bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive evaluation of transcriptome-based cell-type quantification methods for immuno-oncology
Authors: Sturm Gregor , Finotello Francesca , Petitprez Florent , Zhang Jitao David , Baumbach Jan , Fridman Wolf H , List Markus , Aneichyk Tatsiana 
Published: May 2019

Abstract

Motivation
The composition and density of immune cells in the tumor microenvironment (TME) profoundly influence tumor progression and success of anti-cancer therapies. Flow cytometry, immunohistochemistry staining or single-cell sequencing are often unavailable such that we rely on computational methods to estimate the immune-cell composition from bulk RNA-sequencing (RNA-seq) data. Various methods have been proposed recently, yet their capabilities and limitations have not been evaluated systematically. A general guideline leading the research community through cell type deconvolution is missing.

Results
We developed a systematic approach for benchmarking such computational methods and assessed the accuracy of tools at estimating nine different immune- and stromal cells from bulk RNA-seq samples. We used a single-cell RNA-seq dataset of ∼11 000 cells from the TME to simulate bulk samples of known cell type proportions, and validated the results using independent, publicly available gold-standard estimates. This allowed us to analyze and condense the results of more than a hundred thousand predictions to provide an exhaustive evaluation across seven computational methods over nine cell types and ∼1800 samples from five simulated and real-world datasets. We demonstrate that computational deconvolution performs at high accuracy for well-defined cell-type signatures and propose how fuzzy cell-type signatures can be improved. We suggest that future efforts should be dedicated to refining cell population definitions and finding reliable signatures.

Availability and implementation
A snakemake pipeline to reproduce the benchmark is available at https://github.com/grst/immune_deconvolution_benchmark. An R package allows the community to perform integrated deconvolution using different methods (https://grst.github.io/immunedeconv).

Supplementary information
Supplementary data are available at Bioinformatics online.
Persistent neuropathological effects 14 years following amyloid-β immunization in Alzheimer’s disease
Authors: Nicoll James A R , Buckland George R , Harrison Charlotte H , Page Anton , Harris Scott , Love Seth , Neal James W , Holmes Clive , Boche Delphine 
Published: May 2019

AbstractWe performed a 15-year post-mortem neuropathological follow-up of patients in the first trial of amyloid-β immunotherapy for Alzheimer’s disease. Twenty-two participants of a clinical trial of active amyloid-β42 immunization (AN1792, Elan Pharmaceuticals) or placebo were studied. Comprehensive post-mortem neuropathological assessments were performed from 4 months to 15 years after the trial. We analysed the relationships between the topographical distribution of amyloid-β removal from the cerebral cortex and tau pathology, cerebrovascular territories, plasma anti-AN1792 antibody titres and late cognitive status. Seventeen of 22 (77%) participants had Alzheimer’s neuropathological change, whereas 5 of 22 (23%) had alternative causes for dementia (progressive supranuclear palsy = 1, Lewy body disease = 1, vascular brain injury = 1, and frontotemporal lobar degeneration = 2). Nineteen of the 22 participants had received the active agent, three the placebo. Fourteen of 16 (88%) patients with Alzheimer’s disease receiving the active agent had evidence of plaque removal (very extensive removal = 5, intermediate = 4, very limited = 5, no removal = 2). Of particular note, two Alzheimer’s patients who died 14 years after immunization had only very sparse or no detectable plaques in all regions examined. There was a significant inverse correlation between post-vaccination peripheral blood anti-AN1792 antibody titres and post-mortem plaque scores (ρ = − 0.664, P = 0.005). Cortical foci cleared of plaques contained less tau than did cortex with remaining plaques, but the overall distribution of tangles was extensive (Braak V/VI). In conclusion, patients with Alzheimer’s disease actively immunized against amyloid-β can remain virtually plaque-free for 14 years. The extent of plaque removal is related to the immune response. This long duration of efficacy is important in support of active immunization protocols as therapy for, or potentially prevention of, neurodegeneration-associated protein accumulations. Inclusion of patients without Alzheimer’s disease in Alzheimer’s therapy trials is a problem for assessing the efficacy of treatment. Despite modification of Alzheimer’s pathology, most patients had progressed to severe dementia, notably including the five with very extensive plaque removal, possibly due to continued tau propagation. Neuropathology follow-up of patients in therapeutic trials provides valuable information on the causes of dementia and effects of treatment.
Protective effects of Alda-1, an ALDH2 activator, on alcohol-derived DNA damage in the esophagus of human ALDH2*2 (Glu504Lys) knock-in mice
Authors: Hirohashi Kenshiro , Ohashi Shinya , Amanuma Yusuke , Nakai Yukie , Ida Tomomi , Baba Kiichiro , Mitani Yosuke , Mizumoto Ayaka , Yamamoto Yoshihiro , Kikuchi Osamu , Matsubara Junichi , Yamada Atsushi , Miyamoto Shin’ichi , Seno Hiroshi , Matsuda Tomonari , Muto Manabu 
Published: May 2019

AbstractAlcohol consumption is the key risk factor for the development of esophageal squamous cell carcinoma (ESCC), and acetaldehyde, a metabolite of alcohol, is an alcohol-derived major carcinogen that causes DNA damage. Aldehyde dehydrogenase2 (ALDH2) is an enzyme that detoxifies acetaldehyde, and its activity is reduced by ALDH2 gene polymorphism. Reduction in ALDH2 activity increases blood, salivary and breath acetaldehyde levels after alcohol intake, and it is deeply associated with the development of ESCC. Heavy alcohol consumption in individuals with ALDH2 gene polymorphism significantly elevates the risk of ESCC; however, effective prevention has not been established yet. In this study, we investigated the protective effects of Alda-1, a small molecule ALDH2 activator, on alcohol-mediated esophageal DNA damage. Here, we generated novel genetically engineered knock-in mice that express the human ALDH2*1 (wild-type allele) or ALDH2*2 gene (mutant allele). Those mice were crossed, and human ALDH2*1/*1, ALDH2*1/*2 and ALDH2*2/*2 knock-in mice were established. They were given 10% ethanol for 7 days in the presence or absence of Alda-1, and we measured the levels of esophageal DNA damage, represented by DNA adduct (N2-ethylidene-2′-deoxyguanosine). Alda-1 significantly increased hepatic ALDH2 activity both in human ALDH2*1/*2 and/or ALDH2*2/*2 knock-in mice and reduced esophageal DNA damage levels after alcohol drinking. Conversely, cyanamide, an ALDH2-inhibitor, significantly exacerbated esophageal DNA adduct level in C57BL/6N mice induced by alcohol drinking. These results indicate the protective effects of ALDH2 activation by Alda-1 on esophageal DNA damage levels in individuals with ALDH2 gene polymorphism, providing a new insight into acetaldehyde-mediated esophageal carcinogenesis and prevention.
HyDeploy: The UK’s First Hydrogen Blending Deployment Project
Authors: Isaac Tommy 
Published: May 2019

Abstract
The HyDeploy project is the UK’s first practical project to demonstrate that hydrogen can be safely blended into the natural-gas distribution system without requiring changes to appliances and the associated disruption. The project is funded under Ofgem’s Network Innovation Competition and is a collaboration between Cadent Gas, Northern Gas Networks, Progressive Energy Ltd, Keele University (Keele), Health & Safety Laboratory and ITM Power. Cadent and Northern Gas Networks are the Gas Distribution Network sponsors of the project. Keele University is the host site, providing the gas-distribution network, which will receive the hydrogen blend. Keele University is the largest campus university in the UK. Health & Safety Laboratory provides the scientific laboratories and experimental expertise. ITM Power provides the electrolyser that produces the hydrogen. Progressive Energy Ltd is the project developer and project manager. HyDeploy is structured into three distinct phases. The first is an extensive technical programme to establish the necessary detailed evidence base in support of an application to the Health & Safety Executive for Exemption to Schedule 3 of the Gas Safety (Management) Regulations (GS(M)R) to permit the injection of hydrogen at 20 mol%. This is required to allow hydrogen to be blended into a natural-gas supply above the current British limit of 0.1 mol%. The second phase comprises the construction of the electrolyser and grid entry unit, along with the necessary piping and valves, to allow hydrogen to be mixed and injected into the Keele University gas-distribution network and to ensure all necessary training of operatives is conducted before injection. The third phase is the trial itself, which is due to start in the summer of 2019 and last around 10 months. The trial phase also provides an opportunity to undertake further experimental activities related to the operational network to support the pathway to full deployment of blended gas. The outcome of HyDeploy is principally developing the initial evidence base that hydrogen can be blended into a UK operational natural-gas network without disruption to customers and without prejudicing the safety of end users. If deployed at scale, hydrogen blending at 20 mol% would unlock 29 TWh pa of decarbonized heat and provide a route map for deeper savings. The equivalent carbon savings of a national roll-out of a 20-mol% hydrogen blend would be to remove 2.5 million cars from the road. HyDeploy is a seminal UK project for the decarbonization of the gas grid via hydrogen deployment and will provide the first stepping stone for setting technical, operational and regulatory precedents of the hydrogen vector.
Effect of Cannabis Use on Human Immunodeficiency Virus DNA During Suppressive Antiretroviral Therapy
Authors: Chaillon Antoine , Nakazawa Masato , Anderson Christy , Christensen-Quick Aaron , Ellis Ronald J , Franklin Donald , Morris Sheldon R , Gianella Sara 
Published: May 2019

AbstractCannabis use is frequent among people living with human immunodeficiency virus (HIV) and is associated with reduced systemic inflammation. We observed a faster HIV DNA decay during antiretroviral therapy among cannabis users, compared to those with no drug use. No cannabis effect was observed on cellular HIV RNA transcription.
Interpretation of volumetric laser endomicroscopy in Barrett's esophagus using image enhancement software
Authors: Kamboj A K , Hoversten P , Kahn A K , Trindade A J , Iyer P G , Wang K K , Leggett C L 
Published: May 2019

SUMMARY
Image interpretation of Barrett's esophagus (BE) with volumetric laser endomicroscopy (VLE) can be enhanced by image processing software that highlights established features using a color-graded scale (intelligent real-time image segmentation, IRIS). This study aims to provide a description of IRIS features of various gastroesophageal tissue types using histologic correlation. A database of 80 VLE laser-marked targets with histologic correlation was reviewed for various tissue types. IRIS was applied off-line to the VLE scans, laser-marked targets were identified, and feature review was performed. Squamous epithelium targets (N = 7) showed IRIS layered architecture with lack of surface hyper-reflectivity and epithelial glands. Gastric cardia targets (N = 10) showed absent layering (100%) and surface hyper-reflectivity with epithelial glands (40%). Nondysplastic BE targets (N = 39) showed surface hyper-reflectivity (64%), epithelial glands (51%), and lack of layering (74%). Targets of BE with early neoplasia (N = 24), showed surface hyper-reflectivity (96%), epithelial glands (67%), and lack of layering (96%). IRIS features that characterize each tissue type appear to mirror the nonenhanced VLE counterparts that define them.
Impact of new pacemaker implantation following surgical and transcatheter aortic valve replacement on 1-year outcome
Authors: Fujita Buntaro , Schmidt Tobias , Bleiziffer Sabine , Bauer Timm , Beckmann Andreas , Bekeredjian Raffi , Möllmann Helge , Walther Thomas , Landwehr Sandra , Hamm Christian , Beyersdorf Friedhelm , Katus Hugo A , Harringer Wolfgang , Ensminger Stephan , Frerker Christian ,   GARY Executive Board
Published: May 2019

AbstractOBJECTIVESThe purpose of this study was to evaluate the incidence of new pacemaker implantation (NPMI) after surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR), and investigate its influence on 1-year mortality.METHODSPatients who were enrolled in ‘The German Aortic Valve Registry’ undergoing isolated TAVR or SAVR between 2011 and 2015 were analysed. The rate of NPMI was analysed for both groups and multivariable Cox regression analysis was performed to investigate the possible independent association between NPMI and 1-year mortality.RESULTSTwenty thousand eight hundred and seventy-two patients who underwent TAVR and 17 750 patients who received SAVR were included in this study. The rate of NPMI was 16.6% after TAVR and 3.6% after SAVR. In the TAVR group, NPMI was associated with significantly increased 1-year mortality in univariable Cox regression analysis [hazard ratio (HR) 1.29, confidence interval (CI) 1.18–1.41; P &lt; 0.001]. This association persisted after adjustment for confounding factors (HR 1.29, CI 1.16–1.43; P &lt; 0.001). In the SAVR group, NPMI significantly increased 1-year mortality in univariable analysis as well (HR 1.55, CI 1.08–2.22; P = 0.02), whereas after multivariable adjustment, NPMI did not emerge as an independent risk factor (HR 1.29, 0.88–1.89; P = 0.19). NPMI was not associated with 30-day mortality in both procedure groups.CONCLUSIONSThe rate of NPMI was markedly higher after TAVR compared with SAVR and was independently associated with 1-year mortality after TAVR, whereas this was not significant after SAVR. As 30-day mortality was not different for TAVR and SAVR, the subsequent procedure of an NPMI itself seems not to increase the risk of mortality.
Learning EAP at university: perceptions of high-achieving first-year ESL undergraduates
Authors: Yung Kevin Wai-Ho , Fong Natalie 
Published: May 2019

AbstractThis study focuses on the perceptions of learning EAP of first-year undergraduates with high ESL proficiency admitted to an English-medium university in Hong Kong. Two in-depth individual interviews were conducted with nine participants and their written assignments were analysed. The data reveal several challenges facing the high achievers in learning EAP. One evident aspect is how to properly cite academic sources. The participants struggled with selecting suitable texts from sources, paraphrasing them, and using them to support their arguments. They also perceived a need to abandon the recited formulaic expressions which may have helped them score highly in the secondary school examination. This study reveals gaps between the English learnt in secondary school and EAP and offers insight into what first-year students need when they transition from secondary school to university studies. It argues that EAP should be made an essential component of first-year undergraduate programmes.
Forced diuresis with matched hydration during transcatheter aortic valve implantation for Reducing Acute Kidney Injury: a randomized, sham-controlled study (REDUCE-AKI)
Authors: Arbel Yaron , Ben-Assa Eyal , Puzhevsky Daniela , Litmanowicz Batia , Galli Naama , Chorin Ehud , Halkin Amir , Sadeh Ben , Konigstein Maayan , Bassat Orit Kliuk-Ben , Steinvil Arie , Bazan Samuel , Banai Shmuel , Finkelstein Ariel 
Published: May 2019

Abstract

Aims
Acute kidney injury (AKI) is a common complication following transcatheter aortic valve implantation (TAVI) and is associated with increased risk for short- and long-term mortality. In patients undergoing percutaneous coronary intervention (PCI), forced diuresis with matched hydration has been shown to reduce the incidence of AKI by ∼50%. The aim of the present study was to evaluate whether forced diuresis with matched intravenous hydration reduces AKI in patients undergoing TAVI.

Methods and results
Reducing Acute Kidney Injury (REDUCE-AKI) was a single-centre, prospective, randomized, double-blind sham-controlled clinical trial, designed to examine the effect of an automated matched saline infusion with urine output for the prevention of AKI in patients undergoing TAVI. A total of 136 TAVI patients were randomized, 68 in each group. Mean age was 83.9 ± 5 years and 41.2% were males. There were no differences in baseline characteristics between the two groups. The rate of AKI was not statistically different between the groups (25% in the active group vs. 19.1% in the sham group, P = 0.408). There was a significant increase in long-term mortality in the active group (27.9% vs. 13. 2% HR 3.744, 95% CI 1.51–9.28; P = 0.004). The study was terminated prematurely by the Data Safety Monitoring Board for futility and a possible signal of harm.

Conclusions
Unlike in PCI, forced diuresis with matched hydration does not prevent AKI in patients undergoing TAVI, and might be associated with increased long-term mortality. Future studies should focus on understanding the mechanisms behind these findings.

Clinicaltrials.gov registration
NCT01866800, 30 April 2013.
Omics-based comparative analysis of putative mobile genetic elements in Lactococcus lactis
Authors: Andersen Joakim Mark , Pedersen Christine Møller , Bang-Berthelsen Claus Heiner 
Published: May 2019

ABSTRACT
Lactococcus lactis is globally used in food fermentation. Genomics is useful to investigate speciation and differential occurrence of (un)desired gene functions, often related to mobile DNA. This study investigates L. lactis for putative chromosomal mobile genetic elements through comparative genomics, and analyses how they contribute to chromosomal variation at strain level. Our work identified 95 loci that may range over 10% of the chromosome size when including prophages, and the loci display a marked differential occurrence in the analysed strains. Analysis of differential transcriptomics data revealed how mobile genetic elements may impact the host physiology in response to conditional changes. This insight in the genetic variation of mobile genetic elements in L. lactis holds potential to further identify important functions related to food and biotechnology applications within this important species.
Working with Older Adults Scale: Application of the Theory of Planned Behavior
Authors: Graham Kirsten L , Rosén Lee A 
Published: May 2019

Abstract

Background and Objectives
The expanding population of older adults in the United States, coupled with provider hesitance to work with this population, is expected to result in a large service gap, particularly in the health care field. Research on provider hesitancy has largely focused on the impact of attitudes toward older adults and professional competency, with some recent explorations of social influences. There is currently no comprehensive measure that includes all of these areas.

Research Design and Methods
The present study outlines the development of the Working with Older Adults Scale (WOAS), which is grounded in the theory of planned behavior as applied to working with older adults. The WOAS is composed of 20 items, rated on a 7-point Likert scale, that make up four subscales: (i) Attitude, (ii) Subjective Norm, (iii) Perceived Behavioral Control, and (iv) Intention.

Results
Results indicated that, for the young adult college student sample it was developed with, the measure has an excellent factor structure and good internal reliability and construct validity. Consistent with the theory of planned behavior model, intention to work with older adults was significantly predicted by attitudes, subjective norm, and perceived behavioral control. Subjective norm accounted for the greatest amount of variance. Further analyses revealed differential effects of age, gender, and experience on the WOAS subscales.

Discussion and Implications
The WOAS, and underlying theory, offers new insights and ideas for future exploration of the service gap between older adults’ needs and professional availability across health service fields.
Participatory Action Research With Older Adults: A Critical Interpretive Synthesis
Authors: Corrado Ann Marie , Benjamin-Thomas Tanya Elizabeth , McGrath Colleen , Hand Carri , Laliberte Rudman Debbie 
Published: May 2019

AbstractBackground and ObjectivesGiven population aging, the meaningful involvement of older adults in influencing policy and programs through participatory action research (PAR) is increasingly vital. PAR holds promise for equitable participation, co-learning, community mobilization, and personal and social transformation, however, little scholarly attention has been given to critically evaluating how PAR has been taken up with older adults. The objective of this review was to critically evaluate the use of PAR with older adults.Research Design and MethodsA critical interpretive synthesis (CIS) of 40 PAR studies with older adults was conducted. Critical engagement with the articles identified dominant tendencies, limits of these tendencies, and proposed ways forward.ResultsWithin the majority of articles reviewed, older adults were not prominent partners in PAR given their often limited involvement in designing the research questions, learning research skills and knowledge, and implementing findings for change. Furthermore, power differentials between researchers and older adults were evident, as older adults were often positioned as participants rather than partners. Finally, this article demonstrates various boundaries on the foci of studies related to inclusivity and sustainability.Discussion and ImplicationsThis study revealed that the promises PAR holds are often not fully realized in projects with older adults, given that they are rarely positioned as equitable partners, co-learners, or agents for change. The findings have the potential to stimulate further uptake of PAR research with an older adult population, highlighting areas for change in systems and research practices.
Thoracoscopy-assisted repair of comminuted sternal fracture with bioresorbable plates
Authors: Imanishi Naoko , Takeda Yusuke , Ichiki Yoshinobu , Tanaka Fumihiro 
Published: May 2019

Abstract
We present a case of comminuted sternal fracture with posterior displacement, which was successfully repaired by ‘sandwich’ fixation using 2 bioresorbable plates that were placed anterior to and posterior to the sternum. All procedures including retro-sternal dissection for placement of the posterior plate were performed using video-assisted thoracoscopic surgery. The minimally invasive thoracoscopic technique provided effective repair and rigid fixation with immediate relief from intractable chest pain that had persisted before surgery.
Inducing Super-Approximation
Authors: Salehi Golsefidy Alireza , Zhang Xin 
Published: May 2019

Abstract
Let $\Gamma _2\subseteq \Gamma _1$ be finitely generated subgroups of ${\operatorname{GL}}_{n_0}({\mathbb{Z}}[1/q_0])$ where $q_0$ is a positive integer. For $i=1$ or $2$, let ${\mathbb{G}}_i$ be the Zariski-closure of $\Gamma _i$ in $({\operatorname{GL}}_{n_0})_{{\mathbb{Q}}}$, ${\mathbb{G}}_i^{\circ }$ be the Zariski-connected component of ${\mathbb{G}}_i$, and let $G_i$ be the closure of $\Gamma _i$ in $\prod _{p\nmid q_0}{\operatorname{GL}}_{n_0}({\mathbb{Z}}_p)$. In this article we prove that if ${\mathbb{G}}_1^{\circ }$ is the smallest closed normal subgroup of ${\mathbb{G}}_1^{\circ }$ that contains ${\mathbb{G}}_2^{\circ }$ and $\Gamma _2\curvearrowright G_2$ has spectral gap, then $\Gamma _1\curvearrowright G_1$ has spectral gap.