bluuebunny/crossref_metadata_2025 huggingface dataset:
Electrochemical sensing of fentanyl as an anesthesia drug on NiO nanodisks combined with the carbon nanotube-modified electrode
Authors: Li Xi , Luo Bo , Liao Min , Mohamed Abdullah
Published: November 2022

Fentanyl was successfully determined in the current effort based on hexagonal NiO nanodisks (HG-NiO-NDs) fabricated by the hydrothermal protocol. The synergism of HG-NiO-NDs with multiwall carbon nanotubes (MWCNTs), large specific surface area, and active material enabled the electrochemical sensor to show potent electrochemical behavior. Admirable performance was found for the fentanyl measurement by the MWCNT and HG-NiO-ND-modified pencil graphite electrode (MWCNT/HG-NiO-ND/PGE). The correlation of oxidation currents with the pH value, concentration, and sweep rate of supporting electrolytes was determined for the optimization of conditions to detect fentanyl. The surfaces of modified and unmodified electrodes were characterized as well. The diffusion-control processes were confirmed on the basis of anodic peak findings. The results also revealed a two-electron transfer process. The linear range was obtained to be 0.01–800.0 μM for the fentanyl concentrations on the developed electrode, with the sensitivity of 0.1044 μA/mM/cm2. The limit of detection (S/N = 3) was 6.7 nM. The results indicated the ability of the modified electrode to fabricate non-enzymatic fentanyl sensor applications.
Decadal variability of the interannual climate predictability associated with the Indo-Pacific oceanic channel dynamics in CCSM4
Authors: Yuan Dongliang , Xu Peng , Xu Tengfei , Zhao Xia
Published: November 2022

The lag correlations between the observed sea surface temperature anomalies (SSTA) in the southeastern tropical Indian Ocean in fall and those in the Pacific cold tongue at the one-year time lag are calculated in running windows of 7–11 years and are shown to have decadal variability. Similar decadal variability has also been identified in the historical simulations of the Community Climate System Model version 4 (CCSM4) that participates in the Coupled Model Intercomparison Project phase-5 (CMIP5). During the positive phases of the decadal variability, the significant lag correlations are diagnosed to be dominated by the oceanic channel dynamics, i.e., upwelling Kelvin waves associated with the Indian Ocean Dipole (IOD) force enhanced Indonesian Throughflow transport anomalies and western Pacific thermocline anomalies to propagate eastward, resulting in SSTA in the central-eastern equatorial Pacific Ocean. During the negative phases of the decadal variability, the subsurface lag correlations suggest that the western Pacific Ocean are still dominated by the oceanic channel dynamics, but do not correlate well with the SSTA in the cold tongue due to a deeper thermocline in the eastern equatorial Pacific. The IOD-ENSO teleconnection is not affected significantly by the anthropogenic forcing during either the positive or the negative decadal phases. The CCSM4 model is found to underestimate Indonesian Throughflow transport variability but overestimate the westerly wind anomalies in the western-central equatorial Pacific, which forces unrealistic anomalies in the equatorial Pacific Ocean associated with the IOD.
C-reactive protein and coronary atheroma regression following statin therapy: A meta-regression of randomized controlled trials
Authors: Gao Darui , Hua Rong , Jiesisibieke Dina , Ma Yanjun , Li Chenglong , Wu Sijing , Ma Qian , Xie Wuxiang
Published: November 2022

Objective

Several clinical trials have indicated that statins stabilize and reverse atherosclerotic plaque. However, different studies have provided inconsistent findings regarding mechanisms and influencing factors of plaque regression under statin therapy. Apart from lipid-lowering effect, statins have pleiotropic effects including anti inflammation in humans. In this study, meta-analysis and meta-regression were used to determine the effects of statin medications on coronary plaque volume. Meanwhile, to assess whether statins promote plaque regression effect was related to their anti-inflammatory ability, the impact of CRP/hsCRP reduction during statin therapy on plaque regression was investigated.

Methods

Up to June 15, 2022, a systematic PubMed, EMBASE, and Cochrane search was performed for randomized controlled trials that assessed treatment effect using total atheroma volume (TAV), percent atheroma volume (PAV), or plaque volume (PV). Only CRP/hsCRP and LDL-C values reported before and after treatment were considered.

Results

12 studies (2,812 patients with heart and/or vascular disease) fulfilled the inclusion criteria and were included in the systematic review. A meta-analysis of 15 statin-treated arms reported a significant reduction in change of TAV/PV [standardized mean difference (SMD): –0.27, 95% confidence intervals (–CI): –0.42, –0.12, p < 0.001], compared with the control arms. Another meta-analysis of 7 trials also found that patients in the intervention group had a significant reduction in change of PAV (SMD: -0.16, 95% CI: –0.29, –0.03, p = 0.019), compared with those in the control group. Meta-regressionanalysis revealed that the percent change of CRP/hsCRP was significantly associated with SMD in change of TAV/PV after adjusting for percent change of LDL-C, age, gender and study duration. Meta-regression analysis showed that percent change of CRP/hsCRP statistically influenced SMD in change of PAV, when percent change of CRP/hsCRP was included separately. However, the percent change of CRP/hsCRP was not significantly associated with SMD of PAV change after adjusting for all covariates.

Conclusion

In conclusion, statin therapy is beneficial for plaque regression. Statins promote plaque regression, which might be associated to their anti-inflammatory ability.
Risk stratification system and visualized dynamic nomogram constructed for predicting diagnosis and prognosis in rare male breast cancer patients with bone metastases
Authors: Gao Bing , Ou Xiao-lan , Li Mu-feng , Wang Meng-die , Huang Fei
Published: November 2022

Background

Bone metastases (BM) from malignant tumors could disrupt the balance between osteoclasts and osteoblasts and affect bone homeostasis. Malignant breast cancer (BC) is rare in male patients, and co-occurrence of BM is even rarer. Given its low incidence, there is limited research evaluating risk and prognosis. Despite the widespread application of nomograms to predict uncommon malignancies, no studies have constructed predictive models focusing on the diagnosis and prognosis of male breast cancer with bone metastases (MBCBM).

Methods

This study selected all male breast cancer patients (MBC) between 2010 and 2019 in the Surveillance, Epidemiology, and End Results (SEER) database. We used simple and multivariate Logistic regression analyses to identify independent risk factors for BM in MBC patients. Then simple and multivariate Cox regression analyses were employed to determine the independent prognostic factors for overall survival (OS) and cancer-specific survival (CSS) in MBCBM patients. We established and validated three new nomograms based on these independent factors.

Result

A total of 4187 MBC patients were included, with 191 (4.56%) having bone metastases at the time of diagnosis. The independent risk factors of BM in MBC patients included age, tumor size, marital status, T stage, and N stage. In MBCBM patients, independent prognostic factors for OS and CSS were both age, T stage, ER status, PR status, and surgery. The concordance index (C-index), the area under the curve (AUC) of the receiver operating characteristic curve (ROC), the calibration curve, and the decision curve analysis (DCA) confirmed that these three nomograms could accurately predict the diagnosis and prognosis of MBCBM patients with excellent discrimination and clinical utility superior to the TNM staging system. We then established two prognostic-based risk stratification systems and three visualized dynamic nomograms that could be applied in clinical practice.

Conclusion

In conclusion, this study aimed to establish and validate an accurate novel nomogram to objectively predict the diagnosis and prognosis of MBCBM patients. On this basis, prognostic-based risk stratification systems and visualized dynamic nomograms were constructed to facilitate doctors and patients to quantify individual BM risk probability and survival probability to assist in personalized risk assessment and clinical decision-making.
A review on phytochemical and pharmacological facets of tropical ethnomedicinal plants as reformed DPP-IV inhibitors to regulate incretin activity
Authors: Chhabria Srishti , Mathur Shivangi , Vadakan Sebastian , Sahoo Dipak Kumar , Mishra Pragnyashree , Paital Biswaranjan
Published: November 2022

Type 2 diabetes mellitus is a metabolic disorder resulting from impaired insulin secretion and resistance. Dipeptidyl peptidase (DPP)-IV is an enzyme known to trigger the catalysis of insulinotropic hormones, further abating the endogenous insulin levels and elevating the glucose levels in blood plasma. In the field of drug development, DPP-IV inhibitors have opened up numerous opportunities for leveraging this target to generate compounds as hypoglycemic agents by regulating incretin activity and subsequently decreasing blood glucose levels. However, the practice of synthetic drugs is an apparent choice but poses a great pharmacovigilance issue due to their incessant undesirable effects. The ideology was set to inventively look upon different ethnomedicinal plants for their anti-diabetic properties to address these issues. To date, myriads of phytochemicals are characterized, eliciting an anti-diabetic response by targeting various enzymes and augmenting glucose homeostasis. Antioxidants have played a crucial role in alleviating the symptoms of diabetes by scavenging free radicals or treating the underlying causes of metabolic disorders and reducing free radical formation. Plant-based DPP-IV inhibitors, including alkaloids, phenolic acid, flavonoids, quercetin, and coumarin, also possess antioxidant capabilities, providing anti-diabetic and antioxidative protection. This review article provides a new gateway for exploring the ability of plant-based DPP-IV inhibitors to withstand oxidative stress under pathological conditions related to diabetes and for reforming the strategic role of ethnomedicinal plants as potent DPP-IV inhibitors through the development of polyherbal formulations and nanophytomedicines to regulate incretin activity.
Role of EGFR expressed on the granulosa cells in the pathogenesis of polycystic ovarian syndrome
Authors: Zhang Jun-Hui , Zhan Lei , Zhao Ming-Ye , Wang Jin-Juan , Xie Fen-Fen , Xu Zu-Ying , Xu Qian , Cao Yun-Xia , Liu Qi-Wei
Published: November 2022

Polycystic ovarian syndrome (PCOS) is one of the most common endocrinological disorders affecting between 6 to 20% of reproductive aged women. However, the etiology of PCOS is still unclear. Epidermal growth factor receptor (EGFR) plays a critical role in the growth and development of ovarian follicles. In our previous study, we showed that the expression level of EGFR was significantly higher in the cumulus granulosa cells from women with PCOS than that of normal women, suggesting that EGFR may play a potential role in the pathogenesis of PCOS. The present study further evaluated the association between EGFR and PCOS through both in clinical observation and animal experiments. We firstly validated the differential expression of EGFR in cumulus granulosa cells between PCOS patients and normal subjects by qRT-PCR and immunofluorescence staining. Then we generated a mouse model (n=20) of PCOS by injecting dehydroepiandrosterone (DHEA). The PCOS mice were then injected with an E corpus GFR inhibitor (AG1478) (n=10), which significantly improved the sex hormone levels in the estrous cycle stage, and the serum levels of LH, FSH and testosterone were compared with the PCOS mice without EGFR inhibitor treatment (n=10). Decreasing the expression level of EGFR in the PCOS mice also improved the ovulatory function of their ovaries which was indicated by the multifarious follicle stage in these mice as compared with the PCOS mice without EGFR inhibitor treatment. Also, the number of corpopa lutea were higher in the control group and the EGFR inhibitor treated group than in the PCOS group. The sex hormone levels and reproductive function were not significantly different between the control mice and the PCOS mice treated with the EGFR inhibitor. Our results demonstrated that EGF/EGFR signaling affected the proliferation of cumulus granulosa cells, oocyte maturation and meiosis, and played a potential role in the pathogenesis of PCOS. Therefore, the selective inhibition of EGFR may serve as a novel strategy for the clinical management of PCOS.
Grandfathering or benchmarking: Which is more viable for the manufacturer’s low-carbon activities?
Authors: Wang Zhanjie , Wang Fei , Wang Yongjian
Published: November 2022

Under the emissions trading policy, two typical carbon allowance allocation rules of grandfathering and benchmarking are widely adopted in the present carbon markets. Based on the mathematical modeling method, this paper explores which allocation rule is more viable for manufacturers’ low-carbon activities including abatement investment and remanufacturing activities. Meanwhile, the effects on total profit, total carbon emissions, consumer surplus, and social welfare are discussed through numerical analysis. The results show that benchmarking is more viable for abatement investment activities of manufacturers than grandfathering. Additionally, benchmarking is always more viable for remanufacturing activities of manufacturers only in a situation with a higher consumer low-carbon preference. Otherwise, which allocation rule is more beneficial for remanufacturing activities mainly depends on the abatement cost coefficient. Correspondingly, the higher the consumer low-carbon preference or the lower the abatement cost, the more viable the benchmarking is to achieve each performance target (e.g., total profit, emissions control, consumer surplus, and social welfare). Based on these findings, this paper also recommends managerial insights for manufacturers and policy implications for policy-makers.
Prediction of wastewater treatment system based on deep learning
Authors: Lin Wei , Hanyue Yu , Bin Li
Published: November 2022

Introduction

In order to accurately model the IC reactor of the wastewater treatment system and efficiently control and adjust the water treatment process, this paper proposes a method to predict the operation effect of the IC reactor using an artificial neural network model. This paper takes the IC reactor section of a papermaking wastewater treatment plant as the research object, and predicts the COD value of its effluent through the neural network model established. The experimental results show that the simulation prediction value of BP neural network is basically consistent with the change trend of the actual value, and has a certain prediction ability. Among the 20 groups of sample data for simulation prediction, the prediction relative error value of 9 sample data pairs is less than 5%, that is, the prediction error of 45% sample data pairs is within 5%; The relative error value of 15 sample data pairs is less than 10%, that is, 75% of sample data pairs have a prediction error of less than 10%; The maximum relative error is 18.6%. Through the regression analysis of the real value and the predicted value, the correlation coefficient is 0.7431.

Conclusion

The BP neural network can capture the non-linear mapping relationship between the selected input factors and the output, and can predict the COD value of the effluent of IC reactor in advance.
Making Green(s) With Black and White: Constructing Soils for Urban Agriculture Using Earthworms, Organic and Mineral Wastes
Authors: Araujo J. H. R. , Pando-Bahuon A. , Hartmann C. , Aroui-Boukbida H. , Desjardins T. , Lerch Thomas Z.
Published: November 2022

Urban agriculture has been of growing interest for a decade because it can address many economic and societal issues in the development of modern cities. However, urban agriculture is often limited by the availability of fertile and non-contaminated soils in the cities. Recycling excavated mineral wastes from building activities to construct fertile soils may be a more sustainable alternative than the importation of topsoils from rural zones. The present study aims to evaluate the possibility to grow green vegetables on soils made with excavated deep horizon of soils and green waste compost. During three consecutive seasons, we tested in situ the effects of different amounts of compost (10, 20, and 30%) and the addition of an earthworm species (Lumbricus terrestris) on the production of lettuce (Lactuca sativa L.), arugula (Eruca sativa Mill.), and spinach (Spinacia oleracea L.) in mono- and co-culture. Our results demonstrate that it is possible to reuse mineral and organic urban wastes to engineer soils adapted to agriculture. Here, we observed that higher doses of compost significantly increased plant biomass, especially when earthworms were introduced. For example, in the autumn, going from 10 to 30% of compost in the soil mixture allows to multiply by 2 the arugula biomass, and even by 4 in the presence of earthworms. These results were partly due to the positive effects of these two factors on soil physical properties (micro- and macro-porosity). This preliminary study also showed that some plants (arugula) are more adapted than others (lettuce) to the soil properties and that it only takes few months to get the highest yields. These promising results for the development of urban agricultures encourage to test many other combination of plant and earthworm species but also to conduct experiments over long-term periods.
Characterization of glycosylation regulator-mediated glycosylation modification patterns and tumor microenvironment infiltration in hepatocellular carcinoma
Authors: Zhao Linlin , Guo Yang , Liu Zhanfeng , Ma Jing , Peng Yanfeng , Zhang Dejun
Published: November 2022

Background: Previous studies have shown that glycosylation of proteins ofen plays an important role in HCC. However, the potential mechanism of glycosylation in HCC has not been described systematically.

Methods: We comprehensively evaluated the glycosylation patterns in HCC samples based on 43 glycosylation regulators, and annotated the modification patterns with the enrichment of immune cells and stromal cells. Considering the heterogeneity of HCC patients, the glycosylation score was constructed using single-sample gene set enrichment analysis (ssGSEA). We also explored the drugs that different HCC patients were sensitive to based on glycosylation mode and score.

Results: We identified three glycosylation-regulated gene subtypes. By annotating the subtypes, it was found that the glycosylation regulated gene subtypes was highly matched with three immunophenotypes of HCC (immune-inflamed, immune-excluded, and immune-desert), regardless of the characteristics of immune cell infiltration or prognosis. Based on the characteristic genes of glycosylation-regulated gene subtypes, we constructed a glycosylation-related model, and found that glycosylation-related model was highly consistent with the glycosylation regulated gene subtypes. The glycosylation score that evaluates the glycosylation characteristics of a single HCC sample has high prognostic value, and the prognosis of patients with high glycosylation score is significantly worse. Interestingly, we found that the glycosylation score was closely related to tumor node metastasis (TNM) staging. By applying glycosylation-regulated gene subtypes and glycosylation score to explore the sensitivity of different patients to anticancer drugs, it was found that the sensitivity of Thapsigargin, Shikonin, Embelin and Epothilone. B was closely related to the glycosylation mode.

Conclusion: This study reveals that the diversity of glycosylation patterns plays an important role in HCC. Therefore, evaluating the glycosylation patterns of patients with HCC will be helpful in identifying the characteristics of immune cell infiltration and selecting accurate treatment methods.
Genome-wide association studies reveal putative QTLs for physiological traits under contrasting phosphorous conditions in wheat (Triticum aestivum L.)
Authors: Dharmateja Palaparthi , Yadav Rajbir , Kumar Manjeet , Babu Prashanth , Jain Neelu , Mandal Pranab Kumar , Pandey Rakesh , Shrivastava Manoj , Gaikwad Kiran B. , Bainsla Naresh Kumar , Tomar Vipin , Sugumar S. , Saifi Nasreen , Ranjan Rumesh
Published: November 2022

A Genome-wide association (GWAS) study was conducted for phosphorous (P)-use responsive physiological traits in bread wheat at the seedling stage under contrasting P regimes. A panel of 158 diverse advanced breeding lines and released varieties, and a set of 10,800 filtered single nucleotide polymorphism (SNP) markers were used to study marker-trait associations over the eight shoot traits. Principle component analysis separated the two environments (P regimes) because of the differential response of the traits indicating the essentiality of the separate breeding programmes for each environment. Significant variations for genotypic, environmental, and genotype × environment (GEI) effects were observed for all the traits in the combined analysis of variance with moderately high broad sense heritability traits (0.50–0.73). With the different algorithms of association mapping viz., BLINK, FarmCPU, and MLM, 38 unique QTLs under non-limiting P (NLP) and 45 QTLs for limiting P (LP) conditions for various shoot traits were identified. Some of these QTLs were captured by all three algorithms. Interestingly, a Q.iari.dt.sdw.1 on chromosome 1D was found to explain the significant variations in three important physiological traits under non-limiting phosphorus (NLP) conditions. We identified the putative candidate genes for QTLs namely Q.iari.dt.chl.1, Q.iari.dt.sdw.16, Q.iari.dt.sdw.9 and Q.iari.dt.tpc.1 which are potentially involved in the mechanism regulating phosphorus use efficiency through improved P absorption due to improved root architectural traits and better mobilization such as sulfotransferase involved in postembryonic root development, WALLS ARE THIN1 (WAT1), a plant-specific protein that facilitates auxin export; lectin receptor-like kinase essentially involved in plant development, stress response during germination and lateral root development and F-box component of the SKP-Cullin-F box E3 ubiquitin ligase complex and strigolactone signal perception. Expression profiling of putative genes located in identified genomic regions against the wheat expression atlas revealed their significance based on the expression of these genes for stress response and growth development processes in wheat. Our results thus provide an important insight into understanding the genetic basis for improving PUE under phosphorus stress conditions and can shape the future breeding programme by developing and integrating molecular markers for these difficult-to-score important traits.
LINC00958 may be a new prognostic biomarker in various cancers: A meta-analysis and bioinformatics analysis
Authors: Zhang Helin , Zhang Guangming , Zhang Fan , Yang Xiaochun , Li Erqiang , Wang Bo , Xu Peng , Zhang Dengxiao , Guo Lijun , Huang Xiande
Published: November 2022

Background: There have been many studies on long non-coding RNAs (lncRNAs) as tumor markers. LINC00958 is a lncRNA that has been studied in a variety of tumor types. This meta-analysis aims to explore the relationship between LINC00958 and clinical prognosis and pathological characteristics in various cancers.

Methods: We searched for related studies from PubMed, Web of Science, The Cochrane Library and Embase (up to October 2021). The association of LINC00958 expression with clinicopathological characteristics and prognosis was evaluated using the pooled odds ratios (ORs) or hazard ratios (HRs) with 95% confidence intervals (CIs).

Results: 16 studies (1,121 patients) were included in this meta-analysis, we found that overexpression of LINC00958 was associated with poor overall survival (OS) (HR = 1.84; 95% CI: 1.36–2.49; p < 0.001). We also found that LINC00958 overexpression was correlated with positive lymph node metastasis (LNM) (OR = 1.91; 95% CI: 1.39–2.63; p < 0.001), advanced degree of infiltration (OR = 1.64; 95% CI: 1.11–2.41; p = 0.013), advanced tumor-node-metastasis (TNM) stage (OR = 2.80; 95% CI: 1.48–5.33; p = 0.002). Other clinicopathological characteristics have no obvious correlation, such as age, sex, tumor size, distant metastasis, and differentiation grade (p > 0.05).

Conclusion: In summary, the overexpression of LINC00958 is significantly correlated with poor OS, positive LNM, advanced degree of infiltration, and advanced TNM stage. LINC00958 might serve as a potential prognostic biomarker and therapeutic target for a variety of cancers. However, rigorous studies with large sample sizes are still needed for further research and demonstration.
MyD88-dependent signaling drives toll-like receptor-induced trained immunity in macrophages
Authors: Owen Allison M. , Luan Liming , Burelbach Katherine R. , McBride Margaret A. , Stothers Cody L. , Boykin Olivia A. , Sivanesam Kalkena , Schaedel Jessica F. , Patil Tazeen K. , Wang Jingbin , Hernandez Antonio , Patil Naeem K. , Sherwood Edward R. , Bohannon Julia K.
Published: November 2022

Immunocompromised populations are highly vulnerable to developing life-threatening infections. Strategies to protect patients with weak immune responses are urgently needed. Employing trained immunity, whereby innate leukocytes undergo reprogramming upon exposure to a microbial product and respond more robustly to subsequent infection, is a promising approach. Previously, we demonstrated that the TLR4 agonist monophosphoryl lipid A (MPLA) induces trained immunity and confers broad resistance to infection. TLR4 signals through both MyD88- and TRIF-dependent cascades, but the relative contribution of each pathway to induction of trained immunity is unknown. Here, we show that MPLA-induced resistance to Staphylococcus aureus infection is lost in MyD88-KO, but not TRIF-KO, mice. The MyD88-activating agonist CpG (TLR9 agonist), but not TRIF-activating Poly I:C (TLR3 agonist), protects against infection in a macrophage-dependent manner. MPLA- and CpG-induced augmentation of macrophage metabolism and antimicrobial functions is blunted in MyD88-, but not TRIF-KO, macrophages. Augmentation of antimicrobial functions occurs in parallel to metabolic reprogramming and is dependent, in part, on mTOR activation. Splenic macrophages from CpG-treated mice confirmed that TLR/MyD88-induced reprogramming occurs in vivo. TLR/MyD88-triggered metabolic and functional reprogramming was reproduced in human monocyte-derived macrophages. These data show that MyD88-dependent signaling is critical in TLR-mediated trained immunity.
Real-world landscape transition of death causes in the immunotherapy era for metastatic non-small cell lung cancer
Authors: Wu Yijun , Yao Zhuoran , Zhang Jianhui , Han Chang , Kang Kai , Zhao Ailin
Published: November 2022

Background

With approval of anti-PD-1/PD-L1, metastatic non-small cell lung cancer (NSCLC) has entered the era of immunotherapy. Since immune-related adverse events (irAEs) occur commonly in patients receiving anti-PD-1/PD-L1, the landscape of death causes may have changed in metastatic NSCLC. We aim to compare patterns of death causes in metastatic NSCLC between the pre-immunotherapy and immunotherapy era to identify the consequent landscape transition of death causes.

Methods

In this cohort study, 298,485 patients with metastatic NSCLC diagnosed between 2000 and 2018 were identified from the Surveillance, Epidemiology, and End Results Program. Unsupervised clustering with Bayesian inference method was performed for all patients’ death causes, which separated them into two death patterns: the pre-immunotherapy era group and the immunotherapy era group. Relative risk (RR) of each death cause between two groups was estimated using Poisson regression. Reduced death risk as survival time was calculated with locally weighted scatterplot smooth (Lowess) regression.

Results

Two patterns of death causes were identified by unsupervised clustering for all patients. Thus, we separated them into two groups, the immunotherapy era (2015-2017, N=40,172) and the pre-immunotherapy era (2000-2011, N=166,321), in consideration of obscure availability to immunotherapy for patients diagnosed in 2012-2014, when the follow-up cutoff was set as three years. Although all-cause death risk had reduced (29.2%, 13.7% and 27.8% for death risks of lung cancer, non-cancer and other cancers), non-cancer deaths in the immunotherapy era (N=2,100, 5.2%; RR=1.155, 95%CI: 1.101-1.211, P<0.001) significantly increased than that in the pre-immunotherapy era (N=7,249, 5.0%), which included causes of chronic obstructive pulmonary disease, cerebrovascular disease, pneumonia and influenza, septicemia, infectious diseases, accidents and adverse effects, hypertension, and chronic liver disease and cirrhosis. However, cancer-caused deaths (excluding lung cancer) had no significant changes.

Conclusions

The real-world landscape of death causes has changed in metastatic NSCLC when entering the immunotherapy era, and the increased non-cancer diseases may contribute to the changes that may be associated with commonly occurring irAEs.
NFIL3 and its immunoregulatory role in rheumatoid arthritis patients
Authors: Du Juping , Zheng Liyuan , Chen Shuaishuai , Wang Na , Pu Xia , Yu Die , Yan Haixi , Chen Jiaxi , Wang Donglian , Shen Bo , Li Jun , Pan Shaobiao
Published: November 2022

Nuclear-factor, interleukin 3 regulated (NFIL3) is an immune regulator that plays an essential role in autoimmune diseases. However, the relationship between rheumatoid arthritis (RA) and NFIL3 remains largely unknown. In this study, we examined NFIL3 expression in RA patients and its potential molecular mechanisms in RA. Increased NFIL3 expression levels were identified in peripheral blood mononuclear cells (PBMCs) from 62 initially diagnosed RA patients and 75 healthy controls (HCs) by quantitative real-time PCR (qRT-PCR). No correlation between NFIL3 and disease activity was observed. In addition, NFIL3 expression was significantly upregulated in RA synovial tissues analyzed in the Gene Expression Omnibus (GEO) dataset (GSE89408). Then, we classified synovial tissues into NFIL3-high (≥75%) and NFIL3-low (≤25%) groups according to NFIL3 expression levels. Four hundred five differentially expressed genes (DEGs) between the NFIL3-high and NFIL3-low groups were screened out using the “limma” R package. Enrichment analysis showed that most of the enriched genes were primarily involved in the TNF signaling pathway via NFκB, IL-17 signaling pathway, and rheumatoid arthritis pathways. Then, 10 genes (IL6, IL1β, CXCL8, CCL2, PTGS2, MMP3, MMP1, FOS, SPP1, and ADIPOQ) were identified as hub genes, and most of them play a key role in RA. Positive correlations between the hub genes and NFIL3 were revealed by qRT-PCR in RA PBMCs. An NFIL3-related protein–protein interaction (PPI) network was constructed using the STRING database, and four clusters (mainly participating in the inflammatory response, lipid metabolism process, extracellular matrix organization, and circadian rhythm) were constructed with MCODE in Cytoscape. Furthermore, 29 DEGs overlapped with RA-related genes from the RADB database and were mainly enriched in IL-17 signaling pathways. Thus, our study revealed the elevated expression of NFIL3 in both RA peripheral blood and synovial tissues, and the high expression of NFIL3 correlated with the abnormal inflammatory cytokines and inflammatory responses, which potentially contributed to RA progression.
Integrative sperm DNA methylation and miRomics analysis highlights interaction of two epigenetic patterns of pseudomale inheritance in teleost
Authors: Zhao Na , Jia Lei , Chen Lu , Lin Jieyan , Dong Zhongdian , Zhang Bo
Published: November 2022

Proper DNA methylation in spermatozoa is essential for the normal development of fertilized embryos through gene expression regulation. Abnormal sperm DNA methylation is associated with male fertility impairment, offspring quality decline, and disease susceptibility. Compared with other epigenetic regulatory mechanisms (e.g., histone modification), DNA methylation is a stable regulator for the long-term transcriptional activity of genes. Sperm DNA methylation is crucial to offspring’s survival, development, and reproduction. However, it has not been well studied in teleost to a large extent, especially in some species with sex deviation or congenital sex abnormality in offspring. In the present study, DNA methylation profiles of pseudomale (ZW) and male (ZZ) tongue sole (Cynoglossus semilaevis) spermatozoa were characterized for differential methylation regions (DMRs) screening. The global methylation levels of the two sperm groups were highly methylated with no significant differences. For all kinds of genomic elements, the mean methylation level of the ZW group was higher than that of the ZZ group. The total numbers of Covered C annotated on the W chromosome of both groups were extremely small, suggesting that W-type sperm did not exist in pseudomales. A comparison of methylation levels on 20 sex-related genes between sperm and gonad showed that the heterogeneity between tissue resources was greater than that between sexes, and the methylation level of most genes in gonads was lower than that in sperm. For integrative analysis of DNA methylation and miRomic profiles, 11 sex-related DMRs associated with 15 differentials micro RNAs (miRNAs) in spermatozoa were identified to present targeting relationships and regulatory trends of the two distinct epigenetic patterns. This study provides valuable and potential targets of coordination between two epigenetic mechanisms in the process of C. semilaevis sex congenital bias.
Form identification of purple flying squid (Sthenoteuthis oualaniensis) based on gladius morphology
Authors: Zhu Kai , Lin Dongming , Chen Xinjun , Xu Kaida
Published: November 2022

Stock structure information is an important part of bases for understanding the dynamics of cephalopod populations. Purpleback flying squid Sthenoteuthis oualaniensis is an abundant and highly productive species in tropical and subtropical waters of the Indo-Pacific region. However, it is characterized by a complex stock structure, and the stock discrimination is an urgent priority to understand basic biology and for stock assessment and management purposes. Here, we used gladius morphology to identify and discriminate the dwarf without a dorsal photophore and middle-sized typical forms of S. oualaniensis in the South China Sea. Results showed that both forms had double axes on the gladius and females consistently had a larger gladius than males. Multivariate analyses using the gladius morphometric characteristics indicated that individuals of dwarf form without a dorsal photophore were distinguished from those of middle-sized typical form, which was evidenced by the obvious groups and significant dissimilarity of gladii of these two forms. The discrimination based on the gladius morphometric characteristics showed a high rate of accuracy, in which a global discrimination accuracy was estimated to be 92.36% for both forms without regarding sexes and 65.82% for the discrimination to form and sex. In combination, these lines of evidence indicated that individuals of dwarf without a dorsal photophore and middle-sized typical forms of S. oualaniensis can be accurately distinguished using the gladius morphometric characteristics, and these results will warrant the application of the gladius to study the stock structure of S. oualaniensis and other squid else.
A dual decoder U-Net-based model for nuclei instance segmentation in hematoxylin and eosin-stained histological images
Authors: Mahbod Amirreza , Schaefer Gerald , Dorffner Georg , Hatamikia Sepideh , Ecker Rupert , Ellinger Isabella
Published: November 2022

Even in the era of precision medicine, with various molecular tests based on omics technologies available to improve the diagnosis process, microscopic analysis of images derived from stained tissue sections remains crucial for diagnostic and treatment decisions. Among other cellular features, both nuclei number and shape provide essential diagnostic information. With the advent of digital pathology and emerging computerized methods to analyze the digitized images, nuclei detection, their instance segmentation and classification can be performed automatically. These computerized methods support human experts and allow for faster and more objective image analysis. While methods ranging from conventional image processing techniques to machine learning-based algorithms have been proposed, supervised convolutional neural network (CNN)-based techniques have delivered the best results. In this paper, we propose a CNN-based dual decoder U-Net-based model to perform nuclei instance segmentation in hematoxylin and eosin (H&E)-stained histological images. While the encoder path of the model is developed to perform standard feature extraction, the two decoder heads are designed to predict the foreground and distance maps of all nuclei. The outputs of the two decoder branches are then merged through a watershed algorithm, followed by post-processing refinements to generate the final instance segmentation results. Moreover, to additionally perform nuclei classification, we develop an independent U-Net-based model to classify the nuclei predicted by the dual decoder model. When applied to three publicly available datasets, our method achieves excellent segmentation performance, leading to average panoptic quality values of 50.8%, 51.3%, and 62.1% for the CryoNuSeg, NuInsSeg, and MoNuSAC datasets, respectively. Moreover, our model is the top-ranked method in the MoNuSAC post-challenge leaderboard.
Altered functional connectivity of cerebellar networks in first-episode schizophrenia
Authors: Feng Sitong , Zheng Sisi , Zou Haoming , Dong Linrui , Zhu Hong , Liu Shanshan , Wang Dan , Ning Yanzhe , Jia Hongxiao
Published: November 2022

Introduction

Abnormalities of the cerebellum have been displayed to be a manifestation of schizophrenia (SCH) which is a detrimental psychiatric disorder. It has been recognized that the cerebellum contributes to motor function, sensorimotor function, cognition, and other brain functions in association with cerebral functions. Multiple studies have observed that abnormal alterations in cerebro-cerebellar functional connectivity (FC) were shown in patients with SCH. However, the FC of cerebellar networks in SCH remains unclear.

Methods

In this study, we explored the FC of cerebellar networks of 45 patients with first-episode SCH and 45 healthy control (HC) subjects by using a defined Yeo 17 network parcellation system. Furthermore, we performed a correlation analysis between cerebellar networks’ FC and positive and negative symptoms in patients with first-episode SCH. Finally, we established the classification model to provide relatively suitable features for patients with first-episode SCH concerning the cerebellar networks.

Results

We found lower between-network FCs between 14 distinct cerebellar network pairs in patients with first-episode SCH, compared to the HCs. Significantly, the between-network FC in N2-N15 was positively associated with positive symptom severity; meanwhile, N4-N15 was negatively associated with negative symptom severity. Besides, our results revealed a satisfactory classification accuracy (79%) of these decreased between-network FCs of cerebellar networks for correctly identifying patients with first-episode SCH.

Conclusion

Conclusively, between-network abnormalities in the cerebellum are closely related to positive and negative symptoms of patients with first-episode SCH. In addition, the classification results suggest that the cerebellar networks can be a potential target for further elucidating the underlying mechanisms in first-episode SCH.
Human periventricular nodular heterotopia shows several interictal epileptic patterns and hyperexcitability of neuronal firing
Authors: Frazzini Valerio , Whitmarsh Stephen , Lehongre Katia , Yger Pierre , Lemarechal Jean-Didier , Mathon Bertrand , Adam Claude , Hasboun Dominique , Lambrecq Virginie , Navarro Vincent
Published: November 2022

Periventricular nodular heterotopia (PNH) is a malformation of cortical development that frequently causes drug-resistant epilepsy. The epileptogenicity of ectopic neurons in PNH as well as their role in generating interictal and ictal activity is still a matter of debate. We report the first in vivo microelectrode recording of heterotopic neurons in humans. Highly consistent interictal patterns (IPs) were identified within the nodules: (1) Periodic Discharges PLUS Fast activity (PD+F), (2) Sporadic discharges PLUS Fast activity (SD+F), and (3) epileptic spikes (ES). Neuronal firing rates were significantly modulated during all IPs, suggesting that multiple IPs were generated by the same local neuronal populations. Furthermore, firing rates closely followed IP morphologies. Among the different IPs, the SD+F pattern was found only in the three nodules that were actively involved in seizure generation but was never observed in the nodule that did not take part in ictal discharges. On the contrary, PD+F and ES were identified in all nodules. Units that were modulated during the IPs were also found to participate in seizures, increasing their firing rate at seizure onset and maintaining an elevated rate during the seizures. Together, nodules in PNH are highly epileptogenic and show several IPs that provide promising pathognomonic signatures of PNH. Furthermore, our results show that PNH nodules may well initiate seizures.
Socioeconomic and demographic determinants of radiation treatment and outcomes in glioblastoma patients
Authors: Hsu Eric J. , Thomas Jamie , Timmerman Robert D. , Wardak Zabi , Dan Tu D. , Patel Toral R. , Sanford Nina N. , Vo Dat T.
Published: November 2022

Introduction

Poor outcomes in glioblastoma patients, despite advancing treatment paradigms, indicate a need to determine non-physiologic prognostic indicators of patient outcome. The impact of specific socioeconomic and demographic patient factors on outcomes is unclear. We sought to identify socioeconomic and demographic patient characteristics associated with patient survival and tumor progression, and to characterize treatment options and healthcare utilization.

Methods

A cohort of 169 patients with pathologically confirmed glioblastomas treated at our institution was retrospectively reviewed. Multivariable cox proportional hazards analysis for overall survival (OS) and cumulative incidence of progression was performed. Differences in treatment regimen, patient characteristics, and neuro-oncology office use between different age and depressive disorder history patient subgroups were calculated two-sample t-tests, Fisher's exact tests, or linear regression analysis.

Results

The median age of all patients at the time of initiation of radiation therapy was 60.5 years. The median OS of the cohort was 13.1 months. Multivariable analysis identified age (Hazard Ratio 1.02, 95% CI 1.00–1.04) and total resection (Hazard Ratio 0.52, 95% CI 0.33–0.82) as significant predictors of OS. Increased number of radiation fractions (Hazard Ratio 0.90, 95% CI 0.82–0.98), depressive disorder history (Hazard Ratio 0.59, 95% CI 0.37–0.95), and total resection (Hazard Ratio 0.52, 95% CI 0.31–0.88) were associated with decreased incidence of progression. Notably, patients with depressive disorder history were observed to have more neuro-oncology physician office visits over time (median 12 vs. 16 visits, p = 0.0121). Patients older than 60 years and those with Medicare (vs. private) insurance were less likely to receive as many radiation fractions (p = 0.0014) or receive temozolomide concurrently with radiation (Odds Ratio 0.46, p = 0.0139).

Conclusion

Older glioblastoma patients were less likely to receive as diverse of a treatment regimen as their younger counterparts, which may be partially driven by insurance type. Patients with depressive disorder history exhibited reduced incidence of progression, which may be due to more frequent health care contact during neuro-oncology physician office visits.
A brief review of motor imagery and bimanual coordination
Authors: Sisti Helene M. , Beebe Annika , Bishop Mercedes , Gabrielsson Elias
Published: November 2022

Motor imagery is increasingly being used in clinical settings, such as in neurorehabilitation and brain computer interface (BCI). In stroke, patients lose upper limb function and must re-learn bimanual coordination skills necessary for the activities of daily living. Physiotherapists integrate motor imagery with physical rehabilitation to accelerate recovery. In BCIs, users are often asked to imagine a movement, often with sparse instructions. The EEG pattern that coincides with this cognitive task is captured, then used to execute an external command, such as operating a neuroprosthetic device. As such, BCIs are dependent on the efficient and reliable interpretation of motor imagery. While motor imagery improves patient outcome and informs BCI research, the cognitive and neurophysiological mechanisms which underlie it are not clear. Certain types of motor imagery techniques are more effective than others. For instance, focusing on kinesthetic cues and adopting a first-person perspective are more effective than focusing on visual cues and adopting a third-person perspective. As motor imagery becomes more dominant in neurorehabilitation and BCIs, it is important to elucidate what makes these techniques effective. The purpose of this review is to examine the research to date that focuses on both motor imagery and bimanual coordination. An assessment of current research on these two themes may serve as a useful platform for scientists and clinicians seeking to use motor imagery to help improve bimanual coordination, either through augmenting physical therapy or developing more effective BCIs.