bluuebunny/crossref_metadata_2025_split huggingface dataset:
PARP1/2 imaging with 18F-PARPi in patients with head and neck cancer
Authors: Schöder Heiko , De Souza França Paula Demétrio , Nakajima Reiko , Burnazi Eva , Roberts Sheryl , Brand Christian , Grkovski Milan , Mauguen Audrey , Dunphy Mark P. , Ghossein Ronald A. , Lyashchenko Serge , Lewis Jason S. , O’Donoghue Joseph A. , Ganly Ian , Patel Snehal G. , Lee Nancy Y. , Reiner Thomas 
Published: November 2019

AbstractPurposeWe performed a first-in-human clinical trial. The aim of this study was to determine safety and feasibility of PET imaging with 18F-PARPi in patients with head and neck cancer.Patients and MethodsEleven patients (age 49 to 86 years) with newly diagnosed or recurrent oral and oropharyngeal cancer were injected intravenously with 18F-PARPi (331 ± 42 MBq) and dynamic PET/CT imaging was performed between 0 min and 25 min post-injection. Static PET/CT scans were obtained at 30 min, 60 min and 120 min p.i. Blood samples for tracer concentration and metabolite analysis were collected. Blood pressure, ECG, oxygen levels, clinical chemistry and CBC were obtained before and after administration of 18F-PARPi.Results18F-PARPi was well-tolerated by all patients without any safety concerns. Of the 11 patients included in the analysis, 18F-PARPi had focal uptake in all primary lesions (n = 10, SUVmax = 2.8 ± 1.2) and all 18F-FDG positive lymph nodes (n = 34). 18F-PARPi uptake was seen in 18F-FDG negative lymph nodes of three patients (n = 6). Focal uptake of tracer in primary and metastatic lesions was corroborated by CT alone or in combination with 18F-FDG. Contrast for 18F-PARPi and 18F-FDG was comparable (SUVmax(lesion)/SUVmax(genioglossus) = 3.3 and 3.0, respectively; p = 0.23), and SUVmax values for 18F-PARPi were less variable compared to 18F-FDG (1.3 versus 6.0, p = 0.001).ConclusionsImaging of head and neck cancer with 18F-PARPi is feasible and safe. 18F-PARPi detects primary and metastatic lesions, and retention in tumors is longer than in healthy tissues.
Aggregating Multiple Real-World Data Sources using a Patient-Centered Health Data Sharing Platform: an 8-week Cohort Study among Patients Undergoing Bariatric Surgery or Catheter Ablation of Atrial Fibrillation
Authors: Dhruva Sanket S. , Ross Joseph S. , Akar Joseph G. , Caldwell Brittany , Childers Karla , Chow Wing , Ciaccio Laura , Coplan Paul , Dong Jun , Dykhoff Hayley J. , Johnston Stephen , Kellogg Todd , Long Cynthia , Noseworthy Peter A. , Roberts Kurt , Saha Anindita , Yoo Andrew , Shah Nilay D. 
Published: November 2019

ABSTRACTReal-world data sources, including electronic health records (EHR) and personal digital device data, are increasingly available, but are often siloed and cannot be easily integrated for clinical, research, or regulatory purposes. We conducted a prospective cohort study of 60 patients undergoing bariatric surgery or catheter-based atrial fibrillation ablation at two U.S. tertiary care hospitals, testing the feasibility of using a patient-centered health data sharing platform to obtain and aggregate health data from multiple sources. We successfully obtained EHR data for all patients at both hospitals, as well as from 10 additional health systems, which were successfully aggregated with pharmacy data obtained for patients using CVS or Walgreens pharmacies, personal digital device data from activity monitors, digital weight scales, and single-lead ECGs, and patient-reported outcome measure data obtained through surveys to assess post-procedure recovery and disease-specific symptoms. A patient-centered health data sharing platform successfully aggregated data from multiple sources.
Predicting Current Juul use among Emerging Adults through Twitter Feeds
Authors: Tran Tung , Ickes Melinda , Hester Jakob W. , Kavuluru Ramakanth 
Published: November 2019

AbstractIntroductionCan we predict whether someone uses Juul based on their social media activities? This is the central premise of the effort reported in this paper. Several recent social media-related studies on Juul use tend to focus on the characterization of Juul-related messages on social media. In this study, we assess the potential in using machine learning methods to automatically identify whether an individual uses Juul (past 30-day usage) based on their Twitter data.MethodsWe obtained a collection of 588 instances, for training and testing, of Juul use patterns (along with associated Twitter handles) via survey responses of college students. With this data, we built and tested supervised machine learning models based on linear and deep learning algorithms with textual, social network (friends and followers), and other hand-crafted features.ResultsThe linear model with textual and follower network features performed best with a precision-recall trade-off such that precision (PPV) is 57% at 24% recall (sensitivity). Hence, at least every other college-attending Twitter user flagged by our model is expected to be a Juul user. Additionally, our results indicate that social network features tend to have a large impact (positive) on predictive performance.ConclusionThere are enough predictive signals from social feeds for supervised modeling of Juul use, even with limited training data, implying that such models are highly beneficial to very focused intervention campaigns. Moreover, this initial success indicates potential for more involved automated surveillance of Juul use based on social media data, including Juul usage patterns, nicotine dependency, and risk awareness.
DNA methylation outlier burden, health and ageing in Generation Scotland and the Lothian Birth Cohorts of 1921 and 1936
Authors: Seeboth Anne , McCartney Daniel L. , Wang Yunzhang , Hillary Robert F. , Stevenson Anna J. , Walker Rosie M. , Evans Kathryn L. , McIntosh Andrew M. , Hägg Sara , Deary Ian J. , Marioni Riccardo E. 
Published: November 2019

AbstractDNA methylation outlier burden has been suggested as a potential marker of biological age. An outlier is typically defined as DNA methylation levels at any one CpG site that are three times beyond the inter-quartile range from the 25th or 75th percentiles compared to the rest of the population. DNA methylation outlier burden (the number of such outlier sites per individual) increases exponentially with age. However, these findings have been observed in small samples. Here, we showed an association between age and log10-transformed DNA methylation outlier burden in a large cross-sectional cohort, the Generation Scotland Family Health Study (N=7,010, β=0.0091, p<2×10−16), and in two longitudinal cohort studies, the Lothian Birth Cohorts of 1921 (N=430, β=0.033, p=7.9×10−4) and 1936 (N=898, β=7.9×10−3, p=0.074). Significant confounders of both cross-sectional and longitudinal associations between outlier burden and age included white blood cell proportions, BMI, smoking, and batch effects. In Generation Scotland, the increase in epigenetic outlier burden with age was not purely an artefact of an increase in DNA methylation level variability with age (epigenetic drift). Log10-transformed DNA methylation outlier burden in Generation Scotland was not related to self-reported, or family history of, age-related diseases and it was not heritable (SNP-based heritability of 4.4%, p=0.18). Finally, DNA methylation outlier burden was not significantly related to survival in either of the Lothian Birth Cohorts individually but it was in a meta-analysis (HRmeta=1.12; 95%CImeta=[1.02; 1.21]; pmeta=0.021). These findings suggest that, while it does not associate with ageing-related health outcomes, DNA methylation outlier burden does track chronological ageing and may also relate to survival. DNA methylation outlier burden may thus be useful as a marker of biological ageing.
Effect of indoor air pollution on infant and child-mortality in Myanmar: Evidence from the first Demographic and Health Survey
Authors: Rana Juwel , Khan Md Nuruzzaman , Aliani Razia , Islam Rakibul M 
Published: November 2019

AbstractBackgroundIndoor air pollution (IAP) from solid fuels for cooking has been considered as a public health threat, particularly for women and children in low- and lower-middle-income countries (LMICs). We investigated the effects of solid fuel use (SFU) on neonatal, infant and under-five child mortality in Myanmar.Materials and MethodsWe used data from Myanmar’s first Demographic and Health Survey conducted in 2016. The sample consists of ever-married mothers with under-five children in the household (n=3249). We calculated the adjusted odds ratio (aOR) to investigate the effects of SFU on neonatal, infant, and under-five mortality using multivariable logistic regression model accounting for survey weight and clustering. Additional analysis was conducted using an augmented measure of the exposure to IAP accounting for both SFU and the location of cooking (high exposure, moderate, and unexposed).ResultsThe prevalence of SFU was 79.0%, and the neonatal, infant and the under-five mortality rates were 26, 45 and 49 per 1,000 live births, respectively. The odds of infant (aOR 2.17, 95% CI: 1.21, 3.88) and under-five child mortality (aOR 2.22, 95% CI: 1.24, 3.95) were higher in households with SFU compared with households with clean fuel use. When applying an augmented measure of exposure to IAP by incorporating both SFU and the kitchen’s location, the likelihood of infant and under-five mortality was higher among moderately and highly exposed children compared to unexposed children with similar trends. Neonatal mortality was not associated with both SFU and levels of exposure to IAP.ConclusionInfants and under-five children are at higher risk of mortality from exposure to IAP. The findings suggest that the risk of infants and under-five child mortality may be reduced by increasing access to clean cookstoves and clean fuels in LMICs, especially in Myanmar.
Impact of Radiation on Cardiovascular Outcomes in Patients with Resectable Esophageal Cancer
Authors: Sarkar Reith R , Hatamipour Ahmadreza , Panjwani Neil , Courtney Patrick T , Cherry Daniel R , Salans Mia A , Yip Anthony T , Rose Brent S , Simpson Daniel R , Banegas Matthew P , Murphy James D 
Published: November 2019

AbstractPurposePreoperative radiation therapy improves outcomes for operable esophageal cancer patients, though the proximity of the heart to the esophagus puts patients at risk of radiation-induced cardiovascular disease. This study characterizes the impact of radiation therapy and different radiation techniques on cardiovascular morbidity among a large cohort of esophageal cancer patients.MethodsWe identified 1,125 Medicare beneficiaries diagnosed between 2000 and 2011 with esophageal cancer who received surgery alone, or surgery preceded by either preoperative chemotherapy or preoperative chemoradiation. We used Medicare claims to identify severe adverse cardiovascular events in the perioperative and postoperative periods. Multivariable logistic regression and Fine-Gray models were used to determine the effect of pre-surgery treatment on the risk of perioperative and postoperative cardiovascular disease.ResultsPreoperative chemotherapy or preoperative chemoradiation did not significantly increase the risk of perioperative cardiovascular complications compared to surgery alone. Patients treated with preoperative chemoradiation had a 36% increased risk of having a postoperative cardiovascular event compared to patients treated with surgery alone (subdistribution hazard ratio [SDHR] 1.36; p=0.035). There was no significant increase in cardiovascular events among patients treated with preoperative chemotherapy (SDHR 1.18; p=0.40). Among patients treated with preoperative chemoradiation, those receiving intensity modulated radiotherapy (IMRT) had a 68% decreased risk of having a cardiovascular event compared to patients receiving conventional radiation (SDHR 0.32; p=0.007).ConclusionsThis study demonstrates an increased risk of cardiovascular complications among operative esophageal cancer patients treated with preoperative chemoradiation, though these risks might be reduced with more cardioprotective radiation techniques such as IMRT.
Validity of using cancer registry data for comparative effectiveness research
Authors: Kumar Abhishek , Guss Zachary D , Courtney Patrick T , Nalawade Vinit , Sheridan Paige , Sarkar Reith R , Banegas Matthew P , Rose Brent S , Xu Ronghui , Murphy James D 
Published: November 2019

AbstractPurposeResearchers often analyze cancer registry data to assess for differences in survival among cancer treatments. However, the retrospective non-random design of these analyses raise questions about study validity. The purpose of this study was to determine the extent to which comparative effectiveness analyses using cancer registry data produces results concordant with randomized clinical trials.MethodsWe identified 141 randomized clinical trials referenced in the National Comprehensive Cancer Network Clinical Practice Guidelines for 8 common solid tumor types. For each trial we identified subjects from the National Cancer Database (NCDB) matching the eligibility criteria of the randomized trial. With each trial we used three Cox regression models to determine hazard ratios (HRs) for overall survival including univariable, multivariable, and propensity score adjusted models. Multivariable and propensity score analyses controlled for potential confounders including demographic, comorbidity, clinical, treatment, and tumor-related variables. Each NCDB survival analysis was defined as discordant if the HR for the NCDB analysis fell outside the 95% confidence interval of the corresponding randomized trial.ResultsNCDB analyses produced HRs for survival discordant with randomized trials in 62 (44%) univariable analyses, 43 (30%) multivariable analyses, and 51 (36%) propensity score models. NCDB analyses produced p-values discordant with randomized trials in 83 (59%) univariable analyses, 76 (54%) multivariable analyses, and 78 (55%) propensity score models. We did not identify any clinical trial characteristic associated with discordance between NCDB analyses and randomized trials including disease site, type of clinical intervention, or severity of cancer.ConclusionComparative effectiveness research with cancer registry data often produces survival outcomes discordant to randomized clinical data. These findings help provide context for providers interpreting observational comparative effectiveness research in oncology.
Physicians’ learning in the workplace: use of informal feedback cues in daily practice
Authors: Sehlbach Carolin , Teunissen Pim W , Driessen Erik W , Mitchell Sharon , Rohde Gernot GU , Smeenk Frank WJM , Govaerts Marjan JB 
Published: November 2019

ABSTRACTPurposeWe expect physicians to be lifelong learners. Learning from clinical practice is an important potential source for that learning. To support physicians in this process, a better understanding of how they learn in clinical practice is necessary. This study investigates how physicians use informal feedback as learning cues to adjust their communication from interactions with patients in the outpatient setting.MethodsTo understand physicians’ use of informal feedback, we combined non-participant ethnographic observations with semi-structured interviews. We enrolled 10 respiratory physicians and observed 100 physician-patient interactions at one academic and one non-academic hospital in the Netherlands. Data collection and analysis were performed iteratively according to the principles of constructivist grounded theory. Our conceptual model describes how physicians use cues to reflect on and adjust their communication as well as to further develop their adaptive expertise.ResultsIn addition to vast variations within and across patient encounters, we observed recurring patterns in physicians’ communications in reaction to specific learning cues. Physicians had learnt to recognise and use different cues to adjust their communication in patient encounters. They established a ‘communication repertoire’ based on multiple patient interactions, which many saw as learning opportunities, contributing to the development of adaptive expertise. Our findings show differences in physicians’ sensitivity to recognising learning opportunities in daily practice which was further influenced by contextual, personal and interpersonal factors. Whereas some reported to have little inclination to change, others used critical incidents to fine-tune their communication repertoire, while others constantly reshaped it, seeking learning opportunities in their daily work.ConclusionsThere is a large variation in how physicians use learning cues from daily practice. Learning from daily practice is a collaborative effort and requires a culture that promotes lifelong learning. Raising physicians’ awareness of experiences as potential learning opportunities might enhance their development of adaptive expertise.
Functional role of respiratory supercomplexes in mice: segmentation of the Qpool and SCAF1
Authors: Calvo Enrique , Cogliati Sara , Hernansanz-Agustín Pablo , Loureiro-López Marta , Guarás Adela , Casuso Rafael A. , García-Marqués Fernando , Acín-Pérez Rebeca , Martí-Mateos Yolanda , Silla-Castro JC. , Carro-Alvarellos Marta , Huertas Jesús R. , Vázquez Jesús , Enríquez J.A. 
Published: November 2019

SummaryMitochondrial respiratory complexes assemble into different forms of supercomplexes (SC). In particular, SC III2+IV require the SCAF1 protein. However, the structural role of this factor in the formation of the respirasome (I+III2+IV) and the physiological role of SCs are controversial. Here, we study C57BL/6J mice harbouring either non-functional SCAF1, the full knock-out for SCAF1 or the wild-type version of the protein and found a growth and exercise phenotype due to the lack of functional SCAF1. By combining quantitative data-independent proteomics, high resolution 2D Blue Native Gel Electrophoresis and functional analysis of enriched respirasome fractions, we show that SCAF1 confers structural attachment between III2 and IV within the respirasome, increases NADH-dependent respiration and reduces ROS production. Furthermore, through the expression of AOX in cells and mice we confirm that CI-CIII superassembly segments the CoQ in two pools and modulates CI-NADH oxidative capacity. These data demonstrate that SC assembly, regulated by SCAF1, modulates the functionality of the electron transport chain.
Experimental control of macrophage pro-inflammatory dynamics using predictive models
Authors: Weinstock Laura D. , Forsmo James E. , Wilkinson Alexis , Ueda Jun , Wood Levi B. 
Published: November 2019

ABSTRACTMacrophage activity is a major component of the healthy response to infection and injury that consists of tightly regulated early pro-inflammatory activation followed by anti-inflammatory and regenerative activity. In numerous diseases, however, macrophage polarization becomes dysregulated and can not only impair recovery, but can also promote further injury and pathogenesis, e.g. after injury, in diabetes, or in Alzheimer’s disease. Dysregulated macrophages may either fail to polarize or become chronically polarized, resulting in increased production of cytotoxic factors, diminished capacity to clear pathogens, or failure to promote tissue regeneration. In these cases, a method of predicting and dynamically controlling macrophage polarization will enable a new strategy for treating diverse inflammatory diseases. In this work, we developed a model-predictive control framework to temporally regulate macrophage polarization. Using RAW 264.7 macrophages as a model system, we enabled temporal control by identifying transfer function models relating the polarization marker iNOS to exogenous pro- and anti-inflammatory stimuli. These stimuli-to-iNOS response models were identified using linear autoregressive with exogenous input terms (ARX) equations and were coupled with nonlinear elements to account for experimentally identified supra-additive and hysteretic effects. Using this model architecture, we were able to reproduce experimentally observed temporal iNOS dynamics induced with lipopolysaccharides (LPS) and interferon gamma (IFN-γ). Moreover, the identified model enabled the design of time-varying input trajectories to experimentally sustain the duration and magnitude of iNOS expression. By designing transfer function models with the intent to predict cell behavior, we were able to predict and experimentally obtain temporal regulation of iNOS expression using LPS and IFN-γ from both naïve and non-naïve initial states. Moreover, our data driven models revealed decaying magnitude of iNOS response to LPS stimulation over time that could be recovered using combined treatment with both LPS and IFN-γ. Given the importance of dynamic tissue macrophage polarization and overall inflammatory regulation to a broad number of diseases, the temporal control methodology presented here will have numerous applications for regulating immune activity dynamics in chronic inflammatory diseases.
A statistical framework for measuring reproducibility and replicability of high-throughput experiments from multiple sources
Authors: Ranalli Monia , Lyu Yafei , Koch Hillary , Li Qunhua 
Published: November 2019

SummaryReplication is essential to reliable and consistent scientific discovery in high-throughput experiments. Quantifying the replicability of scientific discoveries and identifying sources of irreproducibility have become important tasks for quality control and data integration. In this work we introduce a novel statistical model to measure the reproducibility and replicability of findings from replicate experiments in multi-source studies. Using a nested copula mixture model that characterizes the interdependence between replication experiments both across and within sources, our method quantifies reproducibility and replicability of each candidate simultaneously in a coherent framework. Through simulation studies, an ENCODE ChIP-seq dataset and a SEQC RNA-seq dataset, we demonstrate the effectiveness of our method in diagnosing the source of discordance and improving the reliability of scientific discoveries.
Soil Water Carrying Capacity for Vegetation
Authors: Guo Zhong-sheng 
Published: November 2019

AbstractNon-native plantation can effectively conserve soil and water and improve ecological environment,but soil desiccation occurs and then changes to severe desiccation in most forest and grass lands of water-limited regions, which causes soil degradation, vegetation decline and crop failure, so it is necessary to regulate the changed relationship between plant growth and soil water. However, there is a lack of a universally accepted theory to provide guidance of sustainable use of soil water resources and sustainable management of forest and sustainable produce of crop in such regions. The theory of regulating the relationship between plant growth and soil water in water-limited regions includes the Soil Water Resources Use Limit by Plant (SWRULP) and Soil Water Carrying Capacity for Vegetation (SWCCV). The SWCCV is the population in a plant population or density of indicator plants in a plant community when the soil water supply is equal to soil water consumption in the root zone and a given time, and changes with plant community type, location and time. The degree of coverage, productivity and benefits of a plant community when population quantity of an indicator plant equals SWCCV should be the theoretical basis for ensuring sustainable use of soil water resources and sustainable development of forest.