bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effectiveness of Electronic Cigarettes in Smoking Cessation: A Systematic Review and Meta-analysis
Authors: Grabovac Igor , Oberndorfer Moritz , Fischer Jismy , Wiesinger Winfried , Haider Sandra , Dorner Thomas Ernst 
Published: September 2020

AbstractIntroductionReports of the effectiveness of e-cigarettes (ECs) for smoking cessation vary across different studies making implementation recommendations hard to attain. We performed a systematic review and meta-analysis to assess the current evidence regarding effectiveness of ECs for smoking cessation.MethodsPubMed, PsycInfo, and Embase databases were searched for randomized controlled trials comparing nicotine ECs with non-nicotine ECs or with established smoking cessation interventions (nicotine replacement therapy [NRT] and or counseling) published between 1 January 2014 and 27 June 2020. Data from eligible studies were extracted and used for random-effects meta-analyses (PROSPERO registration number: CRD42019141414).ResultsThe search yielded 13 950 publications with 12 studies being identified as eligible for systematic review (N = 8362) and 9 studies for random-effects meta-analyses (range: 30–6006 participants). The proportion of smokers achieving abstinence was 1.71 (95 CI: 1.02–2.84) times higher in nicotine EC users compared with non-nicotine EC users. The proportion of abstinent smokers was 1.69 (95 CI: 1.25–2.27) times higher in EC users compared with participants receiving NRT. EC users showed a 2.04 (95 CI: 0.90–4.64) times higher proportion of abstinent smokers in comparison with participants solely receiving counseling.ConclusionsOur results suggest that nicotine ECs may be more effective in smoking cessation when compared with placebo ECs or NRT. When compared with counseling alone, nicotine ECs are more effective short term, but its effectiveness appears to diminish with later follow-ups. Given the small number of studies, heterogeneous design, and the overall moderate to low quality of evidence, it is not possible to offer clear recommendations.ImplicationsThe results of this study do not allow for a conclusive argument. However, pooling current evidence points toward a potential for ECs as a smoking cessation tool. Though, given the overall quality of evidence, future studies should aim for more clarity in terms of interventions and larger study populations.
Transdisciplinary research outcomes based on the Transdisciplinary Research on Energetics and Cancer II initiative experience
Authors: Hohl Sarah D , Knerr Sarah , Gehlert Sarah , Neuhouser Marian L , Beresford Shirley A A , Unger Joseph M , Fishman Paul A , Thompson Beti 
Published: September 2020

Abstract
Intractable public health problems are influenced by interacting multi-level factors. Dynamic research approaches in which teams of scientists collaborate beyond traditional disciplinary, institutional, and geographic boundaries have emerged as promising strategies to address pressing public health priorities. However, little prior work has identified, defined, and characterized the outcomes of transdisciplinary (TD) research undertaken to address public health problems. Through a mixed methods approach, we identify, define, and characterize TD outcomes and their relevance to improving population health using the Transdisciplinary Research on Energetics and Cancer (TREC) II initiative as a case example. In Phase I, TREC II leadership (n = 10) identified nine initial TD outcomes. In Phase II (web-based survey; n = 23) and Phase III (interviews; n = 26; and focus groups, n = 23) TREC members defined and characterized each outcome. The resulting nine outcomes are described. The nine complementary TD outcomes can be used as a framework to evaluate progress toward impact on complex public health problems. Strategic investment in infrastructure that supports team development and collaboration, such as a coordination center, cross-center working groups, annual funded developmental projects, and face-to-face meetings, may foster achievement of these outcomes. This exploratory work provides a basis for the future investigation and development of quantitative measurement tools to assess the achievement of TD outcomes that are relevant to solving multifactorial public health problems.
A Review of the Functional Roles of the Zebrafish Aryl Hydrocarbon Receptors
Authors: Shankar Prarthana , Dasgupta Subham , Hahn Mark E , Tanguay Robyn L 
Published: September 2020

Abstract
Over the last 2 decades, the zebrafish (Danio rerio) has emerged as a stellar model for unraveling molecular signaling events mediated by the aryl hydrocarbon receptor (AHR), an important ligand-activated receptor found in all eumetazoan animals. Zebrafish have 3 AHRs—AHR1a, AHR1b, and AHR2, and studies have demonstrated the diversity of both the endogenous and toxicological functions of the zebrafish AHRs. In this contemporary review, we first highlight the evolution of the zebrafish ahr genes, and the characteristics of the receptors including developmental and adult expression, their endogenous and inducible roles, and the predicted ligands from homology modeling studies. We then review the toxicity of a broad spectrum of AHR ligands across multiple life stages (early stage, and adult), discuss their transcriptomic and epigenetic mechanisms of action, and report on any known interactions between the AHRs and other signaling pathways. Through this article, we summarize the promising research that furthers our understanding of the complex AHR pathway through the extensive use of zebrafish as a model, coupled with a large array of molecular techniques. As much of the research has focused on the functions of AHR2 during development and the mechanism of TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) toxicity, we illustrate the need to address the considerable knowledge gap in our understanding of both the mechanistic roles of AHR1a and AHR1b, and the diverse modes of toxicity of the various AHR ligands.
Tobacco Smoke Exposure Exacerbated Crystalline Silica-Induced Lung Toxicity in Rats
Authors: Sager Tina M , Umbright Christina M , Mustafa Gul Mehnaz , Yanamala Naveena , Leonard Howard D , McKinney Walter G , Kashon Michael L , Joseph Pius 
Published: September 2020

Abstract
Smoking may modify the lung response to silica exposure including cancer and silicosis. Nevertheless, the precise role of exposure to tobacco smoke (TS) on the lung response to crystalline silica (CS) exposure and the underlying mechanisms need further clarification. The objectives of the present study were to determine the role of TS on lung response to CS exposure and the underlying mechanism(s). Male Fischer 344 rats were exposed by inhalation to air, CS (15 mg/m3, 6 h/day, 5 days), TS (80 mg/m3, 3 h/day, twice weekly, 6 months), or CS (15 mg/m3, 6 h/day, 5 days) followed by TS (80 mg/m3, 3 h/day, twice weekly, 6 months). The rats were euthanized 6 months and 3 weeks following initiation of the first exposure and the lung response was assessed. Silica exposure resulted in significant lung toxicity as evidenced by lung histological changes, enhanced neutrophil infiltration, increased lactate dehydrogenase levels, enhanced oxidant production, and increased cytokine levels. The TS exposure alone had only a minimal effect on these toxicity parameters. However, the combined exposure to TS and CS exacerbated the lung response, compared with TS or CS exposure alone. Global gene expression changes in the lungs correlated with the lung toxicity severity. Bioinformatic analysis of the gene expression data demonstrated significant enrichment in functions, pathways, and networks relevant to the response to CS exposure which correlated with the lung toxicity detected. Collectively our data demonstrated an exacerbation of CS-induced lung toxicity by TS exposure and the molecular mechanisms underlying the exacerbated toxicity.
Role of Nurse Practitioners in Caring for Patients With Complex Health Needs
Authors: Fraze Taressa K. , Briggs Adam D.M. , Whitcomb Elizabeth K. , Peck Kristen A. , Meara Ellen 
Published: September 2020

Objective:
The objective of this study was to estimate trends in the percentage of Medicare beneficiaries cared for by nurse practitioners from 2012 to 2017, to characterize beneficiaries cared for by nurse practitioners in 2017, and to examine how the percentage of beneficiaries cared for by nurse practitioners varies by practice characteristics.

Design:
An observational study of 2012–2017 Medicare fee-for-service beneficiaries’ ambulatory visits. We computed the percentage of beneficiaries with 1 or more ambulatory visits from nurse practitioners and the percentage of beneficiaries receiving the plurality of their ambulatory visits from a nurse practitioner versus a physician (ie, predominant provider). We compared beneficiary demographics, clinical characteristics, and utilization by the predominant provider. We then characterized the predominant provider by practice characteristics.

Key Results:
In 2017, 28.9% of beneficiaries received any care from a nurse practitioner and 8.0% utilized nurse practitioners as their predominant provider—an increase from 4.4% in 2012. Among beneficiaries cared for by nurse practitioners in 2017, 25.9% had 3 or more chronic conditions compared with 20.8% of those cared for by physicians. Beneficiaries cared for in practices owned by health systems were more likely to have a nurse practitioner as their predominant provider compared with those attending practices that were independently owned (9.3% vs. 7.0%).

Conclusions:
Nurse practitioners are caring for Medicare beneficiaries with complex needs at rates that match or exceed their physician colleagues. The growing role of nurse practitioners, especially in health care systems, warrants attention as organizations embark on payment and delivery reform.
Learning by Doing: Design and Evaluation of a Quality Improvement Curriculum for Pediatric Hospitalists
Authors: Szymusiak John , McCormick Andrew 
Published: September 2020

Introduction:
Quality improvement (QI) is a core competency for Pediatric Hospital Medicine (PHM) and required for maintenance of certification, but many hospitalists lack QI training. This project set out to increase a PHM faculty’s QI knowledge and comfort participating in QI projects, while concurrently applying the skills learned to a QI project in the hospital.

Methods:
We designed a 4-session curriculum utilizing principles of adult learning. Faculty immediately applied learned concepts to a QI project to increase the percentage of patients who were seen by an attending and billed for on the same day as admission to the PHM service. Attitudinal data and scores on the validated Quality Improvement Knowledge Application Tool- Revised knowledge assessment were compared precurriculum and postcurriculum. A manifest content analysis was carried out for qualitative questions.

Results:
Twenty faculty (83%) completed the preassessment; 15 (63%) completed the postassessment. Respondents showed statistically significant improvements in their perceived ability to participate in QI projects and their Quality Improvement Knowledge Application Tool- Revised scores. The group completed a QI project that increased revenue for the division. Faculty appreciated that the curriculum was applied to a real QI project and felt they would use the new skills in their daily practice.

Discussion:
This curricular model based on adult learning theory, with immediate application to a real QI project, conclusively showed attitudinal, knowledge-based, and hospital system-level improvements, and was well received by faculty.
Feasibility of Integrating Canine Olfaction with Chemical and Microbial Profiling of Urine to Detect Lethal Prostate Cancer
Authors: Guest Claire , Harris Rob , Sfanos Karen S. , Shrestha Eva , Partin Alan W. , Trock Bruce , Mangold Leslie , Bader Rebecca , Kozak Adam , Mclean Scott , Simons Jonathan , Soule Howard , Johnson Thomas , Lee Wen-Yee , Gao Qin , Aziz Sophie , Stathatou Patritsia , Thaler Stephen , Foster Simmie , Mershin Andreas 
Published: September 2020

AbstractProstate cancer is the second leading cause of cancer death in men in the developed world. A more sensitive and specific detection strategy for lethal prostate cancer beyond serum prostate specific antigen (PSA) population screening is urgently needed. Diagnosis by canine olfaction, using dogs trained to detect cancer by smell, has been shown to be both specific and sensitive. While dogs themselves are impractical as scalable diagnostic sensors, machine olfaction for cancer detection is testable. However, studies bridging the divide between clinical diagnostic techniques, artificial intelligence, and molecular analysis remains difficult due to the significant divide between these disciplines. We tested the clinical feasibility of a cross-disciplinary, integrative approach to early prostate cancer biosensing in urine using trained canine olfaction, volatile organic compound (VOC) analysis by gas chromatography-mass spectroscopy (GC-MS) artificial neural network (ANN)-assisted examination, and microbial profiling in a double-blinded pilot study. Two dogs were trained to detect Gleason 9 prostate cancer in urine collected from biopsy-confirmed patients. Biopsy-negative controls were used to assess canine specificity as prostate cancer biodetectors. Urine samples were simultaneously analyzed for their VOC content in headspace via GC-MS and urinary microbiota content via 16S rDNA Illumina sequencing. In addition, the dogs’ diagnoses were used to train an ANN to detect significant peaks in the GC-MS data. The canine olfaction system was 71% sensitive and between 70-76% specific at detecting Gleason 9 prostate cancer. We have also confirmed VOC differences by GC-MS and microbiota differences by 16S rDNA sequencing between cancer positive and biopsy-negative controls. Furthermore, the trained ANN identified regions of interest in the GC-MS data, informed by the canine diagnoses. Methodology and feasibility are established to inform larger-scale studies using canine olfaction, urinary VOCs, and urinary microbiota profiling to develop machine olfaction diagnostic tools. Scalable multi-disciplinary tools may then be compared to PSA screening for earlier, non-invasive, more specific and sensitive detection of clinically aggressive prostate cancers in urine samples.
High-throughput discovery and characterization of human transcriptional effectors
Authors: Tycko Josh , DelRosso Nicole , Hess Gaelen T. , Aradhana  , Banerjee Abhimanyu , Mukund Aditya , Van Mike V. , Ego Braeden K. , Yao David , Spees Kaitlyn , Suzuki Peter , Marinov Georgi K. , Kundaje Anshul , Bassik Michael C. , Bintu Lacramioara 
Published: September 2020

SummaryThousands of proteins localize to the nucleus; however, it remains unclear which contain transcriptional effectors. Here, we develop HT-recruit - a pooled assay where protein libraries are recruited to a reporter, and their transcriptional effects are measured by sequencing. Using this approach, we measure gene silencing and activation for thousands of domains. We find a relationship between repressor function and evolutionary age for the KRAB domains, discover Homeodomain repressor strength is collinear withHoxgenetic organization, and identify activities for several Domains of Unknown Function. Deep mutational scanning of the CRISPRi KRAB maps the co-repressor binding surface and identifies substitutions that improve stability/silencing. By tiling 238 proteins, we find repressors as short as 10 amino acids. Finally, we report new activator domains, including a divergent KRAB. Together, these results provide a resource of 600 human proteins containing effectors and demonstrate a scalable strategy for assigning functions to protein domains.
Evolution of kinase polypharmacology across HSP90 drug discovery
Authors: Antolin Albert A. , Clarke Paul A. , Collins Ian , Workman Paul , Al-Lazikani Bissan 
Published: September 2020

AbstractMost small molecules interact with several target proteins but this polypharmacology is seldom comprehensively investigated or explicitly exploited during drug discovery. Here, we use computational and experimental methods to systematically characterize the kinase cross-pharmacology of representative HSP90 inhibitors. We demonstrate that the resorcinol clinical candidates ganetespib and, to a lesser extent, luminespib, display unique off-target kinase pharmacology as compared to other HSP90 inhibitors. We also demonstrate that polypharmacology evolved during the optimisation to discover luminespib and that the hit, leads and clinical candidate all have different polypharmacological profiles. We conclude that the submicromolar target inhibition of protein kinases by ganetespib may have potential clinical significance and we recommend the computational and experimental characterization of polypharmacology earlier in drug discovery projects to unlock new multi-target drug design opportunities.
Does offspring demand affect parental life-history trade-offs?
Authors: Mäenpää M.I. , Smiseth P.T. 
Published: September 2020

AbstractLife-history trade-offs between the number and size of offspring produced, and the costs of reproduction on future reproduction and survival can all be affected by different levels of parental effort. Because of these trade-offs the parents and the offspring have different optima for the amount of care given to the current brood, which leads to a conflict between parents and offspring. The offspring, as well as the parents, have the ability to affect parental effort, and thus changes in offspring traits have the potential to cause reproductive costs on the parents. Here, we used a repeated cross-fostering design to manipulate offspring demand during juvenile development in the burying beetleNicrophorus vespilloidesto examine whether responding to offspring begging incurs reproductive costs to the parent. After a manipulated first reproductive event, we gave each experimental female, that had been exposed to different levels of offspring demand, a chance to breed again, and monitored their survival. We found that larval demand influences the trade-off between the size and number of offspring produced, but has no impact on the reproductive costs through future reproduction or survival of the parent. The parents do, however, pay an overall fecundity cost for the general success of their first broods, but this cost was not related to the changes in the levels of larval begging. Other traits, including survival showed no costs of reproduction. Survival and the number of larvae successfully raised in the second broods correlated positively, indicating differences in the individual quality of the parents.
Glycosyltransferase POMGNT1 deficiency affects N-cadherin-mediated cell-cell adhesion
Authors: Noor Sina Ibne , Hoffmann Marcus , Rinis Natalie , Bartels Markus F. , Winterhalter Patrick , Hoelscher Christina , Hennig René , Himmelreich Nastassja , Thiel Christian , Ruppert Thomas , Rapp Erdmann , Strahl Sabine 
Published: September 2020

AbstractDefects in proteinO-mannosylation lead to severe congenital muscular dystrophies known as α-dystroglycanopathy. A hallmark of these diseases is the loss of theO-mannose-bound matriglycan on α-dystroglycan, which leads to a reduction in cell adhesion to the extracellular matrix. Mutations in proteinO-mannose β1,2-N-acetylglucosaminyltransferase 1 (POMGNT1), which is crucial for the elongation ofO-mannosyl glycans, are mainly associated with muscle-eye-brain (MEB) disease. In addition to defects in cell-extracellular matrix adhesion, aberrant cell-cell adhesion has occasionally been observed in response to defects in POMGNT1. However, direct molecular mechanisms are largely unknown. We used POMGNT1 knock-out HEK293T cells and fibroblasts from a MEB patient to gain a deeper insight into the molecular changes in POMGNT1 deficiency. A combination of biochemical and molecular biological techniques with proteomics, glycoproteomics and glycomics revealed that a lack of POMGNT1 activity strengthens cell-cell adhesion. We demonstrate that the altered intrinsic adhesion properties are due to an increased abundance of N-cadherin (N-Cdh). In addition, site-specific changes in theN-glycan structures in the extracellular domain of N-Cdh were detected, which positively impact on homotypic interactions. We found that in POMGNT1 deficient cells ERK1/2 and p38 signaling pathways are activated and transcriptional changes that are comparable to the epithelial-mesenchymal transition (EMT) are triggered, defining a possible molecular mechanism underlying the observed phenotype. Our study indicates that changes in cadherin-mediated cell-cell adhesion and other EMT-related processes may contribute to the complex clinical symptoms of MEB or α-dystroglycanopathy in general, and suggests a previously underestimated impact of changes inO-mannosylation onN-glycosylation.
Caenorhabditis elegans: a model to study the anthelmintic effects of polyphenolic compounds on the fertility of parasitic gastrointestinal nematodes?
Authors: Arroyo-Lopez C 
Published: September 2020

AbstractWe set up a Caenorhabditis elegansmodel to extrapolate anthelmintic (AH) effects of commercial polyphenols to related gastrointestinal zoonotic species. We compared the practical convenience of S liquid to solid agar Nematode grown medium in daily reproduction patterns and total brood size. Solid agar resulted a highly effective, reproducibly medium, in a less costly and rapid time manner. A minimum of three replications per monomer concentration are suggested to get a robust statistical analysis. Flavonoids Quercetin and Rutin potentially decrease brood sizes and percentage of development, with the exception of 20μM concentration. Flavanols resulted heterogeneous. In a dose-dependent manner Catechin 20μM significantly decreased egg output, and egg hatching in a 15% on respect to control values. Contrary, Epigallocatechin-gallate, seems to stimulate brood sizes and egg-hatching, however, EGCG10μM decreased reproduction but with no in a significative manner. We found a nematocidal effect on the reproductive parameters ofC. elegansexposed to the chalcones Phloretin and Phloridzin, and Flavones Flavone and Genistein. A significant general decrease on reproductive parameters were found, particularly significant for Genistein 20μM in the percentage of hatching respect to control. Effects of time schedule and monomer concentration were found for the Hydrolysable tannins Gallic and Tannic acid. Tannic acid showed effectiveness against egg-hatching. The spectrum of percentages of change compared to each blank resulted negative decreasing fertility values, but for GA5, associated with a net increase of larvae hatched.1AH, GIN, CTS, HTs Q) Quercetin, (R) Rutin, (C) (+)-Catechin hydrate, (EGCG) (-)-Epigallocatechin Gallate, (PTN) Phloretin, (PDN) Phloridzin Dihydrate, (GE) Genistein, (FLA) Flavone, (GA) Gallic acid and (TA) Tannic acid., G1 (adult worm originally seeded per plate and monomer concentration at time 0. Two replications were performed per plate). Solvents: PBS (Phosphate Buffer Solution), CH4O (Methanol 0,002%) L3
Critical events of the origins of life
Authors: Bastian Caleb Deen , Rabitz Herschel 
Published: September 2020

AbstractWe discuss some critical events of the origins of life using a mathematical model and simulation studies. We find that for a replicating population of RNA molecules participating in template-directed polymerization, the hitting and establishment of a high-fidelity replicator depends critically on the polymerase fitness and sequence specificity landscapes and on genome dimension. Probability of hitting is dominated by polymerase landscape curvature, whereas hitting time is dominated by genome dimension. Surface chemistries, compartmentalization, and decay increase hitting times. These results suggest replication to be the first ‘privileged function’ marking the start of Darwinian evolution, possibly in conjunction with clay minerals or preceded by metabolism, whose dynamics evolved mostly during the final period of the search.