bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reducing weight and increasing physical activity in people at high risk of cardiovascular disease: a randomised controlled trial comparing the effectiveness of enhanced motivational interviewing intervention with usual care
Authors: Ismail Khalida , Bayley Adam , Twist Katherine , Stewart Kurtis , Ridge Katie , Britneff Emma , Greenough Anne , Ashworth Mark , Rundle Jennifer , Cook Derek G , Whincup Peter , Treasure Janet , McCrone Paul , Winkley Kirsty , Stahl Daniel 
Published: December 2019

ObjectiveThe epidemic of obesity is contributing to the increasing prevalence of people at high risk of cardiovascular disease (CVD), negating the medical advances in reducing CVD mortality. We compared the clinical and cost-effectiveness of an intensive lifestyle intervention consisting of enhanced motivational interviewing in reducing weight and increasing physical activity for patients at high risk of CVD.MethodsA three-arm, single-blind, parallel-group randomised controlled trial was conducted in consenting primary care centres in south London. We recruited patients aged 40–74 years with a QRisk2 score ≥20.0%, which indicates the probability of having a CVD event in the next 10 years. The intervention was enhanced motivational interviewing which included additional behaviour change techniques and was delivered by health trainers in 10 sessions over 1 year, in either group (n=697) or individual (n=523) format. The third arm received usual care (UC; n=522). The primary outcomes were physical activity (mean steps/day) and weight (kg). Secondary outcomes were changes in low-density lipoprotein cholesterol and CVD risk score. We estimated the relative cost-effectiveness of each intervention.ResultsAt 24 months, the group and individual interventions were not more effective than UC in increasing physical activity (mean difference=70.05 steps, 95% CI −288.00 to 147.90 and mean difference=7.24 steps, 95% CI −224.01 to 238.50, respectively), reducing weight (mean difference=−0.03 kg, 95% CI −0.49 to 0.44 and mean difference=−0.42 kg, 95% CI −0.93 to 0.09, respectively) or improving any secondary outcomes. The group and individual interventions were not cost-effective at conventional thresholds.ConclusionsEnhancing motivational interviewing with additional behaviour change techniques was not effective in reducing weight or increasing physical activity in those at high CVD risk.
Do Family Firms Choose Conservative Accounting Practices?
Authors: Raithatha Mehul , Shaw Tara Shankar 
Published: December 2019

We investigate whether family firms are motivated to adopt conservative accounting practices, given their unique characteristics of high promoter holdings, less diversified equity, and long-term interest in the business. We examine whether heterogeneity within family firms, captured through family members’ involvement in management and the firm’s affiliation to a business group, drives conservative behavior. We test our model on a sample of 2534 listed Indian firms from 2006 to 2015. Our results indicate that family-controlled firms are more conditionally conservative in their accounting practices, especially when family members manage them and when they are affiliated with a business group. These findings are robust to alternative measures of conservatism and also after controlling for omitted variable bias and reverse causality.
Beyond Angiogenesis: Exploiting Angiocrine Factors to Restrict Tumor Progression and Metastasis
Authors: Singhal Mahak , Augustin Hellmut G. 
Published: December 2019

Abstract
Looking beyond tumor angiogenesis, the past decade has witnessed a fundamental change of paradigm with the discovery that the vascular endothelium does not just respond to exogenous cytokines, but exerts active “angiocrine” gatekeeper roles, controlling their microenvironment in an instructive manner. While vascular niches host disseminated cancer cells and promote their stemness, endothelial cell–derived angiocrine signals orchestrate a favorable immune milieu to facilitate metastatic growth. Here, we discuss recent advances in the field of tumor microenvironment research and propose angiocrine signals as promising targets of future mechanism-driven antimetastatic therapies, which may prove useful to synergistically combine with chemotherapy and immunotherapy.
lncRNA THAP9-AS1 Promotes Pancreatic Ductal Adenocarcinoma Growth and Leads to a Poor Clinical Outcome via Sponging miR-484 and Interacting with YAP
Authors: Li Nan , Yang Guohua , Luo Liyun , Ling Li , Wang Xiaorong , Shi Lejuan , Lan Junsong , Jia Xiaoting , Zhang Qiong , Long Ze , Liu Jinbao , Hu Weimin , He Zhimin , Liu Haiying , Liu Wanqing , Zheng Guopei 
Published: December 2019

Abstract

Purpose:
Long noncoding RNAs (lncRNA) have been observed in various cancer types. Our bioinformatic analysis of existing databases demonstrated overexpression of lncRNA THAP9-AS1 in pancreatic ductal adenocarcinoma (PDAC). We aimed to investigate the roles and mechanisms of THAP9-AS1 in PDAC.

Experimental Design:
The overexpression of THAP9-AS1 in samples of patients with pancreatic cancer was characterized and was associated with clinical outcomes. The nonprotein coding property of the THAP9-AS1 was verified. Various in vitro and in vivo experiments were performed to investigate the interaction between THAP9-AS1 and YAP signaling.

Results:
We demonstrated that lncRNA THAP9-AS1 is overexpressed in PDAC in multiple patient sample sets, which is significantly associated with poor outcome of patients with PDAC. THAP9-AS1 promotes PDAC cells growth both in vitro and in vivo. THAP9-AS1 exerts its effects via enhancing YAP signaling. Ectopic YAP expression overcame the effects of THAP9-AS1 knockdown. Inversely, YAP knockdown diminished the effects of THAP9-AS1 overexpression. THAP9-AS1 acts as a competing endogenous RNA for miR-484, leading to YAP upregulation. Moreover, THAP9-AS1 binds to YAP protein and inhibits the phosphorylation-mediated inactivation of YAP by LATS1. Reciprocally, YAP/TEAD1 complex promotes THAP9-AS1 transcription to form a feed-forward circuit. Importantly, THAP9-AS1 level positively correlates with YAP expression in PDAC tissues. YAP overexpression also predicts a poor outcome in patients with PDAC.

Conclusions:
Our findings indicate that THAP9-AS1 plays an important role in PDAC growth via enhancing YAP signaling, which in turn also modulates THAP9-AS1 transcription. THAP9-AS1/YAP axis may serve as a potential biomarker and therapeutic target for PDAC treatment.
A Randomized Phase II Trial of Epigenetic Priming with Guadecitabine and Carboplatin in Platinum-resistant, Recurrent Ovarian Cancer
Authors: Oza Amit M. , Matulonis Ursula A. , Alvarez Secord Angeles , Nemunaitis John , Roman Lynda D. , Blagden Sarah P. , Banerjee Susana , McGuire William P. , Ghamande Sharad , Birrer Michael J. , Fleming Gini F. , Markham Merry Jennifer , Hirte Hal W. , Provencher Diane M. , Basu Bristi , Kristeleit Rebecca , Armstrong Deborah K. , Schwartz Benjamin , Braly Patricia , Hall Geoff D. , Nephew Kenneth P. , Jueliger Simone , Oganesian Aram , Naim Sue , Hao Yong , Keer Harold , Azab Mohammad , Matei Daniela 
Published: December 2019

Abstract

Purpose:
Platinum resistance in ovarian cancer is associated with epigenetic modifications. Hypomethylating agents (HMA) have been studied as carboplatin resensitizing agents in ovarian cancer. This randomized phase II trial compared guadecitabine, a second-generation HMA, and carboplatin (G+C) against second-line chemotherapy in women with measurable or detectable platinum-resistant ovarian cancer.

Patients and Methods:
Patients received either G+C (guadecitabine 30 mg/m2 s.c. once-daily for 5 days and carboplatin) or treatment of choice (TC; topotecan, pegylated liposomal doxorubicin, paclitaxel, or gemcitabine) in 28-day cycles until progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS); secondary endpoints were RECIST v1.1 and CA-125 response rate, 6-month PFS, and overall survival (OS).

Results:
Of 100 patients treated, 51 received G+C and 49 received TC, of which 27 crossed over to G+C. The study did not meet its primary endpoint as the median PFS was not statistically different between arms (16.3 weeks vs. 9.1 weeks in the G+C and TC groups, respectively; P = 0.07). However, the 6-month PFS rate was significantly higher in the G+C group (37% vs. 11% in TC group; P = 0.003). The incidence of grade 3 or higher toxicity was similar in G+C and TC groups (51% and 49%, respectively), with neutropenia and leukopenia being more frequent in the G+C group.

Conclusions:
Although this trial did not show superiority for PFS of G+C versus TC, the 6-month PFS increased in G+C treated patients. Further refinement of this strategy should focus on identification of predictive markers for patient selection.
Preclinical Efficacy of a PSMA-Targeted Thorium-227 Conjugate (PSMA-TTC), a Targeted Alpha Therapy for Prostate Cancer
Authors: Hammer Stefanie , Hagemann Urs B. , Zitzmann-Kolbe Sabine , Larsen Aasmund , Ellingsen Christine , Geraudie Solene , Grant Derek , Indrevoll Baard , Smeets Roger , von Ahsen Oliver , Kristian Alexander , Lejeune Pascale , Hennekes Hartwig , Karlsson Jenny , Bjerke Roger M. , Ryan Olav B. , Cuthbertson Alan S. , Mumberg Dominik 
Published: December 2019

Abstract

Purpose:
Prostate-specific membrane antigen (PSMA) is an attractive target for radionuclide therapy of metastatic castration-resistant prostate cancer (mCRPC). PSMA-targeted alpha therapy (TAT) has shown early signs of activity in patients with prostate cancer refractory to beta radiation. We describe a novel, antibody-based TAT, the PSMA-targeted thorium-227 conjugate PSMA-TTC (BAY 2315497) consisting of the alpha-particle emitter thorium-227 complexed by a 3,2-HOPO chelator covalently linked to a fully human PSMA-targeting antibody.

Experimental Design:
PSMA-TTC was characterized for affinity, mode of action, and cytotoxic activity in vitro. Biodistribution, pharmacokinetics, and antitumor efficacy were investigated in vivo using cell line and patient-derived xenograft (PDX) models of prostate cancer.

Results:
PSMA-TTC was selectively internalized into PSMA-positive cells and potently induced DNA damage, cell-cycle arrest, and apoptosis in vitro. Decrease in cell viability was observed dependent on the cellular PSMA expression levels. In vivo, PSMA-TTC showed strong antitumor efficacy with T/C values of 0.01 to 0.31 after a single injection at 300 to 500 kBq/kg in subcutaneous cell line and PDX models, including models resistant to standard-of-care drugs such as enzalutamide. Furthermore, inhibition of both cancer and cancer-induced abnormal bone growth was observed in a model mimicking prostate cancer metastasized to bone. Specific tumor uptake and efficacy were demonstrated using various PSMA-TTC doses and dosing schedules. Induction of DNA double-strand breaks was identified as a key mode of action for PSMA-TTC both in vitro and in vivo.

Conclusions:
The strong preclinical antitumor activity of PSMA-TTC supports its clinical evaluation, and a phase I trial is ongoing in mCRPC patients (NCT03724747).
Investigation of Antigen-Specific T-Cell Receptor Clusters in Human Cancers
Authors: Zhang Hongyi , Liu Longchao , Zhang Jian , Chen Jiahui , Ye Jianfeng , Shukla Sachet , Qiao Jian , Zhan Xiaowei , Chen Hao , Wu Catherine J. , Fu Yang-Xin , Li Bo 
Published: December 2019

Abstract

Purpose:
Cancer antigen–specific T cells are key components in antitumor immune response, yet their identification in the tumor microenvironment remains challenging, as most cancer antigens are unknown. Recent advance in immunology suggests that similar T-cell receptor (TCR) sequences can be clustered to infer shared antigen specificity. This study aims to identify antigen-specific TCRs from the tumor genomics sequencing data.

Experimental Design:
We used the TRUST (Tcr Repertoire Utilities for Solid Tissue) algorithm to assemble the TCR hypervariable CDR3 regions from 9,700 bulk tumor RNA-sequencing (RNA-seq) samples, and developed a computational method, iSMART, to group similar TCRs into antigen-specific clusters. Integrative analysis on the TCR clusters with multi-omics datasets was performed to profile cancer-associated T cells and to uncover novel cancer antigens.

Results:
Clustered TCRs are associated with signatures of T-cell activation after antigen encounter. We further elucidated the phenotypes of clustered T cells using single-cell RNA-seq data, which revealed a novel subset of tissue-resident memory T-cell population with elevated metabolic status. An exciting application of the TCR clusters is to identify novel cancer antigens, exemplified by our identification of a candidate cancer/testis gene, HSFX1, through integrated analysis of HLA alleles and genomics data. The target was further validated using vaccination of humanized HLA-A*02:01 mice and ELISpot assay. Finally, we showed that clustered tumor-infiltrating TCRs can differentiate patients with early-stage cancer from healthy donors, using blood TCR repertoire sequencing data, suggesting potential applications in noninvasive cancer detection.

Conclusions:
Our analysis on the antigen-specific TCR clusters provides a unique resource for alternative antigen discovery and biomarker identification for cancer immunotherapies.
Aggressive Mammary Cancers Lacking Lymphocytic Infiltration Arise in Irradiated Mice and Can Be Prevented by Dietary Intervention
Authors: Omene Coral , Ma Lin , Moore Jade , Ouyang Haoxu , Illa-Bochaca Irineu , Chou William , Patel Manan S. , Sebastiano Christopher , Demaria Sandra , Mao Jian-Hua , Karagoz Kubra , Gatza Michael L. , Barcellos-Hoff Mary Helen 
Published: December 2019

Abstract
Because the incidence of breast cancer increases decades after ionizing radiation exposure, aging has been implicated in the evolution of the tumor microenvironment and tumor progression. Here, we investigated radiation-induced carcinogenesis using a model in which the mammary glands of 10-month-old BALB/c mice were transplanted with Trp53-null mammary tissue 3 days after exposure to low doses of sparsely ionizing γ-radiation or densely ionizing particle radiation. Mammary transplants in aged, irradiated hosts gave rise to significantly more tumors that grew more rapidly than those in sham-irradiated mice, with the most pronounced effects seen in mice irradiated with densely ionizing particle radiation. Tumor transcriptomes identified a characteristic immune signature of these aggressive cancers. Consistent with this, fast-growing tumors exhibited an immunosuppressive tumor microenvironment with few infiltrating lymphocytes, abundant immunosuppressive myeloid cells, and high COX-2 and TGFβ. Only irradiated hosts gave rise to tumors lacking cytotoxic CD8+ lymphocytes (defined here as immune desert), which also occurred in younger irradiated hosts. These data suggest that host irradiation may promote immunosuppression. To test this, young chimera mice were fed chow containing a honeybee-derived compound with anti-inflammatory and immunomodulatory properties, caffeic acid phenethyl ester (CAPE). CAPE prevented the detrimental effects of host irradiation on tumor growth rate, immune signature, and immunosuppression. These data indicated that low-dose radiation, particularly densely ionizing exposure of aged mice, promoted more aggressive cancers by suppressing antitumor immunity. Dietary intervention with a nontoxic immunomodulatory agent could prevent systemic effects of radiation that fuel carcinogenesis, supporting the potential of this strategy for cancer prevention.
Extracorporeal Membrane Oxygenation Use in Acute Myocardial Infarction in the United States, 2000 to 2014
Authors: Vallabhajosyula Saraschandra , Prasad Abhiram , Bell Malcolm R. , Sandhu Gurpreet S. , Eleid Mackram F. , Dunlay Shannon M. , Schears Gregory J. , Stulak John M. , Singh Mandeep , Gersh Bernard J. , Jaffe Allan S. , Holmes David R. , Rihal Charanjit S. , Barsness Gregory W. 
Published: December 2019

Background:
Extracorporeal membrane oxygenation (ECMO) is increasingly used in acute myocardial infarction (AMI); however, there are limited large-scale national data.

Methods:
Using the National Inpatient Sample database from 2000 to 2014, a retrospective cohort of AMI utilizing ECMO was identified. Use of percutaneous coronary intervention, intra-aortic balloon pump, and percutaneous left ventricular assist device (LVAD) was also identified in this population. Outcomes of interest included temporal trends in utilization of ECMO alone and with concomitant procedures (percutaneous coronary intervention, intra-aortic balloon pump, and percutaneous LVAD), in-hospital mortality, and resource utilization.

Results:
In ≈9 million AMI admissions, ECMO was used in 2962 (<0.01%) and implanted a median of 1 day after admission. ECMO was used in 0.5% and 0.3% AMI admissions complicated by cardiogenic shock and cardiac arrest, respectively. ECMO was used more commonly in admissions that were younger, nonwhite, and with less comorbidity. ECMO use was 11× higher in 2014 as compared with 2000 (odds ratio, 11.37 [95% CI, 7.20–17.97]). Same-day percutaneous coronary intervention was performed in 23.1%; intra-aortic balloon pump/percutaneous LVAD was used in 57.9%, of which 30.3% were placed concomitantly. In-hospital mortality with ECMO was 59.2% overall but decreased from 100% (2000) to 45.1% (2014). Durable LVAD and cardiac transplantation were performed in 11.7% as an exit strategy. Of the hospital survivors, 40.8% were discharged to skilled nursing facilities. Older age, male sex, nonwhite race, and lower socioeconomic status were independently associated with higher in-hospital mortality with ECMO use.

Conclusions:
In AMI admissions, a steady increase was noted in the utilization of ECMO alone and with concomitant procedures (percutaneous coronary intervention, intra-aortic balloon pump, and percutaneous LVAD). In-hospital mortality remained high in AMI admissions treated with ECMO.
Neuroimaging in Ischemic Stroke Is Different Between Men and Women in the DEFUSE 3 Cohort
Authors: Dula Adrienne N. , Mlynash Michael , Zuck Nathan D. , Albers Gregory W. , Warach Steven J. ,   for the DEFUSE 3 Investigators
Published: December 2019

Background and Purpose—
Clinical deficits from ischemic stroke are more severe in women, but the pathophysiological basis of this sex difference is unknown. Sex differences in core and penumbral volumes and their relation to outcome were assessed in this substudy of the DEFUSE 3 clinical trial (Endovascular Therapy Following Imaging Evaluation for Ischemic Stroke).

Methods—
DEFUSE 3 randomized patients to thrombectomy or medical management who presented 6 to 16 hours from last known well with proximal middle cerebral artery or internal carotid artery occlusion and had target core and perfusion mismatch volumes on computed tomography or magnetic resonance imaging. Using univariate and adjusted regression models, the effect of sex was assessed on prerandomization measures of core, perfusion, and mismatch volumes and hypoperfusion intensity ratio, and on core volume growth using 24-hour scans.

Results—

All patients were included in the analysis (n=182) with 90 men and 92 women. There was no sex difference in the site of baseline arterial occlusion. Adjusted by age, baseline National Institutes of Health Stroke Scale, baseline modified Rankin Scale score, time to randomization, and imaging modality, women had smaller core, hypoperfusion, and penumbral volumes than men. Median (interquartile range) volumes for core were 8.0 mL (1.9–18.4) in women versus 12.6 mL (2.7–29.6) in men, for T
max
>6 seconds 89.0 mL (63.8–131.7) versus 133.9 mL (87.0–175.4), and for mismatch 82.1mL (53.8–112.8) versus 108.2 (64.1–149.2). The hypoperfusion intensity ratio was lower in women, 0.31 (0.15–0.46) versus 0.39 (0.26–0.57),
P
=0.006, indicating better collateral circulation, which was consistent with the observed slower ischemic core growth than men within the medical group (
P
=0.003).

Conclusions—
In the large vessel ischemic stroke cohort selected for DEFUSE 3, women had imaging evidence of better collateral circulation, smaller baseline core volumes, and slower ischemic core growth. These observations suggest sex differences in hemodynamic and temporal features of anterior circulation large artery occlusions.

Registration—

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT02586415.
Mantik, Rhetorik und Poetologie
Authors: Kuhn-Treichel Thomas 
Published: December 2019

Abstract
Lucian’s dialogue with Hesiod appears to be a straightforward dispute on a defined topic in which the poet rather awkwardly defends himself against a most legitimate charge and ends up being justly convicted by Lycinus. Upon closer investigation, however, one can detect several remarkable subtexts that make the dialogue a sophisticated pleasure for learned readers. This paper discusses three possible subtexts: mantic, rhetoric, and poetology. Seen against this backdrop, Lucian’s Hesiod emerges as a pretentious mantis, rhetor and (maybe) poetologist, who, in a certain sense, can be compared to the pretentious πεπαιδευµένοι attacked in so many of Lucian’s works.
Marx’s Economic Manuscript of 1867–68 (Excerpt)
Authors: Marx Karl 
Published: December 2019

Abstract
This archive manuscript is an English translation of a 25-page excerpt from Marx’s Manuscript of 1867–68, which was published for the first time in German in 2012 in the MEGA, Volume II/4.3. This excerpt is Marx’s first and only attempt to incorporate unequal turnover times across industries into his theory of the equalisation of the profit rate and prices of production. The excerpt considers three cases: unequal turnover times across industries, unequal compositions of capital across industries, and both of these inequalities together. It also emphasises two concepts of the rate of profit: rate of profit on capital advanced and rate of profit on the cost price (capital consumed).