Associations between CDH1 gene polymorphisms and the risk of gastric cancer: A meta-analysis based on 44 studies.

BACKGROUND: Numerous studies have investigated the association between CDH1 polymorphisms and gastric cancer (GC) risk. However, the results have been inconsistent and controversial. To further determine whether CDH1 polymorphisms increase the risk of GC, we conducted a meta-analysis by pooling the data. METHODS: Relevant case-control studies were collected from PubMed, Embase, Web of Science and Cochrane databases up to January 7, 2024. Subsequently, odds ratios (ORs) with 95% confidence intervals (CIs) were used to evaluate the strength of correlations. A sensitivity analysis was performed to evaluate the robustness and reliability of these included studies. RESULTS: A total of 25 articles including 44 studies, were included in this meta-analysis, including 26 studies on rs16260, 6 studies on rs3743674, 7 studies on rs5030625, and 5 studies on rs1801552. The pooled results showed that rs16260 was remarkably associated with an increased GC risk of GC among Caucasians. Moreover, the rs5030625 variation dramatically enhanced GC predisposition in the Asian population. However, no evident correlations between CDH1 rs3743674 and rs1801552 polymorphisms and GC risk were observed. CONCLUSIONS: Our findings suggested that CDH1 gene polymorphisms were significantly correlated with GC risk, especially in rs16260 and rs5030625 polymorphisms.

The association of COVID-19 vaccination and menstrual health: A period-tracking app-based cohort study.

Background: In initial COVID-19 clinical trials, menstrual health was not formally monitored, yet anecdotal reports of menstruation changes surfaced on social media. This study aims to assess the association between COVID-19 vaccines and menstruation using Clue, a period-tracking application. Study design: A survey assessing demographics, menstrual health, stress levels, and COVID-19 vaccination was sent to Clue users between 12/7/2021 and 2/9/2022. Inclusion criteria were (1) 18 years or older (2) currently menstruating (3) not pregnant or breastfeeding since 1/2020. Menstrual data was collected for each participant. Users with cycle lengths more than 90 days were excluded. Cycle lengths were calculated for the 6-month average pre-vaccination (PRIOR), the cycle during which vaccination was administered (DURING), the cycle following DURING (AFTER1), and the cycle following AFTER1 (AFTER2). For periods, individuals were stratified based on whether vaccination was received during their menstrual period (DURING). Period lengths were additionally calculated for the 6-month average pre-vaccination (PRIOR), the first period following vaccination (AFTER1), and the period following AFTER1 (AFTER2). For unvaccinated participants, an index date (4/1/2022) was used to similarly designate menstrual cycles and periods. For each participant, cycle length changes for DURING, AFTER1, and AFTER2 compared to PRIOR were determined. Student's t-test compared the mean of these changes between vaccinated and unvaccinated groups. Results: Of 7,559 participants, 6,897 (91 %) were vaccinated. Compared to PRIOR, individuals vaccinated during their menstrual period demonstrated a statistically significant increase in the DURING period length, but not AFTER1 (p = 0.463) and AFTER2 (p = 0.692). No statistically significant changes were observed in period lengths of those vaccinated in between periods or in cycle lengths overall. Conclusion: A small but statistically significant change in period length was observed only in individuals vaccinated for COVID-19 during their menstrual period. Providers can better counsel menstruating individuals to reduce vaccine misinformation.

Insulin-Like Growth Factor 1 Receptor Deficiency Alleviates Angiotensin II-Induced Cardiac Fibrosis Through the Protein Kinase B/Extracellular Signal-Regulated Kinase/Nuclear Factor-κB Pathway.

Background The renin-angiotensin system plays a crucial role in the development of heart failure, and Ang II (angiotensin II) acts as the critical effector of the renin-angiotensin system in regulating cardiac fibrosis. However, the mechanisms of cardiac fibrosis are complex and still not fully understood. IGF1R (insulin-like growth factor 1 receptor) has multiple functions in maintaining cardiovascular homeostasis, and low-dose IGF1 treatment is effective in relieving Ang II-induced cardiac fibrosis. Here, we aimed to investigate the molecular mechanism of IGF1R in Ang II-induced cardiac fibrosis. Methods and Results Using primary mouse cardiac microvascular endothelial cells and fibroblasts, in vitro experiments were performed. Using C57BL/6J mice and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9)-mediated IGF1R heterozygous knockout (Igf1r+/-) mice, cardiac fibrosis mouse models were induced by Ang II for 2 weeks. The expression of IGF1R was examined by quantitative reverse transcription polymerase chain reaction, immunohistochemistry, and Western blot. Mice heart histologic changes were evaluated using Masson and picro sirius red staining. Fibrotic markers and signal molecules indicating the function of the Akt (protein kinase B)/ERK (extracellular signal-regulated kinase)/nuclear factor-κB pathway were detected using quantitative reverse transcription polymerase chain reaction and Western blot. RNA sequencing was used to explore IGF1R-mediated target genes in the hearts of mice, and the association of IGF1R and G-protein-coupled receptor kinase 5 was identified by coimmunoprecipitation. More important, blocking IGF1R signaling significantly suppressed endothelial-mesenchymal transition in primary mouse cardiac microvascular endothelial cells and mice in response to transforming growth factor-ß1 or Ang II, respectively. Deficiency or inhibition of IGF1R signaling remarkably attenuated Ang II-induced cardiac fibrosis in primary mouse cardiac fibroblasts and mice. We further observed that the patients with heart failure exhibited higher blood levels of IGF1 and IGF1R than healthy individuals. Moreover, Ang II treatment significantly increased cardiac IGF1R in wild type mice but led to a slight downregulation in Igf1r+/- mice. Interestingly, IGF1R deficiency significantly alleviated cardiac fibrosis in Ang II-treated mice. Mechanistically, the phosphorylation level of Akt and ERK was upregulated in Ang II-treated mice, whereas blocking IGF1R signaling in mice inhibited these changes of Akt and ERK phosphorylation. Concurrently, phosphorylated p65 of nuclear factor-κB exhibited similar alterations in the corresponding group of mice. Intriguingly, IGF1R directly interacted with G-protein-coupled receptor kinase 5, and this association decreased ≈50% in Igf1r+/- mice. In addition, Grk5 deletion downregulated expression of the Akt/ERK/nuclear factor-κB signaling pathway in primary mouse cardiac fibroblasts. Conclusions IGF1R signaling deficiency alleviates Ang II-induced cardiac fibrosis, at least partially through inhibiting endothelial-mesenchymal transition via the Akt/ERK/nuclear factor-κB pathway. Interestingly, G-protein-coupled receptor kinase 5 associates with IGF1R signaling directly, and it concurrently acts as an IGF1R downstream effector. This study suggests the promising potential of IGF1R as a therapeutic target for cardiac fibrosis.

Identifying predictors of resilience to stressors in single-arm studies of pre-post change.

Many older adults experience a major stressor at some point in their lives. The ability to recover well after a major stressor is known as resilience. An important goal of geriatric research is to identify factors that influence resilience to stressors. Studies of resilience in older adults are typically conducted with a single-arm where everyone experiences the stressor. The simplistic approach of regressing change versus baseline yields biased estimates due to mathematical coupling and regression to the mean (RTM). We develop a method to correct the bias. We extend the method to include covariates. Our approach considers a counterfactual control group and involves sensitivity analyses to evaluate different settings of control group parameters. Only minimal distributional assumptions are required. Simulation studies demonstrate the validity of the method. We illustrate the method using a large, registry of older adults (N  =7239) who underwent total knee replacement (TKR). We demonstrate how external data can be utilized to constrain the sensitivity analysis. Naive analyses implicated several treatment effect modifiers including baseline function, age, body-mass index (BMI), gender, number of comorbidities, income, and race. Corrected analysis revealed that baseline (pre-stressor) function was not strongly linked to recovery after TKR and among the covariates, only age and number of comorbidities were consistently and negatively associated with post-stressor recovery in all functional domains. Correction of mathematical coupling and RTM is necessary for drawing valid inferences regarding the effect of covariates and baseline status on pre-post change. Our method provides a simple estimator to this end.

Food insecurity gaps in the Supplemental Nutrition Assistance Program based on disability status.

BACKGROUND: Households including someone with disabilities experience disproportionately high food insecurity rates and likely face disproportionate barriers accessing Supplemental Nutrition Assistance Program (SNAP) benefits. OBJECTIVE: This article aims to examine the role of SNAP with regard to food insecurity disparities based on disability status. METHODS: Modified Poisson regression models examined food insecurity risk based on disability status (household includes no one with disabilities vs. those with work-limiting disabilities or non-work-limiting disabilities) among 2018 Survey of Income and Program Participation households eligible for SNAP (income ≤130% of the poverty threshold). Weighted estimates were used to account for the study design and non-response. RESULTS: Households including someone with work-limiting disabilities were more than twice as likely to be food insecure than households including no one with disabilities (PR = 2.16, 95% CI: 1.90, 2.45); households including someone with non-work-limiting disabilities were 65% more likely (PR = 1.65, 95% CI: 1.39, 1.95). However, disparities were more pronounced among households not participating in SNAP (PR = 2.67, 95% CI: 2.22, 3.23 for work-limiting disabilities and PR = 1.86, 95% CI: 1.44, 2.40 for non-work-limiting disabilities) than SNAP-participating households (PR = 1.71, 95% CI: 1.45, 2.03 and PR = 1.46, 95% CI: 1.17, 1.82, respectively). Approximately 4.2 million low-income U.S. households including someone with disabilities are food insecure. Of these, 1.4 million were not participating in SNAP and another 2.8 million households were food insecure despite participating in SNAP. CONCLUSIONS: Access to SNAP benefits is not proportionate to the scale of food insecurity among households that include people with disabilities. Action is needed to strengthen food assistance for those with disabilities.

Supplemental Nutrition Assistance Program Access and Racial Disparities in Food Insecurity.

Importance: Racially minoritized people experience disproportionately high rates of food insecurity. The Supplemental Nutrition Assistance Program (SNAP) reduces food insecurity. Objective: To evaluate SNAP access with regard to racial disparities in food insecurity. Design, Setting, and Participants: This cross-sectional study used data from the 2018 Survey of Income and Program Participation (SIPP). On the basis of random sampling strategies, 44 870 households were eligible for the SIPP, and 26 215 (58.4%) participated. Sampling weights accounted for survey design and nonresponse. Data were analyzed from February 25 to December 12, 2022. Exposures: This study examined disparities based on household racial composition (entirely Asian, entirely Black, entirely White, and multiple races or multirace based on SIPP categories). Main Outcomes and Measures: Food insecurity during the prior year was measured using the validated 6-item US Department of Agriculture Food Security Survey Module. SNAP participation during the prior year was classified based on whether anyone in the household received SNAP benefits. Modified Poisson regression tested hypothesized disparities in food insecurity. Results: A total of 4974 households that were eligible for SNAP (income ≤130% of the poverty threshold) were included in this study. A total of 218 households (5%) were entirely Asian, 1014 (22%) were entirely Black, 3313 (65%) were entirely White, and 429 (8%) were multiracial or of other racial groups. Adjusting for household characteristics, households that were entirely Black (prevalence rate [PR], 1.18; 95% CI, 1.04-1.33) or multiracial (PR, 1.25; 95% CI, 1.06-1.46) were more likely to be food insecure than entirely White households, but associations differed depending on SNAP participation. Among households that did not participate in SNAP, those that were entirely Black (PR, 1.52; 97.5% CI, 1.20-1.93) or multiracial (PR, 1.42; 97.5% CI, 1.04-1.94) were more likely to be food insecure than White households; however, among SNAP participants, Black households were less likely than White households to be food insecure (PR, 0.84; 97.5% CI, 0.71-0.99). Conclusions and Relevance: In this cross-sectional study, racial disparities in food insecurity were found among low-income households that do not participate in SNAP but not among those that do, suggesting that access to SNAP should be improved. These results also highlight the need to examine the structural and systemic racism in food systems and in access to food assistance that may contribute to disparities.

Development and validation of dynamic nomogram of frailty risk for older patients hospitalized with heart failure.

Objective: This study aimed to establish and validate a dynamic online nomograph for predicting the risk of frailty in older patients hospitalized with heart failure in China. Methods: A total of 451 older adults with heart failure hospitalized were selected between December 2021 and November 2022 at the Department of Cardiovascular Medicine in a Class A tertiary hospital in Shandong, China. The data of patients were obtained by using Barthel Index, instrumental activity of daily living scale, mini nutrition assessment-short form, Pittsburgh sleep quality index scale, Morse fall risk assessment scale and general information scale. The brain natriuretic peptide and echocardiographic indexes of patients were collected by electronic medical records. All participants were randomly divided into the training set (n = 319) and the validation set (n = 132) at the ratio of 7:3. The training set is used for model construction, and the validation set is used for internal validation. Using the Least Absolute Shrinkage and Selection Operator (LASSO) regression method to filter modeling variables, while the multivariable logistic regression was used to establish the nomogram based on the screened optimal variables. The performance of the model was evaluated by the area under the curve (AUC) of the receiver operator characteristic (ROC) curve, Hosmer-Lemeshow test, calibration plot, and decision curve analysis (DCA). Results: The prevalence of frailty in 451 patients was 50.6%, 51.4%, and 48.5% in the training and validation sets, respectively. Drinking, grip strength, New York Heart Association (NYHA) class, multimorbidity, hospitalization history of heart failure, Barthel Index, the instrumental activities of daily living, nutritional status, sleep, fall, and left atrial end-diastolic diameter were used for LASSO regression analysis as the significant predictors of frailty. According to internal validation, the AUC of the ROC curve for the nomogram was 0.920, with a sensitivity of 86.8% and specificity of 84.4%. Moreover, in the validation set, the P-values of the H-L test were 0.742, and the calibration curve had good concordance between the estimated frailty risk and actual observation, indicating the model was well-calibrated. The DCA results confirmed that the nomogram had a well-performance in clinical suitability. Conclusions: An online dynamic nomogram predicting frailty for older patients hospitalized for heart failure in China was well-established and identified in this study. This model benefits medical professionals in identifying high-risk frailty in older hospitalized patients with heart failure, which could reduce the medical and disease burden of heart failure to a certain extent. However, further verification is needed in the future.

Bladder capacity and growth in classic bladder exstrophy: A novel predictive tool.

INTRODUCTION: Bladder capacity (BC) is an important metric in the management of patients with classic bladder exstrophy (CBE). BC is frequently used to determine eligibility for surgical continence procedures, such as bladder neck reconstruction (BNR), and is associated with the likelihood of achieving urinary continence. OBJECTIVE: To use readily available parameters to develop a nomogram that could be used by patients and pediatric urologists to predict BC in patients with CBE. STUDY DESIGN: An institutional database of CBE patients was reviewed for those who have undergone annual gravity cystogram 6 months after bladder closure. Candidate clinical predictors were used to model BC. Linear mixed effects models with random intercept and slope were used to construct models predicting log transformed BC and were compared with adjusted R2, Akaike Information Criterion (AIC), and cross-validated mean square error (MSE). Final model evaluated via K-fold cross-validation. Analyses were performed using R version 3.5.3 and the prediction tool was developed with ShinyR. RESULTS: In total, 369 patients (107 female, 262 male) with CBE had at least one BC measurement after bladder closure. Patients had a median of 3 annual measurements (range 1-10). The final nomogram includes outcome of primary closure, sex, log-transformed age at successful closure, time from successful closure, and interaction between outcome of primary closure and log-transformed age at successful closure as the fixed effects with random effect for patient and random slope for time since successful closure (Extended Summary). DISCUSSION: Using readily accessible patient and disease related information, the bladder capacity nomogram in this study provides a more accurate prediction of bladder capacity ahead of continence procedures when compared to the age-based Koff equation estimates. A multi-center study using this web-based CBE bladder growth nomogram (https://exstrophybladdergrowth.shinyapps.io/be_app/) will be needed for widespread application. CONCLUSION: Bladder capacity in those with CBE, while known to be influenced by a broad swath of intrinsic and extrinsic factors, may be modeled by the sex, outcome of primary bladder closure, age at successful bladder closure and age at evaluation.

COVID-19 clinical outcomes by patient disability status: A retrospective cohort study.

BACKGROUND: People with disabilities might experience worse clinical outcomes of SARS-CoV-2 infection, but evidence is limited. OBJECTIVE: To investigate if people with disabilities requiring assistance are more likely to experience severe COVID-19 or death. METHODS: Data from the Johns Hopkins COVID-19 Precision Medicine Analytics Platform Registry (JH-CROWN) included 6494 adult patients diagnosed with COVID-19 and admitted between March 4, 2020-October 29, 2021. Severe COVID-19 and death were defined using the occurrence and timing of clinical events. Assistive needs due to disabilities were reported by patients or their proxies upon admission. Multivariable-adjusted Cox proportional hazards models were used to examine the associations between disability status and severe COVID-19 or death. Primary models adjusted for demographics and secondary models additionally adjusted for clinical covariates. RESULTS: In this clinical cohort (47-73 years, 49% female, 39% Black), patients with disabilities requiring assistance had 1.35 times (95% confidence interval [CI]:1.01, 1.81) the hazard of severe COVID-19 among patients <65 years, but not among those ≥65 years, equating to an additional 17.5 severe COVID-19 cases (95% CI:7.7, 28.2) per 100 patients. A lower risk of mortality was found among patients <65 years, but this finding was not robust due to the small number of deaths. CONCLUSIONS: People with disabilities requiring assistance aged <65 years are more likely to develop severe COVID-19. Although our study is limited by using a medical model of disability, these analyses intend to further our understanding of COVID-19 outcomes among people with disabilities. Also, standardized disability data collection within electronic health records is needed.

Antiresorptive Medications Prior to Stereotactic Body Radiotherapy for Spinal Metastasis are Associated with Reduced Incidence of Vertebral Body Compression Fracture.

STUDY DESIGN: Retrospective Cohort. OBJECTIVE: Antiresorptive drugs are often given to minimize fracture risk for bone metastases, but data regarding optimal time or ability to reduce stereotactic body radiotherapy (SBRT)-induced fracture risk is limited. This study examines the association between antiresorptive use surrounding spinal SBRT and vertebral compression fracture (VCF) incidence to provide information regarding effectiveness and optimal timing of use. METHODS: Patients treated with SBRT for spinal metastases at a single institution between 2009-2020 were included. Kaplan-Meier analysis was used to compare cumulative incidence of VCF for those taking antiresorptive drugs pre-SBRT, post-SBRT only, and none at all. Cox proportional hazards and Fine-Gray competing risk models were used to identify additional factors associated with VCF. RESULTS: Of the 234 patients (410 vertebrae) analyzed, 49 (20.9%) were taking bisphosphonates alone, 42 (17.9%) were taking denosumab alone, and 25 (10.7%) were taking both. Kaplan-Meier analysis revealed a statistically significant lower VCF incidence for patients initiating antiresorptive drugs before SBRT compared to those taking none at all (4% vs 12% at 1 year post-SBRT, P = .045; and 4% vs 23% at 2 years, P = .008). On multivariate analysis, denosumab duration (HR: .87, P = .378) or dose (HR: 1.00, P = .644) as well as bisphosphonate duration (HR: .98, P= .739) or dose (HR: .99, P= .741) did not have statistical significance on VCF incidence. CONCLUSION: Initiating antiresorptive agents before SBRT may reduce the risk of treatment-induced VCF. Antiresorptive drugs are underutilized in patients with spine metastases and may represent a useful intervention to minimize toxicity and improve long-term outcomes.

Enhancement of Cell Adhesion by Anaplasma phagocytophilum Nucleolin-Interacting Protein AFAP.

Anaplasma phagocytophilum, the aetiologic agent of human granulocytic anaplasmosis (HGA), is an obligate intracellular Gram-negative bacterium. During infection, A. phagocytophilum enhances the adhesion of neutrophils to the infected endothelial cells. However, the bacterial factors contributing to this phenomenon remain unknown. In this study, we characterized a type IV secretion system substrate of A. phagocytophilum, AFAP (an actin filament-associated Anaplasma phagocytophilum protein) and found that it dynamically changed its pattern and subcellular location in cells and enhanced cell adhesion. Tandem affinity purification combined with mass spectrometry identified host nucleolin as an AFAP-interacting protein. Further study showed the disruption of nucleolin by RNA interference, and the treatment of a nucleolin-binding DNA aptamer AS1411 attenuated AFAP-mediated cell adhesion, indicating that AFAP enhanced cell adhesion in a nucleolin-dependent manner. The characterization of cell adhesion-enhancing AFAP and the identification of host nucleolin as its interaction partner may help understand the mechanism underlying A. phagocytophilum-promoting cell adhesion, facilitating the elucidation of HGA pathogenesis.

Interface modified BTO@PS-co-mah/PS composite dielectrics with enhanced breakdown strength and ultralow dielectric loss.

Dielectrics of the polymer-matrix composite are considered to present combined advantages from both the polymer matrix and inorganic fillers. However, the breakdown strength, as well as energy density, is not effectively enhanced due to the poor compatibility between the organic and inorganic components. Herein, polymer composites derived from polystyrene (PS) and barium titanate (BTO) are proposed and beneficial interface modification by poly(styrene-co-maleic anhydride) (PS-co-mah) is conducted to improve compatibility between the inorganic filler and polymer matrix. The results show that the BTO@PS-co-mah/PS composites, in which the interfacial layer of PS-co-mah would undergo chemical reactions with the aminated BTO and blend PS matrix with excellent physical compatibility, exhibit enhanced breakdown strength and declined dielectric loss compared with both pure PS and BTO/PS without interfacial modulation. Particularly, the BTO@PS-co-mah/PS composite with 5 wt% filler content indicates optimized performance with an E b of 507 MV m-1 and tan δ of 0.085%. It is deduced that the deep energy traps introduced by the PS-co-mah layer would weaken the local electric field and suppress the space charge transporting so as to optimize the performance of composites. Consequently, the interfacial-modified BTO@PS-co-mah/PS would present great potential for applications, such as film capacitors.

The prevalence of mental health disorders in people with HIV and the effects on the HIV care continuum.

OBJECTIVE: To describe the prevalence of diagnosed depression, anxiety, bipolar disorder, and schizophrenia in people with HIV (PWH) and the differences in HIV care continuum outcomes in those with and without mental health disorders (MHDs). DESIGN: Observational study of participants in the North American AIDS Cohort Collaboration on Research and Design. METHODS: PWH (≥18 years) contributed data on prevalent schizophrenia, anxiety, depressive, and bipolar disorders from 2008 to 2018 based on International Classification of Diseases code mapping. Mental health (MH) multimorbidity was defined as having two or more MHD. Log binomial models with generalized estimating equations estimated adjusted prevalence ratios (aPR) and 95% confidence intervals for retention in care (≥1 visit/year) and viral suppression (HIV RNA ≤200 copies/ml) by presence vs. absence of each MHD between 2016 and 2018. RESULTS: Among 122 896 PWH, 67 643 (55.1%) were diagnosed with one or more MHD: 39% with depressive disorders, 28% with anxiety disorders, 10% with bipolar disorder, and 5% with schizophrenia. The prevalence of depressive and anxiety disorders increased between 2008 and 2018, whereas bipolar disorder and schizophrenia remained stable. MH multimorbidity affected 24% of PWH. From 2016 to 2018 (N = 64 684), retention in care was marginally lower among PWH with depression or anxiety, however those with MH multimorbidity were more likely to be retained in care. PWH with bipolar disorder had marginally lower prevalence of viral suppression (aPR = 0.98 [0.98-0.99]) as did PWH with MH multimorbidity (aPR = 0.99 [0.99-1.00]) compared with PWH without MHD. CONCLUSION: The prevalence of MHD among PWH was high, including MH multimorbidity. Although retention and viral suppression were similar to people without MHD, viral suppression was lower in those with bipolar disorder and MH multimorbidity.

Accessibility and disability inclusion among top-funded U.S. Undergraduate Institutions.

BACKGROUND: There is limited data to assess, track, or quantify accessibility and disability inclusion across universities. OBJECTIVE: This cross-sectional study assessed disability inclusion and accessibility at the top 50 National Institutes of Health (NIH)-funded undergraduate programs in the United States. We hypothesized that there is no association between NIH funding and the University Disability Inclusion Score. METHODS: A novel tool, the University Disability Inclusion Score assessed disability inclusion and accessibility using 10 indicators spanning 4 categories: (1) accessibility of built and virtual environment, (2) public image of disability inclusion, (3) accommodations processes and procedures, and (4) grievance policy. Based upon the total points (out of a total score of 100), each university was assigned a letter grade (A-F). RESULTS: Of the top 50 NIH-funded institutions, 6% received an A grade on the Score, while 60% received D or F. The mean scores were 15.2 (SD = 5) for accessibility of built and virtual environment (20 points), 10 (SD = 3) for public image of disability inclusion (20 points), 30.6 (SD = 10) for accommodations processes and procedures (50 points), and 8.1 (SD = 3) for grievance policy (10 points). CONCLUSIONS: Our findings suggest room for improvement in disability inclusion and accessibility among top university recipients of NIH funding. To provide an equitable academic experience, universities must prioritize disability inclusion.

Intratumoral delivered novel circular mRNA encoding cytokines for immune modulation and cancer therapy.

The success of the two mRNA vaccines developed by Moderna and BioNTech during the COVID-19 pandemic increased research interest into the application of mRNA technologies. Compared with the canonical linear mRNA used in these vaccines, circular mRNA has been found to mediate more potent and durable protein expression and demands a simpler manufacturing procedure. However, the application of circular mRNA is still at the initiation stage, and proof of concept for its use as a future medicine or vaccine is required. In the current study, we established a novel type of circular mRNA, termed cmRNA, based on the echovirus 29-derived internal ribosome entry site element and newly designed homology arms and RNA spacers. Our results demonstrated that this type of circular mRNA could mediate strong and durable expression of various types of proteins, compared with typical linear mRNA. Moreover, for the first time, our study demonstrated that direct intratumoral administration of cmRNA encoding a mixture of cytokines achieved successful modulation of intratumoral and systematic anti-tumor immune responses and enhanced anti-programmed cell death protein 1 (PD-1) antibody-induced tumor repression in a syngeneic mouse model. This novel circular mRNA platform is thereby suitable for direct intratumoral administration for cancer therapy.

Physical Resilience Phenotype Trajectories in Incident Hemodialysis: Characterization and Mortality Risk Assessment.

Introduction: Although life-saving, the physiologic stress of hemodialysis initiation contributes to physical impairment in some patients. Mortality risk assessment following hemodialysis initiation is underdeveloped and does not account for change over time. Measures of physical resilience, the ability of a physiologic state to overcome physiologic stressors, may help identify patients at higher mortality risk and inform clinical management. Methods: We created 3 resilience categories (improving, stable, and declining) for trajectories of 4 phenotypes (physical function [PF], mental health [MH], vitality [VT], and general health [GH]) using SF-36 data collected the first year after hemodialysis initiation in the Choices for Healthy Outcomes in Caring for ESKD (CHOICE) study on 394 adults aged more than 55 years. Using mixed effects and Cox proportional hazard modeling, we assessed mortality following the first year on dialysis by resilience categories for each phenotype, adjusting for baseline phenotype and other confounders defined a priori over 4 years average follow-up. Results: Based on global Wald tests, statistically significant associations of PF (P = 0.03) and VT (P = 0.0004) resilience categories with mortality were found independent of covariates. Declining PF trajectory was associated with higher mortality risk (hazard ratio [HR] = 1.32; 95% confidence interval [CI], 1.05-1.66), whereas improving VT trajectory was associated with lower mortality risk (HR= 0.73; 95% CI, 0.53 to 1.00), each as compared to stable trajectory. Conclusion: Decreased resilience in PF and VT was independently associated with mortality. Phenotypic trajectories provide added value to baseline markers and patient characteristics when evaluating mortality. Hence, resilience measures hold promise for targeting population health interventions to the highest risk patients.

The development of the Supplemental Nutrition Assistance Program enrollment accessibility (SNAP-access) score.

BACKGROUND: The Supplemental Nutrition Assistance Program (SNAP) is a federal public benefit providing food assistance to millions of Americans. However, it is typically administered by states, creating potential variation in accessibility and transparency of information about enrollment for people with disabilities. OBJECTIVE: To develop and demonstrate the use of a method to assess the accessibility and transparency of information about the disability-inclusive process and practices of SNAP enrollment. METHODS: Cross-sectional data was collected from SNAP landing and enrollment webpages from all 50 U.S. states, the District of Columbia, and New York City from June-August 2021. Based on principles of universal design and accessibility, scores were determined for each SNAP program across three areas: flexibility in the enrollment process (6 points), efficiency of finding information about enrollment on SNAP websites (6 points), and the accessibility of SNAP webpages (6 points). Total scores were the sum of these sub-categories (18 points maximum). RESULTS: Of the 52 SNAP programs assessed, mean scores were 10.66 (SD = 2.51) for the total score, 2.67 (SD = 0.91) for flexibility in the enrollment process, 3.32 (SD = 1.19) for efficiency of finding information about enrollment on SNAP websites, and 4.67 (SD = 1.72) for the accessibility of SNAP webpages. No programs received the maximum flexibility score (6 points) on flexibility, 2 programs received the maximum on efficiency, and 31 programs the maximum on accessibility. CONCLUSIONS: We found differences in the accessibility, flexibility, and efficiency of SNAP program enrollment information available on SNAP websites and outline room for improvement across all three of these areas.

COVID-19 vaccine website accessibility dashboard.

BACKGROUND: The COVID-19 pandemic has exacerbated historical inequities for people with disabilities including barriers in accessing online information and healthcare appointment websites. These barriers were brought to the foreground during the vaccine rollout and registration process. OBJECTIVE: This cross-sectional study aimed to examine accessibility of U.S. state and territory COVID-19 information and registration centralized websites. METHODS: The Johns Hopkins Disability Health Research Center created a COVID-19 Vaccine Dashboard compiling COVID-19 information and vaccine registration web pages from 56 states and territories in the United States (U.S.) reviewed between March 30 through April 5, 2021 and analyzed accessibility using WAVE Web Accessibility Evaluation Tool (WAVE). WAVE identifies website accessibility barriers, including insufficient contrast, alternative text, unlabeled buttons, total number of errors, and error density. Web pages were ranked and grouped into three groups by number of errors, creating comparisons between states on accessibility barriers for people with disabilities. RESULTS: All 56 U.S states and territories had COVID-19 information web pages and 29 states had centralized state vaccine registration web pages. Total errors, error density, and alert data were utilized to generate accessibility scores for each web page, the median score was 259 (range = 14 to 536 and IQR = 237) for information pages, and 146 (range = 10 to 281 and IQR = 105) for registration pages. CONCLUSIONS: These results highlight barriers people with disabilities may encounter when accessing information and registering for the COVID-19 vaccine, which underscore inequities in the pandemic response for the disability community and elevate the need to prioritize accessibility of public health information.

Risk Factors for Nonresilient Outcomes in Older Adults After Total Knee Replacement.

BACKGROUND: Total knee replacement (TKR) is a common procedure in older adults. Physical resilience may be a useful construct to explain variable outcomes. We sought to define a simple measure of physical resilience and identify risk factors for nonresilient patient outcomes. METHODS: Secondary analysis of Function and Outcomes Research for Comparative Effectiveness in Total Joint Replacement (FORCE-TJR) cohort study, a prospective registry of total joint replacement. The analysis included 7 239 adults aged 60 or older who underwent TKR between 2011 and 2015. Measures included sociodemographic and health factors. Outcomes were categorized as physically resilient versus nonresilient based on the change from baseline to 1-year follow-up for 3 patient-reported outcomes: the physical component summary (PCS), bodily pain (BP), and vitality (VT) from the Short Form-36 subcomponent scores, at preop and 1-year postprocedure. Associations were expressed as relative risk (RR) of physically nonresilient outcomes using generalized linear regression models, with Poisson distribution and log link. RESULTS: Age, body mass index, and Charlson Comorbidity Index (CCI) were associated with increased risk of physically nonresilient outcomes across PCS, BP, and VT: age, per 5 years for PCS (RR = 1.18 [1.12-1.23]), BP (RR = 1.06 [1.01-1.11), and VT (RR = 1.09 [1.06-1.12]); body mass index, per 5 kg/m2, for PCS (RR = 1.13 [1.07-1.19]), BP (RR = 1.06 [1.00-1.11]), and VT (RR = 1.08 [1.04-1.11]); and CCI for PCS CCI = 1 (RR = 1.38 [1.20-1.59]), CCI = 2-5 (RR = 1.59 [1.35-1.88]), CCI ≥6 (RR = 1.55 [1.31-1.83]. Household income >$45 000 associated with lower risk for PCS (RR = 0.81 [0.70-0.93]), BP (RR = 0.80 [0.69-0.91]), and VT (RR = 0.86 [0.78-0.93]). CONCLUSIONS: We operationalized physical resilience and identified factors predicting resilience after TKR. This approach may aid clinical risk stratification, guide further investigation of causes, and ultimately aid patients through the design of interventions to enhance physical resilience.