bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rare but heard: using asynchronous virtual focus groups, interviews and roundtable discussions to create a personalised psychological intervention for primary sclerosing cholangitis: a protocol
Authors: Ranieri Veronica , Kennedy Eilis , Walmsley Martine , Thorburn Doug , McKay Kathy 
Published: October 2019

IntroductionPrimary sclerosing cholangitis (PSC) is a rare and chronic disease characterised by inflammation and fibrosis of the liver’s bile ducts. There is no known cause or cure for the illness, which often progresses to end-stage liver disease requiring liver transplantation. Symptoms of PSC can be very burdensome on those living with the illness, leading to restrictions in daily living, as well as a greater risk of colorectal and biliary tract cancers. Limited voices from lived experience suggest that living with PSC can cause considerable psychological distress. This study, therefore, aims to explore how the illness impacts the psychological well-being of those living with the illness, and those supporting them. It also aims to create a personalised psychological intervention to support all groups.Methods and analysisThis project will take a layered qualitative approach to understanding the ways in which people experience living with PSC within their day-to-day lives. There will be two stages to this study, which will pilot a unique methodological process using online resources. The first stage will consist of asynchronous virtual focus groups (AVFGs) with those living with PSC and those who provide support for those diagnosed with PSC, and narrative interviews with both groups and health professionals. Both the AVFGs and the narrative interviews will be analysed using thematic narrative analysis. The second stage will comprise a roundtable discussion where the researchers and health professionals will devise a personalised psychological intervention to help to support those living with PSC and their supporters. The study duration is expected to be 18 months.Ethics and disseminationThe proposed study has been approved by the UK Health Research Authority and London—Queen Square Research Ethics Committee as application 18/LO/1075. Results from the AVFGs and the narrative interviews will be submitted for peer-reviewed publication. The findings of the study will also be presented nationally to PSC and medical communities, and a summary of the findings will be shared with participants.
The association of ischaemic stroke in patients with heart failure without atrial flutter/fibrillation
Authors: Chou Yen-Lien , Liou Jun-Ting , Cheng Cheng-Chung , Tsai Min-Chien , Lin Wei-Shiang , Cheng Shu-Meng , Lin Cheng-Li , Lin Chin-Sheng , Kao Chia-Hung 
Published: October 2019

PurposeThis study evaluated the association between ischaemic stroke (IS) and heart failure (HF) in the absence of atrial fibrillation (AF) or atrial flutter (AFL) using a population-based nation-wide cohort database.MethodNewly diagnosed patients with HF without previous stroke and acute myocardial infarction (AMI) were enrolled. Based on the propensity scores matching age, sex and all comorbidities, our studies comprised 12 179 patients with HF and 12 179 patients without HF. Cox proportion hazard regression models and competing-risk regression models were used to evaluate the risk of IS among patients with HF without AF or AFL.ResultsIn the multivariable analysis, older age (adjusted HR (95% CI)=1.05 (1.04 to 1.05)), male sex (adjusted HR (95% CI)=1.36 (1.24 to 1.50)), diabetes (adjusted HR (95% CI)=2.22 (1.97 to 2.49)) and hypertension (adjusted HR (95% CI)=1.60 (1.41 to 1.82)) were markedly associated with IS in patients with HF. The HF group had a markedly higher risk of IS than did the non-HF group (subdistribution HR (SHR)=1.51, 95% CI: 1.37 to 1.66) and AMI (SHR=3.40, 95% CI: 2.71 to 4.28). Additionally, according to the Kaplan-Meier analysis, patients with HF were at a significantly higher risk of cumulative incidence of IS and AMI than did patients with non-HF (p value of log-rank test <0.001).ConclusionThis study indicated that HF is a strong independent risk factor for IS, even in the absence of AF or AFL. Clinical physicians should investigate IS through routine screening and careful monitoring of patients with HF.
Survival estimates and outcome predictors in dogs with newly diagnosed diabetes mellitus treated in a veterinary teaching hospital
Authors: Tardo Antonio Maria , Del Baldo Francesca , Dondi Francesco , Pietra Marco , Chiocchetti Roberto , Fracassi Federico 
Published: October 2019

BackgroundDiabetes mellitus (DM) is one of the most common endocrine disorders in dogs, but prognostic factors are still largely unknown. The aim of this retrospective, single‐centre, case series study was to determine overall survival time and identify the prognostic value of several clinical and clinicopathological variables in dogs with newly diagnosed DM.MethodsCases of DM were identified within the electronic medical records of one referral centre. Sixty‐eight dogs with DM were included. Cox proportional hazards models were used to analyse variables associated with survival.ResultsThe median survival time was 964 days (range 22–3140). In multivariable model analysis, length of survival was significantly shorter for dogs with higher haematocrit value (hazard ratio (HR) 1.06, 95 per cent confidence interval (CI) 1.00 to 1.13) and higher serum phosphate concentrations (HR 1.83, 95 per cent CI 1.13 to 2.97). Serum phosphate concentrations were above the reference interval in 24 of 65 (37 per cent) dogs.ConclusionDiabetic dogs have a good life expectancy. Hyperphosphataemia is a relatively common finding in dogs with newly diagnosed DM and represents a negative prognostic factor. The presence of pancreatitis might not be associated with an unfavourable outcome.
Constraints on dark matter-photon coupling in the presence of time-varying dark energy
Authors: Yadav Santosh Kumar 
Published: October 2019

In a recent work [S. Kumar, R. C. Nunes and S. K. Yadav, Phys. Rev. D 98, 043521 (2018)], we have investigated a dark matter (DM)-photon coupling model in which the DM decays into photons in the presence of dark energy (DE) with constant equation of state (EoS) parameter. Here, we study an extension of the DM-photon coupling model by considering a time-varying EoS of DE via Chevalier–Polarski–Linder (CPL) parametrization. We derive observational constraints on the model parameters by using the data from cosmic microwave background (CMB), baryonic acoustic oscillations (BAO), the local value of Hubble constant from Hubble Space Telescope (HST), and large-scale structure (LSS) information from the abundance of galaxy clusters, in four different combinations. We find that in this DM-photon coupling scenario the mean values of [Formula: see text] are in quintessence region [Formula: see text] whereas they were in the phantom region [Formula: see text] in our previous study with all data combinations. The constraints on the DM-photon coupling parameter do not reflect any significant deviation from the previous results. Due to the decay of DM into photons, we obtain higher values of [Formula: see text], consistent with the local measurements, similar to our previous study. But, the time-varying DE leads to lower values of [Formula: see text] in the DM-photon coupling model with all data combinations, in comparison to the results in our previous study. Thus, allowing time-varying DE in the DM-photon coupling scenario is useful to alleviate the [Formula: see text] and [Formula: see text] tensions.
A sensor based on D-shaped photonic crystal fiber with elliptical holes
Authors: Bing Pibin , Huang Shichao , Sui Jialei , Wang Hua , Ren Yongen 
Published: October 2019

A sensor based on D-shaped photonic crystal fiber (PCF) with elliptical holes is designed and numerical studied by finite element method (FEM). The refractive index (RI) of analyte can be detected by using surface plasma resonance effect and optical fiber with elliptical holes can solve the phase matching problem. The size of central hole, the major axis of the two elliptical holes near polishing plane in first layer and polishing depth are adjusted to explore the influence of these parameters on wavelength sensitivity and amplitude sensitivity of the sensor. Polishing depth has a great influence on wavelength sensitivity of the sensor. As a result, higher sensitivity is obtained with larger polishing depth in the range of 1.33–1.39 and smaller polishing depth is more suitable with RI changing from 1.39–1.42. The wavelength sensitivity of the designed sensor is 10,200 nm/RIU, which means the designed sensor has a promising application prospect.
Intratumoral Delivery of Plasmid IL12 Via Electroporation Leads to Regression of Injected and Noninjected Tumors in Merkel Cell Carcinoma
Authors: Bhatia Shailender , Longino Natalie V. , Miller Natalie J. , Kulikauskas Rima , Iyer Jayasri G. , Ibrani Dafina , Blom Astrid , Byrd David R. , Parvathaneni Upendra , Twitty Christopher G. , Campbell Jean S. , Le Mai H. , Gargosky Sharron , Pierce Robert H. , Heller Richard , Daud Adil I. , Nghiem Paul 
Published: October 2019

AbstractPurpose:IL12 promotes adaptive type I immunity and has demonstrated antitumor efficacy, but systemic administration leads to severe adverse events (AE), including death. This pilot trial investigated safety, efficacy, and immunologic activity of intratumoral delivery of IL12 plasmid DNA (tavo) via in vivo electroporation (i.t.-tavo-EP) in patients with Merkel cell carcinoma (MCC), an aggressive virus-associated skin cancer.Patients and Methods:Fifteen patients with MCC with superficial injectable tumor(s) received i.t.-tavo-EP on days 1, 5, and 8 of each cycle. Patients with locoregional MCC (cohort A, N = 3) received one cycle before definitive surgery in week 4. Patients with metastatic MCC (cohort B, N = 12) received up to four cycles total, administered at least 6 weeks apart. Serial tumor and blood samples were collected.Results:All patients successfully completed at least one cycle with transient, mild (grades 1 and 2) AEs and without significant systemic toxicity. Sustained (day 22) intratumoral expression of IL12 protein was observed along with local inflammation and increased tumor-specific CD8+ T-cell infiltration, which led to systemic immunologic and clinical responses. The overall response rate was 25% (3/12) in cohort B, with 2 patients experiencing durable clinical benefit (16 and 55+ months, respectively). Two cohort A patients (1 with pathologic complete remission) were recurrence-free at 44+ and 75+ months, respectively.Conclusions:I.t.-tavo-EP was safe and feasible without systemic toxicity. Sustained local expression of IL12 protein and local inflammation led to systemic immune responses and clinically meaningful benefit in some patients. Gene electrotransfer, specifically i.t.-tavo-EP, warrants further investigation for immunotherapy of cancer.
The Novel ATR Inhibitor BAY 1895344 Is Efficacious as Monotherapy and Combined with DNA Damage–Inducing or Repair–Compromising Therapies in Preclinical Cancer Models
Authors: Wengner Antje M. , Siemeister Gerhard , Lücking Ulrich , Lefranc Julien , Wortmann Lars , Lienau Philip , Bader Benjamin , Bömer Ulf , Moosmayer Dieter , Eberspächer Uwe , Golfier Sven , Schatz Christoph A. , Baumgart Simon J. , Haendler Bernard , Lejeune Pascale , Schlicker Andreas , von Nussbaum Franz , Brands Michael , Ziegelbauer Karl , Mumberg Dominik 
Published: October 2019

Abstract
The DNA damage response (DDR) secures the integrity of the genome of eukaryotic cells. DDR deficiencies can promote tumorigenesis but concurrently may increase dependence on alternative repair pathways. The ataxia telangiectasia and Rad3-related (ATR) kinase plays a central role in the DDR by activating essential signaling pathways of DNA damage repair. Here, we studied the effect of the novel selective ATR kinase inhibitor BAY 1895344 on tumor cell growth and viability. Potent antiproliferative activity was demonstrated in a broad spectrum of human tumor cell lines. BAY 1895344 exhibited strong monotherapy efficacy in cancer xenograft models that carry DNA damage repair deficiencies. The combination of BAY 1895344 with DNA damage–inducing chemotherapy or external beam radiotherapy (EBRT) showed synergistic antitumor activity. Combination treatment with BAY 1895344 and DDR inhibitors achieved strong synergistic antiproliferative activity in vitro, and combined inhibition of ATR and PARP signaling using olaparib demonstrated synergistic antitumor activity in vivo. Furthermore, the combination of BAY 1895344 with the novel, nonsteroidal androgen receptor antagonist darolutamide resulted in significantly improved antitumor efficacy compared with respective single-agent treatments in hormone-dependent prostate cancer, and addition of EBRT resulted in even further enhanced antitumor efficacy. Thus, the ATR inhibitor BAY 1895344 may provide new therapeutic options for the treatment of cancers with certain DDR deficiencies in monotherapy and in combination with DNA damage–inducing or DNA repair–compromising cancer therapies by improving their efficacy.
Ibrutinib Potentiates Antihepatocarcinogenic Efficacy of Sorafenib by Targeting EGFR in Tumor Cells and BTK in Immune Cells in the Stroma
Authors: Lin Cho-Hao , Elkholy Khadija H. , Wani Nissar A. , Li Ding , Hu Peng , Barajas Juan M. , Yu Lianbo , Zhang Xiaoli , Jacob Samson T. , Khan Wasif N. , Bai Xue-Feng , Noonan Anne M. , Ghoshal Kalpana 
Published: October 2019

Abstract
Hepatocellular carcinoma (HCC), the most prevalent primary liver cancer, is a leading cause of cancer-related death worldwide because of rising incidence and limited therapy. Although treatment with sorafenib or lenvatinib is the standard of care in patients with advanced-stage HCC, the survival benefit from sorafenib is limited due to low response rate and drug resistance. Ibrutinib, an irreversible tyrosine kinase inhibitor (TKI) of the TEC (e.g., BTK) and ErbB (e.g., EGFR) families, is an approved treatment for B-cell malignancies. Here, we demonstrate that ibrutinib inhibits proliferation, spheroid formation, and clonogenic survival of HCC cells, including sorafenib-resistant cells. Mechanistically, ibrutinib inactivated EGFR and its downstream Akt and ERK signaling in HCC cells, and downregulated a set of critical genes involved in cell proliferation, migration, survival, and stemness, and upregulated genes promoting differentiation. Moreover, ibrutinib showed synergy with sorafenib or regorafenib, a sorafenib congener, by inducing apoptosis of HCC cells. In vivo, this TKI combination significantly inhibited HCC growth and prolonged survival of immune-deficient mice bearing human HCCLM3 xenograft tumors and immune-competent mice bearing orthotopic mouse Hepa tumors at a dose that did not exhibit systemic toxicity. In immune-competent mice, the ibrutinib–sorafenib combination reduced the numbers of BTK+ immune cells in the tumor microenvironment. Importantly, we found that the BTK+ immune cells were also enriched in the tumor microenvironment in a subset of primary human HCCs. Collectively, our findings implicate BTK signaling in hepatocarcinogenesis and support clinical trials of the sorafenib–ibrutinib combination for this deadly disease.
Minicircle DNA-Engineered CAR T Cells Suppressed Tumor Growth in Mice
Authors: Han Jinsheng , Gao Fei , Geng Songsong , Ye Xueshuai , Wang Tie , Du Pingping , Cai Ziqi , Fu Zexian , Zhao Zhilong , Shi Long , Li Qingxia , Cai Jianhui 
Published: October 2019

Abstract
Viral-based chimeric antigen receptor-engineered T (CAR T)–cell manufacturing has potential safety risks and relatively high costs. The nonviral minicircle DNA (mcDNA) is safer for patients, cheaper to produce, and may be a more suitable technique to generate CAR T cells. In this study, we produced mcDNA-based CAR T cells specifically targeting prostate stem cell antigen (PSCA; mcDNA-PSCA-CAR T cells). Our results showed that mcDNA-PSCA-CAR T cells persisted in mouse peripheral blood as long as 28 days and demonstrated more CAR T-cell infiltration, higher cytokine secretion levels, and better antitumor effects. Together, our results suggest that mcDNA-CAR can be a safe and cost-effective platform to produce CAR T cells.
Ciência econômica e economia da cultura
Authors: Toniol Ana Paula Nobile , Albieri Sara 
Published: October 2019

A proposta de uma economia da cultura recorre à lógica econômica, seus conceitos e metodologia para uma análise econômica da indústria cultural, compreendendo: efeitos externos, investimentos a longo prazo, especificidade de remuneração, importância do subsidio público ou privado, aliados a um forte componente de incerteza. Ao transpor o valor econômico à cultura, tanto fomenta discussões sobre orçamentos públicos como envolve o setor corporativo nas questões culturais, criando metodologias para avaliação do impacto econômico da cultura na geração de riqueza e empregos Essa avaliação inclui: valor do capital cultural, participação no mercado, direitos de propriedade intelectual, justificativas para a interferência estatal no mercado, estimativa dos impactos dos acordos multilaterais nas relações sociais e na preservação das expressões culturais de um povo. A economia da cultura se utiliza das técnicas oferecidas pelo conhecimento econômico para defender a importância da cultura como geradora de crescimento econômico e seu potencial para o desenvolvimento socioeconômico.
Functional Analysis of LDLR (Low-Density Lipoprotein Receptor) Variants in Patient Lymphocytes to Assess the Effect of Evinacumab in Homozygous Familial Hypercholesterolemia Patients With a Spectrum of LDLR Activity
Authors: Banerjee Poulabi , Chan Kuo-Chen , Tarabocchia Michel , Benito-Vicente Asier , Alves Ana C. , Uribe Kepa B. , Bourbon Mafalda , Skiba Paul J. , Pordy Robert , Gipe Daniel A. , Gaudet Daniel , Martin Cesar 
Published: October 2019

Objective:
Homozygous familial hypercholesterolemia is a rare disease usually caused by LDLR (low-density lipoprotein receptor) mutations. Homozygous familial hypercholesterolemia is characterized by markedly elevated LDL-C (low-density lipoprotein cholesterol) levels and an extremely high risk of premature atherosclerotic cardiovascular disease. A phase 2, proof-of-concept study (NCT02265952) demonstrated that evinacumab, a fully human monoclonal antibody to ANGPTL3 (angiopoietin-like 3 protein), reduced LDL-C levels in 9 patients with genotypically confirmed homozygous familial hypercholesterolemia and was well tolerated. The aim of this study was to analyze the effects of evinacumab on LDLR activity in lymphocytes purified from patients in the proof-of-concept study.

Approach and Results:

LDLR activity was assessed in patient lymphocytes before and after treatment with evinacumab and versus lymphocytes carrying wild-type LDLR, and also in an LDLR-defective Chinese hamster ovary cell line (CHO-
ldl
A7) transfected with plasmids encoding the LDLR variants. Overall mean peak reduction in LDL-C with evinacumab was −58±18%, occurring between Week 4 and Week 12. Mutations identified in the 9 patients were shown to be pathogenic, with loss of LDLR activity versus wild type. Two of the LDLR variants, p.(Cys681*) and p.(Ala627Profs*38), were class 2 type mutations that are retained in the endoplasmic reticulum. Six variants were class 3 type mutations with impaired LDL-C binding activity: p.(Trp87Gly), occurring in 2 patients, p.(Gln254Pro), p.(Ser177Leu), p.(Gly335Val), and p.(Ser306Leu). Evinacumab had no effect on LDLR activity.

Conclusions:
These results suggest that evinacumab is effective for lowering LDL-C in patients with homozygous familial hypercholesterolemia, and the inhibition of ANGPTL3 in humans lowers LDL-C in a mechanism independent of the LDLR.
Desistance from Crime during the Transition to Adulthood: The Influence of Parents, Peers, and Shifts in Identity
Authors: Copp Jennifer E. , Giordano Peggy C. , Longmore Monica A. , Manning Wendy D. 
Published: October 2019

Objectives: Research on criminal continuity and change has traditionally focused on elements of the adult life course (e.g., marriage and employment); however, recent social and economic changes suggest the need to consider a broader range of factors. In addition, researchers have increasingly recognized the importance of identity changes in the desistance process. Methods: Using five waves of structured data from the Toledo Adolescent Relationships Study (TARS), we examined identity changes, shifts in involvement with delinquent peers, and variability in closeness with parents as influences on desistance. In-depth interviews with a subset of TARS respondents offered a person-centered lens on individual and social processes associated with variability in criminal behavior. Results: Findings indicated that identity changes were associated with declines in offending. In addition, changes in parental closeness and the extent of affiliation with antisocial peers contributed to patterns of offending, net of these subjectively experienced cognitive changes. Conclusions: Cognitive processes are important to desistance. However, they do not independently provide a path to sustained behavioral change. Social experiences, including changes in relationships/supports from parents and affiliation with delinquent peers, also figure into change processes. We discuss the implications of our findings for future research and programmatic efforts.
When does job dissatisfaction lead to deviant behaviour? The critical roles of abusive supervision and adaptive humour
Authors: De Clercq Dirk , Haq Inam Ul , Azeem Muhammad Umer 
Published: October 2019

With a basis in conservation of resources theory, this study investigates the relationship between employees’ sense of job dissatisfaction and their engagement in deviant behaviour, as well as the moderating roles that their exposure to abusive leadership and possession of adaptive humour skills can play in this process. Based on two-way survey data collected from employees in Pakistan, the findings show that employees’ unhappy feelings about their job situations enhance the likelihood that they undertake negative behaviours that can harm their organization, especially when they suffer from abusive leadership or lack adaptive humour skills. The buffering effect of their adaptive humour on the positive relationship between job dissatisfaction and deviant behaviour is also particularly salient in the presence of abusive leadership. JEL Classification: D23, D91, M50