bluuebunny/crossref_metadata_2025_split huggingface dataset:
THRIVE study protocol: a randomized controlled trial evaluating a web-based app and tailored messages to improve adherence to adjuvant endocrine therapy among women with breast cancer
Authors: Paladino Andrew J. , Anderson Janeane N. , Krukowski Rebecca A. , Waters Teresa , Kocak Mehmet , Graff Carolyn , Blue Ryan , Jones Tameka N. , Buzaglo Joanne , Vidal Gregory , Schwartzberg Lee , Graetz Ilana 
Published: December 2019

AbstractBackgroundLong-term use of adjuvant endocrine therapy (AET) among women with early-stage, hormone receptor-positive breast cancer significantly reduces the risk of hospitalizations, cancer recurrence, and mortality. AET is associated with adverse symptoms that often result in poor adherence. A web-enabled app offers a novel way to communicate and manage symptoms for women on AET. In a region with significant racial disparities in breast cancer outcomes, our study tests the impact of a web-enabled app that collects and transmits patient-reported symptoms to healthcare teams to facilitate timely and responsive symptom management on medication adherence.MethodsIn this randomized controlled trial, we randomize 300 patients initiating AET to one of three arms: 1) an “App” group (n = 100) that receives weekly reminders to use the THRIVE study app; 2) an “App+Feedback” group (n = 100) that receives weekly reminders and tailored feedback based on their use of the app; or 3) a “Usual Care” group (n = 100) that receives usual care only. Participants are stratified by race: 50% White and 50% Black. The duration of the intervention is six months following enrollment, and outcomes are assessed at 12-months. The primary outcome is adherence, which is captured using an electronic monitoring pillbox. Secondary outcomes include symptom burden, quality of life, self-efficacy for managing symptoms, and healthcare costs. We also evaluate the impact of the intervention on racial disparities in adherence. Data are derived from three sources: electronic health record data to capture treatment changes, healthcare utilization, and health outcomes; self-report survey data related to adherence, symptom burden, and quality of life; and an electronic medication monitoring device that captures adherence.DiscussionA successful web-enabled intervention could be disseminated across systems, conditions, and populations. By evaluating the impact of this intervention on a comprehensive set of measures, including AET adherence, patient outcomes, and costs, our study will provide valuable and actionable results for providers, policy makers, and insurers who strive to achieve the “Triple Aim” – reduce costs while improving health outcomes and the patient care experience.Trial registrationNCT03592771. Prospectively registered on July 19, 2018.
Multiple chronic conditions and associated health care expenses in US adults with cancer: a 2010–2015 Medical Expenditure Panel Survey study
Authors: Davis-Ajami Mary Lynn , Lu Zhiqiang K. , Wu Jun 
Published: December 2019

Abstract
Background
Cancer increases the risk of developing one or more chronic conditions, yet little research describes the associations between health care costs, utilization patterns, and chronic conditions in adults with cancer. The objective of this study was to examine the treated prevalence of chronic conditions and the association between chronic conditions and health care expenses in US adults with cancer.

Methods
This retrospective observational study used US Medical Expenditure Panel Survey (MEPS) Household Component (2010–2015) data sampling adults diagnosed with cancer and one or more of 18 select chronic conditions. The measures used were treated prevalence of chronic conditions, and total and chronic condition-specific health expenses (per-person, per-year). Generalized linear models assessed chronic condition-specific expenses in adults with cancer vs. without cancer and the association of chronic conditions on total health expenses in adults with cancer, respectively, by controlling for demographic and health characteristics. Accounting for the complex survey design in MEPS, all data analyses and statistical procedures applied longitudinal weights for national estimates.

Results
Among 3657 eligible adults with cancer, 83.9% (n = 3040; representing 16 million US individuals per-year) had at least one chronic condition, and 29.7% reported four or more conditions. Among those with cancer, hypertension (59.7%), hyperlipidemia (53.6%), arthritis (25.6%), diabetes (22.2%), and coronary artery disease (18.2%) were the five most prevalent chronic conditions. Chronic conditions accounted for 30% of total health expenses. Total health expenses were $6388 higher for those with chronic conditions vs. those without (p < 0.001). Health expenses associated with chronic conditions increased by 34% in adults with cancer vs. those without cancer after adjustment.

Conclusions
In US adults with cancer, the treated prevalence of common chronic conditions was high and health expenses associated with chronic conditions were higher than those without cancer. A holistic treatment plan is needed to improve cost outcomes.
Identifying relevant concepts and factors for the sustainability of evidence-based practices within acute care contexts: a systematic review and theory analysis of selected sustainability frameworks
Authors: Nadalin Penno Letitia , Davies Barbara , Graham Ian D. , Backman Chantal , MacDonald Ibo , Bain Julie , Johnson Alekhya Mascarenhas , Moore Julia , Squires Janet 
Published: December 2019

Abstract
Background
There is growing recognition among healthcare professionals that the sustainability of evidence-based practices (EBPs) within different settings is variable and suboptimal. Understanding why a particular EBP might be sustained in one setting and not another remains unclear. Recent reviews illustrate the need to identify and analyze existing frameworks/models/theories (F/M/Ts) that focus solely on the sustainability of EBPs in specific healthcare settings, such as acute care, to illuminate key determinants and facilitate appropriate selection to guide practice and research.

Methods
We conducted a systematic review to extract sustainability frameworks. This involved using two available syntheses of the literature and a systematic search of four databases from January 2015 to July 2018: CINHAL, MEDLINE, Embase, and ProQuest. We included studies published in English, and if they included sustainability F/M/Ts recommended for use in acute care or an unspecified healthcare organization/setting. F/M/Ts explicitly recommended for use in public health and or community settings were excluded. We then conducted a comparative analysis of F/M/Ts using a modified theory analysis approach, to understand the theoretical underpinnings of each F/M/T, their determinants and concepts hypothesized to influence the sustained use of EBPs within an acute care context.

Results
Of 2967 identified citations from the 2 available syntheses and the systematic review, 8 F/M/Ts met the inclusion criteria. We identified 37 core factors, of which 16 were recorded as common factors (occurring within 4 or more of the 8 included F/M/Ts). All factors grouped into 7 main themes: innovation, adopters, leadership and management, inner context, inner processes, outer context, and outcomes.

Conclusions
This systematic review is the first to include a comprehensive analysis of healthcare sustainability F/M/Ts for the sustained use of EBPs in acute care settings. Findings reveal insights into sustainability as a “process or ongoing stage of use” following initial implementation, suggesting this construct should be added to the definition of sustainability. Results provide a resource of available F/M/Ts and hypothesized factors to consider for acute care team members who are planning or currently implementing EBPs with the goal of improving patient outcomes. It also provides a basis for future research on sustainability in acute care.
The accuracy of species-specific allometric equations for estimating aboveground biomass in tropical moist montane forests: case study of Albizia grandibracteata and Trichilia dregeana
Authors: Daba Damena Edae , Soromessa Teshome 
Published: December 2019

Abstract
Background
Application of allometric equations for quantifying forests aboveground biomass is a crucial step related to efforts of climate change mitigation. Generalized allometric equations have been applied for estimating biomass and carbon storage of forests. However, adopting a generalized allometric equation to estimate the biomass of different forests generates uncertainty due to environmental variation. Therefore, formulating species-specific allometric equations is important to accurately quantify the biomass. Montane moist forest ecosystem comprises high forest type which is mainly found in the southwestern part of Ethiopia. Yayu Coffee Forest Biosphere Reserve is categorized into Afromontane Rainforest vegetation types in this ecosystem. This study was aimed to formulate species-specific allometric equations for Albizia grandibracteata Tuab. and Trichilia dregeana Sond. using the semi-destructive method.

Results
Allometric equations in form of power models were developed for each tree species by evaluating the statistical relationships of total aboveground biomass (TAGB) and dendrometric variables. TAGB was regressed against diameter at breast height (D), total height (H), and wood density (ρ) individually and in a combination. The allometric equations were selected based on model performance statistics. Equations with the higher coefficient of determination (adj.R2), lower residual standard error (RSE), and low Akaike information criterion (AIC) values were found best fitted. Relationships between TAGB and predictive variables were found statistically significant (p ≤ 0.001) for all selected equations. Higher bias was reported related to the application of pan-tropical or generalized allometric equations.

Conclusions
Formulating species-specific allometric equations is found important for accurate tree biomass estimation and quantifying the carbon stock. The developed biomass regression models can be applied as a species-specific equation to the montane moist forest ecosystem of southwestern Ethiopia.
Generating microglia from human pluripotent stem cells: novel in vitro models for the study of neurodegeneration
Authors: Speicher Anna M. , Wiendl Heinz , Meuth Sven G. , Pawlowski Matthias 
Published: December 2019

AbstractMicroglia play an essential role for central nervous system (CNS) development and homeostasis and have been implicated in the onset, progression, and clearance of numerous diseases affecting the CNS. Previous in vitro research on human microglia was restricted to post-mortem brain tissue-derived microglia, with limited availability and lack of scalability. Recently, the first protocols for the generation of microglia from human pluripotent stem cells have become available, thus enabling the implementation of powerful platforms for disease modeling, drug testing, and studies on cell transplantation. Here we give a detailed and comprehensive overview of the protocols available for generating microglia from human pluripotent stem cells, highlighting the advantages, drawbacks, and operability and placing them into the context of current knowledge of human embryonic development. We review novel insights into microglia biology and the role of microglia in neurological diseases as drawn from the new methods and provide an outlook for future lines of research involving human pluripotent stem cell-derived microglia.
The variome concept: focus on CNVariome
Authors: Iourov Ivan Y. , Vorsanova Svetlana G. , Yurov Yuri B. 
Published: December 2019

AbstractBackgroundVariome may be used for designating complex system of interplay between genomic variations specific for an individual or a disease. Despite the recognized complexity of genomic basis for phenotypic traits and diseases, studies of genetic causes of a disease are usually dedicated to the identification of single causative genomic changes (mutations). When such an artificially simplified model is employed, genomic basis of phenotypic outcomes remains elusive in the overwhelming majority of human diseases. Moreover, it is repeatedly demonstrated that multiple genomic changes within an individual genome are likely to underlie the phenome. Probably the best example of cumulative effect of variome on the phenotype is CNV (copy number variation) burden. Accordingly, we have proposed a variome concept based on CNV studies providing the evidence for the existence of a CNVariome (the set of CNV affecting an individual genome), a target for genomic analyses useful for unraveling genetic mechanisms of diseases and phenotypic traits.ConclusionVariome (CNVariome) concept suggests that a genomic milieu is determined by the whole set of genomic variations (CNV) within an individual genome. The genomic milieu is likely to result from interplay between these variations. Furthermore, such kind of variome may be either individual or disease-specific. Additionally, such variome may be pathway-specific. The latter is able to affect molecular/cellular pathways of genome stability maintenance leading to occurrence of genomic/chromosome instability and/or somatic mosaicism resulting in somatic variome. This variome type seems to be important for unraveling disease mechanisms, as well. Finally, it appears that bioinformatic analysis of both individual and somatic variomes in the context of diseases- and pathway-specific variomes is the most promising way to determine genomic basis of the phenome and to unravel disease mechanisms for the management and treatment of currently incurable diseases.
Two case reports of fetal alcohol syndrome: broadening into the spectrum of cardiac disease to personalize and to improve clinical assessment
Authors: Onesimo R. , De Rose C. , Delogu A. B. , Battista A. , Leoni C. , Veltri S. , De Rosa G. , Zampino G. 
Published: December 2019

Abstract
Background
Fetal alcohol spectrum disorder (FASD) refers to a broad spectrum of disabilities, in infants and children, resulting from moderate to excessive prenatal alcohol exposure.
Significant associations with alcohol exposure were already reported with congenital structural heart defects: i.e. ventricular septal defects, atrial septal defects, conotruncal defects.

Cases presentation
We describe two cases of children with FASD, both admitted to the Center for Rare Diseases and Birth Defects of Policlinico Universitario Agostino Gemelli, in whom asymptomatic cardiac rhythm alterations were detected in absence of structural cardiovascular system anomalies or cardiac channelopathies.

Conclusions
No other reports about cardiac rhythm anomalies in individuals affected by FASD are actually available from the literature.
We would like to make an alert for clinician, given the possibility of finding anomalies of heart conduction and rhythm in children affected by FASD even without structural congenital heart disease.
Variable- versus constant-frequency deep-brain stimulation in patients with advanced Parkinson’s disease: study protocol for a randomized controlled trial
Authors: Jia Fumin , Zhang Jianguo , Wang Huimin , Liang Zhanhua , Liu Weiguo , Wang Xuelian , Liu Yiming , Guo Yi , Ling Zhipei , Cai Xiaodong , Wu Xi , Wu Jianjun , Lv Wen , Xu Xin , Zhang Wenbin , Li Luming 
Published: December 2019

Abstract
Background
Deep-brain stimulation targeting the subthalamic nucleus (STN) can be used to treat motor symptoms and dyskinesia in the advanced stages of Parkinson’s disease (PD). High-frequency stimulation (HFS) of the STN can lead to consistent, long-term improvement of PD symptoms. However, the effects of HFS on the axial symptoms of PD, specifically freezing of gait, can be limited or cause further impairment. While this can be alleviated via relatively low-frequency stimulation (LFS) in selected patients, LFS does not control all motor symptoms of PD. Recently, the National Engineering Laboratory for Neuromodulation reported preliminary findings regarding an efficient way to combine the advantages of HFS and LFS to form variable-frequency stimulation (VFS). However, this novel therapeutic strategy has not been formally tested in a randomized trial.

Methods/design
We propose a multicenter, double-blind clinical trial involving 11 study hospitals and an established deep-brain stimulation team. The participants will be divided into a VFS and a constant-frequency stimulation group. The primary outcome will be changes in stand–walk–sit task scores after 3 months of treatment in the “medication off” condition. Secondary outcome measures include specific item scores on the Freezing of Gait Questionnaire and quality of life. The aim of this trial is to investigate the efficacy and safety of VFS compared with constant-frequency stimulation.

Discussion
This is the first randomized controlled trial to comprehensively evaluate the effectiveness and safety of VFS of the STN in patients with advanced PD. VFS may represent a new option for clinical treatment of PD in the future.

Trial registration
ClinicalTrials.gov, NCT03053726. Registered on February 15, 2017.
Contribution of aroma compounds to the antioxidant properties of roasted white yam (Dioscorea rotundata)
Authors: Lasekan Ola , Teoh Li Shing 
Published: December 2019

Abstract
Background
The aroma chemistry and the contribution of the aroma compounds to the anti-oxidative properties of roasted yam have yet to be characterized. The growing popularity of roasted yam in regions where they are being consumed calls for a concerted effort to elucidate their aroma chemistry as well as their anti-oxidative properties.

Results
The aroma compounds in roasted white yam (Dioscorea rotundata) were isolated and identified using static headspace-gas chromatography-mass spectrometry (SH–GC–MS) and gas chromatography–olfactometry (GC–O). In addition, the anti-oxidative activities of the most abundant volatile heterocyclic compounds (2 pyrroles, 4 furans and 3 pyrazines) were evaluated on their inhibitory effect towards the oxidation of hexanal for a period of 30 days. Twenty-nine aroma-active compounds with a flavour dilution (FD) factor range of 2–256 and an array of odour notes were obtained. Among them, the highest odour activities (FD ≥ 128) factors were determined for 2-acetyl furan and 2-acetylpyrrole. Other compounds with significant FD factors ≥ 32 were; 2-methylpyrazine, ethyl furfural, and 5-hydroxy methyl furfural.

Conclusion
Results of the anti-oxidative activity showed that the pyrroles exhibited the greatest antioxidant activity among all the tested heterocyclic compounds. This was followed by the furans and the pyrazines which had the least antioxidant activity.
Efficacy and safety of evogliptin in the treatment of type 2 diabetes mellitus in a Brazilian population: a randomized bridging study
Authors: Cercato Cintia , Felício Joao Soares , Russo Luis Augusto Tavares , Borges Joao Lindolfo Cunha , Salles Joao , Muskat Patricia , Bonansea Teresa , Chacra Antonio Roberto , Eliaschewitz Freddy Goldberg , Forti Adriana Costa 
Published: December 2019

Abstract
Background
Evogliptin (EVO) is a potent and selective dipeptidyl peptidase-4 inhibitor (DPP4i) developed for the treatment of type 2 diabetes mellitus (T2DM). DPP4is are known to exhibit a better glucose-lowering effect in Asians compared to other ethnic groups. Once EVO’s clinical development program was conducted in Asian patients, this bridging study was designed to validate for the Brazilian population the efficacy and safety of the approved dose regimen (once-daily 5.0 mg).

Methods
In this randomized, double-blind, double-dummy, parallel trial, 146 patients with T2DM with inadequate glycemic control on diet and exercise (7.5% ≤ HbA1c ≤ 10.5%) were randomly assigned to a 12-week once-daily treatment with EVO 2.5 mg (N = 35), EVO 5 mg (N = 36), EVO 10 mg (N = 36), or sitagliptin (SITA) 100 mg (N = 39). Absolute changes (Week 12—baseline) in HbA1c, fasting plasma glucose (FPG) and body weight (BW) were obtained. One-sided one sample t test was used to determine if mean HbA1c reduction in each group was < − 0.5% (beneficial metabolic response). An analysis of covariance estimated the change in HbA1c and FPG adjusted by baseline HbA1c, FPG, body mass index (BMI) and study site. Response rates to treatment were also established. No between-group statistical comparisons were planned.

Results
HbA1c mean reductions were − 1.26% (90% CI − 1.7%, − 0.8%), − 1.12% (90% CI − 1.4%, − 0.8%), − 1.29% (90% CI − 1.6%, − 1.0%), and − 1.15% (90% CI − 1.5%, − 0.8%) in groups EVO 2.5 mg, EVO 5 mg, EVO 10 mg, and SITA 100 mg, respectively. FPG levels showed a mean increase of 10.89 mg/dL in group EVO 2.5 mg, with significant mean reductions of − 18.94 mg/dL, − 21.17 mg/dL, and − 39.90 mg/dL in those treated with EVO 5 mg, EVO 10 mg, and SITA 100 mg, respectively. BW showed significant reductions of approximately 1 kg in patients treated with EVO 5 mg, EVO 10 mg, and SITA 100 mg. Mean adjusted reductions of HbA1c and FPG levels confirmed the significant clinical benefit of all study treatments. The clinical benefit of EVO’s “target” dose (5 mg) was confirmed. No safety concerns were identified.

Conclusions
These results validate for the Brazilian population the approved dose regimen of EVO (once-daily 5 mg).
Trial registration ClinicalTrials.gov Identifier: NCT02689362 (first posted on 02/23/2016).
64Cu-ATSM/64Cu-Cl2 and their relationship to hypoxia in glioblastoma: a preclinical study
Authors: Pérès Elodie A. , Toutain Jérôme , Paty Louis-Paul , Divoux Didier , Ibazizène Méziane , Guillouet Stéphane , Barré Louisa , Vidal Aurélien , Cherel Michel , Bourgeois Mickaël , Bernaudin Myriam , Valable Samuel 
Published: December 2019

Abstract
Background
Diacetyl-bis(N4-methylthiosemicarbazone), labeled with 64Cu (64Cu-ATSM) has been suggested as a promising tracer for imaging hypoxia. However, various controversial studies highlighted potential pitfalls that may disable its use as a selective hypoxic marker. They also highlighted that the results may be tumor location dependent. Here, we first analyzed uptake of Cu-ATSM and its less lipophilic counterpart Cu-Cl2 in the tumor over time in an orthotopic glioblastoma model. An in vitro study was also conducted to investigate the hypoxia-dependent copper uptake in tumor cells. We then further performed a comprehensive ex vivo study to compare 64Cu uptake to hypoxic markers, specific cellular reactions, and also transporter expression.

Methods
μPET was performed 14 days (18F-FMISO), 15 days (64Cu-ATSM and 64Cu-Cl2), and 16 days (64Cu-ATSM and 64Cu-Cl2) after C6 cell inoculation. Thereafter, the brains were withdrawn for further autoradiography and immunohistochemistry. C6 cells were also grown in hypoxic workstation to analyze cellular uptake of Cu complexes in different oxygen levels.

Results
In vivo results showed that Cu-ASTM and Cu-Cl2 accumulated in hypoxic areas of the tumors. Cu-ATSM also stained, to a lesser extent, non-hypoxic regions, such as regions of astrogliosis, with high expression of copper transporters and in particular DMT-1 and CTR1, and also characterized by the expression of elevated astrogliosis. In vitro results show that 64Cu-ATSM showed an increase in the uptake only in severe hypoxia at 0.5 and 0.2% of oxygen while for 64Cu-Cl2, the cell retention was significantly increased at 5% and 1% of oxygen with no significant rise at lower oxygen percentages.

Conclusion
In the present study, we show that Cu-complexes undoubtedly accumulate in hypoxic areas of the tumors. This uptake may be the reflection of a direct dependency to a redox metabolism and also a reflection of hypoxic-induced overexpression of transporters. We also show that Cu-ATSM also stained non-hypoxic regions such as astrogliosis.