APOE ε4 carrier status modifies plasma p-tau181 concentrations in cognitively healthy super-seniors.

INTRODUCTION: This study investigates the effect of apolipoprotein E (APOE) genotype on neurology plasma biomarkers in cognitively healthy Super-Seniors. METHODS: Three hundred seventy plasma specimens from Super-Senior participants ≥ 85 years old, who have never been diagnosed with dementia, cancer, diabetes, cardiovascular, or major pulmonary disease, were analyzed on the Quanterix Simoa HD-X analyzer using commercial Neurology 4-plex E and phosphorylated tau (p-tau)181 assays. RESULTS: Eighty (22%) participants were APOE ε4 carriers and 290 (73%) were non-carriers. No significant differences were found between APOE ε4 carriers and non-carriers regarding age, sex, or Mini-Mental State Examination scores. In APOE ε4 carriers, plasma amyloid beta 42/40 was lower and p-tau181 and glial fibrillary acidic protein were higher compared to non-APOE ε4 carriers. After adjusting for demographic variables, p-tau181 was the only biomarker to remain significantly associated with APOE ε4 carrier status. DISCUSSION: APOE ε4 genotype modifies plasma p-tau181 concentration in seniors resilient to age-related clinical disease, suggesting that some Super-Seniors may have Alzheimer's disease pathology without progressing to cognitive decline. HIGHLIGHTS: Healthy seniors enable identification of associations that may be masked by disease. Plasma phosphorylated tau (p-tau)181 concentrations associate with apolipoprotein E (APOE) ε4 carriership in healthy seniors. APOE should be accounted for when interpreting p-tau181, regardless of disease.

Cost Savings of Whole Blood Versus Component Therapy at a Community Level 1 Trauma Center.

BACKGROUND: Blood product component-only resuscitation (CORe) has been the standard of practice in both military and civilian trauma care with a 1:1:1 ratio used in attempt to recreate whole blood (WB) until recent data demonstrated WB to confer a survival advantage, leading to the emergence of WB as the contemporary resuscitation strategy of choice. Little is known about the cost and waste reduction associated with WB vs CORe. METHODS: This study is a retrospective single-center review of adult trauma patients admitted to a community trauma center who received WB or CORe as part of their massive transfusion protocol (MTP) resuscitation from 2017 to 2021. The WB group received a minimum of one unit WB while CORe received no WB. Univariate and multivariate analyses were completed. Statistical analysis was conducted using a 95% confidence level. Non-normally distributed, continuous data were analyzed using the Wilcoxon rank sum test. RESULTS: 576 patients were included (201 in WB and 375 in CORe). Whole blood conveyed a survival benefit vs CORe (OR 1.49 P < .05, 1.02-2.17). Whole blood use resulted in an overall reduction in products prepared (25.8%), volumes transfused (16.5%), product waste (38.7%), and MTP activation (56.3%). Cost savings were $849 923 annually and $3 399 693 over the study period. DISCUSSION: Despite increased patient volumes over the study period (43.7%), the utilization of WB as compared to CORe resulted in an overall $3.39 million cost savings while improving mortality. As such, we propose WB should be utilized in all resuscitation strategies for the exsanguinating trauma patient.

Cavity-modified molecular dipole switching dynamics.

Polaritonic states, which are formed by resonances between a molecular excitation and the photonic mode of a cavity, have a number of useful properties that offer new routes to control molecular photochemistry using electric fields. To provide a theoretical description of how polaritonic states affect the real-time electron dynamics in molecules, a new method is described where the effects of strong light-molecule coupling are implemented using real-time electronic structure theory. The coupling between the molecular electronic states and the cavity is described by the Pauli-Fierz Hamiltonian, and transitions between polaritonic states are induced via an external time-dependent electric field using time-dependent configuration interaction (TDCI) theory, producing quantum electrodynamics TDCI (QED-TDCI). This method is used to study laser-induced ultrafast charge transfer and dipole-switching dynamics of the LiCN molecule inside a cavity. The increase in cavity coupling strength is found to have a significant impact on the energies and transition dipole moments of the molecule-cavity system. The convergence of the polaritonic state energies as a function of the number of included electronic and photonic basis states is discussed.

Unraveling the electronic structure of LuH, LuN, and LuNH: building blocks of new materials.

Advances in superconductor technology have been pursued for decades, moving towards room temperature models, such as a postulated nitrogen-doped lutetium hydride network. While experimental observations have been contradictory, insight into the building blocks of potential new superconductor materials can be gained theoretically, unravelling the fascinating electronic structure of these compounds at a molecular level. Here, the fundamental building blocks of lutetium materials (LuH, LuN, and LuNH) have been examined. The structures, spectroscopic constants for the ground and excited states, and the potential energy curves have been obtained for these species using complete active self-consistent field (CASSCF) and multireference configuration interaction with Davidson's correction (MRCI+Q) methods. For LuNH, the energetic properties of its isomers are determined. The bond dissociation energies of the three building blocks are calculated with the state-of-the-art f-block ab initio correlation consistent composite approach (f-ccCA) and the high accuracy extrapolated ab initio thermochemistry (HEAT) scheme. As well, an analysis of different formation pathways of LuNH has been provided.

Potential energy surfaces and dynamic properties via ab initio composite and density functional approaches.

Vibrational spectroscopy enables critical insight into the structural and dynamic properties of molecules. Presently, the majority of theoretical approaches to spectroscopy employ wavefunction-based ab initio or density functional methods that rely on the harmonic approximation. This approximation breaks down for large molecules with strongly anharmonic bonds or for molecules with large internuclear separations. An alternative to these methods involves generating molecular anharmonic potential energy surfaces (potentials) and using them to extrapolate the vibrational frequencies. This study examines the efficacy of density functional theory (DFT) and the correlation consistent Composite Approach (ccCA) in generating anharmonic frequencies from potentials of small main group molecules. Vibrational self-consistent field Theory (VSCF) and post-VSCF methods were used to calculate the fundamental frequencies of these molecules from their potentials. Functional choice, basis set selection, and mode-coupling are also examined as factors in influencing accuracy. The absolute deviations for the calculated frequencies using potentials at the ccCA level of theory were lower than the potentials at the DFT level. With DFT resulting in bending modes that are better described than those of ccCA, a multilevel DFT:ccCA approach where DFT potentials are used for single vibrational mode potentials and ccCA is used for vibrational mode-mode couplings can be utilized for larger polyatomic systems. The frequencies obtained with this multilevel approach using VCIPSI-PT2 were closer to experimental frequencies than the scaled harmonic frequencies, indicating the success of utilizing post-VSCF methods to generate more accurate representations of computed infrared spectra.

Atypical beta-band effects in children with dyslexia in response to rhythmic audio-visual speech.

OBJECTIVE: Previous studies have reported atypical delta phase in children with dyslexia, and that delta phase modulates the amplitude of the beta-band response via delta-beta phase-amplitude coupling (PAC). Accordingly, the atypical delta-band effects in children with dyslexia may imply related atypical beta-band effects, particularly regarding delta-beta PAC. Our primary objective was to explore beta-band oscillations in children with and without dyslexia, to explore potentially atypical effects in the beta band in dyslexic children. METHODS: We collected EEG data during a rhythmic speech paradigm from 51 children (21 control; 30 dyslexia). We then assessed beta-band phase entrainment, beta-band angular velocity, beta-band power responses and delta-beta PAC. RESULTS: We found significant beta-band phase entrainment for control children but not for dyslexic children. Furthermore, children with dyslexia exhibited significantly faster beta-band angular velocity and significantly greater beta-band power. Delta-beta PAC was comparable in both groups. CONCLUSION: Atypical beta-band effects were observed in children with dyslexia. However, delta-beta PAC was comparable in both dyslexic and control children. SIGNIFICANCE: These findings offer further insights into the neurophysiological basis of atypical rhythmic speech processing by children with dyslexia, suggesting the involvement of a wide range of frequency bands.

Correlation consistent basis sets designed for density functional theory: Third-row atoms (Ga-Br).

The correlation consistent basis sets (cc-pVnZ with n = D, T, Q, 5) for the Ga-Br elements have been redesigned, tuning the sets for use for density functional approximations. Steps to redesign these basis sets for an improved correlation energy recovery and efficiency include truncation of higher angular momentum functions, recontraction of basis set coefficients, and reoptimization of basis set exponents. These redesigned basis sets are compared with conventional cc-pVnZ basis sets and other basis sets, which are, in principle, designed to achieve systematic improvement with respect to increasing basis set size. The convergence of atomic energies, bond lengths, bond dissociation energies, and enthalpies of formation to the Kohn-Sham limit is improved relative to other basis sets where convergence to the Kohn-Sham limit is typically not observed.

Physiological phenotypes have optimal values relevant to healthy aging: sweet spots deduced from the Canadian Longitudinal Study on Aging.

Previous observations on a group of exceptionally healthy "Super-Seniors" showed a lower variance of multiple physiological measures relevant for health than did a less healthy group of the same age. The finding was interpreted as the healthier individuals having physiological measurement values closer to an optimal level, or "sweet spot." Here, we tested the generalizability of the sweet-spot hypothesis in a larger community sample, comparing differences in the variance between healthier and less healthy groups. We apply this method to the Canadian Longitudinal Study on Aging (CLSA) comprehensive cohort of 30,097 participants aged 45 to 85 years with deep phenotype data. Data from both sexes and four age ranges were analyzed. Five instruments were used to represent different aspects of health, physical, and cognitive functioning. We tested 231 phenotypic measures for lower variance in the most healthy vs. least healthy quartile of each sex and age group, as classified by the five instruments. Segmented regression was used to determine sex-specific optimal values. One hundred forty-two physiological measures (61%) showed lower variance in the healthiest than in the least healthy group, in at least one sex and age group. The difference in variance was most significant for hemoglobin A1c and was also significant for many body composition measurements, but not for bone mineral density. Ninety-four phenotypes showed a nonmonotonic relationship with health, consistent with the idea of a sweet spot; for these, we determined optimal values and 95% confidence intervals that were generally narrower than the ranges of current clinical reference intervals. These findings for sweet spot discovery validate the proposed approach for identifying traits important for healthy aging.

Atypical speech production of multisyllabic words and phrases by children with developmental dyslexia.

The prevalent "core phonological deficit" model of dyslexia proposes that the reading and spelling difficulties characterizing affected children stem from prior developmental difficulties in processing speech sound structure, for example, perceiving and identifying syllable stress patterns, syllables, rhymes and phonemes. Yet spoken word production appears normal. This suggests an unexpected disconnect between speech input and speech output processes. Here we investigated the output side of this disconnect from a speech rhythm perspective by measuring the speech amplitude envelope (AE) of multisyllabic spoken phrases. The speech AE contains crucial information regarding stress patterns, speech rate, tonal contrasts and intonational information. We created a novel computerized speech copying task in which participants copied aloud familiar spoken targets like "Aladdin." Seventy-five children with and without dyslexia were tested, some of whom were also receiving an oral intervention designed to enhance multi-syllabic processing. Similarity of the child's productions to the target AE was computed using correlation and mutual information metrics. Similarity of pitch contour, another acoustic cue to speech rhythm, was used for control analyses. Children with dyslexia were significantly worse at producing the multi-syllabic targets as indexed by both similarity metrics for computing the AE. However, children with dyslexia were not different from control children in producing pitch contours. Accordingly, the spoken production of multisyllabic phrases by children with dyslexia is atypical regarding the AE. Children with dyslexia may not appear to listeners to exhibit speech production difficulties because their pitch contours are intact. RESEARCH HIGHLIGHTS: Speech production of syllable stress patterns is atypical in children with dyslexia. Children with dyslexia are significantly worse at producing the amplitude envelope of multi-syllabic targets compared to both age-matched and reading-level-matched control children. No group differences were found for pitch contour production between children with dyslexia and age-matched control children. It may be difficult to detect speech output problems in dyslexia as pitch contours are relatively accurate.

Binding of Per- and Polyfluoroalkyl Substances (PFAS) to the PPARγ/RXRα-DNA Complex.

Nuclear receptors are the fundamental building blocks of gene expression regulation and the focus of many drug targets. While binding to DNA, nuclear receptors act as transcription factors, governing a multitude of functions in the human body. Peroxisome proliferator-activator receptor γ (PPARγ) and the retinoid X receptor α (RXRα) form heterodimers with unique properties and have a primordial role in insulin sensitization. This PPARγ/RXRα heterodimer has been shown to be impacted by per- and polyfluoroalkyl substances (PFAS) and linked to a variety of significant health conditions in humans. Herein, a selection of the most common PFAS (legacy and emerging) was studied utilizing molecular dynamics simulations for PPARγ/RXRα. The local and global structural effects of PFAS binding on the known ligand binding pockets of PPARγ and RXRα as well as the DNA binding domain (DBD) of RXRα were inspected. The binding free energies were predicted computationally and were compared between the different binding pockets. In addition, two electronic structure approaches were utilized to model the interaction of PFAS within the DNA binding domain, density functional theory (DFT) and domain-based pair natural orbital coupled cluster with perturbative triples (DLPNO-CCSD(T)) approaches, with implicit solvation. Residue decomposition and hydrogen-bonding analysis were also performed, detailing the role of prominent residues in molecular recognition. The role of l-carnitine is explored as a potential in vivo remediation strategy for PFAS interaction with the PPARγ/RXRα heterodimer. In this work, it was found that PFAS can bind and act as agonists for all of the investigated pockets. For the first time in the literature, PFAS are postulated to bind to the DNA binding domain in a nonspecific manner. In addition, for the PPARγ ligand binding domain, l-carnitine shows promise in replacing smaller PFAS from the pocket.

Health Profession Students' Interprofessional Socialization and Values Toward a College-Based Virtual Interprofessional Education Activity.

PURPOSE: The inclusion of interprofessional education (IPE) is essential for the health professions curricula and establishes the expectation of collaborative patient-centered care. The COVID-19 pandemic has required educators to develop innovative methods for IPE student engagement. The purpose of this study was to evaluate a college-based virtual IPE activity for first-year health profession students and measure their interprofessional socialization and values (ISVS) toward IPE teams. The validated interprofessional socialization and valuing scales (ISVS-9A/9B) were used. METHODS: A one-group pre-post-test design examined health profession students' ISVS from seven health programs before and after a virtual IPE activity. The IPE activity was a case-study grounded in the Interprofessional Education Collaborative (IPEC) core competencies that addressed each of the student learners' professional roles. RESULTS: A total of 244 students and 122 students completed the ISVS-9A/9B, respectively. A significant increase in the average total ISVS-9A/9B scores was observed among all student learners for 85 matched pairs (5.27 ± 1.11 vs 5.56 ± 1.02, p=0.01). Participating students generally found the activity valuable to their learning. CONCLUSIONS: The virtual composition of the IPE activity reduced logistical barriers and allowed for collaboration and awareness among students. Virtual IPE activities may be the cornerstone for interdisciplinary student engagement.

Tailoring light-induced charge transfer and intersystem crossing in FeCO using time-dependent spin-orbit configuration interaction.

Real-time (RT) electronic structure methods provide a natural framework for describing light-matter interactions in arbitrary time-dependent electromagnetic fields (EMF). Optically induced excited state transitions are of particular interest, which require tuned EMF to drive population transfer to and from the specific state(s) of interest. Intersystem crossing, or spin-flip, may be driven through shaped EMF or laser pulses. These transitions can result in long-lived "spin-trapped" excited states, which are especially useful for materials requiring charge separation or protracted excited state lifetimes. Time-dependent configuration interaction (TDCI) is unique among RT methods in that it may be implemented in a basis of eigenstates, allowing for rapid propagation of the time-dependent Schrödinger equation. The recent spin-orbit TDCI (TD-SOCI) enables a real-time description of spin-flip dynamics in an arbitrary EMF and, therefore, provides an ideal framework for rational pulse design. The present study explores the mechanism of multiple spin-flip pathways for a model transition metal complex, FeCO, using shaped pulses designed to drive controlled intersystem crossing and charge transfer. These results show that extremely tunable excited state dynamics can be achieved by considering the dipole transition matrix elements between the states of interest.

Concurrent RB1 loss and BRCA-deficiency predicts enhanced immunological response and long-term survival in tubo-ovarian high-grade serous carcinoma.

Background: Somatic loss of the tumour suppressor RB1 is a common event in tubo-ovarian high-grade serous carcinoma (HGSC), which frequently co-occurs with alterations in homologous recombination DNA repair genes including BRCA1 and BRCA2 (BRCA). We examined whether tumour expression of RB1 was associated with survival across ovarian cancer histotypes (HGSC, endometrioid (ENOC), clear cell (CCOC), mucinous (MOC), low-grade serous carcinoma (LGSC)), and how co-occurrence of germline BRCA pathogenic variants and RB1 loss influences long-term survival in a large series of HGSC. Patients and methods: RB1 protein expression patterns were classified by immunohistochemistry in epithelial ovarian carcinomas of 7436 patients from 20 studies participating in the Ovarian Tumor Tissue Analysis consortium and assessed for associations with overall survival (OS), accounting for patient age at diagnosis and FIGO stage. We examined RB1 expression and germline BRCA status in a subset of 1134 HGSC, and related genotype to survival, tumour infiltrating CD8+ lymphocyte counts and transcriptomic subtypes. Using CRISPR-Cas9, we deleted RB1 in HGSC cell lines with and without BRCA1 mutations to model co-loss with treatment response. We also performed genomic analyses on 126 primary HGSC to explore the molecular characteristics of concurrent homologous recombination deficiency and RB1 loss. Results: RB1 protein loss was most frequent in HGSC (16.4%) and was highly correlated with RB1 mRNA expression. RB1 loss was associated with longer OS in HGSC (hazard ratio [HR] 0.74, 95% confidence interval [CI] 0.66-0.83, P = 6.8 ×10-7), but with poorer prognosis in ENOC (HR 2.17, 95% CI 1.17-4.03, P = 0.0140). Germline BRCA mutations and RB1 loss co-occurred in HGSC (P < 0.0001). Patients with both RB1 loss and germline BRCA mutations had a superior OS (HR 0.38, 95% CI 0.25-0.58, P = 5.2 ×10-6) compared to patients with either alteration alone, and their median OS was three times longer than non-carriers whose tumours retained RB1 expression (9.3 years vs. 3.1 years). Enhanced sensitivity to cisplatin (P < 0.01) and paclitaxel (P < 0.05) was seen in BRCA1 mutated cell lines with RB1 knockout. Among 126 patients with whole-genome and transcriptome sequence data, combined RB1 loss and genomic evidence of homologous recombination deficiency was correlated with transcriptional markers of enhanced interferon response, cell cycle deregulation, and reduced epithelial-mesenchymal transition in primary HGSC. CD8+ lymphocytes were most prevalent in BRCA-deficient HGSC with co-loss of RB1. Conclusions: Co-occurrence of RB1 loss and BRCA mutation was associated with exceptionally long survival in patients with HGSC, potentially due to better treatment response and immune stimulation.

Neural responses to natural and enhanced speech edges in children with and without dyslexia.

Sensory-neural studies indicate that children with developmental dyslexia show impairments in processing acoustic speech envelope information. Prior studies suggest that this arises in part from reduced sensory sensitivity to amplitude rise times (ARTs or speech "edges") in the envelope, accompanied by less accurate neural encoding of low-frequency envelope information. Accordingly, enhancing these characteristics of the speech envelope may enhance neural speech processing in children with dyslexia. Here we applied an envelope modulation enhancement (EME) algorithm to a 10-min story read in child-directed speech (CDS), enhancing ARTs and also enhancing low-frequency envelope information. We compared neural speech processing (as measured using MEG) for the EME story with the same story read in natural CDS for 9-year-old children with and without dyslexia. The EME story affected neural processing in the power domain for children with dyslexia, particularly in the delta band (0.5-4 Hz) in the superior temporal gyrus. This may suggest that prolonged experience with EME speech could ameliorate some of the impairments shown in natural speech processing by children with dyslexia.

The Effectiveness of a Mobile Health Clinic Delivering Mandatory and Elective Middle School Immunizations: A Descriptive Analysis.

INTRODUCTION: Mobile health clinics serve a unique role in which they can offer affordable and adaptable care to the population they serve. The Edward Via College of Osteopathic Medicine (VCOM) mobile clinics began in 2020 as a partnership with the South Carolina Department of Health and Environmental Control (SCDHEC) to address the low vaccination rates that resulted from the COVID-19 pandemic. METHODS:  This study is a descriptive analysis that examines the number of vaccinations of tetanus, diphtheria, and pertussis (Tdap) and human papillomavirus (HPV) at different locations of administration including pediatrician offices, the novel VCOM mobile vaccination clinic, and the Spartanburg Health Department. The variables of interest and the study endpoints focused on Tdap and HPV vaccinations among students aged 11-12 years old in Spartanburg County according to the type of healthcare delivery location. RESULTS: From April to May of 2021, the VCOM mobile clinic was able to administer 279 Tdap vaccines and 189 HPV vaccines to students at local middle schools, which surpasses the number of vaccines administered at other sites from August 2020 to May 2021 when compared individually for both Tdap and HPV vaccinations. CONCLUSIONS: By assessing the total volume of vaccines administered by each group, the VCOM mobile clinic was established as an effective method of delivery and played a crucial role in the vaccination efforts of the Spartanburg community. Mobile medical units should be considered for similar efforts in providing care to resource-limited communities and those with limited access to care.

A genome-wide gene-environment interaction study of breast cancer risk for women of European ancestry.

BACKGROUND: Genome-wide studies of gene-environment interactions (G×E) may identify variants associated with disease risk in conjunction with lifestyle/environmental exposures. We conducted a genome-wide G×E analysis of ~ 7.6 million common variants and seven lifestyle/environmental risk factors for breast cancer risk overall and for estrogen receptor positive (ER +) breast cancer. METHODS: Analyses were conducted using 72,285 breast cancer cases and 80,354 controls of European ancestry from the Breast Cancer Association Consortium. Gene-environment interactions were evaluated using standard unconditional logistic regression models and likelihood ratio tests for breast cancer risk overall and for ER + breast cancer. Bayesian False Discovery Probability was employed to assess the noteworthiness of each SNP-risk factor pairs. RESULTS: Assuming a 1 × 10-5 prior probability of a true association for each SNP-risk factor pairs and a Bayesian False Discovery Probability < 15%, we identified two independent SNP-risk factor pairs: rs80018847(9p13)-LINGO2 and adult height in association with overall breast cancer risk (ORint = 0.94, 95% CI 0.92-0.96), and rs4770552(13q12)-SPATA13 and age at menarche for ER + breast cancer risk (ORint = 0.91, 95% CI 0.88-0.94). CONCLUSIONS: Overall, the contribution of G×E interactions to the heritability of breast cancer is very small. At the population level, multiplicative G×E interactions do not make an important contribution to risk prediction in breast cancer.

Equal but Separate: The Slow Assimilation of Osteopathic Surgery Residents Two Years After the Unified Match.

OBJECTIVES: The purpose of this study was to monitor the integration of general surgery residency programs before and after the 2020 unified match. We hypothesized that integration of osteopathic (DO) surgery residents would increase. DESIGN: We performed a retrospective cohort study of surgery residency programs between 2019 and 2021 utilizing data provided by the Association of American Medical Colleges. Program composition (2021) and changes in composition (2019-2021) were compared by program type. Multivariable logistic regression models assessed variables associated with DO presence (2021) and integration (2019-2021). SETTING: General surgery residency programs across the United States. PARTICIPANTS: Civilian surgery residencies that completed the 2019-2021 program survey. RESULTS: Out of 320 programs, DO residents were integrated at 69% (221/320), including 52% (63/122) university programs, 78% (101/129) university-affiliated programs and 83% (57/69) community programs (p < 0.01). Overall, 23 (8%) programs integrated DO residents from 2019 to 2021, and 9 (21%) ex-American Osteopathic Association programs integrated MD residents (both p < 0.01). The median number of DO residents was 1 (interquartile range, IQR 0-2) at university programs, 2 (IQR 1-7) at university-affiliated programs, and 5 (IQR 2-12) at community programs (p < 0.01). The median number of DO residents at all programs increased from 1 (IQR 0-5) to 2 (IQR 0-6) since 2019 (p < 0.01). Community (OR 2.6, p = 0.04), university-affiliated (OR 2.3, p = 0.02), and programs with DOs in 2019 (OR 19.0, p < 0.01) were associated with increased odds of DOs present in 2021, while DO faculty (OR 2.6, p = 0.02) was the only factor independently associated with integrating DOs after 2019. CONCLUSIONS: While some programs have integrated DO residents, progress is slow, median numbers of DO residents remain low, and familiarity with DOs is most associated with integration. We explore barriers to integration, and advance recommendations to eliminate potential disparities.

A RE-AIM Analysis of a Mental Health App for Undergraduate and Medical Students during the COVID-19 Pandemic: A Retrospective Cross-Sectional Study.

OBJECTIVE: The purpose of this study was to use the RE-AIM framework to evaluate the implementation of a mental health app designed for undergraduate and medical students during the COVID-19 pandemic. PARTICIPANTS: Medical (n = 270) and undergraduate students (n = 1386) from five universities in the Appalachian region in the United States participated in this study. METHODS: Universities from the United States were recruited to deploy the Sharpen app for medical and undergraduate students. The Sharpen app provided psychoeducational modules in mental health literacy, social-emotional learning, mindfulness-based stress reduction, and suicide prevention to promote protective factors for students. The utilization of the Sharpen app was analyzed using the RE-AIM framework using a retrospective, cross-sectional design. RESULTS: Reach: A total of 12.72% of medical students and 6.00% of undergraduate students participated in the study. EFFICACY: Medical students viewed significantly more pages, had a significantly higher unique page view average, and a statistically significant exit percentage when compared to undergraduate students. Adoption: A total of 100% of the universities that were recruited participated in the study. IMPLEMENTATION: Five out of six implementation criteria were included, indicating high implementation. Maintenance: All of the universities continued using the Sharpen app following the end of data collection, resulting in a 100% maintenance rate. CONCLUSIONS: The RE-AIM framework indicated usability and maintenance by medical and undergraduate students. Future research needs to implement a more rigorous design to determine the impact of the Sharpen app on mental health outcomes in medical and undergraduate students.