bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biological Age in Healthy Elderly Predicts Dementia in the Absence of a Brain Marker
Authors: Wu Julia , Yaqub Amber , Ma Yuan , Koudstaal Wouter , Hofman Albert , Ikram Mohammad Arfan , Ghanbari Mohsen , Goudsmit Jaap 
Published: December 2020

Abstract
Application of biological age as a measure of an individual´s health status offers new perspectives into extension of both lifespan and healthspan. While algorithms predicting mortality and most aging-related morbidities have been reported, the major shortcoming has been an inability to predict dementia. We present a community-based cohort study of 1930 participants with a mean age of 72 years and a follow-up period of over 7 years, using two variants of a phenotypic blood-based algorithm that either excludes (BioAge1) or includes (BioAge2) neurofilament light chain (NfL) as a neurodegenerative marker. BioAge1 and BioAge2 predict dementia equally well, as well as lifespan and healthspan. Each one-year increase in BioAge1/2 was associated with 11% elevated risk (HR=1.11; 95%CI 1.08-1.14) of mortality and 7% elevated risk (HR=1.07; 95%CI 1.05-1.09) of first morbidities. We additionally tested the association of microRNAs with age and identified 263 microRNAs significantly associated with biological and chronological age alike. Top differentially expressed microRNAs based on biological age had a higher significance level than those based on chronological age, suggesting that biological age captures aspects of aging signals at the epigenetic level. We conclude that biological age is a predictor of major age-related diseases, including dementia, among healthy elderly.
The Designation of Micronutrients Foliar Application Influence on Rice (Oryza Sativa L. cv. Shiroodi) Yield and Yield Components
Authors: Lahijani Ashkan Daneshtalab , Mosavi Amir abbas , Moballeghi Morteza 
Published: December 2020

Abstract
Pursuant to micronutrients critical role in the plant nutrition and metabolism, accurate determination of the best term of foliar application as a practical plant nutritional pathway has substantial circumstances in the novel agricultural approaches. In order to properly assess micronutrients liquid fertilizer with commercial name of Rooyesh no and mentioned ingredients (Fe EDTA 0.1%, Zn EDTA 0.05%, B 0.02%, Cu EDTA 0.05%, and Mn EDTA 0.05%) influence on Shiroodi cultivar yield, this investigation implemented in the Iran Rice Research Institution (Amol, Mazandaran) during two consecutive years (2017-2018). This extensive research conducted in the form of RCBD with eight treatments and three independent replications. The treatments were T0 (control), T1 (one foliar application) to T7 (seven foliar applications). The frequent intervals of foliar applications were seven days and the first foliar application done nine days after transplantation. The results revealed that the micronutrients application effect was significant about plant dry weight, grain yield, 1,000 grains yield and harvest index. Also, the interaction of the year and foliar application was significant about seed Zn content, chlorophyll b and 1,000 grains yield. According to statistical data, it can be concluded that T4 with 4257 kg/ha grain yield compare to control yield 3499.1 kg/ha that indicated 20 percentage approximate enhancement about foliar application treatments, four leaf spraying with 2 liters/ 1000 liters of water dosage of micronutrients could affect grain yield and yield components of rice (shiroodi cv.) significantly through increasing the number of tillers/plant, improvement of panicle length and increasing the number of grains/ panicle. The micronutrients supply through leaves is more effective procedure in the field of rice nutrition compare to soil application method due to higher absorption velocity.
Gating transitions and modulation of a hetero-octameric AMPA glutamate receptor
Authors: Greger Ingo , Zhang Danyang , Watson Jake , Matthews Peter , Cais Ondrej 
Published: December 2020

Abstract
AMPA glutamate receptors (AMPARs) mediate the majority of excitatory transmission in the brain, and enable synaptic plasticity that underlies learning 1. A diverse array of AMPAR signaling complexes are established by receptor auxiliary subunits, associating in various combinations to modulate trafficking, gating and synaptic strength 2. However, their mechanisms of action are poorly understood. Here, we determine cryo-electron microscopy structures of the heteromeric GluA1/2 receptor assembled with both TARP-γ8 and CNIH2, the predominant AMPAR complex in the forebrain, in both resting and active states (at 3.2 and 3.7 Å, respectively). Consequential for gating regulation, two γ8 and two CNIH2 subunits lodge at distinct sites beneath the ligand-binding domains of the receptor tetramer, with site-specific lipids shaping each interaction. Activation leads to a stark asymmetry between GluA1 and GluA2 along the ion conduction path, and an outward expansion of the channel triggers counter-rotations of both auxiliary subunit pairs, that promotes the active-state conformation. In addition, both γ8 and CNIH2 pivot towards the pore exit on activation, extending their reach for cytoplasmic receptor elements. CNIH2 achieves this through its uniquely extended M2 helix, which has transformed this ER-export factor into a powerful positive AMPAR modulator, capable of providing hippocampal pyramidal neurons with their integrative synaptic properties.
Effects of Cadmium Stress on Physiological Indexes and Fruiting Body Nutritions of Agaricus Brasiliensis
Authors: Liu Lingyun , Chen Hua , Yuan Jing , Wang Yixiang , Weng Boqi , Liu Penghu , Li Guoxue 
Published: December 2020

Abstract
In this study, 0, 0.5, 1, 1.5, 2, 4, 6 and 8 mg·kg-1 of cadmium were added to the cultivation materials. In order to study the effects of different concentrations of Cd stress on J1 and J77, the contents of antioxidant enzymes, proline and malondialdehyde, Cd content, agronomic traits and yield of fruiting bodies of Agaricus brasiliensis were determined, and the nutritional components such as polysaccharide, triterpene, protein, total sugar and total amino acid were determined. The results showed that the physiological indexes of strain J1 and J77 changed regularly under different concentrations of Cd stress. J1 was a high absorption and low tolerance variety, while J77 was a low absorption and high tolerance variety. Low concentration of cadmium promoted the growth of strain J1, and higher concentration of Cd promoted the growth of strain J77. The contents of protein and total amino acids in the two strains changed greatly, followed by polysaccharides, which indicated that Cd stress had the greatest impact on the three nutrients, and other nutrients were not sensitive to Cd stress.
Gut microbiota signatures are associated with toxicity to combined CTLA-4 and PD-1 blockade
Authors: Wargo Jennifer , Andrews Miles , Duong Connie , Gopalakrishnan Vancheswaran , Iebba Valerio , Chen Wei-Shen , Derosa Lisa , Routy Bertrand , Ferrere Gladys , Fluckiger Aurélie , Roberti Maria , Opolon Paule , Roh Whijae , Spencer Christine , Curbelo Irina Fernandez , Vence Luis , Reuben Alexandre , Cooper Zachary , Prieto Peter , Khan M. A. Wadud , Lazar Alexander , Tetzlaff Michael , Hudgens Courtney , Gaudreau Pierre-Olivier , Nezi Luigi , Raoult Didier , Haydu Lauren , Tawbi Hussein , Hwu Patrick , Hwu Wen-Jen , Amaria Rodabe , Burton Elizabeth , Woodman Scott , Diab Adi , Patel Sapna , Glitza Isabella , Zhang Jianhua , Ajami Nadim , Petrosino Joseph , Jenq Robert , Davies Michael , Gershenwald Jeffrey , Sharma Padmanee , Allison James , Futreal Andrew , Zitvogel Laurence , ALOU Maryam TIDJANI , Yonekura Satoru , Cogdill Alexandria , Arora Reetakshi , Little Latasha , Gumbs Curtis , Wani Khalida , Callahan Margaret , Adamow Mathew , Postow Michael , Ariyan Charlotte , Gardner Julie , McQuade Jennifer , Wong Michael , Zhao Li 
Published: December 2020

Abstract
Treatment with combined immune checkpoint blockade (CICB) targeting CTLA-4 and PD-1 is associated with clinical benefit across tumor types, but a high rate of immune-related adverse events (irAE). Insights into biomarkers and mechanisms of response and toxicity to CICB are needed. To address this, we profiled the blood, tumor and gut microbiome of 77 advanced melanoma patients treated with CICB, with a high rate of any ≥Grade 3 irAEs (49%) with parallel studies in pre-clinical models. Tumor-associated immune and genomic biomarkers of response to CICB were similar to those identified for ICB monotherapy, and toxicity from CICB was associated with a more diverse peripheral T cell repertoire. Profiling of gut microbiota demonstrated a significantly higher abundance of Bacteroides intestinalis in patients with toxicity, with upregulation of mucosal IL-1b in patient samples of colitis and in pre-clinical models. Together, these data offer potential new therapeutic angles for targeting toxicity to CICB.
TRIM47 Promotes Malignant Progression of Renal Cell Carcinoma by Degrading P53 Through Ubiquitination
Authors: Chen Jia-xin , Xu Da , Cao Jian-wei , Zuo Li , Han Zhi-tao , Tian Yi-jun , Chu Chuan-min , Zhou Wang , Pan Xiu-wu , Cui Xingang 
Published: December 2020

Abstract
Background: Renal cell carcinoma (RCC) is one of the most common malignant tumors originating from the renal parenchymal urinary epithelial system. Tripartite motif 47 (TRIM47) is a member of the TRIM family proteins, which has E3 ligase activity and has been demonstrated to be involved in the occurrence and prognosis of many tumors. The main purpose of this study is to explore the role and potential mechanism of TRIM47 in promoting malignant biological behavior of RCC. Materials and Methods: TRIM47 mRNA and protein levels in human renal cancer and paired normal adjacent tissues were detected by qRT-PCR and Western blot. The effects of TRIM47 knockdown and overexpression in renal cell carcinoma cells on cell proliferation, invasion and xenograft tumor growth in nude mice were analyzed. The molecular mechanism was explored by mass spectrometric exploration,Western blot and immunoprecipitation assays. Results: TRIM47 promoted RCC cell proliferation in vitro and in vivo as an oncogene. Mechanistically, TRIM47 exerted an E3 ligase activity by interacting with P53 protein to increase its ubiquitination and degradation, which further promoted the malignant biological behavior of RCC. Conclusion: Our study demonstrated that the TRIM47-P53 axis played a functional role in RCC progression and suggested a potential therapeutic target for RCC.
Comparison of Polysomnographic Features in Geriatric and Adult Patients
Authors: Balcı Aydın , Cilekar Sule 
Published: December 2020

Abstract
Objectives: In our study, it was aimed to compare polysomnography features in geriatric and adult patients.Materials and Methods: Our study was conducted as a retrospective case-control study. Sleep Patients who were hospitalized in the polysomnography laboratory with a pre-diagnosis of the disorder were divided into 2 groups according to their age as younger than 65 years old and over. Alice 6 computerized system (Respironics; Philips, Illinois, USA) polysomnography was applied to detect sleep disorders.Results: A total of 500 people, including 180 (36%) women, 320 (64%) men, were included in our study. The mean age was 52.36 ± 13.69. Posittive Airvey Pressure (Pap) treatment rates were significantly higher in the geriatric age group compared to adults. Sleep efficiency, mean sleep time, and total sleep time were higher in adults compared to geriatric patients. In the geriatric patient group, the most common diagnosis as a result of PSG was the diagnosis of Severe OSAS with 84 (%) people. When the lower extremity mobility measurements during sleep were evaluated, the values ​​were found to be significantly higher in geriatric patients with severe OSAS. Stage 3 and Rem stage were significantly higher in adults in terms of NREM3 (%) and REM (%) measurements.Conclusion: Sleep times are reduced in geriatric patients, restless leg movements during sleep are more common than adult patients, and sleep-disordered breathing is generally more severe in geriatric patients.
Non-pharmacological Interventions of Pain Management Used During Labour; an Exploratory Descriptive Qualitative Study of Puerperal Women in Adidome Government Hospital of the Volta Region, Ghana
Authors: Konlan Kennedy Diema , Afaya Agani , Mensah Eugenia , Suuk Amos Nawunimali , Kombat Dahamata Issahaku 
Published: December 2020

Abstract
Background: Women have experienced labour pain over the years as various attempts have been made to effectively manage this pain. There is paucity of literature on the experiences and perceptions about labour pain management with the contemporary Ghanaian health system. This study explored the perspective of puerperal women on the use of non-pharmacological labour pain management at Adidome Government Hospital. Methods: The study adopted an exploratory descriptive qualitative approach as data was collected through individual interviews. Informed consent was obtained from all participants who were purposively sampled. Interviews were audio recorded and transcribed immediately. Thematic analysis was engaged in three interrelated stages, namely data reduction, data display, and data conclusion to analyse the transcript and field notes. Results were presented with supporting quotes from the transcripts. Results: The majority (41.2%) of the women described labour pain as very severe, severe (35.3%) and moderate (23.5%) as the pain lasted more than 12 hours (58.8%). The various strategies adopted in managing labour pains included shouting and walking around (47.1%), crying and screaming (35.3%) and staying calm and snapping the fingers (17.6%). Women indicated they were satisfied (52.9%) and very satisfied (23.5%) of the midwives' attitude towards pain management. The pain management strategies adopted during labour included women engaged in deep breathing exercises, chatting with other people and relatives, diversion therapy, reassurance, taking a shower, assuming side lying positions, and receiving intravenous therapy. The presence of the husband of a labouring woman during improved pain bearing ability.Conclusion: It is important that midwives institute pragmatic protocols in the labour ward that ensure a relaxing atmosphere for women in labour, respond to the sensitivity and specificity of labouring women needs and when possible significant others of the labouring women could be allowed to visit. Expectant mothers should be educated more on non – pharmacological pain management to reduce anxieties and improve decision making.
Modeling the Risk of Radiation Pneumonitis in Esophageal Squamous Cell Carcinoma Treated with Definitive Chemoradiotherapy
Authors: Lan Kaiqi , Xu Cheng , Liu Shiliang , Zhu Jinhan , Yang Yadi , Zhang Li , Xi Mian 
Published: December 2020

Abstract
Purpose: To develop and validate a nomogram for the prediction of symptomatic radiation pneumonitis (RP) in patients with esophageal squamous cell carcinoma (ESCC) who received definitive concurrent chemoradiotherapy.Methods: Clinical factors, dose-volume histogram parameters, and pulmonary function parameters were collected from 402 ESCC patients between 2010 and 2017, including 321 patients in the primary cohort and 81 in the validation cohort. The end-point was the occurrence of symptomatic RP (grade ≥2) within the first 12 months after radiotherapy. Univariate and multivariate logistic regression analyses were applied to evaluate the predictive value of each factor for RP. A prediction model was generated in the primary cohort, which was internally validated to assess its performance.Results: In the primary cohort, 31 patients (9.7%) experienced symptomatic RP. Based on logistic regression model, patients with larger planning target volumes (PTVs) or higher lung V20 had a higher predictive risk of RP, whereas the overall risk was substantially higher for three-dimensional conformal radiotherapy (3DCRT) than intensity-modulated radiotherapy. On multivariate analysis, independent predictive factors for RP were smoking history (P=0.018), radiotherapy modality (P<0.001), PTV (P=0.014), and lung V20 (P=0.002), which were incorporated into the nomogram. The areas under the receiver operating characteristic curve of the nomogram in the primary and validation cohorts were 0.772 and 0.900, respectively, which were superior to each predictor alone.Conclusions: Non-smoking status, 3DCRT, lung V20 (>27.5%), and PTV (≥713.0 cc) were significantly associated with a higher risk of RP. A nomogram was built with satisfactory prediction ability.
The Association Between Homocysteine Levels and Cardiovascular Disease Risk Among Middle-Aged and Elderly Adults in Taiwan
Authors: Shih Chin-Chuan , Shih Yu-Lin , Chen Jau-Yuan 
Published: December 2020

Abstract
Background Our study aimed to determine the association between homocysteine levels and cardiovascular disease (CVD) risk in middle-aged and elderly adults in a community in northern Taiwan.MethodsParticipants in our study included adults aged 50 to 85 years old during community health examinations on 2019. A total of 396 people were enrolled. We divided participants according to tertiles of homocysteine level (low, middle and high groups). The CVD risk was calculated by the Framingham cardiovascular risk score (FRS). An FRS ≥ 20% indicated high CVD risk. Pearson correlation coefficients were calculated between homocysteine level and other cardio-metabolic risk factors while adjusting for age. High CVD risk in the middle and high homocysteine groups was compared with that in the low homocysteine group by multivariate logistic regression with adjustments for age, sex, smoking, hypertension (HTN), diabetes mellitus (DM), body mass index (BMI) and hyperlipidemia. The Youden index and receiver operating characteristic (ROC) curves were performed to determine the optimized cut-off value.ResultsThere were 396 people enrolled for analysis; 41.4% of participants were male, and the average age was 63.72 (±8.76). In our study, we showed a positive correlation of homocysteine with FRS. In the logistic regression models, the prevalence of high CVD risk was increased as homocysteine increased. The odds ratio (OR) and 95% confidence interval for high CVD risk was 2.851 (1.402 to 5.801) in the high homocysteine level group compared with the low homocysteine group after adjusting for traditional CVD risk factors (P=0.004). The area under the ROC curve was 0.67, and a homocysteine cut-off value of 12.15 µmol/L was determined.ConclusionsMiddle-aged and elderly people with increased homocysteine levels were associated with higher FRSs in this Taiwan community. Furthermore, homocysteine was an independent risk factor for high CVD risk in this study.
Chromobox4/5 Serve as Potential Prognostic Biomarkers and Targets for Breast Invasive Carcinoma
Authors: Dai Libing , Yao Yicun , Ye Dongping 
Published: December 2020

Abstract
Background: Chromebox (CBX) is a family of epigenetic regulation complexes. Many shreds of evidence suggest that CBXs play a vital role in the tumorigenesis and progression of breast invasive carcinoma (BRCA). However, little is known about the alteration and exact roles of each CBX in BRCA. Methods: In this study, we explored the exact roles of CBXs in the prognosis of BRCA by analyzing ONCOMINE, UALCAN, Kaplan-Meier Plotter, cBioProtal, STRING, and Metascape databases. Results: The mRNA expression of CBX1/2/3/4/6/7/8 was significantly altered and associated with the tumor stage. The protein expression level of 8 CBXs was significantly changed and associated with the tumor stage.Moreover, aberrant expression of CBX3/5/7/8 was significantly associated with clinical outcome for BRCA. Multivariate analysis indicated that genetic alteration of CBX4/5 was an independent prognostic factor for the OS in BRCA patients. Conclusions: These results imply that CBX4/5 might serve as prognostic biomarkers for survival in BRCA patients.
Inulin and Galacto-oligosaccharides Increase the Genotoxic Effect of Colibactin Produced by pks+ Escherichia Coli Strains
Authors: Oliero Manon , Calvé Annie , Fragoso Gabriela , Cuisiniere Thibault , Hajjar Roy , Dobrindt Ulrich , Santos Manuela M. 
Published: December 2020

Abstract
Background: Colibactin is a genotoxin that induces double-strand DNA breaks and is produced by Escherichia coli strains harboring the pks island. Human and animal studies have shown that colibactin-producing gut bacteria promote carcinogenesis and enhance the progression of colorectal cancer through cellular senescence and chromosomal abnormalities. In this study, we investigated the impact of prebiotics on the genotoxicity of colibactin-producing E. coli strains Nissle 1917 and NC101. Methods: Bacteria were grown in medium supplemented with 20, 30 and 40 mg/mL of prebiotics inulin or galacto-oligosaccharide, and with or without 5 µM, 25 µM and 125 µM of iron sulfate. Colibactin expression was assessed by luciferase reporter assay for the clbA gene, essential for colibactin production, in E. coli Nissle 1917 and by RT-PCR in E. coli NC101. The human epithelial colorectal adenocarcinoma cell line, Caco-2, was used to assess colibactin-induced megalocytosis by methylene blue binding assay and genotoxicity by γ-H2AX immunofluorescence analysis. Results: Inulin and galacto-oligosaccharide enhanced the expression of clbA in pks+ E. coli. However, the addition of 125 µM of iron sulfate inhibited the expression of clbA triggered by oligosaccharides. In the presence of either oligosaccharide, E. coli NC101 increased dysplasia and double-strand DNA breaks in Caco-2 cells compared to untreated cells. Conclusion: Our results suggest that, in vitro, prebiotic oligosaccharides exacerbate DNA damage induced by colibactin-producing bacteria. Further studies are necessary to establish whether these results are reproducible in vivo.
Does Fingolimod have anticancer effects? A meta-analysis and systematic review based on experimental animal models of various cancers
Authors: Ge Yuze , Zhou Ping , Kong Lu 
Published: December 2020

Abstract
Background: Numerous studies have explored the anticancer effect of FTY720 (Fingolimod) in animal models, a sphingosine-1-phosphate (S1P) receptor antagonist and an immunosuppressant, but little clinical evidence guides the use of FTY720 in cancer patients.Methods: Strictly, only related published articles about the treatment with FTY720 for various cancers in vivo from January 1998 to January 2020 were selected from PubMed, Web of Science, Ovid, Embase, CNKI and Cochrane databases, and which were qualified. We acquired agreement through discussion. Then, we conducted meta-analysis, subgroups analysis, publication bias analysis and sensitivity analysis based on selected studies. In the last two sections, we summaried and compared side effects, drug combination effects and molecular pathways from selected studies.Results: In the 31 articles included from 2002 to 2019, FTY720 was found to reduce tumor volume (SMD =-2.58, 95% CI: -3.42, -1.75, Z = 6.09, P = 0.000), tumor weight (SMD = -3.69, 95% CI: -5.17, -2.21, Z = 4.88, P = 0.000) and body weight (SMD = -0.86, 95% CI: -1.61, -0.11, Z = 2.23, P = 0.025) in 14 types of cancer. Relevant frequent signal pathways include the Akt pathway, S1PRs-Caspase pathway and the STAT3-PP2A pathway. FTY720 has significant independent or in combination anticancer effects and a lower toxicity in renal cell carcinoma and neuroblastoma mice models. However, it should be noted that FTY720 achieved a significant therapeutic effect in immunodeficient mice, not in immunecompetent mice. Also, the dosage-safety of FTY720 alone in clinical use is a noteworthy issue. In mouse models, the mechanism of the FTY720 treatment of tumors lies in inducing the tumor cells apoptosis through important signaling moleculars.Conclusions: FTY720 alone or in combination exerted significant anti-tumor effects for neuroblastoma and renal cell carcinoma, however not for melanoma. Due to insufficient evidence, more specific studies of FTY720 only and in combination included in immunity, inflammation and melanoma should be carried out in the future preclinical and clinical studies.