bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cardiovascular risk factors are associated with augmented thrombogenicity in healthy individuals: analysis using the Total Thrombus-formation Analysis System
Authors: Oda Yuu , Ito Takashi , Yamada Yoichiro , Koga Tadashi , Nagasato Tomoka , Ohnishi-Wada Tomoko , Hosokawa Kazuya , Fukase Hiroyuki , Hashiguchi Teruto , Maruyama Ikuro 
Published: November 2021

Abstract
Background
Rupture of an atherosclerotic plaque and subsequent exposure of the subendothelial prothrombotic matrix to blood cause arterial thrombosis. Circulating platelets play an indispensable role in the growth of arterial thrombi partially owing to their unique ability to adhere to the subendothelial matrix and to aggregate to each other under flow conditions. Recently, the Total Thrombus-formation Analysis System (T-TAS) was developed for ex vivo analysis of the thrombogenic potential of whole blood samples under flow conditions. Despite the potential clinical utility of the T-TAS in assessing the risk for thrombosis and bleeding, reference intervals for T-TAS analysis in healthy individuals have not been determined.

Methods
In total, 122 whole blood samples were collected from healthy volunteers ranging in age from 25 to 45 years. T-TAS analysis and hematological, physiological, and lifestyle assessments were conducted in these subjects. Whole blood samples anticoagulated with hirudin were perfused into a collagen-coated microchip (PL chip). The time to 10 kPa and the area under the flow pressure curve up to 10 min (AUC10) were analyzed as representative variables for thrombogenic potential. Reference intervals, which were defined as 2.5–97.5 percentiles, were determined. Additionally, univariate and multivariate analyses were performed to identify factors associated with the AUC10 in the T-TAS.

Results
The time to 10 kPa and the AUC10 widely varied, even in healthy volunteers. The reference intervals were 1.50–4.02 min and 223.4–456.8, respectively, at a shear rate of 1500 s− 1. Univariate and multivariate analyses showed that platelet counts were most significantly associated with the AUC10 of the T-TAS. The presence of one or more cardiovascular risk factors of a high body mass index, a high pulse pressure, high fasting serum glucose levels, high low-density lipoprotein-cholesterol levels, a history of smoking, and no habitual exercise, had the second largest effect on the AUC10 of the T-TAS.

Conclusions
Healthy volunteers who had any cardiovascular risk factors showed augmented thrombogenicity, even in artificial uniform capillaries, compared with those without any risk factors in the T-TAS.
Value of statistical life year in extreme poverty: a randomized experiment of measurement methods in rural Burkina Faso
Authors: Trautmann Stefan T. , Xu Yilong , König-Kersting Christian , Patenaude Bryan N. , Harling Guy , Sié Ali , Bärnighausen Till 
Published: November 2021

Abstract
Background
Value of a Statistical Life Year (VSLY) provides an important economic measure of an individual’s trade-off between health risks and other consumption, and is a widely used policy parameter. Measuring VSLY is complex though, especially in low-income and low-literacy communities.

Methods
Using a large randomized experiment (N = 3027), we study methodological aspects of stated-preference elicitation with payment cards (price lists) in an extreme poverty context. In a 2 × 2 design, we systematically vary whether buying or selling prices are measured, crossed with the range of the payment card.

Results
We find substantial effects of both the pricing method and the list range on elicited VSLY. Estimates of the gross domestic product per capita multiplier for VSLY range from 3.5 to 33.5 depending on the study design. Importantly, all estimates are economically and statistically significantly larger than the current World Health Organization threshold of 3.0 for cost-effectiveness analyses.

Conclusions
Our results inform design choice in VSLY measurements, and provide insight into the potential variability of these measurements and possibly robustness checks.
TRPV4-induced Müller cell gliosis and TNF-α elevation-mediated retinal ganglion cell apoptosis in glaucomatous rats via JAK2/STAT3/NF-κB pathway
Authors: Li Qian , Cheng Yun , Zhang Shenghai , Sun Xinghuai , Wu Jihong 
Published: November 2021

Abstract
Background
Glaucoma, the leading cause of irreversible blindness worldwide, is a type of retinal disease characterized by the selective death of retinal ganglion cells (RGCs). However, the pathogenesis of glaucoma has not been fully elucidated. Transient receptor potential vanilloid 4 (TRPV4) is a pressure-sensitive and calcium-permeable cation channel. TRPV4 is widely distributed in the retina and its sustained activation leads to RGC death; indicating that TRPV4 may be a possible target for glaucoma treatment. Here, we investigated the effects of TRPV4 on RGC apoptosis in a rat model of chronic ocular hypertension (COH), then examined the mechanism underlying these effects.

Methods
The COH model was established by injection of micro-magnetic beads into the anterior chamber of adult male rats. The expression levels of TRPV4, glial fibrillary acidic protein, and inflammatory factors were assessed by immunohistochemistry and immunoblotting. RGC apoptosis and visual dysfunction were evaluated by TUNEL assay and photopic negative response. Functional expression of TRPV4 was examined by electrophysiology and calcium imaging. Real-time polymerase chain reaction and immunoblotting were employed to investigate the molecular mechanism underlying the effects of TRPV4 on tumor necrosis factor-α (TNF-α) release.

Results
We found that TRPV4 played an essential role in glaucoma, such that high levels of TRPV4 expression were associated with elevated intraocular pressure. Furthermore, TRPV4 activation was involved in glaucoma-induced RGC apoptosis and RGC-related reductions in visual function. Mechanistic investigation demonstrated that TRPV4 activation led to enhanced Müller cell gliosis and TNF-α release via the JAK2/STAT3/NF-kB pathway, while TRPV4 inhibition could reverse these effects. Finally, TRPV4 activation could lead to elevated expression of TNF receptor 1 in RGCs, while inhibition of TNF-α could reduce TRPV4-mediated RGC apoptosis.

Conclusions
TRPV4 activation induces Müller cell gliosis and TNF-α elevation via the JAK2/STAT3/NF-κB pathway, which may exacerbate RGC apoptosis in glaucoma; these results suggest that TRPV4 can serve as a therapeutic target in glaucoma treatment.
Measuring the capacity to combat illicit tobacco trade in 160 countries
Authors: Ulep Valerie Gilbert , Lavares Monica Paula , Francisco Ariza 
Published: November 2021

AbstractBackgroundIllicit trade of tobacco negatively affects countries’ tobacco control efforts. It leads to lower tobacco prices and makes tobacco products more accessible to vulnerable populations. In this study, we constructed an illicit tobacco trade index, which measures the structural and institutional capabilities of 160 countries in addressing illicit tobacco trade. We collected the most recent and best available data on general governance, tobacco control policies, and trade and customs practices.ResultsSingapore, New Zealand, Finland and Sweden lead countries with the most favorable illicit tobacco trade score. We observed a positive relationship between illicit tobacco trade scores and Gross National Income (GNI) per capita and a negative relationship with the share of illicit tobacco trade to total tobacco consumption.ConclusionsThe capability to combat illicit trade varies across countries. However, on average, low and middle-income countries (LMICs) are less capable of addressing illicit tobacco trade as suggested by the lower illicit tobacco trade index score. The lower index score in low and middle-income countries was mainly driven by low scores in tobacco control policies and trade and customs practices and conditions. Our study reinforces the importance for LMICs to adopt the WHO’s Protocol to Eliminate Illicit Tobacco Trade Products, particularly committing to treaty obligations and investing on track and trace system and other customs reforms.
The loneliness of the long-distance ethnobotanist: a constructive critique of methods used in an ethnoveterinary study in Mongolia
Authors: Seele Barbara C. , Dreyer Léanne , Esler Karen J. , Cunningham Anthony B. 
Published: November 2021

Abstract
Background
Fieldwork plays an important role in research projects across a variety of fields, especially in the multidisciplinary setting of natural and social science research. As is the nature of fieldwork, things do not always work out as planned, and yet this is not often written about. In response to the need for honest and transparent accounts of fieldwork, the purpose of this article is to review the methods used during fieldwork for the first author’s dissertation research on ethnoveterinary knowledge.

Methods
To critically review and reflect on the fieldwork methods used for an ethnoveterinary study in Mongolia, we compare the theory underpinning each method with the practical reality of implementing the method in the field. From this comparison, we draw out and discuss a number of key themes.

Results
Eighteen methods and approaches used for the research project are reviewed and compared. From this, we distil and further discuss the following five overarching themes: reflections on specific data collection methods (free listing, semi-structured interviews with interpreters, voucher specimen collection); assumptions around involving local people; power dynamics; gender relations; and researcher well-being.

Conclusion
By juxtaposing the theory and practical reality of the methods used, we highlight many potential fieldwork challenges and, within this context, offer general pointers, especially for novice female researchers doing fieldwork in foreign countries. A critical review of this type, where the experience and use of various methods, techniques, and approaches are openly shared and evaluated, is a contribution to selecting, adapting, and fine-tuning the methods best suited to a particular research context.
Integration of a task strengthening strategy for hypertension management into HIV care in Nigeria: a cluster randomized controlled trial study protocol
Authors: Aifah Angela A. , Odubela Oluwatosin , Rakhra Ashlin , Onakomaiya Deborah , Hu Jiyuan , Nwaozuru Ucheoma , Oladele David A. , Odusola Aina Olufemi , Idigbe Ifeoma , Musa Adesola Z. , Akere Ayodeji , Tayo Bamidele , Ogedegbe Gbenga , Iwelunmor Juliet , Ezechi Oliver 
Published: November 2021

Abstract
Background
In regions with weak healthcare systems, critical shortages of the healthcare workforce, and increasing prevalence of dual disease burdens, there is an urgent need for the implementation of proven effective interventions and strategies to address these challenges. Our mixed-methods hybrid type II effectiveness-implementation study is designed to fill this evidence-to-practice gap. This study protocol describes a cluster randomized controlled trial which evaluates the effectiveness of an implementation strategy, practice facilitation (PF), on the integration, adoption, and sustainability of a task-strengthening strategy for hypertension control (TASSH) intervention within primary healthcare centers (PHCs) in Lagos State, Nigeria.

Design
Guided by the Consolidated Framework for Implementation Research (CFIR) and the Reach Effectiveness Adoption Implementation and Maintenance (RE-AIM), this study tests the impact of a proven effective implementation strategy to integrate hypertension management into the HIV care cascade, across 30 PHCs. The study will be conducted in three phases: (1) a pre-implementation phase that will use CFIR to develop a tailored PF intervention for integrating TASSH into HIV clinics; (2) an implementation phase that will use RE-AIM to compare the clinical effectiveness of PF vs. a self-directed condition (receipt of information on TASSH without PF) on BP reduction; and (3) a post-implementation phase that will use RE-AIM to evaluate the effect of PF vs. self-directed condition on adoption and sustainability of TASSH. The PF intervention components comprise (a) an advisory board to provide leadership support for implementing TASSH in PHCs; (b) training of the HIV nurses on TASSH protocol; and (c) training of practice facilitators, who will serve as coaches, provide support, and performance feedback to the HIV nurses.

Discussion
This study is one of few, if any trials, to evaluate the impact of an implementation strategy for integrating hypertension management into HIV care, on clinical and implementation outcomes. Findings from this study will advance implementation science research on the effectiveness of tailoring an implementation strategy for the integration of an evidence-based, system-level hypertension control intervention into HIV care and treatment.

Trial registration
ClinicalTrials.gov (NCT04704336). Registered on 11 January 2021.
Simultaneous radiosurgery for multiple brain metastases: technical overview of the UCLA experience
Authors: Agazaryan Nzhde , Tenn Steve , Lee Chul , Steinberg Michael , Hegde John , Chin Robert , Pouratian Nader , Yang Isaac , Kim Won , Kaprealian Tania 
Published: November 2021

Abstract
Purpose/objective(s)
To communicate our institutional experience with single isocenter radiosurgery treatments for multiple brain metastases, including challenges with determining planning target volume (PTV) margins and resulting consequences, image-guidance translational and rotational tolerances, intra-fraction patient motion, and prescription considerations with larger PTV margins.

Materials/methods
Eight patient treatments with 51 targets were planned with various margins using Elements Multiple Brain Mets SRS treatment planning software (Brainlab, Munich, Germany). Forty-eight plans with 0 mm, 1 mm and 2 mm margins were created, including plans with variable margins, where targets more than 6 cm away from the isocenter were planned with larger margins. The dosimetric impact of the margins were analyzed with V5Gy, V8Gy, V10Gy, V12Gy values. Additionally, 12 patient motion data were analyzed to determine both the impact of the repositioning threshold and the distributions of the patient translational and rotational movements.

Results
The V5Gy, V8Gy, V10Gy, V12Gy volumes approximately doubled when margins change from 0 to 1 mm and tripled when change from 0 to 2 mm. With variable margins, the aggregated results are similar to results from plans using the lower of two margins, since only 12.2% of the targets were more than 6 cm away from the isocenter. With 0.5 mm re-positioning threshold, 57.4% of the time the patients are repositioned. Reducing the threshold to 0.25 mm results in 91.7% repositioning rate, due to limitations of the fusion algorithm and actual patient motion. The 90th percentile of translational movements in all directions is 0.7 mm, while the 90th percentile of rotational movements in all directions is 0.6 degrees. Median translations and rotations are 0.2 mm and 0.2 degrees, respectively.

Conclusions
Based on the data presented, we have switched our modus operandi from 2 to 1 mm PTV margins, with an eventual goal of using 0.5 and 1.0 mm variable margins when an automated margin assignment method becomes available. The 0.5 mm and 0.5 degrees repositioning thresholds are clinically appropriate with small residual patient movements.
The effect of self-reported knee instability on plantar pressure and postural sways in women with knee osteoarthritis
Authors: Chaharmahali Liana , Gandomi Farzaneh , Yalfani Ali , Fazaeli Alireza 
Published: November 2021

Abstract
Background
Giving way and knee instability are common problems in patients with knee osteoarthritis, disrupting the daily activities and balance of the affected individual. The present study aimed to evaluate the postural control status of women with knee osteoarthritis with and without self-report knee instability (KI).

Methods
This cross-sectional, single-blind study was conducted on 57 female patients with knee osteoarthritis. The patients were selected based on the inclusion and exclusion criteria and divided into two groups of with KI (n = 26) and without KI (n = 31). Fear of movement was assessed using the Tampa questionnaire, the degree of knee instability was measured based on the Fitzgard scale, the static and dynamic balance of the subjects were evaluated with open and closed eyes using a Biodex balance device, and foot pressure distribution situation was measured using a FDM-S-Zebris device.

Results
Mean comparison showed a significant difference between the subjects with and without KI in static balance only in anterior–posterior direction with open eyes (p = 0.01) and closed eyes (p = 0.0001). In the dynamic balance test, the subjects in both groups had significant differences in terms of all the indicators of anterior–posterior stability (p = 0.001), medial–lateral stability (p = 0.0001), and overall stability (p = 0.0001) with closed eyes. However, no significant difference was observed with open eyes (p > 0.05). Multiple regression also indicated significant positive correlations between pain intensity and disease duration with the degree of KI (p < 0.05).

Conclusions
According to the results, there were significant differences between the mean pain scores, static and dynamic balance, and the rate of fall between the women with knee osteoarthritis with and without the KI index. Therefore, patients with knee osteoarthritis, which also has an index of KI, are more susceptible to falls, and proper strategies are required to reduce the level of KI in these patients.
Evaluating Diuretics in Normal Care (EVIDENCE): protocol of a cluster randomised controlled equivalence trial of prescribing policy to compare the effectiveness of thiazide-type diuretics in hypertension
Authors: Rogers Amy , Flynn Angela , Mackenzie Isla S. , McConnachie Lewis , Barr Rebecca , Flynn Robert W. V. , Morant Steve , MacDonald Thomas M. , Doney Alexander 
Published: November 2021

Abstract
Introduction
Healthcare systems must use treatments that are effective and safe. Regulators licensed many currently used older medications before introducing the stringent evidential requirements imposed on modern treatments. Also, there has been little encouragement to carry out within-class, head-to-head comparisons of licensed medicines. For commonly prescribed drugs, even small differences in effectiveness or safety could have significant public health implications. However, conventional clinical trials that randomise individual subjects are costly and unwieldy. Such trials are also often criticised as having low external validity. We describe an approach to rapidly generate externally valid evidence of comparative safety and effectiveness using the example of two widely used diuretics for the management of hypertension.

Methods and analysis
The EVIDENCE (Evaluating Diuretics in Normal Care) study has a prospective, cluster-randomised, open-label, blinded end-point design. By randomising prescribing policy in primary care practices, the study compares the safety and effectiveness of commonly used diuretics in treating hypertension. Participating practices are randomised 1:1 to a policy of prescribing either indapamide or bendroflumethiazide when clinically indicated. Suitable patients who are not already taking the policy diuretic are switched accordingly. All patients taking the study medications are written to explaining the rationale for changing the prescribing policy and notifying them they can opt-out of any switch. The prescribing policies’ effectiveness and safety will be compared using rates of major adverse cardiovascular events (hospitalisation with myocardial infarction, heart failure or stroke or cardiovascular death), routinely collected in national healthcare administrative datasets. The study will seek to recruit 250 practices to provide a study population of approximately 50,000 individuals with a mean follow-up time of two years. A primary intention-to-treat time-to-event analysis will be used to estimate the relative effect of the two policies.

Ethics and dissemination
EVIDENCE has been approved by the East of Scotland Research Ethics Service (17/ES/0016, current approved protocol version 5, 26 August 2021). The results will be disseminated widely in peer reviewed journals, guideline committees, National Health Service (NHS) organisations and patient groups.

Trial registration
ISRCTN46635087. Registered on 11 August 2017 (pre-recruitment).
Registration, publication, and outcome reporting among pivotal clinical trials that supported FDA approval of high-risk cardiovascular devices before and after FDAAA
Authors: Swanson Matthew J. , Johnston James L. , Ross Joseph S. 
Published: November 2021

Abstract
Background
Selective registration, publication, and outcome reporting of clinical trials distort the primary clinical evidence that is available to patients and clinicians regarding the safety and efficacy of US Food and Drug Administration (FDA)-approved medical devices. The purpose of this study is to compare registration, publication, and outcome reporting among pivotal clinical trials that supported FDA approval of high-risk (class III) cardiovascular devices before and after the FDA Amendment Act (FDAAA) was enacted in 2007.

Methods
Using publicly available data from ClinicalTrials.gov, FDA summaries, and PubMed, we determined registration, publication, and reporting of findings for all pivotal clinical studies supporting FDA approval of new high-risk cardiovascular devices between 2005 and 2020, before and after FDAAA. For published studies, we compared both the primary efficacy outcome with the FDA’s Premarket Approval (PMA) primary efficacy outcome and the published interpretation of findings with the FDA reviewer’s interpretation (positive, equivocal, or negative).

Results
Between 2005 and 2020, the FDA approved 156 high-risk cardiovascular devices on the basis of 165 pivotal trials, 48 (29%) of which were categorized as pre-FDAAA and 117 (71%) as post-FDAAA. Post-FDAAA, pivotal clinical trials were more likely to be registered (115 of 117 (98%) vs 24 of 48 (50%); p < 0.001), to report results (98 of 117 (87%) vs 7 of 48 (15%); p < 0.001) on ClinicalTrials.gov, and to be published (100 or 117 (85%) vs 28 of 48 (58%); p < 0.001) in peer-reviewed literature when compared to pre-FDAAA. Among published trials, rates of concordant primary efficacy outcome reporting were not significantly different between pre-FDAAA trials and post-FDAAA trials (24 of 28 (86%) vs 96 of 100 (96%); p = 0.07), nor were rates of concordant trial interpretation (27 of 28 (96%) vs 93 of 100 (93%); p = 0.44).

Conclusions
FDAAA was associated with increased registration, result reporting, and publication for trials supporting FDA approval of high-risk medical devices. Among published trials, rates of accurate primary efficacy outcome reporting and trial interpretation were high and no different post-FDAAA.