bluuebunny/crossref_metadata_2025_split huggingface dataset:
RETRACTED ARTICLE: Circular RNA circ-CSPP1 regulates CCNE2 to facilitate hepatocellular carcinoma cell growth via sponging miR-577
Authors: Sun Qian , Yu Rui , Wang Chunfeng , Yao Jianning , Zhang Lianfeng 
Published: May 2020

Abstract
Objective
Circ-centro-some/spindle pole-associated protein (CSPP1) has been confirmed to be characterized in diverse human malignancies and its ectopic expression may regulate tumor progression and development. However, in hepatocellular carcinoma (HCC), its biological role, clinical significance and molecular mechanism are still unclear.

Methods
Circ-CSPP1 expression and its prognostic values in HCC tissues were detected by qRT-PCR or in situ hybridization (ISH), and enriched by using Rnase R. The functional experiments (Circ-CSPP1 was overexpressed or knocked down) were performed in HCC cells. The HCC cell growth was analyzed by CCK-8 assay, transwell, wound healing and colony formation assays. The interation between circ-CSPP1 and miR-577/miR-577 and cyclin E2 (CCNE2) were determined by dual luciferase assay or RNA binding protein immunoprecipitation (RIP) assay. The RNA fluorescence in situ hybridization (FISH) assay was used to detect the subcellular distribution. Finally, an in vivo nude mouse tumor model was constructed.

Results
In HCC patients and cells, circ-CSPP1 was aberrantly expressed, and its upregulation predicted poor prognosis, and closely correlated with tumor size and TNM stage. Circ-CSPP1 resisted RnaseR digestion, indicating it is a circular RNA structure. Moreover, overexpression of circ-CSPP1 promoted HCC cell viability, colony formation, migration, and invasion in vitro. Knockdown of circ-CSPP1 showed contrary results. Circ-CSPP1 acts as a miR-577 sponge and positively regulated the target of miR-577, CCNE2. Besides, miR-577 inhibitor rescued the suppressive effects of circ-CSPP1 knockdown on HCC cell growth, whereas was completely reversed by silencing of CCNE2. Finally, the in vivo experiments confirmed that circ-CSPP1 knockdown regulated xenograft tumor volume and downregulated CCNE2, p-Rb, E2F1 and c-myc expression.

Conclusion
These findings revealed that circ-CSPP1 contributed to HCC progression by positively regulating CCNE2 via miR-577, thus established its potential as new a prognostic and therapeutic marker for HCC patients.
A meta-analysis on the prevalence, associated factors and diagnostic methods of mental stress induced myocardial ischemia
Authors: Zhang Lijun , Bao Yanping , Wang Xi , Zhou Yuxin , Tao Shuhui , Xu Wan , Liu Meiyan 
Published: May 2020

AbstractBackgroundThe high prevalence of mental stress induced myocardial ischemia (MSIMI) causes double risk of adverse cardiac events in patients with MSIMI. However, multiple types of mental stress, diagnostic techniques, and diagnostic measurements may increase the complexity and heterogeneity in the assessment of MSIMI. Therefore, we performed this meta-analysis to assess the prevalence, associated factors, and diagnostic methods of MSIMI.MethodsWe systematically searched PubMed, EMBACE, Web of Science, CNKI, Wanfang through 1 Feb 2020 in English and Chinese. Review Manager (RevMan) Version 5.3 and Stata 12.0 were used for data analyses.ResultsTwenty articles were enrolled. The pooled estimates for the prevalence of MSIMI in CAD patients was 32%. Potential associated factors of MSIMI involved history of post myocardial infarction (MI), or coronary artery bypass graft (CABG) (RR: 1.29, 95% CI 1.00–1.66, P = 0.05; RR: 1.59, 95% CI 1.00–2.52, P = 0.05). Evidence supported that diagnostic methods could influence the prevalence of MSIMI. Significant differences of MSIMI prevalence were found in different types of mental stress (Public Speaking: 22%; Mental arithmetic: 26%; Anger recall: 34%; Two types: 37%; Three or more than three types: 43%, P = 0.02), diagnostic techniques (SPECT: 26%; RNV: 38%; ECG: 16%; Echocardiography: 41%; Two types: 43%, P < 0.0001), and diagnostic measurements (LVEF decrease: 19%; WMA: 51%; ST depression: 16%; MPD: 26%; Two or more than two measurements: 45%, P < 0.00001). Moreover, univariate meta-regression demonstrated that MSIMI was linked with mental stress (exp(b): 1.0508, SE: 0.0201, P: 0.018).ConclusionsThis meta-analysis implicated that patients with diabetes, post MI or CABG might be more vulnerable to MSIMI. However, the prevalence of MSIMI could be influenced by diagnostic methods, especially the adopted types of mental stress, diagnostic techniques and measurements. Therefore, it is necessary to formulate a standard diagnostic method for MSIMI, which should be adequate, assessable, and affordable worldwide.RegistrationPROSPERO. Online Protocol: CRD42020162822.
Retention in care in aging adults with a dual diagnosis of HIV infection and type 2 diabetes mellitus: a longitudinal retrospective cross-sectional study
Authors: Zuniga Julie Ann , García Alexandra A. , Lee Junse , Park Jungmin 
Published: May 2020

Abstract
Background
This study aimed to investigate the measures of retention in care (RIC) in persons living with HIV (PLWH) and type 2 diabetes mellitus (T2DM) by age group (younger vs. older adults).

Methods
This was a longitudinal retrospective cross-sectional study that used secondary data from the Center for AIDS Research Network of Integrated Clinical Systems (CNICS). We examined RIC in 798 adult PLWH + T2DM who visited a CNICS clinic at least once in 2015. Six measures of RIC were examined: missed visits [measured as a continuous variable (total number of missed visits) and dichotomous variable (0 = never missed, 1 = missed)], visit adherence, 6-month visit gap, 4-month visit constancy, and the Health and Resources Services Administration HIV/AIDS Bureau’s RIC measure. We calculated Spearman correlation coefficients and conducted logistic regression and multi-group path analysis.

Results
Most RIC measures were significantly correlated (p < 0.05) with one another; only 4-month visit constancy was not correlated with other measures. Except for the number of missed visits in older adult PLWH + T2DM, we found no significant relationships between RIC measures and CD4 cell count using logistic regression. However, multi-group path analysis demonstrated significant positive relationships between most RIC measures and CD4 cell count in both age groups. In younger adults living with HIV (YALWH) + T2DM, HbA1c level, but not CD4 count, was significantly associated with most RIC measures.

Conclusions
RIC is related to disease control (CD4 cell count and HbA1c level) in PLWH + T2DM and notably, HbA1c level was only significantly affected in YALWH + T2DM. A future study is needed to find more accurate reasons for the fact that only HbA1c level had significant relationships in YALWH + T2DM. The findings from this study provide guidance in measuring RIC in PLWH who have comorbidities.
Going for brokerage: strategies and strains in commercial healthcare facilitation
Authors: Hunter Benjamin M. 
Published: May 2020

AbstractBackgroundThe formation of domestic and global marketplaces during the past 50 years has opened up new commercial opportunities for third-party activity in healthcare systems. Commercial mediation of access to healthcare is one recent area of activity that sees companies and individuals offering to organise healthcare and travel in return for payment. With varying degrees of control over the location, type, cost and experiences of healthcare provisioning, these intermediaries occupy potentially influential positions in healthcare systems and yet much of their work is poorly understood.MethodsDrawing on social science theories of brokerage, this article presents a novel analysis of commercial healthcare facilitation. It focuses on facilitation companies and their workers as central, intermediating actors for people to access healthcare in markets characterised by complexity. Semi-structured interviews were conducted with people working in domestic and international healthcare facilitation in London and Delhi, and data were analysed using a framework approach that emphasises the structural features and personal agencies for this area of work.ResultsFindings point to an institutional environment for commercial healthcare facilitation marked by competition and the threat of obsolescence. The activities of rivals, and the risk that users and providers will bypass intermediaries, compels facilitation companies to respond strategically and to continuously pursue new populations and activities to mediate – to go for broke. These pressures percolate into the lives of people who perform facilitation work and who describe a physical and mental burden of labour incurred by onerous processes for generating and completing facilitation work. The need for language interpretation services introduces an additional set of relations and has created further points of tension. It is an environment that engenders mistrust and anxiety, and which incentivises exploitation and a commodification of users whose associated commissions are highly prized.ConclusionBrokerage analysis provides valuable insights into the strategies and strains for commercial mediation of access to healthcare, and the findings indicate opportunities for further research on the contributions of interpreters, diplomatic and business networks, and new technologies, and on the growth of new forms of mediation in domestic and overseas settings.
Early circulating tumour DNA kinetics measured by ultra-deep next-generation sequencing during radical radiotherapy for non-small cell lung cancer: a feasibility study
Authors: Walls G. M. , McConnell L. , McAleese J. , Murray P. , Lynch T. B. , Savage K. , Hanna G. G. , de Castro D. Gonzalez 
Published: May 2020

AbstractBackgroundThe evaluation of circulating tumour DNA (ctDNA) from clinical blood samples, liquid biopsy, offers several diagnostic advantages compared with traditional tissue biopsy, such as shorter processing time, reduced patient risk and the opportunity to assess tumour heterogeneity. The historically poor sensitivity of ctDNA testing, has restricted its integration into routine clinical practice for non-metastatic disease. The early kinetics of ctDNA during radical radiotherapy for localised NSCLC have not been described with ultra-deep next generation sequencing previously.Materials and methodsPatients with CT/PET-staged locally advanced, NSCLC prospectively consented to undergo serial venepuncture during the first week of radical radiotherapy alone. All patients received 55Gy in 20 fractions. Plasma samples were processed using the commercially available Roche AVENIO Expanded kit (Roche Sequencing Solutions, Pleasanton, CA, US) which targets 77 genes.ResultsTumour-specific mutations were found in all patients (1 in 3 patients; 2 in 1 patient, and 3 in 1 patient). The variant allele frequency of these mutations ranged from 0.05–3.35%. In 2 patients there was a transient increase in ctDNA levels at the 72 h timepoint compared to baseline. In all patients there was a non-significant decrease in ctDNA levels at the 7-day timepoint in comparison to baseline (p = 0.4627).ConclusionThis study demonstrates the feasibility of applying ctDNA-optimised NGS protocols through specified time-points in a small homogenous cohort of patients with localised lung cancer treated with radiotherapy. Studies are required to assess ctDNA kinetics as a predictive biomarker in radiotherapy. Priming tumours for liquid biopsy using radiation warrants further exploration.
Randomized clinical trials in ANCA-associated vasculitis: a systematic analysis of the WHO - International Clinical Trials Registry Platform
Authors: Iudici Michele , Puéchal Xavier , Brigante Alejandro , Atal Ignacio , Gabay Cem 
Published: May 2020

Abstract
Background
The analysis of the main features of randomized controlled trials (RCTs) on ANCA-associated vasculitis (AAV) can inform future study design.

Methods
We searched within the International Clinical Trials Registry Platform all registered RCTs on AAV from October 2008 to December 2018. Two reviewers selected studies according to pre-specified eligibility criteria. We retrieved information including countries, funding, design, sample sizes, eligibility criteria, primary outcomes (POs), and treatments.

Results
Among the 40 RCTs identified, 22 (55%) were conducted in Europe, 29 (72,5%) in a single country, 14 (35%) were industry-funded. The median number of patients planned to enrol was 68 (IQR 36–138). Only 28% of RCTs targeted a single vasculitis, and ANCA negative patients were not included in about 40% of studies. Interventions investigated were mainly drugs given to induce (40%) or maintain (32.5%) remission. Eighty-five percent of POs were considered being ‘patient-important’, but discrepancies in definition of disease states, such as remission or relapse were observed. Glucocorticoids use was part of the PO in < 25% of studies. The number of trials targeting a single disease, non-industry funded, incorporating glucocorticoids in PO, as well as the planned sample size increased over time.

Conclusion
Despite the important achievements in the field, a better harmonization of eligibility, and outcome criteria across studies is an important objective to pursue in next future.
The first seven years of nationally organized helicopter emergency medical services in Finland – the data from quality registry
Authors: Saviluoto Anssi , Björkman Johannes , Olkinuora Anna , Virkkunen Ilkka , Kirves Hetti , Setälä Piritta , Pulkkinen Ilkka , Laukkanen-Nevala Päivi , Raatiniemi Lasse , Jäntti Helena , Iirola Timo , Nurmi Jouni 
Published: May 2020

Abstract
Background
Helicopter Emergency Medical Services (HEMS) play an important role in prehospital care of the critically ill. Differences in funding, crew composition, dispatch criteria and mission profile make comparison between systems challenging. Several systems incorporate databases for quality control, performance evaluation and scientific purposes. FinnHEMS database was incorporated for such purposes following the national organization of HEMS in Finland 2012. The aims of this study are to describe information recorded in the database, data collection, and operational characteristics of Finnish HEMS during 2012–2018.

Methods
All dispatches of the six Finnish HEMS units recorded in the national database from 2012 to 2018 were included in this observational registry study. Five of the units are physician staffed, and all are on call 24/7. The database follows a template for uniform reporting in physician staffed pre-hospital services, exceeding the recommended variables of relevant guidelines.

Results
The study included 100,482 dispatches, resulting in 33,844 (34%) patient contacts. Variables were recorded with little or no missing data. A total of 16,045 patients (16%) were escorted by HEMS to hospital, of which 2239 (2%) by helicopter. Of encountered patients 4195 (4%) were declared deceased on scene. The number of denied or cancelled dispatches was 66,638 (66%). The majority of patients were male (21,185, 63%), and the median age was 57.7 years. The median American Society of Anesthesiologists Physical Scale classification was 2 and Eastern Cooperative Oncology Group performance class 0. The most common reason for response was trauma representing 26% (8897) of the patients, followed by out-of-hospital cardiac arrest 20% (6900), acute neurological reason excluding stroke 13% (4366) and intoxication and related psychiatric conditions 10% (3318). Blunt trauma (86%, 7653) predominated in the trauma classification.

Conclusions
Gathering detailed and comprehensive data nationally on all HEMS missions is feasible. A national database provides valuable insights into where the operation of HEMS could be improved. We observed a high number of cancelled or denied missions and a low percentage of patients transported by helicopter. The medical problem of encountered patients also differs from comparable systems.
Point-of-care ultrasound induced changes in management of unselected patients in the emergency department - a prospective single-blinded observational trial
Authors: Weile Jesper , Frederiksen Christian A. , Laursen Christian B. , Graumann Ole , Sloth Erik , Kirkegaard Hans 
Published: May 2020

Abstract
Background
Point-of-Care ultrasound (POCUS) changes the management in specific groups of patients in the Emergency Department (ED). It seems intuitive that POCUS holds an unexploited potential on a wide variety of patients. However, little is known about the effect of ultrasound on the broad spectrum of unselected patients in the ED. This study aimed to identify the effect on the clinical management if POCUS was applied on unselected patients. Secondarily the study aimed to identify predictors of ultrasound changing management.

Methods
This study was a blinded observational single center trial. A basic whole body POCUS protocol was performed in extension to the physical examination. The blinded treating physicians were interviewed about the presumptive diagnosis and plan for the patient. Subsequently the physicians were unblinded to the POCUS results and asked to choose between five options regarding the benefit from POCUS results.

Results
A total of 403 patients were enrolled in this study. The treating physicians regarded POCUS examinations influence on the diagnostic workup or treatment as following: 1) No new information: 249 (61.8%), 2) No further action: 45 (11.2%), 3) Further diagnostic workup needed: 52 (12.9%), 4) Presumptive diagnosis confirmed 38 (9.4%), and 5) Immediate treatment needed: 19 (4.7%). Predictors of beneficial ultrasound were: (a) triage > 1, (b) patient comorbidities (cardiac disease, hypertension or lung disease), or (c) patients presenting with abdominal pain, dyspnea, or syncope.

Conclusion
POCUS was found to be potentially beneficial in 27.0% of all patients. High triage score, known cardiac disease, hypertension, pulmonary diseases, a clinical presentation with abdominal pain, dyspnea, or syncope are predictors of this. Future research should focus on patient-important outcomes when applying POCUS on these patients.

Trial registration
The trail was registered prior to patient inclusion with the Danish Data Protection Agency (https://www.datatilsynet.dk/ Case no: 1–16–02-603-14) and Clinical Trials (www.clinicaltrials.gov/ Protocol ID: DNVK1305018).
IL-23 in arthritic and inflammatory pain development in mice
Authors: Lee Kevin M.-C. , Zhang Zihao , Achuthan Adrian , Fleetwood Andrew J. , Smith Julia E. , Hamilton John A. , Cook Andrew D. 
Published: May 2020

Abstract
Background
The cytokine, interleukin-23 (IL-23), can be critical for the progression of inflammatory diseases, including arthritis, and is often associated with T lymphocyte biology. We previously showed that certain lymphocyte-independent, inflammatory arthritis and pain models have a similar requirement for tumour necrosis factor (TNF), granulocyte macrophage-colony stimulating factor (GM-CSF), and C-C motif ligand 17 (CCL17). Given this correlation in cytokine requirements, we explored whether IL-23 might interact with this cytokine cluster in the control of arthritic and inflammatory pain.

Methods
The role of IL-23 in the development of pain-like behaviour was investigated using mouse arthritis models (zymosan-induced arthritis and GM-CSF-, TNF-, and CCL17-driven monoarticular arthritis) and inflammatory pain models (intraplantar zymosan, GM-CSF, TNF, and CCL17). Additionally, IL-23-induced inflammatory pain was measured in GM-CSF−/−, Tnf−/−, and Ccl17E/E mice and in the presence of indomethacin. Pain-like behaviour and arthritis were assessed by relative weight distribution in hindlimbs and histology, respectively. Cytokine mRNA expression in knees and paw skin was analysed by quantitative PCR. Blood and synovial cell populations were analysed by flow cytometry.

Results
We report, using Il23p19−/− mice, that innate immune (zymosan)-driven arthritic pain-like behaviour (herein referred to as pain) was completely dependent upon IL-23; optimal arthritic disease development required IL-23 (P < 0.05). Zymosan-induced inflammatory pain was also completely dependent on IL-23. In addition, we found that exogenous TNF-, GM-CSF-, and CCL17-driven arthritic pain, as well as inflammatory pain driven by each of these cytokines, were absent in Il23p19−/− mice; optimal disease in these mBSA-primed models was dependent on IL-23 (P < 0.05). Supporting this cytokine connection, it was found conversely that IL-23 (200 ng) can induce inflammatory pain at 4 h (P < 0.0001) with a requirement for each of the other cytokines as well as cyclooxygenase activity.

Conclusions
These findings indicate a role for IL-23 in innate immune-mediated arthritic and inflammatory pain with potential links to TNF, GM-CSF, CCL17, and eicosanoid function.
Tonsillar granuloma associated with hypogammaglobulinemia
Authors: Laajala Aleksi , Kuismin Outi , Tastula Mikko , Tiitto Leena , Kauppila Saila , Salo Anna , Åström Pirjo , Nissinen Antti , Glumoff Virpi , Seppänen Mikko R. J. , Hautala Timo 
Published: May 2020

Abstract
Background
Rare tonsillar granulomas may be caused for example by infections, malignancies or sarcoidosis. Granulomas also occur in inborn errors of immunity (IEI) such as common variable immunodeficiency (CVID) with B cell maturation defects and hypogammaglobulinemia. CVID shares various features with sarcoidosis and drug-induced secondary hypogammaglobulinemia; careful consideration of differential diagnosis between these conditions is warranted.

Case presentation
A 29-year-old female with epilepsy developed dysphagia, dyspnea and impaired exercise tolerance. Obstruction caused by swollen lingual tonsil and edema in the epiglottis and arytenoid mucosa were found. Lingual tonsil and epiglottis biopsies displayed non-necrotizing granulomas. There was no evidence of viral, bacterial, mycobacterial or fungal infections. Chest X-ray, computerized tomography of chest and ultrasound of neck and abdomen remained unremarkable. Positron emission tomography/computed tomography (PET/CT) showed laryngeal enhancement. Empiric antimicrobials combined with prednisolone were insufficient to control her disease. In immunological evaluation, the patient had normal counts of B and T cells. Proportions of CD27+ memory B cells (30.3%) and IgD−IgM−CD27+ switched memory B cells (7.2%; normal range 6.5–29.2%) were normal. Percentage of activated CD21low B cells was high (6.6%; normal range 0.6–3.5%). IgG (3.5 g/L; normal range 6.77–15.0 g/l) and all IgG subclass concentrations were low. Anti-polysaccharide responses were impaired, with 3/10 serotypes reaching a level of 0.35 µg/ml after immunization with Pneumovax®. The findings were consistent with hypogammaglobulinemia resembling CVID, possibly secondary to antiepileptic medication. Her dyspnea and dysphagia responded favorably to subcutaneous IgG and rituximab.

Conclusions
Tonsillar granulomas can be the presenting and only clinical feature of B cell deficiency, highlighting the diversity of symptoms and findings in primary or secondary immunodeficiencies.