bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validity arguments for patient-reported outcomes: justifying the intended interpretation and use of data
Authors: Hawkins Melanie , Elsworth Gerald R. , Nolte Sandra , Osborne Richard H. 
Published: July 2021

Abstract
Background
Contrary to common usage in the health sciences, the term “valid” refers not to the properties of a measurement instrument but to the extent to which data-derived inferences are appropriate, meaningful, and useful for intended decision making. The aim of this study was to determine how validity testing theory (the Standards for Educational and Psychological Testing) and methodology (Kane’s argument-based approach to validation) from education and psychology can be applied to validation practices for patient-reported outcomes that are measured by instruments that assess theoretical constructs in health.

Methods
The Health Literacy Questionnaire (HLQ) was used as an example of a theory-based self-report assessment for the purposes of this study. Kane’s five inferences (scoring, generalisation, extrapolation, theory-based interpretation, and implications) for theoretical constructs were applied to the general interpretive argument for the HLQ. Existing validity evidence for the HLQ was identified and collated (as per the Standards recommendation) through a literature review and mapped to the five inferences. Evaluation of the evidence was not within the scope of this study.

Results
The general HLQ interpretive argument was built to demonstrate Kane’s five inferences (and associated warrants and assumptions) for theoretical constructs, and which connect raw data to the intended interpretation and use of the data. The literature review identified 11 HLQ articles from which 57 sources of validity evidence were extracted and mapped to the general interpretive argument.

Conclusions
Kane’s five inferences and associated warrants and assumptions were demonstrated in relation to the HLQ. However, the process developed in this study is likely to be suitable for validation planning for other measurement instruments. Systematic and transparent validation planning and the generation (or, as in this study, collation) of relevant validity evidence supports developers and users of PRO instruments to determine the extent to which inferences about data are appropriate, meaningful and useful (i.e., valid) for intended decisions about the health and care of individuals, groups and populations.
Prognostic value of DCE-CT-derived blood volume and flow compared to core biopsy microvessel density in patients with metastatic renal cell carcinoma
Authors: Drljevic-Nielsen Aska , Rasmussen Finn , Nielsen Patricia Switten , Stilling Christina , Thorup Kennet , Mains Jill Rachel , Madsen Hans Henrik Torp , Donskov Frede 
Published: July 2021

Abstract
Background
Angiogenesis is prominent in metastatic renal cell carcinoma (mRCC). We compared two angiogenesis assessment methods: dynamic contrast-enhanced computed tomography (DCE-CT)-derived blood volume (BV) and blood flow (BF) and core biopsy microvessel density (MVD).

Methods
As planned in DaRenCa Study-1 study, DCE-CT and core biopsy were performed from the same tumour/metastasis at baseline. MVD was assessed by CD34 immunostaining in tumour (CD34-indexT) or tumour including necrosis (CD34-indexTN). BV and BF were assessed using the DCE-CT software. Overall survival (OS) and progression-free survival (PFS) were assessed by Kaplan-Meier analysis. Spearman coefficient (rho) tested the correlation between MVD and BV, BF, or CT density (HU).

Results
At baseline, 25 patients had analysable scans and tissue. BVdeconv, BVPatlak, and BFdeconv > median were associated with favourable OS (43.2 versus 14.6 months, p = 0.002; 31.6 versus 20.2 months, p = 0.015; and 31.6 versus 24.5 months, p = 0.019). CD34-indexT and CD34-indexTN did not correlate with age (p = 0.543), sex (p = 0.225), treatment (p = 0.848), International mRCC Database Consortium category (p = 0.152), synchronous versus metachronous metastatic disease (p = 0.378), or tumour volume (p = 0.848). CD34-indexT or CD34-indexTN > median was not associated with PFS (p = 0.441 and p = 0.854, respectively) or OS (p = 0.987 and p =0.528, respectively). CD34-indexT or CD34-indexTN was not correlated with BV, BF, or HU (rho 0.20–0.26).

Conclusions
Differently from MVD, DCE-CT-derived BV and BF had prognostic impact and may better reflect angiogenesis in mRCC.

Trial registration
NCT01274273
Establishment of particulate matter-induced lung injury model in mouse
Authors: Park Se Yong , An Kyu Sup , Lee Buhyun , Kang Ju-Hee , Jung Hyun Jin , Kim Min Woo , Ryu Hyeon Yeol , Shim Kyu-Suk , Nam Ki Taek , Yoon Yeo Sung , Oh Seung Hyun 
Published: July 2021

Abstract
Background
Particulate matter (PM) is one of the principal causes of human respiratory disabilities resulting from air pollution. Animal models have been applied to discover preventive and therapeutic drugs for lung diseases caused by PM. However, the induced severity of lung injury in animal models using PM varies from study to study due to disparities in the preparation of PM, and the route and number of PM administrations. In this study, we established an in vivo model to evaluate PM-induced lung injury in mice.

Results
PM dispersion was prepared using SRM2975. Reactive oxygen species were increased in MLE 12 cells exposed to this PM dispersion. In vivo studies were conducted in the PM single challenge model, PM multiple challenge model, and PM challenge with ovalbumin-induced asthma using the PM dispersion. No histopathological changes were observed in lung tissues after a single injection of PM, whereas mild to moderate lung inflammation was obtained in the lungs of mice exposed to PM three times. However, fibrotic changes were barely seen, even though transmission electron microscopy (TEM) studies revealed the presence of PM particles in the alveolar macrophages and alveolar capillaries. In the OVA-PM model, peribronchial inflammation and mucous hypersecretion were more severe in the OVA+PM group than the OVA group. Serum IgE levels tended to increase in OVA+PM group than in OVA group.

Conclusions
In this study, we established a PM-induced lung injury model to examine the lung damage induced by PM. Based on our results, repeated exposures of PM are necessary to induce lung inflammation by PM alone. PM challenge, in the presence of underlying diseases such as asthma, can also be an appropriate model for studying the health effect of PM.
Review: distributed time-domain sensors based on Brillouin scattering and FWM enhanced SBS for temperature, strain and acoustic wave detection
Authors: Bao Xiaoyi , Zhou Zichao , Wang Yuan 
Published: July 2021

AbstractDistributed time-domain Brillouin scattering fiber sensors have been widely used to measure the changes of the temperature and strain. The linear dependence of the temperature and strain on the Brillouin frequency shift enabled the distributed temperature and strain sensing based on mapping of the Brillouin gain spectrum. In addition, an acoustic wave can be detected by the four wave mixing (FWM) associated SBS process, in which phase matching condition is satisfied via up-down conversion of SBS process through birefringence matching before and after the conversion process. Brillouin scattering can be considered as the scattering of a pump wave from a moving grating (acoustic phonon) which induces a Doppler frequency shift in the resulting Stokes wave. The frequency shift is dependent on many factors including the velocity of sound in the scattering medium as well as the index of refraction. Such a process can be used to monitor the gain of random fiber laser based on SBS, the distributed acoustic wave reflect the distributed SBS gain for random lasing radiation, as well as the relative intensity noise inside the laser gain medium. In this review paper, the distributed time-domain sensing system based on Brillouin scattering including Brillouin optical time-domain reflectometry (BOTDR), Brillouin optical time-domain analysis (BOTDA), and FWM enhanced SBS for acoustic wave detection are introduced for their working principles and recent progress. The distributed Brillouin sensors based on specialty fibers for simultaneous temperature and strain measurement are summarized. Applications for the Brillouin scattering time-domain sensors are briefly discussed.
Data-driven clustering differentiates subtypes of major depressive disorder with distinct brain connectivity and symptom features
Authors: Wang Yanlin , Tang Shi , Zhang Lianqing , Bu Xuan , Lu Lu , Li Hailong , Gao Yingxue , Hu Xinyu , Kuang Weihong , Jia Zhiyun , Sweeney John A. , Gong Qiyong , Huang Xiaoqi 
Published: July 2021

BackgroundMajor depressive disorder (MDD) is a clinically and biologically heterogeneous syndrome. Identifying discrete subtypes of illness with distinguishing neurobiological substrates and clinical features is a promising strategy for guiding personalised therapeutics.AimsThis study aimed to identify depression subtypes with correlated patterns of functional network connectivity and clinical symptoms by clustering patients according to a weighted linear combination of both features in a relatively large, medication-naïve depression sample.MethodWe recruited 115 medication-naïve adults with MDD and 129 matched healthy controls, and evaluated all participants with magnetic resonance imaging. We used regularised canonical correlation analysis to identify component mapping relationships between functional network connectivity and symptom profiles, and K-means clustering was used to define distinct subtypes of patients.ResultsTwo subtypes of MDD were identified: insomnia-dominated subtype 1 and anhedonia-dominated subtype 2. Subtype 1 was characterised by abnormal hyperconnectivity within the ventral attention network and sleep maintenance insomnia. Subtype 2 was characterised by abnormal hypoconnectivity in the subcortical and dorsal attention networks, and prominent anhedonia symptoms.ConclusionsOur study identified two distinct subtypes of patients with specific neurobiological and clinical symptom profiles. These findings advance understanding of the biological and clinical heterogeneity of MDD, offering a pathway for defining categorical subtypes of illness via consideration of both biological and clinical features.
Are adverse effects of cannabidiol (CBD) products caused by tetrahydrocannabinol (THC) contamination?
Authors: Lachenmeier Dirk W. , Habel Stephanie , Fischer Berit , Herbi Frauke , Zerbe Yvonne , Bock Verena , Rajcic de Rezende Tabata , Walch Stephan G. , Sproll Constanze 
Published: July 2021

Cannabidiol (CBD)-containing products are widely marketed as over the counter products, mostly as food supplements. Adverse effects reported in anecdotal consumer reports or during clinical studies were first assumed to be due to hydrolytic conversion of CBD to psychotropic Δ9-tetrahydrocannabinol (Δ9-THC) in the stomach after oral consumption. However, research of pure CBD solutions stored in simulated gastric juice or subjected to various storage conditions such as heat and light with specific liquid chromatographic/tandem mass spectrometric (LC/MS/MS) and ultra-high pressure liquid chromatographic/quadrupole time-of-flight mass spectrometric (UPLC-QTOF) analyses was unable to confirm THC formation. Another hypothesis for the adverse effects of CBD products may be residual Δ9-THC concentrations in the products as contamination, because most of them are based on hemp extracts containing the full spectrum of cannabinoids besides CBD. Analyses of 181 food products of the German market (mostly CBD oils) confirmed this hypothesis: 21 products (12%) contained Δ9-THC above the lowest observed adverse effect level (2.5 mg/day). Inversely, CBD was present in the products below the no observed adverse effect level. Hence, it may be assumed that the adverse effects of some commercial CBD products are based on a low-dose effect of Δ9-THC and not due to effects of CBD itself. The safety, efficacy and purity of commercial CBD products is highly questionable, and all of the products in our sample collection showed various non-conformities to European food law such as unsafe Δ9-THC levels, hemp extracts or CBD isolates as non-approved novel food ingredients, non-approved health claims, and deficits in mandatory food labelling requirements. In view of the growing market for such lifestyle products, the effectiveness of the instrument of food business operators' own responsibility for product safety and regulatory compliance must obviously be challenged, and a strong regulatory framework for hemp products needs to be devised.
Eating versus skipping breakfast has no discernible effect on obesity-related anthropometric outcomes: a systematic review and meta-analysis
Authors: Bohan Brown Michelle M. , Milanes Jillian E. , Allison David B. , Brown Andrew W. 
Published: July 2021

Background:Eating or skipping breakfast for weight interests scientific and lay communities. Our objective was to systematically review and meta-analyze causal effects of eating versus skipping breakfast on obesity-related anthropometric outcomes in humans.Methods:Six databases were searched for obesity- and breakfast-related terms (final search: 02 JAN 2020). Studies needed to isolate eating versus skipping breakfast in randomized controlled trials. Mean differences were synthesized using inverse variance random effects meta-analysis for each outcome. Positive estimates indicate higher outcomes in breakfast conditions (e.g., weight gain). Leave-one-out sensitivity analysis, secondary baseline habit-by-breakfast assignment analysis, and study duration cumulative analysis were performed. Risk of bias was assessed using Cochrane risk of bias tool.Results:Ten articles (12 comparisons; 6d-12wk) were included. Conditions included recommendations to eat versus skip breakfast, or provision of some or all meals. 95% confidence intervals of all main analyses included the null value of no difference for each outcome: body weight (0.17 kg [-0.40,0.73], k=12, n=487, I2=74.5), BMI (0.07 kg/m2[-0.10,0.23, k=8, n=396, I2=54.1), body fat percentage (-0.27% [-1.01,0.47], k=6, n=179, I2=52.4), fat mass (0.24 kg [-0.21,0.69], k=6, n=205, I2=0.0), lean mass (0.18 kg [-0.08,0.44], k=6, n=205, I2=6.7), waist circumference (0.18 cm [-1.77,2.13], k=4, n=102, I2=78.7), waist:hip ratio (0.00 [-0.01,0.01], k=4, n=102, I2=8.0), sagittal abdominal diameter (0.19 cm [-2.35,2.73], k=2, n=56, I2=0.0), and fat mass index (0.00 kg/m2[-0.22,0.23], k=2, n=56, I2=0.0). Subgroup analysis showed only one statistically significant result. The interaction effect for BMI (–0.36[-0.65,-0.07]) indicates assignment to conditions consistent with baseline habits had lower BMI. Leave-one-out analysis did not indicate substantial influence of any one study.Conclusions:There was no discernible effect of eating or skipping breakfast on obesity-related anthropometric measures when pooling studies with substantial design heterogeneity and sometimes statistical heterogeneity.Registration:PROSPEROCRD42016033290.
Economic burden of out-of-pocket expenditure, productivity cost during pregnancy and COVID-19 impact on household economy in a cohort of pregnant women in Anuradhapura District, Sri Lanka; A study protocol
Authors: Gunarathne Sajaan Praveena , Wickramasinghe Nuwan Darshana , Agampodi Thilini Chanchala , Prasanna Indika Ruwan , Agampodi Suneth Buddhika 
Published: July 2021

Background: Investigating the out-of-pocket expenditure (OOPE) associated with maternal health is important since OOPE directly affects the affordability of health services. Global evidence suggests the importance of capturing the productivity cost during pregnancy in terms of absenteeism and presenteeism. Furthermore, the impact of the ongoing COVID-19 pandemic on the household economy needs to be further evaluated as pregnant women are one of the most vulnerable groups. This study aims at determining the economic burden of OOPE, productivity cost, and COVID-19 impact on pregnant women's household economy in a cohort of pregnant women in Anuradhapura District, Sri Lanka. Methods: The study setting is all 22 Medical Officer of Health (MOH) areas in Anuradhapura district, Sri Lanka. The study has three components; a follow-up study of a cohort of pregnant women to assess the magnitude and associated factors of OOPE and to assess the productivity cost (Component 1), a qualitative case study to explore the impact and causes of the OOPE under free health services (Component 2) and a cross-sectional study to describe the effects of COVID-19 outbreak on household economy (Component 3). The study samples consist of 1,393 and 1,460 participants for components one and three, respectively, and 25 pregnant women will be recruited for component two. The data will be analyzed using descriptive, parametric, and non-parametric statistics for the first and third components and thematic analysis for the second component. Discussion: With the lack of evidence on OOPE, productivity loss/cost in terms of maternal health, and COVID-19 impact on household economy in Sri Lanka, the evidence generated from this study would be valuable for policymakers, health care administrators, and health care practitioners globally, regionally, and locally to plan for future measures for reducing the OOPE, productivity loss/cost, and minimizing the economic hardship of the COVID-19 outbreak during pregnancy.
Differential CTCF binding in motor neurons and lymphocytes
Authors: Atasever Arslan Belkis , Brady Scott T. , Gunal Sadik Gamze 
Published: July 2021

Background: Diversity is critical to lymphocyte roles in the immune system and to neurons, which form complex network structures in the brain. Emerging evidence suggests that an increasing number of molecules associated with the immune system are also expressed in various central nervous system (CNS) regions and play crucial roles in brain development. Examination of shared molecular mechanisms underlying neurogenesis and lymphocyte differentiation may clarify relevant pathways, and suggests additional biomarkers in lymphocytes for neurological disorders. These results can contribute to find biomarkers that can be monitored through patient lymphocyte populations. Methods: We analysed similarities and conserved regions in several genes regulated by CCCTC-binding factor (CTCF) during lymphocyte and neuronal developmental stages. We performed epigenetic analyses of CTCF binding Trak1, Gabpa, Gabpb1, Gabpb2, Gfi1, Gfi1b gene loci in T and B lymphocytes at different developmental stages, as well as in neural progenitor cells and motor neurons. Results: Common and shared CTCF binding events at Trak1 suggest additional transcriptional regulatory factors that control Trak1 gene expression levels differ in neurons and lymphocytes. Gabpb1 includes a common CTCF binding site shared with neurons and lymphocytes. Correlation of CTCF binding analysis and gene expression profile suggests that CTCF binding plays a role in epigenetic regulation of Gabpb1 gene. While Gfi1a is phylogenetically well-conserved and CTCF sites are occupied in lymphocytes, there are no CTCF binding occupied in neurons and neural progenitor cells. Although Gfi1b is highly homologous to Gfi1, differences in expression levels suggest that Gfi1b is critical for both lymphogenesis and neurogenesis. Neurons and lymphocytes have multiple common CTCF binding sites in the Gfi1b gene. Conclusions: The partial overlap in CTCF regulatory sites for some genes in neurons and lymphocytes suggests that there may be markers which can exhibit parallel changes in these cells and serve as biomarkers.
Predicting coronary artery disease risk in firefighters – a cross-sectional study
Authors: Ras Jaron , Leach Lloyd 
Published: July 2021

Background: Firefighters are placed under severe cardiovascular load in performing active duty and, when carrying various coronary artery disease (CAD) risk factors, firefighters are predisposed to significant morbidity and mortality. Reducing the incidence of these risk factors is paramount. The purpose of this study is to determine the predictors of CAD risk. Methods: This study used a quantitative, cross-sectional and correlational design. The researchers conveniently sampled 124 full-time firefighters from the City of Cape Town Fire and Rescue Service. A researcher-generated questionnaire was used to collect sociodemographic and CAD risk factors information, such as age, gender, ethnicity, family history of CAD, cigarette smoking and physical activity levels, and all research procedures were conducted according to the American College of Sports Medicine guidelines. Data collection took place between September and November 2019. Linear and logistic regression were used to determine the relationship between the various CAD risk factors and the predictors of CAD risk. Results: Age was a significant predictor of hypertension (p <0.01), dyslipidemia (p <0.01), diabetes (p <0.01), obesity (p <0.01) and central obesity (p <0.01). Gender was a significant predictor of obesity, central obesity and cigarette smoking (p <0.05). Waist circumference was a significant predictor of hypertension (p <0.01), dyslipidemia (p <0.01) and diabetes (p <0.05). Conclusion: Age was a significant predictor of various modifiable CAD risk factors, including obesity, in both genders and all ethnicities. Attentive monitoring should be in place as firefighters age, along with behavioural modifications designed to reduce age-related increases in CAD risk factors.
Human-centred design of a new microneedle-based hormonal contraceptive delivery system
Authors: Gualeni Benedetta , Hughes Louise , Stauber Isabelle , Ackers Louise , Gorman Angela , Gashuga Dorothy , Dzabala Nettie , Chimimba Frider , Chikowe Ibrahim , Coulman Sion A. , Birchall James C. 
Published: July 2021

Background: It is estimated that 225 million women worldwide have an unmet need for family planning, and more than half live in low- and middle-income countries. Increasing the choice of contraceptive methods available can reduce this unmet need. Microneedle drug delivery systems represent a new technology for minimally invasive self-administration of contraceptives. We explored stakeholders’ views on different aspects of a proposed microneedle-based hormonal contraceptive delivery system. The feedback was used to iteratively develop this delivery system. Methods: Focus group discussions and semi-structured interviews were conducted with potential stakeholders (women and trans males of childbearing age, their partners, and health professionals and organisations that provide family planning advice and contraception services) in Uganda, The Gambia, Malawi, and the UK, exploring concept acceptability and gathering feedback on different aspects of design and usability of the proposed delivery system. Results: Participants viewed the concept of a new, microneedle-based contraceptive favourably. In Uganda, participants were presented with 7 different prototype applicators and identified desirable features of a preferred delivery device; their input reducing the number of prototypes that were subsequently evaluated by stakeholders in The Gambia and the UK. Participants in these countries helped to identify and/or confirm the most desirable characteristics of the applicator, resulting in design consolidation into a refined concept applicator. The final, optimised applicator prototype was validated during user research in Malawi. This human-centred design approach was also used to iteratively develop an information leaflet for the device. During these user studies, other preferred aspects of a contraceptive delivery system were also evaluated, such as anatomical site of application, duration of action, and return to fertility. Conclusions: A new microneedle-based contraceptive delivery system was iteratively developed using a human-centred design approach and was favourably received by potential stakeholders. The product is now being refined for testing in pre-clinical studies.