Earth at risk: An urgent call to end the age of destruction and forge a just and sustainable future.

Human development has ushered in an era of converging crises: climate change, ecological destruction, disease, pollution, and socioeconomic inequality. This review synthesizes the breadth of these interwoven emergencies and underscores the urgent need for comprehensive, integrated action. Propelled by imperialism, extractive capitalism, and a surging population, we are speeding past Earth's material limits, destroying critical ecosystems, and triggering irreversible changes in biophysical systems that underpin the Holocene climatic stability which fostered human civilization. The consequences of these actions are disproportionately borne by vulnerable populations, further entrenching global inequities. Marine and terrestrial biomes face critical tipping points, while escalating challenges to food and water access foreshadow a bleak outlook for global security. Against this backdrop of Earth at risk, we call for a global response centered on urgent decarbonization, fostering reciprocity with nature, and implementing regenerative practices in natural resource management. We call for the elimination of detrimental subsidies, promotion of equitable human development, and transformative financial support for lower income nations. A critical paradigm shift must occur that replaces exploitative, wealth-oriented capitalism with an economic model that prioritizes sustainability, resilience, and justice. We advocate a global cultural shift that elevates kinship with nature and communal well-being, underpinned by the recognition of Earth's finite resources and the interconnectedness of its inhabitants. The imperative is clear: to navigate away from this precipice, we must collectively harness political will, economic resources, and societal values to steer toward a future where human progress does not come at the cost of ecological integrity and social equity.

Role of atmospheric resonance and land-atmosphere feedbacks as a precursor to the June 2021 Pacific Northwest Heat Dome event.

We demonstrate an indirect, rather than direct, role of quasi-resonant amplification of planetary waves in a summer weather extreme. We find that there was an interplay between a persistent, amplified large-scale atmospheric circulation state and soil moisture feedbacks as a precursor for the June 2021 Pacific Northwest "Heat Dome" event. An extended resonant planetary wave configuration prior to the event created an antecedent soil moisture deficit that amplified lower atmospheric warming through strong nonlinear soil moisture feedbacks, favoring this unprecedented heat event.

Postoperative shunt failure following hemispherectomy in pediatric patients with pre-existing hydrocephalus.

OBJECTIVE: The risk of hydrocephalus following hemispherectomy for drug resistant epilepsy (DRE) remains high. Patients with pre-existing hydrocephalus pose a postoperative challenge, as maintaining existing shunt patency is necessary but lacks a clearly defined strategy. This study examines the incidence and predictors of shunt failure in pediatric hemispherectomy patients with pre-existing ventricular shunts. METHODS: We performed a retrospective chart review at our center to identify pediatric patients diagnosed with DRE who were treated with ventricular shunt prior to their first hemispherectomy surgery. Demographic and perioperative data were obtained including shunt history, hydrocephalus etiology, epilepsy duration, surgical technique, and postoperative outcomes. Univariate analysis was performed using Fisher's exact test and Pearson correlation, with Bonferroni correction to a = 0.00625 and a = 0.01, respectively. RESULTS: Five of nineteen (26.3%) patients identified with ventriculoperitoneal shunting prior to hemispherectomy experienced postoperative shunt malfunction. All 5 of these patients underwent at least 1 shunt revision prior to hemispherectomy, with a significant association between pre- and post-hemispherectomy shunt revisions. There was no significant association between post-hemispherectomy shunt failure and valve type, intraoperative shunt alteration, postoperative external ventricular drain placement, hemispherectomy revision, lateralization of shunt relative to resection, postoperative complications, or postoperative aseptic meningitis. There was no significant correlation between number of post-hemispherectomy shunt revisions and age at shunt placement, age at hemispherectomy, epilepsy duration, or shunt duration prior to hemispherectomy. CONCLUSIONS: Earlier shunt revision surgery may portend a subsequent need for shunt revision following hemispherectomy. These findings may guide neurosurgeons in counseling patients with pre-existing ventricular shunts prior to hemispherectomy surgery.

Predictive factors of hydrocephalus development in pediatric patients undergoing hemispherectomy for intractable epilepsy.

OBJECTIVE: Hemispherectomy surgery is an effective procedure for pediatric patients with intractable hemispheric epilepsy. Hydrocephalus is a well-documented complication of hemispherectomy contributing substantially to patient morbidity. Despite some clinical and operative factors demonstrating an association with hydrocephalus development, the true mechanism of disease is incompletely understood. The aim of this study was to investigate a range of clinical and surgical factors that may contribute to hydrocephalus to enhance understanding of the development of this complication and to aid the clinician in optimizing peri- and postoperative surgical management. METHODS: A retrospective chart review was conducted on all pediatric patients younger than 21 years who underwent hemispherectomy surgery at the Cleveland Clinic between 2002 and 2016. Data collected for each patient included general demographic information, neurological and surgical history, surgical technique, pathological analysis, presence and duration of perioperative CSF diversion, CSF laboratory values obtained while an external ventricular drain (EVD) was in place, length of hospital stay, postoperative aseptic meningitis, and in-hospital surgical complications (including perioperative stroke, hematoma formation, wound breakdown, and/or infection). Outcomes data included hemispherectomy revision and Engel grade at last follow-up (based on the Engel Epilepsy Surgery Outcome Scale). RESULTS: Data were collected for 204 pediatric patients who underwent hemispherectomy at the authors' institution. Twenty-eight patients (14%) developed hydrocephalus requiring CSF diversion. Of these 28 patients, 13 patients (46%) presented with hydrocephalus during the postoperative period (within 90 days), while the remaining 15 patients (54%) presented later (beyond 90 days after surgery). Multivariate analysis revealed postoperative aseptic meningitis (OR 7.0, p = 0.001), anatomical hemispherectomy surgical technique (OR 16.3 for functional/disconnective hemispherectomy and OR 7.6 for modified anatomical, p = 0.004), male sex (OR 4.2, p = 0.012), and surgical complications (OR 3.8, p = 0.031) were associated with an increased risk of hydrocephalus development, while seizure freedom (OR 0.3, p = 0.038) was associated with a decreased risk of hydrocephalus. CONCLUSIONS: Hydrocephalus remains a prominent complication following hemispherectomy, presenting both in the postoperative period and months to years after surgery. Aseptic meningitis, anatomical hemispherectomy surgical technique, male sex, and surgical complications show an association with an increased rate of hydrocephalus development while seizure freedom postsurgery is associated with a decreased risk of subsequent hydrocephalus. These findings speak to the multifactorial nature of hydrocephalus development and should be considered in the management of pediatric patients undergoing hemispherectomy for medically intractable epilepsy.

Social Support for Rural Gender Diverse Youth Compared to Cisgender Peers.

PURPOSE: Gender diverse youth (GDY) experience higher rates of mental health concerns than their cisgender peers, but these can be ameliorated by feeling support from family, school, and community. Little is known about how youth perceptions of support vary by gender identity, especially for younger adolescents and those living in rural areas. METHODS: Youth ages 12-19 years completed anonymous surveys including measures of perceived support and a two-step gender identity question. GDY (n = 206) were further categorized into binary and nonbinary gender identities. An additional 500 randomly selected cisgender youth were included for comparison. Multivariate analyses of variance with Tukey post hoc tests were employed to test GDY group differences while accounting for the interaction between scaled measures. RESULTS: Cisgender youth had the highest perceived support across all support measures while youth who shared both binary and nonbinary aspects of their gender identity had the lowest rates of perceived support. The F tests for between-subject effects were statistically significant (p <.001) for all six support measures, and multivariate group testing was statistically significant with Wilks' λ 6.38(18,1621.17) = 0.82; p <.001. DISCUSSION: Despite research demonstrating a strong association between perceived support and improved mental health outcomes, GDY in our sample had lower rates of perceived support at the family, school, and community levels. GDY with both binary and nonbinary gender identities had the lowest levels of perceived support. Further research is needed to see if this finding is consistent in other populations and to develop targeted interventions to improve perceived support for this population.

The impact of adjuvant EGFR-TKIs and 14-gene molecular assay on stage I non-small cell lung cancer with sensitive EGFR mutations.

Background: Currently, the role of EGFR-TKIs as adjuvant therapy for stage I, especially IA NSCLC, after surgical resection remains unclear. We aimed to compare the effect of adjuvant EGFR-TKIs with observation in such patients by incorporating an established 14-gene molecular assay for risk stratification. Methods: This retrospective cohort study was conducted at the First Affiliated Hospital of Guangzhou Medical University (Study ID: ChNCRCRD-2022-GZ01). From March 2013 to February 2019, completely resected stage I NSCLC (8th TNM staging) patients with sensitive EGFR mutation were included. Patients with eligible samples for molecular risk stratification were subjected to the 14-gene prognostic assay. Inverse probability of treatment weighting (IPTW) was employed to minimize imbalances in baseline characteristics. Findings: A total of 227 stage I NSCLC patients were enrolled, with 55 in EGFR-TKI group and 172 in the observation group. The median duration of follow-up was 78.4 months. After IPTW, the 5-year DFS (HR = 0.30, 95% CI, 0.14-0.67; P = 0.003) and OS (HR = 0.26, 95% CI, 0.07-0.96; P = 0.044) of the EGFR-TKI group were significantly better than the observation group. For subgroup analyses, adjuvant EGFR-TKIs were associated with favorable 5-year DFS rates in both IA (100.0% vs. 84.5%; P = 0.007), and IB group (98.8% vs. 75.3%; P = 0.008). The 14-gene assay was performed in 180 patients. Among intermediate-high-risk patients, EGFR-TKIs were associated with a significant improvement in 5-year DFS rates compared to observation (96.0% vs. 70.5%; P = 0.012), while no difference was found in low-risk patients (100.0% vs. 94.9%; P = 0.360). Interpretation: Our study suggested that adjuvant EGFR-TKI might improve DFS and OS of stage IA and IB EGFR-mutated NSCLC, and the 14-gene molecular assay could help patients that would benefit the most from treatment. Funding: This work was supported by China National Science Foundation (82022048, 82373121).

Climate change will accelerate the high-end risk of compound drought and heatwave events.

Compound drought and heatwave (CDHW) events have garnered increased attention due to their significant impacts on agriculture, energy, water resources, and ecosystems. We quantify the projected future shifts in CDHW characteristics (such as frequency, duration, and severity) due to continued anthropogenic warming relative to the baseline recent observed period (1982 to 2019). We combine weekly drought and heatwave information for 26 climate divisions across the globe, employing historical and projected model output from eight Coupled Model Intercomparison Project 6 GCMs and three Shared Socioeconomic Pathways. Statistically significant trends are revealed in the CDHW characteristics for both recent observed and model simulated future period (2020 to 2099). East Africa, North Australia, East North America, Central Asia, Central Europe, and Southeastern South America show the greatest increase in frequency through the late 21st century. The Southern Hemisphere displays a greater projected increase in CDHW occurrence, while the Northern Hemisphere displays a greater increase in CDHW severity. Regional warmings play a significant role in CDHW changes in most regions. These findings have implications for minimizing the impacts of extreme events and developing adaptation and mitigation policies to cope with increased risk on water, energy, and food sectors in critical geographical regions.

Possible role of caffeine in nicotine use onset among early adolescents: Evidence from the Young Mountaineer Health Study Cohort.

BACKGROUND: Preventing nicotine use onset among children and youth is an important public health goal. One possible contributor that has received little empirical investigation is caffeine use. The goal of this study was to examine the possible contribution of caffeine to nicotine onset during early adolescence. METHODS: We used data from the Young Mountaineer Health Study Cohort. Survey data were collected from 1,349 (response rate: 80.7%) 6th grade students (mean age at baseline 11.5 years) in 20 middle schools in West Virginia during the fall of 2020 and spring of 2021. We limited our analyses to students reporting never having used any form of nicotine at baseline. Logistic regression was employed in analyses. RESULTS: Approximately 8% of participants reported having used nicotine at least once between baseline and the follow-up, and 4.7% reported solely using electronic nicotine delivery systems (ENDS) and no other forms of nicotine. In multivariable analyses, we controlled for many environmental, social, and behavioral variables known to influence nicotine use such as alcohol use, peer substance use, and perceived access to nicotine. We formulated our main independent variable, caffeine consumption, as continuous deciles. Any nicotine use, as well as ENDS use only at follow-up, were modeled as dependent variables. Caffeine was significantly associated with nicotine use in both models with ORs of 1.15 (1.04-1.27) and 1.13 (1.00-1.28). CONCLUSIONS: Caffeine consumption among 6th grade non-nicotine users was associated with nicotine use at approximately 6-months follow-up.

Preliminary impact of the adoption of the Icelandic Prevention Model in Tarragona City, 2015-2019: A repeated cross-sectional study.

Background: There is a great need for effective primary prevention intervention strategies to reduce and delay onset of adolescent substance use. The Icelandic Prevention Model (IPM) showed great success in Iceland over the past twenty plus years, however, evidence for the transferability of model is still somewhat limited. Using data collected in Tarragona during regional efforts to begin adoption of the IPM in Catalonia, this study tested the transferability and stability of the core risk and protective factor assumptions of the IPM overtime and examined trends of lifetime smoking, e-cigarette-use, alcohol-use, intoxication, and cannabis-use within the same time period. Methods: This study includes responses from 15- to 16-years-olds from two region-wide samples taken in 2015 and 2019 in Tarragona (N = 2,867). Survey questions assessed frequency of lifetime: smoking, e-cigarette-use, alcohol-use, intoxication, and cannabis-use, and the core model assumptions. Demographic data were also collected. Logistic regression models of main effects with and without time interaction were used to test assumptions and their stability across time. Chi-square tests and Wilcoxon-Mann-Whitney U tests were used to compare prevalence of substance use and mean scores of primary prevention variables respectively. Results: Lifetime: smoking (-7%, p < 0.001) and cannabis-use (-4%, p < 0.001) decreased, and e-cigarette-use increased (+33%, p < 0.001) in Tarragona. Lifetime intoxication (-7%, p < 0.001) decreased in a single zone exclusively. Most core model assumptions held in their hypothesised direction across time. The strongest positive association was observed between time spent with parents during weekends and reduced odds of lifetime smoking (OR: 0.62, 95%CI: 0.57-0.67) and the strongest negative association was observed between being outside after midnight and increased odds of lifetime intoxication (OR: 1.41, 95%CI: 1.32-1.51). Mean scores of primary prevention variables also changed disproportionately in Tarragona. Conclusion: This study confirms that the core IPM assumptions are similar in Tarragona as in Iceland and other contexts previously examined. They also indicate that prevalence of lifetime smoking, intoxication, and cannabis-use decreased disproportionately in Tarragona between 2015 and 2019 during the first phase of regional adoption of the model. Thus, targeting model assumptions represents a viable primary prevention strategy for communities that hope to reduce smoking, alcohol-use, intoxication, and cannabis-use among adolescents.

Management of Patients with Spine Tumors Strengthened by a Dedicated Multidisciplinary Spine Tumor Board: A 15-Year Single-Institutional Experience.

BACKGROUND: Patients with spine tumors frequently require timely, multistep, and multidisciplinary care. A Spine Tumor Board (STB) provides a consistent forum wherein diverse specialists can interact, facilitating complex coordinated care for these patients. This study aims to present a single, large academic center's STB experience specifically reviewing case diversity, recommendations, and quantifying growth over time. METHODS: All patient cases discussed at STB from May 2006 (STB inception) to May 2021 were evaluated. Collected data submitted by presenting physicians and formal documentation completed during the STB are summarized. RESULTS: A total of 4549 cases were reviewed by STB over the study period, representing 2618 unique patients. Over the course of the study, a 266% increase in number of cases presented per week was observed (4.1 to 15.0). Cases were presented by surgeons (74%), radiation oncologists (18%), neurologists (2%), and other specialists (6%). The most common pathologic diagnoses discussed were spinal metastases (n = 1832; 40%), intradural extramedullary tumors (n = 798; 18%), and primary glial tumors (n = 567; 12%). Treatment recommendations included surgery, radiation therapy, or systemic therapy for 1743 cases (38%), continued routine follow-up/expectant management for 1592 cases (35%), supplementary imaging to better clarify the diagnosis for 549 cases (12%), and variable tailored recommendations for the remainder of cases (18%). CONCLUSIONS: Care of patients with spine tumors is complex. We believe that the formation of a stand-alone STB is instrumental to accessing multidisciplinary input, enhancing confidence in management decisions for both patients and providers, assisting with care orchestration, and improving quality of care for patients with spine tumors.

Characterization of root-associated fungi and reduced plant growth in soils from a New Mexico uranium mine.

Characterizing the diverse, root-associated fungi in mine wastes can accelerate the development of bioremediation strategies to stabilize heavy metals. Ascomycota fungi are well known for their mutualistic associations with plant roots and, separately, for roles in the accumulation of toxic compounds from the environment, such as heavy metals. We sampled soils and cultured root-associated fungi from blue grama grass (Bouteloua gracilis) collected from lands with a history of uranium (U) mining and contrasted against communities in nearby, off-mine sites. Plant root-associated fungal communities from mine sites were lower in taxonomic richness and diversity than root fungi from paired, off-mine sites. We assessed potential functional consequences of unique mine-associated soil microbial communities using plant bioassays, which revealed that plants grown in mine soils in the greenhouse had significantly lower germination, survival, and less total biomass than plants grown in off-mine soils but did not alter allocation patterns to roots versus shoots. We identified candidate culturable root-associated Ascomycota taxa for bioremediation and increased understanding of the biological impacts of heavy metals on microbial communities and plant growth.

Social Support and Perceptions of COVID-19-related Emotional Impact on Mental Health Among Early Adolescents in Appalachia.

BACKGROUND: Young people who experience higher levels of social support from their schools and families have been shown to be less likely to develop symptoms of negative mental health outcomes such as depression and anxiety.1-4 This raises questions concerning how young people's stress and psychological changes due to the COVID-19 pandemic as well as social support during this time have affected their overall mental health. The aim of this study was to assess the association between sources of parental- and school-level social support and youth perceptions of COVID-19-related emotional impact on mental health among early adolescent girls and boys in Appalachia. METHODS: Using linear regression, we analyzed the first and third wave of survey data from the larger parent study (Young Mountaineer Health Study) cohort, collected in 20 middle schools throughout West Virginia in the fall of 2020 and fall of 2021 (N = 1349, mean age: 11.5, response rate: 80.7%). RESULTS: Approximately half of participants reported knowing someone that had been sick with COVID-19. Those experiencing higher levels of perceived COVID-19-related emotional impact reported greater levels of depression, anxiety, and anger. Both parental and school-level social support were associated with better mental health outcomes. CONCLUSIONS: Early adolescent perceptions of COVID-19-related emotional impact were associated with depression, anxiety, and anger and moderated by social support at home and in school among 11-12-year-old youth in Appalachia.

Another Year of Record Heat for the Oceans.

Changes in ocean heat content (OHC), salinity, and stratification provide critical indicators for changes in Earth's energy and water cycles. These cycles have been profoundly altered due to the emission of greenhouse gasses and other anthropogenic substances by human activities, driving pervasive changes in Earth's climate system. In 2022, the world's oceans, as given by OHC, were again the hottest in the historical record and exceeded the previous 2021 record maximum. According to IAP/CAS data, the 0-2000 m OHC in 2022 exceeded that of 2021 by 10.9 ± 8.3 ZJ (1 Zetta Joules = 1021 Joules); and according to NCEI/NOAA data, by 9.1 ± 8.7 ZJ. Among seven regions, four basins (the North Pacific, North Atlantic, the Mediterranean Sea, and southern oceans) recorded their highest OHC since the 1950s. The salinity-contrast index, a quantification of the "salty gets saltier-fresh gets fresher" pattern, also reached its highest level on record in 2022, implying continued amplification of the global hydrological cycle. Regional OHC and salinity changes in 2022 were dominated by a strong La Niña event. Global upper-ocean stratification continued its increasing trend and was among the top seven in 2022.

Estimating acid soil effects on selected cereal crop productivities in Ethiopia: Comparing economic cost-effectiveness of lime and fertilizer applications.

Acid soils are a major constraint to agricultural productivity in many parts of sub-Saharan Africa, including Ethiopia. Restoring soil pH to optimal ranges for agriculture can have a significant impact on yields, particularly for acid intolerant crops like wheat and barley. The application of agricultural lime is the standard corrective, although the large application requirements, lack of farmer awareness, and weak or non-existent lime supply chains make this a complex problem to address at scale. To date, no large-scale farmer trials of lime application have been undertaken in Ethiopia. This leaves open the question to local policy makers as to the economic benefits given the enormous capital and logistics investments required. To help address this we leverage existing spatial edaphic data and longitudinal crop surveys to simulate the productivity impact of varying lime and fertilizer applications. Our estimates find the impact of moving pH from 5.5 to 6.5, modeled as a lime soil remediation strategy, increases yields by 22% and 19% for wheat and barley, respectively. In addition, at lower pH levels our models indicate that commonly used nitrogen-based fertilizers are less cost-effective. For wheat in highly acidic soils, we find that fertilizers cost over two times as much as a single application of lime over a five-year period. The cost savings of the use of lime reaches as high as 121% of average one-year agricultural household income for wheat; with barley these savings are lower but still substantial at 24%. In general, we advocate for an integrated soil fertility management strategy that applies appropriate levels of fertilizer on pH balanced soil. If successful, Ethiopia's acid soil reclamation could become a modest version of Brazil's successful "cerrado miracle" and serve as an example for Africa.

Transposon Mutagenesis Reveals RBMS3 Silencing as a Promoter of Malignant Progression of BRAFV600E-Driven Lung Tumorigenesis.

Mutationally activated BRAF is detected in approximately 7% of human lung adenocarcinomas, with BRAFT1799A serving as a predictive biomarker for treatment of patients with FDA-approved inhibitors of BRAFV600E oncoprotein signaling. In genetically engineered mouse (GEM) models, expression of BRAFV600E in the lung epithelium initiates growth of benign lung tumors that, without additional genetic alterations, rarely progress to malignant lung adenocarcinoma. To identify genes that cooperate with BRAFV600E for malignant progression, we used Sleeping Beauty-mediated transposon mutagenesis, which dramatically accelerated the emergence of lethal lung cancers. Among the genes identified was Rbms3, which encodes an RNA-binding protein previously implicated as a putative tumor suppressor. Silencing of RBMS3 via CRISPR/Cas9 gene editing promoted growth of BRAFV600E lung organoids and promoted development of malignant lung cancers with a distinct micropapillary architecture in BRAFV600E and EGFRL858R GEM models. BRAFV600E/RBMS3Null lung tumors displayed elevated expression of Ctnnb1, Ccnd1, Axin2, Lgr5, and c-Myc mRNAs, suggesting that RBMS3 silencing elevates signaling through the WNT/ß-catenin signaling axis. Although RBMS3 silencing rendered BRAFV600E-driven lung tumors resistant to the effects of dabrafenib plus trametinib, the tumors were sensitive to inhibition of porcupine, an acyltransferase of WNT ligands necessary for their secretion. Analysis of The Cancer Genome Atlas patient samples revealed that chromosome 3p24, which encompasses RBMS3, is frequently lost in non-small cell lung cancer and correlates with poor prognosis. Collectively, these data reveal the role of RBMS3 as a lung cancer suppressor and suggest that RBMS3 silencing may contribute to malignant NSCLC progression. SIGNIFICANCE: Loss of RBMS3 cooperates with BRAFV600E to induce lung tumorigenesis, providing a deeper understanding of the molecular mechanisms underlying mutant BRAF-driven lung cancer and potential strategies to more effectively target this disease.

Risk and Resilience Pathways, Community Adversity, Decision-making, and Alcohol Use Among Appalachian Adolescents: Protocol for the Longitudinal Young Mountaineer Health Study Cohort.

BACKGROUND: Alcohol use impairs psychosocial and neurocognitive development and increases the vulnerability of youth to academic failure, substance use disorders, and other mental health problems. The early onset of alcohol use in adolescents is of particular concern, forecasting substance abuse in later adolescence and adulthood. To date, evidence suggests that youth in rural areas are especially vulnerable to contextual and community factors that contribute to the early onset of alcohol use. OBJECTIVE: The objective of the Young Mountaineer Health Study is to investigate the influence of contextual and health behavior variables on the early onset of alcohol use among middle school-aged youth in resource-poor Appalachian rural communities. METHODS: This is a program of prospective cohort studies of approximately 2200 middle school youth from a range of 20 rural, small town, and small city (population <30,000) public schools in West Virginia. Students are participating in 6 waves of data collection (2 per year) over the course of middle school (sixth to eighth grades; fall and spring) from 2020 to 2023. On the basis of an organizational arrangement, which includes a team of local data collection leaders, supervising contact agents in schools, and an honest broker system to deidentify data linked via school IDs, we are able to collect novel forms of data (self-reported data, teacher-reported data, census-linked area data, and archival school records) while ensuring high rates of participation by a large majority of youth in each participating school. RESULTS: In the spring of 2021, 3 waves of student survey data, 2 waves of data from teachers, and a selection of archival school records were collected. Student survey wave 1 comprised 1349 (response rate 80.7%) participants, wave 2 comprised 1649 (response rate 87%) participants, and wave 3 comprised 1909 (response rate 83.1%) participants. The COVID-19 pandemic has had a negative impact on the sampling frame size, resulting in a reduced number of eligible students, particularly during the fall of 2020. Nevertheless, our team structure and incentive system have proven vitally important in mitigating the potentially far greater negative impact of the pandemic on our data collection processes. CONCLUSIONS: The Young Mountaineer Health Study will use a large data set to test pathways linking rural community disadvantage to alcohol misuse among early adolescents. Furthermore, the program will test hypotheses regarding contextual factors (eg, parenting practices and neighborhood collective efficacy) that protect youth from community disadvantage and explore alcohol antecedents in the onset of nicotine, marijuana, and other drug use. Data collection efforts have been successful despite interruptions caused by the COVID-19 pandemic in 2020 and 2021. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/40451.