bluuebunny/crossref_metadata_2025 huggingface dataset:
Clinical and economic impact of coronary artery bypass graft and percutaneous coronary intervention in young individuals with acute coronary syndromes and multivessel disease: A real-world comparison in a middle-income country
Authors: Alexim Gustavo de Almeida , Rocha Luiza Ferreira , Dobri Giovani Prediger , Rosa Júnior Adair da Silva , Reis Ricardo Torres Bispo , Nogueira Ana Claudia Cavalcante , Soares Alexandre Anderson de Souza Munhoz , Sposito Andrei Carvalho , de Paula Ana Patricia , de Carvalho Luiz Sérgio Fernandes
Published: November 2022

Background

In recent decades, the world watched a dramatic increase in the incidence of acute coronary syndromes (ACS) among young individuals (≤55 years-old) and a relative decrease in the elderly. The management of ACS in young patients with multivessel disease still needs to be elucidated, as these individuals maintain a long life expectancy.

Research Question

To compare clinical outcomes and care costs in individuals with premature ACS and multivessel disease undergoing coronary artery bypass graft surgery (CABG) or percutaneous coronary intervention (PCI).

Methods and Results

Participants included all individuals ≤55 years-old admitted with ACS to public hospitals in Brasília (Brazil) between 2013 and 2015 and who underwent cardiac catheterization with SYNTAX score ≥23 or Duke category 6. Outcomes were adjudicated with death certificates and data from medical records. The primary outcome was the occurrence of major adverse cardiovascular events (MACE), defined as death due to cardiovascular causes, recurrent hospitalizations due to cardiovascular ischemic events, and incident heart failure New York Heart Association III-IV. As secondary outcome we assessed indirect and direct costs by evaluating the cost of lost productivity (in international dollars (Int$) per year) due to illness and death, outpatient costs and costs with new hospitalizations. Multivariate and principal components (PC) adjusted analyzes were performed.

Results

Among 1,088 subjects (111 CABG and 977 PCI) followed for 6.2 years (IQR: 1.1), 304 primary events were observed. MACE was observed in 20.7% of the CABG group and 28.8% of the PCI group (p = 0.037). In multivariate analyses, PCI was associated with a hazard ratio (HR) = 1.227 (95% CI: 1.004–1.499; p = 0.0457) for MACE, and in PC-adjusted HR = 1.268 (95% CI: 1.048–1.548; p = 0.0271) compared with CABG. Despite direct costs were equivalent, the cost due to the loss of labor productivity was higher in the PCI group (Int$ 4,511 (IQR: 18,062)/year vs Int$ 3,578 (IQR: 13,198)/year; p = 0.049], compared with CABG.

Conclusions

Among young individuals with ACS and multivessel disease, surgical strategy was associated with a lower occurrence of MACE and lower indirect costs in the long-term.
Perspectives on pediatric congenital aortic valve stenosis: Extracellular matrix proteins, post translational modifications, and proteomic strategies
Authors: Clift Cassandra L. , Saunders Janet , Drake Richard R. , Angel Peggi M.
Published: November 2022

In heart valve biology, organization of the extracellular matrix structure is directly correlated to valve function. This is especially true in cases of pediatric congenital aortic valve stenosis (pCAVS), in which extracellular matrix (ECM) dysregulation is a hallmark of the disease, eventually leading to left ventricular hypertrophy and heart failure. Therapeutic strategies are limited, especially in pediatric cases in which mechanical and tissue engineered valve replacements may not be a suitable option. By identifying mechanisms of translational and post-translational dysregulation of ECM in CAVS, potential drug targets can be identified, and better bioengineered solutions can be developed. In this review, we summarize current knowledge regarding ECM proteins and their post translational modifications (PTMs) during aortic valve development and disease and contributing factors to ECM dysregulation in CAVS. Additionally, we aim to draw parallels between other fibrotic disease and contributions to ECM post-translational modifications. Finally, we explore the current treatment options in pediatrics and identify how the field of proteomics has advanced in recent years, highlighting novel characterization methods of ECM and PTMs that may be used to identify potential therapeutic strategies relevant to pCAVS.
A case report of melanotic neuroectodermal tumor of infancy complicated with congenital heart disease and hypothyroidism
Authors: Zuo Hua-Chu , Huang Jin-Yue , Hu Xiao-Li , Zhao Lin-Sheng
Published: November 2022

To the best of our knowledge, thus far there are no reported cases of melanotic neuroectodermal tumor of infancy (MNTI) with multiple complications. In this case report, we describe the clinical phenotype of MNTI in a 9-month-old female infant associated with tetralogy of Fallot (TOF), a congenital heart defect, and congenital hypothyroidism (CH). Our study showed that the growth of MNTI was delayed by a lower dosage of levothyroxine (L-T4) that was prescribed to treat CH because of the presence of TOF, a severe congenital heart disease. However, the standardized dosage of L-T4 improved thyroid function but stimulated the rapid growth of MNTI. Our report demonstrated that treatment with L-T4 affects the progression of MNTI. Our findings demonstrated the role of thyroid hormone in MNTI growth and progression. Furthermore, our study suggested that the treatment of co-morbidities in children with MNTI requires careful consideration of their effects on the growth and progression of MNTI.
Effects of different types of radiation therapy on cardiac-specific death in patients with thyroid malignancy
Authors: Wang Ruxin , Ye Haowen , Wang Ying , Ma Li , Wei Jinjing , Zhang Xiaofang , Wang Lihong
Published: November 2022

Radiation therapy (RT) is one of the common and widely used treatment method for thyroid tumors. Considering that the thyroid is located close to the heart, the radiation generated during the treatment of thyroid tumors may have an adverse greater impact on the heart. This study is to explore the influencing factors, especially additional effects of RT, on cardiac-specific death among patients with malignant thyroid tumors. Collecting information from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) database using SEER*Stat. Patients with malignant thyroid tumors were searched, whether receiving RT or not. Ultimately, 201, 346 eligible patients were included. Propensity Score Matching (PSM) was used to minimize bias of baseline characteristics by adjusting for confounding factors. COX (proportional hazards) and fine-gray (competing risk) model regression analysis were used to explore the effects of various influencing factors on cardiac-specific death. The present analysis showed that, compared with non-RT, RT based upon radioactive implants and beam radiation were associated with lower risk of cardiac-specific death in patients with thyroid malignancy, beam radiation therapy may had a similar effect. Besides, the remaining RT methods did not significantly increase the risk of cardiac-specific death. In addition, Asian or Pacific Islander ethnicity, female sex, marital status, combined summary stage (localized, regional, and distant), high-income, and later year of diagnosis were associated with lower risk of cardiac-specific death. While older age of diagnosis, African ethnicity, non-Hispanic ancestry, and derived AJCC stage (IV) were risk factors for cardiac-specific death. These results help to identify the factors influencing cardiac-specific death among patients with thyroid malignancies. Furthermore, it may helps to improve the clinical application of RT without too much concern about adverse cardiac effects.
Reduction in final year medical students’ knowledge during the COVID-19 pandemic: Insights from an interinstitutional progress test
Authors: Hamamoto Filho Pedro Tadao , Cecilio-Fernandes Dario , Norcia Luiz Fernando , Sandars John , Anderson M. Brownell , Bicudo Angélica Maria
Published: November 2022

There has been little information about how the COVID-19 pandemic has impacted medical students’ knowledge acquisition. The aim of the study was to identify the impact of the COVID-19 pandemic on medical students’ knowledge acquisition by comparing the students’ performance on two Progress Test exams administered in 2019 (pre-pandemic) and 2020 (during the pandemic). We included data from 1,491 students at two medical schools in Brazil. Both schools had experienced interrupted preclinical classes and clinical clerkship rotations in March 2020 but had resumed remote preclinical classes with online activities within 1  month after the interruption and clerkship rotations within five to 6 months after the interruption. We analyzed the data with the Rasch model from Item Response Theory to calibrate the difficulty of the two exams and calculated the performance of the students, with comparison of the differences of mean knowledge for each year and between the two cohorts. We found that the students’ knowledge in the cohort of 2019 was higher than those in the cohort of 2020, except in the second year. Also, the students did not show any increase in knowledge between 2019 and 2020 in the clerkship years. It appears that the pandemic significantly impaired the knowledge acquisition of medical students, mainly in the clerkship years, where practical activities are the central part of training. This is of special concern in low- and middle-income countries where graduated medical doctors are allowed to practice without further training or are required to have continuing professional development.
Endocrine system after 2 years of COVID-19 vaccines: A narrative review of the literature
Authors: Pezzaioli Letizia Chiara , Gatta Elisa , Bambini Francesca , Facondo Paolo , Gava Maria , Cavadini Maria , Buoso Caterina , Di Lodovico Elena , Rotondi Mario , Ferlin Alberto , Cappelli Carlo
Published: November 2022

Purpose

The purpose of this study was to describe the current knowledge on the potential endocrine adverse effects post-COVID-19 vaccines.

Methods

A PubMed/MEDLINE, Web of Science, and Scopus research was performed. Case reports, case series, original studies, and reviews written in English and published online up to 31 July 2022 were selected and reviewed. The final reference list was defined based on the relevance of each paper to the scope of this review.

Results

The available data showed that endocrine side effects are generally rare and with favorable outcome, being thyroid disorders the most common. Conversely, data on type 1 diabetes mellitus are rare; adrenal and pituitary events are even anecdotal. Finally, the available clinical studies suggest no impact on female reproductive system and on male and couple fertility.

Conclusion

Overall, these data show that, after 2 years of COVID-19 vaccines, the endocrine system is not heavily threatened.
Identification of unusual oxysterols biosynthesised in human pregnancy by charge-tagging and liquid chromatography - mass spectrometry
Authors: Dickson Alison L. , Yutuc Eylan , Thornton Catherine A. , Wang Yuqin , Griffiths William J.
Published: November 2022

The aim of this study was to identify oxysterols and any down-stream metabolites in placenta, umbilical cord blood plasma, maternal plasma and amniotic fluid to enhance our knowledge of the involvement of these molecules in pregnancy. We confirm the identification of 20S-hydroxycholesterol in human placenta, previously reported in a single publication, and propose a pathway from 22R-hydroxycholesterol to a C27 bile acid of probable structure 3β,20R,22R-trihydroxycholest-5-en-(25R)26-oic acid. The pathway is evident not only in placenta, but pathway intermediates are also found in umbilical cord plasma, maternal plasma and amniotic fluid but not non-pregnant women.
Type 1 diabetes complicated with cyclic vomiting syndrome and exogenous insulin antibody syndrome: A case report
Authors: Geng Leiluo , Diao Xue , Han Hao , Lin Ying , Liang Wei , Xu Aimin
Published: November 2022

Every fifth individual with type 1 diabetes (T1D) suffers from an additional autoimmune disorder due to shared genetic factors and dysregulated immunity. Here we report an extremely rare case of T1D complicated with cyclic vomiting and hypoglycaemia. A 27-year-old Chinese woman with 14-year history of T1D was periodically hospitalized for severe vomiting of more than 30 times a day without apparent organic causes. The vomiting developed acutely and remitted spontaneously after 2-3 days, followed with intractable hypoglycaemia for another 3-4 days during the hospitalization. A few weeks after discharge, she was admitted once again with the same symptoms and disease course. Cyclic vomiting syndrome (CVS) was diagnosed according to the Rome IV criteria, a system developed to define the functional gastrointestinal disorders. Dynamic association and disassociation of exogenous insulin and insulin antibodies (IAs) were identified in her blood during hypoglycaemia, leading to the diagnosis of exogenous insulin antibody syndrome (EIAS). Treatment with rituximab to suppress the IAs was associated with a striking amelioration of hypoglycaemia. Unexpectedly, the episodes of cyclic vomiting were also dramatically reduced. In conclusion, we identified the first case with alternating CVS and EIAS in the setting of T1D. Dynamic measurements of free and total insulin are helpful for the diagnosis of EIAS. CVS is likely to be a latent autoimmune disorder considering the good response to rituximab treatment.
Does digital financial inclusion matter for firms’ ESG disclosure? Evidence from China
Authors: Lu Yichun , Wang Liang , Zhang Yu
Published: November 2022

Using a sample of Chinese listed firms during 2010–2018, this paper examines the relationship between digital financial inclusion and firms’ ESG disclosure. The results show that 1) digital financial inclusion can significantly promote firms’ ESG disclosure; 2) the promotion effect of digital financial inclusion on firms’ ESG disclosure occurs mainly through channels including the coverage breadth and usage depth; and 3) for firms with higher financing constraints and state-owned enterprises, the promotion effect of digital financial inclusion on firms’ ESG disclosure is more prominent. This paper provides relevant conclusions and insights for promoting firms’ ESG information disclosure, integrating the digital economy, and encouraging innovation development.
Impacts of the development of mineral metal resources on surface water quality in the Mongolian Plateau based on meta-analysis
Authors: Ma Linqian , Liu Huamin , Jing Jin , Liu Yang , Zhang Rui , Xu Zhichao , Qin Wei , Kou Xin , Cao Xiaoai , Wen Lu , Wang Lixin
Published: November 2022

The mining of metal resources is one of the major sources of heavy metals in surface water, but studies on the different characteristics of the impact of the exploitation of mineral metal resources on surface water from a large-scale perspective are lacking. In the present study, we quantified the impacts of mineral metal resource development on As, Cu, Cr, Pb, Zn, Hg, Ni, Cd, Mn, and Fe in the overlying water and sediments of surface water under different scenarios (i.e., different geographic units and different mined metal types) using meta-analysis for the Mongolian Plateau of Mongolia and the Inner Mongolia Autonomous Region of China, which is rich in mineral metal resources and has high exploitation and use intensity. Finally, funnel plots and Egger’s regression analysis were used to test the publication bias of the data. The results show that the order of heavy metal content in the overlying water of the Mongolian Plateau was Fe > Mn > As > Zn > Cu > Pb > Cr > Ni > Cd > Hg, and the order of heavy metal content in the sediment was Fe > Mn > Zn > Cr > Pb > Ni > Cu > As > Cd > Hg. In addition, As, Cr, Zn, Hg, Cd, and Pb in overlying water exceeded the standard to different degrees, among which the contents of As and Pb were 1.4 and 1.3 times higher than the World Health Organization guideline, and the contents of Cr, Pb, Hg, Cd were 1.5, 1.3, 25.4, 2.6 times Chinese environmental quality standards for surface water, and the contents of As, Pb, Zn, Hg were 1.4, 1.3, 4.7, 12.7 times Mongolian water quality standards, respectively. The content of As in sediments was 2.6 times the background value of soil environmental quality in Inner Mongolia. Significant differences existed in the content of heavy metal pollutants in surface water of different countries; the content of heavy metals in the overlying water was significantly higher in Inner Mongolia Autonomous Region of China than in Mongolia. Copper and molybdenum polymetallic mines significantly increased the content of Cd, Cr, Cu, Fe, Hg, Pb, and Zn in the overlying water, while the content of As, Cr, Pb, and Zn in overlying water increased significantly due to lead–zinc mining. However, the mining of gold–silver, lead–zinc, copper–molybdenum, and other polymetallic mines all significantly affected the concentration of As in sediments. The results of the present study can provide data support for environmental protection and the restoration of surface water in metal mining areas of the Mongolian Plateau.
Tax incentives and green innovation—The mediating role of financing constraints and the moderating role of subsidies
Authors: Wang Cong , Chen Pengyu , Hao Yuanyuan , Dagestani Abd Alwahed
Published: November 2022

Government intervention is increasingly vital due to the dual externalities of green innovation. We explored the relationship between tax incentives, subsidies, and green innovation. Based on data from Chinese listed companies from 2010 to 2019, we developed an evaluation system for corporate green innovation. First, we find that tax incentives promote corporate green innovation, while subsidies have little effect on green innovation. Second, we find that financing constraints are the main path of influence of tax incentives. Also, subsidies reverse the positive impact of tax incentives. Third, we further explore the heterogeneity of firms. We find that tax incentives and subsidies only impact green innovation by state-owned enterprises, monopolies, and small and medium-sized enterprises. We hope to provide new theoretical insights into intervention policy improvements and corporate green innovation in developing countries such as China.
Spatial-temporal variation characteristics of cultivated land and controlling factors in the Yangtze River Delta region of China
Authors: Huo Kun , Ruan Yunfeng , Fan Haizhou , Guo Chunhui , Cai Hong
Published: November 2022

Comprehending the change characteristics and controlling factors of regional cultivated land resources is one of the important preconditions for their healthy development. The main objective of this study is to analyze the spatial–temporal variation characteristics of cultivated land and controlling factors in the Yangtze River Delta region. Thus, the mathematical–statistical, land use dynamic degree model, principal component analysis, and geographically weighted regression model were used to analyze the change in cultivated land area and social–economic factors in the Yangtze River Delta region from 2009 to 2018. The results showed that the cultivated land area and per capita cultivated land area had a decreasing trend from 2009 to 2018, decreasing by 8.5 × 104 ha and 0.0039 ha, respectively. From the perspective of spatial patterns, the rapidly decreasing areas of cultivated land were mainly distributed in the southeast, while the slowly decreasing areas of cultivated land were becoming concentrated in the northwest, and the slowly increasing areas presented as scattered distribution, which was also the same spatial distribution for the per capita cultivated land area in the Yangtze River Delta region. Among these factors, population (POP) and the total power of agricultural mechanization (TPAM) had a positive spatial correlation with cultivated land. The gross domestic product (GDP) had a negative spatial correlation with cultivated land, which revealed that cultivated land was intensely affected by human activities. Moreover, the spatial distribution and influence degree of the controlling factors differed in regions. Our research is expected to reveal the relationship between economic development and cultivated land protection for providing references for strengthening regional cultivated land management, maintaining the healthy development of regional resources, and rational utilization of cultivated land.
Aedes aegypti anti-salivary proteins IgG levels in a cohort of DENV-like symptoms subjects from a dengue-endemic region in Colombia
Authors: Olajiga Olayinka M. , Marin-Lopez Alejandro , Cardenas Jenny C. , Gutierrez-Silva Lady Y. , Gonzales-Pabon Maria U. , Maldonado-Ruiz L. Paulina , Worges Matt , Fikrig Erol , Park Yoonseong , Londono-Renteria Berlin
Published: November 2022

Dengue fever, caused by the dengue virus (DENV), is currently a threat to about half of the world's population. DENV is mainly transmitted to the vertebrate host through the bite of a female Aedes mosquito while taking a blood meal. During this process, salivary proteins are introduced into the host skin and blood to facilitate blood acquisition. These salivary proteins modulate both local (skin) and systemic immune responses. Several salivary proteins have been identified as immunogenic inducing the production of antibodies with some of those proteins also displaying immunomodulatory properties enhancing arboviral infections. IgG antibody responses against salivary gland extracts of a diverse number of mosquitoes, as well as antibody responses against the Ae. aegypti peptide, Nterm-34 kDa, have been suggested as biomarkers of human exposure to mosquito bites while antibodies against AgBR1 and NeSt1 proteins have been investigated for their potential protective effect against Zika virus (ZIKV) and West Nile virus infections. Thus, we were interested in evaluating whether IgG antibodies against AgBR1, NeSt1, Nterm-34 kDa peptide, and SGE were associated with DENV infections and clinical characteristics. For this, we tested samples from volunteers living in a dengue fever endemic area in Colombia in 2019 for the presence of IgG antibodies against those salivary proteins and peptides using an ELISA test. Results from this pilot study suggest an involvement of antibody responses against salivary proteins in dengue disease progression.
Water–energy, climate, and habitat heterogeneity mutually drives spatial pattern of tree species richness in the Indian Western Himalaya
Authors: Thakur Shinny , Dhyani Rupesh , Negi Vikram S. , Bhatt Indra D.
Published: November 2022

Analyzing plant species richness across a broad geographic gradient is critical for understanding the patterns and processes of biodiversity. In view of this, a species richness map was developed by stacking the ranges of 51 tree species along an elevational gradient in the Western Himalaya using stacked species distribution models (SSDMs). Among modeling algorithms available in SSDMs, random forest and artificial neural networks exhibited the best performance (r = 0.81, p < 0.001). The predicted tree species richness distribution pattern revealed a mid-elevation peak at around 2,000 m asl, which is in concordance with the observed richness pattern (R2 = 0.94, p < 0.001). Additionally, structural equation models (SEMs) were used to confirm the key factors that influence tree richness. The results based on SEMs confirm that the elevational pattern of predicted tree species richness is explained by mutual effects of water–energy availability, climate, and habitat heterogeneity. This study also validates that the impact of moisture on tree species richness coincides geographically with climate factors. The results have revealed that water–energy-related variables are likely to impact the species richness directly at higher elevations, whereas the effect is more likely to be tied to moisture at lower elevations. SSDMs provide a good tool to predict a species richness pattern and could help in the conservation and management of high biodiverse areas at different spatial scales. However, more investigation is needed to validate the SSDMs in other parts of the Himalayan region to provide a comprehensive synoptic perspective of Himalayan biodiversity at a larger scale.
From the reference human genome to human pangenome: Premise, promise and challenge
Authors: Singh Vipin , Pandey Shweta , Bhardwaj Anshu
Published: November 2022

The Reference Human Genome remains the single most important resource for mapping genetic variations and assessing their impact. However, it is monophasic, incomplete and not representative of the variation that exists in the population. Given the extent of ethno-geographic diversity and the consequent diversity in clinical manifestations of these variations, population specific references were developed overtime. The dramatically plummeting cost of sequencing whole genomes and the advent of third generation long range sequencers allowing accurate, error free, telomere-to-telomere assemblies of human genomes present us with a unique and unprecedented opportunity to develop a more composite standard reference consisting of a collection of multiple genomes that capture the maximal variation existing in the population, with the deepest annotation possible, enabling a realistic, reliable and actionable estimation of clinical significance of specific variations. The Human Pangenome Project thus is a logical next step promising a more accurate and global representation of genomic variations. The pangenome effort must be reciprocally complemented with precise variant discovery tools and exhaustive annotation to ensure unambiguous clinical assessment of the variant in ethno-geographical context. Here we discuss a broad roadmap, the challenges and way forward in developing a universal pangenome reference including data visualization techniques and integration of prior knowledge base in the new graph based architecture and tools to submit, compare, query, annotate and retrieve relevant information from the pangenomes. The biggest challenge, however, will be the ethical, legal and social implications and the training of human resource to the new reference paradigm.
An altered transcriptome underlies cln5-deficiency phenotypes in Dictyostelium discoideum
Authors: Kim William D. , Huber Robert J.
Published: November 2022

Mutations in CLN5 cause a subtype of neuronal ceroid lipofuscinosis (NCL) called CLN5 disease. The NCLs, commonly referred to as Batten disease, are a family of neurodegenerative lysosomal storage diseases that affect all ages and ethnicities globally. Previous research showed that CLN5 participates in a variety of cellular processes. However, the precise function of CLN5 in the cell and the pathway(s) regulating its function are not well understood. In the model organism Dictyostelium discoideum, loss of the CLN5 homolog, cln5, impacts various cellular and developmental processes including cell proliferation, cytokinesis, aggregation, cell adhesion, and terminal differentiation. In this study, we used comparative transcriptomics to identify differentially expressed genes underlying cln5-deficiency phenotypes during growth and the early stages of multicellular development. During growth, genes associated with protein ubiquitination/deubiquitination, cell cycle progression, and proteasomal degradation were affected, while genes linked to protein and carbohydrate catabolism were affected during early development. We followed up this analysis by showing that loss of cln5 alters the intracellular and extracellular amounts of proliferation repressors during growth and increases the extracellular amount of conditioned medium factor, which regulates cAMP signalling during the early stages of development. Additionally, cln5- cells displayed increased intracellular and extracellular amounts of discoidin, which is involved in cell-substrate adhesion and migration. Previous work in mammalian models reported altered lysosomal enzyme activity due to mutation or loss of CLN5. Here, we detected altered intracellular activities of various carbohydrate enzymes and cathepsins during cln5- growth and starvation. Notably, cln5- cells displayed reduced β-hexosaminidase activity, which aligns with previous work showing that D. discoideum Cln5 and human CLN5 can cleave the substrate acted upon by β-hexosaminidase. Finally, consistent with the differential expression of genes associated with proteasomal degradation in cln5- cells, we also observed elevated amounts of a proteasome subunit and reduced proteasome 20S activity during cln5- growth and starvation. Overall, this study reveals the impact of cln5-deficiency on gene expression in D. discoideum, provides insight on the genes and proteins that play a role in regulating Cln5-dependent processes, and sheds light on the molecular mechanisms underlying CLN5 disease.
Genome-wide analysis of NBS-LRR genes in Rosaceae species reveals distinct evolutionary patterns
Authors: Guo Liping , You Chen , Zhang Hanghang , Wang Yukun , Zhang Rui
Published: November 2022

The nucleotide-binding site and leucine-rich repeat (NBS-LRR) genes, one of the largest gene families in plants, are evolving rapidly and playing a critical role in plant resistance to pathogens. In this study, a genome-wide search in 12 Rosaceae genomes screened out 2188 NBS-LRR genes, with the gene number varied distinctively across different species. The reconciled phylogeny revealed 102 ancestral genes (7 RNLs, 26 TNLs, and 69 CNLs), which underwent independent gene duplication and loss events during the divergence of the Rosaceae. The NBS-LRR genes exhibited dynamic and distinct evolutionary patterns in the 12 Rosaceae species due to independent gene duplication/loss events, which resulted the discrepancy of NBS-LRR gene number among Rosaceae species. Specifically, Rubus occidentalis, Potentilla micrantha, Fragaria iinumae and Gillenia trifoliata, displayed a “first expansion and then contraction” evolutionary pattern; Rosa chinensis exhibited a “continuous expansion” pattern; F. vesca had a “expansion followed by contraction, then a further expansion” pattern, three Prunus species and three Maleae species shared a “early sharp expanding to abrupt shrinking” pattern. Overall, this study elucidated the dynamic and complex evolutionary patterns of NBS-LRR genes in the 12 Rosaceae species, and could assist further investigation of mechanisms driving these evolutionary patterns.
Comparisons of constitutive resistances to soybean cyst nematode between PI 88788- and Peking-type sources of resistance in soybean by transcriptomic and metabolomic profilings
Authors: Chu Shanshan , Ma Hui , Li Ke , Li Junfeng , Liu Hongli , Quan Leipo , Zhu Xuling , Chen Meiling , Lu Wenyan , Chen Xiaoming , Qu Xuelian , Xu Jiaqi , Lian Yun , Lu Weiguo , Xiong Erhui , Jiao Yongqing
Published: November 2022

Soybean cyst nematode (SCN) is a serious damaging disease in soybean worldwide. Peking- and PI 88788-type sources of resistance are two most important germplasm used in breeding resistant soybean cultivars against this disease. However, until now, no comparisons of constitutive resistances to soybean cyst nematode between these two types of sources had been conducted, probably due to the influences of different backgrounds. In this study, we used pooled-sample analysis strategy to minimize the influence of different backgrounds and directly compared the molecular mechanisms underlying constitutive resistance to soybean cyst nematode between these two types of sources via transcriptomic and metabolomic profilings. Six resistant soybean accessions that have identical haplotypes as Peking at Rgh1 and Rhg4 loci were pooled to represent Peking-type sources. The PI88788-type and control pools were also constructed in a same way. Through transcriptomic and metabolomics anaylses, differentially expressed genes and metabolites were identified. The molecular pathways involved in the metabolism of toxic metabolites were predicted to play important roles in conferring soybean cyst nematode resistance to soybean. Functions of two resistant candidate genes were confirmed by hairy roots transformation methods in soybean. Our studies can be helpful for soybean scientists to further learn about the molecular mechanism of resistance to soybean cyst nematode in soybean.
HOXA-AS2 may be a potential prognostic biomarker in human cancers: A meta-analysis and bioinformatics analysis
Authors: Zhang Fan , Zhang Guangming , Zhang Helin , Pu Xingyu , Chi Fei , Zhang Dengxiao , Xin Xiaoming , Gao Mingxuan , Luo Wenyuan , Li Xingyong
Published: November 2022

Background: Dysregulation of long non-coding (lncRNA) has been reported in various solid tumors. HOXA cluster antisense RNA 2 (HOXA-AS2) is a newly identified lncRNA with abnormal expression in several human malignancies. However, its prognostic value remains controversial. This meta-analysis synthesized available data to clarify the association between HOXA-AS2 expression levels and clinical prognosis in multiple cancers.

Methods: Four public databases (Embase, PubMed, Web of Science, The Cochrane Library) were used to identify eligible studies. Hazard ratios (HRs) and odds ratios (ORs) with their 95% confidence intervals (CIs) were combined to assess the correlation of HOXA-AS2 expression with survival outcomes and clinicopathological features of cancer patients. Publication bias was measured using Begg’s funnel plot and Egger’s regression test, and the stability of the combined results was measured using sensitivity analysis. Additionally, multiple public databases were screened and extracted to validate the results of this meta-analysis.

Results: The study included 20 studies, containing 1331 patients. The meta-analysis showed that the overexpression of HOXA-AS2 was associated with poor overall survival (HR = 2.06, 95% CI 1.58–2.69, p < 0.001). In addition, the high expression of HOXA-AS2 could forecast advanced tumor stage (OR = 3.89, 95% CI 2.90–5.21, p < 0.001), earlier lymph node metastasis (OR = 3.48, 95% CI 2.29–5.29, p < 0.001), larger tumor size (OR = 2.36, 95% CI 1.52–3.66, p < 0.001) and earlier distant metastasis (OR = 3.54, 95% CI 2.00–6.28, p < 0.001). However, other clinicopathological features, including age (OR = 1.09, 95% CI 0.86–1.38, p = 0.467), gender (OR = 0.92, 95% CI 0.72–1.18, p = 0.496), depth of invasion (OR = 2.13, 95% CI 0.77–5.90, p = 0.146) and differentiation (OR = 1.02, 95% CI 0.65–1.59, p = 0.945) were not significantly different from HOXA-AS2 expression.

Conclusion: Our study showed that the overexpression of HOXA-AS2 was related to poor overall survival and clinicopathological features. HOXA-AS2 may serve as a potential prognostic indicator and therapeutic target for tumor treatment.
Integrative multiomics evaluation reveals the importance of pseudouridine synthases in hepatocellular carcinoma
Authors: Jin Zhipeng , Song Mengying , Wang Jianping , Zhu Wenjing , Sun Dongxu , Liu Huayuan , Shi Guangjun
Published: November 2022

Background: The pseudouridine synthases (PUSs) have been reported to be associated with cancers. However, their involvement in hepatocellular carcinoma (HCC) has not been well documented. Here, we assess the roles of PUSs in HCC.

Methods: RNA sequencing data of TCGA-LIHC and LIRI-JP were downloaded from the Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC), respectively. GSE36376 gene expression microarray was downloaded from the Gene Expression Omnibus (GEO). Proteomics data for an HBV-related HCC cohort was obtained from the CPTAC Data Portal. The RT-qPCR assay was performed to measure the relative mRNA expression of genes in clinical tissues and cell lines. Diagnostic efficiency was evaluated by the ROC curve. Prognostic value was assessed using the Kaplan-Meier curve, Cox regression model, and time-dependent ROC curve. Copy number variation (CNV) was analyzed using the GSCA database. Functional analysis was carried out with GSEA, GSVA, and clusterProfiler package. The tumor microenvironment (TME) related analysis was performed using ssGSEA and the ESTIMATE algorithm.

Results: We identified 7 PUSs that were significantly upregulated in HCC, and 5 of them (DKC1, PUS1, PUS7, PUSL1, and RPUSD3) were independent risk factors for patients’ OS. Meanwhile, the protein expression of DKC1, PUS1, and PUS7 was also upregulated and related to poor survival. Both mRNA and protein of these PUSs were highly diagnostic of HCC. Moreover, the CNV of PUS1, PUS7, PUS7L, and RPUSD2 was also associated with prognosis. Further functional analysis revealed that PUSs were mainly involved in pathways such as genetic information processing, substance metabolism, cell cycle, and immune regulation.

Conclusion: PUSs may play crucial roles in HCC and could be used as potential biomarkers for the diagnosis and prognosis of patients.
Spatial architecture of regulatory T-cells correlates with disease progression in patients with nasopharyngeal cancer
Authors: Zhou Fengge , Shayan Gulidanna , Sun Shiran , Huang Xiaodong , Chen Xuesong , Wang Kai , Qu Yuan , Wu Runye , Zhang Ye , Liu Qingfeng , Zhang Jianghu , Luo Jingwei , Shi Xinqi , Liu Yang , Liang Bin , Li Ye-Xiong , Wang Jingbo , Yi Junlin
Published: November 2022

Purpose

This study aims to investigate the prognostic value of composition and spatial architecture of tumor-infiltrating lymphocytes (TILs) as well as PDL1 expression on TILs subpopulations in nasopharyngeal carcinoma (NPC).

Methods

A total of 121 patients with NPC were included and divided into two groups: favorable (n = 68) and unfavorable (n = 53). The archived tumor tissues of the included patients were retrieved, and a tissue microarray was constructed. The density and spatial distribution of TILs infiltration were analyzed using the multiplex fluorescent immunohistochemistry staining for CD3, CD4, CD8, Foxp3, cytokeratin (CK), PDL1, and 4′,6-diamidino-2-phenylindole (DAPI). The infiltration density of TILs subpopulations and PDL1 expression were compared between the two groups. The Gcross function was calculated to quantify the relative proximity of any two types of cells. The Cox proportional hazards regression model was used to identify factors associated with overall survival (OS) and disease-free survival (DFS).

Results

The densities of regulatory T-cells (Tregs), effector T-cells (Teffs), PDL1+ Tregs, and PDL1+ Teffs were significantly higher in patients with unfavorable outcomes. PDL1 expression on tumor cells (TCs) or overall TILs was not associated with survival. Multivariate analysis revealed that higher PDL1+ Tregs infiltration density was independently associated with inferior OS and DFS, whereas Tregs infiltration density was only a prognostic marker for DFS. Spatial analysis revealed that unfavorable group had significantly stronger Tregs and PDL1+ Tregs engagement in the proximity of TCs and cytotoxic T lymphocyte (CTLs). Gcross analysis further revealed that Tregs and PDL1+ Tregs were more likely to colocalize with CTLs. Moreover, increased GTC : Treg (Tregs engagement surrounding TCs) and GCTL : PDL1+ Treg were identified as independent factors correlated with poor outcomes.

Conclusion

TILs have a diverse infiltrating pattern and spatial distribution in NPC. Increased infiltration of Tregs, particularly PDL1+ Tregs, as well as their proximity to TCs and CTLs, correlates with unfavorable outcomes, implying the significance of intercellular immune regulation in mediating disease progression.
1270 nm near-infrared light as a novel vaccine adjuvant acts on mitochondrial photoreception in intradermal vaccines
Authors: Maki Yohei , Kushibiki Toshihiro , Sano Tomoya , Ogawa Takunori , Komai Eri , Takahashi Shusaku , Kitagami Etsuko , Serizawa Yusuke , Nagaoka Ryosuke , Yokomizo Shinya , Ono Takeshi , Ishihara Miya , Miyahira Yasushi , Kashiwagi Satoshi , Kawana Akihiko , Kimizuka Yoshifumi
Published: November 2022

With the development of laser technology in the 1960s, a technique was developed to inject intradermal vaccines immediately after irradiating the skin with laser light to elicit an adjuvant effect, referred to as “laser adjuvant.” We have been investigating the mechanism of laser adjuvant in influenza mouse models using noninvasive continuous-wave (CW) near-infrared (NIR) light mainly at a wavelength of 1064 nm, and have shown that the production of reactive-oxygen-species (ROS) in the skin and mast cells in the skin tissue plays an important role in the laser adjuvant effect. The new wavelength of 1270 nm NIR light is characterized by its ability to elicit the same vaccine adjuvant effect as other wavelengths at a lower energy, and may be suitable for clinical applications. In this study, we investigated the physiological activity of CW1270 nm NIR light in mast cells, its biological activity on mouse skin, and the durability of the vaccine adjuvant effect in influenza vaccine mouse models. We show that irradiation of mast cells with 1270 nm NIR light produced ROS and ATP, and irradiation of isolated mitochondria also produced ATP. In mouse skin, the relative expression levels of chemokine mRNAs, such as Ccl2 and Ccl20, were increased by irradiation with 1270 and 1064 nm NIR light at minimum safe irradiance. However, the relative expression of Nfkb1 was increased at 1064 nm, but not at 1270 nm. Serum anti-influenza IgG antibody titers increased early after immunization with 1064 nm, whereas with 1270 nm, there was not only an early response of antibody production but also persistence of antibody titers over the medium- to long-term. Thus, to our knowledge, we show for the first time that 1270 nm NIR light induces ROS and ATP production in mitochondria as photoreceptors, initiating a cascade of laser adjuvant effects for intradermal vaccines. Additionally, we demonstrate that there are wavelength-specific variations in the mechanisms and effects of laser adjuvants. In conclusion, CW1270 nm NIR light is expected to be clinically applicable as a novel laser adjuvant that is equivalent or superior to 1064 nm NIR light, because it can be operated at low energy and has a wavelength-specific adjuvant effect with medium- to long-lasting antibody titer.
Ischemic stroke and concomitant gastrointestinal complications- a fatal combination for patient recovery
Authors: Tuz Ali A. , Hasenberg Anja , Hermann Dirk M. , Gunzer Matthias , Singh Vikramjeet
Published: November 2022

Stroke is primarily a neurodegenerative disease but can also severely impact the functions of other vital organs and deteriorate disease outcomes. A malfunction of the gastrointestinal tract (GIT), commonly observed in stroke patients, is often characterized by severe bowel obstruction, intestinal microbiota changes and inflammation. Over-activated immune cells after stroke are the major contributors to endorse intestinal inflammation and may induce damage to single-layer epithelial cell barriers. The post-stroke leakage of intestinal barriers may allow the translocation and dissemination of resident microflora to systemic organs and cause sepsis. This overshooting systemic immune reaction fuels ongoing inflammation in the degenerating brain and slows recovery. Currently, the therapeutic options to treat these GIT-associated anomalies are very limited and further research is required to develop novel treatments. In this mini-review, we first discuss the current knowledge from clinical studies and experimental stroke models that provide strong evidence of the existence of post-stroke GIT complications. Then, we review the literature regarding novel therapeutic approaches that might help to maintain GIT homeostasis and improve neurological outcomes in stroke patients.
ALT-803 in the treatment of non-muscle-invasive bladder cancer: Preclinical and clinical evidence and translational potential
Authors: Chen Wujun , Liu Ning , Yuan Yang , Zhu Meng , Hu Xiaokun , Hu Wenchao , Wang Shuai , Wang Chao , Huang Binghuan , Xing Dongming
Published: November 2022

Bladder cancer (BCa) is one of the most common malignant tumors that cause death. Approximately 75%–85% of BCa develop into non-muscle-invasive bladder cancer (NMIBC). Bacillus Calmette-Guérin (BCG) is the gold standard for avoiding cystectomy in the treatment of NMIBC. Unfortunately, up to 30% of patients do not respond to BCG treatment, and up to 70% of BCG responders relapse. The United States Food and Drug Administration (FDA) approved valrubicin (1998) and pembrolizumab (2020) for the treatment of BCG-unresponsive (BCGu) NMBIC. However, the complete remission rate for valrubicin and pembrolizumab was only 16% and 40.6%, respectively. ALT-803 (N-803) is an IL-15 superagonist and reduces tumor burden by promoting the proliferation and activation of NK cells and CD8+ T cells. The FDA received (23 May 2022) and accepted to review (28 July 2022) the marketing submission of ALT-803 plus BCG for the treatment of BCGu NMIBC. However, the FDA previously rejected the application for oportuzumab monatox (OM) due to a lack of data comparing it with pembrolizumab on August 20, 2021. Interestingly, the clinical efficacy and safety of ALT-803 were higher than that of pembrolizumab and OM, suggesting that ALT-803 may be approved by FDA. This review aims to further knowledge of the preclinical and clinical evidence of ALT-803 in the treatment of NMIBC and discuss its translational potential.
Remodeling tumor microenvironment with natural products to overcome drug resistance
Authors: Zhang Wanlu , Li Shubo , Li Chunting , Li Tianye , Huang Yongye
Published: November 2022

With cancer incidence rates continuing to increase and occurrence of resistance in drug treatment, there is a pressing demand to find safer and more effective anticancer strategy for cancer patients. Natural products, have the advantage of low toxicity and multiple action targets, are always used in the treatment of cancer prevention in early stage and cancer supplement in late stage. Tumor microenvironment is necessary for cancer cells to survive and progression, and immune activation is a vital means for the tumor microenvironment to eliminate cancer cells. A number of studies have found that various natural products could target and regulate immune cells such as T cells, macrophages, mast cells as well as inflammatory cytokines in the tumor microenvironment. Natural products tuning the tumor microenvironment via various mechanisms to activate the immune response have immeasurable potential for cancer immunotherapy. In this review, it highlights the research findings related to natural products regulating immune responses against cancer, especially reveals the possibility of utilizing natural products to remodel the tumor microenvironment to overcome drug resistance.
Phase separation drives the formation of biomolecular condensates in the immune system
Authors: Wen Yuqing , Ma Jian
Published: November 2022

When the external conditions change, such as the temperature or the pressure, the multi-component system sometimes separates into several phases with different components and structures, which is called phase separation. Increasing studies have shown that cells condense related biomolecules into independent compartments in order to carry out orderly and efficient biological reactions with the help of phase separation. Biomolecular condensates formed by phase separation play a significant role in a variety of cellular processes, including the control of signal transduction, the regulation of gene expression, and the stress response. In recent years, many phase separation events have been discovered in the immune response process. In this review, we provided a comprehensive and detailed overview of the role and mechanism of phase separation in the innate and adaptive immune responses, which will help the readers to appreciate the advance and importance of this field.