bluuebunny/crossref_metadata_2025_split huggingface dataset:
Overcoming barriers to recruitment and retention of African–American women with SLE in behavioural interventions: lessons learnt from the WELL study
Authors: Drenkard Cristina , Easley Kirk , Bao Gaobin , Dunlop-Thomas Charmayne , Lim S Sam , Brady Teresa 
Published: June 2020

BackgroundAfrican–Americans are historically under-represented in SLE studies and engaging them in behavioural interventions is challenging. The Women Empowered to Live with Lupus (WELL) study is a trial conducted to examine the effectiveness of the Chronic Disease Self-Management Program (CDSMP) among African–American women with SLE. We describe enrolment and retention challenges and successful strategies of the WELL study.MethodsThe Georgians Organized Against Lupus (GOAL) cohort, a population-based cohort established in Atlanta, Georgia, was used to enrol a sample of 168 African–American women with SLE into the CDSMP. The CDSMP is a 6-week, group-based programme led by peers to enhance self-management skills in people with chronic conditions. Study performance standards were predefined and close monitoring of recruitment and retention progress was conducted by culturally competent staff members. Continuous contact with participants, research coordinators’ notes and regular research team meetings served to assess barriers and define strategies needed to meet the desired recruitment and retention outcomes.ResultsWhile no substantial barriers were identified to enrol GOAL participants into the WELL study, WELL participants faced difficulties registering for and/or completing (attending ≥4 sessions) a CDSMP workshop. Major barriers were unpredicted personal and health-related issues, misunderstanding of the scope and benefits of the intervention, and transportation problems. Early implementation of tailored strategies (eg, CDSMP scheduled on Saturdays, CDSMP delivered at convenient/familiar facilities, transportation services) helped to reduce participant barriers and achieve a CDSMP registration of 168 participants, with 126 (75%) completers. Frequent contact with participants and compensation helped to reach 92.3% retention for the 6-month survey.ConclusionsPredefined standards and monitoring of participant barriers by a culturally competent research team and proactive solutions were critical to implementing successful strategies and achieving the desired recruitment and retention outcomes of a behavioural trial involving African–American women with SLE.Trial registration numberNCT02988661.
APL since 1978
Authors: Hui Roger K. W. , Kromberg Morten J. 
Published: June 2020

The Evolution of APL
, the HOPL I paper by Falkoff and Iverson on APL, recounted the fundamental design principles which shaped the implementation of the APL language in 1966, and the early uses and other influences which shaped its first decade of enhancements.

In the 40 years that have elapsed since HOPL I, several dozen APL implementations have come and gone. In the first decade or two, interpreters were typically born and buried along with the hardware or operating system that they were created for. More recently, the use of C as an implementation language provided APL interpreters with greater longevity and portability.

APL started its life on IBM mainframes which were time-shared by multiple users. As the demand for computing resources grew and costs dropped, APL first moved
in-house
to mainframes, then to
mini
- and
micro
-computers. Today, APL runs on PCs and tablets, Apples and Raspberry Pis, smartphones and watches.

The operating systems, and the software application platforms that APL runs on, have evolved beyond recognition. Tools like database systems have taken over many of the tasks that were initially implemented in APL or provided by the APL system, and new capabilities like parallel hardware have also changed the focus of design and implementation efforts through the years.
The first wave of significant language enhancements occurred shortly after HOPL I, resulting in so-called second-generation APL systems. The most important feature of the second generation is the addition of general arrays—in which any item of an array can be another array—and a number of new functions and operators aligned with, if not always motivated by, the new data structures.
The majority of implementations followed IBM’s path with APL2 “floating” arrays; others aligned themselves with SHARP APL and “grounded” arrays. While the APL2 style of APL interpreters came to dominate the mainstream of the APL community, two new cousins of APL descended from the SHARP APL family tree: J (created by Iverson and Hui) and k (created by Arthur Whitney).
We attempt to follow a reasonable number of threads through the last 40 years, to identify the most important factors that have shaped the evolution of APL. We will discuss the details of what we believe are the most significant language features that made it through the occasionally unnatural selection imposed by the loss of habitats that disappeared with hardware, software platforms, and business models.
The history of APL now spans six decades. It is still the case, as Falkoff and Iverson remarked at the end of the HOPL I paper, that:
Although this is not the place to discuss the future, it should be remarked that the evolution of APL is far from finished.
Engineering the Human Fc Region Enables Direct Cell Killing by Cancer Glycan–Targeting Antibodies without the Need for Immune Effector Cells or Complement
Authors: Vankemmelbeke Mireille , McIntosh Richard S. , Chua Jia Xin , Kirk Thomas , Daniels Ian , Patsalidou Marilena , Moss Robert , Parsons Tina , Scott David , Harris Gemma , Ramage Judith M. , Spendlove Ian , Durrant Lindy G. 
Published: June 2020

AbstractMurine IgG3 glycan-targeting mAb often induces direct cell killing in the absence of immune effector cells or complement via a proinflammatory mechanism resembling oncotic necrosis. This cancer cell killing is due to noncovalent association between Fc regions of neighboring antibodies, resulting in enhanced avidity. Human isotypes do not contain the residues underlying this cooperative binding mode; consequently, the direct cell killing of mouse IgG3 mAb is lost upon chimerization or humanization. Using the Lewisa/c/x -targeting 88mAb, we identified the murine IgG3 residues underlying the direct cell killing and increased avidity via a series of constant region shuffling and subdomain swapping approaches to create improved (“i”) chimeric mAb with enhanced tumor killing in vitro and in vivo. Constant region shuffling identified a major CH3 and a minor CH2 contribution, which was further mapped to discontinuous regions among residues 286–306 and 339–378 that, when introduced in 88hIgG1, recapitulated the direct cell killing and avidity of 88mIgG3. Of greater interest was the creation of a sialyl-di-Lewisa–targeting i129G1 mAb via introduction of these selected residues into 129hIgG1, converting it into a direct cell killing mAb with enhanced avidity and significant in vivo tumor control. The human iG1 mAb, termed Avidimabs, retained effector functions, paving the way for the proinflammatory direct cell killing to promote antibody-dependent cellular cytotoxicity and complement-dependent cytotoxicity through relief of immunosuppression. Ultimately, Fc engineering of human glycan-targeting IgG1 mAb confers proinflammatory direct cell killing and enhanced avidity, an approach that could be used to improve the avidity of other mAb with therapeutic potential.Significance:Fc engineering enhances avidity and direct cell killing of cancer-targeting anti-glycan antibodies to create superior clinical candidates for cancer immunotherapy.
UGT2B10 Genotype Influences Serum Cotinine Levels and Is a Primary Determinant of Higher Cotinine in African American Smokers
Authors: Sipe Christopher J. , Koopmeiners Joseph S. , Donny Eric C. , Hatsukami Dorothy K. , Murphy Sharon E. 
Published: June 2020

Abstract

Background:
Cotinine is the most widely used biomarker of tobacco exposure. At similar smoking levels, African Americans have higher serum cotinine than Whites. UGT2B10-catalyzed cotinine glucuronidation impacts these levels, and African Americans often have low UGT2B10 activity due to a high prevalence of a UGT2B10 splice variant (rs2942857).

Methods:
Two UGT2B10 SNPs (rs6175900 and rs2942857) were genotyped in 289 African Americans and 627 White smokers. Each smoker was assigned a genetic score of 0, 1, or 2 based on the number of variant alleles. Total nicotine equivalents (TNE), the sum of nicotine and six metabolites, and serum cotinine and 3′-hydroxycotinine were quantified. The contribution of UGT2B10 genetic score to cotinine concentration was determined.

Results:
Serum cotinine was significantly higher in smokers with UGT2B10 genetic scores of 2 versus 0 (327 ng/mL vs. 221 ng/mL; P &lt; 0.001); TNEs were not different. In a linear regression model adjusted for age, gender, cigarettes per day, TNE, race, and CYP2A6 activity, geometric mean cotinine increased 43% between genetic score 2 versus 0 (P &lt; 0.001). A 0.1 increase in the CYP2A6 activity ratio, 3′-hydroxycotinine/cotinine, resulted in a 6% decrease in cotinine. After adjustment for UGT2B10 genotype and the other covariants, there was no significant difference in serum cotinine by race.

Conclusions:
UGT2B10 genotype is a major contributor to cotinine levels and explains the majority of high serum cotinine in African American smokers.

Impact:
Cotinine levels in smokers may greatly overestimate tobacco exposure and potentially misinform our understanding of ethnic/racial difference in tobacco-related disease if UGT2B10 genotype is not taken into account.
Patterns of Omega-3 and Omega-6 Fatty Acid Dietary Intake and Melanoma Thickness at Diagnosis
Authors: Mahamat-Saleh Yahya , Hughes Maria Celia B. , Miura Kyoko , Malt Maryrose K. , von Schuckmann Lena , Khosrotehrani Kiarash , Smithers B. Mark , Green Adèle C. 
Published: June 2020

Abstract

Background:
Experimental evidence suggests that dietary intakes of omega-3 and omega-6 polyunsaturated fatty acids have divergent effects on melanoma growth, but epidemiologic evidence on their combined effect is lacking.

Methods:
In 634 Australian patients with primary melanoma, we assessed prediagnosis consumption of 39 food groups by food frequency questionnaires completed within 2 months of diagnosis. We derived, by reduced rank regression, dietary patterns that explained variability in selected omega-3 and omega-6 fatty acid intakes. Prevalence ratios (PR) and 95% confidence intervals (CI) for the association between tertiles of dietary patterns and melanoma thickness &gt;2 mm versus ≤2 mm were estimated using Poisson regression.

Results:
Overall omega-3 fatty acid intakes were low. Two major fatty acid dietary patterns were identified: “meat, fish, and fat,” positively correlated with intakes of all fatty acids; and “fish, low-meat, and low-fat,” positively correlated with long-chain omega-3 fatty acid intake, and inversely with medium-chain omega-3 and omega-6 fatty acid intakes. Prevalence of thick melanomas was significantly higher in those in the highest compared with lowest tertile of the “meat, fish, and fat” pattern (PR, 1.40; 95% CI, 1.01–1.94), especially those with serious comorbidity (PR, 1.83; 95% CI, 1.15–2.92) or a family history (PR, 2.32; 95% CI, 1.00–5.35). The “fish, low-meat, and low-fat” pattern was not associated with melanoma thickness.

Conclusions:
People with high meat, fish, and fat intakes, who thus consumed relatively high levels of omega-3 and high omega-6 fatty acid intakes, are more likely to be diagnosed with thick than thin melanomas.

Impact:
High omega-3 and omega-6 fatty acid intakes may contribute to patients' presentation with thick melanomas.
Randomized Comparison of Intensified and Standard P2Y
12
-Receptor-Inhibition Before Elective Percutaneous Coronary Intervention
Authors: Mehilli Julinda , Baquet Moritz , Hochholzer Willibald , Mayer Katharina , Tesche Christian , Aradi Daniel , Xu Yujun , Thienel Manuela , Gschwendtner Sarah , Zadrozny Magda , Jochheim David , Sibbing Dirk , Schüpke Stefanie , Mansmann Ulrich , Hoffmann Ellen , Kastrati Adnan , Neumann Franz-Josef , Massberg Steffen 
Published: June 2020

Background:
Even among biomarker-negative patients undergoing elective percutaneous coronary intervention (PCI), periprocedural thrombotic and bleeding complications can lead to increased morbidity and mortality. Whether stronger platelet inhibition by an intensified oral loading strategy (ILS) before PCI impacts on outcomes among these patients in contemporary practice remains unclear.

Methods:
This multicenter, randomized, assessor-blinded trial tested the hypothesis that in elective PCI prasugrel 60 mg (ILS) is superior to standard loading strategy with clopidogrel 600 mg regarding a composite primary end point of all-cause death, any myocardial infarction, definite/probable stent thrombosis, stroke, or urgent vessel revascularization. After PCI, all patients were on clopidogrel 75 mg/day and aspirin. The trial was terminated prematurely because of slower-than-expected recruitment and funding discontinuation.

Results:

Of 781 patients included in the final analysis, 382 were assigned to ILS and 399 to standard loading strategy. At 30 days, the primary end point occurred in 66 patients (17.3%) assigned to ILS and 74 patients (18.6%) assigned to standard loading strategy (odds ratio, 0.92 [95% CI, 0.63–1.32];
P
=0.64). Any myocardial infarction and Bleeding Academic Research Consortium ≥2 bleeding rates were similar among ILS and standard loading strategy groups 16.2% versus 17.5%, odds ratio, 0.91 (95% CI, 0.62–1.32),
P
=0.62 and 4.2% versus 4.8%, odds ratio 0.87 (95% CI, 0.44–1.73),
P
=0.70, respectively.

Conclusions:
In biomarker-negative stable and unstable angina patients undergoing elective PCI, the trial did not find a conclusive difference in efficacy or safety. This observation should be interpreted in the context of wide CIs and premature termination of the trial.

Registration:

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT02548611.
Multiple Coalition Memberships: Helping or Hindering Small States in Multilateral (Climate) Negotiations?
Authors: Klöck Carola 
Published: June 2020

Abstract
This study explores multiple coalition memberships in multilateral negotiations, with a focus on climate negotiations. Why do countries engage in multiple coalitions, and how do multiple coalition memberships affect their influence? I argue that coalitions differ in important respects. Accordingly, countries may belong to both, long-term and short-lived coalitions; they may consciously decide to join a coalition, but also be associated by default. Finally, larger coalitions confer numerical strength, while smaller (sub-)coalitions help voice common positions. Regarding effects, I propose two perspectives. The zero-sum perspective highlights coordination costs and potentially incompatible positions, while the win-win perspective focuses on the complementarity of different coalitions and the potential for mutual support. Anecdotal evidence from the climate negotiations offers support for these perspectives, but further empirical research is needed to better understand why countries join several coalitions, how they navigate these multiple coalition memberships, and how these affect their influence.
Outcomes of Paradoxical Vocal Cord Motion Diagnosed in Childhood
Authors: Yibrehu Betel , Georgakopoulos Bianca , Mudd Pamela A. , Rana Md Sohel , Bauman Nancy M. 
Published: June 2020

Objectives: To explore long-term patient reported outcome (PRO) measures of pediatric paradoxical vocal cord motion (PVCM) including ease of diagnosis, management, symptom duration and effect on quality of life. Methods: All children >8 years of age diagnosed with PVCM at a tertiary pediatric hospital between 2006 and 2017 were invited to complete a survey addressing study objectives. Results: 21/47 eligible participants could be contacted and 18/21 (86%) participated. 78% were female with a mean age at diagnosis of 11.6 and 15.0 years at survey completion. Common PVCM symptoms reported were dyspnea (89%), globus sensation (56%), and stridor (50%). The median time to diagnosis was 3 months (IQR 2-5 months). Nearly all reported being misdiagnosed with another condition, usually asthma, until being correctly diagnosed usually by an otolaryngologist. Participants reported undergoing 3.7 diagnostic studies (range 0-8); pulmonary function testing was most common. Of numerous treatments acknowledged, breathing exercises were common (89%) but only reported helpful by 56%. Use of biofeedback was recalled in 1/3 of subjects but reported helpful in only 14% of them. Anti-reflux, allergy, anticholinergics, inhalers and steroids were each used in >50%, but rarely reported effective. PVCM was reportedly a significant stressor when initially diagnosed but despite 2/3 of participants still reporting ongoing PVCM symptoms, the perceived stress significantly decreased over time (Z = 3.26, P = 0.001). Conclusions: This first PVCM PRO study endorses that diagnosis is often delayed and prescribed treatments often viewed as ineffective. While biofeedback and breathing exercises may be critical for short-term control of PVCM episodes, lifestyle changes and stress reduction are likely necessary for long-term management. Increased awareness and improvements in management are needed for this condition.
Inclusion, acceptance, shame and isolation: Attitudes to autism in Aboriginal and Torres Strait Islander communities in Australia
Authors: Lilley Rozanna , Sedgwick Mikala , Pellicano Elizabeth 
Published: June 2020

This is the first qualitative study to investigate experiences of, and attitudes towards, autism in Aboriginal and Torres Strait Islander communities in Australia. Understanding the complexity of these attitudes is crucial because they influence the recognition of autism as well as the ways in which individuals and families are supported. Twelve families with 16 autistic children living in diverse regions of Australia participated in a semi-structured interview. The interviews were thematically analysed using the six-step process outlined by Braun and Clarke. The analysis identified a marked tension in participants’ accounts. On the one hand, participants described negative feelings, including shame associated with atypical behaviour, stigmatisation and the social isolation of families, which potentially point towards under-identification or misdiagnosis. On the other hand, they also described inclusive attitudes, including ‘looking after each other’ and a growing acceptance of autistic differences. This positive model of support for and acceptance of autistic children and their families may well contribute to good outcomes for autistic children and adults in Aboriginal and Torres Strait Islander communities. More research is needed on cross-cultural and pluralistic understandings of autism, parental perceptions and family experience. Lay Abstract There has been almost no research done about autism in Aboriginal and Torres Strait Islander communities in Australia. This article is the first detailed report on attitudes to autism in these communities. Understanding attitudes to autism is important because they influence whether or not children are diagnosed, as well as the kinds of support autistic people are getting. Twelve families who lived in different parts of Australia were interviewed. They told us that there is a range of attitudes to autism in Aboriginal and Torres Strait Islander communities. These include negative ideas such as sometimes feeling shame associated with children’s unusual behaviour, as well as feeling stigmatised and socially isolated. The negative attitudes reported may mean that some children are missing out on an autism diagnosis or being wrongly diagnosed with a different condition in these communities. They also included positive ideas such as the importance of looking after each other and of accepting autistic people and their differences. We can all learn from these positive attitudes. It will be interesting to know in future projects whether these accepting attitudes lead to better outcomes for autistic children and adults in these communities. This research helps us to understand how autism is thought about in different cultures and how attitudes impact diagnosis and support. It will also help people to plan supports that reflect what Aboriginal and Torres Strait Islander families actually want and need.
Bibliometric analysis of adverse drug reactions and pharmacovigilance research activities in Nepal
Authors: Shrestha Sunil , Danekhu Krisha , KC Bhuvan , Palaian Subish , Ibrahim Mohamed Izham Mohamed 
Published: June 2020

Background: Bibliometric analyses have been used previously to study the measures of quality and impact of research performed in several health-related areas such as adverse drug reactions (ADRs) and pharmacovigilance (PV), etc. This method can assess the research performance of publications quantitatively and statistically. There is no evidence of bibilometric studies analyzing ADRs and PV from Nepal. Therefore, the present study aimed to assess scientific output on ADRs and PV-related research activities in Nepal using a bibliometric analysis of publications from 2004 January to December 2018, that is, 15 years. Methods: A systematic search was conducted in PubMed, Web of Science, Google Scholar, Scopus and Nepal Journal Online (NepJOL) databases. ‘Adverse Drug Reactions‘ or ‘ADRs‘ or ‘ADR‘ or ‘Adverse drug reaction‘ or ‘AE‘ or ‘Adverse Event‘ or ‘Drug-Induced Reaction‘ or ‘Pharmacovigilance‘ or ‘PV‘ and ‘Nepal‘. The search covered 15 years (January 2004 to December 2018) of study on ADRs and PV in Nepal. Only articles retrieved from databases were included, whereas published/unpublished drug bulletins, pharmacy newsletters and thesis were excluded. The articles thus retrieved were recorded, and thereafter analyzed. Word count code was used for the analysis of keywords used in the retrieved articles. Results: A total of 124 articles were retrieved, with the highest rate of publications in 2006 and 2007, with 16 papers each. Among the articles, 10 (8.1%) were published in Kathmandu University Medical Journal (KUMJ). Single papers were published in 38 different journals. Brief reports (1.6%), case reports (31.2%), case series (0.8%), education forums (0.8%), letters to the editor (5.6%), original research articles (41.9%), review articles (9.7%), short communications and short reports (8.1%) on ADRs and PV were recorded. Out of 124 papers, 52 (41.9%) were original research publications. The majority (74.1%) of research was done in the category of ADR incidence, types, prevention, and management, followed by policy and suggestions for strengthening national and regional pharmacovigilance centers of Nepal (14.5%). Conclusions: During the study years, there was an increase in scientific publications on drug safety. A total of 124 published articles were found during bibliometric analysis of ADRs and PV research activities in Nepal.