bluuebunny/crossref_metadata_2025 huggingface dataset:
Survival Outcomes of Patients With Mediastinal Germ Cell Tumors: Experience of a Cancer Center in South America
Authors: Vallejo-Yepes Camilo , Carvajal-Fierro Carlos Andrés , Brugés-Maya Ricardo , Beltrán Julian , Buitrago Ricardo , Beltrán-Jimenez Rafael , Carreño-Dueñas José Alexander
Published: January 2022

Purpose

Mediastinal germ cell tumors (GCT) are rare neoplasms associated with poor survival prognosis. Due to their low incidence, limited information is available about this disease in South America. The objective of this study is to report the clinical characteristics and outcomes of patients with mediastinal GCT in a cancer center in Colombia.

Materials and Methods

We conducted a retrospective analysis of patients with mediastinal GCT treated at the National Cancer Institute at Bogota (Colombia) between 2008 and 2020. Survival curves were presented using the Kaplan–Meier method. Chi-square and Cox proportional hazard model tests were used for data analysis.

Results

Sixty-one patients were included in the study. Of them, 60 were male and 51 (83.6%) of whom had non-seminomatous germ cell tumors (NSGCT). Twenty-nine patients (47.5%) presented with superior vena cava syndrome, and 18 (29.5%) patients had extrapulmonary metastatic involvement. The three-year overall survival (OS) of NSGCT patients was 26%. The 3-year OS of NSGCT patients who underwent surgical resection of residual mediastinal mass after chemotherapy was 59%. Non-surgical management after first-line chemotherapy was associated with a worse survival prognosis in NSGCT patients (p = 0.002). Ten patients with mediastinal seminomatous germ cell tumors (SCGT) achieved a 3-year OS of 100%.

Conclusion

Mediastinal NSGCT had poor outcomes. Surgery of the residual mass after first-line chemotherapy seems to improve the outcome of NSGCT patients. Advanced disease at presentation may reflect inadequate access to reference cancer centers in Colombia and potentially explain poor survival outcomes in this cohort. On the other hand, mediastinal SCGT is a biologically different disease; most patients will achieve disease remission and long-term survival with first-line chemotherapy.
A Five-Parameter Logistic Model to Predict the Possibility of Misdiagnosis for Improving the Specificity of Lugol Chromoendoscopy in the Diagnosis of Esophageal Neoplastic Lesions
Authors: Guo Zijun , Meng Lingjun , Tian Shuxin , Chen Lan , Shi Huiying , Fan Mengke , Lin Rong
Published: January 2022

Background

Lugol chromoendoscopy (LCE) is a technique that is inexpensive and convenient for screening esophageal neoplastic lesions. However, the specificity of LCE is limited. The purpose of this study was to determine the risk characteristics of lesions related to false-positive results for LCE.

Methods

In this retrospective study, 871 lesions in 773 patients scheduled for LCE in Wuhan Union Hospital and First Affiliated Hospital of Shihezi University between April 2013 and October 2018 were enrolled. The 871 lesions were used to determine the diagnostic performance of LCE for detecting esophageal neoplastic lesions and were divided into an LCE-positive group (627 lesions) and an LCE-negative group (244 lesions). Six hundred and twenty-seven unstained/understained lesions from 563 patients were used to determine the significant risk factors for misdiagnosis of neoplasms by LCE. Among them, 358 lesions and 269 lesions were classified into the misdiagnosed group and correctly diagnosed group, respectively. A multivariate logistic regression analysis was conducted for suspected esophageal neoplastic lesions during the LCE examination.

Results

The sensitivity, specificity, and overall accuracy for LCE were 100%, 40.5%, and 58.9%, respectively. Among 13 characteristics of lesions, lesions with branching vascular network (OR 4.53, 95% CI 2.23–9.21, p < 0.001), smooth lesions (OR 2.40, 95% CI 1.38–4.18, p = 0.002) under white light endoscopy (WLE), lesions with a size < 5 mm (OR 3.06, 95% CI 1.38–6.78, p = 0.006), ill-demarcated lesions (OR 7.83, 95% CI 4.59–13.37, p < 0.001), and pink color sign (PCS)-negative (OR 4.04, 95% CI 2.38–6.84, p < 0.001) lesions after reaction with iodine solution were independent risk factors for misdiagnosis as neoplastic lesions by LCE.

Conclusion

LCE has a high sensitivity but limited specificity for screening esophageal neoplastic lesions. For unstained or understained lesions, branching vascular network or smooth appearance under WLE, a size < 5 mm in diameter, ill-demarcated, or PCS-negative lesions after staining are related to the misdiagnosis of esophageal neoplastic lesions by LCE based on logistic regression. The multivariate logistic model may be used to predict the possibility of misdiagnosis and help improve the specificity of LCE in diagnosing esophageal neoplastic lesions.
Clinical Trial Eligibility Criteria and Recently Approved Cancer Therapies for Patients With Brain Metastases
Authors: Tan Aaron C. , Boggs Drexell H. , Lee Eudocia Q. , Kim Michelle M. , Mehta Minesh P. , Khasraw Mustafa
Published: January 2022

Brain metastases cause significant morbidity and mortality in patients with advanced cancer. In the era of precision oncology and immunotherapy, there are rapidly evolving systemic treatment options. These novel therapies may have variable intracranial efficacy, and patients with brain metastases remain a population of special interest. Typically, only patients with stable, asymptomatic and/or treated brain metastases are enrolled in clinical trials, or may be excluded altogether, particularly in the setting of leptomeningeal carcinomatosis. Consequently, this leads to significant concerns on the external validity of clinical trial evidence to real-world clinical practice. Here we describe the current trends in cancer clinical trial eligibility for patients with brain metastases in both early and late phase trials, with a focus on targeted and immunotherapies. We evaluate recent newly FDA approved therapies and the clinical trial evidence base leading to approval. This includes analysis of inclusion and exclusion criteria, requirements for baseline screening for brain metastases, surveillance cerebral imaging and incorporation of trial endpoints for patients with brain metastases. Finally, the use of alternative sources of data such as real-world evidence with registries and collaborative studies will be discussed.
Downregulation of SLC27A6 by DNA Hypermethylation Promotes Proliferation but Suppresses Metastasis of Nasopharyngeal Carcinoma Through Modulating Lipid Metabolism
Authors: Zhong Xuemin , Yang Yanping , Li Bo , Liang Pan , Huang Yiying , Zheng Qian , Wang Yifang , Xiao Xue , Mo Yingxi , Zhang Zhe , Zhou Xiaoying , Huang Guangwu , Zhao Weilin
Published: January 2022

Lipid is the building block and an important source of energy, contributing to the malignant behavior of tumor cells. Recent studies suggested that lipid droplets (LDs) accumulations were associated with nasopharyngeal carcinoma (NPC) progression. Solute carrier family 27 member 6 (SLC27A6) mediates the cellular uptake of long-chain fatty acid (LCFA), a necessary lipid component. However, the functions of SLC27A6 in NPC remain unknown. Here, we found a significant reduction of SLC27A6 mRNA in NPC tissues compared with normal nasopharyngeal epithelia (NNE). The promoter methylation ratio of SLC27A6 was greater in NPC than in non-cancerous tissues. The demethylation reagent 5-aza-2’-deoxycytidine (5-aza-dC) remarkably restored the mRNA expression of SLC27A6, suggesting that this gene was downregulated in NPC owing to DNA promoter hypermethylation. Furthermore, SLC27A6 overexpression level in NPC cell lines led to significant suppression of cell proliferation, clonogenicity in vitro, and tumorigenesis in vivo. Higher SLC27A6 expression, on the other hand, promoted NPC cell migration and invasion. In particular, re-expression of SLC27A6 faciliated epithelial-mesenchymal transition (EMT) signals in xenograft tumors. Furthermore, we observed that SLC27A6 enhanced the intracellular amount of triglyceride (TG) and total cholesterol (T-CHO) in NPC cells, contributing to lipid biosynthesis and increasing metastatic potential. Notably, the mRNA level of SLC27A6 was positively correlated with cancer stem cell (CSC) markers, CD24 and CD44. In summary, DNA promoter hypermethylation downregulated the expression of SLC27A6. Furthermore, re-expression of SLC27A6 inhibited the growth capacity of NPC cells but strengthened the CSC markers. Our findings revealed the dual role of SLC27A6 in NPC and shed novel light on the link between lipid metabolism and CSC maintenance.
Multidisciplinary Tumor Board Smart Virtual Assistant in Locally Advanced Cervical Cancer: A Proof of Concept
Authors: Macchia Gabriella , Ferrandina Gabriella , Patarnello Stefano , Autorino Rosa , Masciocchi Carlotta , Pisapia Vincenzo , Calvani Cristina , Iacomini Chiara , Cesario Alfredo , Boldrini Luca , Gui Benedetta , Rufini Vittoria , Gambacorta Maria Antonietta , Scambia Giovanni , Valentini Vincenzo
Published: January 2022

Aim

The first prototype of the “Multidisciplinary Tumor Board Smart Virtual Assistant” is presented, aimed to (i) Automated classification of clinical stage starting from different free-text diagnostic reports; (ii) Resolution of inconsistencies by identifying controversial cases drawing the clinician’s attention to particular cases worthy for multi-disciplinary discussion; (iii) Support environment for education and knowledge transfer to junior staff; (iv) Integrated data-driven decision making and standardized language and interpretation.

Patients and Method

Data from patients affected by Locally Advanced Cervical Cancer (LACC), FIGO stage IB2-IVa, treated between 2015 and 2018 were extracted. Magnetic Resonance (MR), Gynecologic examination under general anesthesia (EAU), and Positron Emission Tomography–Computed Tomography (PET-CT) performed at the time of diagnosis were the items from the Electronic Health Records (eHRs) considered for analysis. An automated extraction of eHR that capture the patient’s data before the diagnosis and then, through Natural Language Processing (NLP), analysis and categorization of all data to transform source information into structured data has been performed.

Results

In the first round, the system has been used to retrieve all the eHR for the 96 patients with LACC. The system has been able to classify all patients belonging to the training set and - through the NLP procedures - the clinical features were analyzed and classified for each patient. A second important result was the setup of a predictive model to evaluate the patient’s staging (accuracy of 94%). Lastly, we created a user-oriented operational tool targeting the MTB who are confronted with the challenge of large volumes of patients to be diagnosed in the most accurate way.

Conclusion

This is the first proof of concept concerning the possibility of creating a smart virtual assistant for the MTB. A significant benefit could come from the integration of these automated methods in the collaborative, crucial decision stages.
Aerial View of the Association Between m6A-Related LncRNAs and Clinicopathological Characteristics of Pancreatic Cancer
Authors: Huang Bowen , Liu Jianzhou , Lu Jun , Gao Wenyan , Zhou Li , Tian Feng , Wang Yizhi , Luo Mingjie , Liu Dong , Xie Congyong , Xun Ziyu , Liu Chengxi , Wang Yu , Ma Haibo , Guo Junchao
Published: January 2022

Pancreatic cancer is a highly malignant tumor with a poor survival prognosis. We attempted to establish a robust prognostic model to elucidate the clinicopathological association between lncRNA, which may lead to poor prognosis by influencing m6A modification, and pancreatic cancer. We investigated the lncRNAs expression level and the prognostic value in 440 PDAC patients and 171 normal tissues from GTEx, TCGA, and ICGC databases. The bioinformatic analysis and statistical analysis were used to illustrate the relationship. We implemented Pearson correlation analysis to explore the m6A-related lncRNAs, univariate Cox regression and Kaplan-Meier methods were performed to identify the seven prognostic lncRNAs signatures. We inputted them in the LASSO Cox regression to establish a prognostic model in the TCGA database, verified in the ICGC database. The AUC of the ROC curve of the training set is 0.887, while the validation set is 0.711. Each patient has calculated a risk score and divided it into low-risk and high-risk subgroups by the median value. Moreover, the model showed a robust prognostic ability in the stratification analysis of different risk subgroups, pathological grades, and recurrence events. We established a ceRNA network between lncRNAs and m6A regulators. Enrichment analysis indicated that malignancy-associated biological function and signaling pathways were enriched in the high-risk subgroup and m6A-related lncRNAs target mRNA. We have even identified small molecule drugs, such as Thapsigargin, Mepacrine, and Ellipticine, that may affect pancreatic cancer progression. We found that seven lncRNAs were highly expressed in tumor patients in the GTEx-TCGA database, and LncRNA CASC19/UCA1/LINC01094/LINC02323 were confirmed in both pancreatic cell lines and FISH relative quantity. We provided a comprehensive aerial view between m6A-related lncRNAs and pancreatic cancer’s clinicopathological characteristics, and performed experiments to verify the robustness of the prognostic model.
Interventions to Improve Safer Sleep Practices in Families With Children Considered to Be at Increased Risk for Sudden Unexpected Death in Infancy: A Systematic Review
Authors: Ellis Catherine , Pease Anna , Garstang Joanna , Watson Debbie , Blair Peter S. , Fleming Peter J.
Published: January 2022

Background: Advice to families to follow infant care practices known to reduce the risks of Sudden Unexpected Death in Infancy (SUDI) has led to a reduction in deaths across the world. This reduction has slowed in the last decade with most deaths now occurring in families experiencing social and economic deprivation. A systematic review of the literature was commissioned by the National Child Safeguarding Practice Review Panel in England. The review covered three areas: interventions to improve engagement with support services, parental decision-making for the infant sleep environment, and interventions to improve safer sleep practices in families with infants considered to be at risk of SUDI.

Aim: To describe the safer sleep interventions tested with families with infants at risk of SUDI and investigate what this literature can tell us about what works to reduce risk and embed safer sleep practices in this group.

Methods: Eight online databases were systematically searched in December 2019. Intervention studies that targeted families with infants (0–1 year) at increased risk of SUDI were included. Studies were limited to those from Western Europe, North America or Australasia, published in the last 15 years. The Quality Assessment Tool for Studies with Diverse Designs was applied to assess quality. Data from included studies were extracted for narrative synthesis, including mode of delivery using Michie et al.'s Mode of Delivery Taxonomy.

Results: The wider review returned 3,367 papers, with 23 intervention papers. Five types of intervention were identified: (1) infant sleep space and safer sleep education programs, (2) intensive or targeted home visiting services, (3) peer educators/ambassadors, (4) health education/raising awareness interventions, (5) targeted health education messages using digital media.

Conclusion: Influencing behavior in families with infants at risk of SUDI has traditionally focused on “getting messages across,” with interventions predominantly using education and awareness raising mechanisms. This review found evidence of interventions moving from “information giving” to “information exchange” models using personalized, longer term relationship-building models. This shift may represent an improvement in how safer sleep advice is implemented in families with infants at risk, but more robust evidence of effectiveness is required.

Systematic Review Registration:https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/901091/DfE_Death_in_infancy_review.pdf, identifier: CRD42020165302.
Natural AMPK Activators in Cardiovascular Disease Prevention
Authors: Heidary Moghaddam Reza , Samimi Zeinab , Asgary Sedigheh , Mohammadi Pantea , Hozeifi Soroush , Hoseinzadeh‐Chahkandak Fatemeh , Xu Suowen , Farzaei Mohammad Hosein
Published: January 2022

Cardiovascular diseases (CVD), as a life-threatening global disease, is receiving worldwide attention. Seeking novel therapeutic strategies and agents is of utmost importance to curb CVD. AMP-activated protein kinase (AMPK) activators derived from natural products are promising agents for cardiovascular drug development owning to regulatory effects on physiological processes and diverse cardiometabolic disorders. In the past decade, different therapeutic agents from natural products and herbal medicines have been explored as good templates of AMPK activators. Hereby, we overviewed the role of AMPK signaling in the cardiovascular system, as well as evidence implicating AMPK activators as potential therapeutic tools. In the present review, efforts have been made to compile and update relevant information from both preclinical and clinical studies, which investigated the role of natural products as AMPK activators in cardiovascular therapeutics.
Protective Effects of Allicin on Acute Myocardial Infarction in Rats via Hydrogen Sulfide-mediated Regulation of Coronary Arterial Vasomotor Function and Myocardial Calcium Transport
Authors: Cui Tianwei , Liu Weiyu , Yu Chenghao , Ren Jianxun , Li Yikui , Shi Xiaolu , Li Qiuyan , Zhang Jinyan
Published: January 2022

Acute myocardial infarction (AMI) is a condition with high morbidity and mortality, for which effective treatments are lacking. Allicin has been reported to exert therapeutic effects on AMI, but the underlying mechanisms of its action have not been fully elucidated. To investigate this, a rat model of AMI was generated by ligating the left anterior descending branch of the coronary artery. DL-propargylglycine (PAG), a specific hydrogen sulfide (H2S) synthetase inhibitor, was used to examine the effects of allicin on H2S production. Isolated coronary arteries and cardiomyocytes were assessed for vascular reactivity and cellular Ca2+ transport using a multiwire myography system and a cell-contraction-ion detection system, respectively. Allicin administration improved cardiac function and myocardial pathology, reduced myocardial enzyme levels, and increased H2S and H2S synthetase levels. Allicin administration resulted in concentration-dependent effects on coronary artery dilation, which were mediated by receptor-dependent Ca2+ channels, ATP-sensitive K+ channels, and sarcoplasmic reticulum (SR) Ca2+ release induced by the ryanodine receptor. Allicin administration improved Ca2+ homeostasis in cardiomyocytes by increasing cardiomyocyte contraction, Ca2+ transient amplitude, myofilament sensitivity, and SR Ca2+ content. Allicin also enhanced Ca2+ uptake via SR Ca2+-ATPase and Ca2+ removal via the Na+/Ca2+ exchanger, and it reduced SR Ca2+ leakage. Notably, the protective effects of allicin were partially attenuated by blockade of H2S production with PAG. Our findings provide novel evidence that allicin-induced production of H2S mediates coronary artery dilation and regulation of Ca2+ homeostasis in AMI. Our study presents a novel mechanistic insight into the anti-AMI effects of allicin and highlights the therapeutic potential of this compound.
Current Advances in Coptidis Rhizoma for Gastrointestinal and Other Cancers
Authors: He Luying , Zhong Zhangfeng , Chen Man , Liang Qilian , Wang Yitao , Tan Wen
Published: January 2022

Canceris a serious disease with an increasing number of reported cases and high mortality worldwide. Gastrointestinal cancer defines a group of cancers in the digestive system, e.g., liver cancer, colorectal cancer, and gastric cancer.Coptidis Rhizoma(C. Rhizoma; Huanglian, in Chinese) is a classical Chinese medicinal botanical drug for the treatment of gastrointestinal disorders and has been shown to have a wide variety of pharmacological activity, including antifungal, antivirus, anticancer, antidiabetic, hypoglycemic, and cardioprotective effects. Recent studies onC. Rhizomapresent significant progress on its anticancer effects and the corresponding mechanisms as well as its clinical applications. Herein, keywords related toC. Rhizoma, cancer, gastrointestinal cancer, and omics were searched in PubMed and the Web of Science databases, and more than three hundred recent publications were reviewed and discussed.C. Rhizomaextract along with its main components, berberine, palmatine, coptisine, magnoflorine, jatrorrhizine, epiberberine, oxyepiberberine, oxyberberine, dihydroberberine, columbamine, limonin, and derivatives, are reviewed. We describe novel and classic anticancer mechanisms from various perspectives of pharmacology, pharmaceutical chemistry, and pharmaceutics. Researchers have transformed the chemical structures and drug delivery systems of these components to obtain better efficacy and bioavailability ofC. Rhizoma. Furthermore,C. Rhizomain combination with other drugs and their clinical application are also summarized. Taken together,C. Rhizomahas broad prospects as a potential adjuvant candidate against cancers, making it reasonable to conduct additional preclinical studies and clinical trials in gastrointestinal cancer in the future.
Kidney-Targeted Redox Scavenger Therapy Prevents Cisplatin-Induced Acute Kidney Injury
Authors: Williams Ryan M. , Shah Janki , Mercer Elizabeth , Tian Helen S. , Thompson Vanessa , Cheung Justin M. , Dorso Madeline , Kubala Jaclyn M. , Gudas Lorraine J. , de Stanchina Elisa , Jaimes Edgar A. , Heller Daniel A.
Published: January 2022

Cisplatin-induced acute kidney injury (CI-AKI) is a significant co-morbidity of chemotherapeutic regimens. While this condition is associated with substantially lower survival and increased economic burden, there is no pharmacological agent to effectively treat CI-AKI. The disease is hallmarked by acute tubular necrosis of the proximal tubular epithelial cells primarily due to increased oxidative stress. We investigated a drug delivery strategy to improve the pharmacokinetics of an approved therapy that does not normally demonstrate appreciable efficacy in CI-AKI, as a preventive intervention. In prior work, we developed a kidney-selective mesoscale nanoparticle (MNP) that targets the renal proximal tubular epithelium. Here, we found that the nanoparticles target the kidneys in a mouse model of CI-AKI with significant damage. We evaluated MNPs loaded with the reactive oxygen species scavenger edaravone, currently used to treat stroke and ALS. We found a marked and significant therapeutic benefit with edaravone-loaded MNPs, including improved renal function, which we demonstrated was likely due to a decrease in tubular epithelial cell damage and death imparted by the specific delivery of edaravone. The results suggest that renal-selective edaravone delivery holds potential for the prevention of acute kidney injury among patients undergoing cisplatin-based chemotherapy.
Molecular Mechanism of Gelsemium elegans (Gardner and Champ.) Benth. Against Neuropathic Pain Based on Network Pharmacology and Experimental Evidence
Authors: Que Wancai , Wu Zhaoyang , Chen Maohua , Zhang Binqing , You Chuihuai , Lin Hailing , Zhao Zhichang , Liu Maobai , Qiu Hongqiang , Cheng Yu
Published: January 2022

Gelsemium elegans (Gardner and Champ.) Benth. (Gelsemiaceae) (GEB) is a toxic plant indigenous to Southeast Asia especially China, and has long been used as Chinese folk medicine for the treatment of various types of pain, including neuropathic pain (NPP). Nevertheless, limited data are available on the understanding of the interactions between ingredients-targets-pathways. The present study integrated network pharmacology and experimental evidence to decipher molecular mechanisms of GEB against NPP. The candidate ingredients of GEB were collected from the published literature and online databases. Potentially active targets of GEB were predicted using the SwissTargetPrediction database. NPP-associated targets were retrieved from GeneCards, Therapeutic Target database, and DrugBank. Then the protein-protein interaction network was constructed. The DAVID database was applied to Gene Ontology and Kyoto Encyclopedia of Genes and Genome pathway enrichment analysis. Molecular docking was employed to validate the interaction between ingredients and targets. Subsequently, a 50 ns molecular dynamics simulation was performed to analyze the conformational stability of the protein-ligand complex. Furthermore, the potential anti-NPP mechanisms of GEB were evaluated in the rat chronic constriction injury model. A total of 47 alkaloids and 52 core targets were successfully identified for GEB in the treatment of NPP. Functional enrichment analysis showed that GEB was mainly involved in phosphorylation reactions and nitric oxide synthesis processes. It also participated in 73 pathways in the pathogenesis of NPP, including the neuroactive ligand-receptor interaction signaling pathway, calcium signaling pathway, and MAPK signaling pathway. Interestingly, 11-Hydroxyrankinidin well matched the active pockets of crucial targets, such as EGFR, JAK1, and AKT1. The 11-hydroxyrankinidin-EGFR complex was stable throughout the entire molecular dynamics simulation. Besides, the expression of EGFR and JAK1 could be regulated by koumine to achieve the anti-NPP action. These findings revealed the complex network relationship of GEB in the “multi-ingredient, multi-target, multi-pathway” mode, and explained the synergistic regulatory effect of each complex ingredient of GEB based on the holistic view of traditional Chinese medicine. The present study would provide a scientific approach and strategy for further studies of GEB in the treatment of NPP in the future.
Elevated Serum Leptin Levels in Patients With Eosinophilic Chronic Rhinosinusitis
Authors: Imoto Yoshimasa , Ueki Shigeharu , Kato Yukinori , Yoshida Kanako , Morikawa Taiyo , Kimura Yukihiro , Kidoguchi Masanori , Tsutsumiuchi Toshiki , Koyama Keisuke , Adachi Naoto , Ito Yumi , Ogi Kazuhiro , Sakashita Masafumi , Yamada Takechiyo , Schleimer Robert P. , Takabayashi Tetsuji , Fujieda Shigeharu
Published: January 2022

Background: Eosinophilic chronic sinusitis (ECRS) is a subtype of CRS with nasal polyps (CRSwNP) that is frequently comorbid with asthma. Notably, ECRS patients often show a high recurrence of NPs after surgical resection. Leptin is a hormone produced by adipocytes that has been implicated in airway inflammatory diseases. However, to date, the role of leptin in ECRS has not been investigated.

Objective: To determine whether the serum levels of leptin are altered in patients with ECRS.

Methods: In total, 40 patients with ECRS, 15 patients with non-eosinophilic CRS (non-ECRS), and 12 individuals without CRS (control) were included in this study. Patient’s serum leptin levels were assessed, and the number of eosinophils in their NPs were measured through a histological evaluation of the three densest areas with cellular infiltrate beneath the epithelial surface. Finally, nasal fibroblast cultures established from NPs were stimulated with varying concentrations of recombinant leptin in vitro to determine whether leptin affects eotaxin-3 (Chemokine (C-C motif) ligand 26 :26: CCL26) expression.

Results: The serum leptin levels in both the ECRS and non-ECRS groups were significantly higher than those in the control subjects (p < 0.0001 vs. ECRS; p < 0.05 vs. non-ECRS). Furthermore, ECRS patients displayed significantly elevated serum leptin levels compared to non-ECRS patients (p < 0.001), although there was no difference in body mass index between the groups. Notably, serum leptin levels were correlated with the proportion of eosinophils in peripheral blood (r = 0.3575, p < 0.01) and the number of eosinophils in NPs (r = 0.5109, p < 0.0001). Serum leptin levels were also correlated with eotaxin-3 mRNA expression in NPs (r = 0.5374, p < 0.01). Finally, leptin significantly augmented eotaxin-3 expression in nasal fibroblasts established in vitro from NPs in a leptin receptor-dependent manner (p < 0.05).

Conclusion: Leptin levels are elevated in ECRS patients and may both promote and indicate the severity of ECRS as well as systemic type 2-biased inflammatory responses. Combined, these data indicate that circulating leptin may play a significant role in the development of eosinophilic inflammation in NPs.
The Glutathione Metabolite γ-Glutamyl-Glutamate Partially Activates Glutamate NMDA Receptors in Central Neurons With Higher Efficacy for GluN2B-Containing Receptors
Authors: Sebih Fatiha , Mokrane Nawfel , Fontanel Pierre , Kayatekin Mete , Kaabeche Mahira , Guiramand Janique , Cohen-Solal Catherine , Cens Thierry , Rousset Matthieu , Charnet Pierre , De Jésus Ferreira Marie-Céleste , Thibaud Jean-Baptiste , Ménard Claudine , Cantel Sonia , Rolland Valérie , Vignes Michel , Roussel Julien
Published: January 2022

Gamma-L-glutamyl-L-glutamate (γ-Glu-Glu) was synthetized and further characterized for its activity on cultured neurons. We observed that γ-Glu-Glu elicited excitatory effects on neurons likely by activating mainly the N-methyl-D-aspartate (NMDA) receptors. These effects were dependent on the integrity of synaptic transmission as they were blocked by tetrodotoxin (TTX). We next evaluated its activity on NMDA receptors by testing it on cells expressing these receptors. We observed that γ-Glu-Glu partially activated NMDA receptors and exhibited better efficacy for NMDA receptors containing the GluN2B subunit. Moreover, at low concentration, γ-Glu-Glu potentiated the responses of glutamate on NMDA receptors. Finally, the endogenous production of γ-Glu-Glu was measured by LC-MS on the extracellular medium of C6 rat astroglioma cells. We found that extracellular γ-Glu-Glu concentration was, to some extent, directly linked to GSH metabolism as γ-Glu-Glu can be a by-product of glutathione (GSH) breakdown after γ-glutamyl transferase action. Therefore, γ-Glu-Glu could exert excitatory effects by activating neuronal NMDA receptors when GSH production is enhanced.
Proanthocyanidins Protect Against Cadmium-Induced Diabetic Nephropathy Through p38 MAPK and Keap1/Nrf2 Signaling Pathways
Authors: Gong Pin , Wang Peipei , Pi Sihui , Guo Yuxi , Pei Shuya , Yang Wenjuan , Chang Xiangna , Wang Lan , Chen Fuxin
Published: January 2022

Diabetic nephropathy (DN) is one of the most devastating complications of diabetes mellitus. Although cadmium (Cd) exposure might be involved in the pathogenesis of DN, the underlying mechanism is still unclear. In this study, we explored the protective effects and possible mechanism of proanthocyanidins (OPC) from grape seed using a mouse model of Cd-induced DN. The successful establishment of this model was verified by analyzing the physiological and biochemical indices of mice, including their body weight and tissue ratio; levels of blood glucose, creatinine, microalbumin, total cholesterol, triglycerides, high-density lipoprotein-cholesterol and low-density lipoprotein-cholesterol; and was based on histopathological examination. Oxidative-antioxidative status, elemental analysis, and key signaling pathway analysis were performed to explore the possible protective mechanism of OPC. The protective effects of OPC and its possible mechanism in preventing the progression of DN were investigated using a multidimensional approach, including its ability in regulating oxidative-antioxidative status (lipid peroxidation, protein carbonyl, superoxide dismutase, and glutathione GST, GSH-Px), metal-binding ability (Cd levels in the kidneys and urine and MT content) and mediation of essential elements (Zn, Ca, Cu, and Fe levels in the kidneys), and activation of the p38 MAPK and Keap1/Nrf2 signaling pathways. OPC exhibited a significant renoprotective effect, attributed to the metal-chelating ability, anti-oxidative effect, and mediation of oxidative stress-related signaling pathway. These results highlight the potential of OPC in preventing or treating DN in humans and suggest the dietary intake of grapes, which are rich in polyphenols, for the prevention of type 2 diabetes mellitus and its complications.
Limonin Alleviates Non-alcoholic Fatty Liver Disease by Reducing Lipid Accumulation, Suppressing Inflammation and Oxidative Stress
Authors: Li Yunjia , Yang Menghan , Lin Haiyan , Yan Weixin , Deng Guanghui , Ye Haixin , Shi Hao , Wu Chaofeng , Ma Guoliang , Xu Shu , Tan Qinxiang , Gao Zhuowei , Gao Lei
Published: January 2022

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease and continues to rise in the worldwide. Limonin is a triterpenoid compound widely found in the fruits of citrus plants with a wide range of pharmacological effects, including anti-cancer, anti-inflammation, anti-viral, anti-oxidation and liver protection properties. However, the potential molecular mechanism of limonin on NAFLD in zebrafish remains unknown. In this study, zebrafish larvae were exposed to thioacetamide to establish an NAFLD model and the larvae were treated with limonin for 72 h simultaneously. The human liver cell line was stimulated with lipid mixture and meanwhile incubated with limonin for 24 h. The results showed that Limonin significantly reduced the accumulation of lipid droplets in the liver and down-regulated the levels of lipogenic transcription factors FASN and SREBP1 in NAFLD. Limonin suppressed macrophages infiltration and the down-regulated the relative expression levels of the pro-inflammatory factors IL-6, IL-1β and TNF-α secreted by macrophages. Besides, limonin could reversed the reduction of glutathione and the accumulation of reactive oxygen species through up-regulating NRF2/HO-1 signaling pathway in the liver. In conclusion, this study revealed that limonin has a protective effect on NAFLD due to its resistance to lipid deposition as well as antioxidant and anti-inflammatory actions.
Inter-Individual Variability in Postural Control During External Center of Mass Stabilization
Authors: Gorjan Daša , Šarabon Nejc , Babič Jan
Published: January 2022

Understanding the relation between the motion of the center of mass (COM) and the center of pressure (COP) is important to understand the underlying mechanisms of maintaining body equilibrium. One way to investigate this is to stabilize COM by fixing the joints of the human and looking at the corresponding COP reactions. However, this approach constrains the natural motion of the human. To avoid this shortcoming, we stabilized COM without constraining the joint movements by using an external stabilization method based on inverted cart-pendulum system. Interestingly, this method only stabilized COM of a subgroup of participants and had a destabilizing effect for others which implies significant variability in inter-individual postural control. The aim of this work was to investigate the underlying causes of inter-individual variability by studying the postural parameters of quiet standing before the external stabilization. Eighteen volunteers took part in the experiment where they were standing on an actuated cart for 335 s. In the middle of this period we stabilized their COM in anteroposterior direction for 105 s. To stabilize the COM, we controlled the position of the cart using a double proportional–integral–derivative controller. We recorded COM position throughout the experiment, calculated its velocity, amplitude, and frequency during the quiet standing before the stabilization, and used these parameters as features in hierarchical clustering method. Clustering solution revealed that postural parameters of quiet standing before the stabilization cannot explain the inter-individual variability of postural responses during the external COM stabilization. COM was successfully stabilized for a group of participants but had a destabilizing effect on the others, showing a variability in individual postural control which cannot be explained by postural parameters of quiet-stance.
A Roadmap for Participatory Chestnut Breeding for Nut Production in the Eastern United States
Authors: Revord Ronald S. , Miller Gregory , Meier Nicholas A. , Webber John Bryan , Romero-Severson Jeanne , Gold Michael A. , Lovell Sarah T.
Published: January 2022

Chestnut cultivation for nut production is increasing in the eastern half of the United States. Chinese chestnuts (Castanea mollissima Blume), or Chinese hybrids with European (C. sativa Mill.) and Japanese chestnuts (C. crenata Sieb. & Zucc.), are cultivated due to their high kernel quality, climatic adaptation, and disease resistance. Several hundred thousand pounds of high-quality fresh nuts are taken to market every fall, and several hundred additional orchards are entering bearing years. Grower-led on-farm improvement has largely facilitated this growth. A lack of significant investments in chestnut breeding in the region, paired with issues of graft incompatibility, has led many growers to cultivate seedlings of cultivars rather than grafted cultivars. After decades of evaluation, selection, and sharing of plant materials, growers have reached a threshold of improvement where commercial seedling orchards can be reliably established by planting offspring from elite selected parents. Growers recognize that if cooperation persists and university expertise and resources are enlisted, improvement can continue and accelerate. To this end, the University of Missouri Center for Agroforestry (UMCA) and chestnut growers throughout the eastern United States are partnering to formalize a participatory breeding program – the Chestnut Improvement Network. This partnership entails the UMCA providing an organizational structure and leadership to coordinate on-farm improvement, implement strategic crossing schemes, and integrate genetic tools. Chestnut growers offer structural capacity by cultivating seedling production orchards that provide financial support for the grower but also house segregating populations with improved individuals, in situ repositories, and selection trials, creating great value for the industry.
De novo Transcriptome Assembly of Senna occidentalis Sheds Light on the Anthraquinone Biosynthesis Pathway
Authors: Kang Sang-Ho , Lee Woo-Haeng , Sim Joon-Soo , Thaku Niha , Chang Saemin , Hong Jong-Pil , Oh Tae-Jin
Published: January 2022

Senna occidentalis is an annual leguminous herb that is rich in anthraquinones, which have various pharmacological activities. However, little is known about the genetics of S. occidentalis, particularly its anthraquinone biosynthesis pathway. To broaden our understanding of the key genes and regulatory mechanisms involved in the anthraquinone biosynthesis pathway, we used short RNA sequencing (RNA-Seq) and long-read isoform sequencing (Iso-Seq) to perform a spatial and temporal transcriptomic analysis of S. occidentalis. This generated 121,592 RNA-Seq unigenes and 38,440 Iso-Seq unigenes. Comprehensive functional annotation and classification of these datasets using public databases identified unigene sequences related to major secondary metabolite biosynthesis pathways and critical transcription factor families (bHLH, WRKY, MYB, and bZIP). A tissue-specific differential expression analysis of S. occidentalis and measurement of the amount of anthraquinones revealed that anthraquinone accumulation was related to the gene expression levels in the different tissues. In addition, the amounts and types of anthraquinones produced differ between S. occidentalis and S. tora. In conclusion, these results provide a broader understanding of the anthraquinone metabolic pathway in S. occidentalis.
Mobile Flowering Locus T RNA – Biological Relevance and Biotechnological Potential
Authors: Yu Zhiming , Chen Weiwei , Wang Yue , Zhang Pengcheng , Shi Nongnong , Hong Yiguo
Published: January 2022

Many systemically mobile mRNAs have been revealed in phloem. However, very few of them have been found to be of clear signaling functions. One of such rare examples is the mobile Flowering locus T (FT) mRNA despite the continuous debate about its mobility and biological relevance to the control of flowering time in plants. Nevertheless, accumulating evidence supports the notion of the long-distance movement of FT mRNA from leaf to shoot apex meristem and its role in flowering. In this review, we discuss the discovery of florigenic FT, the initial debate on long-distance movement of FT mRNA, emerging evidence to prove its mobility, and the use of mobile FT mRNA to generate heritable transgenerational gene editing in plants. We elaborate on evidence from virus-based RNA mobility assay, plant grafting, RNA with fluorescent protein labeling, and CRISPR/Cas9 gene-editing technology, to demonstrate that the FT mRNA besides the FT protein can move systemically and function as an integral component of the florigenic signal in flowering. We also propose a model to prompt further research on the molecular mechanism underlying the long-distance movement of this important mobile signaling RNA in plants.
Analyzing Quantitative Trait Loci for Fiber Quality and Yield-Related Traits From a Recombinant Inbred Line Population With Gossypium hirsutum Race palmeri as One Parent
Authors: Liu Xueying , Yang Le , Wang Jinxia , Wang Yaqing , Guo Zhongni , Li Qingqing , Yang Jinming , Wu Youlin , Chen Li , Teng Zhonghua , Liu Dajun , Liu Dexin , Guo Kai , Zhang Zhengsheng
Published: January 2022

Fiber quality and yield-related traits are important agronomic traits in cotton breeding. To detect the genetic basis of fiber quality and yield related traits, a recombinant inbred line (RIL) population consisting of 182 lines was established from a cross between Gossypium hirsutum cultivar CCRI35 and G. hirsutum race palmeri accession TX-832. The RIL population was deeply genotyped using SLAF-seq and was phenotyped in six environments. A high-density genetic linkage map with 15,765 SNP markers and 153 SSR markers was constructed, with an average distance of 0.30 cM between adjacent markers. A total of 210 fiber quality quantitative trait loci (QTLs) and 73 yield-related QTLs were identified. Of the detected QTLs, 62 fiber quality QTLs and 10 yield-related QTLs were stable across multiple environments. Twelve and twenty QTL clusters were detected on the At and Dt subgenome, respectively. Twenty-three major QTL clusters were further validated through associated analysis and five candidate genes of four stable fiber quality QTLs were identified. This study revealed elite loci influencing fiber quality and yield and significant phenotypic selection regions during G. hirsutum domestication, and set a stage for future utilization of molecular marker assisted breeding in cotton breeding programs.
Incivility and Knowledge Hiding in Academia: Mediating Role of Interpersonal Distrust and Rumination
Authors: Wu Qingyan , Saqib Shahnawaz , Sun Jianhua , Xiao Yuxia , Ma Wenya
Published: January 2022

Workplace incivility is under investigation for the last three decades, and it holds a central position in organizational behavior literature. However, despite the extensive investigations in the past, there exists a missing link between workplace incivility and knowledge hiding in academia. This study aims to tap this missing link for which data were collected from the universities staff. Data were collected in two waves to reduce the common method biases. In the first wave, questions were asked from the respondents regarding their demographic characteristics and exposure to workplace incivility. At this stage, 400 questionnaires were floated and 355 completely filled responses were received back, while in the second wave, those respondents were approached for data collection who have completely filled questionnaires in the first wave. The time interval between the two waves was 1 month. In the second wave, questions related to distrust and knowledge hiding behavior were asked from the respondents. At this stage, 323 questionnaires were received back out of which 290 were filled and these were considered for final data analysis. Collected data were analyzed by applying structural equation modeling (SEM) through SmartPLS. Results indicated that employees tend to hide knowledge when they experience incivility at workplace. Moreover, they develop a sense of distrust in response to workplace incivility which further triggers them to hide knowledge. Limitations and future directions are also discussed.
Risk of Injury to Others: The Development of an Algorithm to Identify Children and Youth at High-Risk of Aggressive Behaviours
Authors: Stewart Shannon L. , Celebre Angela , Hirdes John P. , Poss Jeffrey W.
Published: January 2022

Youth violence is considered one of the most preventable causes of morbidity and premature mortality. Various risk factors have previously been identified, however, there is presently a crucial need to develop effective decision-support tools in order to identify children and youth at increased risk for violence. The current study utilised data collected from the interRAI Child and Youth Mental Health Screener (ChYMH-S), within the province of Ontario, to develop and validate a methodology for the purpose of identifying young persons who were at greater risk of harm to others. Additional data from 59 mental health agencies validated the algorithm, and it was found to be a strong predictor of harmful behaviour toward others. The RIO algorithm provides a valuable decision-support tool with strong psychometric properties that may be used to identify young persons who exhibit signs or symptoms associated with increased likelihood of harm toward others, in order to provide early intervention efforts for these vulnerable youth, thereby reducing the likelihood of future aggressive behaviours.
Psychedelic Mushrooms in the USA: Knowledge, Patterns of Use, and Association With Health Outcomes
Authors: Matzopoulos Richard , Morlock Robert , Morlock Amy , Lerer Bernard , Lerer Leonard
Published: January 2022

Introduction: Popular media coverage of psychedelics use, growing research into this class of compounds for psychiatry and decriminalization initiatives, are transforming the public perception of psychedelics. However, little is known about levels of knowledge and psychedelic mushroom (PM) use among American adults.

Methods: We examined PM use and various measures of health status, quality of life, and self-reported mental health outcome measures obtained through a national on-line, cross-sectional survey of adults with a demographic composition representative of the US adult population by region, gender, age, and race (weighted N = 251,297,495) from November 2020–March 2021.

Results: General mental health and well-being were popular reasons for PM use (63.6%), although use for medically-diagnosed (31.8%) and self-diagnosed (19.0%) conditions was also common. PM users reported more depression and anxiety as reflected in higher GAD-7 and PHQ-9 scores. Factors predictive of PM use included being male [OR 1.54 95%CI 1.09–2.15] and having higher Charlson Comorbidity Index scores [OR 1.42; 95%CI 1.22–1.65]. Self-reported PM use was less likely among participants with health insurance [OR = 0.50 (0.35–0.72)], increased age [OR = 0.92 (0.90–0.93)] and, relative to those living in the west US census region, living in the northeast [OR = 0.27 (0.15–0.50)], midwest [OR = 0.34 (0.20–0.56)], and south [OR = 0.38 (0.26–0.55)].

Discussion and Conclusions: A significant number of Americans are already “self-medicating” with PM and as growing positive media coverage of psychedelics drives public interest in the health benefits of PM, this number will increase. The association between PM use and poor mental health requires further research to inform policy.