HMGA1 chromatin regulators induce transcriptional networks involved in GATA2 and proliferation during MPN progression.

Myeloproliferative neoplasms (MPNs) transform to myelofibrosis (MF) and highly lethal acute myeloid leukemia (AML), although the actionable mechanisms driving progression remain elusive. Here, we elucidate the role of the high mobility group A1 (HMGA1) chromatin regulator as a novel driver of MPN progression. HMGA1 is upregulated in MPN, with highest levels after transformation to MF or AML. To define HMGA1 function, we disrupted gene expression via CRISPR/Cas9, short hairpin RNA, or genetic deletion in MPN models. HMGA1 depletion in JAK2V617F AML cell lines disrupts proliferation, clonogenicity, and leukemic engraftment. Surprisingly, loss of just a single Hmga1 allele prevents progression to MF in JAK2V617F mice, decreasing erythrocytosis, thrombocytosis, megakaryocyte hyperplasia, and expansion of stem and progenitors, while preventing splenomegaly and fibrosis within the spleen and BM. RNA-sequencing and chromatin immunoprecipitation sequencing revealed HMGA1 transcriptional networks and chromatin occupancy at genes that govern proliferation (E2F, G2M, mitotic spindle) and cell fate, including the GATA2 master regulatory gene. Silencing GATA2 recapitulates most phenotypes observed with HMGA1 depletion, whereas GATA2 re-expression partially rescues leukemogenesis. HMGA1 transactivates GATA2 through sequences near the developmental enhancer (+9.5), increasing chromatin accessibility and recruiting active histone marks. Further, HMGA1 transcriptional networks, including proliferation pathways and GATA2, are activated in human MF and MPN leukemic transformation. Importantly, HMGA1 depletion enhances responses to the JAK2 inhibitor, ruxolitinib, preventing MF and prolonging survival in murine models of JAK2V617F AML. These findings illuminate HMGA1 as a key epigenetic switch involved in MPN transformation and a promising therapeutic target to treat or prevent disease progression.

Characterization of myeloproliferative neoplasms in the paediatric and young adult population.

The aim of this study was to compare the genomic features and clinical outcomes between paediatric and young adult patients (PAYA, <40 years) and older adults (OA, ≥40 years) with myeloproliferative neoplasms (MPN) to gain insight into pathogenesis, disease prognosis and management. Of 630 MPN patients, 171 (27%) were PAYA with an average age at diagnosis of 31 years. Females were more prevalent in PAYA than OA (71% vs 58%; p = 0.002), and PAYA more frequently presented with essential thrombocytosis (ET) at diagnosis (67% vs 39%; p < 0.001). The presence of a JAK2 somatic mutation was higher in OA (80.4% vs 64.3%; p < 0.001), while a CALR mutation or lack of any traditional driver mutation was more common in PAYA (20.5% vs 10.5%; p = 0.001, 8.8% vs 3.7%; p = 0.01 respectively). Venous thrombosis was more common in PAYA compared to OA (19.8% vs 10.7%; p = 0.002). PAYA had a higher prevalence of familial MPN and familial cancer predisposition, and two PAYA patients harboured pathogenic germline JAK2 lesions. PAYA demonstrated longer survival from diagnosis than OA (median not reached vs 13 years), while disease transformation was less frequent (19.3% vs 37.9%).

Hematoloechus sp. attachment shifts endothelium in vivo from pro- to anti-inflammatory profile in Rana pipiens: evidence from systemic and capillary physiology.

This prospective, descriptive study focused on lung flukes (Hematoloechus sp., H) and their impact on systemic and individual capillary variables measured in pithed Rana pipiens, a long-standing model for studies of capillary physiology. Three groups were identified based on Hematoloechus attachment: no Hematoloechus (No H), Hematoloechus not attached (H Not Att), and Hematoloechus attached (H Att). Among 38 descriptive, cardiovascular, and immunological variables, 18 changed significantly with H. Symptoms of H included weight loss, elevated immune cells, heart rate variability, faster coagulation, lower hematocrit, and fluid accumulation. Important capillary function discoveries included median baselines for hydraulic conductivity (Lp) of 7.0 (No H), 12.4 (H Not Att), and 4.2 (H Att) × 10-7 cm·s-1·cmH2O-1 (P < 0.0001) plus seasonal adaptation of sigma delta pi [σ(πc-πi), P = 0.03]. Pro- and anti-inflammatory phases were revealed for Lp and plasma nitrite/nitrate concentration ([NOx]) in both H Not Att and H Att, whereas capillary wall tensile strength increased in the H Att. H attachment was advantageous for the host due to lower edema and for the parasite via a sustained food source illustrating an excellent example of natural symbiosis. However, H attachment also resulted in host weight loss: in time, a conundrum for the highly dependent parasite. The study increases overall knowledge of Rana pipiens by revealing intriguing effects of H and previously unknown, naturally occurring seasonal changes in many variables. The data improve Rana pipiens as a general scientific and capillary physiology model. Diseases of inflammation and stroke are among the clinical applications.

Assessing Antigen-Adjuvant Complex Stability Against Physical Stresses By wNMR.

This study applies an emerging analytical technology, wNMR (water proton nuclear magnetic resonance), to assess the stability of aluminum adjuvants and antigen-adjuvant complexes against physical stresses, including gravitation, flow and freeze/thaw. Results from wNMR are verified by conventional analytical technologies, including static light scattering and microfluidic imaging. The results show that wNMR can quickly and noninvasively determine whether an aluminum adjuvant or antigen-adjuvant complex sample has been altered by physical stresses.

A hospital-based therapeutic food pantry study for people living with cancer in New Orleans.

INTRODUCTION: Food pantries have the potential to improve health outcomes and quality of life for individuals living with cancer. Gender has been linked to certain cancer symptoms and dietary patterns. Nevertheless, the extent of research on the utilization of food pantries among this population, particularly with regard to gender differences, remains limited. The objective of this study is to explore the demographic characteristics and gender differences in quality of life, as well as the impact of cancer on the lives of individuals who utilize food pantry services. METHODS: Between February 26, 2019 and July 24, 2022, 400 people living with cancer were eligible to participate the University Medical Center New Orleans (UMC) food pantry. Participants were asked to provide demographic information and completed two health assessments related to the challenges in daily activities, nutrition, and mental health. RESULTS: The study participants had a mean age of 54.1, and the majority of the participants were female. More than half of the participants did not have access to a vehicle or use public transportation to access grocery stores. People living with cancer reported several quality of life issues, with the most prevalent challenges being interference of cancer with work, lack of energy, difficulty affording food, pain, and sleep problems. Additionally, less than half of the patients reported consuming fruits and vegetables on a daily basis, and males were found to be less likely to consume them compared to females. DISCUSSION: The current study sheds light on the characteristics and quality of life of individuals who utilize UMC food pantry services, as well as the impact of cancer on their lives. The findings reveal a gender disparity in fruit and vegetable consumption, with male individuals living with cancer reporting lower levels of consumption. IMPLICATIONS FOR RESEARCH AND PRACTICE: Identifying and addressing food insecurity among people living with cancer are necessary. Meanwhile, partnerships with community organizations may be valuable in finding ways to assist cancer survivors in returning to work. Future studies could also focus on encouraging fruit and vegetable consumption, particularly among male individuals living with cancer.

Ultrastructural study of anther parasitism of Ficus laevigata by Ficophagus laevigatus (Aphelenchoididae).

Transmission electron microscopy (TEM) was used to compare the ultrastructural differences between healthy male florets (anthers) and one floret parasitized by Ficophagus laevigatus in late phase C syconia of Ficus laevigata from southern Florida. Previous light-microscopic examination of paraffin-sectioned material showed that F. laevigatus-infested anthers of F. laevigata manifested as malformed, often with aberrant pollen and hypertrophied epidermal cells closest to regions containing propagating nematodes. Female florets or fig wasp-parasitized female florets were not observed to be parasitized by nematodes. Considering that plant-feeding in the Aphelenchoididae is purportedly much less specialized than in certain groups of the Tylenchomorpha, where specialized hypertrophied feeder cells are produced in response to nematode feeding, we examined the putative induced response in this unusual aphelenchoidid system with the higher resolution afforded by TEM. TEM confirmed the expression of significant epidermal cell hypertrophy of the anther and anther filament in the presence of propagating nematodes, which was expressed as cell enlargement (2-5X), fractionation of large electron-dense stores into smaller aggregates, irregularly shaped nuclei enclosed by an elongated nuclear envelope, nucleolus enlargement, increased organelle production, and apparent metabolism with increased numbers of mitochondria, pro-plastids, and endoplasmic reticulum, as well as increased thickening of the cell walls. Pathological effects were observed in adjacent cells/tissue (e.g., anther and anther filament parenchymal cells, pollen tubes, pollen, and endothecium) with apparent diminishment as the distance from propagating nematodes increased (which was also probably affected by number of nematodes). Some TEM sections captured previously undocumented ultrastructural highlights of propagating individuals of F. laevigatus.

Just-in-Time Teaching (JiTT) Screencasts: a Randomized Controlled Trial of Asynchronous Learning on an Inpatient Hematology-Oncology Teaching Service.

BACKGROUND: The efficacy of just-in-time teaching (JiTT) screencasts for graduate medical education on an inpatient adult hematology-oncology service (HOS) setting is not known. Our preceding pilot data identified six high-yield topics for this setting. The study objective was to evaluate screencast educational efficacy. METHODS: Internal medicine residents scheduled to start a rotation on the primary HOS of an academic medical center were eligible for this parallel, unblinded, randomized controlled trial with concealed allocation. Participants underwent block randomization to the usual educational curriculum either with or without access to a series of novel screencasts; all participants received an anonymous online end-of-rotation survey and a $20 gift certificate upon completion. The primary outcome was the change in attitude among learners, measured as their self-reported confidence for managing the clinical topics. RESULTS: From 12/9/2019 through 6/15/2020, accrual was completed with 67 of 78 eligible residents (86%) enrolled and randomized. Analysis was by intention-to-treat and participant response rate was 91%. Sixty-four percent of residents in the treatment arm rated their clinical management comfort level as "comfortable" or "very comfortable" versus 21% of residents in the usual education arm (p = 0.001), estimated difference = 43% (95% CI: 21-66%), using a prespecified cumulative cutoff score. Treatment arm participants reported that the screencasts improved medical oncology knowledge base (100%), would improve their care for cancer patients (92%), and had an enjoyable format (96%). CONCLUSION: Residents on a busy inpatient HOS found that a JiTT screencast increased clinical comfort level in the management of HOS-specific patient problems.

A Partnership in Health-Related Social Media for Young Breast Cancer Survivors.

In the United States, about 11% (26,393) of those diagnosed with breast cancer in 2016 will be young or less than 45 years old. Young breast cancer survivors, compared to older cancer survivors, are a disparate group that experience higher incidence of advanced disease, greater mortality, and poorer quality of life, and are often faced with difficulty locating support that meet the unique needs of young women. The Gulf States Young Breast Cancer Survivor Network, composed of three sister networks, formed a partnership aimed at harnessing the power of social media to reach and impact the lives of young women with breast cancer. The collaborative partnership framework and the power of synergy are shown in merging two existing programs and incorporating a third new program.

Cervical Human Papillomavirus Testing With Two Home Self-Collection Methods Compared With a Standard Clinically Collected Sampling Method.

BACKGROUND: The purpose of this study was to compare the outcomes of 2 self-collection methods to detect cervical human papillomavirus (HPV) DNA with outcomes from a standard clinical method. The standard method samples were collected by a clinician at a routine pelvic examination. Self-samples were taken at home and mailed to the clinical laboratory. METHODS: The 2 self-collection methods were a tampon-based method and a swab-based method using a commercial device, an Eve Medical HerSwab. All HPV samples were processed by a clinical laboratory using the Food and Drugs Administration approved Roche Cobase HPV method, which specifically identifies HPV 16, HPV 18, and a set of 12 other high-risk subtypes. Patients were recruited from 2 cancer screening clinics 2015 to 2017. All patients signed an informed consent. Screening outcomes, such as prevalence, percent agreement with standard, sensitivity, and specificity, were calculated for each self-collection method. Measures of similarity between self and standard collection outcomes, Cohen's κ, percent concordance, McNemar equivalence, and others were tested statistically. RESULTS: One hundred seventy-four patients were randomized. The prevalence of 1 or more positive HPV high-risk subtypes from the standard clinical specimens was 13.5%. All clinical specimens were sufficient for valid HPV detection. For the tampon method, 15 (27%) of the specimens were insufficient quality. Only 1 (2%) swab specimen was insufficient. Only the swab self-collection method was found to be statistically noninferior to the clinical method. The tampon method had an unacceptably high rate of insufficient quality specimens and also failed the equivalency tests. CONCLUSIONS: The swab home collection samples were equivalent to the clinical samples, but the tampon method had an unacceptably high rate of specimens insufficient for HPV detection.

Two clinical phenotypes in polycythemia vera.

BACKGROUND: Polycythemia vera is the ultimate phenotypic consequence of the V617F mutation in Janus kinase 2 (encoded by JAK2), but the extent to which this mutation influences the behavior of the involved CD34+ hematopoietic stem cells is unknown. METHODS: We analyzed gene expression in CD34+ peripheral-blood cells from 19 patients with polycythemia vera, using oligonucleotide microarray technology after correcting for potential confounding by sex, since the phenotypic features of the disease differ between men and women. RESULTS: Men with polycythemia vera had twice as many up-regulated or down-regulated genes as women with polycythemia vera, in a comparison of gene expression in the patients and in healthy persons of the same sex, but there were 102 genes with differential regulation that was concordant in men and women. When these genes were used for class discovery by means of unsupervised hierarchical clustering, the 19 patients could be divided into two groups that did not differ significantly with respect to age, neutrophil JAK2 V617F allele burden, white-cell count, platelet count, or clonal dominance. However, they did differ significantly with respect to disease duration; hemoglobin level; frequency of thromboembolic events, palpable splenomegaly, and splenectomy; chemotherapy exposure; leukemic transformation; and survival. The unsupervised clustering was confirmed by a supervised approach with the use of a top-scoring-pair classifier that segregated the 19 patients into the same two phenotypic groups with 100% accuracy. CONCLUSIONS: Removing sex as a potential confounder, we identified an accurate molecular method for classifying patients with polycythemia vera according to disease behavior, independently of their JAK2 V617F allele burden, and identified previously unrecognized molecular pathways in polycythemia vera outside the canonical JAK2 pathway that may be amenable to targeted therapy. (Funded by the Department of Defense and the National Institutes of Health.).

Louisiana Physicians Are Increasing HPV Vaccination Rates.

Human papilloma virus (HPV) is a common virus that can cause genital warts and certain cancers. The HPV vaccine is effective in preventing many HPV-associated diseases, however, vaccination rates suggest many remain unprotected. This study examined successful strategies used by physicians to improve HPV vaccination rates. Providers with above average vaccination rates were identified. A representative from each provider participated in an interview to identify strategies used to boost HPV vaccination. Key strategies in ensuring vaccine completion were reminders, education, standing orders, and scheduling future vaccine appointments at time of first dose. Other successful strategies included coupling the HPV vaccine with adolescent vaccines, administering during well-visits, and recommending the vaccine as protection against cancer and genital warts. Findings suggest successful and widely used methods among high performing providers in Louisiana, the majority of which should be easily reproducible with minimal resources to improve HPV vaccination rates.

Defective chloroplast development inhibits maintenance of normal levels of abscisic acid in a mutant of the Arabidopsis RH3 DEAD-box protein during early post-germination growth.

The plastid has its own translation system, and its ribosomes are assembled through a complex process in which rRNA precursors are processed and ribosomal proteins are inserted into the rRNA backbone. DEAD-box proteins have been shown to play roles in multiple steps in ribosome biogenesis. To investigate the cellular and physiological roles of an Arabidopsis DEAD-box protein, RH3, we examined its expression and localization and the phenotypes of rh3-4, a T-DNA insertion mutant allele of RH3. The promoter activity of RH3 is strongest in the greening tissues of 3-day and 1-week-old seedlings but reduced afterwards. Cotyledons were pale and seedling growth was retarded in the mutant. The most obvious abnormality in the mutant chloroplasts was their lack of normal ribosomes. Electron tomography analysis indicated that ribosome density in the 3-day-old mutant chloroplasts is only 20% that of wild-type chloroplasts, and the ribosomes in the mutant are smaller. These chloroplast defects in rh3-4 were alleviated in 2-week-old cotyledons and true leaves. Interestingly, rh3-4 seedlings have lower amounts of abscisic acid prior to recovery of their chloroplasts, and were more sensitive to abiotic stresses. Transcriptomic analysis indicated that nuclear genes for chloroplast proteins are down-regulated, and proteins mediating chloroplast-localized steps of abscisic acid biosynthesis are expressed to a lower extent in 1-week-old rh3-4 seedlings. Taken together, these results suggest that conversion of eoplasts into chloroplasts in young seedlings is critical for the seedlings to start carbon fixation as well as for maintenance of abscisic acid levels for responding to environmental challenges.

Fever after rewarming: incidence of pyrexia in postcardiac arrest patients who have undergone mild therapeutic hypothermia.

BACKGROUND: Induction of mild therapeutic hypothermia (TH; temperature 32-34°C) has become standard of care in many hospitals for comatose survivors of cardiac arrest. Pyrexia, or fever, is known to be detrimental in patients with neurologic injuries such as stroke or trauma. The incidence of pyrexia in the postrewarming phase of TH is unknown. We attempted to determine the incidence of fever after TH and hypothesized that those patients who were febrile after rewarming would have worse clinical outcomes than those who maintained normothermia in the postrewarming period. METHODS: Retrospective data analysis of survivors of out-of-hospital cardiac arrest (OHCA) over a period of 29 months (December 2007 to April 2010). INCLUSION CRITERIA: OHCA, age >18, return of spontaneous circulation, and treatment with TH. EXCLUSION CRITERIA: traumatic arrest and pregnancy. Data collected included age, sex, neurologic outcome, mortality, and whether the patient developed fever (temperature > 100.4°F, 38°C) within 24 hours after being fully rewarmed to a normal core body temperature after TH. We used simple descriptive statistics and Fisher exact test to report our findings. RESULTS: A total of 149 patients were identified; of these, 82 (55%) underwent TH. The mean age of the TH cohort was 66 years, and 28 (31%) were female. In all, 54 patients survived for >24 hours after rewarming and were included in the analysis. Among the analyzed cohort, 28 (52%) of 54 developed fever within 24 hours after being rewarmed. Outcome measures included in-hospital mortality as well as neurologic outcome as defined by a dichotomized Cerebral Performance Category (CPC) score. When comparing neurologic outcomes between the groups, 16 (57%) of 28 in the postrewarming fever group had a poor outcome (CPC score 3-5), while 15 (58%) of 26 in the no-fever group had a favorable outcome (P = .62). In the fever group, 15 (52%) of 28 died, while in the no-fever group, 14 (54%) of 26 died (P = .62). CONCLUSION: Among a cohort of patients who underwent mild TH after OHCA, more than half of these patients developed pyrexia in the first 24 hours after rewarming. Although there were no significant differences in outcomes between febrile and nonfebrile patients identified in this study, these findings should be further evaluated in a larger cohort. Future investigations may be needed to determine whether postrewarming temperature management will improve the outcomes in this population.

Chemical structure requirements and cellular targeting of microRNA-122 by peptide nucleic acids anti-miRs.

Anti-miRs are oligonucleotide inhibitors complementary to miRNAs that have been used extensively as tools to gain understanding of specific miRNA functions and as potential therapeutics. We showed previously that peptide nucleic acid (PNA) anti-miRs containing a few attached Lys residues were potent miRNA inhibitors. Using miR-122 as an example, we report here the PNA sequence and attached amino acid requirements for efficient miRNA targeting and show that anti-miR activity is enhanced substantially by the presence of a terminal-free thiol group, such as a Cys residue, primarily due to better cellular uptake. We show that anti-miR activity of a Cys-containing PNA is achieved by cell uptake through both clathrin-dependent and independent routes. With the aid of two PNA analogues having intrinsic fluorescence, thiazole orange (TO)-PNA and [bis-o-(aminoethoxy)phenyl]pyrrolocytosine (BoPhpC)-PNA, we explored the subcellular localization of PNA anti-miRs and our data suggest that anti-miR targeting of miR-122 may take place in or associated with endosomal compartments. Our findings are valuable for further design of PNAs and other oligonucleotides as potent anti-miR agents.

Sending a Signal: Evaluating the Impact of Program and Geographic Preference Signaling on the Internal Medicine Residency Match.

Background For over a decade, the number of residency applications has surged, a trend known as "application inflation." COVID-19 further intensified this trend, leading the Association of American Medical Colleges (AAMC) to address the issue by introducing a supplemental application in the 2021-2022 cycle, allowing programs to identify applicants with a connection to their program or geographic region. For the 2022-2023 cycle, the number of program signals increased from five to seven. The impact of the supplemental application and the increase in signals on the likelihood of an applicant matching with a program has yet to be evaluated. Methods This retrospective cohort study evaluated the impact of program signaling and geographic preference on the matching likelihood in our internal medicine residency program. Data from MyERAS® and the Supplemental Application for 640 applicants who applied to our large, urban, university-based program in the Southeastern United States during the 2020-2021 and 2022-2023 application cycles were included. Using univariate and multivariate analysis, we examined the correlation between program signal, geographic preference, and final match location. Results Applicants who sent a program signal had nearly three-fold higher odds of matching with our program. Geographic preference was numerically but not statistically associated with higher odds of matching. Both signaling a preference for matching with a program in an urban environment and couples matching correlated with decreased odds of matching with our program. Geography was an important predictor of match location as residing in our AAMC geographic region, our four-state area, and our specific state had increased odds of matching with our program. Conclusions Signaling our program was associated with increased odds of matching with our program. Geographic preferences were less predictive of a match with our program; however, they did predict the likelihood of a match at a program within that region. Future studies are needed to ensure external validity.

Outcomes of the Internal Medicine Supplemental Application: Preliminary Data on the 2022-2023 Match.

INTRODUCTION: Preference signaling (program signals and geographic preference divisions) was introduced as a component of the supplemental application for internal medicine applicants applying to programs within the United States (USA) during the 2021-22 cycle. These signals were intended to address application inflation by allowing applicants to express interest in and increase their likelihood of receiving interviews from their top programs. There is little published data, however, to describe the impact of preference signaling on the likelihood of receiving interviews from a program. This study thus sought to analyze, in a small subset of US applicants, whether preference signals were associated with a higher likelihood of obtaining a residency interview. METHODS: A survey was distributed in March 2023 to US MD seniors from the four allopathic medical schools in North Carolina who applied to categorical internal medicine residency programs during the 2022-23 application cycle. The survey was developed by the research team to provide respondents with the opportunity to report data from the electronic residency application service (ERAS) application and provide data on interviews received, actions taken throughout the application season, and outcomes of the National Residency Match Program (NRMP) using a combination of free response and multiple choice questions. RESULTS: Forty-seven out of a total of 85 contacted (55%) applicants completed some or all of the survey. Of those who completed the entirety of the survey, 39 (82.98%) completed the supplemental portion of the application and the available preference signaling. Applicants in this study were 2.95 (Odds ratio, 95% confidence interval [CI] 2.20 - 3.97, p<0.01) times as likely to receive an interview invitation from a program if they used a program signal. Applicants were 1.75 (odds ratio, 95% CI 1.38 - 2.21, p<0.01) times as likely to receive an interview invitation from a program in an indicated geographic preference division. Forty-seven percent (95% CI 31 - 64%) matched to a program they had sent a program signal to, and 97% (95% CI 78 - 100%) matched to a program in an indicated geographic preference division. CONCLUSIONS: The program signals and geographic preference division components of the supplemental application increased the likelihood of receiving an interview invitation but did not have a clear impact on match outcomes. Further research with larger sample sizes will be necessary to determine how these signals actually modify the outcomes of the NRMP.

Perceived Ageism is Associated With Recurrent Falling Among Older Colombian Adults.

Literature on the association between ageism and falling among older adults is limited. Using data from the nationwide cross-sectional SABE (Salud, Bienestar y Envejecimiento) Colombia Survey in 2015 with 18,875 participants aged ≥60 years living in the communities, the study aims to evaluate the association between perceived ageism within the family, neighborhood, health services, and public services, and recurrent falling. Participants had a mean age of 69.2 ± 7.1; 56.1% were female. Recurrent falling prevalence was 15%, and experiencing any ageism was 10%. Multivariable logistic regression analyses showed higher odds of recurrent falling for any ageism (OR = 1.81, 95% CI 1.61-2.02, p < .0001). High depressive symptoms mediated 10.1% of the association between any ageism and recurrent falling, followed by low instrumental activities of daily living (9.7%) and multimorbidity (9.3%). Current findings open new areas of gerontological research by expanding the risk factors for falling among older adults to include ageism perceptions.

Parallel synthesis and splicing redirection activity of cell-penetrating peptide conjugate libraries of a PNA cargo.

A novel method for the parallel synthesis of peptide-biocargo conjugates was developed that utilizes affinity purification for fast isolation of the conjugates in order to avoid time consuming HPLC purification. The methodology was applied to create two libraries of cell-penetrating peptide (CPP)-PNA705 conjugates from parallel-synthesized peptide libraries. The conjugates were tested for their ability to induce splicing redirection in HeLa pLuc705 cells. The results demonstrate how the novel methodology can be applied for screening purposes in order to find suitable CPP-biocargo combinations and further optimization of CPPs.

The Future of Community Outreach: Using Patient Portals to Provide Voter Resources during the Coronavirus Disease 2019 Pandemic.

BACKGROUND: During the coronavirus disease 2019 (COVID-19) pandemic, there was a concern for the 2020 general election becoming a superspreader event due to in-person voting. OBJECTIVES: Our project addressed this concern by disseminating nonpartisan websites detailing safe voter options in the state of North Carolina to prevent community spread of the virus as much as possible. METHODS: In this study, patient portals were used to disseminate a Research Electronic Data Capture survey containing embedded links to voter resources including nonpartisan websites discussing voting options. The survey also asked for demographic data and sentiments regarding the resources provided. Quick response (QR) codes with the survey link were also placed in the clinics during the study period. RESULTS: The survey was sent to 14,842 patients who had at least one patient encounter in the past 12 months at one of three General Internal Medicine clinics at Atrium Health Wake Forest Baptist. Survey participation through both the patient portals and QR codes was assessed. Patient sentiments toward the voter resources in regard to (1) interest and (2) perceived helpfulness were collected in the survey. In total, 738 (4.99%) patients filled out the survey. Eighty-seven percent of survey respondents reported that the voter resources were helpful. Significantly more black patients than white (29.3 vs. 18.2, p < 0.05) voiced interest in voter resources. There was no statistical significance across gender or reported comorbidities. CONCLUSION: Multicultural, underserved, and underinsured patients perceived the most benefit. During public health crises, patient portal messages can be used to bridge information gaps and promote better health outcomes in a timely and effective manner.