bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence of restless legs syndrome during the 2019 coronavirus disease pandemic in South Korea: A nationwide cross-sectional population-based study
Authors: Kim Jiyoung , Kang Kyung Wook , Kim Keun Tae , Cho Yong Won
Published: December 2022

Background

The 2019 coronavirus disease (COVID-19) pandemic has been associated with a significant increase in sleep disorders. This study aimed to determine the prevalence of restless leg syndrome (RLS) and the effect of COVID-19 on RLS during the pandemic in Korea.

Methods

The National Sleep Survey of South Korea 2022 was employed in this study. This study was a large population-based web survey using a structural questionnaire of a four thousand representative sample of individuals aged 20–69 years in Korea. The survey was conducted between January 2022 and February 2022 during the COVID-19 pandemic. RLS was diagnosed using the Korean version of the paradigm of questions for epidemiological studies of RLS. Chronic persistent RLS was defined for individuals with RLS symptoms at least twice a week.

Results

Six hundred forty-nine (16.2%) and 172 (4.3%) patients were classified as having RLS and chronic persistent RLS, respectively. Female sex, being employed, the presence of COVID-19 vaccine-related adverse events, decreased sleep duration, the presence of EDS, and current treatment for insomnia were significantly associated with chronic persistent RLS.

Conclusion

During the COVID-19 pandemic, the prevalence of RLS and chronic persistent RLS in the adult Korean population was higher than that reported in previous studies.
Altered gut microbiomes are associated with the symptomatic status of unruptured intracranial aneurysms
Authors: Sun Kaijian , Cao Ying , Chen Yiting , Peng Qing , Xie Yugu , Luo Yunhao , Tian Hao , Li Xin , Zeng Meiqin , Zhang Xin , Li Xifeng , Su Shixing , He Xuying , Duan Chuanzhi , Sun Haitao
Published: December 2022

Background

Gut microbiome has recently been recognized as an important environmental factor affecting the occurrence and development of unruptured intracranial aneurysms (UIA). This study aimed to investigate the relationship between gut microbiome and symptomatic UIA, which is a predictor of instability and a high propensity to rupture.

Methods

A total of 132 patients including 86 asymptomatic UIA and 46 symptomatic UIA were recruited in the study. The composition of gut bacterial communities was determined by 16S ribosomal RNA gene sequencing. In addition, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) was used to predict the functional composition of the gut microbiome.

Results

There is no difference in the fecal microbial alpha diversity between symptomatic and asymptomatic UIA, but gut microbiome composition changed significantly. At the order level, the relative abundance of Clostridiales was significantly enriched in the symptomatic compared with asymptomatic UIA (p = 0.043). In addition, similar alterations were observed at the family levels of Ruminococcaceae. The Linear discriminant analysis (LEfSe) revealed Fournierella, Ruthenibacterium, and Anaerotruncus as discriminative features in the symptomatic group. Notably, functional differences in gut microbiome of patients with symptomatic UIA included decreased propionate metabolism pathway and enrichment of peptidoglycan biosynthesis pathways.

Conclusion

The present study comprehensively characterizes gut microbiome in a large cohort of different risk statuses of UIA patients and demonstrates the potential biological function of gut microbiome involved in the development of UIA. It may provide additional benefits in guiding UIA management and improving patient outcomes.
Phosphoproteomic analysis identifies differentially expressed phosphorylation sites that affect muscle fiber type in pigs
Authors: He Yu , Tan Xiaofan , Li Hongqiang , Yan Zhiwei , Chen Jing , Zhao Ruixue , Irwin David M. , Wu Wangjun , Zhang Shuyi , Li Bojiang
Published: December 2022

Skeletal muscle of livestock is composed of both fast- and slow-twitch muscle fibers, which are key factors in their meat quality. However, the role of protein phosphorylation in muscle fiber type is not completely understood. Here, a fast-twitch (biceps femoris, BF) and slow-twitch (soleus, SOL) muscle tissue sample was collected from three male offspring of Duroc and Meishan pigs. We demonstrate that the meat quality of SOL muscle is significantly better than that of BF muscle. We further used phosphoproteomic profiling of BF and SOL muscles to identify differences between these muscle types. A total of 2,327 phosphorylation sites from 770 phosphoproteins were identified. Among these sites, 287 differentially expressed phosphorylation sites (DEPSs) were identified between BF and SOL. GO and KEGG enrichment analysis of proteins containing DEPSs showed that these phosphorylated proteins were enriched in the glycolytic process GO term and the AMPK signaling pathway. A protein-protein interaction (PPI) analysis reveals that these phosphorylated proteins interact with each other to regulate the transformation of muscle fiber type. These analyses reveal that protein phosphorylation modifications are involved in porcine skeletal muscle fiber type transformation. This study provides new insights into the molecular mechanisms by which protein phosphorylation regulates muscle fiber type transformation and meat quality in pigs.
Non-linear connections between maternal hemoglobin during the third trimester of pregnancy and birth weight outcomes in full-term newborns: Estimating the breakpoints
Authors: Xie Guilan , Wang Ruiqi , Zhang Boxing , Sun Landi , Xiang Wanwan , Xu Mengmeng , Zhu Sijing , Guo Leqian , Xu Xu , Yang Wenfang
Published: December 2022

Objective

Anemia is still an unfinished global health problem, and adverse birth weight outcomes have everlasting influences on the health of later life. However, the non-linear connections and breakpoints of maternal hemoglobin with birth weight outcomes are still needed to be further elucidated. We aimed to reveal the non-linear connections between maternal hemoglobin during the third trimester of pregnancy and birth weight, low birth weight (LBW), macrosomia, small for gestational age (SGA), and large for gestational age (LGA) in full-term newborns and elucidate the breakpoints of the connections.

Methods

A total of 11,411 singletons, full-term, and live newborns, whose mothers conducted the examination of hemoglobin concentration before delivery, were included in this study. A generalized additive model was used to identify and visualize the non-linear connections between maternal hemoglobin and birth weight outcomes. Piecewise linear regression model was adopted to estimate the breakpoints of the connections and report the non-linear connections in detail.

Results

There were inverted “U”-shaped exposure–response connections between maternal hemoglobin concentration and birth weight and the risk of macrosomia. There was an increasing trend of the risk of LBW and a decreased trend of LGA with the increase in maternal hemoglobin concentration. The breakpoints of maternal hemoglobin for birth weight were 100 and 138 g/L, and those for SGA were 97 and 138 g/L. The breakpoints of maternal hemoglobin were 119 g/L for LBW, 105 g/L for macrosomia, and 106 g/L for LGA. When maternal hemoglobin concentration ranged from 100 to 138 g/L, maternal hemoglobin concentration increased per 1 g/L, and birth weight significantly decreased by 2.58 g (95% CI: –3.33, –1.83). When maternal hemoglobin concentration ranged from 97 to 138 g/L, maternal hemoglobin concentration increased per 1 g/L, and the risk of SGA significantly increased by 2% (95% CI: 1%, 3%). When maternal hemoglobin concentration was equal to or lower than 119 g/L, maternal hemoglobin concentration increased per 1 g/L, and the risk of LBW significantly increased by 3% (95% CI: 0%, 5%). When maternal hemoglobin concentration was higher than the breakpoints, the risks of macrosomia (OR = 0.99, 95% CI: 0.98, 0.99) and LGA (OR = 0.99, 95% CI: 0.98, 1.00) declined as the increase of maternal hemoglobin concentration.

Conclusions

There were non-linear connections between maternal hemoglobin and birth weight outcomes, and there are breakpoints in the connections. Cost-effective interventions targeting pregnant women in the prevention of abnormal maternal hemoglobin concentration should be taken to reduce the incidence of adverse birth weight outcomes.
A combined predicting model for benign esophageal stenosis after simultaneous integrated boost in esophageal squamous cell carcinoma patients (GASTO1072)
Authors: Liu Weitong , Zeng Chengbing , Wang Siyan , Zhan Yizhou , Huang Ruihong , Luo Ting , Peng Guobo , Wu Yanxuan , Qiu Zihan , Li Derui , Wu Fangcai , Chen Chuangzhen
Published: December 2022

Purpose

We aimed to develop a combined predicting model for benign esophageal stenosis (BES) after simultaneous integrated boost (SIB) with concurrent chemotherapy in patients with esophageal squamous cell carcinoma (ESCC).

Methods

This study included 65 patients with EC who underwent SIB with chemotherapy. Esophageal stenosis was evaluated using esophagograms and the severity of eating disorders. Risk factors were investigated using univariate and multivariate analyses. Radiomics features were extracted based on contrast-enhanced CT (CE-CT) before treatment. The least absolute shrinkage and selection operator (LASSO) regression analysis was used for feature selection and radiomics signature construction. The model’s performance was evaluated using Harrell’s concordance index and receiver operating characteristic curves.

Results

The patients were stratified into low- and high-risk groups according to BES after SIB. The area under the curves of the clinical model, Rad-score, and the combined model were 0.751, 0.820 and 0.864, respectively. In the validation cohort, the AUCs of these three models were 0.854, 0.883 and 0.917, respectively. The Hosmer-Lemeshow test showed that there was no deviation from model fitting for the training cohort (p=0.451) and validation cohort (p=0.481). The C-indexes of the nomogram were 0.864 and 0.958 for the training and validation cohort, respectively. The model combined with Rad-score and clinical factors achieved favorable prediction ability.

Conclusion

Definitive chemoradiotherapy could alleviate tumor-inducing esophageal stenosis but result in benign stenosis. We constructed and tested a combined predicting model for benign esophageal stenosis after SIB. The nomogram incorporating both radiomics signature and clinical prognostic factors showed favorable predictive accuracy for BES in ESCC patients who received SIB with chemotherapy.

Trial registration number and date of registration

Registered in www.Clinicaltrial.gov, ID: NCT01670409, August 12, 2012
Prognostic value of pan-immune-inflammation value in colorectal cancer patients: A systematic review and meta-analysis
Authors: Yang Xiao-Chuan , Liu Hui , Liu Ding-Cheng , Tong Chao , Liang Xian-Wen , Chen Ri-Hui
Published: December 2022

Background

The pan-immune-inflammation value (PIV) has been reported as a novel prognostic biomarker in multiple malignancies. The aim of this study is to investigate the prognostic value of the PIV in patients with colorectal cancer.

Methods

We comprehensively searched electronic databases including PubMed, Embase and Web of Science up to August 2022. The endpoints were survival outcomes. Hazard ratios (HRs) with 95% confidence intervals (CIs) for survival data were collected for analysis.

Results

Six studies including 1879 participants were included. A significant heterogeneity in the PIV cut-off value among studies was observed. The combined results indicated that patients in the high baseline PIV group had a worse overall survival (HR=2.09; 95%CI: 1.67-2.61; P<0.0001; I2 = 7%) and progression-free survival (HR=1.82; 95%CI: 1.49-2.22; P<0.0001; I2 = 15%). In addition, early PIV increase after treatment initiation was significantly associated with decreased overall survival (HR=1.79; 95%CI: 1.13-2.93; P=0.01; I2 = 26%), and a trend toward poor progression-free survival (HR=2.00; 95%CI: 0.90-4.41; P=0.09; I2 = 70%).

Conclusion

Based on existing evidence, the PIV could act as a valuable prognostic index in patients with colorectal cancer. However, the heterogeneity in the PIV cut-off value among studies should be considered when interpreting these findings.
The reduction of 18F-FDG uptake ability of tumor tissue after neoadjuvant chemoradiotherapy in locally advanced rectal cancer can effectively reflect the degree of tumor regression
Authors: Wu Fengpeng , Zhang Xiaoxiao , Yang Congrong , Wang Kanghua , Xiao Linlin , Zhou Chaoxi , Zhao Xinming , Wang Guiying
Published: December 2022

Introduction

To evaluate the predictive value of 18F-fluorodeoxyglucose positron emission tomography–computed tomography (18F-FDG PET-CT) imaging parameters for the response to neoadjuvant chemoradiotherapy (nCRT) in locally advanced rectal cancer (LARC).

Methods

From January 2016 to March 2020, 52 LARC patients who underwent 18F-FDG PET-CT scans within 1 week before and 8-9 weeks after nCRT, were enrolled in this study according to a pre-designed screening criteria. After total mesorectal excision (TME) surgery, we assessed tumor response to treatment and analyzed the correlation between imaging parameters obtained from two PET-CT scans and tumor regression status.

Results

Tumor response assessment showed that 13 of 52 patients received good response (GR), including 9 cases with pathological complete regression (pCR) and 4 cases with near-pathological complete regression (near-pCR). We also found that the maximum standard uptake value after nCRT (post-SUVmax), the response index (RI), the mean standard uptake values after nCRT (post-SUVmean), and the ratio of tumor SUVmean to liver SUVmean after nCRT (post-Ratio), were correlated with GR and pCR. Among these parameters, post-SUVmax and RI had a near-strong correlation with pCR (rs= -0.58 and 0.59, respectively), and also had a strong correlation with GR (rs = -0.7 and 0.63, respectively). Further ROC analysis showed that post-SUVmax and RI had higher values in predicting whether patients could achieve GR and pCR after nCRT, and the area under the curve (AUC) of both were greater than 0.9. The positive predictive values (PPVs) and negative predictive values (NPVs) of post-SUVmax for GR were 80.01% and 97.3%, and for pCR were 66.68% and 97.5%, respectively. The PPVs and NPVs of the RI values for GR were 84.61% and 94.87%, and for pCR were 69.24% and 100%, respectively.

Conclusion

For LARC patients, the analysis of imaging parameters such as post-SUVmax and RI, which can reflect the changes of 18F-FDG uptake capacity of tumor tissues before and after nCRT, is of great value for predicting the response of patients to neoadjuvant therapy and guiding the selection of subsequent treatment strategies.
Association of systemic inflammation index with survival in patients with advanced perihilar cholangiocarcinoma treated with interventional therapy
Authors: Li Jinyu , Gao Long , Liu Tianci , Feng Duiping
Published: December 2022

Objective

Immunity and inflammation are key mediators of carcinoma development, invasion and metastasis. However, it remains unknown whether the systemic immune-inflammation index (SII) can be used as a prognostic indicator for cholangiocarcinoma. In this study, we investigated the association and predictive value of the SII with the prognosis of advanced perihilar cholangiocarcinoma (pCCA) after interventional therapy.

Methods

A retrospective cohort of patients with advanced pCCA treated with interventional therapy at the First Hospital of Shanxi Medical University enrolled in this study from January 2019 through January 2021 was examined. Cox regression models were used to analyze the relationship between the SII and overall survival (OS) of patients with advanced pCCA. Receiver operating characteristic (ROC) analysis was used to evaluate the predictive power of SII.

Results

Preoperative SII was positively associated with poor OS of pCCA after interventional therapy, with corresponding hazard ratios (HR) of 1.57 (95% CI: 1.17 - 2.10) for an inter-quartile range increase. The predictive power of SII was higher than that of other inflammation indexes based on ROC analysis (AUC = 0.835 [95% CI (0.731 - 0.940)]). The optimal cut-off values, sensitivity, and specificity with SII were 700, 0.774 and 0.846, respectively. An SII ≥ 700 was significantly associated with lymph node metastasis and high carbohydrate antigen199 (CA199) level. In multivariate analyses, total bilirubin, carbohydrate antigen 199, vascular invasion, and SII independently predicted overall survival (P < 0.05).

Conclusion

This is the first study demonstrating that an increase in the SII is associated with poor advanced pCCA prognosis, and could serve as a reliable prognostic indicator of pCCA after interventional therapy.
LINC00324 in cancer: Regulatory and therapeutic implications
Authors: Xia Qing , Shen Jinze , Wang Qurui , Ke Yufei , Yan Qibin , Li Hanbing , Zhang Dayong , Duan Shiwei
Published: December 2022

LINC00324 is a 2082 bp intergenic noncoding RNA. Aberrant expression of LINC00324 was associated with the risk of 11 tumors and was closely associated with clinicopathological features and prognostic levels of 7 tumors. LINC00324 can sponge multiple miRNAs to form complex ceRNA networks, and can also recruit transcription factors and bind RNA-binding protein HuR, thereby regulating the expression of a number of downstream protein-coding genes. LINC00324 is involved in 4 signaling pathways, including the PI3K/AKT signaling pathway, cell cycle regulatory pathway, Notch signaling pathway, and Jak/STAT3 signaling pathway. High expression of LINC00324 was associated with larger tumors, a higher degree of metastasis, a higher TNM stage and clinical stage, and shorter OS. Currently, four downstream genes in the LINC00324 network have targeted drugs. In this review, we summarize the molecular mechanisms and clinical value of LINC00324 in tumors and discuss future directions and challenges for LINC00324 research.
Case report: Neurofibromatosis type 1 gastrointestinal stromal tumor and small bowel adenocarcinoma with a novel germline NF1 frameshift mutation
Authors: Zhang Wuming , Hu Xianqin , Chen Zhikang , Lai Chen
Published: December 2022

A synchronous case of small bowel adenocarcinoma(SAB) is reported, accompanied with gastrointestinal stromal tumor(GIST),and gangliocytomain in an elderly woman with neurofibromatosis type 1 (NF-1). A 67-year-old female was hospitalized with the chief complaint of abdominal pain, the computed tomography scan indicated a large bowel mass. Multiple tumors were found in the small intestine, through which two larger tumors (7 cm and 1.5 cm) were resected. A novel germline NF1 mutation and a PMS2 mutation were identified after genetic testing, followed by the exploration of possible relationship between them in promoting tumorigenesis. Our results suggest multiple gastrointestinal tumors emerging in NF1 patients, and genetic testing can better guide postoperative treatment in a more efficient way.
PLK4 initiates crosstalk between cell cycle, cell proliferation and macrophages infiltration in gliomas
Authors: Zhang Xiaoyang , Li Zesheng , Wei Cheng , Luo Lin , Li Shenghui , Zhou Junhu , Liang Hao , Li Ying , Han Lei
Published: December 2022

Tumor immune microenvironment plays an important role in tumorigenesis and metastasis. Polo-like kinases 4 (PLK4) is a crucial regulatory factor in the process of cell cycle, and its abnormal regulation often leads to a variety of diseases including tumorigenesis. We have previously explored the function of PLK4 in sensitizing chemotherapy in glioma, but there are few studies on the correlation between PLK4 and tumor immune microenvironment. PLK4 was found to be highly expressed in various types of cancers, including glioma and closely related to histological and genetic features in public databases. Kaplan-Meier survival analysis and Cox regression analysis revealed that higher PLK4 expression is associated with poorer prognosis. GO and KEGG functional enrichment analysis showed that PLK4 expression level was significantly correlated with regulation of immune microenvironment, cell cycle and genomic instability. Immune infiltration analysis showed that high expression of PLK4 resulted in reduced infiltration of macrophages. M1 macrophage infiltration assays showed that PLK4 knockdown GBM cell lines promoted the recruitment of M1-type macrophages via altering expression of chemokines. And in intracranial tumor mouse models, PLK4 inhibition increased tumor-infiltrating M1 macrophages. In summary, our results demonstrated the correlation between high PLK4 expression level and malignant progression of gliomas, and the possible involvement of PLK4 in regulation of cell cycle, cell proliferation and macrophages infiltration in gliomas.
Comprehensive analysis of cuproptosis-related long non-coding RNA signature and personalized therapeutic strategy of breast cancer patients
Authors: Guo Qiaonan , Qiu Pengjun , Pan Kelun , Lin Jianqing
Published: December 2022

Background

Breast cancer (BC) is considered to be one of the primary causes of cancer deaths in women. Cuproptosis was suggested to play an important role in tumor proliferation and tumor immune microenvironment. Therefore, an investigation was conducted to identify the relationship between cuproptosis-related long non-coding RNAs (lncRNAs) and BC prognosis.

Method

Based on The Cancer Genome Atlas (TCGA), nine cuproptosis-related lncRNAs were identified by Pearson’s analysis and Cox regression analysis to create a cuproptosis-related lncRNA signature. Subsequently, patients with BC were divided into high-risk and low-risk groups. The Kaplan–Meier curves and a time-dependent receiver operating characteristic (ROC) analysis were employed to elucidate the predictive capability of the signature. After that, the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was conducted by Gene Set Enrichment Analysis (GSEA), and the lncRNA–mRNA co-expression network was established by Cytoscape software. Furthermore, the ESTIMATE score was calculated, and the immune cell type component analysis was conducted. Eventually, immunotherapy response analysis was applied to identify the predictive power of cuproptosis-related lncRNAs to tumor immunotherapy response, including immune checkpoint gene expression levels, tumor mutational burden (TMB), and microsatellite instability (MSI).

Results

Patients with BC in the low-risk groups showed better clinical outcomes. The KEGG pathways in the high-risk groups were mainly enriched in immune response and immune cell activation. Furthermore, the ESTIMATE scores were higher in the low-risk groups, and their immune cell infiltrations were dramatically different from those of the high-risk groups. The low-risk groups were shown to have higher infiltration levels of CD8+ T cells and TMB-high status, resulting in better response to immunotherapies.

Conclusion

The findings of this study revealed that the nine-cuproptosis-related lncRNA risk score was an independent prognostic factor for BC. This signature was a potential predictor for BC immunotherapy response. What we found will provide novel insight into immunotherapeutic treatment strategies in BC.
Cancer diagnosis in areas of conflict
Authors: Al-Ibraheem Akram , Abdlkadir Ahmed Saad , Mohamedkhair Ali , Mikhail-Lette Miriam , Al-Qudah Mohammad , Paez Diana , Mansour Asem H.
Published: December 2022

To date, many Arab countries within the Middle East are facing political, financial, and social instability from war and conflicts. These conflicts have led to severe resources shortages and sometimes complete breakdowns in cancer care and diagnosis. Cancer diagnosis at early stages is the most vital step in achieving optimal cancer care and outcomes. Shortages in cancer diagnostic services have meant that many people within areas of conflict are ultimately deprived of these services in their own countries. Therefore, many of these cancer sufferers must bear travel expenses to neighboring countries in order to seek these services. A lack of prevention, screening, and diagnostic services for this population is known to deepen the cancer care deficit within these areas. Additionally, the financial burden of traveling abroad alongside the need to secure childcare and time off work can be overwhelming. As a result, patients within areas of conflict are frequently diagnosed at later stages and are less likely to receive optimal management plans. Though conflict-affected regions encounter many similar challenges in delivering quality cancer care, pronounced region-specific differences do exist. Therefore, it is important to build a roadmap that can provide tailored solutions to deficits in instruments, manpower, and facilities for each and every region involved. Keeping in mind the importance of collaboration and coordination on national and international levels to address the ground disparity in cancer diagnostic services, the main objective of this review article is to examine the significant problems, shortages, and difficulties in providing cancer diagnosis with a focus on imaging to conflict-affected populations in the Middle East (mainly Iraq, Syria, Yemen, and Sudan). Finally, we discuss how access to cancer diagnostic imaging services has been impacted by these conflicts.
Diagnostic and prognostic role of circulating neutrophil extracellular trap markers and prekallikrein in patients with high-grade serous ovarian cancer
Authors: Kim Jisoo G. , Kim Se Ik , Song Sang Hoon , Gu Ja-Yoon , Lee Maria , Kim Hyun Kyung
Published: December 2022

Objective

Tumor-promoting inflammation is among the hallmarks of cancer. Prekallikrein is among the acute-phase reactants in the inflammatory response; moreover, neutrophils release nuclear contents into the extracellular space to create neutrophil extracellular traps (NET). We aimed to investigate the diagnostic and prognostic utilities of circulating plasma NET markers and prekallikrein for high-grade serous ovarian cancer (HGSOC).

Methods

Circulating levels of three NET markers (histone-DNA complex, cell-free DNA, and neutrophil elastase) and prekallikrein were measured in 75 patients with HGSOC and 23 healthy controls. We used an area under the receiver operating characteristic curve (AUC) analysis to investigate their diagnostic and prognostic utilities for HGSOC.

Results

Compared with healthy controls, patients with HGSOC showed significantly higher levels of the three NET markers and prekallikrein. Patients with advanced-stage HGSOC showed significantly higher levels of the cell-free DNA (87.4 vs. 79.5 ng/ml; P = 0.013), compared with those with early-stage HGSOC. Further, the levels of histone-DNA complex, neutrophil elastase, and prekallikrein did not significantly differ according to the cancer stage. All markers showed significant diagnostic utility. Notably, a logistic regression-based model that comprised all four markers showed the strongest diagnostic power (AUC, 0.966; 95% confidence interval [CI], 0.933−1.000). Specifically, neutrophil elastase was identified as an independent poor prognostic factor for overall survival (adjusted hazard ratio [aHR], 10.17; 95% CI, 1.09−94.97; P = 0.042) and progression-free survival (aHR, 14.47; 95% CI, 1.52−137.35; P = 0.020) in patients with HGSOC.

Conclusions

The levels of the three NET markers and prekallikrein might be novel diagnostic and prognostic markers for HGSOC.
Susceptibility of ECE1 polymorphisms to Hirschsprung's disease in southern Chinese children
Authors: Lan Chaoting , Liu Yanqing , Wu Xiao , Wang Bingtong , Xin Songqing , He Qiuming , Zhong Wei , Liu Zipeng
Published: December 2022

Background

Hirschsprung's disease (HSCR) is currently considered to be a congenital gastrointestinal malformation caused mainly by genetic factors. Endothelin Converting Enzyme-1 (ECE1) has been reported to be associated with HSCR. However, the relationship between ECE1 single nucleotide polymorphism (SNP) rs169884 and HSCR in the southern Chinese population remains unknown.

Methods

1,470 HSCR patients and 1,473 controls from a southern Chinese population were recruited. The intronic SNP rs169884 in ECE1 was genotyped in all samples. We tested the association between rs169884 and HSCR under various genetic models. We also evaluated the effect of rs169884 on HSCR subtypes, including short-segment HSCR (S-HSCR), long-segment HSCR (L-HSCR) and total colonic aganglionosis (TCA). External epigenetic data were integrated to investigate the potential biological function of rs169884.

Results

Chromatin states data from derived neuron cells or fetal colon tissue revealed that rs169884 might control ECE1 expression through regulating its enhancer function. We did not find a significant association between rs169884 and HSCR. For HSCR subtypes, although no significant associations were detected between rs169884 and S-HSCR (OR = 1.00, 95% CI: 0.89∼1.12, Padj = 0.77) or TCA (OR = 1.00, 95% CI: 0.72∼1.38, Padj = 0.94), we found that rs169884 could increase the risk of L-HSCR (OR = 1.23, 95% CI 1.02∼1.45, Padj = 0.024).

Conclusion

These results suggested that rs169884 might play a regulatory role for ECE1 expression and increase susceptibility of L-HSCR in southern Chinese children.
Provision of mother's own milk for preterm infants during the COVID-19 pandemic: Differential effect of insurance
Authors: Boudreau Lauren E. , Vohr Betty R. , Tucker Richard , McGowan Elisabeth C.
Published: December 2022

Mother-infant dyads faced many challenges during the COVID-19 pandemic; however, the impact was different depending on socio-economic determinants. This study aims to investigate the impact of the COVID-19 pandemic on maternal provision of mother's own milk (MOM) at neonatal intensive care unit (NICU) discharge among preterm infants. We hypothesized that fewer infants would be discharged home on any MOM during the pandemic period compared to a pre-pandemic period. This is a retrospective analysis of infants born <34 weeks' gestation admitted to the Women and Infant's Hospital NICU. Infants born pre-pandemic (1/1/2019 to 2/29/2020) were compared to infants born during the pandemic (3/1/2020 to 4/30/2021). Maternal and neonatal variables were analyzed by group. The primary outcome was provision of MOM (defined as feeding exclusively MOM, or a combination of MOM and formula) at NICU discharge. Analyses were performed for time periods, and multivariable regression analyses were run for the total cohort and by insurance type. Analysis included 268 infants born pre-pandemic and 262 infants born during the pandemic. Pandemic group mothers vs. pre-pandemic were less likely to be single (27%, 63/233 vs. 38%, 93/243; p = 0.01) and more likely to have a diagnosis of chorioamnionitis (16%, 38/236 vs. 7%, 17/243; p = 0.002). Rates of public insurance were similar (55% pre-pandemic and 50% pandemic). There was no significant change in provision of MOM between time periods. In multivariable analysis, public insurance decreased the odds of MOM at discharge for the entire study period (aOR 0.31, 95% CI: 0.19–0.50; p = 0.0001). On analysis by insurance type, rates of MOM increased from 77% pre-pandemic to 88% during the pandemic (p = 0.03) for mothers with private insurance and remained unchanged for mothers with public insurance (52% pre-pandemic and 53% pandemic; p = 0.86). Mothers with private insurance had twice the odds (aOR 2.02, 95% CI: 1.02–3.97; p = 0.04) of providing MOM during the pandemic vs. pre-pandemic. For those with public insurance, the odds for any MOM provision during the pandemic were unchanged (aOR 0.95, 95% CI: 0.5–1.7; p = 0.86). These differences may be related to health care disparities requiring additional exploration of risk factors and the need for equitable opportunities for all mother-infant dyads.
Flecainide and risk of skin neoplasms: Results of a large nested case–control study in Spain and Denmark
Authors: Reyes Carlen , León-Muñoz Luz M , Pistillo Andrea , Jóhannesdóttir Schmidt Sigrún Alba , Kristensen Kasper Bruun , Puente Diana , LLorente-García Ana , Huerta-Álvarez Consuelo , Pottegård Anton , Duarte-Salles Talita
Published: December 2022

Background: A previous study in Denmark suggested an increased melanoma risk associated with the use of flecainide.

Objective: To study the association between flecainide use and the risk of melanoma and non-melanoma skin cancer in Spain and Denmark.

Methods: We conducted a multi-database case–control study in (database/study period) Spain (SIDIAP/2005–2017 and BIFAP/2007–2017) and Denmark (Danish registries/2001–2018). We included incident cases of melanoma or non-melanoma skin cancer (NMSC) aged ≥18 with ≥2 years of previous data (≥10 years for Denmark) before the skin cancer and matched them to controls (10:1 by age and sex). We excluded persons with immunosuppression or previous cancer. We defined ever-use as any prescription fill and high-use as a cumulative dose of at least 200 g (reference: never-use). We categorized a cumulative dose for a dose–response assessment. We used conditional logistic regression to compute ORs (95% CI) adjusted for photosensitizing, anti-neoplastic, disease-specific drugs and comorbidities.

Results: The total numbers of melanoma/NMSC cases included were 7,809/64,230 in SIDIAP, 4,661/31,063 in BIFAP, and 27,978/152,821 in Denmark. In Denmark, high-use of flecainide was associated with increased adjusted ORs of skin cancer compared with never-use [melanoma: OR 1.97 (1.38–2.81); NMSC: OR 1.34 (1.15–1.56)]. In Spain, an association between high-use of flecainide and NMSC was also observed [BIFAP: OR 1.42 (1.04–1.93); SIDIAP: OR 1.19 (0.95–1.48)]. There was a non-significant dose–response pattern for melanoma in Denmark and no apparent dose–response pattern for NMSC in any of the three databases. We found similar results for ever-use of flecainide.

Conclusion: Flecainide use was associated with an increased risk of melanoma (Denmark only) and NMSC (Denmark and Spain) but without substantial evidence of dose–response patterns. Further studies are needed to assess for possible unmeasured confounders.
On the effect of the thermal cross-talk in a photonic feed-forward neural network based on silicon microresonators
Authors: Biasi Stefano , Franchi Riccardo , Bazzanella Davide , Pavesi Lorenzo
Published: December 2022

Local heating is widely used to trim or tune photonic components in integrated optics. Typically, it is achieved through the power dissipation of metal microwires driven by a current and placed nearby the photonic component. Then, via the thermo-optic effect, both the amplitude and the phase of the complex optical field propagating in the component can be controlled. In the last decade, optical integrated circuits with a cascade of more than 60 thermo-optical phase shifters were demonstrated for quantum simulators or optical neural networks. In this work, we demonstrate a simple two layers feed-forward neural network based on cascaded of thermally controlled Mach-Zehnder interferometers and microring resonators. We show that the dynamics of a high quality factor microresonator integrated into a Silicon On Insulator (SOI) platform is strongly affected by the current flowing in metal heaters where these last generate both local as well as global heating on the integrated photonic circuit. Interestingly, microheaters, even when they are at distances of a few millimetres from the optical component, influence all the microresonators and the Mach-Zehnder interferometers in the photonic circuit. We model the heat flux they generate and modify accordingly the non-linear equations of a system formed by a microresonator coupled to a bus waveguide. Furthermore, we show experimentally that the use of microheaters can be a limiting factor for the feed-forward neural network where three microresonators are used as non-linear nodes. Here, the information encoding, as well as the signal processing, occurs within the photonic circuit via metal heaters. Specifically, the network reproduces a given non-linear surjective function based on a domain of at most two inputs and a co-domain of just one output. As a result, its training aims to determine the values of the currents to apply to the heaters in the hidden layers, which allows replicating a certain shape. We demonstrate how the network exploits mainly the heat flow generated by the information encoding to reproduce a target avoiding the use of all the hidden layer heaters. This work shows that in large thermally actuated integrated photonic circuit, the thermal cross talk is an issue.
Incorporating structural abnormalities in equivalent dipole layer based ECG simulations
Authors: Boonstra Machteld J , Oostendorp Thom F , Roudijk Rob W , Kloosterman Manon , Asselbergs Folkert W , Loh Peter , Van Dam Peter M
Published: December 2022

Introduction: Electrical activity of the myocardium is recorded with the 12-lead ECG. ECG simulations can improve our understanding of the relation between abnormal ventricular activation in diseased myocardium and body surface potentials (BSP). However, in equivalent dipole layer (EDL)-based ECG simulations, the presence of diseased myocardium breaks the equivalence of the dipole layer. To simulate diseased myocardium, patches with altered electrophysiological characteristics were incorporated within the model. The relation between diseased myocardium and corresponding BSP was investigated in a simulation study.

Methods: Activation sequences in normal and diseased myocardium were simulated and corresponding 64-lead BSP were computed in four models with distinct patch locations. QRS-complexes were compared using correlation coefficient (CC). The effect of different types of patch activation was assessed. Of one patient, simulated electrograms were compared to electrograms recorded during invasive electro-anatomical mapping.

Results: Hundred-fifty-three abnormal activation sequences were simulated. Median QRS-CC of delayed versus dyssynchronous were significantly different (1.00 vs. 0.97, p < 0.001). Depending on the location of the patch, BSP leads were affected differently. Within diseased regions, fragmentation, low bipolar voltages and late potentials were observed in both recorded and simulated electrograms.

Discussion: A novel method to simulate cardiomyopathy in EDL-based ECG simulations was established and evaluated. The new patch-based approach created a realistic relation between ECG waveforms and underlying activation sequences. Findings in the simulated cases were in agreement with clinical observations. With this method, our understanding of disease progression in cardiomyopathies may be further improved and used in advanced inverse ECG procedures.
TREK-1 in the heart: Potential physiological and pathophysiological roles
Authors: Bechard Emilie , Bride Jamie , Le Guennec Jean-Yves , Brette Fabien , Demion Marie
Published: December 2022

The TREK-1 channel belongs to the TREK subfamily of two-pore domains channels that are activated by stretch and polyunsaturated fatty acids and inactivated by Protein Kinase A phosphorylation. The activation of this potassium channel must induce a hyperpolarization of the resting membrane potential and a shortening of the action potential duration in neurons and cardiac cells, two phenomena being beneficial for these tissues in pathological situations like ischemia-reperfusion. Surprisingly, the physiological role of TREK-1 in cardiac function has never been thoroughly investigated, very likely because of the lack of a specific inhibitor. However, possible roles have been unraveled in pathological situations such as atrial fibrillation worsened by heart failure, right ventricular outflow tract tachycardia or pulmonary arterial hypertension. The inhomogeneous distribution of TREK-1 channel within the heart reinforces the idea that this stretch-activated potassium channel might play a role in cardiac areas where the mechanical constraints are important and need a particular protection afforded by TREK-1. Consequently, the main purpose of this mini review is to discuss the possible role played by TREK -1 in physiological and pathophysiological conditions and its potential role in mechano-electrical feedback. Improved understanding of the role of TREK-1 in the heart may help the development of promising treatments for challenging cardiac diseases.
Genome-wide identification, characterization, evolution, and expression pattern analyses of the typical thioredoxin gene family in wheat (Triticum aestivum L.)
Authors: Zhou Jianfei , Song Tianqi , Zhou Hongwei , Zhang Mingfei , Li Nan , Xiang Jishan , Zhang Xiaoke
Published: December 2022

Typical thioredoxin (TRX) plays an important role in maintaining redox balance in plants. However, the typical TRX genes in wheat still need to be comprehensively and deeply studied. In this research, a total of 48 typical TaTRX genes belonging to eight subtypes were identified via a genome-wide search in wheat, and the gene structures, protein conserved motifs, and protein 3D structures of the same subtype were very similar. Evolutionary analysis showed that there are two pairs of tandem duplication genes and 14 clusters of segmental duplication genes in typical TaTRX family members; TaTRX15, TaTRX36, and TaTRX42 had positive selection compared with the orthologs of their ancestral species; rice and maize have 11 and 13 orthologous typical TRXs with wheat, respectively. Gene Ontology (GO) analysis indicated that typical TaTRXs were involved in maintaining redox homeostasis in wheat cells. Estimation of ROS content, determination of antioxidant enzyme activity, and gene expression analysis in a line overexpressing one typical TaTRX confirmed that TRX plays an important role in maintaining redox balance in wheat. A predictive analysis of cis-acting elements in the promoter region showed that typical TaTRXs were extensively involved in various hormone metabolism and response processes to stress. The results predicted using public databases or verified using RT-qPCR show that typical TaTRXs were able to respond to biotic and abiotic stresses, and their expression in wheat was spatiotemporal. A total of 16 wheat proteins belonging to four different families interacting with typical TaTRXs were predicted. The above comprehensive analysis of typical TaTRX genes can enrich our understanding of this gene family in wheat and provide valuable insights for further gene function research.
Gibberellic acid sensitive dwarf encodes an ARPC2 subunit that mediates gibberellic acid biosynthesis, effects to grain yield in rice
Authors: Um Tae Young , Hong So Yeon , Han Ji Sung , Jung Ki Hong , Moon Sunok , Choi Beom-Soon , Basnet Prakash , Chung Young Soo , Lee Seon Woo , Yang Won Tae , Kim Doh Hoon
Published: December 2022

The plant hormone gibberellic acid (GA) is important for plant growth and productivity. Actin-related proteins (ARPs) also play central roles in plant growth, including cell elongation and development. However, the relationships between ARPs and GA signaling and biosynthesis are not fully understood. Here, we isolated OsGASD, encoding an ARP subunit from rice (Oryza sativa), using the Ac/Ds knockout system. The osgasd knockout (Ko) mutation reduced GA3 content in shoots as well as plant growth and height. However, GA application restored the plant height of the osgasd Ko mutant to a height similar to that of the wild type (WT). Rice plants overexpressing OsGASD (Ox) showed increased plant height and grain yield compared to the WT. Transcriptome analysis of flag leaves of OsGASD Ox and osgasd Ko plants revealed that OsGASD regulates cell development and the expression of elongation-related genes. These observations suggest that OsGASD is involved in maintaining GA homeostasis to regulate plant development, thereby affecting rice growth and productivity.
S-ResNet: An improved ResNet neural model capable of the identification of small insects
Authors: Wang Pei , Luo Fan , Wang Lihong , Li Chengsong , Niu Qi , Li Hui
Published: December 2022

Introduction

Precise identification of crop insects is a crucial aspect of intelligent plant protection. Recently, with the development of deep learning methods, the efficiency of insect recognition has been significantly improved. However, the recognition rate of existing models for small insect targets is still insufficient for insect early warning or precise variable pesticide application. Small insects occupy less pixel information on the image, making it more difficult for the model to extract feature information.

Methods

To improve the identification accuracy of small insect targets, in this paper, we proposed S-ResNet, a model improved from the ResNet, by varying its convolution kernel. The branch of the residual structure was added and the Feature Multiplexing Module (FMM) was illustrated. Therefore, the feature expression capacity of the model was improved using feature information of different scales. Meanwhile, the Adjacent Elimination Module (AEM) was furtherly employed to eliminate the useless information in the extracted features of the model.

Results

The training and validation results showed that the improved residual structure improved the feature extraction ability of small insect targets compared to the original model. With compare of 18, 30, or 50 layers, the S-ResNet enhanced the identification accuracy of small insect targets by 7% than that on the ResNet model with same layer depth.
Loss of linker histone H1 in the maternal genome influences DEMETER-mediated demethylation and affects the endosperm DNA methylation landscape
Authors: Han Qiang , Hung Yu-Hung , Zhang Changqing , Bartels Arthur , Rea Matthew , Yang Hanwen , Park Christine , Zhang Xiang-Qian , Fischer Robert L. , Xiao Wenyan , Hsieh Tzung-Fu
Published: December 2022

The Arabidopsis DEMETER (DME) DNA glycosylase demethylates the central cell genome prior to fertilization. This epigenetic reconfiguration of the female gamete companion cell establishes gene imprinting in the endosperm and is essential for seed viability. DME demethylates small and genic-flanking transposons as well as intergenic and heterochromatin sequences, but how DME is recruited to these loci remains unknown. H1.2 was identified as a DME-interacting protein in a yeast two-hybrid screen, and maternal genome H1 loss affects DNA methylation and expression of selected imprinted genes in the endosperm. Yet, the extent to which H1 influences DME demethylation and gene imprinting in the Arabidopsis endosperm has not been investigated. Here, we showed that without the maternal linker histones, DME-mediated demethylation is facilitated, particularly in the heterochromatin regions, indicating that H1-bound heterochromatins are barriers for DME demethylation. Loss of H1 in the maternal genome has a very limited effect on gene transcription or gene imprinting regulation in the endosperm; however, it variably influences euchromatin TE methylation and causes a slight hypermethylation and a reduced expression in selected imprinted genes. We conclude that loss of maternal H1 indirectly influences DME-mediated demethylation and endosperm DNA methylation landscape but does not appear to affect endosperm gene transcription and overall imprinting regulation.