bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reconstructing Herbivore Diets: A Multivariate Statistical Approach To Interpreting Compound-Specific Isotope Values
Authors: Chen Mickey Hong Yi , Kendall Iain P. , Evershed Richard P. , Bogaard Amy , Styring Amy K. 
Published: November 2021

Abstract
Stable nitrogen (N) isotope analysis of bulk tissues is a technique for reconstructing the diets of organisms. However, bulk nitrogen isotope (δ15N) values can be influenced by a variety of metabolic and environmental factors that can confound accurate dietary reconstruction. Compound-specific isotope analyses of amino acids (CSIA-AA) have demonstrated the power of the approach in understanding how the δ15N values of bulk collagen are assembled from the constituent AAs. Furthermore, by connecting these AA δ15N values within a robust biochemical framework interpretation of diet and environment are greatly enhanced. Several new proxies have emerged, built around selected AAs; however, the interconnectedness of AA biosynthetic pathways means that patterning of δ15N values across a wider suite of collagen AAs will occur under different environmental or dietary influences. This work seeks to test this idea by situating CSIA-AA within a robust statistical framework using principal component analysis (PCA) and Bayesian statistics to increase the interpretability of a wider range of AA δ15N values in terms of reconstructing herbivore diet. The model was tested using wild and domestic herbivores from the Neolithic settlements of Çatalhöyük (Turkey), Makriyalos (Greece), and Vaihingen (Germany) as case studies. It was found that at Makriyalos there was a sharp separation between domesticated and wild herbivores, which was present to a lesser extent at Çatalhöyük and not observed at Vaihingen. The case studies presented in this work demonstrate that multivariate statistical treatment of CSIA-AA data can deliver new insights into herbivore diet, exceeding those achievable with the Bayesian model.
Human Urine-Derived Stem Cells Improve Partial Bladder Outlet Obstruction in Rats: Preliminary Data And microRNA-mRNA Expression Profile
Authors: Tu Menjiang , Wang Rui , Zhu Pei , Wang Qingqing , Sun Bishao , Lu Keshi , Zhang Jiawei , Xie Weijie , Guo Huan , Li Shulin , Wu Yuqi , Wang Xiangwei 
Published: November 2021

Abstract
Partial bladder outlet obstruction (pBOO) often results in bladder tissue inflammation and remodeling. As human urine-derived stem cells (USCs) have demonstrated therapeutic benefits, we used a rat model to investigate the effect of USCs on bladder function and explore the miRNA and gene expression profiles in bladder tissue using RNA sequencing. Eighteen rats were assigned to a sham surgery group, pBOO group, and pBOO+USC group (six biweekly treatments). Routine urodynamic monitoring, analysis of detrusor muscle strips, and pathophysiology assessments were conducted. Finally, altered miRNA and mRNA expression profiles of bladder tissue were examined using RNA sequencing and bioinformatics analysis. After USC treatment, elevated bladder compliance and maximal voiding pressure, declined end filling pressure and voided volume, and improved detrusor muscle contractility and carbachol sensitivity were found. Histology and TUNEL assay revealed reduced collagen deposition and muscle cell apoptosis in bladder tissue. The differential expression of eight miRNAs was reversed by USC treatment. Two large nodes (miR-142 and miR-9a) were identified in the miRNA‑gene interaction network in the USC-treated group. The Kyoto Encyclopedia of Genes and Genomes analysis revealed enrichment of multiple significant pathways, including those involved in necroptosis and cytokine-cytokine receptor interactions. This is the first study to demonstrate the protective effect of USCs on bladder function and remodeling in pBOO rats. The miRNA and mRNA expression levels differed in the bladder of pBOO rats with and without USC treatment. Although the mechanism underlying these effects has not been fully elucidated, necroptosis and cytokine-cytokine receptor interaction-related pathways may be involved.
Taste and chemical composition as drives for utilitarian redundancy and equivalence: a case study in local medical systems in Northeastern Brazil
Authors: REINALDO RAFAEL CORRÊA PROTA DOS SANTOS , Santoro Flávia Rosa , ALBUQUERQUE ULYSSES PAULINO , MEDEIROS PATRÍCIA MUNIZ 
Published: November 2021

Abstract
Background
We aimed to verify whether the taste and chemical composition influence the selection of plants in each medicinal category, whether within a socio-ecological system or between different socio-ecological systems. To this end, we use the theoretical bases of the Utilitarian Redundancy Model and the Utilitarian Equivalence Model. We studied the local medical systems of four rural communities in northeastern Brazil, used as models to test our assumptions.
Methods
The data on medicinal plants and local therapeutic function were obtained from semi-structured interviews associated with the free-listing method, allowing to generate indexes of similarity of therapeutic use between the plants cited in each region. During the interviews, each informer was also asked to report the tastes of the plants cited. Subsequently, we classified each plant in each region according to the most cited taste. The data about the chemical composition of each plant were obtained from a systematic review, using Web of Knowledge and Scopus databases.
Results
Pairs of plants with similar tastes are 1.46 times more likely to have the same therapeutic function within a local medical system (redundancy), but not between medical systems (equivalence). We also find that chemical compounds are not primarily responsible for utilitarian redundancy and equivalence. However, there was a tendency for alkaloids to be doubly present with greater expressiveness in pairs of equivalent plants.
Conclusions
The results indicate that each social group can create its means of using the organoleptic characteristics as clues to select new species as medicinal. Furthermore, this study corroborates the main prediction of the Utilitarian Equivalence Model, that people in different environments choose plants with traits in common for the same functions.
Can Integrative Oncology Increase Adherence to Chemotherapy in Advanced Gynecologic Cancer?
Authors: Ben-Arye Eran , Nijk Naama , Lavie Ofer , Gressel Orit , Schiff Elad , Samuels Noah 
Published: November 2021

Abstract
Objective
Integrative oncology (IO) has been shown to improve quality-of-life (QoL) and increase adherence to planned chemotherapy regimens. This study examined the impact of a patient-tailored IO program on adherence to chemotherapy among patients with advanced gynecological cancer.
Methods
This prospective pragmatic study examined patients with stage III/IV gynecological cancers undergoing 6 weeks of weekly IO treatments. Adherence to the planned chemotherapy regimen was assessed using the relative dose intensity (RDI) calculation. Patients consistently attending IO treatments (consistent-IO group) were compared to those who were not (non-consistent IO group).
Results
RDI was calculated for 73 patients in the consistent-IO group (99 chemotherapy cycles) and 61 in the non-consistent-IO group (96 cycles with IO care, 126 cycles without). Both groups had similar baseline demographic characteristics, with endometrial cancer more prevalent in the consistent-IO group. RDI was significantly less reduced in the consistent-IO chemotherapy group (p = 0.005). During taxane-based regimens RDI was better maintained in the consistent-IO group (0.93 vs. 0.87, p = 0.012), though not with platinum-based cycles. Linear regression model found a correlation between preserved RDI and consistent attendance at weekly IO treatments, and lower rates of chemotherapy-induced peripheral neuropathy and pain.
Conclusion
Patient-tailored IO programs for patients with advanced gynecological cancer may help preserve adherence to chemotherapy at 6 weeks, especially with taxane-based regimens. Further research needs to explore whether this correlation is chemotherapy agent-specific.
Sustainment of Diverse Evidence-Based Practices Disseminated in the Veterans Health Administration (VHA): Development and Administration of a Pragmatic Instrument
Authors: Reardon Caitlin , Nevedal Andrea , Widerquist Marilla A. Opra , Arasim Maria , Jackson George L. , White Brandolyn , Cutrona Sarah L. , Fix Gemmae M. , Gifford Allen L. , DeLaughter Kathryn , King Heather A. , Henderson Blake , Vega Ryan , Damschroder Laura 
Published: November 2021

Abstract
Background There are challenges associated with measuring sustainment of evidence-based practices (EBPs). First, the terms sustainability and sustainment are often falsely conflated: sustainability assesses the likelihood of an EBP being in use in the future while sustainment assesses the extent to which an EBP is (or is not) in use. Second, grant funding often ends before sustainment can be assessed. The Veterans Health Administration (VHA) Diffusion of Excellence (DoE) is one of few large-scale models of diffusion; it seeks to identify and disseminate practices across the VHA system. The DoE sponsors “Shark Tank” competitions, in which leaders bid on the opportunity to implement a practice with 6 months of implementation support. As part of an ongoing evaluation of the DoE, we sought to develop and administer a pragmatic instrument to assess sustainment of DoE practices.Methods In June 2020, surveys were sent to 64 facilities that were part of the DoE evaluation. We began analysis by comparing alignment of quantitative and qualitative responses; some facility representatives reported in the open text box of the survey that their practice was on a temporary hold due to COVID-19 but answered the primary outcome question differently. As a result, the team reclassified the primary outcome of these facilities to Sustained: Temporary COVID-Hold. Following this reclassification, the number and percent of facilities in each category was calculated. We used directed content analysis, guided by the Consolidated Framework for Implementation Research (CFIR), to analyze open text box responses. Results A representative from forty-one facilities (64%) completed the survey. Among responding facilities, 29/41 sustained their practice, 1/41 partially sustained their practice, 8/41 had not sustained their practice, and 3/41 had never implemented their practice. Sustainment rates increased between Cohorts 1 – 4. Conclusions The development and administration of our pragmatic survey allowed us to assess sustainment of DoE practices. Planned updates to the survey will enable flexibility in assessing sustainment and its determinants at any phase after adoption. This assessment approach can flex with the longitudinal and dynamic nature of sustainment, including capturing nuances in outcomes when practices are on a temporary hold.
A Web-based Prediction Model for Overall Survival of Elderly Patients With Malignant Bone Tumors: a Population-based Study
Authors: Tang Jie , Wang Jinkui , Pan Xiudan 
Published: November 2021

Abstract
Background: Malignant bone tumors(MBT) are one of the causes of death in elderly patients. The purpose of our study is to establish a nomogram to predict the overall survival(OS) of elderly patients with MBT.Methods: The clinicopathological data of all elderly patients with MBT from 2004 to 2018 were downloaded from the SEER database. They were randomly assigned to the training set (70%) and validation set (30%). Univariate and multivariate Cox regression analysis was used to identify independent risk factors for elderly patients with MBT. A nomagram was built based on these risk factors to predict the 1-, 3-, and 5-year OS of elderly patients with MBT. Then, used the consistency index (C-index), calibration curve, and the area under the receiver operating curve(AUC) to evaluate the accuracy and discrimination of the prediction model. Decision curve analysis(DCA) was used to evaluate the clinical potential application value of nomogram. Based on the scores on the nomogram, patients were divided into high- and low-risk groups. Kaplan-Meier (K-M) curve was used to test the difference in survival between the two groups of patients.Results: A total of 1641 patients were included, and they were randomly assigned to the training set (N=1156) and the validation set (N=485). The univariate and multivariate analysis of the training set suggested that age, sex, race, primary site, histologic type, grade, stage, M stage, surgery, and tumor size were independent risk factors for elderly patients with MBT. The C-index of the training set and the validation set were 0.779[0.759-0.799] and 0.801[0.772-0.830], respectively. The AUC of the training set and the validation set also showed similar results. The calibration curves of the training set and the validation set both showed that the observed value and the predicted value were highly consistent. DCA suggested that the nomogram had potential clinical value compared with traditional TNM staging.Conclusion: We had established a new nomogram to predict the 1-, 3-, 5-year OS of elderly patients with MBT. This predictive model can help doctors and patients develop treatment plans and follow-up strategies.
Applied causal inference methods for sequential mediators
Authors: Zugna Daniela , Popovic Maja , Heude Barbara , Fasanelli Francesca , Scelo Ghislaine , Richiardi Lorenzo 
Published: November 2021

Abstract
Background: Mediation analysis aims at estimating to what extent the effect of an exposure on an outcome is explained by a set of mediators on the causal pathway between the exposure and the outcome. The total effect of the exposure on the outcome can be decomposed into an indirect effect, i.e. the effect explained by the mediators jointly, and a direct effect, i.e. the effect unexplained by the mediators. However finer decompositions are possible in presence of independent or sequential mediators. Methods: We review four statistical methods to analyse multiple sequential mediators , the inverse odds ratio weighting approach, the inverse probability weighting approach, the imputation approach and the extended imputation approach. These approaches are compared and implemented using a case-study with the aim to investigate the role of adverse reproductive outcomes and infant respiratory infections on infant wheezing in the Ninfea birth cohort. Results: Using the inverse odds ratio weighting approach, the direct effect of maternal depression or anxiety in pregnancy is equal to a 59% (95% CI: 27%-94%) increased prevalence of infant wheezing and the mediated effect through adverse reproductive outcomes is equal to a 3% (95% CI:-6%-12%) increased prevalence of infant wheezing. When including infant lower respiratory infections in the mediation pathway, the direct effect decreases to 57% (95% CI: 25%-92%) and the indirect effect increases to 5% (95% CI:-5%,15%). The estimates of the effects obtained using the weighting and the imputation approaches are similar. The extended imputation approach suggests that the small joint indirect effect through adverse reproductive outcomes and lower respiratory infections is due entirely to the contribution of infant lower respiratory infections, independently from the increased prevalence of adverse reproductive outcomes. Conclusions: The use of these methods allows the study of multiple mechanisms underlying the association between an exposure and an outcome and provides a solution for the problem of intermediate confounding by considering the intermediate confounder as a sequential mediator. The choice of the method may depend on what is the effect of main interest, the nature of the variables involved in the analysis and the truthfulness of the underlying assumptions.
Effects of intensive agriculture and hydrological changes on macrophyte and macroinvertebrate assemblages in lowland riverine wetlands
Authors: Altieri Paula , Ocon Carolina , Jensen Roberto , Capítulo Alberto Rodrigues 
Published: November 2021

Abstract
The aim of this study was to investigate the effects of agricultural land use and periods of hydrological variability on the environmental variables, as well as macrophyte and macroinvertebrate assemblages in lowland riverine wetlands. We compared two wetlands with intensive agricultural land use against two others with extensive livestock considered references for the region during a normal and a dry flow period. Nutrient concentrations were significantly higher in agricultural riverine wetlands. These wetlands exhibited higher relative coverage of floating anchored macrophytes and the absence of submerged vegetation. They showed significantly lower taxonomic richness and density of macroinvertebrates and a higher relative abundance of scrapers and predators. Wetlands of both land uses had a lower total density of macroinvertebrates and a higher proportion of tolerant desiccation taxa in the dry period. Particular differences between land uses, such as lower dissolved oxygen concentrations and lower macroinvertebrate diversity in agricultural wetlands, were found during the dry period. These findings indicate that the differences between land uses increased during the aforementioned period. This study provides evidence of the effects of the surrounding landscape and hydrologic periods in the environmental characteristics as well as the macrophyte and macroinvertebrate assemblages of the riverine wetlands studied.
A sense-antisense RNA interaction promotes breast cancer metastasis via regulation of NQO1 expression
Authors: Culbertson Bruce , Garcia Kristle , Markett Daniel , Asgharian Hosseinali , Chen Li , Fish Lisa , Navickas Albertas , Yu Johnny , Woo Brian , Nanda Arjun , Rabinowitz Joshua , Goodarzi Hani 
Published: November 2021

Abstract
Antisense RNAs are ubiquitous in human cells, yet the role that they play in healthy and diseased states remains largely unexplored. Here, we developed a computational framework to catalog and profile antisense RNAs and applied it to poorly and highly metastatic breast cancer cell lines. We identified one antisense RNA that plays a functional role in driving breast cancer progression by upregulating the redox enzyme NQO1, and hence named NQO1-antisense RNA or NQO1-AS. This upregulation occurs via a stabilizing interaction between NQO1-AS and its complementary region in the 3’UTR of NQO1 mRNA. By increasing expression of NQO1 protein, breast cancer cells are able to tolerate higher levels of oxidative stress, enabling them to colonize the lung. During this process the cancer cells become dependent on NQO1 to protect them from ferroptosis. We have shown that this dependence can be exploited therapeutically in xenograft models of metastasis. Together, our findings establish a previously unknown role for NQO1-AS in the progression of breast cancer by serving as a post-transcriptional regulator of RNA processing and decay for its sense mRNA.
Monitoring and Modelling of Butyltin Compounds in Finnish Inland Lake
Authors: Ahkola Heidi , Juntunen Janne , Krogerus Kirsti , Huttula Timo 
Published: November 2021

Abstract
Butyltin compounds (BTCs) in surface waters is seldom studied due to their low concentrations and limitations of analytical techniques. In this study we measured total concentration of BTCs with grab water sampling, dissolved concentration with passive samplers and particle bound fraction with sedimentation traps in Finnish inland lake. The sampling was conducted from May to September during two study years. The differences between sampling techniques and the concentrations were obvious. E.g. tributyltin (TBT) was detected only in 4-24 % of the grab samples when the detection with passive samplers was 93% and with sedimentation traps 50%. The dissolved BTC concentrations measured with grab and passive sampling suggested hydrological differences between the study years. This was confirmed with flow velocity measurements. However, the annual difference was not observed in BTC concentrations of settled particle.The extreme value analysis suggested that grab sampling and sedimentation trap sampling results contain more extreme peak values than passive sampling. This indicates that BTCs are present in surface water in trace concentrations despite they are not detected with all the sampling techniques. The assumption that WWTP, located in the study area, was the source of BTCs was not valid as elevated BTC concentrations were detected also at the reference site, located upstream of WWTP. Computational modelling and back tracking simulations also supported the concept that WWTP cannot be the only source but BTCs can come even from upstream of the sampling area where there is e.g. wood processing industry.
Enhancer Promoter Interactome and Mendelian Randomization Identify Network of Druggable Vascular Genes in Coronary Artery Disease
Authors: Chignon Arnaud , Mathieu Samuel , Rufiange Anne , Argaud Deborah , Voisine Pierre , Bossé Yohan , Arsenault Benoit , Thériault Sébastien , Mathieu Patrick 
Published: November 2021

Abstract
Coronary artery disease (CAD) is a multifactorial disorder, which is partly heritable. Herein, we implemented a mapping of CAD-associated candidate genes by using genome-wide enhancer-promoter conformation (H3K27ac-HiChIP) and expression quantitative trait loci (eQTL). Enhancer-promoter anchor loops from human coronary artery smooth muscle cells (HCASMC) explained 22% of the heritability for CAD. 3D enhancer-promoter genome mapping of CAD-genes in HCASMC was enriched in vascular eQTL genes. By using colocalization and Mendelian randomization analyses, we identified 58 causal candidate vascular genes including some druggable targets (MAP3K11, CAMK1D, PDGFD, IPO9 and CETP). A network analysis of causal candidate genes was enriched in TGF beta and MAPK pathways. The pharmacologic inhibition of causal candidate gene MAP3K11 in vascular SMC reduced the expression of athero-relevant genes and lowered cell migration, a cardinal process in CAD. Genes connected to enhancers are enriched in vascular eQTL and druggable genes causally associated with CAD.