bluuebunny/crossref_metadata_2025_split huggingface dataset:
Home care for the elderly in Sweden, Germany and Italy: A case of multi‐level governance strategy‐making
Authors: Longo Francesco , Notarnicola Elisabetta 
Published: February 2018

AbstractHome care is a policy field characterized by strong interdependencies and multi‐level governance. In such a setting, decision‐ and strategy‐making is complex, with interrelated governance mechanisms between the private and public actors involved, and the risk of lack of a clear and sharp definition of public contents. In this article we are interested in understanding “if and how” multi‐level governance influences planning in home care and, more generally, social care fields. Through the analysis of home care services for the elderly in three prominent European countries, the article highlights critical dimensions that should be taken into consideration in such contexts: users' selection, services features, coordination and funding mechanisms, provision forms. These dimensions turn out to be representative of key processes of strategic development within multi‐level settings.
Association of killer cell immunoglobulin‐like receptors with spontaneous clearance of hepatitis C virus in the Chinese population
Authors: Shan Zhengang , Huang Jieting , Liao Qiao , Huang Ke , Wang Min , Xu Ru , Tang Xi , Zhang Weiyun , Nelson Kenrad , Fu Yongshui , Li Chengyao , Rong Xia 
Published: February 2018

BACKGROUNDNatural killer (NK) cells are critical components in innate immune response to viral infection. Killer cell immunoglobulin‐like receptors (KIRs) are involved in regulating the balance of activation or inhibitory function of NK cells. However, the association of KIRs with the spontaneous clearance of hepatitis C virus (HCV) remains unclear in the Chinese population.STUDY DESIGN AND METHODSA total of 407 HCV‐seropositive voluntary blood donors were recruited, including 203 with spontaneous viral clearance and 204 with chronic infection. The presence of KIR genes was detected individually by polymerase chain reaction with sequence‐specific primers. Data of HLA and interleukin‐28B (IL28B) genotypes were extracted from our previous study.RESULTSOur results showed that KIR2DL2, 2DS2, 2DL2/2DL3, and 2DL5A–/2DL5B+ were more frequent in subjects with HCV clearance than those with chronic infection (odds ratio [OR], 1.640, p = 0.034; OR, 1.664, p = 0.032; OR, 1.636, p = 0.040; and OR, 2.601, p = 0.012, respectively). Multivariate logistic regression analysis showed that KIR2DL5A–/2DL5B+ associated with HCV clearance (OR, 2.448, p = 0.027), independent of sex, IL28B, and other KIRs. In contrast, KIR2DL3/2DL3 (OR, 0.610, p = 0.034) as well as 2DL3/2DL3+HLA‐C1 or C1C1 (OR, 0.580, p = 0.017; and OR, 0.639, p = 0.025, respectively) was found associated with chronic HCV infection. The presence of the homozygous KIR2DL3 with or without its HLA ligand increased the OR of developing chronic HCV infection in the context of IL28B.CONCLUSIONSIn this study we identified KIR2DL5A–/2DL5B+ associated with HCV spontaneous clearance, while KIR2DL3/2DL3, 2DL3/2DL3+HLA‐C1, or C1C1 associated with chronic infection. Our study highlighted the fact that the roles of KIR and KIR‐HLA contributed to the control of HCV infection by innate immune responses.
Lenograstim 5 µg/kg is not superior to biosimilar filgrastim 10 µg/kg in lymphoma patients undergoing peripheral blood stem cell mobilization after chemotherapy: preliminary results from a prospective randomized study
Authors: Marchesi Francesco , Vacca Michele , Giannarelli Diana , Ipsevich Francesco , Pandolfi Annino , Gumenyuk Svitlana , Renzi Daniela , Palombi Francesca , Pisani Francesco , Romano Atelda , Spadea Antonio , Papa Elena , Canfora Marco , Pierelli Luca , Mengarelli Andrea 
Published: February 2018

BACKGROUNDRandomized trials comparing chemomobilization efficiency between lenograstim and biosimilar filgrastim are lacking. Our previous retrospective study suggested that lenograstim could be more effective than biosimilar filgrastim when used at the same conventional dosage (5 µg/kg) only in lymphoma patients undergoing peripheral blood stem cell mobilization. We planned a prospective randomized study comparing lenograstim 5 µg/kg with biosimilar filgrastim 10 µg/kg to verify the hypothesis of lenograstim superiority even at half the dosage (stress test). Herein we report data after enrolling 60% of planned patients.STUDY DESIGN AND METHODSFrom October 2014 to November 2017, a total of 42 of 70 planned patients with lymphoma were randomly assigned to receive lenograstim 5 µg/kg (21) or biosimilar filgrastim 10 µg/kg (21). Patients were stratified according to treatment line at the time of mobilization (1 or ≥2). Primary endpoint was the rate of achievement of the CD34+ cell collection target dose (≥ 4 × 106/kg). An improvement by 23% was expected to validate the hypothesis of lenograstim superiority.RESULTSThe two cohorts were balanced for all the baseline features. We observed an identical rate of patients able to reach the targeted CD34+ cell dose and of mobilization failures (90.4 and 4.8% in both cohorts) and a perfect equivalence in any of the secondary collection outcomes. The hypothesis of lenograstim superiority was not corroborated at interim analysis.CONCLUSIONLenograstim at conventional dosage has failed to demonstrate its superiority over biosimilar filgrastim at double the dosage at interim analysis in their first head‐to‐head trial.
A 3‐dimensional‐printed patient‐specific guide system for minimally invasive plate osteosynthesis of a comminuted mid‐diaphyseal humeral fracture in a cat
Authors: Oxley Bill 
Published: February 2018

AbstractObjectiveTo report the use of a 3‐dimensional (3D)‐printed patient‐specific reduction guide system to facilitate minimally invasive plate osteosynthesis (MIPO) of a humeral fracture in a cat.Study designCase report.AnimalsA 9‐year‐old male neutered domestic short hair cat weighing 4.4 kg.MethodsA 9‐year‐old male domestic short hair cat was presented with a comminuted, mid‐diaphyseal left humeral fracture. Computed tomographic data were processed to yield 3D mesh representations of both humeri and subsequently manipulated in computer‐aided design software. The mirrored, intact humerus was used as a template for appropriate spatial orientation of the major proximal and distal fracture fragments. Patient‐specific Ellis pin orientation guides and a reduction guide were designed and 3D printed. The guide system was used intraoperatively to align the major fracture fragments before application of locking internal fixation via standard MIPO surgical portals.ResultsInternal fixation of the fracture resulted in appropriate bone alignment. Recovery was uncomplicated, with early return to normal limb function and radiographic evidence of advanced fracture healing after 4 months.ConclusionA 3D‐printed patient‐specific reduction guide system facilitated accurate alignment of a comminuted humeral fracture during MIPO without intraoperative imaging.
The Superimposed Deubiquitination Effect of OTULIN and Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) Nsp11 Promotes Multiplication of PRRSV
Authors: Su Yanxin , Shi Peidian , Zhang Lilin , Lu Dong , Zhao Chengxue , Li Ruiqiao , Zhang Lei , Huang Jinhai 
Published: February 2018

ABSTRACT

Linear ubiquitination plays an important role in the regulation of the immune response by regulating nuclear factor κB (NF-κB). The linear ubiquitination-specific deubiquitinase ovarian tumor domain deubiquitinase with linear linkage specificity (OTULIN) can control the immune signaling transduction pathway by restricting the Met1-linked ubiquitination process. In our study, the porcine OTLLIN gene was cloned and deubiquitin functions were detected in a porcine reproductive and respiratory syndrome virus (PRRSV)-infected-cell model. PRRSV infection promotes the expression of the OTULIN gene; in turn, overexpression of OTULIN contributes to PRRSV proliferation. There is negative regulation of innate immunity with OTULIN during viral infection. The cooperative effects of swine OTULIN and PRRSV Nsp11 potentiate the ability to reduce levels of cellular protein ubiquitin associated with innate immunity. Importantly, PRRSV Nsp11 recruits OTULIN through a nonenzymatic combination to enhance its ability to remove linear ubiquitination targeting NEMO, resulting in a superimposed effect that inhibits the production of type I interferons (IFNs). Our report presents a new model of virus utilization of the ubiquitin-protease system
in vivo
from the perspective of the viral proteins that interact with cell deubiquitination enzymes, providing new ideas for prevention and control of PRRSV.

IMPORTANCE
Deubiquitination effects of swine OTULIN were identified. The interaction between porcine OTULIN and PRRSV Nsp11 is dependent on the OTU domain. PRRSV Nsp11 recruits OTULIN through a nonenzymatic combination to promote removal of linear ubiquitination targeting NEMO, resulting in a superimposed effect that inhibits the production of type I IFNs.
Community-based rehabilitation training after stroke: results of a pilot randomised controlled trial (ReTrain) investigating acceptability and feasibility
Authors: Dean Sarah G , Poltawski Leon , Forster Anne , Taylor Rod S , Spencer Anne , James Martin , Allison Rhoda , Stevens Shirley , Norris Meriel , Shepherd Anthony I , Landa Paolo , Pulsford Richard M , Hollands Laura , Calitri Raff 
Published: February 2018

ObjectivesTo assess acceptability and feasibility of trial processes and the Rehabilitation Training (ReTrain) intervention including an assessment of intervention fidelity.DesignA two-group, assessor-blinded, randomised controlled trial with parallel mixed methods process and economic evaluations.SettingCommunity settings across two sites in Devon.ParticipantsEligible participants were: 18 years old or over, with a diagnosis of stroke and with self-reported mobility issues, no contraindications to physical activity, discharged from National Health Service or any other formal rehabilitation programme at least 1 month before, willing to be randomised to either control or ReTrain and attend the training venue, possessing cognitive capacity and communication ability sufficient to participate. Participants were individually randomised (1:1) via a computer-generated randomisation sequence minimised for time since stroke and level of functional disability. Only outcome assessors independent of the research team were blinded to group allocation.InterventionsReTrain comprised (1) an introductory one-to-one session; (2) ten, twice-weekly group classes with up to two trainers and eight clients; (3) a closing one-to-one session, followed by three drop-in sessions over the subsequent 3 months. Participants received a bespoke home-based training programme. All participants received treatment as usual. The control group received an exercise after stroke advice booklet.Outcome measuresCandidate primary outcomes included functional mobility and physical activity.ResultsForty-five participants were randomised (ReTrain=23; Control=22); data were available from 40 participants at 6 months of follow-up (ReTrain=21; Control=19) and 41 at 9 months of follow-up (ReTrain=21; Control=20). We demonstrated ability to recruit and retain participants. Participants were not burdened by the requirements of the study. We were able to calculate sample estimates for candidate primary outcomes and test procedures for process and health economic evaluations.ConclusionsAll objectives were fulfilled and indicated that a definitive trial of ReTrain is feasible and acceptable.Trial registration numberNCT02429180; Results.
PFN2 and GAMT as common molecular determinants of axonal Charcot-Marie-Tooth disease
Authors: Juneja Manisha , Azmi Abdelkrim , Baets Jonathan , Roos Andreas , Jennings Matthew J , Saveri Paola , Pisciotta Chiara , Bernard-Marissal Nathalie , Schneider Bernard L , Verfaillie Catherine , Chrast Roman , Seeman Pavel , Hahn Angelika F , de Jonghe Peter , Maudsley Stuart , Horvath Rita , Pareyson Davide , Timmerman Vincent 
Published: February 2018

BackgroundCharcot-Marie-Tooth type 2 (CMT2) neuropathy is characterised by a vast clinical and genetic heterogeneity complicating its diagnosis and therapeutic intervention. Identification of molecular signatures that are common to multiple CMT2 subtypes can aid in developing therapeutic strategies and measuring disease outcomes.MethodsA proteomics-based approach was performed on lymphoblasts from CMT2 patients genetically diagnosed with different gene mutations to identify differentially regulated proteins. The candidate proteins were validated through real-time quantitative PCR and western blotting on lymphoblast samples of patients and controls, motor neurons differentiated from patient-derived induced pluripotent stem cells (iPSCs) and sciatic nerves of CMT2 mouse models.ResultsProteomic profiling of patient lymphoblasts resulted in the identification of profilin 2 (PFN2) and guanidinoacetate methyltransferase (GAMT) as commonly downregulated proteins in different genotypes compared with healthy controls. This decrease was also observed at the transcriptional level on screening 43 CMT2 patients and 22 controls, respectively. A progressive decrease in PFN2 expression with age was observed in patients, while in healthy controls its expression increased with age. Reduced PFN2 expression was also observed in motor neurons differentiated from CMT2 patient-derived iPSCs and sciatic nerves of CMT2 mice when compared with controls. However, no change in GAMT levels was observed in motor neurons and CMT2 mouse-derived sciatic nerves.ConclusionsWe unveil PFN2 and GAMT as molecular determinants of CMT2 with possible indications of the role of PFN2 in the pathogenesis and disease progression. This is the first study describing biomarkers that can boost the development of therapeutic strategies targeting a wider spectrum of CMT2 patients.
How much does a heart valve implantation cost and what are the health care costs afterwards?
Authors: Huygens Simone A , Goossens Lucas M A , van Erkelens Judith A , Takkenberg Johanna J M , Rutten-van Mölken Maureen P M H 
Published: February 2018

ObjectiveIn the era of limited healthcare budgets, healthcare costs of heart valve implantations need to be considered to inform cost-effectiveness analyses. We aimed to provide age group-specific costs estimates of heart valve implantations, related complications and other healthcare utilisation following the intervention.MethodsWe performed retrospective analyses of healthcare costs of patients who had undergone heart valve implantations in 2010–2013 and controls using claims data from Dutch health insurers. Heart valve implantations included surgical valve replacement and transcatheter valve implantation in all heart valve positions. Patients were divided in four age groups. Control groups were created by taking random samples of the Dutch population stratified by age, gender, socioeconomic status and comorbidities. We applied non-parametric bootstrapping to address uncertainty of the cost estimates. The association of patient and intervention characteristics with costs was determined by (multilevel) generalised linear models.ResultsThe baseline characteristics of 18 903 patients and 188 925 controls were comparable. The annual healthcare costs were substantially higher for surgical heart valve replacement patients than for controls, especially in the year of heart valve implantation. Factors associated with increased annual healthcare costs for patients were older age, female gender, comorbidities, low socioeconomic status and complications.ConclusionsWe provided a comprehensive overview of age group-specific incidence of heart valve implantations, subsequent survival and complications as well as associated healthcare costs of all patients in the Netherlands. Our results provide real-world costs estimates that can be used as a benchmark for costs of future innovative heart valve implantations.
Nesting habitat selection and distribution of an avian top predator in the Canadian Arctic
Authors: Peck Kristen , Franke Alastair , Lecomte Nicolas , Bêty Joël 
Published: February 2018

Detecting and planning for ecosystem changes from climate and land-use alteration is limited by uncertainty about the current distribution of many species. This is exacerbated in remote areas like the Arctic, where the impacts of climate change are the strongest and where industrial exploration and development are expanding. Using remotely-sensed environmental information and known nest sites, we estimated the breeding distribution and habitat selection of the peregrine falcon (Falco peregrinus) throughout most of Nunavut, a massive northern Canadian territory (>1.8 M km2) encompassing ∼15% of the world’s tundra biome. Our results show that peregrine falcons selected features of prior known importance such as rugged topography, but also sites with higher than average summer temperatures, more productive land classes, lower mean elevations, and lower mean summer precipitation. Our model identifies several areas of high relative probability of peregrine occurrence, some of which were unrecognized to date. Some of these areas may be targets for future industrial developments and are located in an area where some of the fastest climate changes are expected. Our model will allow managers to identify the areas that could be the most critical for monitoring in the context of future development and climate change.
Mitigation of airways responsiveness by deep inflation of the lung
Authors: Bates Jason H. T. , Rajendran Vignesh 
Published: February 2018

Stretching activated strips of airway smooth muscle (ASM) significantly affects both active force and stiffness due to a temporary reduction of the proportion of cycling myosin cross bridges that are bound to their actin binding sites. For the same reason, stretch applied to ASM in situ by a deep inflation (DI) of the lungs is one of the most potent means of reversing bronchoconstriction. When the DI is sufficiently large, however, and is applied while bronchoconstriction is in the process of developing, the subsequent depression in airway resistance is more persistent than can be attributed simply to temporary detachment of ASM cross bridges. In the present study, we use a computational model to demonstrate that this DI-induced ablation of airway responsiveness can be explained by a dose-dependent reduction in the number of cross bridges available to bind to actin when the ASM in the airway wall is stretched above a critical threshold strain and that this disruption of the contractile apparatus recovers over an order of magnitude longer time scale than that of the simple reattachment of unbound cross bridges.NEW & NOTEWORTHY The mechanisms by which deep inflation of the lung reverse bronchoconstriction and affect subsequent airway responsiveness have important potential implications for asthma, yet remain controversial. This study uses computational modeling to posit a mechanism by which sufficiently vigorous inflations applied during active bronchoconstriction not only transiently reverse bronchoconstriction, but also reduce subsequent airways responsiveness for a period of time. Fitting the model to published data in mice supports this notion.
Abstract BS3-1: Manifestations and implications of subclonal alterations in metastatic breast cancer
Authors: Chandarlapaty S 
Published: February 2018

Abstract
Clinical and pathological evidence for intratumoral heterogeneity (ITH) in breast cancer has long existed, however recent advances in genomic sequencing have revealed a remarkable depth and complexity to ITH. This is further magnified in the study of metastatic breast cancer where there has been significant expansion in the number of tumors as well as the selective pressures faced by individual tumor cells. The near universality of such heterogeneity has led many to question whether ITH is of any biologic or clinical significance or it is simply an intrinsic property of a large population of cancer cells with unstable genomes. We would posit that the significance of ITH can be observed by understanding the pressures that may have generated them. In particular, drug therapy such as anti-estrogen or HER2 targeted therapy can influence the manifestation of ITH. This can reveal underlying vulnerabilities and resiliencies in different cases. In this talk, we will review the evidence that ITH exists for important drivers of breast cancer growth, elucidate the biologic and clinical significance of such findings with a focus on resistance to hormone therapy, and discuss potential strategies to overcome it.
Citation Format: Chandarlapaty S. Manifestations and implications of subclonal alterations in metastatic breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr BS3-1.
Abstract BS3-2: Breast cancer intra-tumor heterogeneity and its clinical implications
Authors: Perou Perou CM 
Published: February 2018

Abstract
Breast cancer is a known heterogeneous disease with significant inter-tumor differences being manifested on many levels including histology, response to therapy, and patient survival outcomes. Importantly, even within an individual tumor, significant heterogeneity may exist. This intra-tumor heterogeneity (ITH) poses a challenge to understanding the biology of breast cancer, and an open question is what impact does ITH have on the clinical decision making process?
Over the past ten years, a rich body of genetic, genomic, and proteomic data has been accumulated concerning the ITH of breast cancers. Much of these data is coming from Massively Parallel Sequencing, and it is yielding a wealth of quantitative data concerning DNA- and RNA-based ITH. This variation can be in the form of somatic mutations, DNA copy number changes, and gene expression differences due to epigenetic differences (i.e. cell state changes) and or microenvironmental influences. Notable recent examples of DNA-based ITH include PIK3CA mutation heterogeneity across different metastatic sites within the same patient with some lesions responding to PI3K inhibitors while others did not. Another key example of ITH are ESR1 mutations that arise within the setting of aromatase inhibitor treatment, where it is sometimes seen that within an individual, multiple different mutations in ESR1 can occur and that confer estrogen independence. Lastly, significant epigenetic ITH can also occur, with a prime example being epithelial tumor cell plasticity, which is often manifested as “state changes”. Examples of this include chemotherapy induced changes that may select for epithelial cells with more mesenchymal features (often referred to as EMT), and which is also typically linked to a more treatment resistant state.
Another important concept that is emerging is that it might be better to target the clonal (or trunk) alterations, as opposed to targeting the subclonal variation. The latter, by definition, is not present within all tumor cells, and thus even if that therapy is effective, it will not target all tumor cells. Conversely, if clonal variants (i.e. those present within the founding clone) are targeted, the treatment may be more effective and cause regression and/or complete response. These multiple examples of ITH are biologically important, but the question still remains, what are the clinical implications? These ITH topics will be presented and discussed within the context of how these findings might affect treatment options and decision making.
Citation Format: Perou Perou CM. Breast cancer intra-tumor heterogeneity and its clinical implications [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr BS3-2.