitive impairment and alcohol drinking in patients with or without diabetes, hypertension, and chronic kidney disease (CKD). Multivariate analysis showed that alcohol heavy drinkers was significantly associated with a higher risk of cognitive impairment in patients with hypertension (aOR 6.089, 95% CI 1.318–28.13) and CKD (aOR 6.324, 95% CI 1.158–34.52) compared with light drinkers. The dose-response analyses revealed that moderate to heavy alcohol use was associated with a higher risk of cognitive decline in patients with diabetes and CKD, heavy drinking increased the risk of cognitive impairment in patients with hypertension. The impacts of alcohol drinking on cognitive impairment are significantly different in patients with different comorbidities.
The Association Between Smoking and Renal Function in People Over 20 Years Old
Authors: Fu Yi-Cheng , Xu Zhi-Liang , Zhao Ming-Yi , Xu Ke
Published: June 2022

Background

Many conclusions have been reached in renal function studies in direct smokers.

Aim

This study aimed to determine the relationship between smoking and decreased renal function to ensure that reduced chronic kidney disease incidence can be achieved by limiting smoking, we assessed the relationship between cigarette smoking and renal function.

Methods

We recruited 10,267 people from the National Health and Nutrition Program Testing Survey (NHANES) aged over 20 years from 2013 to 2018 to assess smoking exposure by serum cotinine. We estimated the glomerular filtration rate (eGFR) and used multivariate linear regression models and smooth curve fittings to assess the relationship between smoking and renal function.

Results

We found an inverse relationship between serum cotinine and the eGFR. In a subgroup analysis, we found a non-linear relationship between serum cotinine and the eGFR in different ethnic groups or in different sexes. In a subgroup analysis of sex, we found inflection points between men and women for the relationship between serum cotinine and the eGFR (men 183 ng/ml and 465 ng/ml; women 227 ng/ml and 412 ng/ml). However, in a subgroup analysis by age, we found that serum cotinine showed a clear negative correlation with the eGFR in people aged 20–39 years, but in people older than 40 years, a weak correlation was shown. In stratified analysis by ethnicity, we found significant negative associations in Mexican American and Other Hispanic individuals and weaker associations in Non-Hispanic White and Non-Hispanic Black individuals.

Conclusion

Through the negative correlation between serum cotinine and the eGFR, we can conclude that as the smoking quantity increases, smoking leads to a decrease in renal function. The results of the subgroup analysis indicate that in young people, by advocating smoking cessation early, we can very effectively prevent kidney disease in this population and thus reduce the incidence of chronic kidney disease. Smoking should be included as an independent risk factor for chronic kidney disease.
Changes in Thoracic Cavity Volume After Bilateral Lung Transplantation
Authors: Yu Woo Sik , Park Chul Hwan , Paik Hyo Chae , Lee Jin Gu , You Seulgi , Shin Jaeyong , Jung Junho , Haam Seokjin
Published: June 2022

Purpose

End-stage lung diseases result in anatomical changes of the thoracic cavity. However, very few studies have assessed changes in the thoracic cavity after lung transplantation (LTx). This study aimed to evaluate the relationships between thoracic cavity volume (TCV) changes after LTx and underlying lung disease.

Methods

We reviewed 89 patients who underwent a pre-LTx pulmonary function test (PFT), chest computed tomography (CT) scan, and 1-year follow-up CT after LTx. These patients were classified into two groups according to pre-LTx PFT as follows: obstructive group [forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio < 70%] and restrictive group (FEV1/FVC ratio > 70%). We measured TCV using CT scan before and at 1 year after LTx and compared the TCV change in the two groups.

Results

In the restrictive group, TCV increased after LTx (preop: 2,347.8 ± 709.5 mL, 1-year postop: 3,224.4 ± 919.0 mL, p < 0.001). In contrast, in the obstructive group, it decreased after LTx (preop: 4,662.9 ± 1,296.3 mL, 1-year postop: 3,711.1 ± 891.7 mL, p < 0.001). We observed that restrictive lung disease, taller stature, lower body mass index, and larger donor lung were independently associated with increased TCV after LTx.

Conclusion

The disease-specific chest remodeling caused by restriction and hyperinflation is at least, in part, reversible. After LTx, the chest remodeling appears to occur in the opposite direction to the disease-specific remodeling caused by the underlying lung disease in recipients.
Research Trends on Pulmonary Rehabilitation: A Bibliometric Analysis From 2011 to 2020
Authors: Li Tao , Chen Jia
Published: June 2022

Background and Objective

A mounting body of evidence suggests that lung function may deteriorate over time with the development of chronic lung diseases (CRDs). Pulmonary rehabilitation has been proved to improve exercise capacity and quality of life in individuals with CRDs. However, PR remains grossly underutilized all around the world. This study aimed to analyze the research trends on PR over the past 10 years.

Methods

The publications related to pulmonary rehabilitation in the Web of Science Core Collection (WoSCC) from 2011 to 2020 were searched. VOSviewer (1.6.15) and CiteSpace Software (5.5.R2) were used to analyze authors and co-cited authors, countries and institutions, journals and co-cited journals, co-cited references, and keywords.

Results

A total of 4,521 publications were retrieved between 2011 and 2020, and the number of annual publications on pulmonary rehabilitation has shown an overall upward trend in the past decade. The USA was the most productive country, the University of Toronto from Canada was both the first in publications and citations. Spruit MA was both the most productive author and the one with the highest number of co-citations. The first productive journal was the International Journal of Chronic Obstructive Pulmonary Disease, while the first co-cited journal was the American Journal of Respiratory and Critical Care Medicine. The hot keywords were grouped into three clusters, while “Asthma” and “Respiratory society statement” were determined as the frontier topics.

Conclusions

The present study successfully revealed the research status and development trends of pulmonary rehabilitation from 2011 to 2020 by using bibliometric analysis, which may help researchers explore and discover new research directions in the future.
Integrated Microbiome and Host Transcriptome Profiles Link Parkinson’s Disease to Blautia Genus: Evidence From Feces, Blood, and Brain
Authors: Guo Xingzhi , Tang Peng , Hou Chen , Chong Li , Zhang Xin , Liu Peng , Chen Li , Liu Yue , Zhang Lina , Li Rui
Published: June 2022

A link between the gut microbiome and Parkinson’s disease (PD) has been intensively studied, and more than 100 differential genera were identified across the studies. However, the predominant genera contributing to PD remain poorly understood. Inspired by recent advances showing microbiota distribution in the blood and brain, we, here, comprehensively investigated currently available fecal microbiome data (1,914 samples) to identify significantly altered genera, which were further validated by comparison to the results from microbiome analysis of blood (85 samples) and brain (268 samples). Our data showed that the composition of fecal microbiota was different from that of blood and brain. We found that Blautia was the unique genus consistently depleted across feces, blood, and brain samples of PD patients (P < 0.05), despite using rigorous criteria to remove contaminants. Moreover, enrichment analyses revealed that host genes correlated with Blautia genus abundance were mainly involved in mitochondrial function and energy metabolism, and mapped to neurodegenerative diseases (NDDs) and metabolic diseases. A random forest classifier constructed with fecal microbiota data demonstrated that Blautia genus was an important feature contributing to discriminating PD patients from controls [receiver operating characteristic (ROC)-area under curve (AUC) = 0.704, precision-recall curve (PRC)-AUC = 0.787]. Through the integration of microbiome and transcriptome, our study depicted microbial profiles in the feces, blood, and brain of PD patients, and identified Blautia genus as a potential genus linked to PD. Further studies are greatly encouraged to determine the role of Blautia genus in the pathogenesis of PD.
Morphology and Molecular Phylogeny of Two New Trachelophyllid Ciliates, Monolamellophrya terricola gen. nov., sp. nov. and Trachelophyllum parapiculatum sp. nov. (Litostomatea, Haptoria), From South Korea
Authors: Omar Atef , Moon Ji Hye , Jung Jae-Ho
Published: June 2022

The morphology and molecular phylogeny of two new ciliates, Monolamellophrya terricola gen. nov., sp. nov. and Trachelophyllum parapiculatum sp. nov., discovered in South Korea, were investigated. The two species belong to the suborder Trachelophyllina, which is characterized by the presence of a mucilaginous layer containing lepidosomes covering the cortex. Monolamellophrya terricola gen. nov., sp. nov. is characterized by the presence of a single layer of type II lepidosomes, representing a new genus. Trachelophyllum parapiculatum sp. nov. has only type I lepidosomes covering the cortex, a generic character of the genus Trachelophyllum, and is distinguished from other congeners by a combination of morphological features, including the 15–24 μm long rod-shaped extrusomes, the 9–13 ciliary rows, the 7–11 and 17–25 dikinetids in brush rows 1 and 2, respectively, and the bipolar brush row 3. Furthermore, the 18S rRNA gene sequences of the two new species were provided. The phylogenetic analyses show that the sequence of M. terricola gen. nov., sp. nov. clusters with two other trachelophyllid sequences, and the sequence of T. parapiculatum sp. nov. is placed at the base of these three sequences with full support. Furthermore, the four trachelophyllid sequences that are available so far form a monophyletic clade.
A Predictive Growth Model for Pro-technological and Probiotic Lacticaseibacillus paracasei Strains Fermenting White Cabbage
Authors: Di Biase Mariaelena , Le Marc Yvan , Bavaro Anna Rita , De Bellis Palmira , Lonigro Stella Lisa , Lavermicocca Paola , Postollec Florence , Valerio Francesca
Published: June 2022

Bacterial strains belonging to Lacticaseibacillus paracasei species are generally used as starters in food fermentations and/or as probiotics. In the current study, the growth cardinal parameters of four L. paracasei strains (IMPC2.1, IMPC4.1, P40 and P101), isolated from table olives or human source, were determined. Strains were grown in liquid medium and incubated at several temperatures (10 values from 5.5°C–40°C) and pH (15 values from 3.2 to 9.1) along the growth range. The cardinal temperature model was used to describe temperature effects on the maximum specific growth rate of L. paracasei whereas new equations were developed for the effect of pH. The estimated Tmin values ranged between −0.97°C and 1.95°C and were lower than 0°C for strains IMPC4.1 and P101. Strain P40 was able to grow in the most restricted range of temperature (from 1.95°C to 37.46°C), while strain IMPC4.1 was estimated to survive at extreme conditions showing the lowest pHmin. Maximum specific growth rates of L. paracasei IMPC2.1 in white cabbage (Brassica oleracea var. capitata) were used to calculate the correction factor (Cf) defined as the bias between the bacterial maximum specific growth rate in broth and in the food matrix. A simple bi-linear model was also developed for the effect of temperature on the maximum population density reached in white cabbage. This information was further used to simulate the growth of L. paracasei strains in cabbage and predict the time to reach the targeted probiotic level (7 log10 CFU/g) using in silico simulations. This study demonstrates the potential of the predictive microbiology to predict the growth of beneficial and pro-technological strains in foods in order to optimize the fermentative process.
The Antibacterial Activity of Thymol Against Drug-Resistant Streptococcus iniae and Its Protective Effect on Channel Catfish (Ictalurus punctatus)
Authors: Yin Lizi , Liang Chao , Wei Wenyan , Huang Shuanghui , Ren Yongqiang , Geng Yi , Huang Xiaoli , Chen Defang , Guo Hongrui , Fang Jing , Deng Huidan , Lai Weimin , Yu Shumin , Ouyang Ping
Published: June 2022

Streptococcus iniae is a zoonotic pathogen, which seriously threatens aquaculture and human health worldwide. Antibiotics are the preferred way to treat S. iniae infection. However, the unreasonable use of antibiotics leads to the enhancement of bacterial resistance, which is not conducive to the prevention and treatment of this disease. Therefore, it is urgent to find new efficient and environmentally friendly antibacterial agents to replace traditional antibiotics. In this study, the antibacterial activity and potential mechanism of thymol against S. iniae were evaluated by electron microscopy, lactate dehydrogenase, DNA and protein leakage and transcriptomic analysis. Thymol exhibited potent antibacterial activity against S. iniae in vitro, and the MIC and MBC were 128 and 256μg/mL, respectively. SEM and TEM images showed that the cell membrane and cell wall were damaged, and the cells were abnormally enlarged and divided. 2MIC thymol disrupted the integrity of cell walls and membranes, resulting in the release of intracellular macromolecules including nucleotides, proteins and inorganic ions. The results of transcriptomic analysis indicated that thymol interfered with energy metabolism and membrane transport, affected DNA replication, repair and transcription in S. iniae. In vivo studies showed that thymol had a protective effect on experimental S. iniae infection in channel catfish. It could reduce the cumulative mortality of channel catfish and the number of S. iniae colonization in tissues, and increase the activities of non-specific immune enzymes in serum, including catalase, superoxide dismutase, lysozyme and acid phosphatase. Taken together, these findings suggested that thymol may be a candidate plant agent to replace traditional antibiotics for the prevention and treatment of S. iniae infection.
Repurposing the Sphingosine-1-Phosphate Receptor Modulator Etrasimod as an Antibacterial Agent Against Gram-Positive Bacteria
Authors: Zore Matej , Gilbert-Girard Shella , San-Martin-Galindo Paola , Reigada Inés , Hanski Leena , Savijoki Kirsi , Fallarero Adyary , Yli-Kauhaluoma Jari , Patel Jayendra Z.
Published: June 2022

New classes of antibiotics are urgently needed in the fight against multidrug-resistant bacteria. Drug repurposing has emerged as an alternative approach to accelerate antimicrobial research and development. In this study, we screened a library of sphingosine-1-phosphate receptor (S1PR) modulators against Staphylococcus aureus and identified five active compounds. Among them, etrasimod (APD334), an investigational drug for the treatment of ulcerative colitis, displayed the best inhibitory activity against S. aureus when growing as free-floating planktonic cells and within biofilms. In follow-up studies, etrasimod showed bactericidal activity and drastic reduction of viable bacteria within 1 h of exposure. It also displayed a potent activity against other Gram-positive bacteria, including penicillin- and methicillin-resistant S. aureus strains, S. epidermidis, and Enterococcus faecalis, with a minimum inhibitory concentration (MIC) ranging from 5 to 10 μM (2.3–4.6 μg/mL). However, no inhibition of viability was observed against Gram-negative bacteria Acinetobacter baumannii, Escherichia coli, and Pseudomonas aeruginosa, showing that etrasimod preferably acts against Gram-positive bacteria. On the other hand, etrasimod was shown to inhibit quorum sensing (QS) signaling in Chromobacterium violaceum, suggesting that it may block the biofilm formation by targeting QS in certain Gram-negative bacteria. Furthermore, etrasimod displayed a synergistic effect with gentamicin against S. aureus, thus showing potential to be used in antibiotic combination therapy. Finally, no in vitro toxicity toward mammalian cells was observed. In conclusion, our study reports for the first time the potential of etrasimod as a repurposed antibacterial compound against Gram-positive bacteria.
Effect of Exercise on Breast Cancer: A Systematic Review and Meta-analysis of Animal Experiments
Authors: Li Yuxi , Xiao Xili , Zhang Yue , Tang Wenjing , Zhong Dongling , Liu Tianyu , Zhu Yuanyuan , Li Juan , Jin Rongjiang
Published: June 2022

Objective: Exercise is reported to be beneficial for breast cancer. However, the results seem inconsistent. We conducted this systematic review and meta-analysis of animal experimental studies to fully understand the effect of exercise on breast cancer in animal model.

Methods: We searched databases from inception to April 2022 and manually searched related references to retrieve eligible studies. We screened eligible studies and extracted related data. We assessed the risk of bias and reporting quality using the SYstematic Review Centre for Laboratory animal Experimentation Risk of Bias tool and the Animal Research: Reporting of In Vivo Experiments guidelines 2.0, respectively. We summarized the study characteristics and findings of included studies and conducted meta-analysis with RevMan software. Subgroup analysis and sensitivity analysis were also performed.

Results: We identified 537 potential literatures and included 47 articles for analysis. According to the results of risk of bias assessment, only selective outcome reporting was in low risk of bias. Items of sequence generation, random outcome assessment, and incomplete outcome data were rated as high risk of bias. Most of other items were rated unclear risk of bias. In reporting quality assessment, all included articles reported grouping method and experimental procedures. However, no study provided information of the study protocol registration. Meta-analysis showed that, compared with sedentary lifestyle, exercise reduced more tumor weight (MD = −0.76, 95%CI −0.88 to −0.63, p = 0.85, I2 = 0%) and tumor number per animal (MD = −0.61, 95%CI −0.91 to −0.31, p = 0.34, I2 = 8%). Exercise decreased more tumor incidence than sedentary lifestyle both in motorized wheel/high-intensity (OR = 0.22, 95%CI 0.11 to 0.46, p = 0.09, I2 = 41%) and free wheel/low-intensity treadmill running (OR = 0.45, 95%CI 0.14 to 1.44, p = 0.04, I2 = 60%). Sensitivity analysis showed that the results were robust.

Conclusion: Exercise could reduce tumor weight, number of tumors per animal, and incidence of tumor in breast cancer model of mice and rats. However, the risk of bias items and reporting guidelines in preclinical studies should be concerned. Future research should consider standards of conducting and reporting preclinical studies and choose suitable exercise protocol for higher quality evidence of exercise for breast cancer.
In vivo Proximity Labeling of Nuclear and Nucleolar Proteins by a Stably Expressed, DNA Damage-Responsive NONO-APEX2 Fusion Protein
Authors: Trifault Barbara , Mamontova Victoria , Burger Kaspar
Published: June 2022

Cellular stress can induce DNA lesions that threaten the stability of genes. The DNA damage response (DDR) recognises and repairs broken DNA to maintain genome stability. Intriguingly, components of nuclear paraspeckles like the non-POU domain containing octamer-binding protein (NONO) participate in the repair of DNA double-strand breaks (DSBs). NONO is a multifunctional RNA-binding protein (RBP) that facilitates the retention and editing of messenger (m)RNA as well as pre-mRNA processing. However, the role of NONO in the DDR is poorly understood. Here, we establish a novel human U2OS cell line that expresses NONO fused to the engineered ascorbate peroxidase 2 (U2OS:NONO-APEX2-HA). We show that NONO-APEX2-HA accumulates in the nucleolus in response to DNA damage. Combining viability assays, subcellular localisation studies, coimmunoprecipitation experiments and in vivo proximity labeling, we demonstrate that NONO-APEX2-HA is a stably expressed fusion protein that mimics endogenous NONO in terms of expression, localisation and bona fide interactors. We propose that in vivo proximity labeling in U2OS:NONO-APEX2-HA cells is capable for the assessment of NONO interactomes by downstream assays. U2OS:NONO-APEX2-HA cells will likely be a valuable resource for the investigation of NONO interactome dynamics in response to DNA damage and other stimuli.
Neuroligin Plays a Role in Ethanol-Induced Disruption of Memory and Corresponding Modulation of Glutamate Receptor Expression
Authors: Rose Jacqueline K. , Butterfield Michael , Liang Joseph , Parvand Mahraz , Lin Conny H. S. , Rankin Catharine H.
Published: June 2022

Exposure to alcohol causes deficits in long-term memory formation across species. Using a long-term habituation memory assay in Caenorhabditis elegans, the effects of ethanol on long-term memory (> 24 h) for habituation were investigated. An impairment in long-term memory was observed when animals were trained in the presence of ethanol. Cues of internal state or training context during testing did not restore memory. Ethanol exposure during training also interfered with the downregulation of AMPA/KA-type glutamate receptor subunit (GLR-1) punctal expression previously associated with long-term memory for habituation in C. elegans. Interestingly, ethanol exposure alone had the opposite effect, increasing GLR-1::GFP punctal expression. Worms with a mutation in the C. elegans ortholog of vertebrate neuroligins (nlg-1) were resistant to the effects of ethanol on memory, as they displayed both GLR-1::GFP downregulation and long-term memory for habituation after training in the presence of ethanol. These findings provide insights into the molecular mechanisms through which alcohol consumption impacts memory.