bluuebunny/crossref_metadata_2025_split huggingface dataset:
Providing person-centred care for people with multiple chronic conditions: protocol for a qualitative study incorporating client and staff perspectives
Authors: Peart Annette , Lewis Virginia , Barton Christopher , Brown Ted , White Julie , Gascard Debra , Russell Grant 
Published: October 2019

IntroductionChronic conditions are associated with over one-third of potentially avoidable hospitalisations. Integrated care programmes aim to help people with chronic conditions to self-manage their health, thus avoiding hospital admissions. While founded on principles of person-centred care, the experiences of people with multiple chronic conditions in integrated care programmes are not widely known. Our study will explore how person-centred care is incorporated into an integrated care programme for people with multiple chronic conditions.Methods and analysisThis is a qualitative phenomenological study being conducted from March 2018 to June 2019, in a large metropolitan health service in Melbourne, Australia. Participants will be programme clients (and/or their carers) and staff working in the programme. We will interview staff about their experiences of the programme. Recruited staff will assist with recruitment of clients who recently completed an episode of care, to participate in a semistructured interview in their home. We will also analyse the medical records of interviewed clients, and observe outpatient clinics connected to the programme, based on the findings of the interviews. We will analyse all data using thematic analysis, with overarching themes representing staff and client perspectives of person-centred care.Ethics and disseminationEthical approval was granted by Monash Health (HREC/18/MonH/33) and Monash University (12260) Human Research Ethics Committees. Our study will provide a comprehensive exploration of person-centred care in an integrated care programme. It will add information to person-centred care literature on participants’ perceptions of what works and why, including barriers and enablers to person-centred care in a complex environment. Findings of this study will be disseminated via publications, conferences and presentations to the health service participants.
Anisotropic neutron stars by gravitational decoupling
Authors: Torres-Sánchez V. A. , Contreras E. 
Published: October 2019

Abstract
In this work we obtain an anisotropic neutron star solution by gravitational decoupling starting from a perfect fluid configuration which has been used to model the compact object PSR J0348+0432. Additionally, we consider the same solution to model the Binary Pulsar SAX J1808.4-3658 and X-ray Binaries Her X-1 and Cen X-3 ones. We study the acceptability conditions and obtain that the MGD-deformed solution obey the same physical requirements as its isotropic counterpart. Finally, we conclude that the most stable solutions, according to the adiabatic index and gravitational cracking criterion, are those with the smallest compactness parameters, namely SAX J1808.4-3658 and Her X-1.
Effect of γ-irradiation on adsorption and photocatalytic ability of MoS2nanomaterials
Authors: He Yupu , Xiang Xia , Sun Lijie , Tian Chengxiang , Yang Guixia , Zu Xiaotao 
Published: October 2019

The ability of MoS2nanomaterials as adsorbent and photocatalytic materials of methylene blue (MB) dye after [Formula: see text]-ray irradiation is investigated. The MoS2nanomaterials are prepared by a simple hydrothermal route, and then irradiated with Co-60 gamma radioisotope at different doses of 1, 10, 100, 1000 kGy. All the samples are characterized by X-ray Diffraction (XRD), Scanning Electron Microscopy (SEM), Fourier Transform Infrared Spectroscopy (FTIR), Diffusivity Reflectance Spectroscopy (DRS) and Brunauer–Emmet–Teller (BET). The XRD analysis shows no change in crystal structure of MoS2nanomaterials after irradiation. The DRS analysis indicates the optical bandgap increases from 1.73 to 1.82, 1.86, 1.94 and 2.00 eV, respectively. The performance of the dye-absorbing solutions and the photocatalytic dye solutions before and after irradiation is compared. After [Formula: see text]-ray irradiation, the adsorption capacity of the MoS2nanomaterials degrades, which can be attributed to the decreased specific surface area, from 77.060 to 48.812, 35.855, 38.789 and 27.137 m2/g, respectively. The photocatalytic degradation ability for the MB solution also decreases due to the increase of optical bandgap of the samples after [Formula: see text]-ray irradiation.
PGC1α Suppresses Prostate Cancer Cell Invasion through ERRα Transcriptional Control
Authors: Valcarcel-Jimenez Lorea , Macchia Alice , Crosas-Molist Eva , Schaub-Clerigué Ariane , Camacho Laura , Martín-Martín Natalia , Cicogna Paolo , Viera-Bardón Cristina , Fernández-Ruiz Sonia , Rodriguez-Hernandez Irene , Hermanova Ivana , Astobiza Ianire , Cortazar Ana R. , Corres-Mendizabal Jon , Gomez-Muñoz Antonio , Sanz-Moreno Victoria , Torrano Verónica , Carracedo Arkaitz 
Published: October 2019

Abstract

The PPARγ coactivator 1 alpha (PGC1α) is a prostate tumor suppressor that controls the balance between anabolism and catabolism. PGC1A downregulation in prostate cancer is causally associated with the development of metastasis. Here we show that the transcriptional complex formed by PGC1α and estrogen-related receptor 1 alpha (ERRα) controls the aggressive properties of prostate cancer cells. PGC1α expression significantly decreased migration and invasion of various prostate cancer cell lines. This phenotype was consistent with remarkable cytoskeletal remodeling and inhibition of integrin alpha 1 and beta 4 expression, both in vitro and in vivo. CRISPR/Cas9-based deletion of ERRα suppressed PGC1α regulation of cytoskeletal organization and invasiveness. Mechanistically, PGC1α expression decreased MYC levels and activity prior to inhibition of invasiveness. In addition, PGC1α and ERRα associated at the MYC promoter, supporting the inhibitory activity PGC1α. The inverse correlation between PGC1α–ERRα activity and MYC levels was corroborated in multiple prostate cancer datasets. Altogether, these results support that PGC1α–ERRα functions as a tumor-suppressive transcriptional complex through the regulation of metabolic and signaling events.

Significance:
These findings describe how downregulation of the prostate tumor suppressor PGC1 drives invasiveness and migration of prostate cancer cells.
Exportin 1 Inhibition Induces Nerve Growth Factor Receptor Expression to Inhibit the NF-κB Pathway in Preclinical Models of Pediatric High-Grade Glioma
Authors: DeSisto John A. , Flannery Patrick , Lemma Rakeb , Pathak Amrita , Mestnik Shelby , Philips Natalie , Bales Natalie J. , Kashyap Trinayan , Moroze Erin , Venkataraman Sujatha , Kung Andrew L. , Carter Bruce D. , Landesman Yosef , Vibhakar Rajeev , Green Adam L. 
Published: October 2019

Abstract
High-grade glioma (HGG) is the leading cause of cancer-related death among children. Selinexor, an orally bioavailable, reversible inhibitor of the nuclear export protein, exportin 1, is in clinical trials for a range of cancers, including HGG. It inhibits the NF-κB pathway and strongly induces the expression of nerve growth factor receptor (NGFR) in preclinical cancer models. We hypothesized that selinexor inhibits NF-κB via upregulation of NGFR. In HGG cells, sensitivity to selinexor correlated with increased induction of cell surface NGFR expression. Knocking down NGFR in HGG cells increased proliferation, anchorage-independent growth, stemness markers, and levels of transcriptionally available nuclear NF-κB not bound to IκB-α, while decreasing apoptosis and sensitivity to selinexor. Increasing IκB-α levels in NGFR knockdown cells restored sensitivity to selinexor. Overexpression of NGFR using cDNA reduced levels of free nuclear NF-κB, decreased stemness markers, and increased markers of cellular differentiation. In all HGG lines tested, selinexor decreased phosphorylation of NF-κB at serine 536 (a site associated with increased transcription of proliferative and inflammatory genes). Because resistance to selinexor monotherapy occurred in our in vivo model, we screened selinexor with a panel of FDA-approved anticancer agents. Bortezomib, a proteasome inhibitor that inhibits the NF-κB pathway through a different mechanism than selinexor, showed synergy with selinexor against HGG in vitro. Our results help elucidate selinexor's mechanism of action and identify NGFR as a potential biomarker of its effect in HGG and in addition suggest a combination therapy strategy for these challenging tumors.
ADP-Ribosylation Levels and Patterns Correlate with Gene Expression and Clinical Outcomes in Ovarian Cancers
Authors: Conrad Lesley B. , Lin Ken Y. , Nandu Tulip , Gibson Bryan A. , Lea Jayanthi S. , Kraus W. Lee 
Published: October 2019

Abstract
Inhibitors of nuclear PARP enzymes (e.g., PARP-1) have improved clinical outcomes in ovarian cancer, especially in patients with BRCA1/2 gene mutations or additional homologous recombination (HR) DNA repair pathway deficiencies. These defects serve as biomarkers for response to PARP inhibitors (PARPi). We sought to identify an additional biomarker that could predict responses to both conventional chemotherapy and PARPi in ovarian cancers. We focused on cellular ADP-ribosylation (ADPRylation), which is catalyzed by PARP enzymes and detected by detection reagents we developed previously. We determined molecular phenotypes of 34 high-grade serous ovarian cancers and associated them with clinical outcomes. We used the levels and patterns of ADPRylation and PARP-1 to distribute ovarian cancers into distinct molecular phenotypes, which exhibit dramatically different gene expression profiles. In addition, the levels and patterns of ADPRylation, PARP-1 protein, and gene expression correlated with clinical outcomes in response to platinum-based chemotherapy, with cancers exhibiting the highest levels of ADPRylation having the best outcomes independent of BRCA1/2 status. Finally, in cell culture-based assays using patient-derived ovarian cancer cell lines, ADPRylation levels correlated with sensitivity to the PARPi, Olaparib, with cell lines exhibiting high levels of ADPRylation having greater sensitivity to Olaparib. Collectively, our study demonstrates that ovarian cancers exhibit a wide range of ADPRylation levels, which correlate with therapeutic responses and clinical outcomes. These results suggest ADPRylation may be a useful biomarker for PARPi sensitivity in ovarian cancers, independent of BRCA1/2 or homologous recombination deficiency status.
PTEN Loss Mediates Clinical Cross-Resistance to CDK4/6 and PI3Kα Inhibitors in Breast Cancer
Authors: Costa Carlotta , Wang Ye , Ly Amy , Hosono Yasuyuki , Murchie Ellen , Walmsley Charlotte S. , Huynh Tiffany , Healy Christopher , Peterson Rachel , Yanase Shogo , Jakubik Charles T. , Henderson Laura E. , Damon Leah J. , Timonina Daria , Sanidas Ioannis , Pinto Christopher J. , Mino-Kenudson Mari , Stone James R. , Dyson Nicholas J. , Ellisen Leif W. , Bardia Aditya , Ebi Hiromichi , Benes Cyril H. , Engelman Jeffrey A. , Juric Dejan 
Published: October 2019

Abstract

The combination of CDK4/6 inhibitors with antiestrogen therapies significantly improves clinical outcomes in ER-positive advanced breast cancer. To identify mechanisms of acquired resistance, we analyzed serial biopsies and rapid autopsies from patients treated with the combination of the CDK4/6 inhibitor ribociclib with letrozole. This study revealed that some resistant tumors acquired RB loss, whereas other tumors lost PTEN expression at the time of progression. In breast cancer cells, ablation of PTEN, through increased AKT activation, was sufficient to promote resistance to CDK4/6 inhibition in vitro and in vivo. Mechanistically, PTEN loss resulted in exclusion of p27 from the nucleus, leading to increased activation of both CDK4 and CDK2. Because PTEN loss also causes resistance to PI3Kα inhibitors, currently approved in the post-CDK4/6 setting, these findings provide critical insight into how this single genetic event may cause clinical cross-resistance to multiple targeted therapies in the same patient, with implications for optimal treatment-sequencing strategies.

Significance:
Our analysis of serial biopsies uncovered RB and PTEN loss as mechanisms of acquired resistance to CDK4/6 inhibitors, utilized as first-line treatment for ER-positive advanced breast cancer. Importantly, these findings have near-term clinical relevance because PTEN loss also limits the efficacy of PI3Kα inhibitors currently approved in the post-CDK4/6 setting.
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Automatic Identification and Production of Related Words for Historical Linguistics
Authors: Ciobanu Alina Maria , Dinu Liviu P. 
Published: October 2019

Language change across space and time is one of the main concerns in historical linguistics. In this article, we develop tools to assist researchers and domain experts in the study of language evolution. First, we introduce a method to automatically determine whether two words are cognates. We propose an algorithm for extracting cognates from electronic dictionaries that contain etymological information. Having built a data set of related words, we further develop machine learning methods based on orthographic alignment for identifying cognates. We use aligned subsequences as features for classification algorithms in order to infer rules for linguistic changes undergone by words when entering new languages and to discriminate between cognates and non-cognates. Second, we extend the method to a finer-grained level, to identify the type of relationship between words. Discriminating between cognates and borrowings provides a deeper insight into the history of a language and allows a better characterization of language relatedness. We show that orthographic features have discriminative power and we analyze the underlying linguistic factors that prove relevant in the classification task. To our knowledge, this is the first attempt of this kind. Third, we develop a machine learning method for automatically producing related words. We focus on reconstructing proto-words, but we also address two related sub-problems, producing modern word forms and producing cognates. The task of reconstructing proto-words consists of recreating the words in an ancient language from its modern daughter languages. Having modern word forms in multiple Romance languages, we infer the form of their common Latin ancestors. Our approach relies on the regularities that occurred when words entered the modern languages. We leverage information from several modern languages, building an ensemble system for reconstructing proto-words. We apply our method to multiple data sets, showing that our approach improves on previous results, also having the advantage of requiring less input data, which is essential in historical linguistics, where resources are generally scarce.
Scalable Micro-planned Generation of Discourse from Structured Data
Authors: Laha Anirban , Jain Parag , Mishra Abhijit , Sankaranarayanan Karthik 
Published: October 2019

We present a framework for generating natural language description from structured data such as tables; the problem comes under the category of data-to-text natural language generation (NLG). Modern data-to-text NLG systems typically use end-to-end statistical and neural architectures that learn from a limited amount of task-specific labeled data, and therefore exhibit limited scalability, domain-adaptability, and interpretability. Unlike these systems, ours is a modular, pipeline-based approach, and does not require task-specific parallel data. Rather, it relies on monolingual corpora and basic off-the-shelf NLP tools. This makes our system more scalable and easily adaptable to newer domains. Our system utilizes a three-staged pipeline that: (i) converts entries in the structured data to canonical form, (ii) generates simple sentences for each atomic entry in the canonicalized representation, and (iii) combines the sentences to produce a coherent, fluent, and adequate paragraph description through sentence compounding and co-reference replacement modules. Experiments on a benchmark mixed-domain data set curated for paragraph description from tables reveals the superiority of our system over existing data-to-text approaches. We also demonstrate the robustness of our system in accepting other popular data sets covering diverse data types such as knowledge graphs and key-value maps.
Fuzzy Logic Algorithms to Identify Birds, Precipitation, and Ground Clutter in S-Band Radar Data Using Polarimetric and Nonpolarimetric Variables
Authors: Radhakrishna Basivi , Fabry Frédéric , Kilambi Alamelu 
Published: October 2019

AbstractThe statistical properties of the radar echoes from biological, precipitation, and ground targets observed with the McGill S-band dual-polarization radar have been used to devise a polarimetric and a nonpolarimetric fuzzy logic algorithm for pixel-by-pixel target identification. Radar observations of migrating birds show distinctly different polarimetric features during their relative approach and departure from the radar site illustrating the dependency of radar parameters on the canting angle and scattering cross section. The devised algorithms have been tested with two independent events, each consisting of 2 h of radar observations with a 5-min temporal resolution. One event consisted of precipitation without birds while the other contained only birds. The misclassifications were 10.12% and 9.6%, respectively, for the two cases for the nonpolarimetric algorithm, and 1.99% and 0.92% for the polarimetric algorithm. The results indicate that even though nonpolarimetric radar membership functions may be considered adequate for separating radar echo returns from birds, precipitation, and ground targets, they are not sufficiently skilled if a greater accuracy is required. Target identification without polarimetric variables especially fails in the region of zero isodop and in precipitation with an echo top below 4 km.
Arthroscopic Assessment of Syndesmotic Instability in the Sagittal Plane in a Cadaveric Model
Authors: Lubberts Bart , Massri-Pugin Jafet , Guss Daniel , Wolf Jonathon C. , Bhimani Rohan , Waryasz Gregory R. , DiGiovanni Christopher W. 
Published: October 2019

Background: Syndesmotic instability is multidirectional, occurring in the coronal, sagittal, and rotational planes. Despite the multitude of studies examining such instability in the coronal plane, other studies have highlighted that syndesmotic instability may instead be more evident in the sagittal plane. The aim of this study was to arthroscopically assess the degree of syndesmotic ligamentous injury necessary to precipitate fibular translation in the sagittal plane. Methods: Twenty-one above-knee cadaveric specimens underwent arthroscopic evaluation of the syndesmosis, first with all syndesmotic and ankle ligaments intact and subsequently with sequential sectioning of the anterior inferior tibiofibular ligament (AITFL), the interosseous ligament (IOL), the posterior inferior tibiofibular ligament (PITFL), and deltoid ligament (DL). In all scenarios, an anterior to posterior (AP) and a posterior to anterior (PA) fibular translation test were performed under a 100-N applied force. AP and PA sagittal plane translation of the distal fibula relative to the fixed tibial incisura was arthroscopically measured. Results: Compared with the intact ligamentous state, there was no difference in sagittal fibular translation when only 1 or 2 ligaments were transected. After transection of all the syndesmotic ligaments (AITFL, IOL, and PITFL) or after partial transection of the syndesmotic ligaments (AITFL, IOL) alongside the DL, fibular translation in the sagittal plane significantly increased as compared with the intact state ( P values ranging from .041 to <.001). The optimal cutoff point to distinguish stable from unstable injuries was equal to 2 mm of fibular translation for the total sum of AP and PA translation (sensitivity 77.5%; specificity 88.9%). Conclusion: Syndesmotic instability appears in the sagittal plane after injury to all 3 syndesmotic ligaments or after partial syndesmotic injury with concomitant deltoid ligament injury in this cadaveric model. The optimal cutoff point to arthroscopically distinguish stable from unstable injuries was 2 mm of total fibular translation. Clinical Relevance: These data can help surgeons arthroscopically distinguish between stable syndesmotic injuries and unstable ones that require syndesmotic stabilization.
Relative Efficacy of Nonoperative Treatment of Keratoacanthomas
Authors: Seger Edward W. , Tarantino Isadore S. , Neill Brett C. , Wang Ting 
Published: October 2019

BackgroundKeratoacanthomas (KAs) are neoplasms of squamous epithelium which exhibit rapid growth and are often difficult to distinguish clinically from squamous cell carcinoma. Excision is the most common treatment, but in refractory cases or for KAs in cosmetically sensitive areas, nonoperative modalities may be better suited.ObjectiveTo compare efficacies of topical and intralesional therapies for the treatment of KAs.MethodsA systematic literature review was performed using Medline, Ovid, and Embase. Studies looking at the efficacy of topical or intralesional treatments for KAs were included. To compare efficacy, 2-tailed t-tests were performed, with P < .05 considered statistically significant.ResultsForty-one studies were identified across 5 modalities. Both topical and intralesional treatments had high KA eradication rates (92%-100%). Intralesional 5-fluorouracil led to faster KA healing times when compared to intralesional methotrexate (3.7 vs 4.6 weeks, P = .017). Similarly, topical 5-fluorouracil led to faster time to heal than topical imiquimod (3.8 vs 7.6 weeks with imiquimod, P < .0001).ConclusionFor nonoperative treatment of KAs, strong evidence currently exists for both topical and intralesional therapies. Decisions on which modality to use should be made on a case-by-case basis.