bluuebunny/crossref_metadata_2025_split huggingface dataset:
Study protocol: a randomized controlled trial comparing the efficacy of therapist guided internet-delivered cognitive therapy (TG-iConquerFear) with augmented treatment as usual in reducing fear of cancer recurrence in Danish colorectal cancer survivors
Authors: Lyhne Johanne Dam , Smith Allan ‘ Ben’ , Frostholm Lisbeth , Fink Per , Jensen Lars Henrik 
Published: March 2020

Abstract
Background
Cognitive therapy has been shown to reduce fear of cancer recurrence (FCR), mainly in breast cancer survivors. The accessibility of cognitive behavioural interventions could be further improved by Internet delivery, but self-guided interventions have shown limited efficacy. The aim of this study is to test the efficacy of a therapist guided internet-delivered intervention (TG-iConquerFear) vs. augmented treatment as usual (aTAU) in Danish colorectal cancer survivors.

Methods/design
A population-based randomized controlled trial (RCT) comparing TG-iConquerFear with aTAU (1:1) in n = 246 colorectal cancer survivors who suffer from clinically significant FCR (Fear of Cancer Recurrence Inventory Short Form (FCRI-SF) ≥ 22 and semi-structured interview). Evaluation will be conducted at 2 weeks, 3 and 6 months post-treatment and between-group differences will be evaluated. Long-term effects will be evaluated after one year. Primary outcome will be post-treatment FCR (FCRI-SF). Secondary outcomes are global overall health and global quality of life (Visual Analogue Scales 0–100), bodily distress syndrome (BDS checklist), health anxiety (Whiteley-6), anxiety (SCL4-anx), depression (SCL6-dep) and sickness absence and health expenditure (register data). Explanatory outcomes include: Uncertainty in illness (Mishels uncertainty of illness scale, short form, MUIS), metacognitions (MCQ-30 negative beliefs about worry subscale), and perceived risk of cancer recurrence (Visual analogue Scale 1–100).

Discussion
This RCT will provide valuable information on the clinical and cost-effectiveness of TG-iConquerFear vs. aTAU for CRC survivors with clinical FCR, as well as explanatory variables that may act as outcome moderators or mediators.

Trial registration
ClinicalTrials.gov; NCT04287218, registered 25.02.2020.
https://clinicaltrials.gov/ct2/results?cond=&term=NCT04287218&cntry=&state=&city=&dist=.
A randomised controlled trial comparing the effectiveness of surgical and nonsurgical treatment for cervical radiculopathy
Authors: Taso Mirad , Sommernes Jon Håvard , Kolstad Frode , Sundseth Jarle , Bjorland Siri , Pripp Are Hugo , Zwart John Anker , Brox Jens Ivar 
Published: March 2020

Abstract
Background
Cervical radiculopathy is usually caused by disc herniation or spondylosis. The prognosis is expected to be good in most patients, but there is limited scientific evidence on the indications for nonsurgical and surgical treatments. The aim of the present study is to evaluate and compare the effectiveness of surgical and nonsurgical treatment in two trials – including disc herniation and spondylosis, respectively, and to evaluate factors that contribute to better decision making.

Methods/design
Patients with disabling radicular arm pain and MRI-proven cervical disc herniation or spondylosis will be randomised to receive nonsurgical or surgical treatment. The follow-up period is one year and the sample size is estimated to be 50 for each arm in the two trials, giving a total of 200 patients. The primary outcomes are the Neck Disability Index and arm pain. Secondary outcomes include neck pain; EQ-5D and costs to evaluate cost-effectiveness; prognostic factors; CT and MRI scans, to estimate intervertebral foraminal area and nerve root compression; and the expected minimal improvement for willingness to undergo treatment.

Discussion
The outcomes of this study will contribute to better decision making in the treatment of cervical radiculopathy.

Trial registration
This study has been registered at ClinicalTrials.gov as NCT03674619, on September 17, 2018.
Determinants of aggression against all health care workers in a large-sized university hospital
Authors: Viottini Elena , Politano Gianfranco , Fornero Giulio , Pavanelli Pier Luigi , Borelli Paola , Bonaudo Marco , Gianino Maria Michela 
Published: March 2020

Abstract
Background
The paper aims to describe the 3-year incidence (2015/17) of aggressive acts against all healthcare workers to identify risk factors associated to violence among a variety of demographic and professional determinants of assaulted, and risk factors related to the circumstances surrounding these events.

Methods
A retrospective observational study of all 10,970 health workers in a large-sized Italian university hospital was performed.
The data, obtained from the “Aggression Reporting Form”, which must be completed by assaulted workers within 72 h of aggression, were collected for the following domains: worker assaulted (sex, age class, years worked); profession (nurses, medical doctors, non-medical support staff, administrative staff, midwives); aggressive acts (activity type during aggressive acts, season, time and location of aggressive acts); and type of aggressive acts (verbal, non-verbal, consequences, aggressors).

Results
Three hundred sixty-four (3.3%) workers experienced almost one aggression. The majority of the assaulted workers were female (77.5%), had worked for 6/15 years and were Nurses (64.3%). The majority of aggressive acts occurred during assistance and patient care (38.2%), in the spring and during the afternoon/morning shifts and took place in locations where patients were present (47.3%). The most prevalent aggression type was verbal (76.9%). The patient was the most common aggressor (46.7%). 56% of those assaulted experienced interruptions in their work.
Being female, being < 50 years of age, having worked for 6–15 years were significant risk factors for aggression. Midwives suffered the highest risk of experiencing aggression (RR = 12.95).
The risk analysis showed that non-verbally aggressive acts were related to assistance and patient care with respect to activity type, to the presence of patients and during the spring and afternoon/evening.

Conclusions
The findings suggest the parallel use of future qualitative studies to clarify the motivation behind aggression. These suggestions are needed for the implementation of additional adequate prevention strategies on either an organizational or a personal level.
Safety of occasional ingestion of gluten in patients with celiac disease: a real-life study
Authors: Elli Luca , Bascuñán Karla , di Lernia Lorenzo , Bardella Maria Teresa , Doneda Luisa , Soldati Laura , Orlando Stefania , Ferretti Francesca , Lombardo Vincenza , Barigelletti Giulio , Scricciolo Alice , Fabiano Sabrina , Vecchi Maurizio , Roncoroni Leda 
Published: March 2020

Abstract
Background
Gluten-free diet (GFD) decreases the quality of life of celiac disease (CD) patients, who frequently ask to occasionally ingest gluten-containing food. We evaluated CD patients reporting voluntary and occasional transgressions to their GFD.

Methods
From October 2017 to September 2018, the patients reporting occasional and voluntary gluten ingestion (GFD-noncompliant) were prospectively enrolled. These patients underwent clinical examination, blood tests, duodenal biopsy, capsule enteroscopy (CE), and a validated food-frequency questionnaire (FFQ) assessing the frequency and quantity of gluten intake. Mortality was calculated and compared to the general population. A group of patients on strict GFD (GFD-adherent) acted as controls.

Results
One thousand three hundred seventy-eight CD patients were evaluated during the study period. One hundred nine (8%) reported occasional (weekly or monthly) voluntary ingestion of gluten. The mean gluten intake was 185.2 ± 336.9 g/year, and the duration of their incorrect GFD was 8.6 ± 6.9 years. Among the noncompliant patients, 57% did not present any histological alteration; furthermore, the Marsh score profile was not different between compliant and noncompliant patients. Seventy percent did not present any alteration at CE. Seventy-five percent of patients reported no gastrointestinal symptoms after gluten ingestion. Twenty-three percent of patients in the GFD-noncompliant group presented positive tTG-IgA. No association was found between gluten intake, clinical symptoms, and biomarkers. Mortality was not different between the groups and the general population.

Conclusions
Our results are that in a real-life scenario, a group of CD patients on long-term gluten intake showed no significant clinical symptoms or small bowel damage, thus suggesting that a degree of tolerance towards gluten consumption can be reached.
Robust microorganisms for biofuel and chemical production from municipal solid waste
Authors: Dornau Aritha , Robson James F. , Thomas Gavin H. , McQueen-Mason Simon J. 
Published: March 2020

Abstract
Background
Worldwide 3.4 billion tonnes of municipal solid waste (MSW) will be produced annually by 2050, however, current approaches to MSW management predominantly involve unsustainable practices like landfilling and incineration. The organic fraction of MSW (OMSW) typically comprises ~ 50% lignocellulose-rich material but is underexplored as a biomanufacturing feedstock due to its highly inconsistent and heterogeneous composition. This study sought to overcome the limitations associated with studying MSW-derived feedstocks by using OMSW produced from a realistic and reproducible MSW mixture on a commercial autoclave system. The resulting OMSW fibre was enzymatically hydrolysed and used to screen diverse microorganisms of biotechnological interest to identify robust species capable of fermenting this complex feedstock.

Results
The autoclave pre-treated OMSW fibre contained a polysaccharide fraction comprising 38% cellulose and 4% hemicellulose. Enzymatic hydrolysate of OMSW fibre was high in d-glucose (5.5% w/v) and d-xylose (1.8%w/v) but deficient in nitrogen and phosphate. Although relatively low levels of levulinic acid (30 mM) and vanillin (2 mM) were detected and furfural and 5-hydroxymethylfurfural were absent, the hydrolysate contained an abundance of potentially toxic metals (0.6% w/v). Hydrolysate supplemented with 1% yeast extract to alleviate nutrient limitation was used in a substrate-oriented shake-flask screen with eight biotechnologically useful microorganisms (Clostridium saccharoperbutylacetonicum, Escherichia coli, Geobacillus thermoglucosidasius, Pseudomonas putida, Rhodococcus opacus, Saccharomyces cerevisiae, Schizosaccharomyces pombe and Zymomonas mobilis). Each species’ growth and productivity were characterised and three species were identified that robustly and efficiently fermented OMSW fibre hydrolysate without significant substrate inhibition: Z. mobilis, S. cerevisiae and R. opacus, respectively produced product to 69%, 70% and 72% of the maximum theoretical fermentation yield and could theoretically produce 136 kg and 139 kg of ethanol and 91 kg of triacylglycerol (TAG) per tonne of OMSW.

Conclusions
Developing an integrated biorefinery around MSW has the potential to significantly alleviate the environmental burden of current waste management practices. Substrate-oriented screening of a representative and reproducible OMSW-derived fibre identified microorganisms intrinsically suited to growth on OMSW hydrolysates. These species are promising candidates for developing an MSW biorefining platform and provide a foundation for future studies aiming to valorise this underexplored feedstock.
Endotoxin clustering with allergens in house dust and asthma outcomes in a U.S. national study
Authors: Mendy Angelico , Wilkerson Jesse , Salo Pӓivi M. , Zeldin Darryl C. , Thorne Peter S. 
Published: March 2020

AbstractBackgroundEndotoxin is ubiquitous in the environment, but its clustering with indoor allergens is not well characterized. This study examined the clustering patterns of endotoxin with allergens in house dust and their association with asthma outcomes.MethodsWe analyzed data from 6963 participants of the 2005–2006 National Health and Nutrition Examination Survey. House dust sampled from bedroom floor and bedding was evaluated for endotoxin and allergens from fungi, cockroach, dog, cat, mites, and rodents. Two-step cluster analysis and logistic regressions were performed to identify the clustering patterns and their associations with current asthma and wheeze in the past 12 months, adjusting for covariates.ResultsOf the homes, 17.8% had low endotoxin and allergen levels in house dust (Cluster 1). High endotoxin level clustered withAlternariaand pet allergens in the homes of participants with a high socioeconomic status who own pets (Cluster 2) (48.9%). High endotoxin clustered withAspergillus, dust mites, cockroach, and rodent allergens in the homes of participants with low socioeconomic status (Cluster 3) (33.3%). Compared to Cluster 1, Cluster 2 was associated with higher asthma prevalence (OR 1.42, 95% CI: 1.06–1.91) and wheeze (OR 1.32, 95% CI: 1.07–1.63). Cluster 3 was positively associated with wheeze only in participants sensitized to inhalant allergens (OR 1.42, 95% CI: 1.06–1.91) or exposed to tobacco smoke (OR 1.72, 95% CI: 1.15–2.60).ConclusionsThe clustering of endotoxin with allergens in dust from homes with pets or of people with low socioeconomic status is associated with asthma and wheeze.
Exosomal miRNA-128-3p from mesenchymal stem cells of aged rats regulates osteogenesis and bone fracture healing by targeting Smad5
Authors: Xu Tao , Luo Yongjun , Wang Jiaxing , Zhang Ning , Gu Changjiang , Li Linwei , Qian Dingfei , Cai Weihua , Fan Jin , Yin Guoyong 
Published: March 2020

AbstractTransplantation of mesenchymal stem cells (MSCs) has been considered an effective therapeutic treatment for a variety of diseases including bone fracture. However, there are associated complications along with MSCs transplantation. There is evidence to show that exosomes (Exos) derived from MSCs exert a similar paracrine function. In addition, repair capabilities of MSCs decline with age. Hence, this study aims to confirm whether the Exos protective function on osteogenic differentiation and fracture healing from aged MSCs was attenuated. This information was used in order to investigate the underlying mechanism. MSCs were successfully isolated and identified from young and aged rats, and Exos were then obtained. Aged-Exos exhibited significantly attenuated effects on MSCs osteogenic differentiation in vitro and facture healing in vivo. Using miRNA array analysis, it was shown that miR-128-3p was markedly upregulated in Aged-Exos. In vitro experiments confirmed that Smad5 is a direct downstream target of miR-128-3p, and was inhibited by overexpressed miR-128-3p. A series gain- and loss- function experiment indicated that miR-128-3P serves a suppressor role in the process of fracture healing. Furthermore, effects caused by miR-128-3P mimic/inhibitor were reversed by the application of Smad5/siSmad5. Taken together, these results suggest that the therapeutic effects of MSCs-derived Exos may vary according to differential expression of miRNAs. Exosomal miR-128-3P antagomir may act as a promising therapeutic strategy for bone fracture healing, especially for the elderly.
Determinants of health-related quality of life: a cross-sectional investigation in physician-managed anticoagulated patients using vitamin K antagonists
Authors: Magon Arianna , Arrigoni Cristina , Moia Marco , Mancini Michela , Dellafiore Federica , Manara Duilio F. , Caruso Rosario 
Published: March 2020

AbstractBackgroundLiterature has paid little attention in describing the specific contribution of each modifiable and non-modifiable characteristics on health-related quality of life (HRQoL) in physician-managed anticoagulated patients using vitamin K antagonists (VKAs). To describe how patients’ treatment-specific knowledge, health literacy, treatment beliefs, clinical, and socio-demographic characteristics influence HRQoL in Italian physician-managed anticoagulated patients using VKAs.MethodsCross-sectional multicentre study with a consecutive sampling strategy, enrolling 164 long-term anticoagulated patients. Clinical and socio-demographic characteristics were collected from electronic medical records. Valid and reliable questionnaires were used to collect patients’ treatment-specific knowledge, health literacy, beliefs about VKAs, physical and health perceptions.ResultsObtaining and understanding health information (i.e., communicative health literacy) positively predicts both adequate mental (ORadjusted = 10.9; 95%CI = 1.99–19.10) and physical (ORadjusted = 11.54; 95%CI = 1.99–34.45) health perceptions. Conversely, the ability to perform proper health decision making (i.e., critical health literacy) was associated with lower rates of adequate mental health perception (ORadjusted = 0.13; 95%CI = 0.03–0.63). Further, age negatively predicted physical health perception (ORadjusted = 0.87; 95%CI = 0.81–0.93).ConclusionsHealth literacy plays an interesting role in predicting HRQoL. The relationship between critical health literacy and mental health perception could be influenced by some psychological variables, such as distress and frustration, which could be present in patients with higher levels of critical health literacy, as they could be more inclined for self-monitoring. For this reason, future research are needed to identify the most suitable patients’ profile for each OAC-management model, by longitudinally describing the predictive performance of each modifiable and non-modifiable determinant of HRQoL.
Estimating physical activity from self-reported behaviours in large-scale population studies using network harmonisation: findings from UK Biobank and associations with disease outcomes
Authors: Pearce Matthew , Strain Tessa , Kim Youngwon , Sharp Stephen J. , Westgate Kate , Wijndaele Katrien , Gonzales Tomas , Wareham Nicholas J. , Brage Søren 
Published: March 2020

Abstract
Background
UK Biobank is a large prospective cohort study containing accelerometer-based physical activity data with strong validity collected from 100,000 participants approximately 5 years after baseline. In contrast, the main cohort has multiple self-reported physical behaviours from > 500,000 participants with longer follow-up time, offering several epidemiological advantages. However, questionnaire methods typically suffer from greater measurement error, and at present there is no tested method for combining these diverse self-reported data to more comprehensively assess the overall dose of physical activity. This study aimed to use the accelerometry sub-cohort to calibrate the self-reported behavioural variables to produce a harmonised estimate of physical activity energy expenditure, and subsequently examine its reliability, validity, and associations with disease outcomes.

Methods
We calibrated 14 self-reported behavioural variables from the UK Biobank main cohort using the wrist accelerometry sub-cohort (n = 93,425), and used published equations to estimate physical activity energy expenditure (PAEESR). For comparison, we estimated physical activity based on the scoring criteria of the International Physical Activity Questionnaire, and by summing variables for occupational and leisure-time physical activity with no calibration. Test-retest reliability was assessed using data from the UK Biobank repeat assessment (n = 18,905) collected a mean of 4.3 years after baseline. Validity was assessed in an independent validation study (n = 98) with estimates based on doubly labelled water (PAEEDLW). In the main UK Biobank cohort (n = 374,352), Cox regression was used to estimate associations between PAEESR and fatal and non-fatal outcomes including all-cause, cardiovascular diseases, respiratory diseases, and cancers.

Results
PAEESR explained 27% variance in gold-standard PAEEDLW estimates, with no mean bias. However, error was strongly correlated with PAEEDLW (r = −.98; p < 0.001), and PAEESR had narrower range than the criterion. Test-retest reliability (Λ = .67) and relative validity (Spearman = .52) of PAEESR outperformed two common approaches for processing self-report data with no calibration. Predictive validity was demonstrated by associations with morbidity and mortality, e.g. 14% (95%CI: 11–17%) lower mortality for individuals meeting lower physical activity guidelines.

Conclusions
The PAEESR variable has good reliability and validity for ranking individuals, with no mean bias but correlated error at individual-level. PAEESR outperformed uncalibrated estimates and showed stronger inverse associations with disease outcomes.
A peripheral neutrophil-related inflammatory factor predicts a decline in executive function in mild Alzheimer’s disease
Authors:   for the Alzheimer’s Disease Neuroimaging Initiative, Bawa Kritleen K. , Krance Saffire H. , Herrmann Nathan , Cogo-Moreira Hugo , Ouk Michael , Yu Di , Wu Che-Yuan , Black Sandra E. , Lanctôt Krista L. , Swardfager Walter 
Published: March 2020

AbstractBackgroundStudies suggest a role of the innate immune system, including the activity of neutrophils, in neurodegeneration related to Alzheimer’s disease (AD), but prospective cognitive data remain lacking in humans. We aimed to investigate the predictive relationship between neutrophil-associated inflammatory proteins in peripheral blood and changes in memory and executive function over 1 year in patients with AD.MethodsParticipants with AD were identified from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Neutrophil gelatinase-associated lipocalin (NGAL), myeloperoxidase (MPO), interleukin-8 (IL-8), macrophage inflammatory protein-1 beta (MIP-1β), and tumor necrosis factor (TNF) were assayed by luminex immunofluorescence multiplex assay at baseline. Confirmatory factor analysis was used to test an underlying neutrophil associated plasma inflammatory factor. Compositez-scores for memory and executive function were generated from multiple tests at baseline and at 1 year. A multiple linear regression model was used to investigate the association of the baseline inflammatory factor with changes in memory and executive function over 1 year.ResultsAmong AD patients (n = 109, age = 74.8 ± 8.1, 42% women, Mini Mental State Examination [MMSE] = 23.6 ± 1.9), the neutrophil-related inflammatory proteins NGAL (λ = 0.595,p < .001), MPO (λ = 0.575,p < .001), IL-8 (λ = 0.525,p < .001), MIP-1β (λ = 0.411,p = .008), and TNF (λ = 0.475,p < .001) were found to inform an underlying factor. Over 1 year, this inflammatory factor predicted a decline in executive function (β = − 0.152,p = 0.015) but not memory (β = 0.030,p = 0.577) in models controlling for demographics, brain atrophy, white matter hyperintensities, the ApoE ε4 allele, concomitant medications, and baseline cognitive performance.ConclusionsAn inflammatory factor constructed from five neutrophil-related markers in peripheral blood predicted a decline in executive function over 1 year in people with mild AD.
Low grade malignant eccrine spiradenoma of the vulva: case report, review of the literature and discussion about the role of p53 and HPV
Authors: Catteau Xavier , D’haene Nicky , Noël Jean-Christophe 
Published: March 2020

Abstract
Background
Malignant eccrine spiradenoma is one of the rarest sweat-gland tumors. Here, we describe a rare case of low grade malignant eccrine spiradenoma located at the vulva.

Case presentation
The vulvar lesion was described as a mass measured 3.5 cm and located in the dermis and subcutis with no attachment to the epidermis. The neoplasm was arranged in ragged sheets or solid nodules sometimes with focal necrosis. The tumor cells had hyperchromatism, pleomorphism, and prominent nucleoli with high mitotic index and KI-67 estimated at 70–80%.

Conclusions
It’s only the fifth case of malignant eccrine spiradenoma localized at the vulva. This is the first time that an HPV genotyping was made in this type of lesion with no HPV found while the p16 expression was diffuse. Moreover, it’s the first time that a p53 mutation is detected by sequencing in this location.