bluuebunny/crossref_metadata_2025_split huggingface dataset:
Malignant transformation of oral lichen planus: a retrospective study of 565 Japanese patients
Authors: Tsushima Fumihiko , Sakurai Jinkyo , Uesugi Atsushi , Oikawa Yu , Ohsako Toshimitsu , Mochizuki Yumi , Hirai Hideaki , Kayamori Kou , Harada Hiroyuki 
Published: June 2021

Abstract
Background
Oral lichen planus (OLP) is a chronic inflammatory oral mucosa disease that is recognized as an oral potentially malignant disorder. However, the potentially malignant nature of OLP remains unclear.

Methods
We designed this study to examine the demographic and clinical characteristics of patients with OLP and evaluate the associated malignant transformation rate. A total of 565 patients with a clinical and histopathological diagnosis of OLP who presented at our department between 2001 and 2017 were retrospectively studied. Patients who had clinical and histopathological features of oral lichenoid lesions (OLLs) classified as oral lichenoid contact lesions, oral lichenoid drug reactions and oral lichenoid lesions of graft-versus-host disease were excluded.

Results
The study population included 123 men and 442 women aged 21–93 years (mean ± standard deviation, 60.5 ± 11.8). The 565 patients were followed up for a duration of 55.9 ± 45.3 months, during which 4 (0.7%) patients developed squamous cell carcinoma (SCC). In three of these 4 patients who developed SCC, the clinical type of OLP was the red type.

Conclusions
Our results suggested that OLP was associated with a low risk of malignant transformation. We recommend regular follow-up for OLP patients and clear differentiation of oral epithelial dysplasia and OLLs to enable early detection of malignant transformation. Further investigation of the clinical risk factors associated with malignant transformation is necessary.
Empowering patient education on self-care activity among patients with colorectal cancer – a research protocol for a randomised trial
Authors: Tuominen Leena , Ritmala-Castrén Marita , Nikander Pia , Mäkelä Siru , Vahlberg Tero , Leino-Kilpi Helena 
Published: June 2021

Abstract
Background
Chemotherapy-induced side effects may have a negative effect on nutrition intake, thus increasing the risk of malnutrition and consequently, other serious complications for patients with cancer. The prevalence of malnutrition is common among patients with colorectal cancer. Nurse-led empowering education may have a positive effect on self-care activity in this patient group. Therefore, our purpose is to develop an empowering educational nursing intervention and test its effect on self-care activation and knowledge level among patients with colorectal cancer during chemotherapy. Secondary outcomes are quality of life and risk of malnutrition.

Methods
An interdisciplinary expert group developed a face-to-face empowering educational intervention using teach-back method. A two-arm, single-centre, superiority trial with stratified randomisation (1:1) and pre-post measures will be used to assess the effect of the intervention compared to standard care. Patients (N = 40 + 40) will be recruited in one university hospital outpatient clinic in Finland. Eligibility criteria are adult patients diagnosed with colorectal cancer starting oral fluoropyrimidine or combination chemotherapy treatment. A registered nurse experienced in oncology will deliver the intervention 2 weeks after the first chemotherapy. Outcomes are measured before intervention (M0) and after a two-month follow-up period (M1).

Discussion
This study will assess whether nurse-led empowering education using teach-back method is effective on self-care activity among patients with colorectal cancer. If the intervention has a positive effect, it may be implemented into patient education in a corresponding context.

Trial registration
ClinicalTrials.gov: NCT04160650 Registered 12 November 2019 - retrospectively registered
USP9X promotes apoptosis in cholangiocarcinoma by modulation expression of KIF1Bβ via deubiquitinating EGLN3
Authors: Chen Weiqian , Song Jingjing , Liu Siyu , Tang Bufu , Shen Lin , Zhu Jinyu , Fang Shiji , Wu Fazong , Zheng Liyun , Qiu Rongfang , Chen Chunmiao , Gao Yang , Tu Jianfei , Zhao Zhongwei , Ji Jiansong 
Published: June 2021

Abstract
Background
Cholangiocarcinoma represents the second most common primary liver malignancy. The incidence rate has constantly increased over the last decades. Cholangiocarcinoma silent nature limits early diagnosis and prevents efficient treatment.

Methods
Immunoblotting and immunohistochemistry were used to assess the expression profiling of USP9X and EGLN3 in cholangiocarcinoma patients. ShRNA was used to silence gene expression. Cell apoptosis, cell cycle, CCK8, clone formation, shRNA interference and xenograft mouse model were used to explore biological function of USP9X and EGLN3. The underlying molecular mechanism of USP9X in cholangiocarcinoma was determined by immunoblotting, co-immunoprecipitation and quantitative real time PCR (qPCR).

Results
Here we demonstrated that USP9X is downregulated in cholangiocarcinoma which contributes to tumorigenesis. The expression of USP9X in cholangiocarcinoma inhibited cell proliferation and colony formation in vitro as well as xenograft tumorigenicity in vivo. Clinical data demonstrated that expression levels of USP9X were positively correlated with favorable clinical outcomes. Mechanistic investigations further indicated that USP9X was involved in the deubiquitination of EGLN3, a member of 2-oxoglutarate and iron-dependent dioxygenases. USP9X elicited tumor suppressor role by preventing degradation of EGLN3. Importantly, knockdown of EGLN3 impaired USP9X-mediated suppression of proliferation. USP9X positively regulated the expression level of apoptosis pathway genes de through EGLN3 thus involved in apoptosis of cholangiocarcinoma.

Conclusion
These findings help to understand that USP9X alleviates the malignant potential of cholangiocarcinoma through upregulation of EGLN3. Consequently, we provide novel insight into that USP9X is a potential biomarker or serves as a therapeutic or diagnostic target for cholangiocarcinoma.
Refactoring of a synthetic raspberry ketone pathway with EcoFlex
Authors: Moore Simon J. , Hleba Yonek B. , Bischoff Sarah , Bell David , Polizzi Karen M. , Freemont Paul S. 
Published: June 2021

Abstract
Background
A key focus of synthetic biology is to develop microbial or cell-free based biobased routes to value-added chemicals such as fragrances. Originally, we developed the EcoFlex system, a Golden Gate toolkit, to study genes/pathways flexibly using Escherichia coli heterologous expression. In this current work, we sought to use EcoFlex to optimise a synthetic raspberry ketone biosynthetic pathway. Raspberry ketone is a high-value (~ £20,000 kg−1) fine chemical farmed from raspberry (Rubeus rubrum) fruit.

Results
By applying a synthetic biology led design-build-test-learn cycle approach, we refactor the raspberry ketone pathway from a low level of productivity (0.2 mg/L), to achieve a 65-fold (12.9 mg/L) improvement in production. We perform this optimisation at the prototype level (using microtiter plate cultures) with E. coli DH10β, as a routine cloning host. The use of E. coli DH10β facilitates the Golden Gate cloning process for the screening of combinatorial libraries. In addition, we also newly establish a novel colour-based phenotypic screen to identify productive clones quickly from solid/liquid culture.

Conclusions
Our findings provide a stable raspberry ketone pathway that relies upon a natural feedstock (L-tyrosine) and uses only constitutive promoters to control gene expression. In conclusion we demonstrate the capability of EcoFlex for fine-tuning a model fine chemical pathway and provide a range of newly characterised promoter tools gene expression in E. coli.
High-risk human papillomaviruses and Epstein–Barr virus in breast cancer in Lebanese women and their association with tumor grade: a molecular and tissue microarray study
Authors: Nagi Karim , Gupta Ishita , Jurdi Nawaf , Jabeen Ayesha , Yasmeen Amber , Batist Gerald , Vranic Semir , Al-Moustafa Ala-Eddin 
Published: June 2021

Abstract
Background
High-risk human papillomaviruses (HPVs) are present and can cooperate with Epstein–Barr virus (EBV) to initiate and/or enhance the progression of several types of human carcinomas including cervical as well as head and neck; in parallel, it has been recently pointed out that these oncoviruses can be detected in human breast cancers. Thus, we herein explored the presence/co-presence of high-risk HPVs and EBV in breast cancer in Lebanese women.

Methods
A cohort of 102 breast cancer samples and 14 normal breast tissues were assessed for the presence of HPVs and EBV. Polymerase chain reaction (PCR) and immunohistochemistry (IHC) analysis in addition to tissue microarray (TMA) platform were used in this study.

Results
We found the presence of HPV in 66/102 (65%) of our samples, while EBV is present in 41/102 (40%) of the cohort. Additionally, our data showed that high-risk HPV types (52, 35, 58, 45, 16 and 51) are the most frequent in breast cancer in Lebanese women. Meanwhile, we report that high-risk HPVs and EBV are co-present in 30/102 (29%) of the samples; more significantly, our results indicate that their co-presence is associated with tumor grade (p = 0.03).

Conclusion
Our data revealed that HPVs and EBV are present/co-present in human breast cancer where they may play an important role in its development and/or progression; thus, we believe that further investigations are essential to confirm and elucidate the presence/co-presence of these oncoviruses and the underlying mechanisms of their interaction in breast carcinogenesis.
Experts prioritize osteoarthritis non-surgical interventions from Cochrane systematic reviews for translation into “Evidence4Equity” summaries
Authors: Houlding-Braunberger Elizabeth , Petkovic Jennifer , Lebel Nicholas , Tugwell Peter 
Published: June 2021

Abstract
Objective
Osteoarthritis generates substantial health and socioeconomic burden, which is particularly marked in marginalized groups. It is imperative that practitioners have ready access to summaries of evidence-based interventions for osteoarthritis that incorporate equity considerations. Summaries of systematic reviews can provide this. The present study surveyed experts to prioritize a selection ofinterventions, from which equity focused summaries will be generated. Specifically, the prioritized interventions will be developed into Cochrane Evidence4Equity (E4E) summaries.

Methods
Twenty-seven systematic reviews of OA interventions were found. From these, twenty-nine non-surgical treatments for osteoarthritis were identified, based on statistically significant findings for desired outcome variables or adverse events. Key findings from these studies were summarised and provided to 9 experts in the field of osteoarthritis.. Expert participants were asked to rate interventions based on feasibility, health system effects, universality, impact on inequities, and priority for translation into equity based E4E summaries. Expert participants were also encouraged to make comments to provide context for each rating. Free text responses were coded inductively and grouped into subthemes and themes.

Results
Expert participants rated the intervention home land-based exercise for knee OA highest for priority for translation into an E4E summaries, followed by the interventions individual land-based exercise for knee OA, class land-based exercise for knee OA, exercise for hand OA and land-based exercise for hip OA. Upon qualitative analysis of the expert participants’ comments, fifteen subthemes were identified and grouped into three overall themes: (1) this intervention or an aspect of this intervention is unnecessary or unsafe; (2) this intervention or an aspect of this intervention may increase health inequities; and (3) experts noted difficulties completing rating exercise.

Conclusion
The list of priority interventions and corresponding expert commentary generated information that will be used to direct and support knowledge translation efforts.
Macrophage biomimetic nanocarriers for anti-inflammation and targeted antiviral treatment in COVID-19
Authors: Tan Qingqin , He Lingjie , Meng Xiaojun , Wang Wei , Pan Hudan , Yin Weiguo , Zhu Tianchuan , Huang Xi , Shan Hong 
Published: June 2021

AbstractBackgroundThe worldwide pandemic of COVID-19 remains a serious public health menace as the lack of efficacious treatments. Cytokine storm syndrome (CSS) characterized with elevated inflammation and multi-organs failure is closely correlated with the bad outcome of COVID-19. Hence, inhibit the process of CSS by controlling excessive inflammation is considered one of the most promising ways for COVID-19 treatment.ResultsHere, we developed a biomimetic nanocarrier based drug delivery system against COVID-19 via anti-inflammation and antiviral treatment simultaneously. Firstly, lopinavir (LPV) as model antiviral drug was loaded in the polymeric nanoparticles (PLGA-LPV NPs). Afterwards, macrophage membranes were coated on the PLGA-LPV NPs to constitute drugs loaded macrophage biomimetic nanocarriers (PLGA-LPV@M). In the study, PLGA-LPV@M could neutralize multiple proinflammatory cytokines and effectively suppress the activation of macrophages and neutrophils. Furthermore, the formation of NETs induced by COVID-19 patients serum could be reduced by PLGA-LPV@M as well. In a mouse model of coronavirus infection, PLGA-LPV@M exhibited significant targeted ability to inflammation sites, and superior therapeutic efficacy in inflammation alleviation and tissues viral loads reduction.ConclusionCollectively, such macrophage biomimetic nanocarriers based drug delivery system showed favorable anti-inflammation and targeted antiviral effects, which may possess a comprehensive therapeutic value in COVID-19 treatment.
The prevalence of multimorbidity and its association with physical activity and sleep duration in middle aged and elderly adults: a longitudinal analysis from China
Authors: He Li , Biddle Stuart J. H. , Lee John Tayu , Duolikun Nadila , Zhang Lin , Wang Zijie , Zhao Yang 
Published: June 2021

Abstract
Background
Preventing chronic disease is important in health policy in countries with significantly ageing populations. This study aims to examine the prevalence of chronic disease multimorbidity and its association with physical activity and sleep duration; and to understand whether physical activity modifies associations between sleep duration and multimorbidity.

Methods
We utilized longitudinal data of a nationally-representative sample from the China Health and Retirement Longitudinal Study (in year 2011 and 2015; N = 5321; 54.7% female; age ≥ 45 years old). Fourteen chronic diseases were used to measure multimorbidity (ten self-reported, and four by blood test). Participants were grouped into high, moderate, and low level based on self-reported frequencies and durations of physical activity with different intensities for at least 10 min at a time in a usual week. Poor and good sleepers were categorized according to average hours of actual sleep at each night during the past month. Panel data method of random-effects logistic regression model was applied to estimate the association of physical activity and sleep with multimorbidity, adjusting for social-demographic and behavioural confounders.

Results
From 2011 to 2015, the prevalence of multimorbidity increased from 52.2 to 62.8%. In 2015, the proportion of participants engaging in high, moderate, and low level of physical activity was 30.3, 24.4 and 45.3%, respectively, and 63.6% of adults had good sleep. For both genders, compared with good sleep, poor sleep was associated with higher odds of multimorbidity (OR = 1.527, 95% CI: 1.277, 1.825). Compared to the high-level group, participants with a low level of physical activity were significantly more likely to have multimorbidity (OR = 1.457, 95% CI: 1.277, 1.825), but associations were stronger among women. The relative excess risk due to interaction between poor sleep and moderate or low physical activity was positive but non-significant on multimorbidity.

Conclusions
The burden of multimorbidity was high in China. Low physical activity and poor sleep was independently and significantly associated with a higher likelihood of multimorbidity in women and both genders, separately. Physical activity could modify the association between sleep and multimorbidity.
Radiomic signature of the FOWARC trial predicts pathological response to neoadjuvant treatment in rectal cancer
Authors: Zhuang Zhuokai , Liu Zongchao , Li Juan , Wang Xiaolin , Xie Peiyi , Xiong Fei , Hu Jiancong , Meng Xiaochun , Huang Meijin , Deng Yanhong , Lan Ping , Yu Huichuan , Luo Yanxin 
Published: June 2021

Abstract
Background
We aimed to develop a radiomic model based on pre-treatment computed tomography (CT) to predict the pathological complete response (pCR) in patients with rectal cancer after neoadjuvant treatment and tried to integrate our model with magnetic resonance imaging (MRI)-based radiomic signature.

Methods
This was a secondary analysis of the FOWARC randomized controlled trial. Radiomic features were extracted from pre-treatment portal venous-phase contrast-enhanced CT images of 177 patients with rectal cancer. Patients were randomly allocated to the primary and validation cohort. The least absolute shrinkage and selection operator regression was applied to select predictive features to build a radiomic signature for pCR prediction (rad-score). This CT-based rad-score was integrated with clinicopathological variables using gradient boosting machine (GBM) or MRI-based rad-score to construct comprehensive models for pCR prediction. The performance of CT-based model was evaluated and compared by receiver operator characteristic (ROC) curve analysis. The LR (likelihood ratio) test and AIC (Akaike information criterion) were applied to compare CT-based rad-score, MRI-based rad-score and the combined rad-score.

Results
We developed a CT-based rad-score for pCR prediction and a gradient boosting machine (GBM) model was built after clinicopathological variables were incorporated, with improved AUCs of 0.997 [95% CI 0.990–1.000] and 0.822 [95% CI 0.649–0.995] in the primary and validation cohort, respectively. Moreover, we constructed a combined model of CT- and MRI-based radiomic signatures that achieve better AIC (75.49 vs. 81.34 vs.82.39) than CT-based rad-score (P = 0.005) and MRI-based rad-score (P = 0.003) alone did.

Conclusions
The CT-based radiomic models we constructed may provide a useful and reliable tool to predict pCR after neoadjuvant treatment, identify patients that are appropriate for a 'watch and wait' approach, and thus avoid overtreatment. Moreover, the CT-based radiomic signature may add predictive value to the MRI-based models for clinical decision making.
Uncharted waters: mesenchymal stem cell treatment for pediatric refractory rheumatic diseases; a single center case series
Authors: Wong Stephen C. , Medrano Leah C. , Hoftman Alice D. , Jones Olcay Y. , McCurdy Deborah K. 
Published: June 2021

Abstract
Background
With the advent of innovative therapies including biologics and Janus kinase inhibitors, children with rheumatic diseases are more likely to have improved outcomes. Despite these advances, some children do not respond, or they, or their parents fear adverse events and seek other alternatives. Increasingly, private companies are offering mesenchymal stem cells (MSC) as an alternative, which are described as natural therapies for rheumatic diseases, often insinuating them as a cure. MSC have immunomodulatory properties, and transplantation of these stem cells have been used to successfully treat immunologic conditions like graft-versus-host disease. Lately, MSC research in adult lupus has been encouraging, but the clinical trials are still underway and in most, MSC therapy is not a standalone treatment. This retrospective case series will highlight three cases of pediatric refractory autoimmune disease whose parents sought out and received MSC therapy as a self-decision without first seeking medical advice from our specialty. The three families felt that their children were improved and in two believed that their child was cured. MSC have the potential of beneficial immunomodulation and may be a powerful tool in the therapy of rheumatic disease, but well controlled clinical trials are necessary and should be designed and monitored by experts in childhood rheumatic disease.

Case presentation
Three children with three different rheumatic diseases; systemic lupus erythematosus, mixed connective tissue disease and juvenile idiopathic arthritis were under the care of pediatric rheumatology at a large, tertiary-care, teaching institution. Multiple non-biologic and biologic disease-modifying anti-rheumatic drugs failed to significantly decrease disease activity, and as a result, the families chose to undergo MSC therapy. After transplantation, all children improved per patient and parent report and tapered off conventional immunosuppressive drugs. No serious adverse events occurred in these three patients.

Conclusion
The three cases presented in this report reflect comparable beneficial outcomes and minimal risks published in adult studies. These were not controlled studies, however, and benefit was reported rather than documented. These cases suggest that MSC transplantation may prove a promising adjunctive treatment option; however, further research, development of standardized infusion therapy protocols, and well-designed monitored clinical trials are essential.
Enhancing organizational readiness for implementation: constructing a typology of readiness-development strategies using a modified Delphi process
Authors: Vax Sigal , Farkas Marianne , Russinova Zlatka , Mueser Kim T. , Drainoni Mari-Lynn 
Published: June 2021

AbstractBackgroundKnowledge about the development of organizational readiness for implementation (ORI) is limited. ORI, referred to as the willingness and capacity of all relevant stakeholders to change practice, is critical for increasing the adoption rate of evidence-based practices and improving implementation outcomes. However, no methodology currently guides ORI’s enhancement or addresses differences in readiness needs across an organization. This study used the transtheoretical model (TTM) as a framework for classifying a well-established compilation of implementation strategies into three readiness stages: pre-contemplation, contemplation, and preparation.MethodsA modified Delphi method was used to establish consensus among a panel of purposefully selected research and field implementation experts. The Delphi process involved three rounds of online questionnaires. The third round also included a live video discussion to clarify definitions in an effort to increase consensus among experts.ResultsOf the 73 strategies reviewed, the experts identified 75% (n= 55) as relevant for pre-implementation and reached a high-level agreement on the assignment of 7% (n= 5) of the strategies to the pre-contemplation stage (ORI-1), 25% (n= 18) to the contemplation stage (ORI-2), and 52% (n= 38) to the preparation stage (ORI-3). Several strategies were identified as relevant to more than one stage.ConclusionsParticipating experts were able to reach high-level agreement on the relevance of specific sets of implementation strategies to each of the three ORI stages. The lowest number of strategies was assigned to ORI-1 and the highest number to ORI-3. Given the overlap of strategies across ORI stages, there is a need to better understand the specific utilization of such strategies at different stages. Future studies are needed to empirically evaluate the relevance and applicability of this expert-informed typology based on implementers’ experiences in the field.