bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dimensions of leisure-time physical activity and risk of depression in the “SEGUIMIENTO UNIVERSIDAD DE NAVARRA” (SUN) prospective cohort.
Authors: Montero Alejandro Fernández , Moreno-Galarraga Laura , Sánchez-Villegas Almudena , Lahortiga-Ramos Francisca , Ruiz-Canela Miguel , Martínez-González Miguel Ángel , Molero Patricio 
Published: February 2020

Abstract
Background: An inverse association between total leisure-time physical activity (LTPA) and depression has been previously documented in the scientific literature. Our objective was to prospectively assess the association of LTPA with the risk of depression, focusing on several dimensions of LTPA (intensity, duration and type).Methods: The SUN (Seguimiento Universidad de Navarra) project is a prospective cohort study formed by Spanish university graduates. A total of 15,488 adults (40.2% men, mean age 37±12 years) initially free of depression were assessed. A report of a validated medical diagnosis of depression or the habitual use of antidepressants (any of both) were considered as incident cases of depression. LTPA was estimated through previously validated self-reported questionnaires. Participants were classified following Physical Activity recommendations from the World Health Organization, and according to the intensity, duration and type of LTPA. Cox proportional hazards regression models were run, adjusted for demographic, lifestyle, and dietary factors, to estimate adjusted hazard ratios (HR) of depression and 95% confidence intervals (CI). Results: During 163,059 person-years of follow-up we registered 870 incident cases of depression. Participants with higher total LTPA (METs-h/wk) and higher duration of LTPA (hours/wk) exhibited a lower risk of depression HR=0.84 (95% CI: 0.72-0.99) and HR=0.83 (0.70-0.99) respectively, whereas intensity of LTPA (MET) did not show any association with depression. Conclusion: Participants with higher LTPA had a lower risk of depression. The inverse association was stronger for total LPTA time than for its intensity. Higher duration of LTPA should be encouraged to prevent depression.
Reduced methane oxidizing activity by sediment methanotrophs in shallow coastal zones with high methane emissions
Authors: Broman Elias , Sun Xiaole , Stranne Christian , Salgado Marco G , Bonaglia Stefano , Geibel Marc , Norkko Alf , Humborg Christoph , Nascimento Francisco J.A 
Published: February 2020

Abstract
Background Coastal zones are transitional areas between land and sea where large amounts of organic and inorganic carbon compounds are recycled by microbes. Especially shallow zones near land have been shown to be the main source for oceanic methane (CH4) emissions. Water depth has been predicted as the best explanatory variable, which is related to CH4 ebullition, but exactly how sediment methanotrophic bacteria mediates these emissions along water depth is unknown. Here, we investigated the activity of methanotrophs in the sediment of shallow coastal zones with high CH4 emissions within a depth gradient from 10–45 m. Field sampling consisted of collecting sediment slices from eight stations along a coastal gradient (0–4 km from land) in the coastal Baltic Sea. We combined real-time measurements of surface water CH4 concentrations, acoustic detection of CH4 seeps in the bottom water, and sediment DNA plus RNA sequencing.Results The relative abundance and CH4 oxidizing activity (pMMO; particulate methane monooxygenase) of the dominant methanotroph Methylococcales was significantly higher in deeper costal offshore areas (36–45 m water depth) compared to adjacent shallow zones (10–28 m). This was in accordance with the shallow zones having CH4 concentrations in the surface water, as well as more CH4 seeps from the sediment. Furthermore, our findings indicate that the low prevalence of Methylococcales and their activity was restrained to the euphotic zone (indicated by PAR data, photosynthesis proteins, and 18S rRNA data of benthic diatoms). This was also indicated by a positive relationship between water depth and the relative abundance of Methylococcales and pMMO.Conclusions We detected a low relative abundance of methanotrophs and CH4 oxidizing activity in shallow coastal areas, this can partly explain the difference in CH4 emissions between shallow and deep coastal areas (and the relationship between CH4 emission and water depth). Potentially a reduced activity of methanotrophs also facilities the build-up of CH4 bubbles in the sediment. CH4 emissions from the study area has previously been calculated to be comparable to that of subarctic lakes, and it is suggested that shallow coastal waters, similarly to inland waters, are hotspots for CH4 emissions.
Multiple m6A RNA methylation modulators promote the malignant progression of hepatocellular carcinoma and affect its clinical prognosis
Authors: Qu Nanfang , Qin Sanyu , Zhang Xuemei , Bo Xiaotong , Liu Zhengchun , Tan Chao , Wen Guiqiong , Jiang Haixing 
Published: February 2020

Abstract
Background: Hepatocellular carcinoma (HCC) is the second most common cause of cancer-related death in the world. N 6 -methyladenosine (m 6 A) RNA methylation is dynamically regulated by m 6 A RNA methylation modulators (“writer,” “eraser,” and “reader” proteins), which are associated with cancer occurrence and development. The purpose of this study was to explore the relationships between m 6 A RNA methylation modulators and HCC.
Methods: First, using data from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases, we compared the expression levels of 13 major m6A RNA methylation modulators between HCC and normal tissues. Second, we applied consensus clustering to the expression data on the m 6 A RNA methylation modulators to divide the HCC tissues into two subgroups (clusters 1 and 2), and we compared the clusters in terms of overall survival (OS), World Health Organization (WHO) stage, and pathological grade. Third, using least absolute shrinkage and selection operator (LASSO) regression, we constructed a risk signature involving the m 6 A RNA methylation modulators that affected OS in TCGA and ICGC analyses.
Results: We found that the expression levels of 12 major m6A RNA methylation modulators were significantly different between HCC and normal tissues. After dividing the HCC tissues into clusters 1 and 2, we found that cluster 2 had poorer OS, higher WHO stage, and higher pathological grade. Four m 6 A RNA methylation modulators (YTHDF1, YTHDF2, METTL3, and KIAA1429) affecting OS in the TCGA and ICGC analyses were selected to construct a risk signature, which was significantly associated with WHO stage and was also an independent prognostic marker of OS.
Conclusions: In summary, m 6 A RNA methylation modulators are key participants in the malignant progression of HCC and have potential value in prognostication and treatment decisions.
CA724 predicts overall survival in locally advanced gastric cancer patients with neoadjuvant chemotherapy
Authors: Tong Yilin , Zhao Yan , Shan Zexing , Zhang Jianjun 
Published: February 2020

Abstract
Background: Serum tumor markers are of great importance in diagnosis, prognostic predicting and recurrence monitoring in gastrointestinal malignancy, including AFU, AFP, CEA, CA199, CA125 and CA724. However, their significances in gastric cancer (GC) patients with neoadjuvant therapy (NCT) are still uncertain. The aim of this study is to evaluate the predictive value of these six tumor markers in locally advanced GC patients with NCT and curative surgery.
Methods: 290 locally advanced GC patients with NCT and D2 radical gastrectomy were retrospectively analyzed. Their tumor markers before (pre-) and after (post-) NCT and pathological characters were exacted from the database in our hospital. The optimal cutoff values of six tumor markers were calculated by ROC and Youden index. Their predictive significances were analyzed and survival curves on overall survival (OS) were obtained by Kaplan-Meier method. Associations between categorical variables were explored by Chi-square test or Fisher's exact method. Multivariate analyses were performed by Cox regression model.
Results: Not only the pre- and post- CA199, CA125 and CA724 could predict the OS respectively, but also the changes (diff-) between post- and pre- groups were related to the prognosis (P < 0.05). In multivariable analysis, only pre- (P = 0.016) and post-CA724 (P = 0.033) remained significant, and the significance of diff-CA724 was on borderline (P = 0.085). Besides, pre- and post-CA199, CA125 and CA724 were associated with the metastasis of lymph node (N- vs N+) and pathological stage (Ⅰ-Ⅱ vs Ⅲ) (P < 0.05). Post-CA724 was related to the invasion of vascular or lymphatic vessels (P = 0.019), and pre-CA724 was nearly remarkable (P = 0.082). However, AFU, AFP and CEA showed no association with survival (P > 0.05).
Conclusions: CA724 is an independent factor to prognosis, and could be used to predict the ypN and ypTNM stage in locally advanced GC patients undergone NCT and curative resection.
PNO1 promotes cell proliferation in prostate cancer
Authors: Hu Jianpeng , Cui Feilun , Xv Zhipeng , Tan Jian , Wang Zhengyu 
Published: February 2020

Abstract
BackgroundProstate cancer (PCa) is one of the most commonly diagnosed cancers. The functions of PNO1 in yeasts were involved in regulating ribosome and proteasome biogenesis. Human PNO1 is crucial to the site 3 cleavage at the 3ʹ-end of 18S pre-rRNA. Previous studies indicated that PNO1 may be related to the progression of cancers. However, the functions of PNO1 in PCa remained unclear. MethodsThe present study evaluated the expression levels of PNO1 in PCa by using GSE45016, GSE55945 and GSE17951 datasets. Then, in vivo and in vitro assays were conducted to detect the biological functions of PNO1 in PCa. Microarray and bioinformatic analysis were carried out to detect the downstream targets and pathways regulated by PNO1.ResultsThe present study for the first time demonstrated PNO1 was up-regulated in PCa samples compared to normal tissues. ShRNA mediated knockdown of PNO1 significantly suppressed PCa proliferation and clone formation, however, induced PCa apoptosis. Microarray analysis and bioinformatics analysis revealed PNO1 was involved in regulating multiple cancer related biological processes, such as regulation of DNA repair, single organismal cell-cell adhesion, translational initiation, RNA splicing, transcription, and positive regulation of mRNA catabolic process. OF note, in vivo results showed PNO1 knockdown remarkably reduced the PCa growth rate. ConclusionsDespite more in-depth research is still required, this study showed PNO1 could serve as a potential biomarker for PCa.
The role of residents in medical students’ neurology education: current status and future perspectives
Authors: Keser Zafer , Rodriguez Yvo A , Tremont Jennifer , Hsieh Peggy H , McCullough Louise D. , Sandrone Stefano , Stimming Erin F 
Published: February 2020

Abstract
Background: Neurophobia, a well-described fear of neurology affects medical students worldwide and may be one of the factors contributing to a shortage of neurologists in the United States. Residents spend a considerable amount of time with medical students, therefore, we sought to better understand the impact neurology residents have on the medical students experience during their neurology clerkship and their subsequent interest in neurology. We aimed to identify and implement strategies to decrease neurophobia and increase the number of students pursuing neurology as a career. Methods: Third-year medical students (n=234) of UTHealth’s McGovern Medical School rotating through their neurology core clerkship completed two surveys regarding their rotation experiences. Surveys were completed anonymously before and after the clerkship to measure their interest and confidence in neurology and the impact of their interactions with the neurology residents during the clerkship. In parallel, residents participated in a teaching workshop focused on small group teaching to improve their teaching effectiveness. Non-parametrical comparison and ordinal regression analyses were utilized for data analyses. Results: Medical students reported a statistically significant increase in their confidence in managing neurological conditions and interest in pursuing a neurology residency after their clerkship. There was a significant association between the medical students’ overall rotation experience and the residents’ teaching effectiveness. Their overall clerkship experience correlated with their interest and confidence in neurology. There was a trend towards an increase in residents’ teaching effectiveness and students’ rotation experience after the resident workshop. Additionally, students who rotated in both and outpatient and inpatient site reported an increased interest in neurology. Conclusion: Our study supports that resident-led teaching efforts are important in improving medical students’ neurologic education and their interest in neurology . We examined future strategies to implement “near-peer” teaching activities to enhance the medical students' neurologic educational experience. These strategies could potentially mitigate neurophobia and ultimately lead to a much-needed increase in future neurologists.
Modulation of Actin network and Tau phosphorylation by HDAC6 ZnF UBP domain
Authors: Balmik Abhishek Ankur , Sonawane Shweta Kishor , Chinnathambi Subashchandrabose 
Published: February 2020

Abstract
Background: Microtubule-associated protein Tau undergoes aggregation in Alzheimer`s disease and a group of other related diseases collectively known as Tauopathies. In AD, Tau forms aggregates, which are deposited intracellularly as neurofibrillary tangles. HDAC6 plays an important role in aggresome formation where it recruits poly-ubiquitinated aggregates to the motor protein dynein.
Methods: Here, we have studied the effect of HDAC6 ZnF UBP on Tau phosphorylation, ApoE localization, GSK-3β regulation and cytoskeletal organization in neuronal cells by immunofluorescence analysis using fluorescently tagged molecules or antibodies. We have assessed neuronal cell viability and membrane integrity under different treatment conditions by employing MTT and LDH assay respectively.
Results: Immunocytochemistry reveals that HDAC6 ZnF UBP can modulate Tau phosphorylation and actin cytoskeleton organization when the cells are exposed to the domain. HDAC6 ZnF UBP treatment to cells does not affect their viability and resulted in enhanced neurite extension and formation of structures similar to podosomes, lamellipodia and podonuts suggesting its role in actin re-organization. Also, HDAC6 treatment showed increased nuclear localization of ApoE and tubulin localization in microtubule organizing centre.
Conclusions: Altogether, our studies suggest the regulatory role of this domain in different aspects related to neurodegenerative diseases.
The effect of antiretroviral therapy initiation time and baseline CD4+ cell counts on AIDS-related mortality among former plasma donors in China: a 20-Year retrospective cohort study
Authors: Zhang Xuening , Yang Yongli , Zhang Weiping , Jia Xiaocan , Shi Nian , Gondwe Theodore , Shi Xuezhong 
Published: February 2020

Abstract
Background: To estimate the influence of antiretroviral therapy (ART) initiation time， baseline CD4+ cell counts and other prognostic factors on AIDS-related death among former plasma donors patients (FPD). Methods: A retrospective cohort study was conducted involving 11,905 HIV/AIDS patients in a high-risk area of illicit blood donation of Henan province in China between 1995 and 2016. Demographic and clinical characteristics information was collected. Hazard Ratios (HRs) for AIDS-related mortality by categories of baseline CD4+ cell counts and ART initiation time, were determined using competing risk model. Competing risk model also was used to evaluate the prognostic factors of AIDS-related mortality. The model performance was assessed by time-dependent receiver operating characteristic curve. Results: Patients who initiated ART within 90 days of HIV/AIDS diagnosis (sHR: 0.24, 95% CI: 0.22-0.27) and baseline CD4+ cell counts of ≥500 cells/μL (sHR: 0.23, 95% CI: 0.19-0.28) were associated with lower AIDS-related mortality risk. ART initiation time >1 year and CD4+ counts >350 (sHR: 4.42, 95% CI: 3.30-5.91) had a higher AIDS-related mortality risk than ART initiation time >90 days and CD4+ counts ≤350 (sHR: 4.33, 95% CI: 3.58-5.23). Male (sHR: 1.32, 95% CI: 1.22-1.43), older age (sHR: 1.97, 95% CI: 1.59-2.46), and infection by blood transmission (sHR: 1.57, 95% CI: 1.37-1.80) were risk factors.Conclusions: Early ART should be promoted to improve the survival of HIV/AIDS patients regardless of baseline CD4+ cell counts, especially elders, males, and infected through blood transmission. Key words: HIV/AIDS; antiretroviral therapy; treatment initiation; CD4+ cell counts; AIDS-related mortality; competing risk model
Effect of Residual Extractable Lignin on Acetone-Butanol-Ethanol Production in SHF and SSF Processes
Authors: Li Jing , Zhang Yu , Shi Suan , Tu Maobing 
Published: February 2020

Abstract
Background Lignin played an important role in biochemical conversion of biomass to biofuels. A significant amount of lignin is precipitated on the surface of pretreated substrates after organosolv pretreatment. The effect of this residual lignin on enzymatic hydrolysis has been well understood, however, their effect on subsequent ABE fermentation is still unknown. Results To determine the effect of residual extractable lignin on Acetone-Butanol-Ethanol (ABE) fermentation in separate hydrolysis and fermentation (SHF) and simultaneous saccharification and fermentation (SSF) processes, we compared ABE production from ethanol washed and unwashed substrates. The ethanol organosolv pretreated loblolly pine (OPLP) was used as the substrates. It was observed that butanol production from OPLP-UW (unwashed) and OPLP-W(washed) reached 8.16 and 1.69 g/L, respectively in SHF. The results showed that ABE production in SHF from OPLP-UW prevents an “acid crash” as comparing the OPLP-W. In SSF process, the “acid crash” occurred for both OPLP-W and OPLP-UW. The inhibitory extractable lignin intensified the “acid crash” for OPLP-UW and resulted in less ABE production than OPLP-W. The addition of detoxified prehydrolysates in SSF processes shortened the fermentation time and could potentially prevent the “acid crash”. Conclusions The results suggested that residual extractable lignin in high sugar concentration could help ABE production by slowing the metabolic rate and preventing “acid crash”. However, it became unfavorable in SSF due to its inhibition of both enzymatic hydrolysis and ABE fermentation with low initial sugar concentration. It is essential to remove extractable lignin of substrates for ABE production in SSF processes. And a higher initial sugar concentration is needed to prevent the “acid crash” in SSF processes.
The Distance and Median Problems in the Single-Cut-or-Join model with Single-Gene Duplications
Authors: Mane Aniket , Lafond Manuel , Feijao Pedro , Chauve Cedric 
Published: February 2020

Abstract
Background: In the field of genome rearrangement algorithms, models accounting for gene duplication lead often to hard problems. For example, while computing the pairwise distance is tractable in most duplication-free models, it is NP-complete for most extensions of these models accounting for duplicated genes. Moreover, problems involving more than two genomes, such as the genome median and the Small Parsimony problem, are intractable for most duplication-free models, with some exceptions, for example the Single-Cut-or-Join (SCJ) model. Result: We introduce a variant of the SCJ distance that accounts for duplicated genes, in the context of directed evolution from an ancestral genome to a descendant genome where orthology relations between ancestral genes and their descendant are known. Our model includes two duplication mechanisms: single-gene tandem duplication and the creation of single-gene circular chromosomes. We prove that in this model, computing the directed distance and a parsimonious evolutionary scenario in terms of SCJ and single-gene duplication events can be done in linear time. We also show that the directed median problem is tractable for this distance, while the rooted median problem, where we assume that one of the given genomes is ancestral to the median, is NP-complete. We also describe an Integer Linear Program for solving this problem. We evaluate the directed distance and rooted median algorithms on simulated data. Conclusion: Our results provide a simple genome rearrangement model, extending the SCJ model to account for single-gene duplications, for which we prove a mix of tractability and hardness results. For the NP-complete rooted median problem, we design a simple Integer Linear Program. Our publicly available implementation of these algorithms for the directed distance and median problems allow to solve efficiently these problems on large instances. Availability: https://github.com/cchauve/SCJ-with-SGD
Effect of aspirin and statins on pulmonary function and inflammation in patients with AECOPD
Authors: Duan Guangqing , Li Xiaoshuang , Lyu Juncheng , Tian Na , Lv Kaixuan , Liu Qi , Wang Mengjie , Sun Shiyu , Yu Jielun , Guo Guifang , Tan Wei , Yang Nana 
Published: February 2020

Abstract
Background: The influence of coronary atherosclerosis and related treatment drugs on acute exacerbation of chronic obstructive pulmonary disease (AECOPD) development requires in-depth study. The study investigated the effect of coronary artery calcification (CAC) and drugs for the treatment of CAC on the development of AECOPD. Methods : This retrospective clinical study recruited subjects with AECOPD from Weifang People’s Hospital from May 2017 to May 2019. All subjects were performed spirometry and coronary computed tomography (CT), and were divided into two groups according to whether coronary CT revealed coronary artery calcification: AECOPD group and AECOPD+CAC group. Then the AECOPD+CAC subjects were subdivided into two groups according to whether they had received oral aspirin and statins: AECOPD + CAC non-medication and AECOPD + CAC medication. T he t -test and nonparametric test were used for analyzed the lung function, arterial blood gas, routine blood and blood lipid between groups. Results : AECOPD subjects with CAC had significant increases in FEV 1 %pred, PaO 2 and Lym% ( P <0.05), but WBC, Neu, and Neu% were lower ( P <0.05) compared with the AECOPD group. There were no statistically significant differences in blood lipid levels between the two groups. Compared to the AECOPD group, the AECOPD+CAC medication group also had significantly higher PaO 2 and Lym% ( P <0.05), and WBC, Neu, and Neu% in the AECOPD+CAC medication group were significantly lower ( P <0.05) than in the AECOPD group. Conclusions : Aspirin and statins for the treatment of cardiovascular diseases can improve lung function, normalize blood gas levels, and reduce inflammation in patients with AECOPD and CAC.