bluuebunny/crossref_metadata_2025_split huggingface dataset:
Priorities for research in miscarriage: a priority setting partnership between people affected by miscarriage and professionals following the James Lind Alliance methodology
Authors: Prior Matthew , Bagness Carmel , Brewin Jane , Coomarasamy Arri , Easthope Lucy , Hepworth-Jones Barbara , Hinshaw Kim , O'Toole Emily , Orford Julie , Regan Lesley , Raine-Fenning Nick , Shakespeare Judy , Small Rachel , Thornton Jim , Metcalf Leanne 
Published: August 2017

ObjectivesTo identify and prioritise important research questions for miscarriage.DesignA priority setting partnership using prospective surveys and consensus meetings following methods advocated by the James Lind Alliance.SettingUK.ParticipantsWomen and those affected by miscarriage working alongside healthcare professionals.ResultsIn the initial survey, 1093 participants (932 women who have experienced miscarriage, 8 partners, 17 family members, friends or colleagues, 104 healthcare professionals and eight charitable organisations) submitted 3279 questions. A review of existing literature identified a further 64. Non-questions were removed, and the remaining questions were categorised and summarised into 58 questions. In an interim electronic survey, 2122 respondents chose their top 10 priorities from the 58 summary questions. The 25 highest ranked in the survey were prioritised at a final face-to-face workshop. In summary, the top 10 priorities were ranked as follows: research into preventative treatment, emotional aspects in general, investigation, relevance of pre-existing medical conditions, emotional support as a treatment, importance of lifestyle factors, importance of genetic and chromosomal causes, preconception tests, investigation after different numbers of miscarriage and male causal factors.ConclusionsThese results should be the focus of future miscarriage research. Presently, studies are being conducted to address the top priority; however, many other priorities, especially psychological and emotional support, are less well researched areas. We hope our results will encourage both researchers and funders to focus on these priorities.
What is the impact of giant cell arteritis on patients’ lives? A UK qualitative study
Authors: Liddle Jennifer , Bartlam Roisin , Mallen Christian D , Mackie Sarah L , Prior James A , Helliwell Toby , Richardson Jane C 
Published: August 2017

ObjectivesClinical management of giant cell arteritis (GCA) involves balancing the risks and burdens arising from the disease with those arising from treatment, but there is little research on the nature of those burdens. We aimed to explore the impact of giant cell arteritis (GCA) and its treatment on patients’ lives.MethodsUK patients with GCA participated in semi-structured telephone interviews. Inductive thematic analysis was employed.Results24 participants were recruited (age: 65–92 years, time since diagnosis: 2 months to >6 years). The overarching themes from analysis were: ongoing symptoms of the disease and its treatment; and ‘life-changing’ impacts. The overall impact of GCA on patients’ lives arose from a changing combination of symptoms, side effects, adaptations to everyday life and impacts on sense of normality. Important factors contributing to loss of normality were glucocorticoid-related treatment burdens and fear about possible future loss of vision.ConclusionsThe impact of GCA in patients’ everyday lives can be substantial, multifaceted and ongoing despite apparent control of disease activity. The findings of this study will help doctors better understand patient priorities, legitimise patients’ experiences of GCA and work with patients to set realistic treatment goals and plan adaptations to their everyday lives.
Fluoride exposure and indicators of thyroid functioning in the Canadian population: implications for community water fluoridation
Authors: Barberio Amanda M , Hosein F Shaun , Quiñonez Carlos , McLaren Lindsay 
Published: August 2017

BackgroundThere are concerns that altered thyroid functioning could be the result of ingesting too much fluoride. Community water fluoridation (CWF) is an important source of fluoride exposure. Our objectives were to examine the association between fluoride exposure and (1) diagnosis of a thyroid condition and (2) indicators of thyroid functioning among a national population-based sample of Canadians.MethodsWe analysed data from Cycles 2 and 3 of the Canadian Health Measures Survey (CHMS). Logistic regression was used to assess associations between fluoride from urine and tap water samples and the diagnosis of a thyroid condition. Multinomial logistic regression was used to examine the relationship between fluoride exposure and thyroid-stimulating hormone (TSH) level (low/normal/high). Other available variables permitted additional exploratory analyses among the subset of participants for whom we could discern some fluoride exposure from drinking water and/or dental products.ResultsThere was no evidence of a relationship between fluoride exposure (from urine and tap water) and the diagnosis of a thyroid condition. There was no statistically significant association between fluoride exposure and abnormal (low or high) TSH levels relative to normal TSH levels. Rerunning the models with the sample constrained to the subset of participants for whom we could discern some source(s) of fluoride exposure from drinking water and/or dental products revealed no significant associations.ConclusionThese analyses suggest that, at the population level, fluoride exposure is not associated with impaired thyroid functioning in a time and place where multiple sources of fluoride exposure, including CWF, exist.
The efficacy and safety of endovascular recanalization of occluded large cerebral arteries during the subacute phase of cerebral infarction: a case series report
Authors: Chen Kangning , Hou Xianhua , Zhou Zhenhua , Li Guangjian , Liu Qu , Gui Li , Hu Jun , Shi Shugui 
Published: August 2017

BackgroundIntravenous tissue plasminogen activator with or without mechanical thrombectomy during the acute phase are approved therapies for ischaemic stroke. Due to the short treatment time window (<6 hours) and often treatment failure, these patients would still have an intracranial arterial occlusion (IAO). It is unclear whether these patients can benefit from subsequent interventional recanalizationof their occluded artery in the subacute phase. In this retrospective study, we have examined the efficacy and safety in patients who have received either percutaneous transluminal angioplasty (PTA) or percutaneous transluminal angioplasty and stenting (PTAS) for IAO in the subacute phase of their stroke.MethodsPatients with subacute symptomatic ischaemic stroke caused by IAO were assessed to identify the responsible artery and low perfusion areas by CT angiography, MR angiography or digital subtraction angiography. In eligible patients, a PTA or PTAS was performed to reopen the occluded artery. Regular antithrombotic therapy, use of statins, control of risk factors and rehabilitation therapy were prescribed after the procedure. All patients had regular follow-up up to 12 months.ResultsPTA or PTAS was performed in 16 patients with cerebral infarction caused by IAO in the subacute phase. After the procedure, 12 cases were recanalized, two were partially recanalized and two failed to open. One patient with left C6 segment occlusion of the carotid artery had a central retinal artery embolism after PTAS. The perioperative adverse events were 6.25%. At 3 months, the distribution of modified Rankin scale scores was 0 (seven cases), 1 (three cases), 2 (five cases) and 3 (one case).ConclusionSelective PTA or PTAS could be performed in ischaemic stroke patients with a small infarct size and large area of hypoperfusion from an occluded large cerebral artery after the acute phase. It may improve neurological dysfunction and reduce the incidence of disability.
Ca2+/calmodulin-dependent kinase II-dependent regulation of atrial myocyte late Na+ current, Ca2+ cycling, and excitability: a mathematical modeling study
Authors: Onal Birce , Gratz Daniel , Hund Thomas J. 
Published: August 2017

Atrial fibrillation (AF) affects more than three million people per year in the United States and is associated with high morbidity and mortality. Both electrical and structural remodeling contribute to AF, but the molecular pathways underlying AF pathogenesis are not well understood. Recently, a role for Ca2+/calmodulin-dependent protein kinase II (CaMKII) in the regulation of persistent “late” Na+ current ( INa,L) has been identified. Although INa,L inhibition is emerging as a potential antiarrhythmic strategy in patients with AF, little is known about the mechanism linking INa,L to atrial arrhythmogenesis. A computational approach was used to test the hypothesis that increased CaMKII-activated INa,L in atrial myocytes disrupts Ca2+ homeostasis, promoting arrhythmogenic afterdepolarizations. Dynamic CaMKII activity and regulation of multiple downstream targets [ INa,L, L-type Ca2+ current, phospholamban, and the ryanodine receptor sarcoplasmic reticulum Ca2+-release channel (RyR2)] were incorporated into an existing well-validated computational model of the human atrial action potential. Model simulations showed that constitutive CaMKII-dependent phosphorylation of Nav1.5 and the subsequent increase in INa,L effectively disrupt intracellular atrial myocyte ion homeostasis and CaMKII signaling. Specifically, increased INa,L promotes intracellular Ca2+ overload via forward-mode Na+/Ca2+ exchange activity, which greatly increases RyR2 open probability beyond that observed for CaMKII-dependent phosphorylation of RyR2 alone. Increased INa,L promotes atrial myocyte repolarization defects (afterdepolarizations and alternans) in the setting of acute β-adrenergic stimulation. We anticipate that our modeling efforts will help identify new mechanisms for atrial NaV1.5 regulation with direct relevance for human AF. NEW & NOTEWORTHY Here, we present a novel computational model to study the effects of late Na+ current ( INa,L) in human atrial myocytes. Simulations predict that INa,L promotes intracellular accumulation of Ca2+, with subsequent dysregulation of Ca2+/calmodulin-dependent protein kinase II (CaMKII) signaling and ryanodine receptor 2-mediated Ca2+ release. Although INa,L plays a small role in regulating atrial myocyte excitability at baseline, CaMKII-dependent enhancement of the current promoted arrhythmogenic dynamics. Listen to this article’s corresponding podcast at http://ajpheart.podbean.com/e/camkii-dependent-regulation-of-atrial-late-sodium-current-and-excitability/ .
Carotid artery stenosis in hypertensive rats impairs dilatory pathways in parenchymal arterioles
Authors: Matin Nusrat , Fisher Courtney , Jackson William F. , Diaz-Otero Janice M. , Dorrance Anne M. 
Published: August 2017

Hypertension is a leading risk factor for vascular cognitive impairment and is strongly associated with carotid artery stenosis. In normotensive rats, chronic cerebral hypoperfusion induced by bilateral common carotid artery stenosis (BCAS) leads to cognitive impairment that is associated with impaired endothelium-dependent dilation in parenchymal arterioles (PAs). The aim of this study was to assess the effects of BCAS on PA function and structure in stroke-prone spontaneously hypertensive rats, a model of human essential hypertension. Understanding the effects of hypoperfusion on PAs in a hypertensive model could lead to the identification of therapeutic targets for cognitive decline in a model that reflects the at-risk population. We hypothesized that BCAS would impair endothelium-dependent dilation in PAs and induce artery remodeling compared with sham rats. PAs from BCAS rats had endothelial dysfunction, as assessed using pressure myography. Inhibition of nitric oxide and prostaglandin production had no effect on PA dilation in sham or BCAS rats. Surprisingly, inhibition of epoxyeicosatrienoic acid production increased dilation in PAs from BCAS rats but not from sham rats. Similar results were observed in the presence of inhibitors for all three dilatory pathways, suggesting that epoxygenase inhibition may have restored a nitric oxide/prostaglandin-independent dilatory pathway in PAs from BCAS rats. PAs from BCAS rats underwent remodeling with a reduced wall thickness. These data suggest that marked endothelial dysfunction in PAs from stroke-prone spontaneously hypertensive rats with BCAS may be associated with the development of vascular cognitive impairment. NEW & NOTEWORTHY The present study assessed the structure and function of parenchymal arterioles in a model of chronic cerebral hypoperfusion and hypertension, both of which are risk factors for cognitive impairment. We observed that impaired dilation and artery remodeling in parenchymal arterioles and abolished cerebrovascular reserve capacity may mediate cognitive deficits.
Validation of Immunohistochemical Assays for Integral Biomarkers in the NCI-MATCH EAY131 Clinical Trial
Authors: Khoury Joseph D. , Wang Wei-Lien , Prieto Victor G. , Medeiros L. Jeffrey , Kalhor Neda , Hameed Meera , Broaddus Russell , Hamilton Stanley R. 
Published: August 2017

Abstract
Biomarkers that guide therapy selection are gaining unprecedented importance as targeted therapy options increase in scope and complexity. In conjunction with high-throughput molecular techniques, therapy-guiding biomarker assays based upon immunohistochemistry (IHC) have a critical role in cancer care in that they inform about the expression status of a protein target. Here, we describe the validation procedures for four clinical IHC biomarker assays—PTEN, RB, MLH1, and MSH2—for use as integral biomarkers in the nationwide NCI-Molecular Analysis for Therapy Choice (NCI-MATCH) EAY131 clinical trial. Validation procedures were developed through an iterative process based on collective experience and adaptation of broad guidelines from the FDA. The steps included primary antibody selection; assay optimization; development of assay interpretation criteria incorporating biological considerations; and expected staining patterns, including indeterminate results, orthogonal validation, and tissue validation. Following assay lockdown, patient samples and cell lines were used for analytic and clinical validation. The assays were then approved as laboratory-developed tests and used for clinical trial decisions for treatment selection. Calculations of sensitivity and specificity were undertaken using various definitions of gold-standard references, and external validation was required for the PTEN IHC assay. In conclusion, validation of IHC biomarker assays critical for guiding therapy in clinical trials is feasible using comprehensive preanalytic, analytic, and postanalytic steps. Implementation of standardized guidelines provides a useful framework for validating IHC biomarker assays that allow for reproducibility across institutions for routine clinical use. Clin Cancer Res; 24(3); 521–31. ©2017 AACR.
Radiosensitization In Vivo by Histone Deacetylase Inhibition with No Increase in Early Normal Tissue Radiation Toxicity
Authors: Groselj Blaz , Ruan Jia-Ling , Scott Helen , Gorrill Jessica , Nicholson Judith , Kelly Jacqueline , Anbalagan Selvakumar , Thompson James , Stratford Michael R.L. , Jevons Sarah J. , Hammond Ester M. , Scudamore Cheryl L. , Kerr Martin , Kiltie Anne E. 
Published: August 2017

Abstract
As the population ages, more elderly patients require radiotherapy-based treatment for their pelvic malignancies, including muscle-invasive bladder cancer, as they are unfit for major surgery. Therefore, there is an urgent need to find radiosensitizing agents minimally toxic to normal tissues, including bowel and bladder, for such patients. We developed methods to determine normal tissue toxicity severity in intestine and bladder in vivo, using novel radiotherapy techniques on a small animal radiation research platform (SARRP). The effects of panobinostat on in vivo tumor growth delay were evaluated using subcutaneous xenografts in athymic nude mice. Panobinostat concentration levels in xenografts, plasma, and normal tissues were measured in CD1-nude mice. CD1-nude mice were treated with drug/irradiation combinations to assess acute normal tissue effects in small intestine using the intestinal crypt assay, and later effects in small and large intestine at 11 weeks by stool assessment and at 12 weeks by histologic examination. In vitro effects of panobinostat were assessed by qPCR and of panobinostat, TMP195, and mocetinostat by clonogenic assay, and Western blot analysis. Panobinostat resulted in growth delay in RT112 bladder cancer xenografts but did not significantly increase acute (3.75 days) or 12 weeks' normal tissue radiation toxicity. Radiosensitization by panobinostat was effective in hypoxic bladder cancer cells and associated with class I HDAC inhibition, and protein downregulation of HDAC2 and MRE11. Pan-HDAC inhibition is a promising strategy for radiosensitization, but more selective agents may be more useful radiosensitizers clinically, resulting in fewer systemic side effects. Mol Cancer Ther; 17(2); 381–92. ©2017 AACR.
See all articles in this MCT Focus section, “Developmental Therapeutics in Radiation Oncology.”
Radial Artery and Ulnar Artery Occlusions Following Coronary Procedures and the Impact of Anticoagulation:
ARTEMIS
(Radial and Ulnar
ARTE
ry Occlusion
M
eta‐Analys
IS
) Systematic Review and Meta‐Analysis
Authors: Hahalis George , Aznaouridis Konstantinos , Tsigkas Gregory , Davlouros Periklis , Xanthopoulou Ioanna , Koutsogiannis Nikolaos , Koniari Ioanna , Leopoulou Marianna , Costerousse Olivier , Tousoulis Dimitris , Bertrand Olivier F. 
Published: August 2017

Background
Incidence of radial artery occclusions (RAO) and ulnar artery occclusions (UAO) in coronary procedures, factors predisposing to forearm arteries occlusion, and the benefit of anticoaggulation vary significantly in existing literature. We sought to determine the incidence of RAO/UAO and the impact of anticoagulation intensity.

Methods and Results

Meta‐analysis of 112 studies assessing RAO and/or UAO (N=46 631) were included. Overall, there was no difference between crude RAO and UAO rates (5.2%; 95% confidence interval [CI], 4.4–6.0 versus 4.0%; 95% CI, 2.8–5.8;
P
=0.171). The early occlusion rate (in‐hospital or within 7 days after procedure) was higher than the late occlusion rate. The detection rate of occlusion was higher with vascular ultrasonography compared with clinical evaluation only. Low‐dose heparin was associated with a significantly higher RAO rate compared with high‐dose heparin (7.2%; 95% CI, 5.5–9.4 versus 4.3%; 95% CI, 3.5–5.3; Q=8.81;
P
=0.003). Early occlusions in low‐dose heparin cohorts mounted at 8.0% (95% CI, 6.1–10.6). The RAO rate was higher after diagnostic angiographies compared with coronary interventions, presumably attributed to the higher intensity of anticoagulation in the latter group. Hemostatic techniques (patent versus nonpatent hemostasis), geography (US versus non‐US cohorts) and sheath size did not impact on vessel patency.

Conclusions
RAO and UAO occur with similar frequency and in the order of 7% to 8% when evaluated early by vascular ultrasonography following coronary procedures. More‐intensive anticoagulation is protective. Late recanalization occurs in a substantial minority of patients.
Association Between Smoking and Serum GlycA and High‐Sensitivity C‐Reactive Protein Levels: The Multi‐Ethnic Study of Atherosclerosis (MESA) and Brazilian Longitudinal Study of Adult Health (ELSA‐Brasil)
Authors: Kianoush Sina , Bittencourt Marcio S. , Lotufo Paulo A. , Bensenor Isabela M. , Jones Steven R. , DeFilippis Andrew P. , Toth Peter P. , Otvos James D. , Tibuakuu Martin , Hall Michael E. , Harada Paulo H. N. , Blaha Michael J. 
Published: August 2017

Background
Inflammation is suggested to be a central feature of atherosclerosis, particularly among smokers. We studied whether inflammatory biomarkers GlycA and high‐sensitivity C‐reactive protein are associated with cigarette smoking.

Methods and Results

A total of 11 509 participants, 6774 from the
MESA
(Multi‐Ethnic Study of Atherosclerosis) and 4735 from
ELSA
‐Brasil (The Brazilian Longitudinal Study of Adult Health) were included. We evaluated the cross‐sectional association between multiple measures of smoking behavior and the inflammatory biomarkers, GlycA and high‐sensitivity C‐reactive protein, using regression models adjusted for demographic, anthropometric, and clinical characteristics. Participants were 57.7±11.1 years old and 46.4% were men. Never, former, and current smokers comprised 51.7%, 34.0%, and 14.3% of the population, respectively. Multivariable‐adjusted mean absolute difference in GlycA levels (μmol/L) with 95% confidence interval (CI) were higher for former (4.1, 95% CI, 1.7–6.6 μmol/L) and current smokers (19.9, 95% CI, 16.6–23.2 μmol/L), compared with never smokers. Each 5‐unit increase in pack‐years of smoking was associated with higher GlycA levels among former (0.7, 95% CI, 0.3–1.1 μmol/L) and current smokers (1.6, 95% CI, 0.8–2.4 μmol/L). Among former smokers, each 5‐year increase in time since quitting smoking was associated with lower GlycA levels (−1.6, 95% CI, −2.4 to −0.8 μmol/L) and each 10‐unit increase in number of cigarettes/day was associated with higher GlycA among current smokers (2.8, 95% CI, 0.5–5.2 μmol/L). There were similar significant associations between all measures of smoking behavior, and both log‐transformed GlycA and high‐sensitivity C‐reactive protein.

Conclusions
Acute and chronic exposure to tobacco smoking is associated with inflammation, as quantified by both GlycA and high‐sensitivity C‐reactive protein. These biomarkers may have utility for the study and regulation of novel and traditional tobacco products.
Structure and Variability of the Shelfbreak East Greenland Current North of Denmark Strait
Authors: Håvik L. , Våge K. , Pickart R. S. , Harden B. , Appen W.-J. von , Jónsson S. , Østerhus S. 
Published: August 2017

AbstractData from a mooring array deployed north of Denmark Strait from September 2011 to August 2012 are used to investigate the structure and variability of the shelfbreak East Greenland Current (EGC). The shelfbreak EGC is a surface-intensified current situated just offshore of the east Greenland shelf break flowing southward through Denmark Strait. This study identified two dominant spatial modes of variability within the current: a pulsing mode and a meandering mode, both of which were most pronounced in fall and winter. A particularly energetic event in November 2011 was related to a reversal of the current for nearly a month. In addition to the seasonal signal, the current was associated with periods of enhanced eddy kinetic energy and increased variability on shorter time scales. The data indicate that the current is, for the most part, barotropically stable but subject to baroclinic instability from September to March. By contrast, in summer the current is mainly confined to the shelf break with decreased eddy kinetic energy and minimal baroclinic conversion. No other region of the Nordic Seas displays higher levels of eddy kinetic energy than the shelfbreak EGC north of Denmark Strait during fall. This appears to be due to the large velocity variability on mesoscale time scales generated by the instabilities. The mesoscale variability documented here may be a source of the variability observed at the Denmark Strait sill.