bluuebunny/crossref_metadata_2025_split huggingface dataset:
Facilitators and “deal breakers”: a mixed methods study investigating implementation of the Goal setting and action planning (G-AP) framework in community rehabilitation teams
Authors: Scobbie Lesley , Duncan Edward A. S. , Brady Marian C. , Thomson Katie , Wyke Sally 
Published: August 2020

Abstract
Background
High quality goal setting in stroke rehabilitation is vital, but challenging to deliver. The G-AP framework (including staff training and a stroke survivor held G-AP record) guides patient centred goal setting with stroke survivors in community rehabilitation teams. We found G-AP was acceptable, feasible to deliver and clinically useful in one team. The aim of this study was to conduct a mixed methods investigation of G-AP implementation in diverse community teams prior to a large-scale evaluation.

Methods
We approached Scottish community rehabilitation teams to take part. Following training, G-AP was delivered to stroke survivors within participating teams for 6 months. We investigated staff experiences of G-AP training and its implementation using focus groups and a training questionnaire. We investigated fidelity of G-AP delivery through case note review. Focus group data were analysed using a Framework approach; identified themes were mapped into Normalisation Process Theory constructs. Questionnaire and case note data were analysed descriptively.

Results
We recruited three teams comprising 55 rehabilitation staff. Almost all staff (93%, 51/55) participated in G-AP training; of those, 80% (n = 41/51) completed the training questionnaire. Training was rated as ‘good’ or ‘very good’ by almost all staff (92%, n = 37/41). G-AP was broadly implemented as intended in two teams. Implementation facilitators included - G-AP ‘made sense’; repetitive use of G-AP in practice; flexible G-AP delivery and positive staff appraisals of G-AP impact. G-AP failed to gain traction in the third team. Implementation barriers included - delays between G-AP training and implementation; limited leadership engagement; a poor ‘fit’ between G-AP and the team organisational structure and simultaneous delivery of other goal setting methods. Staff recommended (i) development of training to include implementation planning; (ii) ongoing local implementation review and tailoring, and (iii) development of electronic and aphasia friendly G-AP records.

Conclusions
The interaction between G-AP and the practice setting is critical to implementation success or failure. Whilst facilitators support implementation success, barriers can collectively act as implementation “deal breakers”. Local G-AP implementation efforts should be planned, monitored and tailored. These insights can inform implementation of other complex interventions in community rehabilitation settings.
RETRACTED ARTICLE: Circular RNA circ_0000517 regulates hepatocellular carcinoma development via miR-326/IGF1R axis
Authors: He Shuwei , Yang Jianzeng , Jiang Shitao , Li Yuan , Han Xingmin 
Published: August 2020

Abstract
Background
Circular RNAs (circRNAs) play vital roles in hepatocellular carcinoma development. However, the role and mechanism of circRNA hsa_circ_0000517 (circ_0000517) in hepatocellular carcinoma development were largely unknown.

Methods
45 paired tumor and adjacent nontumor samples were collected from hepatocellular carcinoma patients. The levels of circ_0000517, miR-326 and insulin-like growth factor type 1 receptor (IGF1R) were detected via quantitative reverse transcription polymerase chain reaction or western blot. Cell viability, colony ability, migration, invasion and glycolysis were assessed via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), colony formation, western blot, transwell assay, glucose consumption, lactate production or adenosine triphosphate (ATP) production. The target correlation between miR-326 and circ_0000517 or IGF1R was analyzed via dual-luciferase reporter analysis. The function of circ_0000517 in vivo was assessed via xenograft model.

Results
circ_0000517 expression was elevated in hepatocellular carcinoma tissues and cell lines. circ_0000517 knockdown suppressed cell viability, colony formation, migration, invasion and glycolysis. miR-326 was sponged via circ_0000517 and miR-326 knockdown reversed the effect of circ_0000517 silence on hepatocellular carcinoma development. miR-326 overexpression inhibited hepatocellular carcinoma development through targeting IGF1R. circ_0000517 knockdown decreased IGF1R expression by modulating miR-326. circ_0000517 downregulation reduced xenograft tumor growth.

Conclusion
circ_0000517 knockdown repressed hepatocellular carcinoma development in vitro and in vivo by modulating miR-326 and IGF1R.
Environmental health literacy and household air pollution-associated symptoms in Kenya: a cross-sectional study
Authors: Raufman Jill , Blansky Deanna , Lounsbury David W. , Mwangi Esther Wairimu , Lan Qing , Olloquequi Jordi , Hosgood H. Dean 
Published: August 2020

Abstract
Background
Household air pollution (HAP) is a significant source of the global burden of disease. Our objective was to evaluate the association between environmental health literacy (EHL), a domain of health literacy (HL) that describes the ability to use environmental health information to reduce health risks, and symptoms associated with HAP.

Methods
We performed a cross-sectional population-based study of 353 households in Kasarani, Kenya. One individual from each household was surveyed using our novel EHL survey tool. Baseline characteristics were compared between individuals who were symptomatic (i.e., experiencing cough, shortness of breath, phlegm production, wheeze, chest tightness, headache, eye irritation, or burns from cooking at least 5 times per month) versus individuals who were asymptomatic (i.e., experiencing none or symptoms no more than once per month). Multivariate logistic regression was used to determine the odds ratios (OR) of self-reported symptoms associated with HL, stratified by median EHL, adjusting for education, self-perceived health and solid fuel use.

Results
A total of 100 individuals (28%) reported experiencing one or more symptoms at least 5 times per month, including 31.2% of solid fuel users and 30.3% of non-solid fuel users. Among individuals with high EHL, higher HL was associated with lower risk of experiencing symptoms (OR = 0.26; 95% CI 0.10–0.67), however, there was no association among individuals with low EHL (OR = 0.85; 95% CI 0.34–2.13). Among solid fuel users, the association between HL and risk of experiencing symptoms was driven by individuals with high EHL (OR = 0.30; 95% CI 0.05–1.84), rather than those with low EHL (OR = 1.22; 95% CI 0.36–4.16).

Conclusions
To the best of our knowledge, this was the first study to assess the association between EHL, HL, and HAP-associated symptoms. Our findings highlight the potential importance of EHL in promoting sustainable interventions to reduce symptoms associated with HAP from solid fuel use among communities in Kenya.
Prenatal diagnosis of mosaic trisomy 2 and literature review
Authors: Wang Ting , Lian Jufei , Ren Congmian , Huang Huamei , Huang Yanlin , Xu Ling , Zheng Laiping , Cai Chanhui , Guo Li 
Published: August 2020

Abstract
Background
We presented two cases of mosaic trisomy 2 with high risk of maternal serum screening and non-invasive prenatal testing (NIPT). The invasive amniocentesis was performed and genetic tests including karyotype, single nucleotide polymorphism array(SNP-array), interphase fluorescence in situ hybridization (FISH) were employed to detect the chromosomal abnormality.

Results
Cytogentic analysis of the case 1 and 2 showed a mosaic karyotype consisting of two cell lines (mos 47,XY,+2[8]/46,XY[19] and mos 47,XX,+2[7]/46,XX[28], respectively). SNP-array using DNA extracted from uncultured amniotic fluid cells revealed a result of arr[GRCh38](2)x2~3, which indicated that chromosome 2 may be trisomy of mosaicism in both two cases. The results of interphases FISH confirmation test showed that three red signals of the CEP 2 specific probe in 14%(14/100) and 12%(12/100) of the two cases’ cells, respectively, which indicated a mosaicism for trisomy 2 in the uncultured amniocytes. Fetal ultrasound of case 1 suggested that the long bone is smaller than the gestational age, while the case 2 showed that the biparietal diameter (BPD), head circumference (HC) and femur length (FL) were smaller than gestational age along with abnormal cardiac structure.

Conclusions
We presented two cases with mosaic trisomy 2 and performed confirmatory genetic testing using cultured and uncultured amniocytes. When maternal serum screening and NIPT suggesting high risk, genetic counselor should be alert for increasing possibility of chromosomal anomalies if combined with abnormal ultrasound findings.
Assessing physicians’ and nurses’ experience of dying and death in the ICU: development of the CAESAR-P and the CAESAR-N instruments
Authors: Boissier Florence , Seegers Valérie , Seguin Amélie , Legriel Stéphane , Cariou Alain , Jaber Samir , Lefrant Jean-Yves , Rimmelé Thomas , Renault Anne , Vinatier Isabelle , Mathonnet Armelle , Reuter Danielle , Guisset Olivier , Cracco Christophe , Durand-Gasselin Jacques , Éon Béatrice , Thirion Marina , Rigaud Jean-Philippe , Philippon-Jouve Bénédicte , Argaud Laurent , Chouquer Renaud , Papazian Laurent , Dedrie Céline , Georges Hugues , Lebas Eddy , Rolin Nathalie , Bollaert Pierre-Edouard , Lecuyer Lucien , Viquesnel Gérald , Leone Marc , Chalumeau-Lemoine Ludivine , Garrouste-Orgeas Maité , Azoulay Elie , Kentish-Barnes Nancy 
Published: August 2020

Abstract
Background
As an increasing number of deaths occur in the intensive care unit (ICU), studies have sought to describe, understand, and improve end-of-life care in this setting. Most of these studies are centered on the patient’s and/or the relatives’ experience. Our study aimed to develop an instrument designed to assess the experience of physicians and nurses of patients who died in the ICU, using a mixed methodology and validated in a prospective multicenter study.

Methods
Physicians and nurses of patients who died in 41 ICUs completed the job strain and the CAESAR questionnaire within 24 h after the death. The psychometric validation was conducted using two datasets: a learning and a reliability cohort.

Results
Among the 475 patients included in the main cohort, 398 nurse and 417 physician scores were analyzed. The global score was high for both nurses [62/75 (59; 66)] and physicians [64/75 (61; 68)]. Factors associated with higher CAESAR-Nurse scores were absence of conflict with physicians, pain control handled with physicians, death disclosed to the family at the bedside, and invasive care not performed. As assessed by the job strain instrument, low decision control was associated with lower CAESAR score (61 (58; 65) versus 63 (60; 67), p = 0.002).
Factors associated with higher CAESAR-Physician scores were room dedicated to family information, information delivered together by nurse and physician, families systematically informed of the EOL decision, involvement of the nurse during implementation of the EOL decision, and open visitation. They were also higher when a decision to withdraw or withhold treatment was made, no cardiopulmonary resuscitation was performed, and the death was disclosed to the family at the bedside.

Conclusion
We described and validated a new instrument for assessing the experience of physicians and nurses involved in EOL in the ICU. This study shows important areas for improving practices.
Challenges and contexts in establishing adaptive learning in higher education: findings from a Delphi study
Authors: Mirata Victoria , Hirt Franziska , Bergamin Per , van der Westhuizen Christo 
Published: August 2020

AbstractHigher education institutions are increasingly interested in using adaptive learning as an innovative data-driven approach to teaching. The actual use of adaptive learning in courses remains, however, low. This is despite positive attitudes of institutional leaders towards its adoption and promising results of early studies on its effectiveness.This study examines the challenges that prevent higher education institutions from adopting adaptive learning concepts in teaching. We used a four-stage Delphi design to empirically identify, categorise, and prioritise the challenges of adaptive learning raised and rated by experts from two universities with different organisational and socioeconomic contexts, one from Switzerland and one from South Africa. Considering different contexts allowed us to include various perspectives on the research topic and thus broaden the view on the challenges of adaptive learning. Overall, three main dimensions related to technological, teaching and learning, and organisational challenges with eight corresponding categories were identified. Our findings revealed clear differences between the two universities regarding the emerged challenges and their rankings. These differences are linked to different socioeconomic backgrounds (South Africa and Switzerland) and organisational contexts (e.g., type of the university, teaching model, and implementation phase) of the universities. We conclude by proposing practical recommendations for institutional leaders and project implementers on the factors to be considered when implementing adaptive learning in higher education settings. These recommendations relate to the necessary infrastructure, institutional commitment, support and resources.
Let there be blue-depleted light: in-patient dark therapy, circadian rhythms and length of stay
Authors: Scott Jan , Langsrud Knut , Goulding Ingunn Ro , Kallestad Havard 
Published: August 2020

SUMMARYLight is the most important environmental influence (zeitgeber) on the synchronization of the circadian system in humans. Excess light exposure during the evening and night-time affects secretion of the hormone melatonin, which in turn modifies the temporal organization of circadian rhythms, including the sleep–wake cycle. As sleep disturbances are prominent in critically ill medical and psychiatric patients, researchers began to examine the impact of light exposure on clinical outcomes and length of hospitalization. In psychiatric inpatients, exposure to bright morning light or use of blue blocking glasses have proved useful interventions for mood disorders. Recently, knowledge about light and the circadian system has been applied to the design of inpatient facilities with dynamic lighting systems that change according to time of day. The installation of ‘circadian lighting’ alongside technologies for monitoring sleep–wake patterns could prove to be one of the most practical and beneficial innovations in inpatient psychiatric care for more than half a century.
How effective is augmentation with psychotherapy as a next-step option for treatment-resistant depression?
Authors: Silman Daniel 
Published: August 2020

SUMMARYDetermining the optimum next-step treatment for the numerous patients with depression who do not adequately respond to an initial trial of medication remains a source of uncertainty in clinical practice. Although a number of psychological treatments are known to be effective for depression, their relative merits in the treatment-resistant group have not been ascertained. The Cochrane Collaboration has recently published a meta-analysis of the evidence available for the use of various psychotherapies as an adjunct to antidepressants compared with antidepressants alone in treatment-resistant depression. This article provides a commentary and appraisal of the clinical utility of these findings.
Expression of CD133 and poor outcome in neuroblastoma associated with chemoresistance mediated by AKT pathway
Authors: Sartelet H. , Haddad E. , Imbriglio T. , Arsenault M. , Ohta S. , Barrette S. , Sinnett D. , Laverdiere C. , Oligny L. , Vassal G. 
Published: August 2020

10007 Background: Neuroblastoma is a frequent childhood cancer with very heterogeneous prognosis. Recent studies showed that CD133 expression is an independent prognostic marker for low survival in several cancers like medulloblastoma. The aim of our study is to determine the prognostic value of CD133 expression in a large population of neuroblastoma and to determine the chemoresistance of neuroblasts expressing CD133. Methods: 280 tumor samples of neuroblastoma were screened for CD133 expression. Patients had a median follow-up of 7.15 years. One hundred eighteen patients were under one year of age with a median age of 27 months. There were 67 stage 1, 46 stage 2, 43 stage 3, 99 stage 4, and 25 stage 4S. The association of CD133 expression with relapse and survival were determined through univariate and multivariate analysis. Sensitivity of purified CD133+ neuroblasts isolated from 2 human neuroblastoma cell lines (SKNSH and NB10) to doxorubicin, vincristine and cisplatin was evaluated in vitro, as single agents or in combination with LY294002, a AKT inhibitor. Results: CD133 was expressed in 95 of 280 tumors (33%). There was a significant association between CD133 expression and the following poor prognosis co-variates: age (p<0.0001), INSS stage (p<0.0001), MYCN amplification (p<0.0001). Patients with a CD133+ tumor had a three year event-free and overall survival of 43±5% and 51±5%, respectively, as compared to patients with a CD133- tumor with 88±2% (P<0.001) and 95±2% (p<0.001). In a multivariate model, CD133 expression was independently associated with a decreased overall survival (p = 0.003) in the entire cohort. In vitro purified CD133+ neuroblasts were significantly resistant to chemotherapy as compared to their CD133- cells counterpart, but not in presence of the AKT inhibitor. In vitro treatment of unsorted neuroblasts with the three anticancer drugs significantly enriched the CD133+ subpopulation but not in presence of the AKT inhibitor. CD133plus; significantly expressed higher levels of activated proteins in the AKT pathway than CD133−. Conclusions: CD133 is independently associated with a worse outcome in patents with neuroblastoma. This prognosis factor is associated with in vitro resistance to chemotherapy involving activation of the AKT pathway. No significant financial relationships to disclose.
Inhibition of ALK mutated neuroblastomas by the selective inhibitor PF-02341066
Authors: Wood A. C. , Laudenslager M. , Haglund E. A. , Attiyeh E. F. , Pawel B. , Courtright J. , Plegaria J. , Christensen J. G. , Maris J. M. , Mosse Y. P. 
Published: August 2020

10008b Background: Mutations in the ALK oncogene are the major cause of hereditary neuroblastoma (NB), and may offer a tractable therapeutic target. Methods: We resequenced the ALK tyrosine kinase domain in 496 primary NBs. We integrated data from 76 primary tumors analyzed using Illumina HumanHap550 SNP and Human-6 mRNA expression arrays. We stained a tissue microarray (TMA) of 134 NBs with anti-ALK and anti-pALK antibodies. We evaluated the in vitro and in vivo activity of PF-02341066, a small molecule inhibitor of ALK. Computational chemistry was used to homology map ALK interaction with PF-02341066. Results: Mutations were discovered in 38/496 NBs (8%), across the spectrum of phenotypes. R1275Q substitutions were most common (45%), followed by F1174L (15%). Evaluation of matched constitutional DNAs demonstrated 10% carried occult germline mutations. Integration of primary tumor microarrays from 76 samples showed that ALK mRNA expression was highly correlated with ALK DNA copy number (p=0.0005). ALK protein was nearly universally expressed (129/134; 93%), and there was evidence for ALK activation in 15% of tumors (pALK moderate or strong staining in 20/134), suggesting an additional and alternative pathway to ALK activation. A panel of 18 NB cell lines showed differential in vitro sensitivity to PF-2341066 dependent on ALK mutation and copy number status. A wild type (WT) amplified line and 2 lines harboring R1275Q mutations were sensitive (IC50 145 - 301 nM). Lines harboring F1174L mutations were more resistant (IC50 >950nM) as were lines with no ALK aberrations. Inhibition of proliferation was associated with abolishing phosphorylation of ALK, STAT3 and AKT. PF-02341066 caused complete regression of R1275Q xenografts, but caused only minimal growth delay in F1174L and WT xenografts. Based on homology mapping to a crystal structure of PF-02341066 bound to c-Met, the F1174L mutation is predicted to destabilize the specific conformation of the kinase activation loop required for binding PF-02341066. Conclusions: ALK pathway activation occurs in at least 15% of human neuroblastomas. PF-02341066 is a potent inhibitor of the most common ALK mutation, but there is a structural basis for resistance to F1174L mutations. Co-crystallization studies are ongoing and a phase 1 study is planned. No significant financial relationships to disclose.
Irinotecan plus temozolomide in children with recurrent or refractory neuroblastoma: A phase II Children's Oncology Group study
Authors: Bagatell R. , Wagner L. M. , Cohn S. L. , Maris J. M. , Reynolds C. P. , Stewart C. F. , Voss S. D. , Gelfand M. , Kretschmar C. S. , London W. B. 
Published: August 2020

10011 Background: Treatment of children with relapsed or refractory neuroblastoma (NB) remains a challenge. Responses to irinotecan (IRN) + temozolomide (TEM) were seen in NB xenograft-bearing mice, and objective responses were observed in patients with NB treated on a phase I study of this combination. Methods: A phase II study of IRN (10 mg/m2/dose IV daily × 5 days times; 2 weeks) + TEM (100 mg/m2/dose PO daily × 5 days) for children with relapsed or refractory NB was conducted. A one-stage design (endpoint: best overall response) required 5 or more responders out of the first 25 evaluable patients on each of two strata: 1) patients with disease measurable by CT or MRI; and 2) patients with disease detected only by bone marrow aspirate/biopsy and/or MIBG scan. Patients with stable disease or better after 3 cycles could receive an additional 3 cycles of study therapy. International Neuroblastoma Response Criteria were used for response assessment. Radiographic responses were centrally reviewed. Results: Fifty-five eligible and evaluable patients were enrolled, 28 on stratum 1 and 27 on stratum 2. Four responses were observed in the first 25 evaluable stratum 1 patients, and five responses were observed in the first 25 evaluable stratum 2 patients. Three patients had complete responses, but the overall objective response rate (CR+PR) was 16% (9/55). Eleven (stratum 1) and 13 (stratum 2) patients had stable disease. Less than 5% of patients experienced Grade 3 or 4 diarrhea. Although 18% of patients on stratum 1 and 35% of patients on stratum 2 experienced Grade 3 or 4 neutropenia during the first 3 cycles of therapy, <10% of all patients developed evidence of infection while neutropenic. Thrombocytopenia (Grade 3 or 4) was observed in only 7% of patients on stratum 1 and 12% on stratum 2. Conclusions: The combination of IRN+TEM was well tolerated in patients with recurrent or refractory NB. There were 9 objective responses, including 3 complete responses. The minimum desired response rate was attained within stratum 2, but not stratum 1. IRN+TEM may be an appropriate backbone for further study in the relapse setting in combination with novel, targeted agents. No significant financial relationships to disclose.