bluuebunny/crossref_metadata_2025_split huggingface dataset:
A systematic review of evidence-based practice implementation in drug and alcohol settings: applying the consolidated framework for implementation research framework
Authors: Louie Eva , Barrett Emma L. , Baillie Andrew , Haber Paul , Morley Kirsten C. 
Published: March 2021

Abstract
Background
There is a paucity of translational research programmes to improve implementation of evidence-based care in drug and alcohol settings. This systematic review aimed to provide a synthesis and evaluation of the effectiveness of implementation programmes of treatment for patients with drug and alcohol problems using the Consolidated Framework for Implementation Research (CFIR).

Methods
A comprehensive systematic review was conducted using five online databases (from inception onwards). Eligible studies included clinical trials and observational studies evaluating strategies used to implement evidence-based psychosocial treatments for alcohol and substance use disorders. Extracted data were qualitatively synthesised for common themes according to the CFIR. Primary outcomes included the implementation, service system or clinical practice. Risk of bias of individual studies was appraised using appropriate tools. A protocol was registered with (PROSPERO) (CRD42019123812) and published previously (Louie et al. Systematic 9:2020).

Results
Of the 2965 references identified, twenty studies were included in this review. Implementation research has employed a wide range of strategies to train clinicians in a few key evidence-based approaches to treatment. Implementation strategies were informed by a range of theories, with only two studies using an implementation framework (Baer et al. J Substance Abuse Treatment 37:191-202, 2009) used Context-Tailored Training and Helseth et al. J Substance Abuse Treatment 95:26-34, 2018) used the CFIR). Thirty of the 36 subdomains of the CFIR were evaluated by included studies, but the majority were concerned with the Characteristics of Individuals domain (75%), with less than half measuring Intervention Characteristics (45%) and Inner Setting constructs (25%), and only one study measuring the Outer Setting and Process domains. The most common primary outcome was the effectiveness of implementation strategies on treatment fidelity. Although several studies found clinician characteristics influenced the implementation outcome (40%) and many obtained clinical outcomes (40%), only five studies measured service system outcomes and only four studies evaluated the implementation.

Conclusions
While research has begun to accumulate in domains such as Characteristics of Individuals and Intervention Characteristics (e.g. education, beliefs and attitudes and organisational openness to new techniques), this review has identified significant gaps in the remaining CFIR domains including organisational factors, external forces and factors related to the process of the implementation itself. Findings of the review highlight important areas for future research and the utility of applying comprehensive implementation frameworks.
Combining losartan with radiotherapy increases tumor control and inhibits lung metastases from a HER2/neu-positive orthotopic breast cancer model
Authors: Li Wende , Li Sen , Chen Ivy X. , Liu Yujiao , Ramjiawan Rakesh R. , Leung Chi-Ho , Gerweck Leo E. , Fukumura Dai , Loeffler Jay S. , Jain Rakesh K. , Duda Dan G. , Huang Peigen 
Published: March 2021

Abstract
Background
Patients with metastatic HER2/neu-positive (HER2/neu +) breast cancer (BC) often experience treatment resistance, disease recurrences and metastases. Thus, new approaches for improving the treatment of HER2/neu + BC to prevent metastatic dissemination are urgently needed. Our previous studies have shown that losartan, an angiotensin receptor blocker, increases tumor perfusion and decreases hypoxia in a number of tumor models. Hypoxia reduces the efficacy of radiation and increases metastases. We therefore hypothesized that by modifying tumor stroma and increasing oxygenation, losartan will improve the outcome of radiotherapy and inhibit disease progression in a highly metastatic HER2/neu + murine BC model.

Methods
We established a metastatic HER2/neu + murine BC line (MCa-M3C) and used it to generate mammary fat pad isografts in syngeneic female FVB/N mice. Starting on day 3 after orthotopic tumor implantation, we administered a 7-day losartan treatment (40 mg/kg BW, gavage daily); or a 7-day losartan treatment followed by 20 Gy single dose local irradiation (S-IR) on day 10 (tumor size ~ 100 mm3), or 20 Gy local fractionated (5 × 4 Gy daily) irradiation (F-IR) on days 10–14. We analyzed tumor-growth delay (TGD), development of spontaneous lung metastases, animal survival, tumor vascular density, and tumor hypoxia.

Results
Treatments with S-IR, F-IR, Losartan + S-IR, or Losartan + F-IR resulted in a significantly increased TGD (8–16 days) in MCa-M3C tumors versus controls. However, the combination of Losartan + S-IR and Losartan + F-IR further enhanced tumor response to radiation alone by increasing TGD an additional 5 to 8 days for both single and fractionated dose irradiation (P < 0.01), decreasing lung metastasis (Losartan + IR vs. Control, P < 0.025), and increasing animal survival (Losartan + IR vs. Control, P = 0.0303). In addition, losartan treatment significantly increased tumor vascularity (P = 0.0314) and decreased pimonidazole positive (hypoxic) area (P = 0.0002).

Conclusions
Combining losartan with local irradiation significantly enhanced tumor response, at least in part via reduced tumor hypoxia presumably due to increased tumor perfusion. Our findings suggest that combining losartan with radiotherapy is a potential new treatment strategy for local control and inhibiting metastasis in HER2 + BC.
Survivorship and prognostic factors for pleomorphic liposarcoma: a population-based study
Authors: Wan Lu , Tu Chao , Qi Lin , Li Zhihong 
Published: March 2021

Abstract
Background
Pleomorphic liposarcoma is the least common but most aggressive subtype of liposarcoma. Very few studies have presented data on pleomorphic liposarcoma specifically, often including a limited number of cases and short-term follow-up. As a result, the survivorship and prognostic characteristics of this tumor remain incompletely identified.

Study design and setting
Cross-sectional analysis of the Surveillance Epidemiology and End Results database (1996–2015).

Results
Overall survival for the entire series was 54% (95% confidence interval [CI], 49–58%) and 40% (95% CI, 35–45%) at 5 and 10 years, respectively. Disease-specific survival for the entire series was 60% (95% CI, 56–65%) and 53% (95% CI, 48–58%) at 5 and 10 years, respectively. Patients who survived 10 years or more were more likely to die of events unrelated to pleomorphic liposarcoma. Univariate and multivariate analysis demonstrated that not receiving cancer-directed surgery was an independent poor prognostic factor. Older age (≥ 65 years old) was associated with worse overall survival but not disease-specific survival. Tumor stage and radiotherapy showed different impact on survival depending on tumor size. In comparison to localized staged tumors, regional stage only predicts poor survival in patients with tumor size less than 5 cm, while distant stage is an independent worse prognosis factor. Radiotherapy only benefits patients with tumor size larger than 10 cm. These results were confirmed in competing risk analysis.

Conclusion
Survival rates of patients with pleomorphic liposarcoma has not changed over the past 20 years. Patients with distant stage have poor prognosis; regional stage indicates worse survival in patients with tumor size less than 5 cm. Receiving surgery could prolong the survival, while radiotherapy only benefits patients with large tumor size (> 10 cm). Older age is associated with poor overall survival but not disease-specific survival. Routine patient surveillance following initial diagnosis should at least be 10 years for pleomorphic liposarcoma.
Pluripotent stem cell-derived models of neurological diseases reveal early transcriptional heterogeneity
Authors: Sorek Matan , Oweis Walaa , Nissim-Rafinia Malka , Maman Moria , Simon Shahar , Hession Cynthia C. , Adiconis Xian , Simmons Sean K. , Sanjana Neville E. , Shi Xi , Lu Congyi , Pan Jen Q. , Xu Xiaohong , Pouladi Mahmoud A. , Ellerby Lisa M. , Zhang Feng , Levin Joshua Z. , Meshorer Eran 
Published: March 2021

Abstract
Background
Many neurodegenerative diseases develop only later in life, when cells in the nervous system lose their structure or function. In many forms of neurodegenerative diseases, this late-onset phenomenon remains largely unexplained.

Results
Analyzing single-cell RNA sequencing from Alzheimer’s disease (AD) and Huntington’s disease (HD) patients, we find increased transcriptional heterogeneity in disease-state neurons. We hypothesize that transcriptional heterogeneity precedes neurodegenerative disease pathologies. To test this idea experimentally, we use juvenile forms (72Q; 180Q) of HD iPSCs, differentiate them into committed neuronal progenitors, and obtain single-cell expression profiles. We show a global increase in gene expression variability in HD. Autophagy genes become more stable, while energy and actin-related genes become more variable in the mutant cells. Knocking down several differentially variable genes results in increased aggregate formation, a pathology associated with HD. We further validate the increased transcriptional heterogeneity in CHD8+/− cells, a model for autism spectrum disorder.

Conclusions
Overall, our results suggest that although neurodegenerative diseases develop over time, transcriptional regulation imbalance is present already at very early developmental stages. Therefore, an intervention aimed at this early phenotype may be of high diagnostic value.
Treating to target in psoriatic arthritis: assessing real-world outcomes and optimising therapeutic strategy for adults with psoriatic arthritis—study protocol for the MONITOR-PsA study, a trials within cohorts study design
Authors: Rombach Ines , Tillett William , Jadon Deepak , Tucker Laura , Watson Marion , Francis Anne , Sinomati Yvonne , Eldridge Lucy , Dritsaki Melina , Dutton Susan J. , Al-Mossawi Hussein , Gullick Nicola , Thompson Ben , Coates Laura C. 
Published: March 2021

AbstractBackgroundThe Tight Control of psoriatic arthritis (TICOPA) trial confirmed improved clinical outcomes with a treat to target (T2T) strategy in psoriatic arthritis (PsA). This consisted of 4-weekly review and escalation of ‘step up’ therapy (single disease modifying therapy (DMARD), combination DMARDs and then biologics) based on remission criteria. Based on this, a T2T approach is supported by European PsA treatment recommendations. However, it is not commonly implemented in routine care primarily due to feasibility and cost concerns. In the TICOPA trial, the same treatment regime was used for all participants regardless of their disease profile. Despite the recognition of PsA as a highly heterogeneous condition, no studies have tailored which drugs are used depending on disease severity. The cohort will establish real world outcomes for the T2T approach in PsA and also form the basis of a trials within cohorts (TWiCs) design to test alternative therapeutic approaches within embedded clinical trials providing an evidence base for treatment strategy in PsA.MethodsThe Multicentre Observational Initiative in Treat to target Outcomes in Psoriatic Arthritis (MONITOR-PsA) cohort will apply a T2T approach within routine care. It will recruit newly diagnosed adult patients with PsA starting systemic therapies. The cohort is observational allowing routine therapeutic care within NHS clinics but a T2T approach will be supported when monitoring treatment within the cohort. Eligible participants will be adults (≥18 years) with active PsA with ≥ 1 tender or swollen joints or enthesis who have not previously had treatment with DMARDs for articular disease.DiscussionThis study is the first TWiC designed to support a fully powered randomised drug trial. The results from the observational cohort will be compared with those observed in the TICOPA trial investigating the clinical effectiveness and health care costs of the pragmatic T2T approach. Nested trials will provide definitive RCT evidence establishing the optimal management of PsA within the T2T approach. The TWiCs design allows robust generalizability to routine healthcare, avoids disappointment bias, aids recruitment and in future will allow assessment of longer-term outcomes.Trial registrationClinicalTrials.govNCT03531073. Retrospectively registered on 21 May 2018.
The comparative effect of exposure to various risk factors on the risk of hyperuricaemia: diet has a weak causal effect
Authors: Topless Ruth K. G. , Major Tanya J. , Florez Jose C. , Hirschhorn Joel N. , Cadzow Murray , Dalbeth Nicola , Stamp Lisa K. , Wilcox Philip L. , Reynolds Richard J. , Cole Joanne B. , Merriman Tony R. 
Published: March 2021

Abstract
Background
Prevention of hyperuricaemia (HU) is critical to the prevention of gout. Understanding causal relationships and relative contributions of various risk factors to hyperuricemia is therefore important in the prevention of gout. Here, we use attributable fraction to compare the relative contribution of genetic, dietary, urate-lowering therapy (ULT) and other exposures to HU. We use Mendelian randomisation to test for the causality of diet in urate levels.

Methods
Four European-ancestry sample sets, three from the general population (n = 419,060) and one of people with gout (n = 6781) were derived from the Database of Genotypes and Phenotypes (ARIC, FHS, CARDIA, CHS) and UK Biobank. Dichotomised exposures to diet, genetic risk variants, BMI, alcohol, diuretic treatment, sex and age were used to calculate adjusted population and average attributable fractions (PAF/AAF) for HU (≥0.42 mmol/L [≥7 mg/dL]). Exposure to ULT was also assessed in the gout cohort. Two sample Mendelian randomisation was done in the UK Biobank using dietary pattern-associated genetic variants as exposure and serum urate levels as outcome.

Results
Adherence to dietary recommendations, BMI (< 25 kg/m2), and absence of the SLC2A9 rs12498742 urate-raising allele produced PAFs for HU of 20 to 24%, 59 to 69%, and 57 to 64%, respectively, in the three non-gout cohorts. In the gout cohort, diet, BMI, SLC2A9 rs12498742 and ULT PAFs for HU were 12%, 49%, 48%, and 63%, respectively. Mendelian randomisation demonstrated weak causal effects of four dietary habits on serum urate levels (e.g. preferentially drinking skim milk increased urate, β = 0.047 mmol/L, P = 3.78 × 10−8). These effects were mediated by BMI, and they were not significant (P ≥ 0.06) in multivariable models assessing the BMI-independent effect of diet on urate.

Conclusions
Diet has a relatively minor role in determining serum urate levels and HU. In gout, the use of ULT was the largest attributable fraction tested for HU.
Visit-to-visit variability of serum uric acid measurements and the risk of all-cause mortality in the general population
Authors: Tian Xue , Wang Anxin , Zuo Yingting , Chen Shuohua , Zhang Licheng , Wu Shouling , Luo Yanxia 
Published: March 2021

Abstract
Background
Evidence on longitudinal variability of serum uric acid (SUA) and risk of all-cause mortality in the general population is limited, as many prior studies focused on a single measurement of SUA.

Methods
A total of 53,956 participants in the Kailuan study who underwent three health examinations during 2006 to 2010 were enrolled. Variability of SUA was measured using the coefficient of variation (primary index), standard deviation, average real variability, and variability independent of the mean. Cox proportional hazard regressions were used to calculate the hazard ratio (HR) and 95% confidence interval (CI) for the association of variability of SUA with subsequent risk of all-cause mortality, considering its magnitude and the direction and across different baseline SUA categories.

Results
Over a median follow-up of 7.04 years, 2728 participants died. The highest variability of SUA was associated with an increased risk of all-cause mortality, the HR was 1.33 (95% CI, 1.20–1.49) compared with the lowest variability. In this group, both a large fall (HR, 1.28; 95% CI, 1.14–1.44) and rise (HR, 1.18; 95% 1.05–1.32) in SUA were related to risk of all-cause mortality. These associations were similar across different baseline SUA categories. Consistent results were observed in alternative measures of SUA variability. Moreover, individuals with higher variability in SUA were more related to common risk factors than those with stable SUA.

Conclusions
Higher variability in SUA was independently associated with the risk of all-cause mortality irrespective of baseline SUA and direction of variability in the general population.
The effects of WeChat-based educational intervention in patients with ankylosing spondylitis: a randomized controlled trial
Authors: Song Yuqing , Xie Xia , Chen Yanling , Wang Ying , Yang Hui , Nie Anliu , Chen Hong 
Published: March 2021

Abstract
Background
Ankylosing spondylitis (AS), as a common inflammatory rheumatic disease, often causes depression and impaired health-related quality of life (QoL). Although positive effects of patient education have been demonstrated, limited studies explored the benefits of education via mobile applications for AS patients. This study aimed to evaluate the effects of the WeChat-based educational intervention on depression, health-related QoL, and other clinical outcomes in AS patients.

Methods
We conducted a single-blind randomized controlled trial from March to December 2017. Patients were recruited and randomized into the intervention group which received a 12-week WeChat-based educational intervention (consisting of four individual online educational sessions, online educational materials) or the control group receiving standard care. Data was collected at baseline and 12 weeks. Outcomes were measured by Beck Depression Inventory-II, the Medical Outcomes Study Short Form 36-item Health Survey (SF-36), Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Patient Global Score (BAS-G), and visual analog scales.

Results
A total of 118 patients with AS were included and analyzed. Measures at baseline were comparable between groups. After the intervention, the intervention group reported significant higher scores of all domains of SF-36 except for physical functioning and validity, compared with the control group. Additionally, patients in the intervention group had lower depressive symptoms than the control group. No significant difference in other outcomes was observed at 12 weeks.

Conclusions
This study found that the 12-week educational intervention via WeChat had positive effects on reducing depressive symptoms and improving health-related QoL in Chinese patients with AS. We suggest that this intervention can be integrated into current routine care of AS patients.

Trial registration
This study has been approved by the hospital’s ethics committee (ID: 20160364) in 2016 and registered at the Chinese Clinical Trial Registry (registry number: ChiCTR-IPR-16009293).
Effects of combining diaphragm training with electrical stimulation on pain, function, and balance in athletes with chronic low back pain: a randomized clinical trial
Authors: Otadi Khadijeh , Nakhostin Ansari Noureddin , Sharify Shahriar , Fakhari Zahra , Sarafraz Hadi , Aria Amir , Rasouli Omid 
Published: March 2021

Abstract
Background
It is unknown how diaphragm training combined with electrical stimulation affects pain, function, static stability, and balance in athletes with chronic low back pain (CLBP). This study aimed to explore the effects of combining diaphragm training with electrical stimulation on pain, function, static stability, and dynamic balance in athletes with nonspecific CLBP.

Methods
The design was a randomized clinical trial. A total of 24 amateur athletes (12 women, 12 men, mean age: 35.2 ± 9.8) with nonspecific CLBP were randomly allocated into two groups. The experimental group (n = 12) received diaphragm training plus Transcutaneous Electrical Nerve Stimulation (TENS), while the control group (n = 12) received TENS alone. Both groups underwent 12 sessions over a four-week period. Static stability, dynamic balance, pain, and function were measured pre- and post-intervention.

Results
Analysis of variance 2 × 2 revealed greater improvements in pain (p < 0.001), static stability (p < 0.001), and dynamic balance (p < 0.01) in the experimental group compared to the control group. Function was improved in both groups following the interventions (p < 0.001), and there was a trend of a larger improvement in the experimental group than the control group (p = 0.09). Fisher’s exact test showed that the experimental group reported ≥50% improvement only in the pain score, not function, compared to the group that received TENS alone (p = 0.005).

Conclusions
Pain, function, static stability, and dynamic balance were improved in both groups following 12 intervention sessions. However, pain, static stability, and dynamic balance were improved to a greater extent in diaphragm training plus TENS than TENS alone in amateur athletes with CLBP. Therefore, it seems beneficial to add diaphragm training to the rehabilitation program for athletes with nonspecific CLBP.

Trial registration
The trial was retrospectively registered in the Iranian Registry of Clinical Trials (www.irct.ir) on September 10, 2020 as IRCT20090228001719N8.