bluuebunny/crossref_metadata_2025_split huggingface dataset:
From spreading to embedding innovation in health care: Implications for theory and practice
Authors: Scarbrough Harry , Kyratsis Yiannis 
Published: July 2021

Issue
In broad terms, current thinking and literature on the spread of innovations in health care presents it as the study of two unconnected processes—diffusion across adopting organizations and implementation within adopting organizations. Evidence from the health care environment and beyond, however, shows the significance and systemic nature of postadoption challenges in sustainably implementing innovations at scale. There is often only partial diffusion of innovative practices, initial adoption that is followed by abandonment, incomplete or tokenistic implementation, and localized innovation modifications that do not provide feedback to inform global innovation designs.

Critical Theoretical Analysis
Such important barriers to realizing the benefits of innovation question the validity of treating diffusion and implementation as unconnected spheres of activity. We argue that theorizing the spread of innovations should be refocused toward what we call embedding innovation—the question of how innovations are successfully implemented at scale. This involves making the experience of implementation a central concern for the system-level spread of innovations rather than a localized concern of adopting organizations.

Insight/Advance
To contribute to this shift in theoretical focus, we outline three mechanisms that connect the experience of implementing innovations locally to their diffusion globally within a health care system: learning, adapting, and institutionalizing. These mechanisms support the distribution of the embedding work for innovation across time and space.

Practical Implications
Applying this focus enables us to identify the self-limiting tensions within existing top-down and bottom-up approaches to spreading innovation. Furthermore, we outline new approaches to spreading innovation, which better exploit these embedding mechanisms.
Effect of Donor Age and Corneal Endothelial Cell Density on Non-utilization of Donor Corneal Tissues: A Study From Indian Eye Banks
Authors: Roy Aravind , Chaurasia Sunita , Fernandes Merle , Mohamed Ashik , Murthy Somasheila , Das Sujata 
Published: July 2021

Purpose:
To study the causes of non-utilization of donor corneas and assess whether non-utilized tissues differ from utilized tissues with regard to age and endothelial cell density (ECD).

Methods:
Aretrospective, cross-sectional analyses of all donor corneas collected from a network of 4 eye banks of a tertiary eye care institute in India during a 1-year period (January to December 2019) was conducted. All donor corneas were assessed for tissue quality by slit lamp evaluation, donor age, and specular microscopy. The causes of non-utilization and effect of donor age and ECD on tissue utilization were studied.

Results:
A total of 10,969 corneas were harvested during the study period; 4618 (42.1%) tissues were discarded. The main causes of non-utilization were poor tissue quality accounting for 86.16% (n = 3979) of all discarded corneas. The mean donor age was 50.7 ± 2.9 years and 63.3 ± 2.3 years for used and discarded corneas, respectively (P < 0.0001). The mean ECD of donor tissues was significantly (P < 0.0001) higher in the utilization group (2787.3 ± 77.4 cells/mm2) than that in the non-utilization group (2394.4 ± 82.5 cells/mm2). Donor age and ECD and their interaction were significant (P < 0.001) predictors of tissue utilization rate.

Conclusions:
Donor age and ECD and their interaction were significantly associated with the rate of utilization of donor corneal tissues.
Testing the Use of Data Drawn from the Electronic Health Record to Compare Quality
Authors: Walsh Kathleen E. , Razzaghi Hanieh , Hartley David M. , Utidjian Levon , Alford Shannon , Darwar Rahul A. , Shenkman Elizabeth , Jonas Susannah , Goodick Mary , Finkelstein Jonathan , Ozonoff Al , Black L. Vandy , Shapiro Michael , Shaw Kathryn , McCafferty-Fernandez Jennifer , Marsolo Keith , Kelly Amy , Werk Lloyd N. , Smallwood Jordan , Bailey Charles 
Published: July 2021

Introduction:
Health systems spend $1.5 billion annually reporting data on quality, but efficacy and utility for benchmarking are limited due, in part, to limitations of data sources. Our objective was to implement and evaluate measures of pediatric quality for three conditions using electronic health record (EHR)-derived data.

Methods:
PCORnet networks standardized EHR-derived data to a common data model. In 13 health systems from 2 networks for 2015, we implemented the National Quality Forum measures: % children with sickle cell anemia who received a transcranial Doppler; % children on antipsychotics who had metabolic screening; and % pediatric acute otitis media with amoxicillin prescribed. Manual chart review assessed measure accuracy.

Results:
Only 39% (N = 2,923) of 7,278 children on antipsychotics received metabolic screening (range: 20%–54%). If the measure indicated screening was performed, the chart agreed 88% of the time [95% confidence interval (CI): 81%–94%]; if it indicated screening was not done, the chart agreed 86% (95% CI: 78%–93%). Only 69% (N = 793) of 1,144 children received transcranial Doppler screening (range across sites: 49%–88%). If the measure indicated screening was performed, the chart agreed 98% of the time (95% CI: 94%–100%); if it indicated screening was not performed, the chart agreed 89% (95% CI: 82%–95%). For acute otitis media, chart review identified many qualifying cases missed by the National Quality Forum measure, which excluded a common diagnostic code.

Conclusions:
Measures of healthcare quality developed using EHR-derived data were valid and identified wide variation among network sites. This data can facilitate the identification and spread of best practices.
Standardized Headache Therapy in the Pediatric Emergency Department Using Improvement Methodology
Authors: Vukovic Adam A. , Hariharan Selena , Caruso Michelle C. , Zellner Sara M. , Kabbouche Marielle , Porter Stephen C. , Murtagh-Kurowski Eileen 
Published: July 2021

Introduction:
Primary headache is a common cause of pediatric emergency department (PED) visits. Without published guidelines to direct treatment options, various strategies lacking evidence are often employed. This study aims to standardize primary headache treatment in the PED by promoting evidence-based therapies, reducing nonstandard abortive therapies, and introducing dihydroergotamine (DHE) into practice.

Methods:
A multidisciplinary team developed key drivers, created a clinical care algorithm, and updated electronic medical record order sets. Outcome measures included the percentage of patients receiving evidence-based therapies, nonstandard abortive therapies, DHE given after failed first-line therapies, and overall PED length of stay. Process measures included the percent of eligible patients with the order set usage and medications received within 90 minutes. Balancing measures included hospital admissions and returns to the PED within 72 hours. Annotated control charts depicted results over time.

Results:
We collected data from July 2017 to December 2019. The percent of patients receiving evidence-based therapies increased from 69% to 73%. The percent of patients receiving nonstandard abortive therapies decreased from 2.5% to 0.6%. The percent of patients receiving DHE after failed first-line therapies increased from 0% to 37.2%. No untoward effects on process or balancing measures occurred, with sustained improvement for 14 months.

Conclusion:
Standardization efforts for patients with primary headaches led to improved use of evidence-based therapies and reduced nonstandard abortive therapies. This methodology also led to improved DHE use for migraine headache resistant to first-line therapies. We accomplished these results without increasing length of stay, admission, or return visits.
Incidental Pituitary Adenoma on MIBI Parathyroid Imaging
Authors: Asiri Jaber Abdulwahab , Kulaybi Sami Ahmed , Daghas Fatimah Ahmed 
Published: July 2021

Abstract
A 77-year-old man with a case of hyperthyroidism with high parathyroid hormone (41 pmol/L), low vitamin D, and normal thyroid-stimulating hormone. The SPECT/CT fused images confirmed the evidence of retrotracheal hyperdense mass approximately 1.0 cm of diameter below the lower pole of the right thyroid lobe with increased uptake, highly suggestive of typical parathyroid adenoma. The most significant point is that there was an incidental finding: high focal uptake in the sellar/suprasellar region corresponding to heterogenous soft tissue lesion suspicious for pituitary adenoma. According to the previous scans, nuclear medicine, CT scan, and the MRI scan indicated pituitary adenoma.
FDG PET/CT in Sacroiliac IgG4 Disease
Authors: Elsobky Sherif , Dattani Vruti , Wagner Thomas , Mandumula Sri , Tavare Aniket 
Published: July 2021

Abstract
A 68-year-old woman with abdominal pain and a raised C-reactive protein was investigated with a CT of the abdomen. CT showed an irregular soft tissue mass anterior to the aorta, which was thought to be neoplastic. The patient underwent 18F-FDG PET/CT, which demonstrated hypermetabolic activity in this mass, as well as further foci of hypermetabolic activity in head and neck, sacroiliac joints, and pelvic floor muscles. A CT-guided biopsy of the sacroiliac joint was performed and revealed IgG4-related disease.
High blood uric acid is associated with reduced risks of mild cognitive impairment among older adults in China: a 9-year prospective cohort study
Authors: Chen Chen , Li Xueqin , Lv Yuebin , Yin Zhaoxue , Zhao Feng , Liu Yingchun , Li Chengcheng , Ji Saisai , Zhou Jinhui , Wei Yuan , Cao Xingqi , Wang Jiaonan , Gu Heng , Lu Feng , Liu Zuyun , Shi Xiaoming 
Published: July 2021

AbstractBackgroundIt remains unsolved that whether blood uric acid (UA) is a neuroprotective or neurotoxic agent. This study aimed to evaluate the longitudinal association of blood UA with mild cognitive impairment (MCI) among older adults in China.MethodsA total of 3103 older adults (aged 65+ years) free of MCI at baseline were included from the Healthy Aging and Biomarkers Cohort Study (HABCS). Blood UA level was determined by the uricase colorimetry assay and analyzed as categorical (by quartile) variables. Global cognition was assessed using the Mini-Mental State Examination four times between 2008 and 2017, with a score below 24 being considered as MCI. Cox proportional hazards models were used to examine the associations.ResultsDuring a 9-year follow-up, 486 (15.7%) participants developed MCI. After adjustment for all covariates, higher UA had a dose-response association with a lower risk of MCI (allPfor trend< 0.05). Participants in the highest UA quartile group had a reduced risk (hazard ratio [HR], 0.73; 95% [CI]: 0.55-0.96) of MCI, compared with those in the lowest quartile group. The associations were still robust even when considering death as a competing risk. Subgroup analyses revealed that these associations were statistically significant in younger older adults (65-79 years) and those without hyperuricemia.ConclusionsHigh blood UA level is associated with reduced risks of MCI among Chinese older adults, highlighting the potential of managing UA in daily life for maintaining late-life cognition.
Influence of Novel Coronavirus COVID – 19 and HIV: A Scoping Review of Hospital Course and Symptomatology
Authors: Sheikh Mona , Nagpal Shavy , Zaidi Madiha , Vijayan Rupalakshmi , Matos Wanessa , Ngaba Neguemadji Nagardig , Akano Lordstrong , Jahan Samia , Shah Shazia Q. , Go Camille Celeste , Thevuthasan Sindhu , Michel George 
Published: July 2021

AbstractBackgroundAn outbreak of novel coronavirus (SARS- CoV-2) was observed on December 2019 in Wuhan, China which led to a global pandemic declared in March 2020. As a consequence, it imposed delirious consequences in patients with underlying co – morbid conditions that make them immunocompromised. The purpose of this paper is to provide an in - depth review of influence of COVID – 19 in patients with underlying HIV in terms of mortality and hospitalization.Authors also aim to provide a thorough risk analysis of hospitalization, ICU admission and mortality of PLWH and COVID-19. The secondary objective was to analyze the CD4+ count variations and outcome of COVID - 19 and to correlate if ART provided a protective role. Authors also aim to provide an evaluation of typical clinical presentation of COVID-19 in PLWH. ART is found to show activity against SARS-CoV-2 in vitro, and there is some similarity in the structure of HIV-1 gp41 and S2 proteins of SARS-CoV since they both belong to +ssRNA type.MethodsWe conducted a literature review using search engines namely, Cochrane, PubMed and Google Scholar. The following keywords were targeted: “COVID-19,” “SARS-CoV-2,” and “HIV.” We included case reports, case series, and cohort (retrospective and prospective) studies. We excluded clinical trials and review articles. We came across 23 articles that met the inclusion criteria. PRISMA guidelines were followed for study acquisition (Fig. 9).ResultsFrom the 23 studies, we found a total of 651 PLWH with confirmed COVID-19 (549, 91, and 11 in cohorts, case series, and case reports, respectively). The overall risk of hospital admission from pooled data of the 23 reviewed articles was 69.13% (450/651), ICU admission was 12.90% (84/651) in total infected patients, and 18.67% (84/450) among hospitalized patients. The overall case fatality rate from the 23 reviewed articles was 11.21 (73/651).A weak positive correlation was found between CD4+ counts and hospital admissions in case series and case reports, while the weak negative correlation was found in cohorts. For mortality, there was a negative weak association in the cohorts and in case series, while a weak positive was seen in case reports (Fig.7). We assessed the presenting symptoms of PLWH with COVID-19, and our review demonstrated this group does not greatly differ from the rest of the population, as their common presenting symptoms were cough, fever, and SOB.ConclusionOur results indicated that there was a high rate of hospitalization, ICU admission, and mortality among patients living with HIV and COVID-19. PLWH needs to be noted as a high-risk group for COVID-19 complications and severity. We recommend that PLWH be closely monitored by their physicians and strictly adhere to antiretroviral therapy and standard universal COVID-19 precautions.
Are culturally vibrant communities healthier? Relationships between performing arts activity and health outcomes in the 500 largest US cities
Authors: McCrary J. Matt , Großbach Michael , Altenmüller Eckart 
Published: July 2021

AbstractAimsRecent reviews have demonstrated broad links between performing arts participation (e.g. music-making; dancing; acting) and receptive engagement (e.g. listening to music; attending a dance/theatre performance)and improved health, including reduced disease and mortality risk. However, no investigations to date have interrogated the links between community-level performing arts activity (i.e. participation + receptive engagement) and health outcomes – i.e. do the performing arts help create healthy communities? This study aims to address this question by examining links between performing arts activity and health outcomes across 500 cities in the United States.MethodsSecondary analysis of demographic, health outcome, performing arts activity (estimated by annual performing arts revenue), and preventive/unhealthy behaviour data for 500 large cities in the United States – data extracted from the US Centers for Disease Control 500 Cities Project, Dun & Bradstreet Hoovers Database, and US Census. Links between performing arts activity and 12 health/disease outcomes were evaluated using a series of hierarchical beta regression models which progressively controlled for demographic variables and preventive/unhealthy behaviour prevalence.ResultsThe 500 analysed US cities comprise 33.4% of the total US population and 84,010 performing arts businesses (total annual revenue $27.84 billion). No significant associations were found between performing arts activity and nine of twelve health outcomes in fully adjusted models (p≥.17). Statistically significant relationships (p<.01) between increased performing arts activity and increased prevalence of chronic kidney disease, coronary heart disease, and stroke were determined to be clinically equivocal.ConclusionsThis study contributes to a growing body of conflicting epidemiologic evidence regarding the impact of the performing arts on health/disease and mortality outcomes, evaluated using a range of disparate methodologies. A consensus, psychometrically rigorous approach is required to address this prevailing uncertainty in future epidemiologic studies examining effects of performing arts activities both within and across countries and communities.
Optimizing clinical dosing of combination broadly neutralizing antibodies for HIV prevention
Authors: Mayer Bryan T. , deCamp Allan C. , Huang Yunda , Schiffer Joshua T. , Gottardo Raphael , Gilbert Peter B. , Reeves Daniel B. 
Published: July 2021

AbstractBroadly neutralizing antibodies are promising agents to prevent HIV infection and achieve HIV remission without antiretroviral therapy (ART). As learned from effective ART, HIV viral diversity necessitates combination antibody cocktails. Here, we demonstrate how to optimally choose the ratio within combinations based on the constraint of a total dose size. Optimization in terms of prevention efficacy outcome requires a model that synthesizes 1) antibody pharmacokinetics (PK), 2) a mapping between concentration and neutralization against a genetically diverse pathogen (e.g., distributions of viral IC50 or IC80), 3) a protection correlate to translate in vitro potency to clinical protection, and 4) an in vivo interaction model for how drugs work together. We find that there is not a general solution, and the optimal dose ratio likely will be different if antibodies cooperate versus if both products must be simultaneously present. Optimization requires trade-offs between potency and longevity; using an in silico case-study, we show a cocktail can outperform a bi-specific antibody (a single drug with 2 merged antibodies) with superior potency but worse longevity. In another practical case study, we perform a triple antibody optimization of VRC07, 3BNC117, and 10-1074 bNAb variants using empirical PK and a pre-clinical correlate of protection derived from animal challenge studies. Here, a 2:1:1 dose emphasizing VRC07 would optimally balance protection while achieving practical dosing and given conservative judgements about prior data. Our approach can be immediately applied to optimize the next generation of combination antibody prevention and cure studies.
Allele-specific analysis reveals exon- and cell-type-specific regulatory effects of Alzheimer’s disease-associated genetic variants
Authors: He Liang , Loika Yury , Kulminski Alexander M. 
Published: July 2021

AbstractElucidating regulatory effects of Alzheimer’s disease (AD)-associated genetic variants is critical for unraveling their causal pathways and understanding the pathology. However, their cell-type-specific regulatory mechanisms in the brain remain largely unclear. Here, we conducted an analysis of allele-specific expression quantitative trait loci (aseQTLs) for 33 AD-associated variants in four brain regions and seven cell types using ~3000 bulk RNA-seq samples and >0.25 million single nuclei. We develop a flexible framework using a hierarchical Poisson mixed model unifying samples in both allelic and genotype-level expression data. We identified 24 AD-associated variants (~73%) that are allele-specific eQTLs (aseQTLs) in at least one brain region. Multiple aseQTLs are region-dependent or exon-specific, such as rs2093760 with CR1, rs7982 with CLU, and rs3865444 with CD33. Notably, the APOE ε4 variant reduces APOE expression across all regions, even in healthy controls. In pinpointing the cell types responsible for the observed region-level aseQTLs, we found rs2093760 as an aseQTL of CR1 in oligodendrocytes but not in microglia. Many AD-associated variants are aseQTLs in microglia or monocytes of immune-related genes, including HLA-DQB1, HLA-DQA2, CD33, FCER1G, MS4A6A, SPI1, and BIN1, highlighting the regulatory role of AD-associated variants in the immune response. These findings provide further insights into potential causal pathways and cell types mediating the effects of the AD-associated variants.
Age- and episodic memory-related differences in task-based functional connectivity in women and men
Authors: Subramaniapillai Sivaniya , Rajagopal Sricharana , Ankudowich Elizabeth , Pasvanis Stamatoula , Misic Bratislav , Rajah M.Natasha 
Published: July 2021

AbstractAging is associated with episodic memory decline and changes in functional brain connectivity. Understanding whether and how biological sex influences age- and memory performance-related functional connectivity has important theoretical and clinical implications for our understanding of brain and cognitive aging. Yet, little is known about the effect of sex on neurocognitive aging. Here, we scanned 161 healthy adults between 19-76 yrs of age in an event-related functional magnetic resonance imaging (fMRI) study of face-location spatial context memory. Adults were scanned while performing easy and difficult versions of the task at both encoding and retrieval. We used multivariate whole-brain partial least squares (PLS) connectivity to test the hypothesis that there are sex differences in age- and episodic memory performance-related functional connectivity. We examined how individual differences in age and retrieval accuracy correlated with task-related connectivity. We then repeated this analysis after disaggregating the data by self-reported sex. We found that increased encoding and retrieval-related connectivity within the dorsal attention network (DAN), and between DAN and frontoparietal network (FPN) and visual networks, was positively correlated to retrieval accuracy and negatively correlated with age in both sexes. We also observed sex differences in age- and performance-related functional connectivity: i) greater between-network integration was apparent at both levels of task difficulty in women only, and ii) increased DAN-DMN connectivity with age was observed in men and was correlated with poorer memory performance. Therefore, the neural correlates of age-related episodic memory decline differ in women and men and has important theoretical and clinical implications for the cognitive neuroscience of memory, aging and dementia prevention.