bluuebunny/crossref_metadata_2025_split huggingface dataset:
Competing needs: a qualitative study of cervical cancer screening attendance among HPV-positive women in Tanzania
Authors: Linde Ditte Søndergaard , Rasch Vibeke , Mwaiselage Julius D , Gammeltoft Tine M 
Published: February 2019

ObjectivesThe aim of this study was to understand causes of attendance and non-attendance to a follow-up cervical cancer screening among human papillomavirus (HPV)-positive women.DesignSemistructured, individual interviews with HPV-positive women and cervical cancer screening nurses. The interview guide and initial data analysis were guided by existing health behaviour theories. However, as the theories limited the potential of the data material, a grounded theory framework guided the final data analysis.SettingInterviews were conducted in Dar es Salaam, Tanzania, at Ocean Road Cancer Institute (ORCI) or in the homes of screening clients.Participants15 interviews were conducted with women who had tested HPV-positive during a patient-initiated screening and been appointed for a follow-up screening 14 months later. Nine women had not attended the follow-up appointment, four had delayed attendance and two had attended on the scheduled date. Further, individual interviews were conducted with the two nurses working at ORCI’s screening clinic.ResultsPerceived benefits for attending a patient-initiated screening include treatment of gynaecological symptoms and prevention of disease. The key perceived benefit of a health provider-initiated follow-up screening is prevention, which is challenged by the circumstance that it is seen by women as having merely potential benefit and therefore can be postponed when competing needs are present. Perceived challenges for screening attendance include emotional costs, in the form of fear of the disease, fear of the gynaecological examination as well as direct and indirect economic costs, such as transportation costs, lost income and waiting time.ConclusionCervical cancer screening is one among many tasks that women living in a low-income setting must attend to. Since health provider-initiated follow-up screening is seen as having only potential benefit, attendance can be postponed when competing needs exist.Trial registration numberNCT02509702.
Impact of patient’s health-related quality of life on physicians’ therapy and perceived benefit in acute coronary syndromes: protocol for a systemic review of quantitative and qualitative studies
Authors: Kaambwa Billingsley , Gesesew Hailay , Horsfall Matthew , Chew Derek P 
Published: February 2019

IntroductionPercutaneous coronary interventions (PCIs) and coronary angiography are two of the treatments administered to acute coronary syndrome (ACS) patients. However, whether and how patients’ health-related quality of life (HRQoL) influences treatment decisions and subsequent risk benefit analyses is unclear. In this study, we will review the available evidence on the impact of patients’ HRQoL on physicians’ prescribing or treatment decisions and on the estimation of mortality and bleeding risk in ACS patients.Methods and analysisWe will undertake a systematic review of all quantitative and qualitative studies. The search will include studies that describe the impact of HRQoL on prescribing PCIs or angiography, and impact of HRQoL on perceived risks in terms of mortality and bleeding events. We will conduct an initial search on Google scholar and MEDLINE to build the searching terms followed by a full search strategy using all identified keywords and index terms across the five databases, namely MEDLINE, PubMed, CINAHL, SCOPUS and Web of Sciences. We will use the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for protocol guidelines to present the protocol. Only English language articles will be included for the review. We will use a standardised Joanna Briggs Institute data extraction tool to synthesise the information extracted from the selected studies into themes with summary findings presented in a table.Ethics and disseminationWe will not require a formal ethical approval as we will not be collecting primary data. Review findings will be disseminated through a peer-reviewed publication, workshops, conference presentations and a media release.PROSPERO registration numberCRD42018108438.
A31P-NMR spectroscopic study of phosphorus forms in two phosphorus-fertilized grassland soils in eastern Canada
Authors: Abdi Dalel , Cade-Menun Barbara J. , Ziadi Noura , Shi Yichao , Bélanger Gilles , Lajeunesse Julie , Lafond Jean 
Published: February 2019

Phosphorus (P) fertilization can increase grassland production, but will also alter P forms, changing their cycling and potential for loss in runoff. We assessed the effects of mineral P fertilization on soil P forms in timothy swards at two sites in Quebec, Canada. Soil samples (10 cm depth) were collected in autumn 2013 from replicate plots at Lévis on a Kamouraska clay and at Normandin on a Labarre clay loam, each having received three rates of triple superphosphate (0, 20, and 40 kg P ha−1) for 4 yr. These were analyzed for pH, total carbon (TC), total nitrogen (TN), and total phosphorus (TP); Mehlich-3-extractable aluminium (AlM3), iron (FeM3), calcium (CaM3), and P (PM3); and31P nuclear magnetic resonance spectroscopy (31P-NMR) following sodium hydroxide–ethylenediaminetetraacetic acid (NaOH–EDTA) extraction. Phosphorus fertilization had no significant effects on soil TC, TN, AlM3, FeM3, CaM3, and pH, but significantly increased TP, NaOH–EDTA-extractable total P and total inorganic P, PM3, orthophosphate, and glucose 6-phosphate at both sites. In contrast, NaOH–EDTA-extractable total organic P, total orthophosphate diesters, and scyllo-inositol hexaphosphate decreased with P fertilization. Phosphorus fertilization over 4 yr increased soluble inorganic P and decreased organic P at both grassland sites.
Structural and magnetic study of metallo-organic YIG powder using 2-ethylhexanoate carboxylate-based precursors
Authors: Hosseinzadeh S. , Elahi P. , Behboudnia M. , Sheikhi M. H. , Mohseni S. M. 
Published: February 2019

The crystallization and magnetic behavior of yttrium iron garnet (YIG) prepared by metallo-organic decomposition (MOD) method are discussed. The chemistry and physics related to synthesis of iron and yttrium carboxylates based on 2-ethylhexanoic acid (2EHA) are studied, since no literature was found which elucidates synthesis of metallo-organic precursor of YIG in spite of the literatures of doped YIG samples such as Bi-YIG. Typically, the metal carboxylates used in preparation of ceramic oxide materials are 2-ethylhexanoate (2EH) solvents. Herein, the synthesis, thermal behavior and solubility of yttrium and iron 2EH used in synthesis of YIG powder by MOD are reported. The crystallization and magnetic parameters, including saturation magnetization and coercivity of these samples, smoothly change as a function of the annealing temperature. It is observed that high sintering temperature of [Formula: see text] to [Formula: see text] promotes the diffraction peaks of YIG, therefore, we can conclude that the formation of YIG in MOD method increases the crystallization temperature. The maximum value of saturation magnetization and minimum value of coercivity and remanence are observed for the sample sintered at [Formula: see text] which are 13.7 emu/g, 10.38 Oe and 1.5 emu/g, respectively. This study cites the drawbacks in chemical synthesis of metallo-organic-based YIG production.
Phase 1 Open-Label, Multicenter Study of First-in-Class RORγ Agonist LYC-55716 (Cintirorgon): Safety, Tolerability, and Preliminary Evidence of Antitumor Activity
Authors: Mahalingam Devalingam , Wang Judy S. , Hamilton Erika P. , Sarantopoulos John , Nemunaitis John , Weems Garry , Carter Laura , Hu Xiao , Schreeder Marshall , Wilkins H. Jeffrey 
Published: February 2019

AbstractPurpose:Transcription factor retinoic acid receptor–related orphan receptor γ (RORγ) regulates type 17 effector T-cell differentiation and function and is key to immune cell regulation. Synthetic RORγ agonists modulate immune cell gene expression to increase effector T-cell activity and decrease immune suppression. A phase 1 study evaluated the safety and tolerability of LYC-55716 (cintirorgon), a first-in-class, oral, small-molecule RORγ agonist in adults with relapsed/refractory metastatic cancer.Patients and Methods:Patients received 28-day treatment cycles of oral LYC-55716; dose and dosing regimen were determined according to pharmacokinetic profile and safety. Primary endpoints were safety and tolerability. Secondary endpoints included pharmacokinetics and objective tumor response rate.Results:No dose-limiting toxicities occurred among the 32 enrolled patients who received LYC-55716 150 mg BID to 450 mg BID. Treatment-related adverse events (AE) were primarily grade 1–2 and included diarrhea (n = 11), fatigue (n = 7), anemia (n = 4), decreased appetite (n = 4), and nausea (n = 4). Grade 3 AEs were anemia (n = 2), elevated gamma-glutamyl transferase (n = 1), and hypophosphatemia (n = 1). Pharmacokinetic concentrations achieved levels expected for target gene regulation. Pharmacodynamic results indicated RORγ pathway engagement. Two patients (NSCLC and sarcomatoid breast cancer) had confirmed partial responses; 11 had disease stabilization for 2 to 12 months (6 received &gt;4 months of treatment).Conclusions:These data support the safety and tolerability of LYC-55716 and selection of 450 mg BID dose for a phase 2a study assessing LYC-55716 clinical activity, safety, and biomarkers in patients with NSCLC, head and neck, gastroesophageal, renal cell, urothelial, and ovarian cancers.
Safety and Efficacy of Rivaroxaban When Added to Aspirin Monotherapy Among Stabilized Post‐Acute Coronary Syndrome Patients: A Pooled Analysis Study of ATLAS ACS‐TIMI 46 and ATLAS ACS 2‐TIMI 51
Authors: Gibson William J. , Gibson C. Michael , Yee Megan K. , Korjian Serge , Daaboul Yazan , Plotnikov Alexei N. , Burton Paul , Braunwald Eugene 
Published: February 2019

Background

A residual risk of ischemic events following an acute coronary syndrome (
ACS
) remains despite antiplatelet therapy. The addition of an antithrombin as part of a “dual pathway” approach may further improve outcomes as thrombin generation persists for several months post‐
ACS
. The present study evaluates the safety and efficacy of “dual pathway” therapy (rivaroxaban plus aspirin) as compared with aspirin monotherapy among post‐
ACS
patients.

Methods and Results

A total of 1477 patients were analyzed in a pooled analysis of subsets of the
ATLAS ACS
‐
TIMI
(Anti‐Xa Therapy to Lower cardiovascular events in addition to Aspirin with or without thienopyridine therapy in Subjects with Acute Coronary Syndrome – Thrombolysis in Myocardial Infarction) 46 and
ATLAS ACS
2‐
TIMI
51 trials including post‐
ACS
patients receiving aspirin monotherapy and randomized to either rivaroxaban 2.5 mg
BID
or rivaroxaban 5 mg
BID
or placebo. The primary efficacy end point was a composite of cardiovascular death, myocardial infarction (
MI
), or stroke (ischemic, hemorrhagic, or of uncertain cause). The primary safety end point was
TIMI
‐non‐coronary artery bypass (
CABG
) major bleeding. The combined rivaroxaban group (2.5 or 5 mg
BID
) among stabilized post‐
ACS
patients on a background of aspirin monotherapy was associated with a significant reduction in the primary end point as compared with placebo (hazard ratio=0.65, 95%
CI
=0.45–0.92,
P
=0.016). Although the combined rivaroxaban dose groups were associated with higher rates of non‐
CABG TIMI
major bleeding, the 2.5 mg dose group was not, and the overall number of patients experiencing a non‐
CABG TIMI
major bleeding event was low (1.5%).

Conclusions

Among patients in the immediate post‐
ACS
period, a “dual pathway” approach using aspirin and low‐dose rivaroxaban may reduce the risk of secondary atherothrombotic events, but increase bleeding risk.

Clinical Trial Registration

URL
:
https://www.clinicaltrials.gov
. Unique identifiers:
NCT
00402597;
NCT
00809965.
Catheter Ablation of Ventricular Tachycardia in Patients With Arrhythmogenic Right Ventricular Cardiomyopathy/Dysplasia: A Sequential Approach
Authors: Mathew Shibu , Saguner Ardan M. , Schenker Niklas , Kaiser Lukas , Zhang Pengpai , Yashuiro Yoshiga , Lemes Christine , Fink Thomas , Maurer Tilman , Santoro Francesco , Wohlmuth Peter , Reißmann Bruno , Heeger Christian H. , Tilz Roland , Wissner Erik , Rillig Andreas , Metzner Andreas , Kuck Karl‐Heinz , Ouyang Feifan 
Published: February 2019

Background

It has been suggested that endocardial and epicardial ablation of ventricular tachycardia (
VT
) improves outcome in arrhythmogenic right ventricular cardiomyopathy/dysplasia. We investigated our sequential approach for
VT
ablation in patients with arrhythmogenic right ventricular cardiomyopathy/dysplasia in a single center.

Methods and Results

We included 47 patients (44±16 years) with definite (81%) or borderline (19%) arrhythmogenic right ventricular cardiomyopathy/dysplasia between 1998 and 2016. Our ablation strategy was to target the endocardial substrate. Epicardial ablation was performed in case of acute ablation failure or lack of an endocardial substrate. Single and multiple procedural 1‐ and 5‐year outcome data for the first occurrence of the study end points (sustained
VT
/ventricular fibrillation, heart transplant, and death after the index procedure, and sustained
VT
/ventricular fibrillation for multiple procedures) are reported. Eighty‐one radiofrequency ablation procedures were performed (mean 1.7 per patient, range 1–4). Forty‐five (56%) ablation procedures were performed via an endocardial, 11 (13%) via an epicardial, and 25 (31%) via a combined endo‐ and epicardial approach. Complete acute success was achieved in 65 (80%) procedures, and partial success in 13 (16%). After a median follow‐up of 50.8 (interquartile range, [18.6; 99.2]) months after the index procedure, 17 (36%) patients were free from the primary end point. After multiple procedures, freedom from sustained
VT
/ventricular fibrillation was 63% (95%
CI
, 52–75) at 1 year, and 45% (95%
CI
, 34–61) at 5 years, with 36% of patients receiving only endocardial radiofrequency ablation. A trend (log rank
P
=0.058) towards an improved outcome using a combined endo‐/epicardial approach was observed after multiple procedures.

Conclusion

Endocardial ablation can be effective in a considerable number of arrhythmogenic right ventricular cardiomyopathy/dysplasia patients with
VT
, potentially obviating the need for an epicardial approach.
Abstract 102: An Internal Pool of b-Adrenergic Receptors Activates PLC-mediated PI4P Hydrolysis in Cardiac Myocytes
Authors: Smrcka Alan V , Nash Craig A , Wei Wenhui 
Published: February 2019

Cardiac hypertrophy and subsequent heart failure is a leading cause of morbidity and mortality in the USA. Previously, our laboratory identified a prohypertrophic pathway where PLCε, scaffolded to mAKAPβ at the nuclear envelope, hydrolyzes phosphatidylinositol 4-phosphate (PI4P) at the Golgi to locally generate DAG and drive hypertrophic gene expression. This pathway is activated by multiple upstream signals including the Epac-selective cAMP analogue, cpTOME. However, stimulation of β-adrenergic receptors with Isoproterenol (Iso) does not activate this pathway despite strongly raising cAMP. We were able to uncover Iso stimulated PI4P hydrolysis only in the presence of a cAMP phosphodiesterase 3 inhibitor.
To determine if internal β-adrenergic receptors can stimulate PI4P hydrolysis, we treated NRVMs with the membrane permeable β-adrenergic agonist, dobutamine. In contrast to the membrane impermeable Iso, dobutamine induced rapid and sustained PI4P hydrolysis that was at least partially blocked by the cell permeable β-adrenergic antagonist, metoprolol. The cell impermeable βAR antagonist, sotalol could not block dobutamine effects, suggesting that a pool of internal β-adrenergic receptors can induce PI4P hydrolysis. Over expression of the RA1 domain of PLCε, which competes PLCε away from the mAKAPβ scaffold, also inhibited dobutamine stimulation of PI4P hydrolysis. These data suggest that β-adrenergic stimulation in internal membranes, potentially at the Golgi apparatus or nuclear envelope, can stimulate PI4P hydrolysis. These observations demonstrate a novel mechanism for PLC activation through an internal GPCR, which may participate in development of cardiac hypertrophy and heart failure. Targeting internal β-adrenergic receptors may allow for the development of selective therapies to treat heart failure.
Abstract 270: Long term Caloric Restriction and Myocardial Aging in Non Human Primates
Authors: Natarajan Niranjana , Kiehm Spencer H , Das Jishnu , Wang Annie C , Mattison Julie A , Colman Ricki J , Lee Richard T 
Published: February 2019

Caloric restriction (CR) has been shown to decrease aging and increase the lifespan of several model organisms. However, in two on-going independent, long-term CR studies in non-human primates (NHP) at the National Institute of Aging (NIA) and University of Wisconsin, Madison (UW) the outcome has been more complex. While CR monkeys in the UW study have experienced a significant increase in lifespan relative to their study controls, this was not the case for the NIA study. There, CR did not increase lifespan compared to the already long-lived controls. Yet, in both studies CR was associated with a decrease in the occurrence of age-related diseases. Left ventricle (LV) samples were provided from the rhesus monkeys from both studies to investigate the effect of long-term CR on myocardial pathology and aging in these two cohorts of non-human primates (NHPs). Although CR did not reduce cardiac fibrosis or hypertrophy in either study, there was a 5.9-fold increase in fibrosis (p<0.0001) in LV tissue from the UW study compared to NIA, irrespective of CR treatment. Myocardial mTOR levels were reduced with CR in the UW study, only. These findings indicate that the severity of cardiac fibrosis may not be susceptible to the mechanisms by which CR is affecting disease progression, and myocardial mTOR is apparently differently affected dependent on the study paradigm. Interestingly, the diet administered by the UW study contained a much higher sucrose content (28.5% sucrose by weight), compared to that of the NIA diet (3.9% sucrose by weight). This raises the intriguing possibility that myocardial fibrosis in NHPs may be driven by a high sucrose diet.
Abbreviations:
CR: Caloric Restriction
NHP: Non-human primate
mTOR: mechanistic Target of Rapamycin
NIA: National Institute on Aging
UW: University of Wisconsin, Madison
Abstract 333: TNF Receptor Modulation of Progenitor Cells and Exosomes for Myocardial Repair
Authors: Garikipati Venkata N , Cimini Maria , Wang Chunlin , Roy Rajika , Cheng Zhongjian , Truongcao May M , Benedict Cindy , Verma Suresh K , Koch Walter J , Kishore Raj , Goukassian David A 
Published: February 2019

Our published studies, using TNFR1 and TNFR2 knockout (KO) mice have demonstrated that negative effects of TNF during ischemic tissue repair including enhanced apoptosis and inflammatory cytokines expression and signaling, is largely mediated by TNFR1/p55. Our hypothesis is that inhibition of TNF-TNFR1 signaling inhibits multiple negative effects of TNF after myocardial ischemia by promoting TNF signaling through protective TNFR2 receptor and thereby augmenting EPC-mediated myocardial angiogenesis and repair and this enhanced protective effect of TNFR1 KO EPCs may involve alteration in the cargo and function of TNFR1-KO EPC derived exosomes.
Protective effect of disrupted TNF-TNFR1/p55 signaling in BM-EPCs under stress conditions in WT, p55KO and p75KO EPCs were tested in tube formation assay under hypoxia conditions and H2O2 treatment. In the absence of TNFR1 (p55KO EPCs) - EC function of BM-EPCs is enhanced under normoxia/hypoxia conditions and survival of BM-EPCs is increased under oxidative stress. To test the effect of TNFR1 and TNFR2 loss in the BM-EPCs for recovery after AMI, WT mice were subjected to AMI and WT, p75KO and p55KO BM-EPCs were injected into the myocardium immediately after AMI. Compared to WT and p75KO, injection of p55KO EPCs into WT hosts led to - increased retention of p55KO EPCs in the WT mice hearts; decreased post-MI apoptosis in WT mice; increased vascular network; significantly improved cardiac function; substantially small infarct size; the last three indicating improved cardiac remodeling by day 21 post-AMI. Further, in vitro exosome studies showed that compared to WT and p75KOs, p55KO BM-EPCs-derived exosomes showed positive activities in vitro, including - enhanced angiogenic function in HUVECs and increased survival of H9C2 cells. These effects were mediated via upregulation of miRNA-191-5p as shown by increased levels of angiogenic miR-191-5p in the exosomal cargo of p55KO EPCs and near complete inhibition of HUVEC angiogenic function in vitro by miR-191-5p-antagomiR.
Our findings suggest that decrease/loss of TNFR1 modulates both the content and function of EPC exosomes and enhance reparative and angiogenic capabilities of EPCs and EPC-mediated vascular and anatomical repair in the MI model.
Abstract 340: Cardiomyocyte-Derived Mechanical Signals Function in a Paracrine Manner to Regulate Tissue Stiffness and Myocardial Proliferation
Authors: Zhang Caimei , Emms Sabrina , Radice Glenn 
Published: February 2019

Cells sense and transduce mechanical signals through cell-cell adhesions and cell-extracellular matrix adhesions. After birth, contractile force generation and tissue stiffness increase as cardiac output increases to support the needs of the newborn organism. During this postnatal period, the N-cadherin adhesion complex assembles at the intercalated disc (ID) as integrin-fibronectin (FN) adhesions decrease, accompanying the switch from hyperplastic to hypertrophic growth. However, little is known regarding the reciprocity between integrin and N-cadherin adhesions in the regulation of cell cycle withdrawal that occurs in cardiomyocytes after birth.
α-catenins function as mechanosensors and transduce the intercellular force from N-cadherin to the actin cytoskeleton. Cardiac-specific αE- and αT-catenins double knockout (DKO) mice exhibit sustained cardiomyocyte proliferation beyond the first week of life. To investigate the role of cell-matrix interactions in DKO hearts, the spatial distribution of integrin-FN complexes was examined at postnatal day (P) 4, P7, P14, and P60. DKO hearts exhibited aberrant N-cadherin localization accompanied by altered distribution of α5/β1 integrin, the primary FN receptor. Normally found at the lateral membrane, α5 and β1 accumulated at the ID while N-cadherin was reduced at the termini. FN matrix assembly, as monitored by immunofluorescent staining and its insolubility in the detergent deoxycholate, was increased in DKO hearts. Meanwhile, focal adhesion kinase (FAK) was activated in early postnatal DKO hearts. Complementary experiments performed with deformable substrata demonstrated that stiffness-mediated proliferation was dependent on FAK activity. Finally, treatment of DKO pups with the lysyl oxidase inhibitor, β-aminopropionitrile (BAPN), was sufficient to reduce cardiomyocyte proliferation to wild-type levels suggesting that matrix assembly and tissue stiffness feedback to promote cardiomyocyte proliferation in DKO hearts. This data demonstrates that α-catenins regulate the balance between cell-cell and cell-matrix adhesions, which, in turn, controls cardiomyocyte proliferation, thus providing a molecular explanation for loss of regenerative potential shortly after birth.