bluuebunny/crossref_metadata_2025 huggingface dataset:
Gradient normalized least-squares reverse-time migration imaging technology
Authors: Sun Yanfeng , Xu Xiugang , Tang Le
Published: August 2022

Least-squares reverse-time migration (LSRTM) can overcome the problems of low resolution and unbalanced amplitude energy of deep formation imaging in reverse-time migration (RTM); hence, it can obtain a more accurate imaging profile. In the conventional conjugate gradient LSRTM, the gradient is obtained based on cross correlation without a precondition operator, and the source has a great influence on the gradient, causing the convergence rate to be slow. In the framework of conventional conjugate gradient LSRTM, a normalized cross-correlation of the source wavefield was used in this study to effectively weaken the influence of the source effect and reduce the low-frequency noise. The idea of normalized cross-correlation of the source wavefield was adopted to improve the steepest descent gradient to further accelerate the iterative convergence speed and complete the final migration imaging. Model and field data examples verify the advantages of the proposed methods over conventional methods in reducing source effects, improving convergence speed, and enhancing underground deep illumination.
Optimization of CO2 geological storage sites based on regional stability evaluation—A case study on geological storage in tianjin, china
Authors: Lv Tianxue , Wan Jianhua , Zheng Yajie , He Lusheng , Yi Lixin
Published: August 2022

Carbon dioxide geological storage is one of the important means to mitigate the greenhouse effect and curb global warming. The key to carbon dioxide (CO2) geological storage is to select a suitable storage site. Using the geological analysis method and analytic hierarchy process (AHP)–fuzzy comprehensive evaluation method, combining the qualitative analysis of geological conditions with the quantitative calculation of site parameters, this study determines a site target area suitable for CO2 geological storage in Tianjin. First, the regional crustal stability of Tianjin is discussed, and the characteristics of regional gravity field anomaly, regional crustal thickness, and regional aeromagnetic characteristics are comprehensively analyzed. The site is focused on Banqiao sag, a class ⅳ tectonic unit in Bohai Bay Basin. Second, aiming at the storability, safety, and economy of the site, the expert investigation method is used to construct the target area evaluation index system, including four primary indexes and ten secondary indexes. The weight of each index is determined using the analytic hierarchy process. A two-level fuzzy comprehensive evaluation mathematical model is constructed. The suitability of CO2 geological storage in three sites (site A, site B, and site C) in Banqiao sag is evaluated. The results are as follows: the comprehensive membership of site A, site B, and site C is 0.8629, 0.3926 and 0.1750, respectively. The comprehensive membership of site A is the largest. The evaluation results show that the preferred target area of Tianjin local carbon dioxide geological storage site is located in ‘site A’ near Dazhangtuo fault in Banqiao sag, Huanghua depression, Bohai Bay Basin (with an area of about 5 km2). In this study, a suitable target area is delineated for the local CO2 geological storage site in Tianjin, which can be used as an advantageous location for CO2 geological storage. The conclusion has a positive response to the problem of CO2 emission reduction in Tianjin.
A bibliometric analysis and review of water resources carrying capacity using rené descartes’s discourse theory
Authors: Yang Xiaojing , Sun Boyang , Lei Sheng , Li Fapeng , Qu Yanping
Published: August 2022

Water Resources Carrying Capacity is an important indicator of water sustainable and economic development, yet few studies investigated a bibliometric analysis of Water Resources Carrying Capacity research. In this research, we proposed a four-staged bibliometric analysis method for Water Resources Carrying Capacity studies following the René Descartes’s Discourse on the Method guidelines which makes the bibliometric analysis process more systematic. Our four-staged bibliometric analysis method contains a refined screening process of the records, which can successfully delete poorly correlated data from tens of thousands of data within a short period of time and determined the subject-related data. The screening results shortlisted 271 records from an initial 16,769. We further conducted a complete bibliometric, statistical and meta-analysis of the 271 records. The results showed that China is the major country that conducts research on Water Resources Carrying Capacity. Modeling in various forms and system dynamics are the mainstream methods of Water Resources Carrying Capacity research. Water Resources Carrying Capacity is intrinsically linked to population carrying capacity, groundwater resources, urbanization and water shortage. Based on a comprehensive analysis of the research of Water Resources Carrying Capacity, we divided the research progress into five stages lastly. The method proposed in this research can provide reference for future bibliometric studies.
The effects of a translation training program on English as a foreign language trainees’ translation skills
Authors: Alolaywi Yasamiyan
Published: August 2022

This study aimed to measure the effectiveness of a training experience involving a simulation of the work environment in developing the translation skills of a group of translation trainees. It also sought to investigate the participants’ views about their training experience, as well as measure their level of satisfaction with the program. Thirty participants with qualifications in English language and translation from different regions of the Kingdom of Saudi Arabia participated in this study. This research is a quasi-experimental study in the form of a one-group pretest and posttest design. Initially, the participants underwent a preliminary assessment (pretest) of their translation abilities. Afterward, they undertook the experiment, an intensive course in translation and its required skills, which extended over a 2-month period. At the end of the program, the participants underwent a posttest to measure whether there were statistically significant differences in their performance in the pre- and posttests, with the results showing statistically significant differences in program performance (p < 0.05). The data from the attitudinal questionnaire administered to the participants at the end of the program showed that they held positive opinions about the program and they benefited significantly from the training experience. Based on these results, suggestions and recommendations are proposed to those interested in the field of training and translation to further improve the work.
How to support teachers to carry out educational robotics activities in school? The case of Roteco, the Swiss robotic teacher community
Authors: Mury Sophia Reyes , Negrini Lucio , Assaf Dorit , Skweres Melissa
Published: August 2022

The development of 21st-century transversal competences such as communication, cooperation, and creativity as well as computational thinking and programming may be aided through educational robotics (ER). Different countries have inserted ER in their school curricula, however, to date ER activities are not carried out systematically in all schools and are more an initiative from single pioneer teachers. In Switzerland, to support all teachers to carry out ER activities and to foster the presence of ER in schools, a robotic teacher community (Roteco) has been created. Teachers may obtain assistance, share experiences, and access instructional resources through a digital platform, which will help them and spread the use of robotics in the classroom. For instance, the site enables educators to simply submit their activities, connect with other educators and professionals, choose and download didactic activities from their peers together with the relevant resources, and stay updated on the newest information, events, research, and further education courses in the field of ER. In the first years of the platform’s existence, already more than 1,400 teachers have joined it. The project and the findings of two surveys are presented in this publication. The first survey was carried out in 2020 with 87 teachers and the second one in 2021 with 48 teachers from the community. The findings highlight the community’s greatest accomplishments as well as the motivations for teachers’ recruitment into the Roteco community and their contributions to its expansion. The results of this project allow for discussion on how to support teachers to implement ER activities in schools in a systematic way.
The association of remnant cholesterol (RC) and interaction between RC and diabetes on the subsequent risk of hypertension
Authors: Wang Jie , Sun Qi , An Yu , Liu Jia , Leng Song , Wang Guang
Published: August 2022

Purpose

Whether elevated remnant cholesterol (RC) is associated with hypertension (HTN) and whether elevated RC interacts with diabetes on the subsequent risk of HTN have not been illustrated. Thus, this study is aimed to investigate the associations and interactions of RC, diabetes, and the management of cardiovascular risk factors with the risk of incident HTN in a Chinese population.

Patients and methods

This cohort study included 42,994 individuals who participated in the routine health check-up from April 2016 to August 2020 and follow-ups from April 2017 to August 2021 at the Medical Examination Center of Beijing Chao-Yang Hospital. RC was divided into quintiles as follows: the < 20% group, the 20–39% group, the 40–59% group, the 60–79% group, and the ≥ 80% group. This study finally included 17,006 participants who were free from HTN at baseline.

Results

This study had 1,861 (10.90%) HTN occurred, 205 (5.30%) in the first quintile of RC, 335 (8.98%) in the second quintile of RC, 388 (11.17%) in the third quintile of RC, 420 (13.42%) in the fourth quintile of RC, and 513 (17.91%) in the fifth quintile of RC. Compared with participants in the first quintile of RC, participants in the fifth quintile of RC showed a greater risk of HTN events among participants with diabetes [hazard ratio (HR), 4.95; 95% confidence interval (CI), 1.05–23.39; P = 0.0432) than among participants without diabetes (HR, 1.67; 95% CI, 1.26–2.22, P = 0.0004; P for interaction = 0.0420). Compared with participants without diabetes, participants with diabetes who have the ideal management of RC and other risk factors showed no excess risk of HTN.

Conclusions

Elevated RC is significantly predictive of HTN among the diabetic population. RC and diabetes interacted with each other on the subsequent risk of HTN, and the desired management of RC, glucose, and cardiovascular risk factors on HTN risk was quite favorable.
The changes in peripheral blood Th17 and Treg ratios in Hashimoto’s thyroiditis are accompanied by differential PD-1/PD-L1 expression
Authors: Fang Jun , Yu Lei , Zhuang Lan-Gen , Pei Xiao-Yan , Wang Qiong , Jin Guo-Xi
Published: August 2022

Objective

The aim of this study was to analyze the percentages of T helper 17 cells (Th17s) and T regulatory cells (Tregs) in autoimmune Hashimoto’s thyroiditis (HT), and the expression of the checkpoint molecules programmed death receptor 1/programmed death ligand 1 (PD-1/PD-L1) on these cells.

Methods

This is a case-control study involving 53 initially diagnosed HT patients (HT group) and 21 normal controls (NC group). The peripheral blood mononuclear cells from the individuals of the two groups were isolated and restimulated ex vivo; the percentage of Th17s, Tregs, PD-1+ Th17s, PD-L1+ Th17s, PD-1+ Tregs, and PD-L1+ Tregs was assessed by flow cytometric analysis.

Results

(1) The percentage of Th17s in the peripheral blood of the HT group was significantly higher than that of the NC group [(6.38 ± 1.32)% versus (3.12 ± 0.66)%; t = 14.110, P < 0.001], while the percentage of peripheral blood Tregs was significantly lower [(3.82 ± 1.48)% versus (5.61 ± 1.60)%; t = −4.599, P < 0.001]. (2) HT patients’ Th17s expressed PD-1 at a significantly lower frequency than their counterparts in the NC [(6.46 ± 2.77)% versus (18.51 ± 3.96)%; t = −14.842, P < 0.001], while no difference was observed for PD-L1 between the two groups. (3) In contrast, both PD-1 and PD-L1 were expressed at significantly higher frequency on HT patients’ Tregs than on NC [respectively: (17.01 ± 3.04)% versus (10.23 ± 2.77)%; t = 8.850, P < 0.001 for PD-1; (16.60 ± 9.58)% versus (11.36 ± 10.14)%; t = 2.089, P < 0.005, for PD-L1].

Conclusion

(1) The increased percentage of Th17s and decreased percentage of PD-1+ Th17s in the HT group suggest that a loss of control on Th17 activity through the checkpoint inhibitory axis PD-1/PD-L1 may participate in disease pathogenesis. (2) While the decreased percentage of Tregs in HT patients may explain a lack of regulatory functions able to prevent the autoimmune destruction of the thyroid, the significance of the increased frequency of Tregs expressing PD-1 and PD-L1, previously reported to boost Tregs differentiation, remains to be established. Elucidating this apparent contradiction may reveal important mechanisms underlying HT pathogenesis.
Close association between lifestyle and circulating FGF21 levels: A systematic review and meta-analysis
Authors: Qian Zonghao , Zhang Yucong , Yang Ni , Nie Hao , Yang Zhen , Luo Pengcheng , Wei Xiuxian , Guan Yuqi , Huang Yi , Yan Jinhua , Ruan Lei , Zhang Cuntai , Zhang Le
Published: August 2022

Background

The impact of lifestyle factors on circulating fibroblast growth factor 21 (cFGF21) remains unclear. We conducted this systematic review and meta-analysis to evaluate the association between lifestyle factors and cFGF21 levels.

Methods

We included studies that evaluated the effects of different lifestyles on cFGF21 concentration in adults, which included smoking, exercise, diets, alcohol consumption and weight loss. Random effects models or fixed effects models were used for meta-analysis to calculate the standardized mean difference (SMD) and 95% confidence interval according to the heterogeneity among studies. Study quality was assessed using the Newcastle–Ottawa Scale for cohort studies, the Joanna Briggs Institution Checklist for cross-sectional studies, and the PEDro scale for experimental studies.

Results

A total of 50 studies with 1438 individuals were included. Overall, smoking, a hypercaloric carbohydrate-rich diet, a hypercaloric fat-rich diet, amino acid or protein restriction, excessive fructose intake and alcohol consumption significantly upregulated cFGF21 levels (p<0.05), whereas fish oil intake and calorie restriction with sufficient protein intake significantly decreased cFGF21 (p<0.05). Compared to the preexercise cFGF21 level, the cFGF21 level significantly increased within 3 hours postexercise (p<0.0001), while it significantly decreased in the blood sampled >6 h postexercise (p=0.01). Moreover, higher exercise intensity resulted in higher upregulation of cFGF21 at 1-hour post exercise (p=0.0006).

Conclusion

FGF21 could serve as a potential biomarker for the assessment of different lifestyle interventions. When it is used for this purpose, a standard study protocol needs to be established, especially taking into consideration the intervention types and the sampling time post-intervention.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021254758, identifier CRD42021254758.
Linoleic acid and linoleate diols in neonatal cord blood influence birth weight
Authors: Umeda Naoko , Hirai Takaharu , Ohto-Nakanishi Takayo , Tsuchiya Kenji J. , Matsuzaki Hideo
Published: August 2022

Background

Low-birth-weight infants exhibit a high risk for postnatal morbidity. Cytochrome P450 (CYP) and epoxide hydrolase (EH) are involved in the metabolism of factors responsible for low-birth-weight in infants. Both CYPs and EHs have high substrate specificity and are involved in polyunsaturated fatty acid (PUFA) metabolism. The CYP pathway produces epoxy fatty acids (EpFAs), which are further degraded by soluble EH (sEH). Additionally, sEH inhibition enhances the action of EpFAs and suppresses inflammatory responses. During pregnancy, excessive activation of maternal inflammatory response is a significant factor associated with low-birth-weight. However, the association of EpFAs, which have potential anti-inflammatory properties, with the low-birth-weight of infants remains uninvestigated. This study aimed to clarify the association between the umbilical cord serum EpFA and low-birth-weight using data obtained from the Hamamatsu Birth Cohort for Mothers and Children (HBC Study) by analyzing the umbilical cord blood samples.

Method

We selected a subgroup of 200 infants (106 boys and 94 girls), quantified EpFA concentration in their cord blood samples collected at birth, and examined its correlation with birth weight.

Results

The comparison between the low-birth-weight and normal-birth-weight groups revealed no significant correlation between PUFA and EpFA concentrations, but a significant correlation was observed in the linoleate diol concentrations of the two groups. Furthermore, birth weight did not significantly correlate with PUFA, EpFA, and diol concentrations in cord blood; however, multiple regression analysis showed a significant negative correlation of birth weight with the concentration of linoleic acid (LA) (r = −0.101, p = 0.016) as well as LA-derived dihydroxyoctadecenoic acid (diHOME) (r = −0.126, p = 0.007), 9,10-diHOME (r = −0.115, p = 0.014), and 12,13-diHOME (r = −0.126, p = 0.007) after adjusting for obstetric factors, including gestational age, infant’s sex, childbirth history, delivery method, and maternal height.

Conclusions

Birth weight was significantly correlated with the concentration of LA and linoleate diol diHOME after adjusting for obstetric confounders. Our results show that CYP and sEH involved in PUFA metabolism may influence the birth weight of infants. Further validation is needed to provide insights regarding maternal intervention strategies required to avoid low-birth-weight in infants in the future.
Green energy investment, renewable energy consumption, and carbon neutrality in China
Authors: Li Ying , Li Haoning , Chang Manru , Qiu Shijuan , Fan Yifan , Razzaq Hafiz Kashif , Sun Yunpeng
Published: August 2022

This study investigates the dynamic impact of green energy investment and energy consumption on carbon emissions in China from 1995 to 2020. It employed the Bootstrap Autoregressive Distributed Lag method to examine the short and long-run relationship. The long-run findings indicate that green energy investment and renewable energy consumption decrease carbon emissions, whereas non-renewable energy consumption and economic growth increase carbon emissions in shorter and longer periods. The long-term reduction in carbon emissions may imply the transition toward carbon neutrality. However, the marginal contribution of renewable energy towards carbon neutrality is significantly higher than green energy investment due to investment lag effects. Moreover, the Error Correction Term (ECT) is significantly negative, authorizing the convergence towards steady-state equilibrium in case of any deviation with a 25% adjustment rate. The empirical results suggest that China should encourage green energy investment and increase the share of renewable energy sources to ensure carbon neutrality in the long run.
Methods for robust estimates of tree biomass from pollen accumulation rates: Quantifying paleoecological reconstruction uncertainty
Authors: Knight Clarke A. , Battles John J. , Bunting M. Jane , Champagne Marie , Wanket James A. , Wahl David B.
Published: August 2022

Pollen accumulation rates (PAR, grains cm–2 year–1) have been shown to be a reliable but methodologically complex bioproxy for quantitative reconstruction of past tree abundance. In a prior study, we found that the PARs of major tree taxa – Pseudotsuga, Pinus, Notholithocarpus, and the pollen group TC (Taxaceae and Cupressaceae families) – were robust and precise estimators of contemporary tree biomass. This paper expands our earlier work. Here, we more fully evaluate the errors associated with biomass reconstructions to identify weaknesses and recommend improvements in PAR-based reconstructions of forest biomass. We account for uncertainty in our biomass proxy in a formal, coherent fashion. The greatest error was introduced by the age models, underscoring the need for improved statistical approaches to age-depth modeling. Documenting the uncertainty in pollen vegetation models should be standard practice in paleoecology. We also share insights gained from the delineation of the relevant source area of pollen, advances in Bayesian 210Pb modeling, the importance of site selection, and the use of independent data to corroborate biomass estimates. Lastly, we demonstrate our workflow with a new dataset of reconstructed tree biomass between 1850 and 2018 AD from lakes in the Klamath Mountains, California. Our biomass records followed a broad trend of low mean biomass in the ∼1850s followed by large contemporary increases, consistent with expectations of forest densification due to twentieth century fire suppression policies in the American West. More recent reconstructed tree biomass estimates also corresponded with silviculture treatments occurring within the relevant source area of pollen of our lake sites.
The clonal expression genes associated with poor prognosis of liver cancer
Authors: Zhang Wanfeng , Huang Fang , Tang Xia , Ran Longke
Published: August 2022

The extensive spatial genomic intratumor heterogeneity (ITH) in liver cancer hindered treatment development and limited biomarker design. Early events that drive tumor malignant transformation in tumor founder cells are clonally present in all tumor cell populations, which provide stable biomarkers for the localization of tumor cells and patients’ prognosis. In the present study, we identified the recurrently clonal somatic mutations and copy number alterations (CNAs) (893 clonal somatic mutations and 6,617 clonal CNAs) in 353 liver cancer patients from The Cancer Genome Atlas (TCGA) and evaluated their prognosis potential. We showed that prognosis-related clonal alterations might play essential roles in tumor evolution. We identified 32 prognosis related clonal alterations differentially expressed between paired normal and tumor samples, that their expression was cross-validated by three independent cohorts (50 paired samples in TCGA, 149 paired samples in GSE76297, and 9 paired samples in SUB6779164). These clonal expression alterations were also significantly correlated with clinical phenotypes. Using stepwise regression, we identified five (UCK2, EFNA4, KPAN2, UBE2T, and KIF14) and six (MCM10, UCK2, IQGAP3, EFNA4, UBE2T, and KPNA2) clonal expression alterations for recurrence and survival model construction, respectively. Furthermore, in 10 random repetitions, we showed strong applicability of the multivariate Cox regression models constructed based on the clonal expression genes, which significantly predicted the outcomes of the patients in all the training and validation sets. Taken together, our work may provide a new avenue to overcome spatial ITH and refine biomarker design across cancer types.
Intergeneric hybridization of two stickleback species leads to introgression of membrane-associated genes and invasive TE expansion
Authors: Nedoluzhko Artem , Sharko Fedor , Tsygankova Svetlana , Boulygina Eugenia , Slobodova Natalia , Teslyuk Anton , Galindo-Villegas Jorge , Rastorguev Sergey
Published: August 2022

Interspecific hybridization has occurred relatively frequently during the evolution of vertebrates. This process usually abolishes reproductive isolation between the parental species. Moreover, it results in the exchange of genetic material and can lead to hybridogenic speciation. Hybridization between species has predominately been observed at the interspecific level, whereas intergeneric hybridization is rarer. Here, using whole-genome sequencing analysis, we describe clear and reliable signals of intergeneric introgression between the three-spined stickleback (Gasterosteus aculeatus) and its distant mostly freshwater relative the nine-spined stickleback (Pungitius pungitius) that inhabit northwestern Russia. Through comparative analysis, we demonstrate that such introgression phenomena apparently take place in the moderate-salinity White Sea basin, although it is not detected in Japanese sea stickleback populations. Bioinformatical analysis of the sites influenced by introgression showed that they are located near transposable elements, whereas those in protein-coding sequences are mostly found in membrane-associated and alternative splicing-related genes.
Case Report: Identification of a novel CASK missense variant in a Chinese family with MICPCH
Authors: Zhang Runfeng , Jia Peng , Yao Yanyi , Zhu Feng
Published: August 2022

Mental retardation and microcephaly with pontine and cerebellar hypoplasia (MICPCH) is a rare genetic disorder that results in varying levels of pontocerebellar hypoplasia, microcephaly, and severe intellectual disabilities. Prior genetic analyses have identified the CASK gene as a driver of MICPCH. Herein, we analyzed a Chinese family with MICPCH. The index patient was an 8-year-old male. He and his 3-year-old brother suffered from microcephaly, pontocerebellar hypoplasia, serious mental retardation, ataxia, gait disorder, and inability to speak. Through a combination of whole-exome sequencing and subsequent Sanger sequencing, a novel X-linked missense mutation, c.1882G>C (p.D628H) in the CASK gene, was identified in two siblings, as well as their mother and grandmother, who exhibited mild mental retardation. Other family members with negative genetic testing were normal. In silico analyses indicated that this missense mutation was predicted to reduce CASK protein stability, disrupt the SRC homology 3 (SH3) domain, and abolish its function. In summary, we identified a novel missense variate in CASK associated with MICPCH. Our work facilitates the diagnosis of the disease in this family and broadens the gene variant spectrum of the CASK in MICPCH patients.
Characterization of chromatin regulators in hepatocellular carcinoma to guide clinical therapy
Authors: Jia Xiangen , Zhang Guozhi
Published: August 2022

Background: Hepatocellular carcinoma (HCC) is notorious for its high mortality and incidence. Accumulating evidence confirms that chromatin regulators (CRs) have a significant impact on cancer. Therefore, exploring the mode of action and prognostic value of CRs is imminent for the treatment of hepatocellular carcinoma.

Method: Transcriptome and clinical data for this study have been downloaded from TCGA (https://portal.gdc.cancer.gov/) and ICGC (https://dcc.icgc.org/). Univariate analysis was used to screen CRs with prognostic value, and our prognostic risk score signature was developed using least absolute shrinkage along with selection operator (lasso) Cox regression analysis. The CRs-based prognostic model was constructed in the TCGA dataset, and low-risk HCC patients had a better prognosis, which was finally validated in the ICGC dataset. We used the receiver operating characteristic curve to identify the accuracy of the prediction model and establish a line chart to prove the clinical effectiveness of the model. We also discussed the differences in drug sensitivity via CellMiner database, tumor immune microenvironment via ssGSEA algorithm, and clinical characteristics among different risk groups.

Results: A prognostic model consisting of seven CRs was constructed and verified in HCC patients. Furthermore, we found that this risk score prognostic signature could independently predict the prognosis of HCC patients. Functional enrichment analysis revealed that CRs are mainly associated with cancer-related signaling pathways and metabolic pathways. In addition, immune cell abundance correlates with risk score levels

Conclusion: In brief, we systematically explored the mode of action of CRs in HCC patients and established a reliable prognostic prediction model.
Exonization of a deep intronic long interspersed nuclear element in Becker muscular dystrophy
Authors: Xie Zhiying , Liu Chang , Lu Yanyu , Sun Chengyue , Liu Yilin , Yu Meng , Shu Junlong , Meng Lingchao , Deng Jianwen , Zhang Wei , Wang Zhaoxia , Lv He , Yuan Yun
Published: August 2022

The precise identification of pathogenic DMD variants is sometimes rather difficult, mainly due to complex structural variants (SVs) and deep intronic splice-altering variants. We performed genomic long-read whole DMD gene sequencing in a boy with asymptomatic hyper-creatine kinase-emia who remained genetically undiagnosed after standard genetic testing, dystrophin protein and DMD mRNA studies, and genomic short-read whole DMD gene sequencing. We successfully identified a novel pathogenic SV in DMD intron 1 via long-read sequencing. The deep intronic SV consists of a long interspersed nuclear element-1 (LINE-1) insertion/non-tandem duplication rearrangement causing partial exonization of the LINE-1, establishing a genetic diagnosis of Becker muscular dystrophy. Our study expands the genetic spectrum of dystrophinopathies and highlights the significant role of disease-causing LINE-1 insertions in monogenic diseases.
A novel necroptosis-related lncRNA signature for predicting prognosis and immune response of colon cancer
Authors: Luo Jian , Peng Jiayu , Xiao Wanying , Huang Shujing , Cao Yanqing , Wang Ting , Wang Xicheng
Published: August 2022

Background: Numerous lncRNAs have been shown to affect colon cancer (CC) progression, and tumor necroptosis is regulated by several of them. However, the prognostic value of necroptosis-related lncRNA in CC has rarely been reported. In this study, a necroptosis-related lncRNA prognostic model was constructed, which can provide a reference for clinical diagnosis and treatment.

Methods: The Cancer Genome Atlas (TCGA) database provided gene expression and lncRNA sequencing data for CC patients, and GSEA provided necroptosis gene data. Differentially expressed necroptosis-related lncRNAs related to prognosis were identified by differential expression analysis, Pearson correlation analysis, and least absolute shrinkage and selection operator (LASSO) regression. Based on the results of the multivariate COX regression analysis, a risk scoring model was constructed, A Kaplan-Meier analysis was performed to compare overall survival (OS) between low-risk and high-risk groups. A nomogram was then developed and validated based on the clinical data and risk scores of CC patients. In addition, Gene Set Enrichment Analysis (GSEA) and immune correlation analysis were conducted to explore the possible pathways and immune regulatory effects of these necroptosis-related lncRNAs.

Results: In total, we identified 326 differentially expressed necroptosis-related lncRNAs in the TCGA database. Survival analysis showed that the OS of patients in the low-risk group was significantly better than that in the high-risk group (p < 0.05). Finally, 10 prognostic necroptosis-related lncRNAs were used to construct the nomogram. The composite nomogram prediction model evaluated and validated with good prediction performance (3-year AUC = 0.85, 5-years AUC = 0.82, C-index = 0.78). The GSEA and immune correlation analyses indicated that these lncRNAs may participate in multiple pathways involved in CC pathogenesis and progression.

Conclusion: We established a novel necroptosis-related lncRNA CC prognosis prediction model, which can provide a reference for clinicians to formulate personalized treatment and review plans for CC patients. In addition, we also found that these necroptosis-related lncRNAs may affect the pathogenesis and progression of colon cancer through multiple pathways, including altering the activity of various immune cells.
Consumer acceptance of using a digital technology to manage postpartum depression
Authors: Tang Jian Jenny , Malladi Indira , Covington Melva T. , Ng Eliza , Dixit Shailja , Shankar Sid , Kachnowski Stan
Published: August 2022

The goal of the study was to evaluate the end user experience using the MamaLift Plus app for 2 weeks to support the treatment of their postpartum depression (PPD). A total of 14 participants completed the study and their experiences are reported in this publication. Participants reported that MamaLift Plus is an acceptable, highly usable, and practical mobile tool to use weekly for the management of their PPD. More research is warranted to evaluate the benefit of digital behavior health interventions, especially in patient populations where mental health care may be limited or harder to access by patients.
Innate immunity and immunotherapy for hemorrhagic shock
Authors: Huang Qingxia , Gao Song , Yao Yao , Wang Yisa , Li Jing , Chen Jinjin , guo Chen , Zhao Daqing , Li Xiangyan
Published: August 2022

Hemorrhagic shock (HS) is a shock result of hypovolemic injury, in which the innate immune response plays a central role in the pathophysiology ofthe severe complications and organ injury in surviving patients. During the development of HS, innate immunity acts as the first line of defense, mediating a rapid response to pathogens or danger signals through pattern recognition receptors. The early and exaggerated activation of innate immunity, which is widespread in patients with HS, results in systemic inflammation, cytokine storm, and excessive activation of complement factors and innate immune cells, comprised of type II innate lymphoid cells, CD4+ T cells, natural killer cells, eosinophils, basophils, macrophages, neutrophils, and dendritic cells. Recently, compelling evidence focusing on the innate immune regulation in preclinical and clinical studies promises new treatment avenues to reverse or minimize HS-induced tissue injury, organ dysfunction, and ultimately mortality. In this review, we first discuss the innate immune response involved in HS injury, and then systematically detail the cutting-edge therapeutic strategies in the past decade regarding the innate immune regulation in this field; these strategies include the use of mesenchymal stem cells, exosomes, genetic approaches, antibody therapy, small molecule inhibitors, natural medicine, mesenteric lymph drainage, vagus nerve stimulation, hormones, glycoproteins, and others. We also reviewed the available clinical studies on immune regulation for treating HS and assessed the potential of immune regulation concerning a translation from basic research to clinical practice. Combining therapeutic strategies with an improved understanding of how the innate immune system responds to HS could help to identify and develop targeted therapeutic modalities that mitigate severe organ dysfunction, improve patient outcomes, and reduce mortality due to HS injury.
The effects of nutrition bio-shield superfood powder on immune system function: A clinical trial study among patients with COVID-19
Authors: Azizi Jalilian Farid , Keshavarz Gheisar , Khazaei Salman , Nezamdoost Manije , Hashemi Seyed Hamid , Mamani Mojgan , Ansari Nastaran , Amini Razieh , Khalkhali Aref , Keshavarz Arghavan , Ayubi Erfan , Fazeli Maryam , Heidari Moghadam Rashid , Alizadeh Saeid , Pourhossein Behzad , Teimouri Ali , Keramat Fariba , Karampour Sajad , Khakzad Mohammadreza
Published: August 2022

The present study aimed to evaluate the effects of Nutrition Bio-shield Superfood (NBS) powder on the immune system function and clinical manifestations in patients with COVID-19. We compare the effects of NBS powder on the immune system function and clinical manifestations among two different groups: 1) intervention group receiving standard treatment scheduled according to treatment guidelines plus NBS powder, and 2) control group receiving only the same standard treatment. The serum levels of IL-2, IL-6, IL-17, IFNγ, and TNFα were determined after four weeks of treatment by specific ELISA kits according to the manufacturer’s instructions. Finally, the level of immune system stimulation and inflammatory markers were compared at baseline and after intervention in both groups. Data were analyzed using SPSS (version 22). A p-value of ≤ 0.05 was set as significant. A total of 47 patients with COVID-19 (24 patients in the intervention group and 23 patients in the control group) were included in this study. Results showed that the differences in the mean decrease of IL-2, IL-6, and TNF-α in the intervention group in comparison to the control group were 0.93, 10.28, and 8.11 pg/ml, respectively (P<0.001). On the other hand, there was no difference in IL-17, IFNγ, monocytes, eosinophil, and other inflammatory indices between the intervention and control groups. Although NBS powder was able to significantly decrease the levels of some proinflammatory cytokines in patients with COVID-19, however, it is noteworthy that the course of the disease was to large part unaffected by NBS power and there was a reduction independent of treatment. The present study indicates that NBS powder could provide a beneficial anti-inflammatory effect in patients with COVID-19. Hence, NBS in treating patients with COVID-19 shows promise as an adjuvant to the current standard antiviral treatment of such patients.

Clinical Trial Registration

https://www.irct.ir, identifier IRCT20200426047206N1.
Blockade of Mbd2 by siRNA-loaded liposomes protects mice against OVA-induced allergic airway inflammation via repressing M2 macrophage production
Authors: Wu Guo-Rao , Zhou Min , Wang Yi , Zhou Qing , Zhang Lei , He Long , Zhang Shu , Yu Qilin , Xu Yongjian , Zhao Jianping , Xiong Weining , Wang Cong-Yi
Published: August 2022

Objective

To address the role of methyl-CpG-binding domain 2 (MBD2) in the pathogenesis of asthma and its potential as a target for the asthmatic therapy.

Methods

Studies were conducted in asthmatic patients and macrophage-specific Mbd2 knockout mice to dissect the role of MBD2 in asthma pathogenesis. Additionally, RNAi-based therapy with Mbd2 siRNA-loaded liposomes was conducted in an ovalbumin (OVA)-induced allergic airway inflammation mouse model.

Results

Asthmatic patients and mice challenged with OVA exhibited upregulated MBD2 expression in macrophages, especially in alternatively activated (M2) macrophages. In particular, macrophage-specific knockout of Mbd2 protected mice from OVA-induced allergic airway inflammation and suppressed the M2 program. Notably, intratracheal administration of liposomes carrying Mbd2 siRNA decreased the expression of Mbd2 and prevented OVA-induced allergic airway inflammation in mice, as indicated by the attenuated airway inflammation and mucus production.

Conclusions

The above data indicate that Mbd2 implicates in the pathogenesis of asthma predominantly by regulating the polarization of M2 macrophages, which supports that Mbd2 could be a viable target for treatment of asthma in clinical settings.
Comprehensive analysis of pyroptotic gene prognostic signatures associated with tumor immune microenvironment and genomic mutation in breast cancer
Authors: Zhang Hongfei , Yu Xiafei , Yang Junzhe , He Gao , Zhang Xiaoqiang , Wu Xian , Shen Li , Zhou Yi , Cheng Xuyu , Liu Xiaoan , Zhu Yanhui
Published: August 2022

Background

Breast cancer is becoming a tumor with the highest morbidity rate, and inflammation-induced cell death namely pyroptosis reportedly plays dual roles in cancers. However, the specific mechanism between pyroptosis and the clinical prognosis of breast cancer patients is indistinct. Hence, novel pyroptosis-related biomarkers and their contributing factors deserve further exploration to predict the prognosis in breast cancer.

Methods

Pearson’s correlation analysis, and univariate and multivariate Cox regression analysis were utilized to obtain six optimal pyroptosis-related gene prognostic signatures (Pyro-GPS). The risk score of each breast cancer patient was calculated. Next, a Pyro-GPS risk model was constructed and verified in TCGA cohort (n=1,089) and GSE20711 cohort (n=88). Then analyses of immune microenvironment, genomic variation, functional enrichment, drug response and clinicopathologic feature stratification associated with the risk score of Pyro-GPS were performed. Subsequently, a nomogram based on the risk score and several significant clinicopathologic features was established. Ultimately, we further investigated the role of CCL5 in the biological behavior of MDA-MB-231 cell line.

Results

The low-risk breast cancer patients have better survival outcomes than the high-risk patients. The low-risk patients also show higher immune cell infiltration levels and immune-oncology target expression levels. There is no significant difference in genetic variation between the two risk groups, but the frequency of gene mutations varies. Functional enrichment analysis shows that the low-risk patients are prominently correlated with immune-related pathways, whereas the high-risk patients are enriched in cell cycle, ubiquitination, mismatch repair, homologous recombination and biosynthesis-related pathways. Pyro-GPS is positively correlated with the IC50 of anti-tumor drugs. Furthermore, comprehensive analyses based on risk score and clinicopathological features were performed to predict the prognosis of breast cancer patients. Additionally, in vitro experiments confirmed that breast cancer cells with high expression of CCL5 had weaker proliferation, invasion and metastasis abilities as well as stronger apoptosis and cell cycle arrest abilities.

Conclusions

The risk score of Pyro-GPS can serve as a promising hallmark to predict the prognosis of BRCA patients. Risk score evaluation may assist to acquire relevant information of tumor immune microenvironment, genomic mutation status, functional pathways and drug sensitivity, and thus provide more effective personalized strategies.
Case report: A case of acute mastitis associated with reactive cutaneous capillary endothelial proliferation after camrelizumab treatment: A new immune-related adverse event
Authors: Wu Ping-Shang , Xiong Dan , Feng Yang-Bo , Xiang Luan , Zhu Jian
Published: August 2022

Lung cancer is a malignant tumor with the highest morbidity and mortality rate worldwide, and it seriously endangers human health. In recent years, immunotherapy has been widely used in lung cancer and has achieved great benefits, especially the application of promoting antitumor immune defense. However, immune-related adverse events (irAEs) caused by immune checkpoint inhibitors have received increasing attention, which largely limits their use. We report the first case of new acute mastitis caused by anti-PD1 inhibitors due to lung adenocarcinoma. A 65-year-old female patient came to our hospital for treatment with cough and shortness of breath for one month. Chest CT showed that the malignant tumor in the lower lobe of the right lung with pleural effusion had metastasized to many places, and then pleural effusion was taken for pathological examination. Pathological examination indicated that the pleural fluid originated from lung adenocarcinoma. Subsequently, the patient received platinum-containing dual-agent chemotherapy (carboplatin and pemetrexed disodium) combined with immunotherapy (camrelizumab). During treatment, the patient developed known adverse events and unreported acute mastitis. After stopping camrelizumab, the patient’s mastitis gradually improved. Our case shows that acute mastitis might be a new adverse event after the use of camrelizumab. Since this new adverse event has not been reported, we hope that oncology medical workers can obtain insight from our case and use it as a reference for the identification and management of irAEs.
Role of the hedgehog signaling pathway in rheumatic diseases: An overview
Authors: Su Yazhen , Xing Hao , Kang Jie , Bai Linkun , Zhang Liyun
Published: August 2022

Hedgehog (Hh) signaling pathway is an evolutionarily conserved signal transduction pathway that plays an important regulatory role during embryonic development, cell proliferation, and differentiation of vertebrates, and it is often inhibited in adult tissues. Recent evidence has shown that Hh signaling also plays a key role in rheumatic diseases, as alterations in their number or function have been identified in rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, systemic sclerosis, and Sjogren’s Syndrome. As a result, emerging studies have focused on the blockade of this pathogenic axis as a promising therapeutic target in several autoimmune disorders; nevertheless, a greater understanding of its contribution still requires further investigation. This review aims to elucidate the most recent studies and literature data on the pathogenetic role of Hh signaling in rheumatic diseases.
Current clinical landscape of oncolytic viruses as novel cancer immunotherapeutic and recent preclinical advancements
Authors: Yun Chae-Ok , Hong JinWoo , Yoon A-Rum
Published: August 2022

Oncolytic viruses (OVs) have been gaining attention in the pharmaceutical industry as a novel immunotherapeutic and therapeutic adjuvant due to their ability to induce and boost antitumor immunity through multiple mechanisms. First, intrinsic mechanisms of OVs that enable exploitation of the host immune system (e.g., evading immune detection) can nullify the immune escape mechanism of tumors. Second, many types of OVs have been shown to cause direct lysis of tumor cells, resulting in an induction of tumor-specific T cell response mediated by release of tumor-associated antigens and danger signal molecules. Third, armed OV-expressing immune stimulatory therapeutic genes could be highly expressed in tumor tissues to further improve antitumor immunity. Last, these OVs can inflame cold tumors and their microenvironment to be more immunologically favorable for other immunotherapeutics. Due to these unique characteristics, OVs have been tested as an adjuvant of choice in a variety of therapeutics. In light of these promising attributes of OVs in the immune-oncology field, the present review will examine OVs in clinical development and discuss various strategies that are being explored in preclinical stages for the next generation of OVs that are optimized for immunotherapy applications.