bluuebunny/crossref_metadata_2025_split huggingface dataset:
A robust multiplex immunoaffinity mass spectrometry assay (PromarkerD) for clinical prediction of diabetic kidney disease
Authors: Bringans Scott , Ito Jason , Casey Tammy , Thomas Sarah , Peters Kirsten , Crossett Ben , Coleman Orla , Ebhardt Holger A. , Pennington Stephen R. , Lipscombe Richard 
Published: October 2020

Abstract
Background
PromarkerD is a novel proteomics derived blood test for predicting diabetic kidney disease (DKD). The test is based on an algorithm that combines the measurement of three plasma protein biomarkers (CD5L, APOA4, and IBP3) with three clinical variables (age, HDL-cholesterol, and eGFR). The initial format of the assay used immunodepletion of plasma samples followed by targeted mass spectrometry (MRM-LCMS). The aim of this study was to convert the existing assay into an immunoaffinity approach compatible with higher throughput and robust clinical application.

Methods
A newly optimised immunoaffinity-based assay was developed in a 96 well format with MRM measurements made using a low-flow LCMS method. The stability, reproducibility and precision of the assay was evaluated. A direct comparison between the immunoaffinity method and the original immunodepletion method was conducted on a 100-person cohort. Subsequently, an inter-lab study was performed of the optimised immunoaffinity method in two independent laboratories.

Results
Processing of plasma samples was greatly simplified by switching to an immunoaffinity bead capture method, coupled to a faster and more robust microflow LCMS system. Processing time was reduced from seven to two days and the chromatography reduced from 90 to 8 min. Biomarker stability by temperature and time difference treatments passed acceptance criteria. Intra/Inter-day test reproducibility and precision were within 11% CV for all biomarkers. PromarkerD test results from the new immunoaffinity method demonstrated excellent correlation (R = 0.96) to the original immunodepletion method. The immunoaffinity assay was successfully transferred to a second laboratory (R = 0.98) demonstrating the robustness of the methodology and ease of method transfer.

Conclusions
An immunoaffinity capture targeted mass spectrometry assay was developed and optimised. It showed statistically comparable results to those obtained from the original immunodepletion method and was also able to provide comparable results when deployed to an independent laboratory. Taking a research grade assay and optimising to a clinical grade workflow provides insights into the future of multiplex biomarker measurement with an immunoaffinity mass spectrometry foundation. In the current format the PromarkerD immunoaffinity assay has the potential to make a significant impact on prediction of diabetic kidney disease with consequent benefit to patients.
Development and validation of a fourteen- innate immunity-related gene pairs signature for predicting prognosis head and neck squamous cell carcinoma
Authors: Zhang Fujun , Liu Yu , Yang Yixin , Yang Kai 
Published: October 2020

Abstract
Background
Immune-related genes is closely related to the occurrence and prognosis of head and neck squamous cell carcinoma (HNSCC). At the same time, immune-related genes have great potential as prognostic markers in many types of cancer. The prognosis of HNSCC is still poor currently, and it may be effective to predict the clinical outcome of HNSCC by immunogenic analysis.

Methods
RNASeq and clinical follow-up information were downloaded from The Cancer Genome Atlas (TCGA), the MINiML format GSE65858 chip expression data was downloaded from NCBI, and immune-related genes was downloaded from the InnateDB database. Immune-related genes in 519 HNSC patients were integrated from TCGA dataset. By using multivariate COX analysis and Lasso regression, robust immune-related gene pairs (IRGPs) that predict clinical outcomes of HNSCC were identified. Finally, a risk prognostic model related to immune gene pair was established and verified by clinical features, test sets and GEO external validation set.

Results
A total of 699 IRGPs were significantly correlated with the prognosis of HNSCC patients. Fourteen robust IRGPs were finally obtained by Lasso regression and a prognostic risk prediction model was constructed. Risk score of each sample were calculated based on Risk models and divided into the high-risk group (Risk-H) and low Risk group (Risk-L). Risk models were able to stratify the risk in patients with TNM Stage, Age, gender, and smoking history, and the AUC > 0.65 in training set and test set, shows that 14-IRGPs signature in patients with HNSCC has excellent classification performance. In addition, 14-IRGPs had the highest average C index compared with the prognostic characteristics and T, N, and Age of the 3 previously reported HNSCC.

Conclusion
This study constructed 14-IRGPs as a novel prognostic marker for predicting survival in HNSCC patients.
The impact of hypothetical PErsonalised Risk Information on informed choice and intention to undergo Colorectal Cancer screening colonoscopy in Scotland (PERICCS)—a randomised controlled trial
Authors: Digby Jayne , O’Carroll Ronan E. , Chambers Julie A. , Steele Robert J. C. 
Published: October 2020

Abstract
Background
There is currently no existing evidence on the effects of personalised risk information on uptake of colonoscopy following first line screening for colorectal cancer. This study aimed to measure the impact of providing risk information based on faecal haemoglobin concentration to allow a fully informed choice around whether or not to undergo colonoscopy.

Methods
Two thousand seven hundred sixty-seven participants from the Scottish Bowel Screening Programme (SBoSP) database, who had not recently been invited for screening, were randomised to receive one of three types of hypothetical risk information materials: (1) numerical risk information (risk categories of one in 40, one in 1600 and one in 3500), (2) categorical risk information (highest, moderate and lowest risk), or (3) positive screening result letter (control group). The primary outcome was the impact of the risk materials on intention to undergo colonoscopy, to allow comparison with the current colonoscopy uptake of 77% for those with a positive screening result in the SBoSP. Secondary outcomes were knowledge, attitudes and emotional responses to the materials.

Results
Four hundred thirty-four (15.7%) agreed to participate with 100 from the numerical risk group (69.0%), 104 from the categorical risk group (72.2%) and 104 from the control group (71.7%) returning completed materials. Intention to undergo colonoscopy was highest in the highest risk groups for the numerical and categorical study arms (96.8% and 95.3%, respectively), but even in the lowest risk groups was > 50% (58.1% and 60.7%, respectively). Adequate knowledge of colorectal screening and the risks and benefits of colonoscopy was found in ≥ 98% of participants in all three arms. All participants reported that they found the information easy-to-understand. 19.1%, 24.0% and 29.6% of those in the numerical, categorical and control group, respectively, reported that they found the information distressing (p > 0.05).

Conclusions
Applying the risk categories to existing SBoSP data shows that if all participants were offered an informed choice to have colonoscopy, over two thirds of participants would intend to have the test. Equating to an increase in the number of screening colonoscopies from approx. 14,000 to 400,000 per annum, this would place an unmanageable demand on colonoscopy services, with a very small proportion of cancers and pre-cancers detected. However, the response to the materials were very positive, suggesting that providing risk information to those in lowest and moderate risk groups along with advice that colonoscopy is not currently recommended may be an option. Future research would be required to examine actual uptake.

Trial registration
Date applied 1 December 2017 ISRCTN number 14254582.
Automated computed tomography quantification of fibrosis predicts prognosis in combined pulmonary fibrosis and emphysema in a real-world setting: a single-centre, retrospective study
Authors: Nemoto Masahiro , Nei Yuichiro , Bartholmai Brian , Yoshida Kazuki , Matsui Hiroki , Nakashita Tamao , Motojima Shinji , Aoshima Masahiro , Ryu Jay H. 
Published: October 2020

Abstract
Background
Combined pulmonary fibrosis and emphysema (CPFE) is a heterogeneous clinico-radiological syndrome without a consensus definition. There are limited data on the relation between the amount of parenchymal fibrosis and prognosis. In this study, we assessed the prognostic implications of the extent of fibrosis assessed by an automated quantitative computed tomography (CT) technique and the radiological and functional change over time in patients with a broad spectrum of fibrotic interstitial lung diseases (ILDs) encountered in a real-world setting.

Methods
We conducted a single-centre, retrospective study of 228 consecutive patients with CPFE, encountered from 2007 to 2015 at Kameda Medical Center, Chiba, Japan. We investigated the prognostic value of automated CT fibrosis quantification and the subsequent course of CPFE.

Results
Among 228 patients with CPFE, 89 had fibrosis affecting < 5% of their lungs, 54 had 5 to < 10% fibrosis, and 85 had ≥ 10% fibrosis at the time of diagnosis. Lower volume of fibrosis correlated with lower rates of mortality and acute exacerbation (p < 0.001). In particular, among those with < 5% fibrosis, only 4.5% died and none experienced acute exacerbation during follow-up, whereas 57.6% and 29.4% of those with ≥ 10% fibrosis experienced death and acute exacerbation, respectively. Although, the ≥ 10% fibrosis group had the poorest overall survival as well as the highest incidence of acute exacerbation, the incidence of decline in pulmonary function tests, change per year in total lung volume, and progression of fibrosis on chest CT was highest in the 5 to < 10% fibrosis group. The Cox proportional hazard model for CPFE progression (defined by composite criteria of death, acute exacerbation, and decline in forced vital capacity or diffusing capacity) showed fibrosis proportion was a risk factor independent of age, sex, smoking pack-years, the Charlson Comorbidity Index, lung cancer, connective tissue disease, and idiopathic pulmonary fibrosis.

Conclusions
Less severe (< 5%) fibrosis at baseline was associated with disease stability and better prognosis compared to more severe fibrosis in CPFE occurring with fibrotic ILDs. Further studies including a validation cohort will be needed.
Trial Registration Retrospectively registered.
Improved methods for mass production of magnetosomes and applications: a review
Authors: Basit Abdul , Wang Jiaojiao , Guo Fangfang , Niu Wei , Jiang Wei 
Published: October 2020

AbstractMagnetotactic bacteria have the unique ability to synthesize magnetosomes (nano-sized magnetite or greigite crystals arranged in chain-like structures) in a variety of shapes and sizes. The chain alignment of magnetosomes enables magnetotactic bacteria to sense and orient themselves along geomagnetic fields. There is steadily increasing demand for magnetosomes in the areas of biotechnology, biomedicine, and environmental protection. Practical difficulties in cultivating magnetotactic bacteria and achieving consistent, high-yield magnetosome production under artificial environmental conditions have presented an obstacle to successful development of magnetosome applications in commercial areas. Here, we review information on magnetosome biosynthesis and strategies for enhancement of bacterial cell growth and magnetosome formation, and implications for improvement of magnetosome yield on a laboratory scale and mass-production (commercial or industrial) scale.
A qualitative analysis of vaccine decision makers’ conceptualization and fostering of ‘community engagement’ in India
Authors: Dutta Tapati , Meyerson Beth E. , Agley Jon , Barnes Priscilla A. , Sherwood-Laughlin Catherine , Nicholson-Crotty Jill 
Published: October 2020

Abstract
Background
Globally, and in India, research has highlighted the importance of community engagement in achieving national vaccination goals and in promoting health equity. However, community engagement is not well-defined and remains an underutilized approach. There is also paucity of literature on community engagement’s effectiveness in achieving vaccination outcomes. To address that gap, this study interviewed Indian vaccination decision makers to derive a shared understanding of the evolving conceptualization of community engagement, and how it has been fostered during India’s Decade of Vaccines (2010-2020).

Methods
Semi-structured interviews were conducted with 25 purposefully sampled national-level vaccine decision makers in India, including policymakers, immunization program heads, and vaccine technical committee leads. Participants were identified by their ‘elite’ status among decisionmakers in the Indian vaccination space. Schutz’ Social Phenomenological Theory guided development of an a priori framework derived from the Social Ecological Model. The framework helped organize participants’ conceptualizations of communities, community engagement, and related themes. Inter-rater reliability was computed for a subsample of coded interviews, and findings were validated in a one-day member check-in meeting with study participants and teams.

Results
The interviews successfully elucidated participants’ understanding of key terminology (“community”) and approaches to community engagement propagated by the vaccine decision makers. Participants conceptualized ‘communities’ as vaccine-eligible children, their parents, frontline healthcare workers, and vaccination influencers. Engagement with those communities was understood to mean vaccine outreach, capacity-building of healthcare workers, and information dissemination. However, participants indicated that there were neither explicit policy guidelines defining community engagement nor pertinent evaluation metrics, despite awareness that community engagement is complex and under-researched. Examples of different approaches to community engagement ranged from vaccine imposition to empowered community vaccination decision-making. Finally, participants proposed an operational definition of community engagement and discussed concerns related to implementing it.

Conclusions
Although decision makers had different perceptions about what constitutes a community, and how community engagement should optimally function, the combined group articulated its importance to ensure vaccination equity and reiterated the need for concerted political will to build trust with communities. At the same time, work remains to be done both in terms of research on community engagement as well as development of appropriate implementation and outcome metrics.
Continuum of hepatitis C care cascade in prison and following release in the direct-acting antivirals era
Authors: Hariri Sanam , Sharafi Heidar , Sheikh Mahdi , Merat Shahin , Hashemi Farnaz , Azimian Fatemeh , Tamadoni Babak , Ramazani Rashid , Gouya Mohammad Mehdi , Abbasi Behzad , Tashakorian Mehrzad , Alasvand Ramin , Alavian Seyed Moayed , Poustchi Hossein , Malekzadeh Reza 
Published: October 2020

Abstract
Background
People with criminal justice involvement contribute remarkably to the rising hepatitis C virus (HCV) burden; however, the continuum of care is a major barrier to prison-based programs. We aimed to evaluate a comprehensive HCV care model in an Iranian provincial prison.

Methods
Between 2017–2018, in the Karaj Central Prison, newly admitted male inmates received HCV antibody testing and venipuncture for RNA testing (antibody-positive only). Participants with positive RNA underwent direct-acting antiviral (DAA) therapy (Sofosbuvir/Daclatasvir). Sustained virological response was evaluated at 12 weeks post-treatment (SVR12).

Results
Overall, from 3485 participants, 182 (5.2%) and 117 (3.4%) tested positive for HCV antibody and RNA, respectively. Among 116 patients who were eligible for treatment, 24% (n = 28) were released before treatment and 72% (n = 83) initiated DAA therapy, of whom 81% (n = 67/83) completed treatment in prison, and the rest were released. Of total released patients, 68% (n = 30/44) were linked to care in community, and 70% (n = 21/30) completed treatment, including 60% (n = 12/20) and 90% (n = 9/10) among those who were released before and during treatment, respectively. The overall HCV treatment uptake and completion were 89% (n = 103/116) and 85% (n = 88/103), respectively. From people who completed treatment, 43% (n = 38/88) attended for response assessment and all were cured (SVR12 = 100%).

Conclusions
Integrated HCV care models are highly effective and can be significantly strengthened by post-release interventions. The close collaboration of community and prison healthcare systems is crucial to promote high levels of treatment adherence. Future studies should investigate the predictors of engagement with HCV care following release.
The modifying role of physical activity in the cross-sectional and longitudinal association of health-related quality of life with physiological functioning-based latent classes and metabolic syndrome
Authors: Cerletti Paco , Keidel Dirk , Imboden Medea , Schindler Christian , Probst-Hensch Nicole 
Published: October 2020

AbstractBackgroundSingle cardio-metabolic risk factors are each known modifiable risk factors for adverse health and quality of life outcomes. Yet, evidence on the clustered effect of these parameters and the metabolic syndrome (MetS) on health-related quality of life (HRQoL) is still limited and mostly cross-sectional. The objectives of this study were to identify clusters of cardio-metabolic physiological functioning, to assess their associations with HRQoL in comparison with the MetS, to elucidate the modifying role of physical activity, and to assess differences in health service utilization.MethodsThis study is based on longitudinal data from two time points (2010/11 & 2017/18) of the Swiss Study on Air Pollution and Lung and Heart Diseases (SAPALDIA). Latent class analysis (LCA) grouped participants based on a priori selected cardio-metabolic and MetS related physiological functioning variables(Body mass index, body fat, glycated hemoglobin, blood triglycerides, blood pressure). The 36-item Short-Form Health Survey (SF-36) was used to assess HRQoL. Quantile regressions were performed with and without adjustment for physical activity, to detect independent associations of the latent classes, MetS and physical activity with HRQoL. To assess the modifying role of physical activity, we additionally grouped participants based on the combination of physical activity and latent classes or MetS, respectively. Logistic regressions were used to investigate health service utilization as outcome.ResultsThe LCA resulted in three classes labeled “Healthy” (30% of participants in 2017/18), “At risk” and “Unhealthy” (29%). The Unhealthy class scored lowest in all physical component scores of HRQoL. Compared to healthy and active participants, inactive participants in the “Unhealthy” class showed lower scores in the physical functioning domain both cross-sectionally (− 9.10 (− 12.02; − 6.18)) and longitudinally. This group had an odds ratio of 2.69 (1.52; 4.74) for being hospitalized in the previous 12 months.ConclusionsThese results point to subjects with adverse cardio-metabolic physiological functioning and low activity levels as an important target group for health promotion and maintenance of well-being. The promotion of physical activity at the early stages of aging seems pivotal to mitigate the impact of the MetS on HRQoL at higher age.
Medial humeral epicondylar lesions and discreet calcified structures in the canine elbow: radiographic description of 183 cases
Authors: Rørvik Arne Magnus , Trangerud Cathrine , Grondalen Jorunn 
Published: October 2020

Abstract
Background
In this 4-year prospective observational study, all elbows in a dysplasia screening program including 14,073 dogs were studied using radiographs in two projections. Elbows were evaluated for the presence of medial humeral epicondylar lesions or discreet calcified structures and were described as they appeared. The age, breed, and sex of affected dogs were recorded. The prevalence for each lesion was calculated exclusively on breeds where the number of radiographed dogs exceeded 500.

Results
Medial humeral epicondylar lesions or medial discreet calcified structures were diagnosed in 183 dogs and 211 elbows. The prevalence of true Flexor enthesopathy (FE) in this Norwegian population of mainly young, large breed dogs was calculated to be approximately 1.4 per 1000 dogs and varied by breed. Also, the prevalence of the other lesions varied considerably by breed. The most common finding was discreet calcified structures, termed medial ossified structures (MOS) (0.7%).
In elbows affected with fragmented medial epicondyles (FME) (0.07%) and especially FE (0.14%), the degree of periarticular new bone formation (PNBF) was increased when compared to unaffected elbows. In joints affected with MOSs or medial lucent lesions MLLs (0.25%), there was no difference in the presence or degree of PNBF compared to unaffected joints, even in older dogs.

Conclusions
The prevalence of medial humeral epicondylar lesions and MOSs differs considerably among dog breeds. Elbow joints with FMEs and particularly FE had a highly increased presence and degree of PNBF compared to joints without these lesions. Elbow joints with MOSs or MLLs did not have an increased presence or degree of PNBF compared to joints without these lesions.
The voltage-gated proton channel Hv1 contributes to neuronal injury and motor deficits in a mouse model of spinal cord injury
Authors: Murugan Madhuvika , Zheng Jiaying , Wu Gongxiong , Mogilevsky Rochelle , Zheng Xin , Hu Peiwen , Wu Junfang , Wu Long-Jun 
Published: October 2020

AbstractTraumatic injury to the spinal cord initiates a series of pathological cellular processes that exacerbate tissue damage at and beyond the original site of injury. This secondary damage includes oxidative stress and inflammatory cascades that can lead to further neuronal loss and motor deficits. Microglial activation is an essential component of these secondary signaling cascades. The voltage-gated proton channel, Hv1, functionally expressed in microglia has been implicated in microglia polarization and oxidative stress in ischemic stroke. Here, we investigate whether Hv1 mediates microglial/macrophage activation and aggravates secondary damage following spinal cord injury (SCI). Following contusion SCI, wild-type (WT) mice showed significant tissue damage, white matter damage and impaired motor recovery. However, mice lacking Hv1 (Hv1−/−) showed significant white matter sparing and improved motor recovery. The improved motor recovery in Hv1−/− mice was associated with decreased interleukin-1β, reactive oxygen/ nitrogen species production and reduced neuronal loss. Further, deficiency of Hv1 directly influenced microglia activation as noted by decrease in microglia numbers, soma size and reduced outward rectifier K+ current density in Hv1−/− mice compared to WT mice at 7 d following SCI. Our results therefore implicate that Hv1 may be a promising potential therapeutic target to alleviate secondary damage following SCI caused by microglia/macrophage activation.