bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Phase I Dose-Escalation Trial of BN-CV301, a Recombinant Poxviral Vaccine Targeting MUC1 and CEA with Costimulatory Molecules
Authors: Gatti-Mays Margaret E. , Strauss Julius , Donahue Renee N. , Palena Claudia , Del Rivero Jaydira , Redman Jason M. , Madan Ravi A. , Marté Jennifer L. , Cordes Lisa M. , Lamping Elizabeth , Orpia Alanvin , Burmeister Andrea , Wagner Eva , Pico Navarro Cesar , Heery Christopher R. , Schlom Jeffrey , Gulley James L. 
Published: May 2019

Abstract

Purpose:
BN-CV301 is a poxviral-based vaccine comprised of recombinant (rec.) modified vaccinia Ankara (MVA-BN-CV301; prime) and rec. fowlpox (FPV-CV301; boost). Like its predecessor PANVAC, BN-CV301 contains transgenes encoding tumor-associated antigens MUC1 and CEA as well as costimulatory molecules (B7.1, ICAM-1, and LFA-3). PANVAC was reengineered to make it safer and more antigenic.

Patients and Methods:
This open-label, 3+3 design, dose-escalation trial evaluated three dose levels (DL) of MVA-BN-CV301: one, two, or four subcutaneous injections of 4 × 108 infectious units (Inf.U)/0.5 mL on weeks 0 and 4. All patients received FPV-CV301 subcutaneously at 1 × 109 Inf.U/0.5 mL every 2 weeks for 4 doses, then every 4 weeks. Clinical and immune responses were evaluated.

Results:
There were no dose-limiting toxicities. Twelve patients enrolled on trial [dose level (DL) 1 = 3, DL2 = 3, DL3 = 6). Most side effects were seen with the prime doses and lessened with subsequent boosters. All treatment-related adverse events were temporary, self-limiting, grade 1/2, and included injection-site reactions and flu-like symptoms. Antigen-specific T cells to MUC1 and CEA, as well as to a cascade antigen, brachyury, were generated in most patients. Single-agent BN-CV301 produced a confirmed partial response (PR) in 1 patient and prolonged stable disease (SD) in multiple patients, most notably in KRAS-mutant gastrointestinal tumors. Furthermore, 2 patients with KRAS-mutant colorectal cancer had prolonged SD when treated with an anti-PD-L1 antibody following BN-CV301.

Conclusions:
The BN-CV301 vaccine can be safely administered to patients with advanced cancer. Further studies of the vaccine in combination with other agents are planned.
See related commentary by Repáraz et al., p. 4871
BRD4 Regulates Metastatic Potential of Castration-Resistant Prostate Cancer through AHNAK
Authors: Shafran Jordan S. , Andrieu Guillaume P. , Györffy Balázs , Denis Gerald V. 
Published: May 2019

Abstract

The inevitable progression of advanced prostate cancer to castration resistance, and ultimately to lethal metastatic disease, depends on primary or acquired resistance to conventional androgen deprivation therapy (ADT) and accumulated resistance strategies to evade androgen receptor (AR) suppression. In prostate cancer cells, AR adaptations that arise in response to ADT are not singular, but diverse, and include gene amplification, mutation, and even complete loss of receptor expression. Collectively, each of these AR adaptations contributes to a complex, heterogeneous, ADT-resistant tumor. Here, we examined prostate cancer cell lines that model common castration-resistant prostate cancer (CRPC) subtypes, each with different AR composition, and focused on novel regulators of tumor progression, the Bromodomain and Extraterminal (BET) family of proteins. We found that BRD4 regulates cell migration across all models of CRPC, regardless of aggressiveness and AR status, whereas BRD2 and BRD3 only regulate migration and invasion in less aggressive models that retain AR expression or signaling. BRD4, a coregulator of gene transcription, controls migration and invasion through transcription of AHNAK, a large scaffolding protein linked to promotion of metastasis in a diverse set of cancers. Furthermore, treatment of CRPC cell lines with low doses of MZ1, a small-molecule, BRD4-selective degrader, inhibits metastatic potential. Overall, these results reveal a novel BRD4–AHNAK pathway that may be targetable to treat metastatic CRPC (mCRPC).

Implications:
BRD4 functions as the dominant regulator of CRPC cell migration and invasion through direct transcriptional regulation of AHNAK, which together offer a novel targetable pathway to treat metastatic CRPC.
Visual Overview: http://mcr.aacrjournals.org/content/molcanres/17/8/1627/F1.large.jpg.
Heterogeneity in Colorectal Cancer Stem Cells
Authors: Hirata Akihiro , Hatano Yuichiro , Niwa Masayuki , Hara Akira , Tomita Hiroyuki 
Published: May 2019

Abstract
Cancer stem cells (CSC) have attracted a great deal of interest for their clinical relevance in a range of cancers, including colorectal cancer. CSCs were initially considered to be cell populations with homogeneous, well-defined phenotypic and molecular characteristics. However, accumulating evidence suggests that CSCs represent phenotypically and functionally heterogeneous populations. Recent studies demonstrate colorectal CSCs to be dynamic rather than static, and continuously altered by multiple extrinsic and intrinsic factors. Thus, CSCs no longer should be viewed as a fixed target population, and we should note that their heterogeneous and dynamic nature presents a serious problem for the development and implementation of specific therapeutic strategies. This review summarizes past and current literature related to the heterogeneity and dynamics of colorectal CSC populations, focusing on evidence for distinct subpopulations, and signaling pathways, and intra- and extratumoral factors involved in their regulation in cancer tissues.
TAS-120 Overcomes Resistance to ATP-Competitive FGFR Inhibitors in Patients with FGFR2 Fusion–Positive Intrahepatic Cholangiocarcinoma
Authors: Goyal Lipika , Shi Lei , Liu Leah Y. , Fece de la Cruz Ferran , Lennerz Jochen K. , Raghavan Srivatsan , Leschiner Ignaty , Elagina Liudmila , Siravegna Giulia , Ng Raymond W.S. , Vu Phuong , Patra Krushna C. , Saha Supriya K. , Uppot Raul N. , Arellano Ron , Reyes Stephanie , Sagara Takeshi , Otsuki Sachie , Nadres Brandon , Shahzade Heather A. , Dey-Guha Ipsita , Fetter Isobel J. , Baiev Islam , Van Seventer Emily E. , Murphy Janet E. , Ferrone Cristina R. , Tanabe Kenneth K. , Deshpande Vikram , Harding James J. , Yaeger Rona , Kelley Robin K. , Bardelli Alberto , Iafrate A. John , Hahn William C. , Benes Cyril H. , Ting David T. , Hirai Hiroshi , Getz Gad , Juric Dejan , Zhu Andrew X. , Corcoran Ryan B. , Bardeesy Nabeel 
Published: May 2019

AbstractATP-competitive fibroblast growth factor receptor (FGFR) kinase inhibitors, including BGJ398 and Debio 1347, show antitumor activity in patients with intrahepatic cholangiocarcinoma (ICC) harboring activating FGFR2 gene fusions. Unfortunately, acquired resistance develops and is often associated with the emergence of secondary FGFR2 kinase domain mutations. Here, we report that the irreversible pan-FGFR inhibitor TAS-120 demonstrated efficacy in 4 patients with FGFR2 fusion–positive ICC who developed resistance to BGJ398 or Debio 1347. Examination of serial biopsies, circulating tumor DNA (ctDNA), and patient-derived ICC cells revealed that TAS-120 was active against multiple FGFR2 mutations conferring resistance to BGJ398 or Debio 1347. Functional assessment and modeling the clonal outgrowth of individual resistance mutations from polyclonal cell pools mirrored the resistance profiles observed clinically for each inhibitor. Our findings suggest that strategic sequencing of FGFR inhibitors, guided by serial biopsy and ctDNA analysis, may prolong the duration of benefit from FGFR inhibition in patients with FGFR2 fusion–positive ICC.Significance:ATP-competitive FGFR inhibitors (BGJ398, Debio 1347) show efficacy in FGFR2-altered ICC; however, acquired FGFR2 kinase domain mutations cause drug resistance and tumor progression. We demonstrate that the irreversible FGFR inhibitor TAS-120 provides clinical benefit in patients with resistance to BGJ398 or Debio 1347 and overcomes several FGFR2 mutations in ICC models.This article is highlighted in the In This Issue feature, p. 983
Causes of Mortality After Percutaneous Coronary Intervention
Authors: Bricker Rory S. , Valle Javier A. , Plomondon Mary E. , Armstrong Ehrin J. , Waldo Stephen W. 
Published: May 2019

Background:
Public reporting of percutaneous coronary intervention (PCI) often uses periprocedural (30 days) mortality as a surrogate for procedural quality, though it is unclear how often death is attributable to the PCI. The cause of death among patients who died within 30 days of PCI in a national healthcare system was thus evaluated.

Methods and Results:

We identified all patients who died within 30 days of PCI in the Veterans Affairs (VA) Healthcare System from October 2005 to September 2016. Causes of death were classified through a detailed chart review using definitions from the Academic Research Consortium. Of 115 191 patients undergoing PCI during the study period, 1674 patients died within 30 days of PCI (1.5%). A detailed chart review demonstrated that the majority of patients had an undifferentiated death not definitively attributable to a single cause (981, 59%), whereas a minority had a death directly attributable to a cardiovascular cause (467, 28%). The majority of cardiovascular deaths were unrelated to the interventional procedure (335, 72%). Cardiovascular deaths were more likely to occur in the inpatient setting (95%) compared with noncardiac (89%) or undifferentiated deaths (49%,
P
<0.001).

Conclusions:
A minority of deaths occurring after percutaneous revascularization were definitively due to cardiac causes, with an even smaller proportion related to the PCI. With such a small proportion of deaths directly attributable to the PCI, these data suggest that 30-day mortality may be an inappropriate metric to assess procedural quality.
Vaterschaftstests zwischen religiösem Recht und Medizintechnik: Abstammungsklagen im algerischen Familienrecht
Authors: Guénon Melanie 
Published: May 2019

This article examines the 2005 Algerian family law regulations concerning paternity and the use of DNA tests in Algerian paternity disputes. Specifically, it analyzes the relation between the methods of establishing and negating paternity recognized in Islamic law and the available genetic technology. On the basis of three judgments of the Supreme Court, the present legislation as well as legal practice in Algeria is scrutinized. The article concludes that the Algerian legislator hesitates to dissolve the conflict between genetic technology and the recognized types of evidence of Islamic law. For now, court practice remains ‘traditional’ since judges might feel too much responsibility facing unclear regulations regarding paternity. Nevertheless, the Algerian family code reform offers the opportunity to use DNA-tests to establish nasab for both legitimate and illegitimate children. Due to unclear regulations it also paved the way to use DNA-analysis for paternity negation.*
Financial Management Activity Process: Qualitative inquiry of adults with acquired brain injury
Authors: Engel Lisa L. , Beaton Dorcas E. , Green Robin E. , Dawson Deirdre R. 
Published: May 2019

Background. Little is known about the financial management occupations of people living with brain injury, despite the importance of these to adult autonomy. Purpose. This work aims to develop a conceptual framework for financial management after adulthood acquired brain injury. Method. This qualitative study used grounded theory methods. Data included semistructured interviews of 10 adults living with brain injury and two close others who assist with financial management occupations. Analysis included initial and focused coding, memo writing, constant comparison, theoretical sampling of questions, and member checking. Findings. The Financial Management Activity Process conceptual framework describes a complex action process. This includes accounting for factors influencing financial choices and actions, and identifying and using a trusted personalized process, including using financial management strategies aligned with the constraints of factors. Implications. This conceptual framework may be useful to assessment and intervention development. It highlights the between-person and between-activity variability in financial management processes and strategy use.
Investigating macrophage-mediated inflammation in migraine using ultrasmall superparamagnetic iron oxide-enhanced 3T magnetic resonance imaging
Authors: Khan Sabrina , Amin Faisal Mohammad , Fliedner Frederikke Petrine , Christensen Casper Emil , Tolnai Daniel , Younis Samaira , Olinger Anne Christine Rye , Birgens Henrik , Daldrup-Link Heike , Kjær Andreas , Larsson Henrik Bo Wiberg , Lindberg Ulrich , Ashina Messoud 
Published: May 2019

Background Initiating mechanisms of migraine headache remain poorly understood and a biomarker of migraine does not exist. Inflammation pertaining to the wall of cerebral arteries and brain parenchyma has been suggested to play a role in migraine pathophysiology. Objective We conducted the first experimental human study to investigate macrophage-mediated inflammation as a possible biomarker of migraine. Methods Using ultrasmall superparamagnetic iron oxide (USPIO)-enhanced 3T magnetic resonance imaging (MRI), we investigated the presence of macrophages in cerebral artery walls and in brain parenchyma of patients with migraine without aura. We used the phosphodiesterase-3-inhibitor cilostazol as an experimental migraine trigger, and investigated both patients who received sumatriptan treatment, and patients who did not. To validate our use of USPIO-enhanced MRI, we included a preclinical mouse model with subcutaneous capsaicin injection in the trigeminal V1 area. The study is registered at ClinicalTrials.gov with the identifier NCT02549898. Results A total of 28 female patients with migraine without aura underwent a baseline MRI scan, ingested cilostazol, developed a migraine-like attack, and underwent an USPIO-enhanced MRI scan > 24 hours after intravenous administration of USPIO. Twelve patients treated their attack with 6 mg s.c. sumatriptan, while the remaining 16 patients received no migraine-specific rescue medication. The preclinical model confirmed that USPIO-enhanced MRI detects macrophage-mediated inflammation. In patients, however, migraine attacks were not associated with increased USPIO signal on the pain side of the head compared to the non-pain side. Conclusion Our findings suggest that migraine without aura is not associated with macrophage-mediated inflammation specific to the head pain side.
Revisiting BISFT Summer School 2006, Harriot-Watt University, Edinburgh, ‘What’s God got to do with it? – Politics, Economics, Theology’
Authors: McPhillips Kathleen 
Published: May 2019

This article addresses research that deals with approaches to psychological and social trauma and ways to manage its disruptive power. In the first instance I apply this to the life of my great-grandmother in order to help understand why her life became unbearably difficult, the treatment she received as a female ‘hysteric’ in the 1940s and most importantly the impact that her life has continued to have through four generations of family life. In the second instance, I apply trauma theory to the history of forgetting women and its implications for feminist action and recovery with specific reference to Feminist Theology. I suggest that there are powerful connections between the individual and collective forgetting of women’s lives, and that this forgetting is premised on forms of symbolic violence. I turn to the work of psychiatrists Judith Herman, and Russell Meares and feminist theologian Elisabeth Schüssler Fiorenza, in order to provide an account of forgetting, remembering and finally recovery.
Development of a joint mental-health and drug health assessment unit and short-stay unit
Authors: Kealy-Bateman Warren , McDonald Andrew , Haber Paul S , Green Tim , White Bethany , Sundakov Viktoria , O’Cionnaith Cathal , Glozier Nicholas 
Published: May 2019

Objectives: There is emerging interest in models of care that focus on assessment and brief inpatient treatment (two to three days) including psychiatric emergency care centre units and short-stay units in Australia. We present the development of a functionally integrated Missenden Assessment Unit and six-bed short-stay unit in the new Professor Marie Bashir Centre at Royal Prince Alfred Hospital in inner-city Sydney. The focus was on collaboration between emergency, drug and alcohol and mental-health services in developing the short-stay unit and Missenden Assessment Unit with joint admission and resource use. We outline the models of care and findings from the 2016 evaluation following the initial two years of operation and consider ongoing challenges. Conclusion: The Missenden Assessment Unit provides an alternative point of presentation for mental-health drug and alcohol patients. The short-stay unit provides coordinated, therapeutic interventions. The Missenden Assessment Unit/short-stay unit reduced the burden of presentations to the emergency department while providing the opportunity for training and collaboration. Further refinement of the models of care should occur with policy development and via research.
Prognostic Value of MMP-9 -1562 C/T Gene Polymorphism in Patients With Sepsis
Authors: Bermúdez-Mejía César , Torres-Cordón Melissa F , Becerra-Bayona Silvia , Páez Carolina María , Vargas Clara Inés , Cárdenas María Eugenia , Serrano Sergio Eduardo , Baquero Ingrid , Martínez-Vega Ruth , Schulz Richard , Ilarraza Ramses , Pazin Filho Antonio , Torres-Dueñas Diego 
Published: May 2019

Introduction: Matrix metalloproteinase-9 (MMP-9) plays an important role in the pathophysiology of sepsis. A single-nucleotide polymorphism (SNP) at position -1562 (C/T) in the MMP-9 gene has been associated with differential MMP-9 expression, being higher when the -1562 T allele is present. We evaluated the association of the SNP MMP9 -1562 C/T with severity and mortality in patients with sepsis to establish whether the prognosis of the disease is affected. Materials and Methods: A case-control study exploratory was carried out in a cohort of infected patients. 540 individuals were selected in total, 270 patients with sepsis and 270 controls (infected but non-septic), classified according to the 2016 consensus (Sepsis-3). The presence of the single-nucleotide polymorphism (SNP; allele T and/or allele C) was determined through analyses of restriction fragment length polymorphism and plasma levels of MMP-9 were determined through enzyme-linked immunosorbent assay immunoassay. Results: SNP MMP-9 -1562 has two known alleles (T and C), with predominance of the C over the T allele; in the group of patients with sepsis, T allele was found in 7.2% of cases, while C allele in the rest (92.8%); in comparison, in the group of infected but non-septic patients, frequencies were 9.4% for T allele and 90.6% for the C allele ( P = .33). Also, the presence of the polymorphic T allele was not related to the levels of MMP-9 in patients with sepsis in comparison with infected but non-septic patients 780 (397-1375) ng/mL vs 646 (172-1249) ng/mL ( P = .64). There was also no association between the SNP and sepsis mortality ( P = .78). Conclusions: We concluded that there was no association between the SNP MMP9 -1562 C/T and sepsis or between the SNP MMP9 -1562 C/T and sepsis mortality in the Northeastern Colombian septic patient cohort. Further research is needed to clarify the correlation among sepsis, genetic factors with allele T and MMP-9 plasma concentration.
Alcohol and illicit drug consumption and the association with risky sexual behaviour among Swedish youths visiting youth health clinics
Authors: Strandberg Anna , Skoglund Charlotte , Gripenberg Johanna , Kvillemo Pia 
Published: May 2019

Aims: High alcohol consumption and use of illicit drugs among young people is of great concern and there is a need to identify arenas where this group can be reached by preventive measures. The aim of the present study was to study prevalence of risky alcohol consumption, illicit drug use, and risky sexual behaviour (RSB) among young people visiting youth health clinics in Stockholm county. Another aim was to explore the association between risky alcohol consumption, illicit drug use and RSB. Methods: During autumn 2016, an anonymous questionnaire comprising questions about alcohol, illicit drugs and risky sexual behaviour was given to visitors at 11 youth health clinics in Stockholm county. Results: A total of 328 youths ( M = 18.8 years, 89% girls) answered the questionnaire. Results show that 61.7% had risky alcohol consumption and 41.8% had tried illicit drugs. Risky sexual behaviour was more prevalent among respondents with risky alcohol consumption, and it was more common among non-students than students. Conclusions: Findings indicate that a large proportion of visitors at youth health clinics in Stockholm county has a risky alcohol consumption and experiences of other drugs, and also that risky alcohol consumption is associated with three of five RSB outcomes. Non-students seemed to be a particularly exposed risk group with regard to both risky alcohol consumption and RSB. Overall, the results indicate that youth health clinics are an important arena for alcohol prevention.
LncRNA-SRA1 Suppresses Osteosarcoma Cell Proliferation While Promoting Cell Apoptosis
Authors: Guo Wen , Jiang Haitao , Li Haijun , Li Fang , Yu Qing , Liu Yu , Jiang Weiwei , Zhang Ming 
Published: May 2019

Objective: Osteosarcoma is a common malignant bone tumor that is frequently found in the long bones of children and adolescents. The aim of this study is to examine long noncoding RNA-steroid receptor RNA activator 1 expression in osteosarcoma to explore the biological function of long noncoding RNA steroid receptor RNA activator 1 on proliferation, migration, and invasion along with apoptosis and its regulatory mechanism, which would facilitate the early diagnosis and targeted therapy of osteosarcoma. Methods: First, microarray analysis was applied to determine the expression of long noncoding RNAs in osteosarcoma tissues and paired normal tissues. Then, quantitative real-time polymerase chain reaction was utilized to validate microarray findings. Next, osteosarcoma cancerous cell lines SJSA-1 and U2OS were transfected with pcDNA3.1-SRA1 or pCMV-sh-SRA1 to increase or decrease steroid receptor RNA activator 1 expression levels, and microRNA-208a inhibitors, mimic to investigate the effects of microRNA-208a on osteosarcoma as well as the regulatory relation between long noncoding RNA steroid receptor RNA activator 1 and microRNA-208a. Cell proliferation was evaluated through Cell Counting Kit-8 and colony formation assays. Flow cytometry analysis was conducted to evaluate the apoptosis ratio. The migration and invasion abilities were measured using wound-healing and transwell assays. Results: Long noncoding RNA-steroid receptor RNA activator 1 expression was downregulated in osteosarcoma tissues and cells compared with that in corresponding normal tissues, whereas microRNA-208a expression was upregulated in osteosarcoma tissues. Moreover, the restoration of long noncoding RNA steroid receptor RNA activator 1 inhibited cell proliferation, and upregulation of long noncoding RNA steroid receptor RNA activator 1 restrained cell migration and invasion but boosted the apoptosis rate in osteosarcoma cells. In addition, long noncoding RNA steroid receptor RNA activator 1 targeting microRNA-208a was involved in the progression of osteosarcoma. Furthermore, upregulating microRNA-208a exerted similar roles of silencing long noncoding RNA steroid receptor RNA activator 1 in cell apoptosis, proliferation, migration, and invasion, which were reversed by enhancing the expression of long noncoding RNA steroid receptor RNA activator 1. Conclusions: In our study, long noncoding RNA steroid receptor RNA activator 1 played an antitumor role in osteosarcoma as it reduced cell migration, invasion, and proliferation, but facilitated cell apoptosis via sponging microRNA-208a, which could be regarded as a potential therapeutic target of osteosarcoma treatment.