bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hydro Energy Harvesting by Using Compliant Surfaces: Preliminary Experimental Assessment
Authors: Arias Francisco J. , Heras Salvador De Las 
Published: February 2020

Abstract
In this work consideration is given for hydro energy harvesting contained in residual water streams. The idea lies in the bifurcation of the stream into two channels separated by a compliant surface or membrane which, albeit with equalized static pressure at both sides, nevertheless with a relative velocity. As a result of the differential dynamic pressure, a steady-state harmonic motion is established which might be transformed into an electrical output. A first experimental assessment of this idea constitutes the core of this presentation.
The next step in learning from sentinel events in healthcare
Authors: Bos Kelly , Dongelmans Dave A , Greuters Sjoerd , Kamps Gert-Jan , van der Laan Maarten J 
Published: February 2020

ObjectiveThe aim of this study was to evaluate the current status of handling and learning from sentinel events (SEs) in Dutch academic hospitals and to develop a basis for the first steps in a joint and transparent approach to improve learning from SEs.DesignSurvey by the Netherlands Federation of University Medical Centres (NFU) as part of the project ‘Quality-based Governance’.Participants and settingAll eight Dutch University Medical Centres (UMCs).ResultsThree methods are used to identify the root cause of SEs: the Systematic Incident Reconstruction and Evaluation, Prevention and Recovery Information System for Monitoring and Analysis or TRIPOD method. Experts with different backgrounds are involved in the analysis of SEs. UMCs have different policies regarding the selection of recommendations for implementation. Some UMCs implement all recommendations formulated by the analysis team and in some UMCs the head of the involved department selects recommendations for implementation. No predetermined criteria have been established for this selection. Most UMCs confirm that similar SEs reoccur, which might be due to the quality of the analysis of the SEs or the quality of the recommendations.ConclusionThere is a large variety in handling SEs in Dutch academic hospitals and standards for the selection of recommendations are lacking. A next step to decrease the number of (similar) SEs lies in a joint and transparent approach to objectively assess recommendations and further define strategies for successful implementation. Selecting high-quality recommendations for implementation has the potential to lead to a decrease in the number of (similar) SEs and increase in the quality and safety of Dutch healthcare.
Outcomes and adverse factors for endoscopic mucosal resection (EMR) of colorectal polyps in elderly patients
Authors: Skouras Thomas , Bond Ashley , Gaglia Asimina , Bonnett Laura , Jiang Lim Meng , Sarkar Sanchoy 
Published: February 2020

IntroductionEndoscopic mucosal resection (EMR) is an invaluable technique, however it is associated with significant risks. In the elderly in particular, the long-term survival benefits of polyp resection with EMR are unknown. The aim of this study was to determine the long-term outcomes in elderly patients who had undergone EMR and to identify any adverse factors.MethodA retrospective observational study on patients of 75 years of age or greater, who underwent EMR of colorectal polyps, in a single tertiary centre, from 2005 to 2014. Demographics of the patients, including Charlson Comorbidity Index (CCI), endoscopic and histological data, were reviewed to identify potential factors predicting outcomes.ResultsThe patients’ median age was 80 years. In total 239 procedures were performed in 206 unique patients. The complication rate was 1.6%. Mean overall survival was 6.7 years with only one patient dying from metastatic colorectal cancer (0.5%) and 49 dying from non-colorectal cancer conditions (24%). Age more than 79 years and CCI more than 2 were independent predictors of significantly shorter survival (p=<0.01). Gender, size of the removed polyps and total number of polyps were not statistically significantly affecting survival. Patients who had more than two colonoscopies were found to have a survival benefit (p=0.02).ConclusionEMR of colonic polyps is safe even for elderly patients. However, the decision to proceed to complex endoscopic therapy should be individualised considering the patients’ age and comorbidities. CCI can help to objectively assess the comorbid state of a patient prior to such decisions.
Modes of late mortality in patients with a Fontan circulation
Authors: Poh Chin , Hornung Tim , Celermajer David S , Radford Dorothy J , Justo Robert N , Andrews David , du Plessis Karin , Iyengar Ajay J , Winlaw David , d'Udekem Yves 
Published: February 2020

ObjectivesThe mechanisms of attrition of the Fontan population have been poorly characterised and it is unclear whether some of the deaths are potentially preventable. We analysed the circumstances of late death in patients with a Fontan circulation, with a special focus on identifying lesions amenable to intervention that may have contributed to the decline of their circulation.MethodsBetween 1975 and 2018, a total of 105 patients from a Bi-National Registry died beyond 1 year after Fontan completion, at a median age of 18.6 (IQR 13.8–26.0) years old, 12.7 (IQR 6.0–19.3) years after Fontan completion.ResultsA total of 105 patients died—63 patients (60%) with an atriopulmonary (AP) Fontan, 21 patients (20%) with a lateral tunnel (LT) and 21 patients (20%) with an extracardiac conduit (ECC). 72 patients (69%) were reviewed within 2 years preceding death, with 32% (23/72) deemed to be clinically well. Fontan circulatory failure was the most common cause of death in 42 patients (45%). Other causes of death included sudden death/arrhythmia (19%), perioperative death (12%), neurological complication (7%) and thromboembolism (7%). All patients with an LT or ECC who died from Fontan failure had at least one surgical defect that was amenable to intervention at time of death.ConclusionsConventional clinical surveillance has been insensitive in detecting a significant proportion of patients at risk of late death. Fontan circulatory failure contributes to half of the late deaths. Patients with an LT or ECC Fontan who died with a clinical picture of circulation failure may have potentially correctable lesions.
Variability in echocardiography and MRI for detection of cancer therapy cardiotoxicity
Authors: Lambert James , Lamacie Mariana , Thampinathan Babitha , Altaha Mustafa A , Esmaeilzadeh Maryam , Nolan Mark , Fresno Camila Urzua , Somerset Emily , Amir Eitan , Marwick Thomas H , Wintersperger Bernd J , Thavendiranathan Paaladinesh 
Published: February 2020

ObjectivesTo compare variability of echocardiographic and cardiovascular magnetic resonance (CMR) measured left ventricular (LV) function parameters and their relationship to cancer therapeutics-related cardiac dysfunction (CTRCD).MethodsWe prospectively recruited 60 participants (age: 49.8±11.6 years), 30 women with human epidermal growth factor receptor 2-positive breast cancer (15 with CTRCD and 15 without CTRCD) and 30 healthy volunteers. Patients were treated with anthracyclines and trastuzumab. Participants underwent three serial CMR (1.5T) and echocardiography studies at ~3-month intervals. Cine-CMR for LV ejection fraction (LVEF), myocardial tagging for global longitudinal strain (GLS) and global circumferential strain (GCS), two-dimensional (2D) echocardiography for strain and LVEF and three-dimensional (3D) echocardiography for LVEF measurements were obtained. Temporal, interobserver and intraobserver variability were calculated as the coefficient of variation and as the SE of the measurement (SEM). Minimal detected difference (MDD) was defined as 2xSEM.ResultsPatients with CTRCD demonstrated larger mean temporal changes in all parameters compared with those without: 2D-LVEF: 4.6% versus 2.8%; 3D-LVEF: 5.2% vs 2.3%; CMR-LVEF: 6.6% versus 2.7%; 2D-GLS: 1.9% versus 0.7%, 2D-GCS: 2.5% versus 2.2%; CMR-GCS: 2.7% versus 1.6%; and CMR-GLS: 2.1% versus 1.4%, with overlap in 95% CI for 2D-LVEF, 2D-GCS, CMR-GLS and CMR-GCS. The respective mean temporal variability/MDD in healthy volunteers were 3.3%/6.5%, 1.8%/3.7%, 2.2%/4.4%, 0.8%/1.5%, 1.9%/3.7%, 1.8%/3.6% and 1.4%/2.8%. Although the mean temporal variability in healthy volunteers was lower than the mean temporal changes in CTRCD, at the individual level, 2D-GLS, 3D-LVEF and CMR-LVEF had the least overlap. 2D-GLS and CMR-LVEF had the lowest interobserver/intraobserver variabilities.ConclusionTemporal changes in 3D-LVEF, 2D-GLS and CMR LVEF in patients with CTRCD had the least overlap with the variability in healthy volunteers; however, 2D-GLS appears to be the most suitable for clinical application in individual patients.
Barley (Hordeum vulgare) seedling growth declines with increasing exposure to silver nanoparticles in biosolid-amended soils
Authors: González Linares Mónica , Jia Yu , Sunahara Geoffrey I. , Whalen Joann K. 
Published: February 2020

Silver nanoparticles (AgNPs), a component of many consumer products, are considered an environmental risk due to the broad-spectrum toxicity of Ag+ to non-target organisms. Most AgNPs released from consumer products will end up as biosolids in wastewater treatment plants, which are often applied as a fertilizer to agriculture. Land application of biosolids may add AgNPs to the soil–plant system, with unknown consequences. This study investigated the growth of Hordeum vulgare seedlings, Ag bioconcentration and distribution in shoot and root tissues of barley exposed to biosolid-amended Delacour and Organization for Economic Co-operation and Development (OECD) soils spiked with AgNPs (up to 366 mg Ag kg−1 dry soil). In both soils, root and shoot growth declined linearly as the concentration of AgNPs increased. Barley had higher Ag bioconcentration values when grown in the OECD soil than in the Delacour soil. Silver bioavailability was greater in the OECD soil due to its physicochemical properties, such as low calcium concentration and acidic pH, relative to the Delacour soil. Barley seedlings exhibited morphological changes, including smaller shoots and shorter, thick roots after 14 d exposure to AgNPs. We conclude that plant structural responses, particularly changes in root biomass, could be an early diagnostic of seedling exposure to AgNPs in biosolid-amended soils.
Integrated geophysical, sedimentological and geotechnical investigation of submarine landslides in the Gulf of Lions (Western Mediterranean)
Authors: Badhani Shray , Cattaneo Antonio , Collico Stefano , Urgeles Roger , Dennielou Bernard , Leroux Estelle , Colin Florent , Garziglia Sebastien , Rabineau Marina , Droz Laurence 
Published: February 2020

Abstract

The Gulf of Lions presents recurring mass-transport deposits (MTDs) within the Plio-Quaternary sediments, suggesting a long history of mass movements. The two large, surficial MTDs are located on the eastern and western levee of the Rhone canyon over an area exceeding 6000 km
2
and volumes exceeding 100 km
3
. Both MTDs were emplaced 21 ka ago (peak of the Last Glacial Maximum), suggesting a common trigger. Here, we present a multidisciplinary high-resolution geophysical, sedimentological and
in-situ
geotechnical study of the source and deposit areas of both MTDs to characterize distinct expressions of sediment deformation as well as their spatial and chronological distributions. We show the internal structure of mass movements and resulting MTDs with unprecedented details that were previously represented in the conventional seismic data as transparent and chaotic facies. The combination of multidisciplinary approaches shows new insights into the nature of basal surfaces of the slope failures. In particular, we show that the basal surfaces of the failures consist of clay-rich material contrasting with the overlying turbiditic deposits, suggesting that a strong lithological heterogeneity exists within the strata. We suggest that this change in lithology between clay-rich sediments and turbiditic sequences most likely controls the localization of weak layers and landslide basal surfaces.
On the Power of Border of Depth-3 Arithmetic Circuits
Authors: Kumar Mrinal 
Published: February 2020

We show that over the field of complex numbers,
every
homogeneous polynomial of degree
d
can be approximated (in the border complexity sense) by a depth-3 arithmetic circuit of top fan-in at most 2. This is quite surprising, since there exist homogeneous polynomials
P
on
n
variables of degree 2, such that any depth-3 arithmetic circuit computing
P
must have top fan-in at least Ω (
n
).

As an application, we get a new tradeoff between the top fan-in and formal degree in an approximate analog of the celebrated depth reduction result of Gupta, Kamath, Kayal, and Saptharishi [7, 10]. Formally, we show that if a degree
d
homogeneous polynomial
P
can be computed by an arithmetic circuit of size
s
≥
d
, then for every
t
≤
d
,
P
is in the border of a depth-3 circuit of top fan-in

s

O(
t
)

and formal degree

s

O(
d/t
)

. To the best of our knowledge, the upper bound on the top fan-in in the original proof of Reference [7] is always at least
s

Ω
(√d)

, regardless of the formal degree.
Translational and Rotational Arrow Cues (TRAC) Navigation Method for Manual Alignment Tasks
Authors: Usevitch David E. , Sperry Adam J. , Abbott Jake J. 
Published: February 2020

Many tasks in image-guided surgery require a clinician to manually position an instrument in space, with respect to a patient, with five or six degrees of freedom (DOF). Displaying the current and desired pose of the object on a 2D display such as a computer monitor is straightforward. However, providing guidance to accurately and rapidly navigate the object in 5-DOF or 6-DOF is challenging. Guidance is typically accomplished by showing distinct orthogonal viewpoints of the workspace, requiring simultaneous alignment in all views. Although such methods are commonly used, they can be quite unintuitive, and it can take a long time to perform an accurate 5-DOF or 6-DOF alignment task. In this article, we describe a method of visually communicating navigation instructions using translational and rotational arrow cues (TRAC) defined in an object-centric frame, while displaying a single principal view that approximates the human’s egocentric view of the physical object. The target pose of the object is provided but typically is used only for the initial gross alignment. During the accurate-alignment stage, the user follows the unambiguous arrow commands. In a series of human-subject studies, we show that the TRAC method outperforms two common orthogonal-view methods—the triplanar display, and a sight-alignment method that closely approximates the Acrobot Navigation System—in terms of time to complete 5-DOF and 6-DOF navigation tasks. We also find that subjects can achieve 1 mm and 1° accuracy using the TRAC method with a median completion time of less than 20 seconds.
Harnessing Population Pedigree Data and Machine Learning Methods to Identify Patterns of Familial Bladder Cancer Risk
Authors: Hanson Heidi A. , Leiser Claire L. , O'Neil Brock , Martin Christopher , Gupta Sumati , Smith Ken R. , Dechet Christopher , Lowrance William T. , Madsen Michael J. , Camp Nicola J. 
Published: February 2020

Abstract

Background:
Relatives of patients with bladder cancer have been shown to be at increased risk for kidney, lung, thyroid, and cervical cancer after correcting for smoking-related behaviors that may concentrate in some families. We demonstrate a novel approach to simultaneously assess risks for multiple cancers to identify distinct multicancer configurations (multiple different cancer types that cluster in relatives) surrounding patients with familial bladder cancer.

Methods:
This study takes advantage of a unique population-level data resource, the Utah Population Database (UPDB), containing vast genealogy and statewide cancer data. Familial risk is measured using standardized incidence risk (SIR) ratios that account for sex, age, birth cohort, and person-years of the pedigree members.

Results:
We identify 1,023 families with a significantly higher bladder cancer rate than population controls (familial bladder cancer). Familial SIRs are then calculated across 25 cancer types, and a weighted Gower distance with K-medoids clustering is used to identify familial multicancer configurations (FMC). We found five FMCs, each exhibiting a different pattern of cancer aggregation. Of the 25 cancer types studied, kidney and prostate cancers were most commonly enriched in the familial bladder cancer clusters. Laryngeal, lung, stomach, acute lymphocytic leukemia, Hodgkin disease, soft-tissue carcinoma, esophageal, breast, lung, uterine, thyroid, and melanoma cancers were the other cancer types with increased incidence in familial bladder cancer families.

Conclusions:
This study identified five familial bladder cancer FMCs showing unique risk patterns for cancers of other organs, suggesting phenotypic heterogeneity familial bladder cancer.

Impact:
FMC configurations could permit better definitions of cancer phenotypes (subtypes or multicancer) for gene discovery and environmental risk factor studies.
Discovery of Berberine that Targetedly Induces Autophagic Degradation of both BCR-ABL and BCR-ABL T315I through Recruiting LRSAM1 for Overcoming Imatinib Resistance
Authors: Yin Zhao , Huang Guiping , Gu Chunming , Liu Yanjun , Yang Juhua , Fei Jia 
Published: February 2020

Abstract

Purpose:
Imatinib, the breakpoint cluster region protein (BCR)/Abelson murine leukemia viral oncogene homolog (ABL) inhibitor, is widely used to treat chronic myeloid leukemia (CML). However, imatinib resistance develops in many patients. Therefore, new drugs with improved therapeutic effects are urgently needed. Berberine (BBR) is a potent BCR-ABL inhibitor for imatinib-sensitive and -resistant CML.

Experimental Design:
Protein structure analysis and virtual screening were used to identify BBR targets in CML. Molecular docking analysis, surface plasmon resonance imaging, nuclear magnetic resonance assays, and thermoshift assays were performed to confirm the BBR target. The change in BCR-ABL protein expression after BBR treatment was assessed by Western blotting. The effects of BBR were assessed in vitro in cell lines, in vivo in mice, and in human CML bone marrow cells as a potential strategy to overcome imatinib resistance.

Results:
We discovered that BBR bound to the protein tyrosine kinase domain of BCR-ABL. BBR inhibited the activity of BCR-ABL and BCR-ABL with the T315I mutation, and it also degraded these proteins via the autophagic lysosome pathway by recruiting E3 ubiquitin-protein ligase LRSAM1. BBR inhibited the cell viability and colony formation of CML cells and prolonged survival in CML mouse models with imatinib sensitivity and resistance.

Conclusions:
The results show that BBR directly binds to and degrades BCR-ABL and BCR-ABL T315I via the autophagic lysosome pathway by recruiting LRSAM1. The use of BBR is a new strategy to improve the treatment of patients with CML with imatinib sensitivity or resistance.
See related commentary by Elf, p. 3899
Induced Tumor Heterogeneity Reveals Factors Informing Radiation and Immunotherapy Combinations
Authors: Aguilera Todd A. , Elghonaimy Eslam A. , Shehade Hussein , Rafat Marjan , Castellini Laura , Jiang Dadi , Kariolis Mihalis , Koong Albert C. , Le Quynh-Thu , Ellies Lesley G. , Rankin Erinn B. , Graves Edward E. , Giaccia Amato J. 
Published: February 2020

Abstract

Purpose:
To investigate how induced tumor heterogeneity influences immune responses to radiotherapy with different proportions of mixed immune-responsive and unresponsive tumor cells in a triple-negative breast cancer model. It is hypothesized that studying the immune environment of mixed tumors and responses to radiotherapy could nominate immune active therapies to enhance immune responses after radiotherapy.

Experimental Design:
Evaluate efficacy and immune responses generated by radiotherapy in tumors with different proportions of immunologically responsive and unresponsive tumor cells. Then study the cellular responses and transcriptomic differences between the tumors to nominate immunotherapy combinations with radiotherapy and evaluate the combination.

Results:
The addition of the responsive cells to unresponsive tumors led to a greater than expected therapeutic response to radiotherapy with both innate and adaptive immune components. There was a distinct change in myeloid cells, greater inflammatory macrophage activity, and enhanced antigen presentation with responsive cells after radiotherapy. Because differences in matrix components, cell adhesion biology, and innate immune signaling correlated with myeloid cell response and phenotype, we hypothesized that radiotherapy combined with CD40 agonist antibody would sensitize unresponsive tumors. The combination therapy resulted in improved innate and adaptive immune response. Importantly, CD40 treatment increased tumor response to radiotherapy and protected against metastatic spread in a metastatic model.

Conclusions:
These data combined with transcriptomics from human patients support radiotherapy and myeloid cell targeting for immunologically cold tumors. The established study model presents opportunities to investigate the complex overlapping biologic mechanisms that limit immunotherapy and to implement radiotherapy with different immunotherapy combinations.
Ku80-Targeted pH-Sensitive Peptide–PNA Conjugates Are Tumor Selective and Sensitize Cancer Cells to Ionizing Radiation
Authors: Kaplan Alanna R. , Pham Ha , Liu Yanfeng , Oyaghire Stanley , Bahal Raman , Engelman Donald M. , Glazer Peter M. 
Published: February 2020

Abstract

The development of therapeutic agents that specifically target cancer cells while sparing healthy tissue could be used to enhance the efficacy of cancer therapy without increasing its toxicity. Specific targeting of cancer cells can be achieved through the use of pH-low insertion peptides (pHLIP), which take advantage of the acidity of the tumor microenvironment to deliver cargoes selectively to tumor cells. We developed a pHLIP–peptide nucleic acid (PNA) conjugate as an antisense reagent to reduce expression of the otherwise undruggable DNA double-strand break repair factor, KU80, and thereby radiosensitize tumor cells. Increased antisense activity of the pHLIP–PNA conjugate was achieved by partial mini-PEG sidechain substitution of the PNA at the gamma position, designated pHLIP-αKu80(γ). We evaluated selective effects of pHLIP-αKu80(γ) in cancer cells in acidic culture conditions as well as in two subcutaneous mouse tumor models. Fluorescently labeled pHLIP-αKu80(γ) delivers specifically to acidic cancer cells and accumulates preferentially in tumors when injected i.v. in mice. Furthermore, pHLIP-αKu80(γ) selectively reduced KU80 expression in cells under acidic conditions and in tumors in vivo. When pHLIP-αKu80(γ) was administered to mice prior to local tumor irradiation, tumor growth was substantially reduced compared with radiation treatment alone. Furthermore, there was no evidence of acute toxicity associated with pHLIP-αKu80(γ) administration to the mice. These results establish pHLIP-αKu80(γ) as a tumor-selective radiosensitizing agent.

Implications:
This study describes a novel agent, pHLIP-αKu80(γ), which combines PNA antisense and pHLIP technologies to selectively reduce the expression of the DNA repair factor KU80 in tumors and confer tumor-selective radiosensitization.