bluuebunny/crossref_metadata_2025_split huggingface dataset:
Understanding and optimising patient and public involvement in trial oversight: an ethnographic study of eight clinical trials
Authors: Coulman K. D. , Nicholson A. , Shaw A. , Daykin A. , Selman L. E. , Macefield R. , Shorter G. W. , Cramer H. , Sydes M. R. , Gamble C. , Pick M. E. , Taylor G. , Lane J. A. 
Published: June 2020

Abstract
Background
Trial oversight is important for trial governance and conduct. Patients and/or lay members of the public are increasingly included in trial oversight committees, influenced by international patient and public involvement (PPI) initiatives to improve the quality and relevance of research. However, there is a lack of guidance on how to undertake PPI in trial oversight and tokenistic PPI remains an issue. This paper explores how PPI functions in existing trial oversight committees and provides recommendations to optimise PPI in future trials. This was part of a larger study investigating the role and function of oversight committees in trials facing challenges.

Methods
Using an ethnographic study design, we observed oversight meetings of eight UK trials and conducted semi-structured interviews with members of their trial steering committees (TSCs) and trial management groups (TMGs) including public contributors, trial sponsors and funders. Thematic analysis of data was undertaken, with findings integrated to provide a multi-perspective account of how PPI functions in trial oversight.

Results
Eight TSC and six TMG meetings from eight trials were observed, and 66 semi-structured interviews conducted with 52 purposively sampled oversight group members, including three public contributors. PPI was reported as beneficial in trial oversight, with public members contributing a patient voice and fulfilling a patient advocacy role. However, public contributors were not always active at oversight meetings and were sometimes felt to have a tokenistic role, with trialists reporting a lack of understanding of how to undertake PPI in trial oversight. To optimise PPI in trial oversight, the following areas were highlighted: the importance of planning effective strategies to recruit public contributors; considering the level of oversight and stage(s) of trial to include PPI; support for public contributors by the trial team between and during oversight meetings.

Conclusions
We present evidence-based recommendations to inform future PPI in trial oversight. Consideration should be given at trial design stage on how to recruit and involve public contributors within trial oversight, as well as support and mentorship for both public contributors and trialists (in how to undertake PPI effectively). Findings from this study further strengthen the evidence base on facilitating meaningful PPI within clinical trials.
Neutrophil activation identifies patients with active polyarticular gout
Authors: Vedder D. , Gerritsen M. , Duvvuri B. , van Vollenhoven R. F. , Nurmohamed M. T. , Lood C. 
Published: June 2020

Abstract
Background
Gout is the most prevalent inflammatory arthritis in developed countries. A gout flare is mediated by phagocytosis of monosodium urate crystals by macrophages and neutrophils leading to subsequent activation of neutrophils contributing to synovitis, local joint destruction, and systemic inflammation. We hypothesize that biomarkers from activated neutrophils reflect gout disease activity.
The objective of this study therefore was to investigate the clinical utility of neutrophil-derived biomarkers in gout disease activity.

Methods
Plasma samples from 75 gout patients participating in the “Reade gout cohort Amsterdam” were compared with 30 healthy controls (HC). Levels of neutrophil extracellular traps (NETs) and neutrophil activation markers (calprotectin and peroxidase activity) were analyzed by ELISA and fluorimetry, compared to healthy controls, and related to markers of inflammation and disease activity.

Results
Levels of NETs, as well as neutrophil activation markers, were increased in gout patients compared to HC (p < 0.01). No associations were found between markers of cell death (cell-free DNA and NETs) and disease activity. Cell-free levels of genomic DNA were elevated among gout patients compared to HC (p < 0.05) and related to the number of gout attacks in the last year (β = 0.35, p < 0.01). Peroxidase activity correlated with disease activity (RAPID score: β = 0.49, p < 0.01, MHAQ: β = 0.66, p < 0.01) and inflammation markers (CRP: β = 0.25, p = 0.04, and ESR: β = 0.57, p < 0.001). Involvement of ankle or wrist resulted in significant higher peroxidase levels compared to mono-articular disease (β = 0.34, p < 0.01), indicating that peroxidase activity is a marker of poly-articular gout. Calprotectin (S100A8/A9) correlated with the inflammation marker CRP (β = 0.23, p = 0.05) and morning stiffness, especially in patients with chronic poly-articular gout (β = 0.71, p < 0.01).

Conclusions
Neutrophil activation markers are associated with characteristics of active, polyarticular gout. Furthermore, NETs are present in the peripheral blood of gout patients. However, NETs do not associate with markers of disease activity or inflammation. Future research should point out if peroxidase and calprotectin could be used in clinical practice as biomarkers for monitoring gout disease activity.
Immunoglobulin G from bovine milk primes intestinal epithelial cells for increased colonization of bifidobacteria
Authors: Morrin Sinead T. , McCarthy Geoffrey , Kennedy Deirdre , Marotta Mariarosaria , Irwin Jane A. , Hickey Rita M. 
Published: June 2020

AbstractA bovine colostrum fraction (BCF) was recently shown to enhance the adherence of several commensal organisms to intestinal epithelial cells through modulating the epithelial cell surface. In this study, the main components of the BCF were examined to investigate the active component/s responsible for driving the changes in the intestinal cells. The adherence of various bifidobacteria to HT-29 cells was increased when the intestinal cells were pre-incubated with immunoglobulin G (IgG). Modulation of the intestinal cells by IgG was concentration dependent with 16 mg/mL IgG resulting in a 43-fold increase in the adhesion of Bifidobacterium longum NCIMB 8809 to HT-29 cells. Periodate treatment of colostral IgG prior to performing the colonization studies resulted in a reduction in the adhesion of the strain to the intestinal cells demonstrating that the glycans of IgG may be important in modulating the intestinal cells for enhanced commensal adhesion. IgG isolated from mature milk also resulted in significant increases in adhesion of the Bifidobacterium strains tested albeit at reduced levels (3.9-fold). The impact of IgG on the HT-29 cells was also visualised via scanning electron microscopy. This study builds a strong case for the inclusion of IgG ingredients sourced from cow’s milk in functional foods aimed at increasing numbers of health promoting bacteria in the human gut.
An advanced low-complexity decoding algorithm for turbo product codes based on the syndrome
Authors: Yoon Sungsik , Ahn Byungkyu , Heo Jun 
Published: June 2020

AbstractThis paper introduces two effective techniques to reduce the decoding complexity of turbo product codes (TPC) that use extended Hamming codes as component codes. We first propose an advanced hard-input soft-output (HISO) decoding algorithm, which is applicable if an estimated syndrome stands for double-error. In conventional soft-input soft-output (SISO) decoding algorithms, 2p(p: the number of least reliable bits) number of hard decision decoding (HDD) operations are performed to correct errors. However, only a single HDD is required in the proposed algorithm. Therefore, it is able to lower the decoding complexity. In addition, we propose an early termination technique for undecodable blocks. The proposed early termination is based on the difference in the ratios of double-error syndrome detection between two consecutive half-iterations. Through this early termination, the average iteration number is effectively lowered, which also leads to reducing the overall decoding complexity. Simulation results show that the computational complexity of TPC decoding is significantly reduced via the proposed techniques, and the error correction performance remains nearly the same in comparison with that of conventional methods.
Some new integral inequalities of Wendorff type for discontinuous functions with integral jump conditions
Authors: Xing Lihong , Qiu Donghua , Zheng Zhaowen 
Published: June 2020

AbstractIn this paper, we investigate some new integral inequalities of Wendorff type for discontinuous functions with two independent variables and integral jump conditions. These integral inequalities with discontinuities are of non-Lipschitz type. New lower bounds are obtained, integral inequalities with retardation are also involved.
Comparing data sources in estimating disability-adjusted life years (DALYs) for ischemic heart disease and chronic obstructive pulmonary disease in a cross-sectional setting in Finland
Authors: Paalanen Laura , Reinikainen Jaakko , Härkänen Tommi , Mattila Tiina , Laatikainen Tiina , Jousilahti Pekka , Tolonen Hanna 
Published: June 2020

Abstract
Background
The disability-adjusted life years (DALYs) summarize the burden of years of life lost (YLL) due to premature mortality and years lost due to disability (YLD). Our aim was to estimate the burden of ischemic heart disease (IHD) and chronic obstructive pulmonary disease (COPD) in Finland in 2012, and to examine, how much the YLD are affected by the use of different data sources.

Methods
The YLL were calculated using mortality data for the Finnish 25–74-year-old population in 2012. The YLD were calculated using data from the FINRISK 2012 survey (3041 males, 3383 females aged 25–74 years) and then directly adjusted to the corresponding population. Different administrative registers on 1) hospital inpatient episodes and specialist outpatient visits, 2) entitlement to specially reimbursed medicines, and 3) purchases of prescribed medicines were used for estimation of the YLD in addition to self-reported data. The DALYs were calculated without age-weighting.

Results
The YLL for IHD were 37.5 for males and 9.1 for females per 1000 population among 25–74-year-old people in Finland in 2012. The YLD for IHD varied markedly depending on which data sources were used. All data sources combined, the YLD per 1000 were 5.3 for males and 2.5 for females resulting in estimated 42.8 and 11.6 DALYs per 1000 due to IHD among males and females, respectively. For COPD, the YLL were 4.7 for males and 2.0 for females per 1000. Also for COPD, the YLD varied markedly depending on data sources used. The YLD per 1000 based on all data sources combined were 2.0 for males and 1.6 for females. As a result, estimated 6.7 and 3.6 DALYs per 1000 were due to COPD among males and females, respectively.

Conclusions
Especially for COPD, all mild disease cases could probably not be identified from the included registers. Thereby, including survey data improved the coverage of the data. The YLD of IHD and COPD varied markedly between the data sources used in the calculations. However, as YLL constituted a major part of DALYs for these diseases, the variation in YLD did not lead to substantial variation in DALYs.
Upregulation of RIN3 induces endosomal dysfunction in Alzheimer’s disease
Authors: Shen Ruinan , Zhao Xiaobei , He Lu , Ding Yongbo , Xu Wei , Lin Suzhen , Fang Savannah , Yang Wanlin , Sung Kijung , Spencer Brian , Rissman Robert A. , Lei Ming , Ding Jianqing , Wu Chengbiao 
Published: June 2020

AbstractBackgroundIn Alzheimer’s Disease (AD), about one-third of the risk genes identified by GWAS encode proteins that function predominantly in the endocytic pathways. Among them, the Ras and Rab Interactor 3(RIN3) is a guanine nucleotide exchange factor (GEF) for the Rab5 small GTPase family and has been implicated to be a risk factor for both late onset AD (LOAD) and sporadic early onset AD (sEOAD). However, how RIN3 is linked to AD pathogenesis is currently undefined.MethodsQuantitative PCR and immunoblotting were used to measure the RIN3 expression level in mouse brain tissues and cultured basal forebrain cholinergic neuron (BFCNs). Immunostaining was used to define subcellular localization of RIN3 and to visualize endosomal changes in cultured primary BFCNs and PC12 cells. Recombinant flag-tagged RIN3 protein was purified from HEK293T cells and was used to define RIN3-interactomes by mass spectrometry. RIN3-interacting partners were validated by co-immunoprecipitation, immunofluorescence and yeast two hybrid assays. Live imaging of primary neurons was used to examine axonal transport of amyloid precursor protein (APP) and β-secretase 1 (BACE1). Immunoblotting was used to detect protein expression, processing of APP and phosphorylated forms of Tau.ResultsWe have shown that RIN3 mRNA level was significantly increased in the hippocampus and cortex of APP/PS1 mouse brain. Basal forebrain cholinergic neurons (BFCNs) cultured from E18 APP/PS1 mouse embryos also showed increased RIN3 expression accompanied by early endosome enlargement. In addition, via its proline rich domain, RIN3 recruited BIN1(bridging integrator 1) and CD2AP (CD2 associated protein), two other AD risk factors, to early endosomes. Interestingly, overexpression of RIN3 or CD2AP promoted APP cleavage to increase its carboxyl terminal fragments (CTFs) in PC12 cells. Upregulation of RIN3 or the neuronal isoform of BIN1 increased phosphorylated Tau level. Therefore, upregulation of RIN3 expression promoted accumulation of APP CTFs and increased phosphorylated Tau. These effects by RIN3 was rescued by the expression of a dominant negative Rab5 (Rab5S34N) construct. Our study has thus pointed to that RIN3 acts through Rab5 to impact endosomal trafficking and signaling.ConclusionRIN3 is significantly upregulated and correlated with endosomal dysfunction in APP/PS1 mouse. Through interacting with BIN1 and CD2AP, increased RIN3 expression alters axonal trafficking and procession of APP. Together with our previous studies, our current work has thus provided important insights into the role of RIN3 in regulating endosomal signaling and trafficking.
Adenocarcinoma arising from a heterotopic pancreas in the first portion of the duodenum: a case report
Authors: Minami Teruya , Terada Takuro , Mitsui Takeshi , Nakanuma Yasuni 
Published: June 2020

Abstract
Background
Heterotopic pancreas (HP) is defined as pancreatic tissue in organs with no anatomical continuity with the orthotopic pancreas. Based on the number of cases reported in the literature between the year 2000 and 2020, HP is rarely found causing malignant transformation of the duodenum. We herein report a case of adenocarcinoma arising from the HP in the first portion of the duodenum.

Case presentation
A 77-year-old Japanese man presented to our hospital with epigastric pain. Despite having undergone laparoscopic surgery for early sigmoid colon cancer a month earlier, serum levels of tumor-specific antigens, such as CA19-9, were elevated. After undergoing a series of radiologic examinations, the first portion of the duodenum was found thickened. However, a biopsy of the lesion showed no malignancy. Four months later, follow-up computed tomography (CT) scans showed that the lesion was thicker and involved the gastroduodenal artery (GDA), suggesting tumor invasion. A new biopsy did not detect the malignancy. However, serum tumor-specific antigen levels increased, especially duke pancreatic monoclonal antigen type 2 (5287 U/mL), in the absence of tumor in the orthotopic pancreas. The follow-up CT imaging showed a malignant tumor in the first portion of the duodenum. Five months later, we performed a subtotal stomach-preserving pancreaticoduodenectomy (SSPPD) for duodenal or HP cancer in the first portion of the duodenum, finding a lesion from the pyloric bulbs to the first portion of the duodenum, which invaded the adjacent pancreas and GDA. The pathological examination of the specimens revealed adenocarcinoma arising from HP. Nine months after surgery, no recurrence was found by radiologic imaging or tumor-specific antigen laboratory testing.

Conclusions
HP adenocarcinoma is rare and difficult to diagnose preoperatively due to its submucosal location. Therefore, a careful follow-up with blood testing and radiologic imaging, as well as diagnostic surgery, is recommended.
Intravenous and oral copper kinetics, biodistribution and dosimetry in healthy humans studied by [64Cu]copper PET/CT
Authors: Kjærgaard Kristoffer , Sandahl Thomas Damgaard , Frisch Kim , Vase Karina Højrup , Keiding Susanne , Vilstrup Hendrik , Ott Peter , Gormsen Lars Christian , Munk Ole Lajord 
Published: June 2020

Abstract
Purpose
Copper is essential for enzymatic processes throughout the body. [64Cu]copper (64Cu) positron emission tomography (PET) has been investigated as a diagnostic tool for certain malignancies, but has not yet been used to study copper homeostasis in humans. In this study, we determined the hepatic removal kinetics, biodistribution and radiation dosimetry of 64Cu in healthy humans by both intravenous and oral administration.

Methods
Six healthy participants underwent PET/CT studies with intravenous or oral administration of 64Cu. A 90 min dynamic PET/CT scan of the liver was followed by three whole-body PET/CT scans at 1.5, 6, and 20 h after tracer administration. PET data were used for estimation of hepatic kinetics, biodistribution, effective doses, and absorbed doses for critical organs.

Results
After intravenous administration, 64Cu uptake was highest in the liver, intestinal walls and pancreas; the gender-averaged effective dose was 62 ± 5 μSv/MBq (mean ± SD). After oral administration, 64Cu was almost exclusively taken up by the liver while leaving a significant amount of radiotracer in the gastrointestinal lumen, resulting in an effective dose of 113 ± 1 μSv/MBq. Excretion of 64Cu in urine and faeces after intravenous administration was negligible. Hepatic removal kinetics showed that the clearance of 64Cu from blood was 0.10 ± 0.02 mL blood/min/mL liver tissue, and the rate constant for excretion into bile or blood was 0.003 ± 0.002 min− 1.

Conclusion
64Cu biodistribution and radiation dosimetry are influenced by the manner of tracer administration with high uptake by the liver, intestinal walls, and pancreas after intravenous administration, while after oral administration, 64Cu is rapidly absorbed from the gastrointestinal tract and deposited primarily in the liver. Administration of 50 MBq 64Cu yielded images of high quality for both administration forms with radiation doses of approximately 3.1 and 5.7 mSv, respectively, allowing for sequential studies in humans.

Trial registration number
EudraCT no. 2016–001975-59. Registration date: 19/09/2016.
Evaluative and enabling infrastructures: supporting the ability of urban co-production processes to contribute to societal change
Authors: Palmer Henrietta , Polk Merritt , Simon David , Hansson Stina 
Published: June 2020

AbstractAs widely attested in the literature, the evaluation of co-production is complex and unsuited to the use of conventional quality, monitoring and evaluation indicators. This reflects the uncertainties, co-contributory factors and time lags involved, particularly when seeking to assess institutional and wider societal effects of multi-stakeholder participatory processes and deliberative fora. The most widely assessed effects include the immediate outputs and outcomes of a project or activity (so-called first order effects) while wider societal or third order effects continue to be the most difficult to capture and, consequently, are the least well studied. Because of this difficulty, the intermediate, second order effects of organisational transformation and policy implementation constitute a growing challenge for evaluation. This is our focus here. After 10 years of transdisciplinary co-productive research practice, Mistra Urban Futures, as an interstitial research space bridging academia and practice working through city-based institutional partnerships called platforms, has reached a phase where some of these effects are becoming distinguishable. Accordingly, we discuss the prerequisites for co-production practitioners, including policy makers, to engage their respective organisations in transitional and incremental experimentation in order to achieve relevant institutional changes. This requires enabling infrastructures that support training, facilitation and the creation of ‘safe’ spaces to promote trust and legitimacy. These are needed to underpin the long-lasting personal and organisational commitments which are crucial to achieve transformative organisational effects.
Patient-Level Factors Associated With Lack of Health Care Provider Recommendation for the Human Papillomavirus Vaccine Among Young Cancer Survivors
Authors: York Jocelyn M. , Klosky James L. , Chen Yanjun , Connelly James A. , Wasilewski-Masker Karen , Giuliano Anna R. , Robison Leslie L. , Wong F. Lennie , Hudson Melissa M. , Bhatia Smita , Landier Wendy 
Published: June 2020

PURPOSE Young cancer survivors are at increased risk for morbidities related to infection with the human papillomavirus (HPV), yet their HPV vaccine initiation rates remain low. Patient-/parent-reported lack of health care provider recommendation for HPV vaccination is strongly associated with vaccine noninitiation. We aimed to identify patient-level factors associated with survivor-/parent-reported lack of provider recommendation for HPV vaccination among young cancer survivors. METHODS Cancer survivors ages 9-26 years and 1-5 years off therapy completed a cross-sectional survey (parent-completed for survivors 9-17 years of age). Lack of health care provider HPV vaccine recommendation was the outcome of interest in a multivariable logistic regression model that included relevant patient-level sociodemographic, clinical, and vaccine-related variables. RESULTS Of 955 survivors, 54% were male, 66% were non-Hispanic White, and 36% had leukemia. At survey participation, survivors were an average age (± standard deviation) of 16.3 ± 4.7 years and 32.8 ± 14.7 months off therapy. Lack of provider HPV vaccine recommendation was reported by 73% (95% CI, 70% to 75%) of survivors. For the entire cohort, patient-level factors associated with lack of reported provider recommendation included perceived lack of insurance coverage for the HPV vaccine (odds ratio [OR], 4.0; 95% CI, 2.7 to 5.9; P < .001), male sex (OR, 2.8; 95% CI, 1.9 to 4.0; P < .001), and decreased parent-survivor communication regarding HPV vaccination (OR, 1.7 per unit decrease in score; 95% CI, 1.3 to 2.2; P < .001). In the sex- and age-stratified models, perceived lack of insurance coverage (all models) and male sex (age-stratified models) were also significantly associated with lack of reported provider recommendation. CONCLUSION We identified factors characterizing survivors at risk for not reporting receipt of a health care provider HPV vaccine recommendation. Future research is needed to develop interventions that facilitate effective provider recommendations for HPV vaccination among all young cancer survivors.