Ubiquitin-specific protease 14 targets PFKL-mediated glycolysis to promote the proliferation and migration of oral squamous cell carcinoma.

Aberrant upregulation of the ubiquitin-specific protease 14 (USP14) has been found in some malignant tumors, including oral squamous cell carcinoma (OSCC). In this study, we further demonstrated that aberrantly overexpressed USP14 was also closely related to adverse clinicopathological features and poor prognosis in patients with OSCC, so we hypothesized that USP14 might act as a tumor-promoting factor during the progression of OSCC. Notably, we originally proved that USP14 is a deubiquitinating enzyme for phosphofructokinase-1 liver type (PFKL), a key rate-limiting enzyme involved in the glycolytic pathway. USP14 interacts with PFKL and enhances its stability through deubiquitination in OSCC cells, which in turn enhances PFKL-mediated glycolytic metabolism and ultimately promote cellular proliferation, migration, and tumorigenesis. In this work, we have also demonstrated for the first time that USP14 is a critical regulator of glycolysis in OSCC and verified a novel mechanism whereby it is involved in tumor metastasis and growth. Collectively, our findings provide novel insights into the tumor-promoting role of USP14 and establish mechanistic foundations for USP14-targeting therapies.

Association of Patient-Reported Social Needs with Emergency Department Visits and Hospitalizations Among Federally Qualified Health Center Patients.

BACKGROUND: Health care systems are increasingly screening for unmet social needs. The association between patient-reported social needs and health care utilization is not well understood. OBJECTIVE: To investigate the association between patient-reported social needs, measured by the Protocol for Responding to and Assessing Patients' Assets, Risks, and Experiences (PRAPARE), and inpatient and emergency department (ED) utilization. DESIGN: This cohort study analyzed merged 2017-2019 electronic health record (EHR) data across multiple health systems. PARTICIPANTS: Adult patients from a federally qualified health center (FQHC) in central North Carolina who completed PRAPARE as part of a primary care visit with behavioral health services. MAIN MEASURES: The count of up to 12 unmet social needs, aggregated as 0, 1, 2, or 3 + . Outcomes include the probability of an ED visit and hospitalization 12 months after PRAPARE assessment, modeled by logistic regressions controlling for age, sex, race, ethnicity, comorbidity burden, being uninsured, and prior utilization in the past 12 months. KEY RESULTS: The study population consisted of 1924 adults (38.7% male, 50.1% Black, 36.3% Hispanic, 55.9% unemployed, 68.2% of patients reported 1 + needs). Those with more needs were younger, more likely to be unemployed, and experienced greater comorbidity burden. 35.3% of patients had ED visit(s) and 36.3% had hospitalization(s) 1 year after PRAPARE assessment. In adjusted analysis, having 3 + needs was associated with a percentage point increase in the predicted probability of hospitalization (average marginal effect 0.06, SE 0.03, p < 0.05) compared with having 0 needs. Similarly, having 2 needs (0.07, SE 0.03, p < 0.05) or 3 + needs (0.06, SE 0.03, p < 0.05) was associated with increased probability of ED visits compared to 0 needs. CONCLUSIONS: Patient-reported social needs were common and associated with health care utilization patterns. Future research should identify interventions to address unmet social needs to improve health and avoid potentially preventable escalating medical intervention.

Care sequences leading to the diagnosis of Alzheimer's disease and related dementias: An analysis of electronic health records.

BACKGROUND: We examined the sequences of clinical care leading to diagnoses of Alzheimer's disease and related dementias (ADRD) using electronic health records from a large academic medical center. METHODS: We included patients aged 65+ with their first ADRD diagnoses from January 1, 2014 to December 31, 2019. Using state sequence analysis, care sequences were defined by the ordering of healthcare utilizations occurred in the 2 years before ADRD diagnosis. RESULTS: Of 3621 patients (median age 80), nearly half followed a care sequence of having one primary care visit close to their ADRD diagnosis. Additional care sequences included periodic (n = 322, 8.9%) and multiple (n = 416, 11.5%) outpatient visits to primary care and having one (n = 395, 10.9%), multiple (n = 469, 13.0%), or highly frequent (n = 357, 10.7%) outpatient visits to other specialties. Patients' sociodemographic traits contributed to the variability in care sequences. CONCLUSIONS: Several distinct patterns of care leading to ADRD diagnoses were identified. Integrated care models are needed to promote early identification of ADRD. HIGHLIGHTS: Dementia patients followed distinct care pathways prior to their dementia diagnoses. Key sociodemographic traits contributed to the variation in the sequences of care. Racial differences in the sequencing of care were also found, but only in women.

The forkhead box protein P3 gene rs3761548 promoter polymorphism confers a genetic contribution to the risk of preeclampsia: A systematic review and meta-analysis.

Various studies have investigated the risk of preeclampsia with the forkhead box protein P3 (FOXP3) gene rs2232365 and rs3761548 polymorphisms. However, the results remained contradictory. A comprehensive literature search was conducted using the Cochrane Library, PubMed, and Web of Science (up to Oct 11, 2021). Meta-analysis was carried out in the R language environment for statistical computing and graphics. A fixed-effect or random-effects model was used according to the statistical significance of heterogeneity among included studies. The pooled odds ratios and corresponding 95% confidence intervals were calculated to estimate the strength of the effect. For the rs2232365 polymorphism, statistical significance was detected neither in the overall population nor among the East Asian and West Asian subgroups. However, for rs3761548, the summarized statistics revealed a significant association between the C allele carriage and preeclampsia risk in the homozygote, heterozygote, and dominant models. The further stratified analysis found this effect might be specific to West-South Asian ethnic subgroups. To sum up, this meta-analysis showed that the FOXP3 rs3761548 polymorphism was significantly associated with preeclampsia susceptibility, and it had a deleterious effect especially in the West-South Asian population. In contrast, rs2232365 may serve as neither a protective nor a risk factor for preeclampsia onset.

Cognitive behavioural therapy and medication for treatment of adolescent depression: a network meta-analysis.

BACKGROUND: Cognitive behavioural therapy (CBT) and medication are widely accepted and useful interventions for individuals with depression. However, a gap remains in our current understanding of how CBT directly benefits adolescents with depression. AIMS: The purpose of this study was to examine the short- and long-term effectiveness of CBT only, CBT+Medication, or Medication alone in reducing the duration of major depressive episodes, lessening internalizing and externalizing symptoms and improving global functioning. METHODS: Data were extracted from 14 unique studies with a total of 35 comparisons. Network meta-analysis was conducted and p-scores, a measure of the extent of certainty that one treatment is better than another, were used to rank treatments. RESULTS: There was no significant difference between any two treatments for depression, nor internalizing or externalizing symptoms. For global functioning, CBT had significantly greater effect at the longest follow-up than CBT+Medication. CBT+Medication had the highest p-score for depression, short- and long-term effects, and internalizing and externalizing symptoms long-term effects. No indication of publication bias was found. CONCLUSIONS: Neither modality, CBT nor medication, is superior for treating adolescent depression. However, CBT was superior in improving global functioning, which is essential for meeting developmental goals.

Existing Datasets to Study the Impact of Internal Migration on Caregiving Arrangements among Older Adults in China.

Massive rural-to-urban migration in China has a significant impact on informal caregiving arrangements among Chinese older adults. To stimulate research on the intersection of migration and caregiving, we conducted an inventory of longitudinal aging survey datasets from mainland China. Large publicly available datasets that included measures related to migration and caregiving were searched and reviewed for eligibility. Key characteristics of each dataset, including study design, sample size, and measures, were extracted. Seven eligible datasets were identified, and five included nationally representative samples. Measures for migration varied across datasets. Some datasets included information on the migration history of older adults, whereas others focused on the migration of adult children. Similarly, caregiving was measured using different questions in each dataset. Caregiving activities were assessed with regard to their type, source, and amount. High-quality datasets exist to support research on migration and caregiving arrangements among Chinese older adults.

Parthenolide reveals an allosteric mode to inhibit the deISGylation activity of SARS-CoV­2 papain-like protease.

The coronavirus papain-like protease (PLpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for viral polypeptide cleavage and the deISGylation of interferon-stimulated gene 15 (ISG15), which enable it to participate in virus replication and host innate immune pathways. Therefore, PLpro is considered an attractive antiviral drug target. Here, we show that parthenolide, a germacrane sesquiterpene lactone, has SARS-CoV-2 PLpro inhibitory activity. Parthenolide covalently binds to Cys-191 or Cys-194 of the PLpro protein, but not the Cys-111 at the PLpro catalytic site. Mutation of Cys-191 or Cys-194 reduces the activity of PLpro. Molecular docking studies show that parthenolide may also form hydrogen bonds with Lys-192, Thr-193, and Gln-231. Furthermore, parthenolide inhibits the deISGylation but not the deubiquitinating activity of PLpro in vitro. These results reveal that parthenolide inhibits PLpro activity by allosteric regulation.

Which wound cuts deeper: loss of an only child or loss of a spouse? An examination of bereavement in older adults within a Chinese cultural context.

OBJECTIVES: This study aimed to examine whether the loss of spouse had similar impacts on psychological well-being as the loss of the only child, and whether the presence of one mitigated the absence of the other. METHODS: We used data from a 2013 survey conducted in Shanghai, China. The sample included 1,200 older adults aged 60+, and 200 adults aged 45+ who lost their only child. Psychological well-being consisted of three dimensions: depression, loneliness, and life satisfaction. We applied logistic regression models to assess the impact of loss of spouse or children on psychological well-being. We further tested whether the impact differed by gender and whether social support mediated the relationship. RESULTS: Participants who have at least one living child but lost their spouse had less psychological distress than those who have a living spouse but lost their only child. This effect appeared to be stronger in women than in men. Social support mediated the relationship between bereavement and loneliness among women. CONCLUSION: The findings suggested the loss of the only child is a more devastating event than the loss of spouse in Chinese adults. The loss of the only child is a major chronic stressor that has cumulative negative effect on psychological well-being.

Treatment and Outcomes of Patients With Ischemic Stroke During COVID-19: An Analysis From Get With The Guidelines-Stroke.

[Figure: see text].

Acute Ischemic Stroke in Patients With COVID-19: An Analysis From Get With The Guidelines-Stroke.

[Figure: see text].

The Cumulative Impact of Chronic Stressors on Risks of Myocardial Infarction in US Older Adults.

OBJECTIVE: This study aimed to investigate the association between cumulative exposure to chronic stressors and the incidence of myocardial infarction (MI) in US older adults. METHODS: Nationally representative prospective cohort data of adults 45 years and older (n = 15,109) were used to investigate the association between the cumulative number of chronic stressors and the incidence of MI in US older adults. Proportional hazards models adjusted for confounding risk factors and differences by sex, race/ethnicity, and history of MI were assessed. RESULTS: The median age of participants was 65 years, 714 (4.7%) had a prior MI, and 557 (3.7%) had an MI during follow-up. Approximately 84% of participants reported at least one chronic stressor at baseline, and more than half reported two or more stressors. Multivariable models showed that risks of MI increased incrementally from one chronic stressor (hazard ratio [HR] = 1.28, 95% confidence interval [CI] = 1.20-1.37) to four or more chronic stressors (HR = 2.71, 95% CI = 2.08-3.53) compared with those who reported no stressors. These risks were only partly reduced after adjustments for multiple demographic, socioeconomic, psychosocial, behavioral, and clinical risk factors. In adults who had a prior MI (p value for interaction = .038), we found that risks of a recurrent event increased substantially from one chronic stressor (HR = 1.30, 95% CI = 1.09-1.54) to four or more chronic stressors (HR = 2.85, 95% CI = 1.43-5.69). CONCLUSIONS: Chronic life stressors are significant independent risk factors for cardiovascular events in US older adults. The risks associated with multiple chronic stressors were especially high in adults with a previous MI.

Abdominal aortic calcification and cognitive function among older adults: Cross-sectional analysis of National Health and Nutrition Examination Survey, 2013-2014.

OBJECTIVES: Subclinical atherosclerotic disease is an emerging risk factor for cognitive function among older adults, though less is known about the association between abdominal aortic calcification (AAC) and cognitive function. This study aimed to examine the cross-sectional association of AAC with cognitive function in a nationally representative sample of population in the U.S. METHODS: A total of 1,209 older adults (60 years or older) in the 2013-2014 National Health and Nutrition Examination Survey were included. AAC was obtained with dual-energy X-ray absorptiometry. Cognitive function was examined using the CERAD Word Learning subtest (memory), Digit Symbol Substitution Test (executive function/processing speed), and Animal Fluency Test (language). Test-specific and global cognition z-scores were created based on means and standard deviations of cognitive tests. Multivariable linear regression models were used to examine the associations of presence of AAC and severity of AAC with cognition z-scores. RESULTS: Adjusted for covariates, presence of AAC was associated with poorer global cognition (beta (ß) = -0.17, 95% confidence interval (CI): -0.28, -0.06), memory (ß = -0.20, 95% CI: -0.31, -0.09), and language ability (ß = -0.15, 95% CI: -0.29, -0.01). More severe AAC was associated with poorer cognitive function. The associations were significant among participants <75 years. DISCUSSION: The presence of AAC and greater severity of AAC, were associated with poorer cognitive function, particularly among older adults <75 years. Future research is expected to assess whether lowering global vascular risk can slow cognitive decline.

Wu-5, a novel USP10 inhibitor, enhances crenolanib-induced FLT3-ITD-positive AML cell death via inhibiting FLT3 and AMPK pathways.

The kinase FLT3 internal tandem duplication (FLT3-ITD) is related to poor clinical outcomes of acute myeloid leukemia (AML). FLT3 inhibitors have provided novel strategies for the treatment of FLT3-ITD-positive AML. But they are limited by rapid development of acquired resistance and refractory in monotherapy. Recent evidence shows that inducing the degradation of FLT3-mutated protein is an attractive strategy for the treatment of FLT3-ITD-positive AML, especially those with FLT3 inhibitor resistance. In this study we identified Wu-5 as a novel USP10 inhibitor inducing the degradation of FLT3-mutated protein. We showed that Wu-5 selectively inhibited the viability of FLT3 inhibitor-sensitive (MV4-11, Molm13) and -resistant (MV4-11R) FLT3-ITD-positive AML cells with IC50 of 3.794, 5.056, and 8.386 µM, respectively. Wu-5 (1-10 µM) dose-dependently induced apoptosis of MV4-11, Molm13, and MV4-11R cells through the proteasome-mediated degradation of FLT3-ITD. We further demonstrated that Wu-5 directly interacted with and inactivated USP10, the deubiquitinase for FLT3-ITD in vitro (IC50 value = 8.3 µM) and in FLT3-ITD-positive AML cells. Overexpression of USP10 abrogated Wu-5-induced FLT3-ITD degradation and cell death. Also, the combined treatment of Wu-5 and crenolanib produced synergistic cell death in FLT3-ITD-positive cells via the reduction of both FLT3 and AMPKα proteins. In support of this, AMPKα inhibitor compound C synergistically enhanced the anti-leukemia effect of crenolanib, while AMPKα activator metformin inhibited the anti-leukemia effect of crenolanib. In summary, we demonstrate that Wu-5, a novel USP10 inhibitor, can overcome FLT3 inhibitor resistance and synergistically enhance the anti-AML effect of crenolanib through targeting FLT3 and AMPKα pathway.

Changes in Informed Consent Policy and Treatment Delays in Stroke Thrombolysis.

OBJECTIVES: The efficacy of thrombolytic therapy with tissue plasminogen activator (tPA) is highly time dependent. Although clinical guidelines do not recommend written informed consent as it may cause treatment delays, local policy can supersede and require it. From 2014 to 2017, three out of five public hospitals in Singapore changed from written to verbal consent at different time points. We aimed to examine the association of hospital policy changes regarding informed consent on door-to-needle (DTN) times. MATERIALS AND METHODS: Using data from the Singapore Stroke Registry and surveys of local practice, we analyzed data of 915 acute ischemic stroke patients treated with tPA within 3 hours in all public hospitals between July 2014 to Dec 2017. Patient-level DTN times before and after policy changes were examined while adjusting for clinical characteristics, within-hospital clustering, and trends over time. RESULTS: Patient characteristics and stroke severity were similar before and after the policy changes. Overall, the median DTN times decreased from 68 to 53 minutes after the policy changes. After risk adjustment, changing from written to verbal informed consent was associated with a 5.6 minutes reduction (95% CI 1.1-10.0) in DTN times. After the policy changed, the percentage of patients with DTN ≤60 minutes and ≤45 minutes increased from 35.6% to 66.1% (adjusted OR 1.75; 95% CI 1.12-2.74) and 9.3% to 36.0% (adjusted OR 2.42; 95% CI 1.37-4.25), respectively. CONCLUSION: Changing from written to verbal consent is associated with significant improvement in the timeliness of tPA administration in acute ischemic stroke.

Care partner-assisted intervention to improve oral health for older adults with cognitive impairment: A feasibility study.

BACKGROUND AND OBJECTIVES: Older adults with cognitive impairment often experience poor oral health outcomes due to inadequate oral hygiene practices. This pilot study aimed to evaluate the feasibility of a care partner-assisted intervention to improve the oral hygiene of community-dwelling older adults with cognitive impairment. MATERIAL AND METHODS: The 6-month intervention included 25 older adults with mild dementia or mild cognitive impairment, who were randomly assigned to Treatment Group 1 or Treatment Group 2. Treatment Group 1 (n = 7) received an educational booklet. Treatment Group 2 (n = 18) received a booklet, a tailored care plan for the participants with cognitive impairment and the care partner received four coaching sessions to learn to facilitate good oral hygiene. Both groups received electric toothbrushes. The study consisted of a 3-month active intervention and 3-month maintenance phase. The outcomes of gingival index, plaque index and overall oral health status based on the Oral Health Assessment Tool were measured at baseline, 3 months (end of active intervention) and 6 months of the study. RESULTS: This study had very low dropout rate. Participants' oral hygiene improved in this study. In comparison to Treatment Group 1, participants in Treatment Group 2 had a greater reduction in plaque level and gingival inflammation, and greater improvement in overall oral health status. CONCLUSION: This study demonstrates the feasibility of this intervention designed to improve the oral health of persons with cognitive impairment and it lays the foundation for using this protocol in a future large randomised clinical trial.

Gender differences in quality of life among community-dwelling older adults in low- and middle-income countries: results from the Study on global AGEing and adult health (SAGE).

BACKGROUND: Quality of life (QoL) is an important component of individuals' general well-being, particularly in older adults. However, factors influencing QoL among older adults in low- and middle-income countries (LMICs) have not been fully examined. Furthermore, the role of gender differences in relation to QoL in multiple LMICs has also not been examined in detail. METHODS: This study used data from the World Health Organization's Study on global AGEing and adult health (SAGE), Wave-1. Based on a literature review of existing works, a set of variables-an independent variable and covariates-were selected. The study sample consisted of 33,019 participants aged 50 years and above from China, Ghana, India, Russia, and South Africa. Multivariate linear regression models were estimated with the World Health Organization QoL scores as the dependent variable. To preserve the analytical sample size, multiple imputation was used to account for missing data. RESULTS: The results showed that generally, male older adults reported a better QoL than female older adults across all of the countries. The associations between QoL and sociodemographic factors, health-related factors, and social support factors among older adults differed according to country. CONCLUSIONS: This study provides a better understanding of QoL among older adults in LMICs, which can help prepare LMICs to better address the QoL of older adults. The results of this study can be used to develop programs to promote better living standards and services to reduce gender disparities and ultimately, to improve the QoL among older adults in LMICs.

Quinacrine Depletes BCR-ABL and Suppresses Ph-Positive Leukemia Cells.

Drug resistance to TKIs and the existance of CML leukemia stem cells is an urgent problem. In this study, we demonstrate that quinacrine (QC) induces apoptosis in BCR-ABL positive CML and acute lymphoblastic leukemia (ALL) cells. Interestingly, QC inhibits the colony formation of primary CD34+ progenitor/stem leukemia cells from CML patients. QC targets RNA polymerase I, which produces ribosomal (r)RNA, involving in protein translation process. Also, QC treatment prolongs CML-like mice survival and inhibits K562 tumor growth in vivo. In conclusion, we demonstrate that QC depletes BCR-ABL protein and suppresses Ph-positive leukemia cells in vitro and in vivo.

WP1130 reveals USP24 as a novel target in T-cell acute lymphoblastic leukemia.

BACKGROUND: T-cell acute lymphoblastic leukemia (T-ALL) is a lymphoid malignancy caused by the oncogenic transformation of immature T-cell progenitors with poor outcomes. WP1130 has shown potent activity against a variety of cancer but whether WP1130 has anti-T-ALL activity is not clear. USP24, one target of WP1130, is one of the largest deubiquitinases and its detailed mechanism is poorly understood. The aim of this study was to explore whether WP1130 could suppress T-ALL and the role of USP24 in T-ALL. METHODS: Molecular docking and cellular thermal shift assay were performed to determine whether and how WP1130 directly interact with USP24. Mitochondrial transmembrane potential assay was measured via Rhodamine 123 staining. USP24 was reactivated using the deactivated CRISPR-associated protein 9 (dCas9)-synergistic activation mediator (SAM) system. The in vivo results were examined by tumor xenografts in NOD-SCID mice. All statistical analyses were performed with the SPSS software package. RESULTS: WP1130 treatment decreased the viability and induces apoptosis of T-ALL cells both in vitro and in vivo. Furthermore, we demonstrated that knockdown of USP24 but not USP9X could significantly induce growth inhibition and apoptosis of T-ALL cells. Oncomine database showed that USP24 expression was upregulated in T-ALL samples and Kaplan-Meier results indicated that the USP24 was negatively but USP9X was positively associated with survival in T-ALL patients. Additionally, we proposed that WP1130 directly interacts with the activity site pocket of USP24 in T-ALL cells, which leads to the decrease of its substrates Mcl-1. Mechanistically, WP1130 induces apoptosis by accelerating the collapse of mitochondrial transmembrane potential via USP24-Mcl-1 axis. CONCLUSIONS: Altogether, using WP1130 as a chemical probe, we demonstrate that USP24 but not USP9X is a novel target in T-ALL cells. Moreover, we uncovered that WP1130 induces apoptosis by accelerating the collapse of mitochondrial transmembrane potential via USP24-Mcl-1 axis. These results provide that USP24-Mcl-1 axis may represent a novel strategy in the treatment of T-ALL and WP1130 is a promising lead compound for developing anti-T-ALL drugs.

Neurocognitive and psychiatric comorbidities of posttraumatic stress disorder among older veterans: A systematic review.

OBJECTIVES: Posttraumatic stress disorder (PTSD) is associated with neurocognitive and psychiatric comorbidities, and older adults experience comorbid illnesses disproportionately. Little is known about the comorbidities of PTSD among older veterans. This systematic review examines the prevalence, incidence, and patterns of neurocognitive and psychiatric comorbidities of PTSD among older veterans and explores the factors associated with these comorbidities. METHODS: A systematic literature review was performed using PubMed, CINAHL, and PsycINFO databases. The search was limited to peer-reviewed articles published in English from January 1980 to October 2018. Eligible studies examined the comorbid neurocognitive and psychiatric disorders of PTSD among veterans aged 60 and older. RESULTS: Twenty-four studies met the criteria for inclusion. The risk for dementia was higher in veterans with PTSD than those without PTSD; hazard ratios ranged from 1.21 to 1.77. Depressive disorder was the most prevalent psychiatric comorbidity with estimates ranging from 33% to 52.3%, followed by generalized anxiety disorder (14%-15%) and substance use disorders (1.9%-11.3%). Factors consistently associated with PTSD comorbidities included age, combat-related exposures, clinical conditions, and health-related and psychosocial outcomes. CONCLUSIONS: Despite heterogeneity in research designs and methodological limitations, this review highlights the need to consider comorbid neurocognitive and psychiatric disorders among older veterans with PTSD in order to individualize care approaches. Future research should incorporate factors associated with neurocognitive and psychiatric comorbidities of PTSD into study designs that can help improve prediction of comorbidity and generate evidence for developing and implementing tailored treatments in older veterans.

Measuring the social impact of nursing research: An insight into altmetrics.

AIMS: The objectives of this study were to (a) identify nursing journal articles that provoked the most online activity and discussion and (b) assess the association between these articles' altmetric scores and publication characteristics, citation counts; and publishing journals metrics. BACKGROUND: Altmetrics, or alternative metrics, have recently emerged as a complementary way of measuring the societal impact of research by assessing the public engagement with research output. To date, no studies have yet investigated the online attention about scientific papers published in the nursing field. DESIGN: Integration of quantitative and qualitative synthesized evidence. DATA SOURCES AND REVIEW METHODS: InCites Journal Citation Report was used to identify a list of nursing journals indexed in the Web of Science Core Collection. Altmetric Explorer was selected as an altmetrics harvesting tool. The search in Altmetric Explorer yielded 66,608 research outputs from 118 nursing journals. The articles with the top 100 altmetric attention score (AAS) were identified and a new search, limited to only those 100 articles, was run to produce aggregate metrics specific to those articles. The articles were also exported for thematic analysis. RESULTS: The median AAS for the 100 articles was 248, ranging from 138 - 649. The articles were mostly discussed on Twitter, followed by news outlets and Mendeley. Articles indexed in the nursing journals category attracted low online attention compared with articles published in other health journal categories. Twitter remained the dominant source of attention over the years 2012-2018, followed distantly by news outlets. Most online attention came from the USA and the UK. Of the top 100 articles included in the study, the Journal of Advanced Nursing published the highest number of articles (N = 26; Median AAS = 179). The AAS was not significantly different between articles published in Q1 journals and those published in Q2 and Q3 journals. There was a significant relationship between articles' AASs and their citation counts on Scopus and Web of Science. Publication date was significantly related to citation counts on Scopus and Web of Science but not with AASs. CONCLUSION: Altmetrics will likely continue to evolve alongside the rapidly expanding use of social media and online platforms. As nursing continues to strive to have our research and scholarship inform policy, translated into practice and recognized for its scientific merit, we have to remain vigilant about the best ways to disseminate the important work we are doing. Research, such as this study, will allow nursing scholars to benchmark our progress as we adapt to the changing environment for measuring impact and quality in the digital age.