bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cost-effectiveness of treating head and neck cancer using intensity-modulated radiation therapy: implications for cancer control program in India
Authors: Chauhan Akashdeep Singh , Prinja Shankar , Ghoshal Sushmita , Verma Roshan 
Published: September 2020

BackgroundThe newer cancer treatment technologies hold the potential of providing improved health outcomes at an additional cost. So it becomes obligatory to assess the costs and benefits of a new technology, before defining its clinical value. We assessed the cost-effectiveness of intensity-modulated radiotherapy (IMRT) as compared to 2-dimensional radiotherapy (2-DRT) and 3-dimensional radiotherapy (3D-CRT) for treating head and neck cancers (HNC) in India. The cost-effectiveness of 3-DCRT as compared to 2-DRT was also estimated.MethodsA probabilistic Markov model was designed. Using a disaggregated societal perspective, lifetime study horizon and 3 percent discount rate, future costs and health outcomes were compared for a cohort of 1000 patients treated with any of the three radiation techniques. Data on health system cost, out of pocket expenditure, and quality of life was assessed through primary data collected from a large tertiary care public sector hospital in India. Data on xerostomia rates following each of the radiation techniques was extracted from the existing randomized controlled trials.ResultsIMRT incurs an incremental cost of $7,072 (2,932–13,258) and $5,164 (463–10,954) per quality-adjusted life year (QALY) gained compared to 2-DRT and 3D-CRT, respectively. Further, 3D-CRT as compared to 2-DRT requires an incremental cost of $8,946 (1,996–19,313) per QALY gained.ConclusionBoth IMRT and 3D-CRT are not cost-effective at 1 times GDP per capita for treating HNC in India. The costs and benefits of using IMRT for other potential indications (e.g. prostate, lung) require to be assessed before considering its introduction in India.
John Stuart Mill's Harm Principle and Free Speech: Expanding the Notion of Harm
Authors: Bell Melina Constantine 
Published: September 2020

AbstractThis article advocates employing John Stuart Mill's harm principle to set the boundary for unregulated free speech, and his Greatest Happiness Principle to regulate speech outside that boundary because it threatens unconsented-to harm. Supplementing the harm principle with an offense principle is unnecessary and undesirable if our conception of harm integrates recent empirical evidence unavailable to Mill. For example, current research uncovers the tangible harms individuals suffer directly from bigoted speech, as well as the indirect harms generated by the systemic oppression and epistemic injustice that bigoted speech constructs and reinforces. Using Mill's ethical framework with an updated notion of harm, we can conclude that social coercion is not justified to restrict any harmless speech, no matter how offensive. Yet certain forms of speech, such as bigoted insults, are both harmful and fail to express a genuine opinion, and so do not deserve free speech protection.
Genetic diversity of the Andean blackberry (Rubus glaucusBenth.) in Ecuador assessed by AFLP markers
Authors: Garrido Patricia , Morillo Eduardo , Vásquez-Castillo Wilson 
Published: September 2020

AbstractAndean blackberry (Rubus glaucusBenth.) is an emerging fruit crop with significant commercial potential. Despite its growing popularity, basic research about its genetic resources and breeding remains insufficient. The aim of this study was to assess the genetic diversity of Andean blackberry cultivars and related berries species from the main production areas in Ecuador. We analysed a total of 106 samples and performed DNA screening with different molecular markers: random-amplified polymorphic DNAs (RAPDs), inter-simple sequence repeats (ISSRs) and a set of representative samples with amplified fragment length polymorphisms (AFLPs). The tested RAPD primers did not reveal any differentiation among accessions identified asR. glaucus, however one ISSR primer was useful to find polymorphisms allowing the selection of 29 accessions for the analysis with AFLP markers. AFLP-M13 technology was used for screen genetic variations among these accessions and eight wildRubusaccessions. We scored 203 bands using five primer combinations; out of these 152 were informative inR. glaucus. AFLP markers clearly distinguishR. glaucusfrom the screened wildRubusspecies, also an unexpected genetic structure was revealed amongR. glaucuscultivars. This genetic differentiation and detection of admixed genotypes suggest a possible introgression of wildRubusspecies inR. glaucus. Our findings are relevant for blackberry genetic breeding and use of these genetic resources.
Isotopic Evidence for Multiple Recycled Sulfur Reservoirs in the Mangaia Mantle Plume
Authors: Dottin J. W. , Labidi J. , Jackson M. G. , Woodhead J. , Farquhar J. 
Published: September 2020

AbstractMangaia, an ocean island in the Cook‐Austral volcanic chain, is the type locality for the HIMU mantle reservoir and has also been shown to exhibit evidence for recycled sulfur with anomalous δ34S and Δ33S that has been attributed an Archean origin. Here we report bulk S‐isotope data from sulfide inclusions in olivine and pyroxene phenocrysts from one of the previously analyzed and four additional Mangaia basalts to further test for the prevalence of anomalous S in the HIMU mantle source feeding Mangaia. We document compositions that range from −5.13‰ to +0.21‰ (±0.3 2σ), +0.006‰ to +0.049‰ (±0.016 2σ), −0.81‰ to +0.69‰ (±0.3 2σ) for δ34S, Δ33S, and Δ36S, respectively. These data extend the range of measured compositions and suggest S‐isotope heterogeneity in the HIMU mantle source at Mangaia. We show that S‐isotope compositions of bulk sulfide in olivine is not in isotopic equilibrium with bulk sulfide in pyroxene from the same samples and that samples from a confined area (M4, M10, M12, and M13) in the northern central part of the island show a distinct covariation for δ34S and Δ33S. This isotopic variation (forming an array) suggests mixing of sulfur from two sources that were captured at different stages of crystallization by phenocrysts in the Mangaia HIMU sulfur endmember.
Clustering of Marine‐Debris‐ and Sargassum‐Like Drifters Explained by Inertial Particle Dynamics
Authors: Miron P. , Olascoaga M. J. , Beron‐Vera F. J. , Putman N. F. , Triñanes J. , Lumpkin R. , Goni G. J. 
Published: September 2020

AbstractDrifters designed to mimic floating marine debris and small patches of pelagic Sargassum were satellite tracked in four regions across the North Atlantic. Though subjected to the same initial conditions at each site, the tracks of different drifters quickly diverged after deployment. We explain the clustering of drifter types using a recent Maxey‐Riley theory for surface ocean inertial particle dynamics applied on multidata‐based mesoscale ocean currents and winds from reanalysis. Simulated trajectories of objects at the air‐sea interface are significantly improved when represented as inertial (accounting for buoyancy and size), rather than as perfectly Lagrangian (fluid following) particles. Separation distances between simulated and observed trajectories were substantially smaller for debris‐like drifters than for Sargassum‐like drifters, suggesting that additional consideration of its physical properties relative to fluid velocities may be useful. Our findings can be applied to model variability in movements and distribution of diverse objects floating at the ocean surface.
Transport and Deposition Patterns of Particles Laden by Rising Submarine Hydrothermal Plumes
Authors: Lou Yingzhong , He Zhiguo , Han Xiqiu 
Published: September 2020

AbstractTransport and deposition behavior of mineral particles driven by hydrothermal plumes along mid‐ocean ridges is one of the least understood processes in geoscience. We reveal the mechanism and three typical transport patterns of particles emitted from submarine vents and subsequently laden by plumes in the stratified deep ocean with or without crossflows, that is, suspension, near‐vent deposition, and long‐distance transport, by developing a Lagrangian model coupled with a computational fluid dynamics model and using in situ measurements as model inputs. The particle trajectories suggest a general expression that predicts a linear variation of deposition location with the reciprocal of settling velocity, which potentially leads to a power law distribution of sediment mass along the radial direction. Our findings provide a new perspective on the accumulation of sediments near hydrothermal vents, indicating a critical role of the entrainment of plumes and consequent vortex systems in controlling deposition flux.
Coupling From the Middle Atmosphere to the Exobase: Dynamical Disturbance Effects on Light Chemical Species
Authors: Jones M. , Siskind D. E. , Drob D. P. , McCormack J. P. , Emmert J. T. , Dhadly M. S. , Attard H. E. , Mlynczak M. G. , Brown P. G. , Stober G. , Kozlovsky A. , Lester M. , Jacobi C. 
Published: September 2020

AbstractThis paper characterizes the impacts of sudden stratospheric warmings (SSWs) and mesospheric coolings (MCs) on the light species distribution (i.e., helium [He], and atomic hydrogen [H]) of the thermosphere using a combined data‐modeling approach. Performing a set of numerical experiments with a general circulation model whose middle atmospheric dynamical and thermodynamical fields were constrained using a numerical weather prediction system, we simulate the effects of SSWs and MCs on light chemical species, and via comparisons with two data sets taken from the mesosphere and thermosphere, we quantify the associated variability in light species abundances and mass density. Large depletions in the observed and modeled polar H abundance in the mesosphere and lower thermosphere (MLT) occur with MC onset, as opposed to SSW onset. Depletions in all light thermospheric species at high northern latitudes extend up to the exobase in our model simulations during the January 2013 SSW/MC period, with the largest depletions simulated for the lightest species. Further, our modeling work substantiates the paradigm of increased mixing in the MLT driven by a meridional residual circulation during SSWs resulting from enhanced small‐scale gravity wave and migrating semidiurnal tidal forcing; the former being the primary driver and the latter of secondary but notable importance in our model simulations. SSW/MC induced light species variability then gets projected upward into the thermosphere through molecular diffusion. Modeled light species variability during the January 2013 SSW/MC event suggests SSW/MC signatures could be present in the topside ionosphere and plasmasphere.
Land Use and Season Influence Event‐Scale Nitrate and Soluble Reactive Phosphorus Exports and Export Stoichiometry from Headwater Catchments
Authors: Kincaid Dustin W. , Seybold Erin C. , Adair E. Carol , Bowden William B. , Perdrial Julia N. , Vaughan Matthew C. H. , Schroth Andrew W. 
Published: September 2020

AbstractCatchment nutrient export, especially during high flow events, can influence ecological processes in receiving waters by altering nitrogen (N) and phosphorus (P) concentrations and relative amounts (stoichiometry). Event‐scale N and P export dynamics may be significantly altered by land use/land cover (LULC) and season. Consequently, to manage water resources, it is important to understand how LULC and season interact to influence event N and P export. In situ, high‐frequency spectrophotometers allowed us to continuously and concurrently monitor nitrate (NO3−) and soluble reactive P (SRP) concentrations and therefore examine event‐scale NO3−and SRP export dynamics. Here we analyzed event NO3−and SRP concentration‐discharge hysteresis patterns and yields for >400 events to evaluate how LULC and seasonality influence event NO3−and SRP export dynamics in three low‐order watersheds with different primary LULCs (agricultural, forested, and urban). Differences among event NO3−and SRP hysteresis patterns suggest these nutrients have different source areas and dominant transport pathways that were impacted by both LULC and seasonality. Unexpectedly, we observed similar seasonal patterns in event NO3−:SRP stoichiometry among LULCs, with the most N‐enriched events occurring in spring, and event stoichiometry approaching Redfield N:P ratios in the fall. However, seasonal stoichiometry patterns were driven by unique seasonal NO3−and SRP export patterns at each site. Overall these findings suggest LULC and seasonality interact to alter the timing and magnitude of event NO3−and SRP exports, leading to seasonal patterns in event NO3−to SRP stoichiometry that may influence ecological processes, such as productivity, in receiving waters.
Mouse–human co-clinical trials demonstrate superior anti-tumour effects of buparlisib (BKM120) and cetuximab combination in squamous cell carcinoma of head and neck
Authors: Kim Hye Ryun , Kang Han Na , Yun Mi Ran , Ju Kwon Young , Choi Jae Woo , Jung Dong Min , Pyo Kyoung Ho , Hong Min Hee , Ahn Myoung-Ju , Sun Jong-Mu , Kim Han Sang , Kim Jinna , Yoo Jinseon , Kim Kyu Ryung , Koh Yoon Woo , Kim Se Heon , Choi Eun Chang , Yoon Sun Ock , Shim Hyo Sup , Paik Soonmyung , Kim Tae-Min , Cho Byoung Chul 
Published: September 2020

Abstract
Background
Recurrent and/or metastatic squamous cell carcinoma of head and neck (R/M SCCHN) is a common cancer with high recurrence and mortality. Current treatments have low response rates (RRs).

Methods
Fifty-three patients with R/M SCCHN received continuous oral buparlisib. In parallel, patient-derived xenografts (PDXs) were established in mice to evaluate resistance mechanisms and efficacy of buparlisib/cetuximab combination. Baseline and on-treatment tumour genomes and transcriptomes were sequenced. Based on the integrated clinical and PDX data, 11 patients with progression under buparlisib monotherapy were treated with a combination of buparlisib and cetuximab.

Results
For buparlisib monotherapy, disease control rate (DCR) was 49%, RR was 3% and median progression-free survival (PFS) and overall survival (OS) were 63 and 143 days, respectively. For combination therapy, DCR was 91%, RR was 18% and median PFS and OS were 111 and 206 days, respectively. Four PDX models were originated from patients enrolled in the current clinical trial. While buparlisib alone did not inhibit tumour growth, combination therapy achieved tumour inhibition in three of seven PDXs. Genes associated with apoptosis and cell-cycle arrest were expressed at higher levels with combination treatment than with buparlisib or cetuximab alone.

Conclusions
The buparlisib/cetuximab combination has significant promise as a treatment strategy for R/M SCCHN.

Clinical Trial Registration
NCT01527877.
Examination of potential novel biochemical factors in relation to prostate cancer incidence and mortality in UK Biobank
Authors: Perez-Cornago Aurora , Fensom Georgina K. , Andrews Colm , Watts Eleanor L. , Allen Naomi E. , Martin Richard M. , Van Hemelrijck Mieke , Key Timothy J. , Travis Ruth C. 
Published: September 2020

AbstractBackgroundAlthough prostate cancer is a leading cause of cancer death, its aetiology is not well understood. We aimed to identify novel biochemical factors for prostate cancer incidence and mortality in UK Biobank.MethodsA range of cardiovascular, bone, joint, diabetes, renal and liver-related biomarkers were measured in baseline blood samples collected from up to 211,754 men at recruitment and in a subsample 5 years later. Participants were followed-up via linkage to health administrative datasets to identify prostate cancer cases. Hazard ratios (HRs) and 95% confidence intervals were calculated using multivariable-adjusted Cox regression corrected for regression dilution bias. Multiple testing was accounted for by using a false discovery rate controlling procedure.ResultsAfter an average follow-up of 6.9 years, 5763 prostate cancer cases and 331 prostate cancer deaths were ascertained. Prostate cancer incidence was positively associated with circulating vitamin D, urea and phosphate concentrations and inversely associated with glucose, total protein and aspartate aminotransferase. Phosphate and cystatin-C were the only biomarkers positively and inversely, respectively, associated with risk in analyses excluding the first 4 years of follow-up. There was little evidence of associations with prostate cancer death.ConclusionWe found novel associations of several biomarkers with prostate cancer incidence. Future research will examine associations by tumour characteristics.
BCAS2, a protein enriched in advanced prostate cancer, interacts with NBS1 to enhance DNA double-strand break repair
Authors: Wang Li-Po , Chen Tzu-Yu , Kang Chun-Kai , Huang Hsiang-Po , Chen Show-Li 
Published: September 2020

Abstract
Background
Breast cancer amplified sequence 2 (BCAS2) plays crucial roles in pre-mRNA splicing and androgen receptor transcription. Previous studies suggested that BCAS2 is involved in double-strand breaks (DSB); therefore, we aimed to characterise its mechanism and role in prostate cancer (PCa).

Methods
Western blotting and immunofluorescence microscopy were used to assay the roles of BCAS2 in the DSBs of PCa cells and apoptosis in Drosophila, respectively. The effect of BCAS2 dosage on non-homologous end joining (NHEJ) and homologous recombination (HR) were assayed by precise end-joining assay and flow cytometry, respectively. Glutathione-S-transferase pulldown and co-immunoprecipitation assays were used to determine whether and how BCAS2 interacts with NBS1. The expression of BCAS2 and other proteins in human PCa was determined by immunohistochemistry.

Results
BCAS2 helped repair radiation-induced DSBs efficiently in both human PCa cells and Drosophila. BCAS2 enhanced both NHEJ and HR, possibly by interacting with NBS1, which involved the BCAS2 N-terminus as well as both the NBS1 N- and C-termini. The overexpression of BCAS2 was significantly associated with higher Gleason and pathology grades and shorter survival in patients with PCa.

Conclusion
BCAS2 promotes two DSB repair pathways by interacting with NBS1, and it may affect PCa progression.
The experience of general practitioners with Very Brief Advice in the treatment of tobacco addiction
Authors: van Schayck Onno C. P. , Bindels Lynn , Nijs Ancka , van Engelen Bo , van den Bosch Adrienne , Muller Ilona Statius , Spigt Mark 
Published: September 2020

AbstractAlthough tobacco smoking is the world’s most important preventable cause of many chronic diseases (including COPD and asthma) and premature death, many physicians do not routinely apply smoking cessation in the daily health care of their patients. Two widely felt important concerns of physicians are that smoking cessation as part of a treatment is time-consuming and may jeopardize their relationship with patients. Very Brief Advice (VBA) is a non-confrontational method, which could assist general practitioners (GPs) as a simple, quick first step in getting patients to stop smoking. In this study, we investigated the opinions and experiences of GPs with VBA in their routine care in two rounds of telephone interviews with 19 GPs. The interviews were recorded and transcribed and subsequently analysed with NVivo12. We observed that the GPs had a very positive experience with using VBA. They found the method to be efficient as to the time involved, patient-friendly and easy to implement.
Two hundred and fifty-four metagenome-assembled bacterial genomes from the bank vole gut microbiota
Authors: Lavrinienko Anton , Tukalenko Eugene , Mousseau Timothy A. , Thompson Luke R. , Knight Rob , Mappes Tapio , Watts Phillip C. 
Published: September 2020

AbstractVertebrate gut microbiota provide many essential services to their host. To better understand the diversity of such services provided by gut microbiota in wild rodents, we assembled metagenome shotgun sequence data from a small mammal, the bank vole Myodes glareolus (Rodentia, Cricetidae). We were able to identify 254 metagenome assembled genomes (MAGs) that were at least 50% (n = 133 MAGs), 80% (n = 77 MAGs) or 95% (n = 44 MAGs) complete. As typical for a rodent gut microbiota, these MAGs are dominated by taxa assigned to the phyla Bacteroidetes (n = 132 MAGs) and Firmicutes (n = 80), with some Spirochaetes (n = 15) and Proteobacteria (n = 11). Based on coverage over contigs, Bacteroidetes were estimated to be most abundant group, followed by Firmicutes, Spirochaetes and Proteobacteria. These draft bacterial genomes can be used freely to determine the likely functions of gut microbiota community composition in wild rodents.
Detection of circulating BMP5 as a risk factor for Barrett’s esophagus
Authors: Correia Ana C. P. , Calpe Silvia , Mostafavi Nahid , Hoefnagel Sanne Johanna Maria , Sancho-Serra Maria del Carmen , de Koning Patricia S. , Krishnadath Kausilia K. 
Published: September 2020

AbstractBarrett’s esophagus (BE) predisposes for the malignant condition of esophageal adenocarcinoma (EAC). Since BE patients have few or no symptoms, most of these patients are not identified and not included in surveillance programs. These BE patients are at risk of developing advanced-stage EAC. At present, non-invasive tests to identify BE patients from the general population are lacking. We and others showed that Bone Morphogenetic Protein 4 (BMP4), and other BMPs are upregulated in BE. We aimed to determine if circulating BMPs can be identified and used as blood biomarkers to identify BE patients at high risk in the general population. In this study, we could detect the different BMPs in the blood of 112 BE patients and 134 age- and sex-matched controls. Concentration levels of BMP2, BMP4, and BMP5 were elevated in BE patients, with BMP2 and BMP5 significantly increased. BMP5 remained significant after multivariate analysis and was associated with an increased risk for BE with an OR of 1.49 (p value 0.01). Per log (pg/mL) of BMP5, the odds of having BE increased by 50%. Future optimization and validation studies might be needed to prove its utility as a non-invasive method for the detection of BE in high-risk populations and screening programs.