Many nonnormalities, one simulation: Do different data generation algorithms affect study results?

Monte Carlo simulation studies are among the primary scientific outputs contributed by methodologists, guiding application of various statistical tools in practice. Although methodological researchers routinely extend simulation study findings through follow-up work, few studies are ever replicated. Simulation studies are susceptible to factors that can contribute to replicability failures, however. This paper sought to conduct a meta-scientific study by replicating one highly cited simulation study (Curran et al., Psychological Methods, 1, 16-29, 1996) that investigated the robustness of normal theory maximum likelihood (ML)-based chi-square fit statistics under multivariate nonnormality. We further examined the generalizability of the original study findings across different nonnormal data generation algorithms. Our replication results were generally consistent with original findings, but we discerned several differences. Our generalizability results were more mixed. Only two results observed under the original data generation algorithm held completely across other algorithms examined. One of the most striking findings we observed was that results associated with the independent generator (IG) data generation algorithm vastly differed from other procedures examined and suggested that ML was robust to nonnormality for the particular factor model used in the simulation. Findings point to the reality that extant methodological recommendations may not be universally valid in contexts where multiple data generation algorithms exist for a given data characteristic. We recommend that researchers consider multiple approaches to generating a specific data or model characteristic (when more than one is available) to optimize the generalizability of simulation results.

The role of frailty in the association between depression and fall risk among older adults.

OBJECTIVES: Although there is a recognized association between depression and greater fall risk among older adults, the mechanisms explaining this association are unclear. This study evaluated the role of frailty, a common geriatric syndrome, in determining greater risk of falls among older adults with depression. METHOD: We used longitudinal data from three biennial waves of the Health and Retirement Study (HRS; 2010-2014). The sample included community-dwelling survey respondents age ≥ 65 who participated in objective physiological measures. Major Depression (MD) was measured using Composite International Diagnostic Interview for depression short form. Frailty was measured using criteria outlined in the frailty phenotype model. Causal mediation analysis was used to differentiate the direct effect of depression and indirect effect mediated by frailty on falls, fall injuries, and multiple falls. RESULTS: Major depression was associated with significantly greater odds of experiencing a fall (OR: 1.91; 95% CI: 1.31, 2.77), fall injury (OR: 1.86; 95% CI: 1.17, 2.95), and multiple falls (OR: 2.26; 95% CI: 1.52, 3.37) over a two-year period. Frailty was a significant mediator of the effects of depression on falls and multiple falls, accounting for approximately 18.9% and 21.3% of the total effects, respectively. We found no evidence of depression-frailty interaction. Sensitivity analyses showed that results were robust to unmeasured confounding and alternative operationalizations of depression. CONCLUSION: Frailty explains a significant proportion of increased likelihood of falls among older adults with depression. Treatment and management of frailty symptoms may be an important components of fall prevention among older adults with depression.

Response Inhibition Deficits in Women with the FMR1 Premutation are Associated with Age and Fall Risk.

One in 113-178 females worldwide carry a premutation allele on the FMR1 gene. The FMR1 premutation is linked to neurocognitive and neuromotor impairments, although the phenotype is not fully understood, particularly with respect to age effects. This study sought to define oculomotor response inhibition skills in women with the FMR1 premutation and their association with age and fall risk. We employed an antisaccade eye-tracking paradigm to index oculomotor inhibition skills in 35 women with the FMR1 premutation and 28 control women. The FMR1 premutation group exhibited longer antisaccade latency and reduced accuracy relative to controls, indicating deficient response inhibition skills. Longer response latency was associated with older age in the FMR1 premutation and was also predictive of fall risk. Findings highlight the utility of the antisaccade paradigm for detecting early signs of age-related executive decline in the FMR1 premutation, which is related to fall risk. Findings support the need for clinical prevention efforts to decrease and delay the trajectory of age-related executive decline in women with the FMR1 premutation during midlife.

A Guideline for Reporting Mediation Analyses of Randomized Trials and Observational Studies: The AGReMA Statement.

Importance: Mediation analyses of randomized trials and observational studies can generate evidence about the mechanisms by which interventions and exposures may influence health outcomes. Publications of mediation analyses are increasing, but the quality of their reporting is suboptimal. Objective: To develop international, consensus-based guidance for the reporting of mediation analyses of randomized trials and observational studies (A Guideline for Reporting Mediation Analyses; AGReMA). Design, Setting, and Participants: The AGReMA statement was developed using the Enhancing Quality and Transparency of Health Research (EQUATOR) methodological framework for developing reporting guidelines. The guideline development process included (1) an overview of systematic reviews to assess the need for a reporting guideline; (2) review of systematic reviews of relevant evidence on reporting mediation analyses; (3) conducting a Delphi survey with panel members that included methodologists, statisticians, clinical trialists, epidemiologists, psychologists, applied clinical researchers, clinicians, implementation scientists, evidence synthesis experts, representatives from the EQUATOR Network, and journal editors (n = 19; June-November 2019); (4) having a consensus meeting (n = 15; April 28-29, 2020); and (5) conducting a 4-week external review and pilot test that included methodologists and potential users of AGReMA (n = 21; November 2020). Results: A previously reported overview of 54 systematic reviews of mediation studies demonstrated the need for a reporting guideline. Thirty-three potential reporting items were identified from 3 systematic reviews of mediation studies. Over 3 rounds, the Delphi panelists ranked the importance of these items, provided 60 qualitative comments for item refinement and prioritization, and suggested new items for consideration. All items were reviewed during a 2-day consensus meeting and participants agreed on a 25-item AGReMA statement for studies in which mediation analyses are the primary focus and a 9-item short-form AGReMA statement for studies in which mediation analyses are a secondary focus. These checklists were externally reviewed and pilot tested by 21 expert methodologists and potential users, which led to minor adjustments and consolidation of the checklists. Conclusions and Relevance: The AGReMA statement provides recommendations for reporting primary and secondary mediation analyses of randomized trials and observational studies. Improved reporting of studies that use mediation analyses could facilitate peer review and help produce publications that are complete, accurate, transparent, and reproducible.

Mosaic loss of non-muscle myosin IIA and IIB is sufficient to induce mammary epithelial proliferation.

The mammary epithelium elaborates through hormonally regulated changes in proliferation, migration and differentiation. Non-muscle myosin II (NMII) functions at the interface between contractility, adhesion and signal transduction. It is therefore a plausible regulator of mammary morphogenesis. We tested the genetic requirement for NMIIA and NMIIB in mammary morphogenesis through deletion of the three NMII heavy chain-encoding genes (NMHCIIA, NMHCIIB and NMHCIIC; also known as MYH9, MYH10 and MYH14, respectively) that confer specificity to the complex. Surprisingly, mosaic loss, but not ubiquitous loss, of NMHCIIA and NMHCIIB induced high levels of proliferation in 3D culture. This phenotype was observed even when cells were cultured in basal medium, which does not support tissue level growth of wild-type epithelium. Mosaic loss of NMIIA and NMIIB combined with FGF signaling to induce hyperplasia. Mosaic analysis revealed that the cells that were null for both NMIIA and NMIIB, as well as wild-type cells, proliferated, indicating that the regulation of proliferation is both cell autonomous and non-autonomous within epithelial tissues. This phenotype appears to be mediated by cell-cell contact, as co-culture did not induce proliferation. Mosaic loss of NMIIA and NMIIB also induced excess proliferation in vivo Our data therefore reveal a role for NMIIA and NMIIB as negative regulators of proliferation in the mammary epithelium.

Polyclonal breast cancer metastases arise from collective dissemination of keratin 14-expressing tumor cell clusters.

Recent genomic studies challenge the conventional model that each metastasis must arise from a single tumor cell and instead reveal that metastases can be composed of multiple genetically distinct clones. These intriguing observations raise the question: How do polyclonal metastases emerge from the primary tumor? In this study, we used multicolor lineage tracing to demonstrate that polyclonal seeding by cell clusters is a frequent mechanism in a common mouse model of breast cancer, accounting for >90% of metastases. We directly observed multicolored tumor cell clusters across major stages of metastasis, including collective invasion, local dissemination, intravascular emboli, circulating tumor cell clusters, and micrometastases. Experimentally aggregating tumor cells into clusters induced a >15-fold increase in colony formation ex vivo and a >100-fold increase in metastasis formation in vivo. Intriguingly, locally disseminated clusters, circulating tumor cell clusters, and lung micrometastases frequently expressed the epithelial cytoskeletal protein, keratin 14 (K14). RNA-seq analysis revealed that K14(+) cells were enriched for desmosome and hemidesmosome adhesion complex genes, and were depleted for MHC class II genes. Depletion of K14 expression abrogated distant metastases and disrupted expression of multiple metastasis effectors, including Tenascin C (Tnc), Jagged1 (Jag1), and Epiregulin (Ereg). Taken together, our findings reveal K14 as a key regulator of metastasis and establish the concept that K14(+) epithelial tumor cell clusters disseminate collectively to colonize distant organs.

Assessing Acceptability of the Term: "Psychopathology" Among Youth Aged 18-25.

A prevailing model for mental health care for youth and families is to provide services within a "psychopathology" focused framework. This approach can compound problems for youth by imparting negative labels on them, and may be associated with iatrogenic impacts of interventions (e.g., stigmatization, lowered self-efficacy, dependency). This study assessed perceptions of the term "psychopathology" among 486 youth aged 18-25, with 39% of these youth receiving prior mental health services. Results indicated statistically significant differences in perception of the term, with youth who had received mental health services perceiving it more negatively than youth who had not. Findings suggest receipt of mental health services among young people may sensitize them to negative aspects of the term psychopathology, indicating the need for caution in using this term and other terms that may have negative impacts on mental health service use among youth.

Biobehavioral composite of social aspects of anxiety in young adults with fragile X syndrome contrasted to autism spectrum disorder.

Social anxiety is a common disorder that has negative impacts across multiple domains of function. Several clinical groups are at elevated risk for social anxiety, including those with fragile X syndrome and those with autism spectrum disorder. Measuring social anxiety in these clinical subgroups is fraught with challenge, however, given the complexity of social anxiety and measurement limitations that are particularly acute in persons with neurodevelopmental disorders. The over-arching aim of this study was to contribute to our understanding of the nature of social anxiety in fragile X syndrome and its association with autism spectrum disorder. To address this aim, we created a multi-faceted composite representing behavioral and biological aspects of social anxiety and examined differences in two adolescent and young adult-aged groups: 59 males with fragile X syndrome and 18 males with autism spectrum disorder. Results indicated a lower score on the multivariate composite for the males with fragile X syndrome relative to autism spectrum disorder but with evidence that traits of autism and social anxiety overlap. We conclude that measuring anxiety and autism traits in fragile X syndrome and autism spectrum disorder is complex with features that overlap and interact in a dynamic manner.

Lineage tracing reveals dynamic changes in oligodendrocyte precursor cells following cuprizone-induced demyelination.

The regeneration of oligodendrocytes is a crucial step in recovery from demyelination, as surviving oligodendrocytes exhibit limited structural plasticity and rarely form additional myelin sheaths. New oligodendrocytes arise through the differentiation of platelet-derived growth factor receptor α (PDGFRα) expressing oligodendrocyte progenitor cells (OPCs) that are widely distributed throughout the CNS. Although there has been detailed investigation of the behavior of these progenitors in white matter, recent studies suggest that disease burden in multiple sclerosis (MS) is more strongly correlated with gray matter atrophy. The timing and efficiency of remyelination in gray matter is distinct from white matter, but the dynamics of OPCs that contribute to these differences have not been defined. Here, we used in vivo genetic fate tracing to determine the behavior of OPCs in gray and white matter regions in response to cuprizone-induced demyelination. Our studies indicate that the temporal dynamics of OPC differentiation varies significantly between white and gray matter. While OPCs rapidly repopulate the corpus callosum and mature into CC1 expressing mature oligodendrocytes, OPC differentiation in the cingulate cortex and hippocampus occurs much more slowly, resulting in a delay in remyelination relative to the corpus callosum. The protracted maturation of OPCs in gray matter may contribute to greater axonal pathology and disease burden in MS.

Transfer of myelin-reactive th17 cells impairs endogenous remyelination in the central nervous system of cuprizone-fed mice.

Multiple sclerosis (MS) is a demyelinating disease of the CNS characterized by inflammation and neurodegeneration. Animal models that enable the study of remyelination in the context of ongoing inflammation are greatly needed for the development of novel therapies that target the pathological inhibitory cues inherent to the MS plaque microenvironment. We report the development of an innovative animal model combining cuprizone-mediated demyelination with transfer of myelin-reactive CD4(+) T cells. Characterization of this model reveals both Th1 and Th17 CD4(+) T cells infiltrate the CNS of cuprizone-fed mice, with infiltration of Th17 cells being more efficient. Infiltration correlates with impaired spontaneous remyelination as evidenced by myelin protein expression, immunostaining, and ultrastructural analysis. Electron microscopic analysis further reveals that demyelinated axons are preserved but reduced in caliber. Examination of the immune response contributing to impaired remyelination highlights a role for peripheral monocytes with an M1 phenotype. This study demonstrates the development of a novel animal model that recapitulates elements of the microenvironment of the MS plaque and reveals an important role for T cells and peripheral monocytes in impairing endogenous remyelination in vivo. This model could be useful for testing putative MS therapies designed to enhance remyelination in the setting of active inflammation, and may also facilitate modeling the pathophysiology of denuded axons, which has been a challenge in rodents because they typically remyelinate very quickly.

1,25-Dihydroxyvitamin D3 selectively and reversibly impairs T helper-cell CNS localization.

Pharmacologic targeting of T helper (TH) cell trafficking poses an attractive opportunity for amelioration of autoimmune diseases such as multiple sclerosis (MS). MS risk is associated with vitamin D deficiency, and its bioactive form, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], has been shown to prevent experimental autoimmune encephalomyelitis, a mouse model of MS, via an incompletely understood mechanism. Herein, we systematically examined 1,25(OH)2D3 effects on TH cells during their migration from the lymph nodes to the CNS. Our data demonstrate that myelin-reactive TH cells are successfully generated in the presence of 1,25(OH)2D3, secrete proinflammatory cytokines, and do not preferentially differentiate into suppressor T cells. These cells are able to leave the lymph node, enter the peripheral circulation, and migrate to the s.c. immunization sites. However, TH cells from 1,25(OH)2D3-treated mice are unable to enter the CNS parenchyma but are instead maintained in the periphery. Upon treatment cessation, mice rapidly develop experimental autoimmune encephalomyelitis, demonstrating that 1,25(OH)2D3 prevents the disease only temporarily likely by halting TH cell migration into the CNS.

A faith-based community partnership to address HIV/AIDS in the southern United States: implementation, challenges, and lessons learned.

Though race and region are not by themselves risk factors for HIV infection, regional and racial disparities exist in the burden of HIV/AIDS in the US. Specifically, African Americans in the southern US appear to bear the brunt of this burden due to a complex set of upstream factors like structural and cultural influences that do not facilitate HIV/AIDS awareness, HIV testing, or sexual risk-reduction techniques while perpetuating HIV/AIDS-related stigma. Strategies proposed to mitigate the burden among this population have included establishing partnerships and collaborations with non-traditional entities like African American churches and other faith-based organizations. Though efforts to partner with the African American church are not necessarily novel, most of these efforts do not present a model that focuses on building the capacity of the African American church to address these upstream factors and sustain these interventions. This article will describe Project Fostering AIDS Initiatives That Heal (F.A.I.T.H), a faith-based model for successfully developing, implementing, and sustaining locally developed HIV/AIDS prevention interventions in African American churches in South Carolina. This was achieved by engaging the faith community and the provision of technical assistance, grant funding and training for project personnel. Elements of success, challenges, and lessons learned during this process will also be discussed.

A selective thyroid hormone ß receptor agonist enhances human and rodent oligodendrocyte differentiation.

Nerve conduction within the mammalian central nervous system is made efficient by oligodendrocyte-derived myelin. Historically, thyroid hormones have a well described role in regulating oligodendrocyte differentiation and myelination during development; however, it remains unclear which thyroid hormone receptors are required to drive these effects. This is a question with clinical relevance since nonspecific thyroid receptor stimulation can produce deleterious side-effects. Here we report that GC-1, a thyromimetic with selective thyroid receptor ß action and a potentially limited side-effect profile, promotes in vitro oligodendrogenesis from both rodent and human oligodendrocyte progenitor cells. In addition, we used in vivo genetic fate tracing of oligodendrocyte progenitor cells via PDGFαR-CreER;Rosa26-eYFP double-transgenic mice to examine the effect of GC-1 on cellular fate and find that treatment with GC-1 during developmental myelination promotes oligodendrogenesis within the corpus callosum, occipital cortex and optic nerve. GC-1 was also observed to enhance the expression of the myelin proteins MBP, CNP and MAG within the same regions. These results indicate that a ß receptor selective thyromimetic can enhance oligodendrocyte differentiation in vitro and during developmental myelination in vivo and warrants further study as a therapeutic agent for demyelinating models.

Understanding internet sex-seeking behaviour and sexual risk among young men who have sex with men: evidences from a cross-sectional study.

OBJECTIVE: Internet sex-seeking is common among young men who have sex with men (MSM). However, research examining its association with risky sexual behaviour has produced mixed findings, possibly due to various operational definitions of internet sex-seeking which fail to account for its multi-dimensionality. This study purposed to: (1) examine if the way internet sex-seeking behaviour is operationalised influences its association with risky sexual behaviour (unprotected anal intercourse (UAI) and casual sex) and (2) determine the association of each operational definition with sexual risk. METHODS: We recruited 263 sexually-experienced young MSM (18-29 years) and operationalised internet sex-seeking behaviour in four ways: (i) ever used the internet to meet other men, (ii) currently own a profile on a website dedicated to meeting other men, (iii) ever physically met a man you initially met online and (iv) ever had sex with a man you met online. Using binomial regression, we examined the association of each operationalisation with UAI and casual sex. RESULTS: Only MSM who reported physically meeting a man they met online and those who ever had sex with a man they met online were more likely to report a history of UAI (p<0.05), while MSM who engaged in all forms of internet sex-seeking were more likely to engage in casual sex (p<0.05). However, the strength of these associations varied according to the mode of operationalisation. CONCLUSIONS: The way internet sex-seeking is operationalised in research is differentially associated with sexual risk. Against this backdrop, the utility of these operational definitions in future research and inferences drawn from such research must be interpreted with caution. Findings have important implications for sexual health research and methodology, survey development, sexual health prevention interventions, and evaluating sexual risk among young MSM.

The influence of race and comorbidity on the timely initiation of antiretroviral therapy among older persons living with HIV/AIDS.

OBJECTIVES: We examined whether the timely initiation of antiretroviral therapy (ART) differed by race and comorbidity among older (≥ 50 years) people living with HIV/AIDS (PLWHA). METHODS: We conducted frequency and descriptive statistics analysis to characterize our sample, which we drew from 2005-2007 Medicaid claims data from 14 states. We employed univariate and multivariable Cox regression analyses to evaluate the relationship between race, comorbidity, and timely ART initiation (≤ 90 days post-HIV/AIDS diagnosis). RESULTS: Approximately half of the participants did not commence ART promptly. After we adjusted for covariates, we found that older PLWHA who reported a comorbidity were 40% (95% confidence interval = 0.26, 0.61) as likely to commence ART promptly. We found no racial differences in the timely initiation of ART among older PLWHA. CONCLUSIONS: Comorbidities affect timely ART initiation in older PLWHA. Older PLWHA may benefit from integrating and coordinating HIV care with care for other comorbidities and the development of ART treatment guidelines specific to older PLWHA. Consistent Medicaid coverage helps ensure consistent access to HIV treatment and care and may eliminate racial disparities in timely ART initiation among older PLWHA.

Social Communication Delay in an Unbiased Sample of Preschoolers With the FMR1 Premutation.

PURPOSE: The Fragile X Messenger Ribonucleoprotein-1 (FMR1) premutation (FXpm) is a genetic variant that is common in the general population and is associated with health symptoms and disease in adulthood. However, poor understanding of the clinical phenotype during childhood has hindered the development of clinical practice guidelines for screening and intervention. Given that social communication difficulties have been widely documented in adults with the FXpm and are linked with reduced psychosocial functioning, the present study aimed to characterize the communication profile of the FXpm during early childhood. METHOD: Eighteen children with the FXpm who were identified through cascade testing (89%) or screening at birth (11%) were compared to 21 matched typically developing children, aged 2-4 years. Participants completed standardized assessments of language (Mullen Scales of Early Learning) and adaptive communication (Vineland Adaptive Behavior Scales-II). Social communication was rated from seminaturalistic interaction samples using the Brief Observation of Social Communication Change. RESULTS: Children with the FXpm showed delayed social communication development, with the magnitude of group differences highlighting social communication as a feature that distinguishes children with the FXpm from their peers (p = .046, ηp2 = .12). The groups did not differ on the standardized language and adaptive communication measures (ps > .297, ηp2s < .03). CONCLUSIONS: Early screening and treatment of social communication delays may be key to optimizing outcomes for children with the FXpm. Further research is needed to replicate findings in a larger sample, delineate the trajectory and consequences of social communication difficulties across the life span in the FXpm, and determine the potential epidemiological significance of FMR1 as a mediator of developmental communication differences within the general population.

The Children and Parents in Focus project: a population-based cluster-randomised controlled trial to prevent behavioural and emotional problems in children.

BACKGROUND: There is large body of knowledge to support the importance of early interventions to improve child health and development. Nonetheless, it is important to identify cost-effective blends of preventive interventions with adequate coverage and feasible delivery modes. The aim of the Children and Parents in Focus trial is to compare two levels of parenting programme intensity and rate of exposure, with a control condition to address impact and cost-effectiveness of a universally offered evidence-based parenting programme in the Swedish context. METHODS/DESIGN: The trial has a cluster randomised controlled design comprising three arms: Universal arm (with access to participation in Triple P - Positive Parenting Program, level 2); Universal Plus arm (with access to participation in Triple P - Positive Parenting Program, level 2 as well as level 3, and level 4 group); and Services as Usual arm. The sampling frame is Uppsala municipality in Sweden. Child health centres consecutively recruit parents of children aged 3 to 5 years before their yearly check-ups (during the years 2013-2017). Outcomes will be measured annually. The primary outcome will be children's behavioural and emotional problems as rated by three informants: fathers, mothers and preschool teachers. The other outcomes will be parents' behaviour and parents' general health. Health economic evaluations will analyse cost-effectiveness of the interventions versus care as usual by comparing the costs and consequences in terms of impact on children's mental health, parent's mental health and health-related quality of life. DISCUSSION: This study addresses the need for comprehensive evaluation of the long-term effects, costs and benefits of early parenting interventions embedded within existing systems. In addition, the study will generate population-based data on the mental health and well-being of preschool aged children in Sweden. TRIAL REGISTRATION ISRCTN: ISRCTN16513449.

A Bayesian Approach for Estimating Mediation Effects with Missing Data.

Methodologists have developed mediation analysis techniques for a broad range of substantive applications, yet methods for estimating mediating mechanisms with missing data have been understudied. This study outlined a general Bayesian missing data handling approach that can accommodate mediation analyses with any number of manifest variables. Computer simulation studies showed that the Bayesian approach produced frequentist coverage rates and power estimates that were comparable to those of maximum likelihood with the bias-corrected bootstrap. We share a SAS macro that implements Bayesian estimation and use two data analysis examples to demonstrate its use.

One step at a time: A statistical approach for distinguishing mediators, confounders, and colliders using direction dependence analysis.

In observational data, understanding the causal link when estimating the causal effect of an independent variable (x) on a dependent variable (y) often requires researchers to identify the role of a third variable in the x → y relationship. Mediation, confounding, and colliding are three key third-variable effects that yield different theoretical and methodological implications for drawing causal conclusions. Commonly used covariance-based statistical methods, such as linear regression and structural equation modeling, cannot distinguish these effects in practice, however. In this study, we introduce a statistical approach for distinguishing mediators, confounders, colliders, and potential M-bias structures that uses higher-order moment information from the data. We propose a two-step procedure that uses the Hilbert-Schmidt independence criterion within the direction dependence analysis framework. Results from Monte Carlo simulations show that our proposed approach accurately recovers the true data-generating process of the third variable. We provide an empirical example to demonstrate the application of our proposed approach in psychological research. Finally, we discuss implications and future directions of our work. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

An overview of the Together Everyone Achieves More Physical Activity (TEAM-PA) trial to increase physical activity among African American women.

BACKGROUND: The Together Everyone Achieves More Physical Activity (TEAM-PA) trial is a randomized controlled trial testing the efficacy of a group-based intervention for increasing physical activity (PA) among insufficiently active African American women. DESIGN: The TEAM-PA trial uses a group cohort design, is implemented at community sites, and will involve 360 African American women. The trial compares a 10-week group-based intervention vs. a standard group-delivered PA comparison program. Measures include minutes of total PA/day using 7-day accelerometer estimates (primary outcome), and body mass index, blood pressure, waist circumference, walking speed, sedentary behavior, light physical activity, and the percentage achieving ≥150 min of moderate to vigorous PA/week (secondary outcomes) at baseline, post-intervention, and 6-months post-intervention. INTERVENTION: The intervention integrates elements from Social Cognitive Theory, Self-Determination Theory, Group Dynamics Theory, and a focus on collectivism to evaluate different components of social affiliation (relatedness, reciprocal support, group cohesion, and collective efficacy). The intervention integrates shared goal-setting via Fitbits, group-based problem-solving, peer-to-peer positive communication, friendly competition, and cultural topics related to collectivism. Compared to the standard group-delivered PA program, participants in the intervention are expected to show greater improvements from baseline to post- and 6-month follow-up on minutes of total PA/day and secondary outcomes. Social affiliation variables (vs. individual-level factors) will be evaluated as mediators of the treatment effect. IMPLICATIONS: The results of the TEAM-PA trial will determine the efficacy of the intervention and identify which aspects of social affiliation are most strongly related to increased PA among African American women. TRIAL REGISTRATION: This study was registered on Clinicaltrials.gov (# NCT05519696) in August 2022 prior to initial participant enrollment.