bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using a machine learning approach to identify key prognostic molecules for esophageal squamous cell carcinoma
Authors: Li Meng-Xiang , Sun Xiao-Meng , Cheng Wei-Gang , Ruan Hao-Jie , Liu Ke , Chen Pan , Xu Hai-Jun , Gao She-Gan , Feng Xiao-Shan , Qi Yi-Jun 
Published: August 2021

Abstract
Background
A plethora of prognostic biomarkers for esophageal squamous cell carcinoma (ESCC) that have hitherto been reported are challenged with low reproducibility due to high molecular heterogeneity of ESCC. The purpose of this study was to identify the optimal biomarkers for ESCC using machine learning algorithms.

Methods
Biomarkers related to clinical survival, recurrence or therapeutic response of patients with ESCC were determined through literature database searching. Forty-eight biomarkers linked to recurrence or prognosis of ESCC were used to construct a molecular interaction network based on NetBox and then to identify the functional modules. Publicably available mRNA transcriptome data of ESCC downloaded from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) datasets included GSE53625 and TCGA-ESCC. Five machine learning algorithms, including logical regression (LR), support vector machine (SVM), artificial neural network (ANN), random forest (RF) and XGBoost, were used to develop classifiers for prognostic classification for feature selection. The area under ROC curve (AUC) was used to evaluate the performance of the prognostic classifiers. The importances of identified molecules were ranked by their occurrence frequencies in the prognostic classifiers. Kaplan-Meier survival analysis and log-rank test were performed to determine the statistical significance of overall survival.

Results
A total of 48 clinically proven molecules associated with ESCC progression were used to construct a molecular interaction network with 3 functional modules comprising 17 component molecules. The 131,071 prognostic classifiers using these 17 molecules were built for each machine learning algorithm. Using the occurrence frequencies in the prognostic classifiers with AUCs greater than the mean value of all 131,071 AUCs to rank importances of these 17 molecules, stratifin encoded by SFN was identified as the optimal prognostic biomarker for ESCC, whose performance was further validated in another 2 independent cohorts.

Conclusion
The occurrence frequencies across various feature selection approaches reflect the degree of clinical importance and stratifin is an optimal prognostic biomarker for ESCC.
Diagnostic possibility of the combination of exhaled nitric oxide and blood eosinophil count for eosinophilic asthma
Authors: Li Jiang-Hua , Han Rui , Wang Yu-Bo , Cheng Min , Chen Heng-Yi , Lei Wen-Hui , Li Li , Gao Chen , Zhao Na-Na , Nie Nai-Fu , Li Zhong-Yan , Yin Guo-Qing , Huang Shuai , He Yong 
Published: August 2021

Abstract
Background
Tests to identify reversible airflow limitation are important in asthma diagnosis, but they are time-consuming and it may be difficult for patients to cooperate. We aimed to evaluate whether the combination of fractional exhaled nitric oxide (FeNO) and blood eosinophil (B-Eos) can be used to distinguish some asthma patients who could avoid objective tests.

Methods
We conducted a retrospective cohort study on 7463 suspected asthma cases between January 2014 and December 2019 in Chongqing, China, and identified 2349 patients with complete FeNO, B-Eos count, and spirometry data. Asthma was diagnosed by clinicians by the criteria of recurrent respiratory symptoms and a positive bronchial-provocation or bronchodilation test (BPT, BPD). We evaluated the diagnostic accuracy of FeNO or B-Eos alone or both in combination for asthma using receiver operating characteristic (ROC) curve analysis.

Results
In this study, 824 patients were diagnosed with asthma. When FeNO and B-Eos counts were used in combination, the area under the ROC curve (AUC) for diagnosing asthma increased slightly (0.768 vs. 0.745 [FeNO] or 0.728 [B-Eos]; both P < 0.001). The odds ratio for having asthma increased progressively with a gradual increase in FeNO or B-Eos count (both P < 0.001; assessed using the Cochran–Armitage trend test). Further analysis of in-series combinations of different threshold values for these biomarkers indicated that moderately elevated biomarker levels (FeNO > 40 ppb and B-Eos > 300 cells/μl) support a diagnosis of asthma because diagnostic specificity was > 95% and the positive likelihood ratio (PLR) was > 10. This conclusion was verified when selecting the 2017–2019 data as the internal validation dataset.

Conclusion
FeNO or B-Eos count alone is insufficient to accurately diagnose asthma. Patients with moderately elevated biomarkers (FeNO > 40 ppb and B-Eos > 300 cells/μl) could be diagnosed with asthma and avoid objective tests when such tests are not feasible.
A model of integrated remote monitoring and behaviour change for osteoarthritis
Authors: Tack Christopher 
Published: August 2021

Abstract
Background
The National Institute for Health and Care Excellence recommends the use of digital and mobile health technologies to facilitate behaviour change interventions. Due to its high prevalence and dependence upon patient self-management strategies, osteoarthritis is one musculoskeletal condition which may benefit from such approaches. This is particularly pertinent due to the increasing use of remote monitoring technologies to collect patient data and facilitate self-management in individuals outside of hospital clinics. In practice however, application of digital behaviour change interventions is difficult due to insufficient reporting of behaviour change theories in the current literature. When digital technologies are employed to alter behaviour change in osteoarthritis, they often focus on physical activity. Currently, such interventions focus of self-efficacy but do not often explicitly report the behaviour change techniques they use to facilitate these changes.

Methods
This paper proposes a new model of integrating specific behaviour change principles (persuasive design) in an integrated model of remote monitoring and digital behaviour change interventions for osteoarthritis.

Results
There is potential to combine remote monitoring systems of patient data through digital and mobile technologies with behaviour change principles to improve physical activity behaviours in individuals with osteoarthritis. The use of persuasive design principles (e.g. prompts or nudges) through mobile notifications and strategic system design can be directed to enhance behaviour change. A validated measure of behaviour change, such as the patient activation measure, will allow effective evaluation of such systems.

Conclusions
Digital behaviour change interventions should be directed towards the underlying principles of behaviour change they employ, although this is not commonly reported in practice. Such interventions can be integrated within remote monitoring pathways using persuasive design techniques to enhance patient activation. This approach can enhance self-management in individuals with musculoskeletal conditions, such as osteoarthritis.
Protocol for the Weight-bearing in Ankle Fractures (WAX) trial: a multicentre prospective non-inferiority trial of early versus delayed weight-bearing after operatively managed ankle fracture
Authors: Bretherton C. P. , Claireaux H. A. , Achten J. , Athwal A. , Dutton S. J. , Peckham N. , Petrou S. , Kearney R. S. , Appelbe D. , Griffin X. L. 
Published: August 2021

AbstractBackgroundUnstable ankle fractures represent a substantial burden of disease, accounting for a mean hospital stay of nine days, a mean cost of £4,491 per patient and 20,000 operations per year. There is variation in UK practice around weight-bearing instructions after operatively managed ankle fracture. Early weight-bearing may reduce reliance on health services, time off work, and improve functional outcomes. However, concerns remain about the potential for complications such as implant failure. This is the protocol of a multicentre randomised non-inferiority clinical trial of weight-bearing following operatively treated ankle fracture.MethodsAdults aged 18 years and over who have been managed operatively for ankle fracture will be assessed for eligibility. Baseline function (Olerud and Molander Ankle Score [OMAS]), health-related quality of life (EQ-5D-5L), and complications will be collected after informed consent has been obtained. A randomisation sequence has been prepared by a trial statistician to allow for 1:1 allocation to receive either instruction to weight-bear as pain allows from the point of randomisation, two weeks after the time of surgery (‘early weight-bearing’ group) or to not weight-bear for a further four weeks (‘delayed weight -bearing’ group). All other treatment will be as per the guidance of the treating clinician.Participants will be asked about their weight-bearing status weekly until four weeks post-randomisation. At four weeks post-randomisation complications will be collected. At six weeks, four months, and 12 months post-randomisation, the OMAS, EQ-5D-5L, complications, physiotherapy input, and resource use will be collected. The primary outcome measure is ankle function (OMAS) at four months post-randomisation.A minimum of 436 participants will be recruited to obtain 80% power to detect a non-inferiority margin of -6 points on the OMAS 4 months post-randomisation. A within-trial health economic evaluation will be conducted to estimate the cost-effectiveness of the treatment options.DiscussionThe results of this study will inform national guidance with regards to the most clinically and cost-effective strategy for weight-bearing after surgery for unstable ankle fractures.Trial registrationISRCTN12883981, Registered 02 December 2019.
District health managers perspectives of introducing a new service: a qualitative study of the community-based newborn care programme in Ethiopia
Authors: Berhanu Della , Hashmi Iram , Schellenberg Joanna , Avan Bilal 
Published: August 2021

Abstract
Background
The planning, resourcing, implementation and monitoring of new programmes by district health managers is integral for success and sustainability. Ethiopia introduced the Community-Based Newborn Care programme in 2014 to improve newborn survival: an innovative component allowed community health workers to provide antibiotics for young infants with possible serious bacterial infection when referral was not possible. Informed by the World Health Organization health system building block framework, we aimed to study the capacity and operational challenges of introducing this new health service from the perspective of programme implementers and managers at the district level 20 months after programme initiation.

Methods
This qualitative study was part of a programme evaluation. From November to December of 2015, we conducted 28 semi-structured interviews with staff at district health offices, health centres and implementing Non-Governmental Organisations in 15 districts of four regions of Ethiopia. Verbatim transcripts were analysed using a priori and emerging themes.

Results
In line with the government's commitment to treat sick newborns close to their homes, participants reported that community health workers had been successfully trained to provide injectable antibiotics. However, the Community-Based Newborn Care programme was scaled up without allowing the health system to adapt to programme needs. There were inadequate processes and standards to ensure consistent availability of (1) trained staff for technical supervision, (2) antibiotics and (3) monitoring data specific to the programme. Furthermore, Non-Governmental Organizations played a central implementing role, which had implications for the long-term district level ownership and thus for the sustainability of the programme.

Conclusion
In settings where sustainable local implementation depends on district-level health teams, new programmes should assess health system preparedness to absorb the service, and plan accordingly. Our findings can inform policy makers and implementers about the pre-conditions for a health system to introduce similar services and maximize long-term success.
A survey of Italian cat owners’ attitudes towards cat vaccination through a web-based questionnaire
Authors: Filipe Joel Fernando Soares , Lauzi Stefania , Pina Lucrezia , Dall’Ara Paola 
Published: August 2021

Abstract
Background
Vaccination plays an important role in feline healthcare as it is the most effective measure for prevention against feline infectious diseases. Therefore, it is important to know owners’ opinion towards cats’ vaccination and current veterinary practices in order to advice owners on the use of the correct vaccination protocol.
This study aimed to investigate the proportion of cats regularly vaccinated and identify the main factors motivating cat owners’ decisions related to vaccination in Italy. A questionnaire was disseminated online (mainly via social networks) to collect data regarding Italian cat owners’ demographics, information about cats, factors regarding cats’ vaccination, and veterinary-owner relationship.

Results
A total of 1264 owners participated in the survey and 1247 questionnaires were completed and statistically analyzed. The majority (91%; n = 1131) of cats were vaccinated and 80% (n = 998) had been vaccinated within the last 3 years. Age of 2–4 years old cats and the acquisition from a breeder or cat shop were significantly associated with vaccination within the last 3 years. Cats vaccinated but not within the last 3 years were significantly associated with cat’s indoor lifestyle, cats’ age ≥ 5 years old and low annual household income. Importance of vaccination cost, low annual household income and owners’ job not related to healthcare was statistically associated with the lack of cat’s vaccination. In addition, 86% of the owners took their cat regularly to veterinary clinics. Veterinarians play a significant role in owners’ decision, and they are considered the most useful source of information about vaccination by 97% of owners.

Conclusions
The high number of recently vaccinated cats suggests owner’s attention towards feline vaccination and cat’s health. The importance of veterinarian’s advice along with the knowledge of factors associated to the unvaccinated status of cats may help veterinarians to grow owner’s confidence and increase prevention of feline infectious diseases.
However further investigations based on a more comprehensive sample of the general population are needed to confirm the results of this survey.
Screening and evaluation of the strong endogenous promoters in Pichia pastoris
Authors: Dou Weiwang , Zhu Quanchao , Zhang Meihua , Jia Zuyuan , Guan Wenjun 
Published: August 2021

Abstract
Background
Due to its ability to perform fast and high-density fermentation, Pichia pastoris is not only used as an excellent host for heterologous protein expression but also exhibits good potential for efficient biosynthesis of small-molecule compounds. However, basic research on P. pastoris lags far behind Saccharomyces cerevisiae, resulting in a lack of available biological elements. Especially, fewer strong endogenous promoter elements available for foreign protein expression or construction of biosynthetic pathways were carefully evaluated in P. pastoris. Thus, it will be necessary to identify more available endogenous promoters from P. pastoris.

Results
Based on RNA-seq and LacZ reporter system, eight strong endogenous promoters contributing to higher transcriptional expression levels and β-galactosidase activities in three frequently-used media were screened out. Among them, the transcriptional expression level contributed by P0019, P0107, P0230, P0392, or P0785 was basically unchanged during the logarithmic phase and stationary phase of growth. And the transcriptional level contributed by P0208 or P0627 exhibited a growth-dependent characteristic (a lower expression level during the logarithmic phase and a higher expression level during the stationary phase). After 60 h growth, the β-galactosidase activity contributed by P0208, P0627, P0019, P0407, P0392, P0230, P0785, or P0107 was relatively lower than PGAP but higher than PACT1. To evaluate the availability of these promoters, several of them were randomly applied to a heterogenous β-carotene biosynthetic pathway in P. pastoris, and the highest yield of β-carotene from these mutants was up to 1.07 mg/g. In addition, simultaneously using the same promoter multiple times could result in a notable competitive effect, which might significantly lower the transcriptional expression level of the target gene.

Conclusions
The novel strong endogenous promoter identified in this study adds to the number of promoter elements available in P. pastoris. And the competitive effect observed here suggests that a careful pre-evaluation is needed when simultaneously and multiply using the same promoter in one yeast strain. This work also provides an effective strategy to identify more novel biological elements for engineering applications in P. pastoris.
WD40 repeat 43 mediates cell survival, proliferation, migration and invasion via vimentin in colorectal cancer
Authors: Li Zijian , Feng Min , Zhang Jie , Wang Xingzhou , Xu En , Wang Chao , Lin Fengcen , Yang Zhi , Yu Heng , Guan Wenxian , Wang Hao 
Published: August 2021

Abstract
Background
WD40 repeat (WDR)43 is an RNA-binding protein that belongs to the WDR domain protein family. Its biological function is largely unclear, particularly in colorectal cancer (CRC).

Methods
In the present study, we searched the TCGA database and found the correlation between WDR43 and CRC. Subsequently, the high expression of WDR43 in human clinical samples of CRC was validated and we further examined the biological functions of it in CRC cells. Finally, we explored potential downstream proteins or pathways and established subcutaneous xenograft model to verify our findings.

Results
Immunohistochemistry of 16 patient specimens confirmed that the expression of WDR43 was elevated in CRC. WDR43 knockdown was shown to increase apoptosis and inhibit the proliferation, migration and invasion of CRC cells in vitro and reduce tumorigenesis in animal models. In addition, it was found that WDR43 knockdown inhibited vimentin (VIM) expression in CRC cells and overexpression of VIM can partially reverse the effects of WDR43 both in vitro and in vivo.

Conclusion
In conclusion, the role of WDR43 in the occurrence and development of CRC was investigated in the present study. WDR43 may serve as a valuable biomarker and provide new options for the diagnosis and treatment of colorectal cancer.
Trajectories of objectively measured physical activity and childhood overweight: longitudinal analysis of the IDEFICS/I.Family cohort
Authors: Sprengeler Ole , Pohlabeln Hermann , Bammann Karin , Buck Christoph , Lauria Fabio , Verbestel Vera , Eiben Gabriele , Konstabel Kenn , Molnár Dénes , Moreno Luis A. , Pitsiladis Yannis , Page Angie , Reisch Lucia , Tornaritis Michael , Ahrens Wolfgang 
Published: August 2021

Abstract
Background
Since only few longitudinal studies with appropriate study designs investigated the relationship between objectively measured physical activity (PA) and overweight, the degree PA can prevent excess weight gain in children, remains unclear. Moreover, evidence is limited on how childhood overweight determines PA during childhood. Therefore, we analyzed longitudinal trajectories of objectively measured PA and their bi-directional association with weight trajectories of children at 2- and 6-year follow-ups.

Methods
Longitudinal data of three subsequent measurements from the IDEFICS/I.Family cohort study were used to analyze the bi-directional association between moderate-to-vigorous PA (MVPA) and weight status by means of multilevel regression models. Analyses comprised 3393 (2-year follow-up) and 1899 (6-year follow-up) children aged 2–15.9 years from eight European countries with valid accelerometer data and body mass index (BMI) measurements. For categorized analyses, children’s weight status was categorized as normal weight or overweight (cutoff: 90th percentile of BMI) and children’s PA as (in-) sufficiently active (cutoffs: 30, 45 and 60 min of MVPA per day).

Results
Children engaging in at least 60 min MVPA daily at baseline and follow-ups had a lower odds of becoming overweight (odds ratio [OR] at 2-year follow-up: 0.546, 95% CI: 0.378, 0.789 and 6-year follow-up: 0.393, 95% CI: 0.242, 0.638), compared to less active children. Similar associations were found for 45 min MVPA daily. On the other side, children who became overweight had the lowest odds to achieve 45 or 60 min MVPA daily (ORs: 0.459 to 0.634), compared to normal weight children.

Conclusions
Bi-directional associations between MVPA and weight status were observed. In summary, at least 60 min MVPA are still recommended for the prevention of childhood overweight. To prevent excess weight gain, 45 min MVPA per day also showed preventive effects.
Fe3O4 magnetic nanoparticle-enhanced radiotherapy for lung adenocarcinoma via delivery of siBIRC5 and AS-ODN
Authors: Chen Shuzhen , Han Fushi , Huang Dongdong , Meng Jinqian , Chu Jiapeng , Wang Meng , Wang Peijun 
Published: August 2021

Abstract
Background
Radiotherapy is the mainstay treatment for lung adenocarcinoma, yet remains highly susceptible to resistance. Fe3O4 magnetic nanoparticles (MNPs) possess the ability to induce biological therapeutic effects. Herein, the current study set out to explore the effects of Fe3O4 MNPs on radiosensitivity of lung adenocarcinoma cells.

Methods
Fe3O4 MNPs loaded with both negatively-charged small interfering RNA against baculoviral IAP repeat containing 5 (siBIRC5) and oligodeoxynucleotide antisense (AS-ODN) to generate co-delivery NPs, followed by evaluation. Gel retardation assay was further performed to determine the binding ability of Fe3O4 MNPs to AS-ODN/siBIRC5. The radiosensitizing effect of NPs on lung adenocarcinoma cells was determined in the absence or the presence of NPs or radiotherapy. A549 and H460 tumor-bearing mice were established, where tumor tissues were subjected to immunohistochemistry.

Results
NPs were successfully prepared and characterized. BIRC5 expression levels were augmented in tissues of lung cancer patients. Fe3O4 MNPs enhanced the uptake of siBIRC5 and AS-ODN by lung adenocarcinoma cells. The presence of NPs under magnetic field reduced the BIRC5 expression and elevated the DR5 expression in lung adenocarcinoma cells. Lung adenocarcinoma cells treated with NPs exhibited inhibited tumor cell migration and increased DNA damage. After magnetic field treatment, tumors were better suppressed in the tumor-bearing mice treated with NPs, followed by radiotherapy.

Conclusion
Findings obtained in our study indicated that Fe3O4 MNPs-targeted delivery of siBIRC5 and AS-ODN enhances radiosensitivity, providing an innovative solution for the current clinically existing lung adenocarcinoma patients with radiotherapy resistance with a low risk of toxicity.