bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phase I Trial of N-803, an IL15 Receptor Agonist, with Rituximab in Patients with Indolent Non-Hodgkin Lymphoma
Authors: Foltz Jennifer A. , Hess Brian T. , Bachanova Veronika , Bartlett Nancy L. , Berrien-Elliott Melissa M. , McClain Ethan , Becker-Hapak Michelle , Foster Mark , Schappe Timothy , Kahl Brad , Mehta-Shah Neha , Cashen Amanda F. , Marin Nancy D. , McDaniels Kristen , Moreno Chaz , Mosior Matthew , Gao Feng , Griffith Obi L. , Griffith Malachi , Wagner Julia A. , Epperla Narendranath , Rock Amy D. , Lee John , Petti Allegra A. , Soon-Shiong Patrick , Fehniger Todd A. 
Published: April 2021

Abstract

Purpose:
N-803 is an IL15 receptor superagonist complex, designed to optimize in vivo persistence and trans-presentation, thereby activating and expanding natural killer (NK) cells and CD8+ T cells. Monoclonal antibodies (mAbs) direct Fc receptor–bearing immune cells, including NK cells, to recognize and eliminate cancer targets. The ability of IL15R agonists to enhance tumor-targeting mAbs in patients has not been reported previously.

Patients and Methods:
Relapsed/refractory patients with indolent non-Hodgkin lymphoma were treated with rituximab and intravenous or subcutaneous N-803 on an open-label, dose-escalation phase I study using a 3+3 design (NCT02384954). Primary endpoint was maximum tolerated dose. Immune correlates were performed using multidimensional analysis via mass cytometry and cellular indexing of transcriptomes and epitopes by sequencing (CITE-seq) which simultaneously measures protein and single-cell RNA expression.

Results:
This immunotherapy combination was safe and well tolerated and resulted in durable clinical responses including in rituximab-refractory patients. Subcutaneous N-803 plus rituximab induced sustained proliferation, expansion, and activation of peripheral blood NK cells and CD8 T cells, with increased NK cell and T cells present 8 weeks following last N-803 treatment. CITE-seq revealed a therapy-altered NK cell molecular program, including enhancement of AP-1 transcription factor. Furthermore, the monocyte transcriptional program was remodeled with enhanced MHC expression and antigen-presentation genes.

Conclusions:
N-803 combines with mAbs to enhance tumor targeting in patients, and warrants further investigation in combination with immunotherapies.
International Evidence Based Reappraisal of Genes Associated With Arrhythmogenic Right Ventricular Cardiomyopathy Using the Clinical Genome Resource Framework
Authors: James Cynthia A. , Jongbloed Jan D.H. , Hershberger Ray E. , Morales Ana , Judge Daniel P. , Syrris Petros , Pilichou Kalliopi , Domingo Argelia Medeiros , Murray Brittney , Cadrin-Tourigny Julia , Lekanne Deprez Ronald , Celeghin Rudy , Protonotarios Alexandros , Asatryan Babken , Brown Emily , Jordan Elizabeth , McGlaughon Jennifer , Thaxton Courtney , Kurtz C. Lisa , van Tintelen J. Peter 
Published: April 2021

Background:
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited disease characterized by ventricular arrhythmias and progressive ventricular dysfunction. Genetic testing is recommended, and a pathogenic variant in an ARVC-associated gene is a major criterion for diagnosis according to the 2010 Task Force Criteria. As incorrect attribution of a gene to ARVC can contribute to misdiagnosis, we assembled an international multidisciplinary ARVC Clinical Genome Resource Gene Curation Expert Panel to reappraise all reported ARVC genes.

Methods:
Following a comprehensive literature search, six 2-member teams conducted blinded independent curation of reported ARVC genes using the semiquantitative Clinical Genome Resource framework.

Results:

Of 26 reported ARVC genes, only 6 (
PKP2
,
DSP
,
DSG2
,
DSC2
,
JUP
, and
TMEM43
) had strong evidence and were classified as definitive for ARVC causation. There was moderate evidence for 2 genes,
DES
and
PLN
. The remaining 18 genes had limited or no evidence.
RYR2
was refuted as an ARVC gene since clinical data and model systems exhibited a catecholaminergic polymorphic ventricular tachycardia phenotype. In ClinVar, only 5 pathogenic/likely pathogenic variants (1.1%) in limited evidence genes had been reported in ARVC cases in contrast to 450 desmosome gene variants (97.4%).

Conclusions:

Using the Clinical Genome Resource approach to gene-disease curation, only 8 genes (
PKP2
,
DSP
,
DSG2
,
DSC2
,
JUP
,
TMEM43
,
PLN
, and
DES
) had definitive or moderate evidence for ARVC, and these genes accounted for nearly all pathogenic/likely pathogenic ARVC variants in ClinVar. Therefore, only pathogenic/likely pathogenic variants in these 8 genes should yield a major criterion for ARVC diagnosis. Pathogenic/likely pathogenic variants identified in other genes in a patient should prompt further phenotyping as variants in many of these genes are associated with other cardiovascular conditions.
Global Value Chain Upgrading and Business-academia Collaborations: Case Studies of Successful Innovators
Authors: Paliokaitė Agnė , Jašinskaitė Elžbieta , Tiits Marek 
Published: April 2021

Abstract
The article links upgrading in the global value chains with the triple helix concept by focusing on business-academia collaborations that played a part in firms’ capacity to upgrade. Both are crucial for Central Eastern European countries, which face the need to restructure their economies and escape the “middle income trap”. The article asks the following research question: how can public policy encourage business-academia collaboration or other types of activities that contribute to firm upgrading? Data on four different case studies in Lithuania is analysed to answer this question. Results indicate that building endogenous technological capacity through a variety of business-university collaboration types is needed to attract higher-value foreign direct investment and facilitate intersectoral and functional global value chain upgrading. Furthermore, besides research and development, educating and training the labour force are likely to be even more poweful drivers for business-academia collaboration in Central and Eastern Europe.
The Intentional Compassion Framework for school communities
Authors: Kennedy Carla J , Gardner Fiona , Southall Anne 
Published: April 2021

Objective: This article offers a framework to guide schools in developing a compassionate culture. Using a social constructionist/critical perspective, five spheres of work are identified to help schools achieve this goal. Framing death, dying and bereavement from a health promoting perspective, they involve challenging current cultural perceptions, creating a culture of support, creating a grief-informed culture, establishing a culture of reflection and reflexivity, and developing a whole school plan. Setting: Eight rural primary school communities in central Victoria, Australia. Method: Constructivist grounded theory with interviews and analysis occurring concurrently, allowing categories to develop alongside new questions to explore participants’ thinking and priorities. Results: Participants’ insights, knowledge and priorities fostered understanding and led to the five strategies for change that underpin this framework. Conclusion: Study participants’ desire for a societal, cultural shift in how to understand death, dying and bereavement issues in school communities serves as an important foundation for change.
Prevalence of Effective Audit-and-Feedback Practices in Primary Care Settings: A Qualitative Examination Within Veterans Health Administration
Authors: Hysong Sylvia J. , SoRelle Richard , Hughes Ashley M. 
Published: April 2021

Objective The purpose of this study is to uncover and catalog the various practices for delivering and disseminating clinical performance in various Veterans Affairs (VA) locations and to evaluate their quality against evidence-based models of effective feedback as reported in the literature. Background Feedback can enhance clinical performance in subsequent performance episodes. However, evidence is clear that the way in which feedback is delivered determines whether performance is harmed or improved. Method We purposively sampled 16 geographically dispersed VA hospitals based on high, low, consistently moderate, and moderately average highly variable performance on a set of 17 outpatient clinical performance measures. We excluded four sites due to insufficient interview data. We interviewed four key personnel from each location ( n = 48) to uncover effective and ineffective audit and feedback strategies. Interviews were transcribed and analyzed qualitatively using a framework-based content analysis approach to identify emergent themes. Results We identified 102 unique strategies used to deliver feedback. Of these strategies, 64 (62.74%) have been found to be ineffective according to the audit-and-feedback research literature. Comparing features common to effective (e.g., individually tailored, computerized feedback reports) versus ineffective (e.g., large staff meetings) strategies, most ineffective strategies delivered feedback in meetings, whereas strategies receiving the highest effectiveness scores delivered feedback via visually understood reports that did not occur in a group setting. Conclusions Findings show that current practices are leveraging largely ineffective feedback strategies. Future research should seek to identify the longitudinal impact of current feedback and audit practices on clinical performance. Application Feedback in primary care has little standardization and does not follow available evidence for effective feedback design. Future research in this area is warranted.
Using the Electronic Health Record to Characterize the Hepatitis C Virus Care Cascade
Authors: Christy Shannon M. , Reich Richard R. , Rathwell Julie A. , Vadaparampil Susan T. , Isaacs-Soriano Kimberly A. , Friedman Mark S. , Roetzheim Richard G. , Giuliano Anna R. 
Published: April 2021

Objectives Chronic hepatitis C virus (HCV) infection is one of the main causes of hepatocellular carcinoma. Before initiating a multilevel HCV screening intervention, we sought to (1) describe concordance between the electronic health record (EHR) data warehouse and manual medical record review in recording aspects of HCV testing and treatment and (2) estimate the percentage of patients with chronic HCV infection who initiated and completed HCV treatment using manual medical record review. Methods We examined the medical records for 177 patients (100 randomly selected patients born during 1945-1965 without evidence of HCV testing and 77 adult patients of any birth cohort who had completed HCV testing) with a primary care or relevant specialist visit at an academic health care system in Tampa, Florida, from 2015 through 2018. We used the Cohen κ coefficient to examine the degree of concordance between the searchable data warehouse and the medical record review abstractions. Descriptive statistics characterized referral to and receipt of treatment among patients with chronic HCV infection from medical record review. Results We found generally good concordance between the data warehouse abstraction and medical record review for HCV testing data (κ ranged from 0.66 to 0.87). However, the data warehouse failed to capture data on HCV treatment variables. According to medical record review, 28 patients had chronic HCV infection; 16 patients were prescribed treatment, 14 initiated treatment, and 9 achieved and had a reported posttreatment undetected HCV viral load. Conclusions Using data warehouse data provides generally reliable HCV testing information. However, without the use of natural language processing and purposeful EHR design, manual medical record reviews will likely be required to characterize treatment initiation and completion.
Student Preparedness and Success in Introductory Psychology
Authors: Altman William S. , Pena-Shaff Judith B. , Nicholls Craig , Domingo Cassandra 
Published: April 2021

Background: Reading comprehension and writing ability are critical to students’ success in introductory psychology. However, these generally are not prerequisites. There is conflicting evidence with regard to the effectiveness of remedial reading and writing classes for students with low placement exam scores. Objectives: To explore whether ACCUPLACER® test scores help predict performance in introductory psychology, and the effectiveness of reading and writing remediation classes in helping students, particularly those with low ACCUPLACER® scores. Method: Logistic regression analyses were used, to explore whether ACCUPLACER® test scores helped predict performance, and whether completing remediation classes helped students pass, controlling for ACCUPLACER® and WritePlacer® scores, at an upstate New York community college, between the years 2010 and 2015. Results: Placement test scores did help to predict successful course completion. There was not a statistically significant difference in successful course completion between students who passed the remedial courses and those who did not take them. Conclusions: Success in introductory psychology requires college-level reading and writing. Remedial courses’ value in students’ success in this class appears relatively small or non-significant. Teaching Implications: We propose solutions that may be more effective, involving embedding the remediation in the course, or in closely linked ancillary sections.
United in earnest: First pilot sites for increased surgical capacity for rheumatic heart disease announced by Cardiac Surgery Intersociety Alliance
Authors: Enumah Zachary O , Bolman Ralph M , Zilla Peter , Boateng Percy , Wilson Barry , Kumar AS , Chotivatanapong Taweesak , Beyersdorf Friedhelm , Pomar Jose , Sliwa Karen , Eiselé Jean-Luc , Dearani Joseph , Higgins Robert 
Published: April 2021

Background Rheumatic heart disease affects more than 33,000,000 individuals, mostly from low- and middle-income countries. The Cape Town Declaration on Access to Cardiac Surgery in the Developing World was published in August 2018, signaling the commitment of the global cardiac surgery and cardiology communities to improving care for rheumatic heart disease patients. Methods As the Cape Town Declaration formed the basis for which the Cardiac Surgery Intersociety Alliance was formed, the purpose of this article is to describe the history of the Cardiac Surgery Intersociety Alliance, its formation, ongoing activities, and future directions, including the announcement of selected pilot sites. Results The Cardiac Surgery Intersociety Alliance is an international alliance consisting of representatives from major cardiothoracic surgical societies and the World Heart Federation. Activities have included meetings at annual conferences, exhibit hall participation for advertisement and recruitment, and publication of selection criteria for cardiac surgery centers to apply for Cardiac Surgery Intersociety Alliance support. Criteria focused on local operating capacity, local championing, governmental and facility support, appropriate identification of a specific gap in care and desire to engage in future research. Eleven applications were received for which three finalist sites were selected and site visits conducted. The two selected sites were Hospital Central Maputo (Mozambique) and King Faisal Hospital Kigali (Rwanda). Conclusions Substantial progress has been made since the passing of the Cape Town Declaration and the formation of the Cardiac Surgery Intersociety Alliance, but ongoing efforts with collaboration of all committed parties—cardiac surgery, cardiology, industry, and government—will be necessary to improve access to life-saving cardiac surgery for rheumatic heart disease patients.
Home palliative care professionals perception of challenges during the Covid-19 outbreak: A qualitative study
Authors: Franchini Luca , Varani Silvia , Ostan Rita , Bocchi Ilenia , Pannuti Raffaella , Biasco Guido , Bruera Eduardo 
Published: April 2021

Background: Home palliative care services have played an essential role during the first wave of the SARS-CoV-2 outbreak by providing symptom control, drug procurement, and psychological support for frail patients and their families unable to leave their homes. Aim: To understand how home palliative care professionals were affected by the outbreak, describing changes and challenges in their daily work as well as their reactions to the Covid-19 pandemic in Italy. Design: Qualitative study conducted using telephone semi-structured interviews, with thematic analysis. Setting/participants: Thirty home care professionals working for an Italian non-profit organization which provides home palliative care for cancer patients and their families. Results: Three main themes were identified. The first theme showed both patient-related and practice-related challenges participants faced in their daily work, requiring the implementation of different communication methods and patient and family education on risk prevention. The second theme showed the perception of increased responsibility and being the only landmark for family played a decisive role in participants’ positive attitude. The third theme highlighted the participants’ perception of the critical role of a home care setting in this emergency situation. Conclusions: The first wave of the Covid-19 pandemic brought many challenges and stressors for home palliative care professionals. On the other side, they reported a satisfaction with their critical role in carrying out their work with patients at risk.
Estimating the Prevalence of Mental and Substance Use Disorders: A Systematic Approach to Triangulating Available Data to Inform Health Systems Planning
Authors: Vigo Daniel , Jones Wayne , Dove Naomi , Maidana Daniel E. , Tallon Corinne , Small Will , Samji Hasina 
Published: April 2021

Objective: To estimate the prevalence of specific mental and substance use disorders (MSUDs), by age and sex, as a first step toward informing needs-based health systems planning by decision-makers. Methods: We developed a conceptual framework and a systematic methodology for combining available data sources to yield prevalence estimates for specific MSUDs. Data sources used included published, peer-reviewed literature from Canada and comparable countries, Canadian population survey data, and health administrative data from British Columbia. Several well-established methodologies including systematic review and meta-analyses of published prevalence estimates, modelling of age- and sex-specific distributions, and the Global Burden of Disease severity distribution model were incorporated in a novel mode of triangulation. Results: Using this novel approach, we obtained prevalence estimates for 10 MSUDs for British Columbia, Canada, as well as prevalence distributions across age groups, by sex. Conclusion: Obtaining reliable assessments of disorder prevalence and severity is a useful first step toward rationally estimating service need and plan health services. We propose a methodology to leverage existing information to obtain robust estimates in a timely manner and with sufficient granularity to, after adjusting for comorbidity and matching with severity-specific service bundles, inform need-based planning efforts for adult (15 years and older) mental health and substance use services.
Isolation of hydrodynamic parameters for the fibre length attrition in injection-moulded short-fibre polymer composites
Authors: Ruiz María P , Pontes António J V , Ludueña Leandro N 
Published: April 2021

A comprehensive study of the fibre breakage mechanisms during mould filling in injection moulding of short-fibre polymer composites requires the isolation of the main parameters promoting fibre length attrition. In this work, hydrodynamic parameters such as injection flow rate and residence time in the range of injection moulding were isolated, and their effect on fibre length attrition was studied. Fibre breakage was quantified by means of a capillary rheometer attached to an injection moulding machine minimising fibre-equipment interactions. Fibre breakage increased linearly as a function of injection flow rate in the range of 30–120 cm3.s−1. It was also found that residence time in the order of milliseconds had a significant effect on fibre breakage. The results shown that longer fibres had less breakage probability, which contradicts the buckling failure theory for brittle fibres in a simple shear flow. This result was attributed to the similar rotation period of the fibres in comparison with the test residence times.
Conscience and conscientious objection in nursing: A personalist bioethics approach
Authors: Lamb Christina , Pesut Barbara 
Published: April 2021

The ability of nurses to act as moral agents in accordance with their conscience is both an essential human freedom and an important part of professional ethics. Recent developments in Canada related to Medical Assistance in Dying have revealed new and important challenges related to conscientious objection – challenges that may require rethinking of how nurses do professional ethics. Notably, the inclusion of a personalist bioethical approach is needed to introduce and explicate what conscience is for nurses to be able to apply it to nursing practice. In this article, we explore the importance of conscience and conscientious objection as ethical concepts to support nurses in addressing issues of conscience amid ethically challenging situations. We discuss how a personalist basis for conscience can support nurses to inclusively engage with one another across diverse moral perspectives.
Usefulness of the Biomarker TIMP-2•IGFBP7 for Acute Kidney Injury Assessment in Critically Ill Patients: A Narrative Review
Authors: Erstad Brian L. 
Published: April 2021

Objectives: To review the clinical usefulness of the biomarker TIMP-2•IGFBP7 in adult, general medical-surgical intensive care unit (ICU) settings. Data Sources: PubMed (1946 to mid-February 2021) and EMBASE (1947 to mid-February 2021) with bibliographies of retrieved articles reviewed for additional articles. Study Selection and Data Extraction: Studies evaluating use of the urinary TIMP-2•IGFBP7 assay in adult patients in ICU settings. Data Synthesis: Studies published after investigations leading to TIMP-2•IGFBP7 assay approval confirm the appropriateness of considerations discussed in product labeling, such as use of the test within 12 hours of assessment, use of a dichotomous 0.3 (ng/mL)2/1000 cutoff, and use only in combination with other assessments of acute kidney injury (AKI). However, as a biomarker routinely used for early identification of patients at risk for AKI in mixed ICU populations, the additional resources required for TIMP-2•IGFBP monitoring are difficult to justify because of limited data demonstrating usefulness in preventing or ameliorating AKI and its attendant complications. Relevance to Patient Care and Clinical Practice: Biomarkers are potentially useful not only for assessment and diagnosis of AKI, but also for practitioners involved in the management of nephrotoxic medications and medications needing adjustment for decreased kidney function. Conclusions: Although there is evidence to suggest that the urinary TIMP-2•IGFBP7 biomarker is helpful in predicting AKI progression in general medical-surgical ICU patients when used within 12 hours of patient assessment in combination with routine testing, including serum creatinine and urine output, there is little evidence that its use leads to improvements in clinically important patient outcomes.