bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unpacking complex interventions that manage care for high-need, high-cost patients: a realist review
Authors: Chang Eva , Ali Rania , Berkman Nancy D 
Published: June 2022

ObjectivePayers, providers and policymakers in the USA are interested in developing interventions that reduce preventable or modifiable healthcare use among high-need, high-cost (HNHC) patients. This study seeks to describe how and why complex interventions for HNHC patients lead to more appropriate use of healthcare services.DesignA realist review which develops programme theories from causal explanations generated and articulated through the creation of context–mechanism–outcome configurations.MethodsElectronic databases (including PubMed and Embase) and gray literature from January 2000 to March 2021 were searched. All study designs were included if the article provided data to develop our programme theories. Included studies were conducted in the USA and focused on interventions for adult, HNHC patients.ResultsData were synthesised from 48 studies. Identifying HNHC patients for inclusion in interventions requires capturing a combination of characteristics including their prior use of healthcare services, complexity of chronic disease(s) profile, clinician judgment and willingness to participate. Once enrolled, engaging HNHC patients in interventions requires intervention care providers and patients to build a trusting relationship. Tailored, individualised assistance for medical and non-medical needs, emotional support and self-management education empowers patients to increase their participation in managing their own care. Engagement of care providers in interventions to expand support of HNHC patients is facilitated by targeted outreach, adequate staffing support with shared values and regular and open communication.ConclusionsBuilding relationships with HNHC patients and gaining their trust is a key component for interventions to successfully change HNHC patients’ behaviors. Identifying HNHC patients for an intervention can be best achieved through a multipronged strategy that accounts for their clinical and psychosocial complexity and prior experiences with the healthcare system. Successful interventions recognise that relationships with HNHC patients require the sustained engagement of care providers. To succeed, providers need ongoing emotional, financial, logistical and practical resources.PROSPERO registration numberCRD42020161179.
Perceived usefulness of trauma audit filters in urban India: a mixed-methods multicentre Delphi study comparing filters from the WHO and low and middle-income countries
Authors: Berg Johanna , Alvesson Helle Molsted , Roy Nobhojit , Ekelund Ulf , Bains Lovenish , Chatterjee Shamita , Bhattacharjee Prosanta Kumar , David Siddarth , Gupta Swati , Kamble Jyoti , Khajanchi Monty , Lal Pawanindra , Malhotra Vikas , Meher Ravi , Mishra Anurag , Mohan Lakshmeswar Nagaraj , Petzold Max , Saxena Ritu , Shrivastava Prabhat , Singh Rajdeep , Soni Kapil Dev , Sural Sumit , Gerdin Wärnberg Martin 
Published: June 2022

ObjectiveTo compare experts’ perceived usefulness of audit filters from Ghana, Cameroon, WHO and those locally developed; generate context-appropriate audit filters for trauma care in selected hospitals in urban India; and explore characteristics of audit filters that correlate to perceived usefulness.DesignA mixed-methods approach using a multicentre online Delphi technique.SettingTwo large tertiary hospitals in urban India.MethodsFilters were rated on a scale from 1 to 10 in terms of perceived usefulness, with the option to add new filters and comments. The filters were categorised into three groups depending on their origin: low and middle-income countries (LMIC), WHO and New (locally developed), and their scores compared. Significance was determined using Kruskal-Wallis test followed by Wilcoxon rank-sum test. We performed a content analysis of the comments.Results26 predefined and 15 new filter suggestions were evaluated. The filters had high usefulness scores (mean overall score 9.01 of 10), with the LMIC filters having significantly higher scores compared with those from WHO and those newly added. Three themes were identified in the content analysis relating to medical relevance, feasibility and specificity.ConclusionsAudit filters from other LMICs were deemed highly useful in the urban India context. This may indicate that the transferability of defined trauma audit filters between similar contexts is high and that these can provide a starting point when implemented as part of trauma quality improvement programmes in low-resource settings.
Association between hospital volume, processes of care and outcomes after acute ischaemic stroke: a prospective observational study
Authors: Zhang Runhua , Liu Gaifen , Pan Yuesong , Zhou Maigeng , Wang Yongjun 
Published: June 2022

ObjectivesThere is uncertainty with respect to the hospital volume and clinical outcomes for patients with stroke. This study aimed to assess the association between hospital volume, processes of care and outcomes after ischaemic stroke.DesignA multicentre prospective cohort study.SettingTwo hundred and seventeen secondary or tertiary public hospitals from China.ParticipantsA total of 17 550 patients within 7 days of acute ischaemic stroke were included.Main outcome measuresThe outcomes included all-cause mortality, poor outcome, recurrent stroke, and combined vascular events at 3 months and 1 year. The patients were divided into four groups based on quartiles of the hospital volume. We compared the difference in the process of care across the groups and estimated the effects of hospital volume on mortality, poor outcome, recurrent stroke, and combined vascular events at 3 months and 1 year. Restricted cubic splines were used to illustrate the association between hospital volume and clinical outcomes.ResultsThere were no significant differences in the process of care across the four groups. When adjusted for confounders, the effect of hospital volume on mortality, recurrent stroke and combined vascular events was not significant. However, compared with the highest quartile, the patients in the lowest quartile of hospital volume tend to have poor outcome at 1 year (OR=1.29, 95% CI 1.01 to 1.64, p=0.0393). The restricted cubic spline analyses suggested a non-linear relationship between hospital volume and 1-year combined vascular events and poor outcome at 3 months and 1 year.ConclusionsWe found no significant associations between hospital volume, processes of care at the hospital, and mortality, recurrent stroke, and combined vascular events in patients with ischaemic stroke. However, hospital volume may be associated with poor outcome at 1 year.
Protocol for a feasibility study and process evaluation of a psychosocially modelled diabetes education programme for young people with type 1 diabetes: the Youth Empowerment Skills (YES) programme
Authors: Kariyawasam Dulmini , Soukup Tayana , Parsons Judith , Sevdalis Nick , Baldellou Lopez Maria , Forde Rita , Ismail Khalida , Jones Marie , Ford-Adams Martha , Yemane Nardos , Pender Siobhan , Thomas Stephen , Murrells Trevor , Silverstien Alex , Forbes Angus 
Published: June 2022

IntroductionAdolescence is a challenging period for young people with type 1 diabetes, associated with worsening glycaemia and care disengagement. Educational interventions in this period tend to focus on diabetes-specific skills, with less emphasis on the psychosocial challenges associated with diabetes experienced by young people. To address this limitation, we codesigned with young people a psychosocially modelled programme of diabetes education, named ‘Youth Empowerment Skills’ (YES). The programme aims to facilitate a positive adaptation to life with diabetes and engagement with diabetes care through peer-based learning, immersive simulations and support from an outreach youth worker. Here, we present a protocol for a feasibility study of the YES programme.Methods and analysisThe study was designed following the Medical Research Council Complex Intervention Evaluation Framework to: test the feasibility (acceptance, implementability, recruitment and completion) of the YES programme; and estimate its efficacy in relation to metabolic and psychosocial outcomes. The study will take place in diabetes centres serving socioculturally diverse populations. We will conduct a feasibility randomised controlled trial (waiting-list design) with integrated process evaluation. Fifty young people with type 1 diabetes (aged 14–19 years) will be randomly allocated to either the YES intervention or a waiting-list control. Randomisation acceptability will be assessed with provision for a preference allocation. Outcomes will be evaluated at 6 months, at which point the waiting list participants will be exposed to the YES programme with further follow-up to 12 months. A simultaneous process evaluation will use a mixed-methods approach collecting qualitative and quantitative data. Study findings will be used to optimise the intervention components, outcome measures and recruitment methods to inform a subsequent definitive trial.Ethics and disseminationThe protocol has ethical approval from the UK Health Research Authority (approval IRAS project ID: 279877). Findings will be disseminated in multiple formats for lay and professional audiences.Protocol date and version7 April 2021, V.1.1.Trial registration numberNCT04670198.
Randomised, pragmatic, waitlist controlled trial of cannabis added to prescription opioid support on opioid dose reduction and pain in adults with chronic non-cancer pain: study protocol
Authors: Jashinski Julia , Grossman Ellie , Quaye Aurora , Cather Corinne , Potter Kevin , Schoenfeld David A , Evins A Eden , Gilman Jodi M 
Published: June 2022

IntroductionChronic, non-cancer pain impacts approximately 50 million adults in the USA (20%), approximately 25% of whom receive chronic prescription opioids for pain despite limited empirical efficacy data and strong dose-related risk for opioid use disorder and opioid overdose. Also despite lack of efficacy data, there are many reports of people using cannabis products to manage chronic pain and replace or reduce chronic opioids. Here we describe the protocol for a randomised trial of the effect of cannabis, when added to a behavioural pain management and prescription opioid taper support programme, on opioid utilisation, pain intensity and pain interference.MethodsThis is a pragmatic, single-blind, randomised, wait-list controlled trial that aims to enrol 250 adults taking prescription opioids at stable doses of ≥25 morphine milligram equivalents per day for chronic non-cancer pain who express interest in using cannabis to reduce their pain, their opioid dose or both. All participants will be offered a weekly, 24-session Prescription Opioid Taper Support group behavioural pain management intervention. Participants will be randomly assigned in 1:1 ratio to use cannabis products, primarily from commercial cannabis dispensaries or to abstain from cannabis use for 6 months. Coprimary outcomes are change in prescription monitoring programme-verified opioid dose and change in Pain, Enjoyment, General Activity scale scores. Secondary outcomes include quality of life, depression, anxiety, self-reported opioid dose and opioid and cannabis use disorder symptoms. All other outcomes will be exploratory. We will record adverse events.Ethics and disseminationThis study has ethical approval by the Massachusetts General Brigham Institutional Review Board (#2021P000871). Results will be published in peer-reviewed journals and presented at national conferences.Trial registration numberNCT04827992.
Enhanced antitumor activity of combined methotrexate and histone deacetylase inhibitor valproic acid on mammary cancer in vitro and in vivo
Authors: El Said Hadia H. , Badary Osama A. , Shouman Samia A. , Elmazar Mohamed M. , El-Khatib Aiman S. 
Published: June 2022

Histone deacetylase inhibitors (HDACIs) act as antiproliferative agents by promoting differentiation and inducing apoptosis. Valproic acid (VPA) is a HDACI that shows promising chemotherapeutic effect in a number of tumor cells. The present study aimed to investigate the inhibitory effect of VPA on the viability of mammary cancer cells and its enhancing effect with methotrexate (MTX) in vitro and in vivo. Treatment with VPA or MTX alone induced concentration-dependent cytotoxic effects in two breast cancer cell lines. Valproic acid increased significantly the cytotoxicity of MTX three times against MCF7. Valproic acid addition to MTX, however, did not produce any significant changes on MTX cytotoxicity against MDA-MB231. VPA (150 and 200 mg/kg) significantly inhibited the growth of Ehrlich ascites carcinoma (EAC) and solid Ehrlich carcinoma (SEC) tumor mouse models and improved results were achieved for tumor inhibition when VPA was combined with MTX (1 and 2 mg/kg) in vivo. The antitumor activity was not associated with a significant increase in toxicity or mice mortality rate. All these findings suggest that the combination of MTX and VPA may have clinical and (or) adjuvant therapeutic application in the treatment of mammary cancer.
Domination in edge cycle graphs
Authors: Murugan E. , Sivaprakash G. R. 
Published: June 2022

Let [Formula: see text] be a graph. A subset [Formula: see text] of [Formula: see text] is called a dominating set of [Formula: see text] if every vertex not in [Formula: see text] is adjacent to some vertex in [Formula: see text] The domination number [Formula: see text] of [Formula: see text] is the minimum cardinality taken over all dominating sets of [Formula: see text] A dominating set [Formula: see text] is called a connected dominating set if the induced subgraph [Formula: see text] is connected. The minimum cardinality taken over all connected dominating sets of [Formula: see text] is called the connected domination number of [Formula: see text] and is denoted by [Formula: see text] In this paper, we give the exact values of domination parameters for edge cycle graphs [Formula: see text] where [Formula: see text] and [Formula: see text] Also, we obtain bounds for the domination parameters of edge cycle graphs [Formula: see text] where [Formula: see text] is an arbitrary graph and [Formula: see text] and characterize the extremal graphs. Moreover, Nordhaus–Gaddum-type results are presented for the domination parameters of edge cycle graphs.
Expression of the FOXP1 Transcription Factor Is Strongly Associated with Inferior Survival in Patients with Diffuse Large B-Cell Lymphoma
Authors: Banham Alison H. , Connors Joseph M. , Brown Philip J. , Cordell Jacqueline L. , Ott German , Sreenivasan Gayatri , Farinha Pedro , Horsman Douglas E. , Gascoyne Randy D. 
Published: June 2022

Abstract
Gene expression profiling studies have reported up-regulated mRNA expression of the FOXP1 forkhead transcription factor in response to normal B-cell activation and high expression in a poor prognosis subtype of diffuse large B-cell lymphoma (DLBCL). The purpose of this study was to investigate the prognostic importance of FOXP1 protein expression in an independent series of DLBCL.
First, the specificity of our FOXP1 monoclonal antibody was verified by confirming that it did not recognize the closely related FOXP2, FOXP3, or FOXP4 proteins. FOXP1 protein expression was then analyzed by immunohistochemistry using a DLBCL tissue microarray constructed from 101 previously untreated de novo cases from the British Columbia Cancer Agency. FOXP1 expression was scored as either positive (&gt;30% positive nuclei) or negative (&lt;30% positive nuclei).
The overall survival curves clearly showed that patients grouped as FOXP1-positive (40%) had a significantly decreased overall survival (P = 0.0001). FOXP1-positive patients had a median overall survival of 1.6 years compared with 12.2 years in FOXP1-negative cases. In addition, FOXP1-positive patients showed a clear trend to earlier progression in comparison to the FOXP1-negative patients. The analysis of FOXP1 expression within low, medium, and high International Prognostic Index groupings found that FOXP1-negative patients had better overall survival within each group indicating that FOXP1 expression has predictive value independent of the International Prognostic Index subgrouping, a finding that was confirmed in multivariate analysis. These initial results suggest that FOXP1 expression may be important in DLBCL pathogenesis.
Matrix Metalloproteinase-12 Expression Correlates with Local Recurrence and Metastatic Disease in Non–Small Cell Lung Cancer Patients
Authors: Hofmann Hans-Stefan , Hansen Gesine , Richter Günther , Taege Christiane , Simm Andreas , Silber Rolf-Edgar , Burdach Stefan 
Published: June 2022

Abstract
Purpose: Non–small cell lung cancer (NSCLC) is a very common and aggressive malignancy. Survival after resection of tumor is especially determined by the occurrence of distant metastasis. Matrix metalloproteinases (MMP) support this metastatic process by degradation of the extracellular matrix.
Experimental Design: We used DNA microarray technology to examine the expression of 22 MMPs in 89 surgically treated NSCLC patients. Validation of microarray results was done using reverse transcription-PCR and immunohistology.
Results: MMP-1, MMP-9, and MMP-12 expression was significantly increased in tumors versus corresponding lung tissues. MMP-12 expression significantly correlated with local recurrence and metastatic disease. Multivariate Cox regression analysis revealed MMP-12 expression as an independent prognostic factor for tumor relapse–free interval. Gene expression analysis of 158 healthy tissues from 32 different organs revealed no MMP-12 expression in these organs and immunohistology identified MMP-12 protein in NSCLC only in tumor cells.
Conclusions: MMP-12 might be not only a prognostic marker, but also a valuable therapeutic target.
Peritoneal and Subperitoneal Stroma May Facilitate Regional Spread of Ovarian Cancer
Authors: Wang Ena , Ngalame Yvonne , Panelli Monica C. , Nguyen-Jackson Hoainam , Deavers Michael , Mueller Peter , Hu Wei , Savary Cherylyn A. , Kobayashi Ryuji , Freedman Ralph S. , Marincola Francesco M. 
Published: June 2022

Abstract
Purpose: Epithelial ovarian cancer (EOC) is characterized by early peritoneal involvement ultimately contributing to morbidity and mortality. To study the role of the peritoneum in fostering tumor invasion, we analyzed differences between the transcriptional repertoires of peritoneal tissue lacking detectable cancer in patients with EOC versus benign gynecologic disease.
Experimental Design: Specimens were collected at laparotomy from patients with benign disease (b) or malignant (m) ovarian pathology and comprised primary ovarian tumors, paired bilateral specimens from adjacent peritoneum and attached stroma (PE), subjacent stroma (ST), peritoneal washes, ascites, and peripheral blood mononuclear cells. Specimens were immediately frozen. RNA was amplified by in vitro transcription and cohybridized with reference RNA to a custom-made 17.5k cDNA microarray.
Results: Principal component analysis and unsupervised clustering did not segregate specimens from patients with benign or malignant pathology. Class comparison identified differences between benign and malignant PE and ST specimens deemed significant by permutation test (P = 0.027 and 0.012, respectively). A two-tailed Student's t test identified 402 (bPE versus mPE) and 663 (mST versus bST) genes differentially expressed at a significance level of P2 ≤ 0.005 when all available paired samples from each patient were analyzed. The same comparison using one sample per patient reduced the pool of differentially expressed genes but retained permutation test significance for bST versus mST (P = 0.031) and borderline significance for bPE versus mPE (P = 0.056) differences.
Conclusions: The presence of EOC may foster peritoneal implantation and growth of cancer cells by inducing factors that may represent molecular targets for disease control.
A Predictor Based on the Somatic Genomic Changes of the BRCA1/BRCA2 Breast Cancer Tumors Identifies the Non-BRCA1/BRCA2 Tumors with BRCA1 Promoter Hypermethylation
Authors: Alvarez Sara , Diaz-Uriarte Ramon , Osorio Ana , Barroso Alicia , Melchor Lorenzo , Paz Maria Fe , Honrado Emiliano , Rodríguez Raquel , Urioste Miguel , Valle Laura , Díez Orland , Cigudosa Juan Cruz , Dopazo Joaquin , Esteller Manel , Benitez Javier 
Published: June 2022

Abstract
The genetic changes underlying in the development and progression of familial breast cancer are poorly understood. To identify a somatic genetic signature of tumor progression for each familial group, BRCA1, BRCA2, and non-BRCA1/BRCA2 (BRCAX) tumors, by high-resolution comparative genomic hybridization, we have analyzed 77 tumors previously characterized for BRCA1 and BRCA2 germ line mutations. Based on a combination of the somatic genetic changes observed at the six most different chromosomal regions and the status of the estrogen receptor, we developed using random forests a molecular classifier, which assigns to a given tumor a probability to belong either to the BRCA1 or to the BRCA2 class. Because 76.5% (26 of 34) of the BRCAX cases were classified with our predictor to the BRCA1 class with a probability of &gt;50%, we analyzed the BRCA1 promoter region for aberrant methylation in all the BRCAX cases. We found that 15 of the 34 BRCAX analyzed tumors had hypermethylation of the BRCA1 gene. When we considered the predictor, we observed that all the cases with this epigenetic event were assigned to the BRCA1 class with a probability of &gt;50%. Interestingly, 84.6% of the cases (11 of 13) assigned to the BRCA1 class with a probability &gt;80% had an aberrant methylation of the BRCA1 promoter. This fact suggests that somatic BRCA1 inactivation could modify the profile of tumor progression in most of the BRCAX cases.
Cyclin D1 Is a Valuable Prognostic Marker in Oropharyngeal Squamous Cell Carcinoma
Authors: Yu Ziwei , Weinberger Paul M. , Haffty Bruce G. , Sasaki Clarence , Zerillo Cynthia , Joe John , Kowalski Diane , Dziura James , Camp Robert L. , Rimm David L. , Psyrri Amanda 
Published: June 2022

Abstract
Background: The current tumor-node-metastasis system is inadequate to accurately classify patients in terms of prognosis. Thus, with the availability of recently developed molecular tools, considerable interest lies in discovering prognostic markers in order to guide treatment decisions. In this study, we sought to determine the prognostic significance of the cell cycle regulator cyclin D1 in oropharyngeal squamous cell carcinoma (OSCC).
Experimental Design: We studied the protein expression levels of cyclin D1 on a tissue microarray composed of 63 OSCCs with long-term follow-up data available. Protein expression was analyzed with an automated in situ quantitative (AQUA) method which allows preservation of tissue morphology while quantifying protein expression in paraffin-embedded tissue.
Results: The mean follow-up time was 35 months. High cyclin D1 nuclear expression was associated with increased 5-year local recurrence rate (48% versus 15%), inferior 5-year disease-free survival (16% versus 58%), and inferior 5-year overall survival (17% versus 53%). In multivariate Cox regression, high nuclear cyclin D1 expression was an independent predictor for local recurrence, disease-free survival, and overall survival at 5 years.
Conclusions: Our results indicate that quantitative assessment of nuclear cyclin D1 expression level by automated in situ quantitative analysis is a strong predictor for outcome in OSCC. Thus, cyclin D1 may be a potential target for molecular intervention in patients with oropharyngeal squamous cell cancer.