Facebook Post Credibility as a Predictor of Vaccine Hesitancy in the US.

Vaccine hesitancy represents a barrier to public health efforts aiming to mitigate the pandemic by performing global interventions. One of the reasons behind vaccine hesitancy is mistrust towards the health system that partially originated due to the misinformation shared over the internet. This study examined the association between the credibility of the sources regarding the COVID-19 vaccine posted on social media and the vaccination rate at the state level in the United States. Study findings suggest that sharing more Facebook posts with links to low-credibility sources about vaccination is associated with a lower number of new vaccinations at the state level in the US. This indicates an urgent need for social media-leveraged interventions through which public health officials can share reliable information to educate populations about vaccine benefits and reduce vaccine hesitancy.

Building a More Diverse Public Health Informatics Workforce: Preliminary Results.

The US public health infrastructure has been historically underfunded, a condition that was exacerbated by the COVID-19 pandemic. This was especially noted in the area of public health informatics. It was also acknowledged that the lack of a diverse public health workforce made it more difficult to address biases and disparities effectively. In 2021 the Office of the National Coordinator awarded $73 million to 10 awardees to develop public health informatics and technology (PHIT) workforce training. The Gaining Equity in Training for Public Health Informatics and Technology (GET PHIT) award utilizes various methods to train and engage minority and underserved populations in the field of public health informatics. Evaluations of the bootcamps and internships to date have shown generally positive results, both in terms of skills acquired and overall experiences. These results indicate that integrating the fields of public health and data science in non-degree, short-term experiences can have positive outcomes.

(St)aging in place: Information and communication technologies for a health-centered agile dwelling unit.

As the number of older adults is growing rapidly in the U.S., the need for personalized, innovative, and sustainable Information and Communication Technologies (ICTs) solutions is critical to support individuals' social, emotional, and physical health. Such technology can significantly help older adults' ability to live independently in their homes despite the challenges the aging process may present, referred to as aging or staging in place. In this study, we explored ways to integrate ICTs into Agile Dwelling Units (AgDUs) through affordable, innovative, technology-enabled tools and practices that can be adapted to respond to individual's needs while supporting independent, secure, and engaged healthy living. The technology-enabled and human-centered AgDUs organically transform in response to users' needs. This approach offers a viable solution for older adults at different stages throughout their lifespan to transition into an intimate, technologically-enhanced living environment while allowing for (1) customization to user's needs; (2) cost optimization and maintenance; and (3) accessibility that minimizes gaps in compliance from a provider and user perspectives. Integrating ICTs in AgDUs to support health monitoring and management could reduce forthcoming pressure on the healthcare system and care providers to accommodate the needs of older adults. This approach is described through a collaborative multidisciplinary lens that highlights a partnership between academia, industry experts, and key stakeholders to advance healthy living and extend lifespan through design-build and technology integration. The main goal of this approach is to increase access to health services and optimize healthcare costs.

Spanish Facebook Posts as an Indicator of COVID-19 Vaccine Hesitancy in Texas.

Vaccination represents a major public health intervention intended to protect against COVID-19 infections and hospitalizations. However, vaccine hesitancy due to misinformation/disinformation, especially among ethnic minority groups, negatively impacts the effectiveness of such an intervention. The aim of this study is to provide an understanding of how information gleaned from social media can be used to improve attitudes toward vaccination and decrease vaccine hesitancy. This work focused on Spanish-language posts, and will highlight the relationship between vaccination rates across different Texas counties and the sentiment and emotional content of Facebook data, the most popular platform among the Hispanic population. The analysis of this valuable dataset indicates that vaccination rates among this minority group are negatively correlated with negative sentiment and fear, meaning that a higher prevalence of negative and fearful posts indicates lower vaccination rates in these counties. This first study investigating vaccine hesitancy in the Hispanic population suggests that observation of social media can be a valuable tool for measuring attitudes toward public health interventions.

Your Tweets Matter: How Social Media Sentiments Associate with COVID-19 Vaccination Rates in the US.

Objective: The aims of the study were to examine the association between social media sentiments surrounding COVID-19 vaccination and the effects on vaccination rates in the United States (US), as well as other contributing factors to the COVID-19 vaccine hesitancy. Method: The dataset used in this study consists of vaccine-related English tweets collected in real-time from January 4 - May 11, 2021, posted within the US, as well as health literacy (HL), social vulnerability index (SVI), and vaccination rates at the state level. Results: The findings presented in this study demonstrate a significant correlation between the sentiments of the tweets and the vaccination rate in the US. The results also suggest a significant negative association between HL and SVI and that the state demographics correlate with both HL and SVI. Discussion: Social media activity provides insights into public opinion about vaccinations and helps determine the required public health interventions to increase the vaccination rate in the US. Conclusion: Health literacy, social vulnerability index and monitoring of social media sentiments need to be considered in public health interventions as part of vaccination campaigns.

A 6-Month clinical practice pilot study of sucroferric oxyhydroxide on nutritional status in patients on peritoneal dialysis.

BACKGROUND: Hyperphosphatemia is common in patients on peritoneal dialysis (PD). Restricting dietary phosphorus often leads to a decrease in protein intake, which may result in hypoalbuminemia. The high pill burden of phosphate binders may also contribute to compromised appetite and dietary intake. Hypoalbuminemia is associated with an increased risk of morbidity and mortality in PD patients. The goal of this study was to determine if sucroferric oxyhydroxide improves albumin and self-reported measures of appetite in PD patients. METHODS: We performed a prospective, open-label, 6-month, pilot study of 17 adult PD patients from the Denver Metro Area. Patients had to use automated peritoneal dialysis for ≥ 3 months, have a serum albumin ≤ 3.8 g/dL, and have serum phosphate ≥ 5.5 mg/dL or ≤ 5.5 mg/dL on a binder other than SO. SO was titrated to a goal serum phosphate of < 5.5 mg/dL. The primary outcome was change in serum phosphate, albumin, and phosphorus-attuned albumin (defined as albumin divided by phosphorus) over 6 months. RESULTS: The mean (SD) age and dialysis vintage was 55 ± 13 years and 3.8 ± 2.7 years, respectively. Participants' serum phosphate significantly decreased with fewer phosphate binder pills/day after switching to SO. There was no change in serum albumin, appetite, or dietary intake. However, participants had significant improvements in phosphorus-attuned albumin. CONCLUSION: The transition to SO improved phosphorus control, phosphorus-attuned albumin, and pill burden. There were no significant changes in self-reported appetite or dietary intake during the study. These findings suggest that PD patients maintained nutritional status with SO therapy. TRIAL REGISTRATION: First registered at ClinicalTrials.gov ( NCT04046263 ) on 06/08/2019.

The eHealth4all@eu Pipeline of Course Development: TIGER Recommendations in Action.

This study describes the eHealth4all@eu course development pipeline that builds upon the TIGER educational recommendations and allows a systematic development grounded on scientific and field requirements of competencies, a case/problem-based pedagogical approach and finally results in the syllabus and the course content. The pipeline is exemplified by the course Learning Healthcare in Action: Clinical Data Analytics.

Comparative intervention assessing a catheter stabilization device on peripheral intravenous line loss.

BACKGROUND: Short peripheral intravenous catheters are the most common invasive procedure used to deliver medications, blood products, and fluids to patients, and failure has the potential to impact the quality of care. METHODS: This study compared IVs stabilized with current transparent film dressing to those using an engineered stabilization device. The first phase of the study evaluated documentation; data from patient records were found less than optimal but most complete for securement and removal, the two fields most critical to the study. The second phase measured IV dwell time, restart rates, and time between IV loss and restarts. RESULTS: Although there were no statistically significant differences in restarts, the IV dwell time was longer when the engineered device was in place, helping to extend the life of the IV and prevent interruption of care. In the absence of data on the cost of infections and other complications, the use of an engineered device increased the cost of IV starts. CONCLUSIONS: Adding an engineered stabilization device increases the cost of peripheral IV starts, but contributes to reducing IV restarts and preventing IV complications due to destabilized IVs. Although there were no statistically significant differences in restarts, the IV dwell time was longer when the device was in place, helping to extend the life of the IV and prevent interruption of care. Complete and accurate documentation and improved quality depended upon the ability to abstract unit-level data, which is vital for capturing the appropriate healthcare indicators. Clinical nurses must be involved in the decision-making regarding health records and operability at the unit level.

Health Intelligence Atlas: A Core Tool for Public Health Intelligence.

BACKGROUND: The dramatic increase in complexity and volume of health data has challenged traditional health systems to deliver useful information to their users. The novel coronavirus disease 2019 (COVID-19) pandemic has further exacerbated this problem and demonstrated the critical need for the 21st century approach. This approach needs to ingest relevant, diverse data sources, analyze them, and generate appropriate health intelligence products that enable users to take more effective and efficient actions for their specific challenges. OBJECTIVES: This article characterizes the Health Intelligence Atlas (HI-Atlas) development and implementation to produce Public Health Intelligence (PHI) that supports identifying and prioritizing high-risk communities by public health authorities. The HI-Atlas moves from post hoc observations to a proactive model-based approach for preplanning COVID-19 vaccine preparedness, distribution, and assessing the effectiveness of those plans. RESULTS: Details are presented on how the HI-Atlas merged traditional surveillance data with social intelligence multidimensional data streams to produce the next level of health intelligence. Two-model use cases in a large county demonstrate how the HI-Atlas produced relevant PHI to inform public health decision makers to (1) support identification and prioritization of vulnerable communities at risk for COVID-19 spread and vaccine hesitancy, and (2) support the implementation of a generic model for planning equitable COVID-19 vaccine preparedness and distribution. CONCLUSION: The scalable models of data sources, analyses, and smart hybrid data layer visualizations implemented in the HI-Atlas are the Health Intelligence tools designed to support real-time proactive planning and monitoring for COVID-19 vaccine preparedness and distribution in counties and states.

Development of novel NEMO-binding domain mimetics for inhibiting IKK/NF-κB activation.

Nuclear factor κB (NF-κB) is a transcription factor important for regulating innate and adaptive immunity, cellular proliferation, apoptosis, and senescence. Dysregulation of NF-κB and its upstream regulator IκB kinase (IKK) contributes to the pathogenesis of multiple inflammatory and degenerative diseases as well as cancer. An 11-amino acid peptide containing the NF-κB essential modulator (NEMO)-binding domain (NBD) derived from the C-terminus of ß subunit of IKK, functions as a highly selective inhibitor of the IKK complex by disrupting the association of IKKß and the IKKγ subunit NEMO. A structure-based pharmacophore model was developed to identify NBD mimetics by in silico screening. Two optimized lead NBD mimetics, SR12343 and SR12460, inhibited tumor necrosis factor α (TNF-α)- and lipopolysaccharide (LPS)-induced NF-κB activation by blocking the interaction between IKKß and NEMO and suppressed LPS-induced acute pulmonary inflammation in mice. Chronic treatment of a mouse model of Duchenne muscular dystrophy (DMD) with SR12343 and SR12460 attenuated inflammatory infiltration, necrosis and muscle degeneration, demonstrating that these small-molecule NBD mimetics are potential therapeutics for inflammatory and degenerative diseases.

Development and Implementation of a High-Throughput High-Content Screening Assay to Identify Inhibitors of Androgen Receptor Nuclear Localization in Castration-Resistant Prostate Cancer Cells.

Patients with castration-resistant prostate cancer (CRPC) can be treated with abiraterone, a potent inhibitor of androgen synthesis, or enzalutamide, a second-generation androgen receptor (AR) antagonist, both targeting AR signaling. However, most patients relapse after several months of therapy and a majority of patients with relapsed CRPC tumors express the AR target gene prostate-specific antigen (PSA), suggesting that AR signaling is reactivated and can be targeted again to inhibit the relapsed tumors. Novel small molecules capable of inhibiting AR function may lead to urgently needed therapies for patients resistant to abiraterone, enzalutamide, and/or other previously approved antiandrogen therapies. Here, we describe a high-throughput high-content screening (HCS) campaign to identify small-molecule inhibitors of AR nuclear localization in the C4-2 CRPC cell line stably transfected with GFP-AR-GFP (2GFP-AR). The implementation of this HCS assay to screen a National Institutes of Health library of 219,055 compounds led to the discovery of 3 small molecules capable of inhibiting AR nuclear localization and function in C4-2 cells, demonstrating the feasibility of using this cell-based phenotypic assay to identify small molecules targeting the subcellular localization of AR. Furthermore, the three hit compounds provide opportunities to develop novel AR drugs with potential for therapeutic intervention in CRPC patients who have relapsed after treatment with antiandrogens, such as abiraterone and/or enzalutamide.

HCS campaign to identify selective inhibitors of IL-6-induced STAT3 pathway activation in head and neck cancer cell lines.

Signal transducer and activator of transcription factor 3 (STAT3) is hyperactivated in head and neck squamous cell carcinomas (HNSCC). Cumulative evidence indicates that IL-6 production by HNSCC cells and/or stromal cells in the tumor microenvironment activates STAT3 and contributes to tumor progression and drug resistance. A library of 94,491 compounds from the Molecular Library Screening Center Network (MLSCN) was screened for the ability to inhibit interleukin-6 (IL-6)-induced pSTAT3 activation. For contractual reasons, the primary high-content screening (HCS) campaign was conducted over several months in 3 distinct phases; 1,068 (1.1%) primary HCS actives remained after cytotoxic or fluorescent outliers were eliminated. One thousand one hundred eighty-seven compounds were cherry-picked for confirmation; actives identified in the primary HCS and compounds selected by a structural similarity search of the remaining MLSCN library using hits identified in phases I and II of the screen. Actives were confirmed in pSTAT3 IC50 assays, and an IFNγ-induced pSTAT1 activation assay was used to prioritize selective inhibitors of STAT3 activation that would not inhibit STAT1 tumor suppressor functions. Two hundred three concentration-dependent inhibitors of IL-6-induced pSTAT3 activation were identified and 89 of these also produced IC50s against IFN-γ-induced pSTAT1 activation. Forty-nine compounds met our hit criteria: they reproducibly inhibited IL-6-induced pSTAT3 activation by ≥70% at 20 µM; their pSTAT3 activation IC50s were ≤25 µM; they were ≥2-fold selective for pSTAT3 inhibition over pSTAT1 inhibition; a cross target query of PubChem indicated that they were not biologically promiscuous; and they were ≥90% pure. Twenty-six chemically tractable hits that passed filters for nuisance compounds and had acceptable drug-like and ADME-Tox properties by computational evaluation were purchased for characterization. The hit structures were distributed among 5 clusters and 8 singletons. Twenty-four compounds inhibited IL-6-induced pSTAT3 activation with IC50s ≤20 µM and 13 were ≥3-fold selective versus inhibition of pSTAT1 activation. Eighteen hits inhibited the growth of HNSCC cell lines with average IC50s ≤ 20 µM. Four chemical series were progressed into lead optimization: the guanidinoquinazolines, the triazolothiadiazines, the amino alcohols, and an oxazole-piperazine singleton.

Interprofessional education: Lessons learned from conducting an electronic health record assignment.

Ineffective collaboration and communication contribute to fragmented patient care and potentially increase adverse events, clinical errors, and poor patient outcomes. Improving collaboration and communication is essential; however, interprofessional education (IPE) supporting this cause is not a common practice. Most often healthcare profession students are educated in profession-centered silos limiting opportunities to develop effective communication and collaboration practices. Students from nursing, health informatics, and radiologic technology collaboratively populated an academic electronic health record (AEHR) using fictitious case study data. The assignment was designed to address the Quality and Safety Education for Nurses and IPE Collaborative competencies. The objective was to evaluate students' informatics competency, teamwork behaviors, and communication skills while exploring the different roles and responsibilities for collaborative practice after participating in an interprofessional case study assignment. Students gained experience using the AEHR for data entry, analysis, and application increasing their informatics competency. The assignment required students to communicate and actively collaborate as an interprofessional team to achieve the assignment objectives. Clinical errors often occur during care transitions, so simulating this process in the assignment was essential. Nursing and radiologic technology students had to analyze patient data and develop a hand-off communication template supporting patient safety and optimizing outcomes. The assignment required students to work as an interprofessional team and demonstrate how communication and collaboration is an essential component to quality and safe patient care.

Identification and characterization of a novel small-molecule inhibitor of ß-catenin signaling.

Hepatocellular carcinoma (HCC), the third most common cause of cancer-related deaths worldwide, lacks effective medical therapy. Large subsets of HCC demonstrate Wnt/ß-catenin activation, making this an attractive therapeutic target. We report strategy and characterization of a novel small-molecule inhibitor, ICG-001, known to affect Wnt signaling by disrupting ß-catenin-CREB binding protein interactions. We queried the ZINC online database for structural similarity to ICG-001 and identified PMED-1 as the lead compound, with ≥70% similarity to ICG-001. PMED-1 significantly reduced ß-catenin activity in hepatoblastoma and several HCC cells, as determined by TOPflash reporter assay, with an IC50 ranging from 4.87 to 32 µmol/L. Although no toxicity was observed in primary human hepatocytes, PMED-1 inhibited Wnt target expression in HCC cells, including those with CTNNB1 mutations, and impaired cell proliferation and viability. PMED-1 treatment decreased ß-catenin-CREB binding protein interactions without affecting total ß-catenin levels or activity of other common kinases. PMED-1 treatment of Tg(OTM:d2EGFP) zebrafish expressing GFP under the ß-catenin/Tcf reporter led to a notable decrease in ß-catenin activity. The PMED effect on ß-catenin signaling lasted from 12 to 24 hours in vitro and 6 to 15 hours in vivo. Thus, using a rapid and cost-effective computational methodology, we have identified a novel and specific small-molecule inhibitor of Wnt signaling that may have implications for HCC treatment.

Diacylglycerol kinase α is a critical signaling node and novel therapeutic target in glioblastoma and other cancers.

Although diacylglycerol kinase α (DGKα) has been linked to several signaling pathways related to cancer cell biology, it has been neglected as a target for cancer therapy. The attenuation of DGKα activity via DGKα-targeting siRNA and small-molecule inhibitors R59022 and R59949 induced caspase-mediated apoptosis in glioblastoma cells and in other cancers, but lacked toxicity in noncancerous cells. We determined that mTOR and hypoxia-inducible factor-1α (HIF-1α) are key targets of DGKα inhibition, in addition to its regulation of other oncogenes. DGKα regulates mTOR transcription via a unique pathway involving cyclic AMP. Finally, we showed the efficacy of DGKα inhibition with short hairpin RNA or a small-molecule agent in glioblastoma and melanoma xenograft treatment models, with growth delay and decreased vascularity. This study establishes DGKα as a central signaling hub and a promising therapeutic target in the treatment of cancer.

Synthesis and biological evaluation of a selective N- and p/q-type calcium channel agonist.

The acute effect of the potent cyclin-dependent kinase (cdk) inhibitor (R)-roscovitine on Ca(2+) channels inspired the development of structural analogues as a potential treatment for motor nerve terminal dysfunction. On the basis of a versatile chlorinated purine scaffold, we have synthesized ca. 20 derivatives and characterized their N-type Ca(2+) channel agonist action. Agents that showed strong agonist effects were also characterized in a kinase panel for their off-target effects. Among several novel compounds with diminished cdk activity, we identified a new lead structure with a 4-fold improved N-type Ca(2+) channel agonist effect and a 22-fold decreased cdk2 activity as compared to (R)-roscovitine. This compound was selective for agonist activity on N- and P/Q-type over L-type calcium channels.

Discovery of diverse small molecule chemotypes with cell-based PKD1 inhibitory activity.

Protein kinase D (PKD) is a novel family of serine/threonine kinases regulated by diacylglycerol, which is involved in multiple cellular processes and various pathological conditions. The limited number of cell-active, selective inhibitors has historically restricted biochemical and pharmacological studies of PKD. We now markedly expand the PKD1 inhibitory chemotype inventory with eleven additional novel small molecule PKD1 inhibitors derived from our high throughput screening campaigns. The in vitro IC(50)s for these eleven compounds ranged in potency from 0.4 to 6.1 µM with all of the evaluated compounds being competitive with ATP. Three of the inhibitors (CID 1893668, (1Z)-1-(3-ethyl-5-methoxy-1,3-benzothiazol-2-ylidene)propan-2-one; CID 2011756, 5-(3-chlorophenyl)-N-[4-(morpholin-4-ylmethyl)phenyl]furan-2-carboxamide; CID 5389142, (6Z)-6-[4-(3-aminopropylamino)-6-methyl-1H-pyrimidin-2-ylidene]cyclohexa-2,4-dien-1-one) inhibited phorbol ester-induced endogenous PKD1 activation in LNCaP prostate cancer cells in a concentration-dependent manner. The specificity of these compounds for PKD1 inhibitory activity was supported by kinase assay counter screens as well as by bioinformatics searches. Moreover, computational analyses of these novel cell-active PKD1 inhibitors indicated that they were structurally distinct from the previously described cell-active PKD1 inhibitors while computational docking of the new cell-active compounds in a highly conserved ATP-binding cleft suggests opportunities for structural modification. In summary, we have discovered novel PKD1 inhibitors with in vitro and cell-based inhibitory activity, thus successfully expanding the structural diversity of small molecule inhibitors available for this important pharmacological target.

A novel benzodioxole-containing inhibitor of Toxoplasma gondii growth alters the parasite cell cycle.

Toxoplasma gondii is an obligate intracellular parasite that can cause disease in the developing fetus and in immunocompromised humans. Infections can last for the life of the individual, and to date there are no drugs that eliminate the chronic cyst stages that are characteristic of this parasite. In an effort to identify new chemical scaffolds that could form the basis for new therapeutics, we carried out a chemoinformatic screen for compounds that had the potential to interact with members of a superfamily of parasite-secreted kinases and assayed them for growth inhibition in vitro. Of 17 candidate compounds, we identified one with potent antiparasitic activity. The compound has a 50% inhibitory concentration (IC(50)) of ~2 nM, and structure-function analyses implicate the benzodioxole moiety in its action. The compound does not appear to be cytotoxic to host cells. Using microarray analyses of both parasites and host cells treated with the compound, we found that the levels of very few host cell transcripts are altered by the compound, while a large number of parasite transcripts have a different abundance after compound treatment. Gene ontology analyses of parasite transcripts with a different abundance revealed an enrichment of cell cycle-related genes, suggesting that the compound alters progression of the parasite through the cell cycle. Assaying the nuclear content of treated parasites demonstrated that compound treatment significantly increased the percentage of parasites in the S/M phase of the cell cycle compared to controls. This compound and its analogs represent a novel scaffold with antiparasitic activity.